NORIG 2BC - Blood Collection for DNABC109 Mar 09 BC - Blood Collection for DNA

Keyed: ( )

Purpose: Document the collection of whole blood for shipment to NIDDK Genetics Repository at Rutgers University for DNA extraction and banking. Complete this form only if the patient signed the consent for genetic research. When: Screening visit s1 or s2 and as needed during follow-up due to a low yield (less than 50 μg) of DNA (during follow-up, use the visit code of the follow-up visit that is open). By whom: Clinical Coordinator and laboratory personnel responsible for collection of whole blood. Instructions: (1) Apply MACO labels specific for the patient and visit to the EDTA vacutainer tubes; these labels are generated by the clinical center upon registration (screening labels) or after randomization (follow-up visit labels). Affix duplicate tube label in item 13. (2) Fill two 10 mL EDTA vacutainer tubes with whole blood (see SOP I, section 6.2). (3) Pack the whole blood tubes in the specimen shippers supplied by the NIDDK Genetics Repository and ship to the NIDDK Genetic Repository at Rutgers University on the same day blood is collected. Ship blood at ambient room temperature. Use the preprinted Federal Express shipping label, marked for Priority Overnight Delivery, to ship whole blood to the NIDDK Genetics Repository Monday-Friday.

A. Center, patient and visit identification C. Specimen for Genetics Repository 1. Center code: Attach MACO labels to two 10mL EDTA tubes and fill each with whole blood; invert each tube gently 6 times to mix blood with additives; keep tubes at 2. Patient ID: room temperature until the same day shipment to the NIDDK Genetics Repository (see SOP I, sec- 3. Patient code: tion 6.21). 4. Date of visit: 10. Was blood collected for the NIDDK Genetics Repository at this visit: day mon year Yes ( 1) 5. Visit code: 11. No, (specify reason): ( ) 6. Form & revision: b c 1 2

7. Study: NORIG 2 specify

B. Check on consent 15. 8. Did the patient consent to blood draw for 11. Date and time of blood draw DNA banking: a. Date: Yes No ( 1) ( * 2) day mon year b. Time: * You cannot proceed until you get consent. : ( 1) ( 2) 9. Did the patient previously provide blood hour minute am pm for DNA banking in the Gastroparesis 12. Number of 10 mL EDTA tubes: Registry: Yes No 13. Form copy of tube labels: ( * 1) ( 2) NORIG Form BC 15. * Do not draw additional blood for DNA banking. Pt: ccc- 9999, xyz Gender Age, yrs.: XX

14. Phlebotomist:

print name

Form BC NORIG Revision 1 (09 Mar 09) BC - Blood Collection for DNA 1 of 2 Patient ID:

D. Administrative information 15. Clinical Coordinator PIN:

16. Clinical Coordinator signature:

17. Date form reviewed:

day mon year

Form BC NORIG Revision 1 (09 Mar 09) BC - Blood Collection for DNA 2 of 2 Keyed: ( )

NORIG 2BC - Blood Collection for DNABC221 Jul 11 BC - Blood Collection for DNA

Purpose: Complete this form for all registered NORIG participants to document the collection of whole blood for DNA extraction and banking at the NIDDK Genetics Repository at Rutgers University. When: Screening visit s1 or s2 and as needed during follow-up due to a low yield (less than 50 μg) of DNA (during follow-up, use the visit code of the follow-up visit that is open). By whom: Clinical Coordinator and laboratory personnel responsible for collection of whole blood. Instructions: (1) Apply MACO labels specific for the patient and visit to the EDTA vacutainer tubes; these labels are generated by the clinical center upon registration (screening labels) or after randomization (follow-up visit labels). Affix duplicate tube label in item 13. (2) Fill two 10 mL EDTA vacutainer tubes with whole blood (see SOP I, section 6.20). (3) Pack the whole blood tubes in the specimen shippers supplied by the NIDDK Genetics Repository and ship to the NIDDK Genetic Repository at Rutgers University on the same day blood is collected. Ship blood at ambient room temperature. Use the preprinted Federal Express shipping label, marked for Priority Overnight Delivery, to ship whole blood to the NIDDK Genetics Repository Monday-Friday.

A. Center, patient and visit identification C. Specimen for Genetics Repository 1. Center code: Attach MACO labels to two 10mL EDTA tubes and fill each with whole blood; invert each tube gently 6 times to mix blood with additives; keep tubes at 2. Patient ID: room temperature until the same day shipment to the NIDDK Genetics Repository (see SOP I, sec- 3. Patient code: tion 6.20). 4. Date of visit: 10. Was blood collected for the NIDDK Genetics Repository at this visit: day mon year Yes ( 1) 5. Visit code: 11. No, (specify reason): ( ) 6. Form & revision: b c 2 2

7. Study: NORIG 2 specify

B. Check on consent 15. 8. Did the patient previously provide blood 11. Date and time of blood draw for DNA banking in the Gastroparesis a. Date: Registry: Yes No day mon year ( 1) ( 2) b. Time: 15. : ( 1) ( 2) 9. Did the patient consent to blood draw for hour minute am pm DNA banking: 12. Number of 10 mL EDTA tubes:

Yes ( 1) 13. Form copy of tube labels: No, patient did not consent to Genetic Research ( ) 2 NORIG Form BC 15. Pt: ccc- 9999, xyz Gender Age, yrs.: XX

14. Phlebotomist:

print name

Form BC NORIG Revision 2 (21 Jul 11) BC - Blood Collection for DNA 1 of 2 Patient ID:

D. Administrative information 15. Clinical Coordinator PIN:

16. Clinical Coordinator signature:

17. Date form reviewed:

day mon year

Form BC NORIG Revision 2 (21 Jul 11) BC - Blood Collection for DNA 2 of 2 Keyed: ( )

NORIG 8BH - Baseline Medical HistoryBH110 Mar 09 BH - Baseline Medical History Purpose: To collect baseline history information about the patient. When: Screening visit s1. Administered by: Clinical Coordinator, reviewed by Study Physician. Respondent: Patient. Instructions: The Clinical Coordinator should collect the information by either interview or chart review necessary to complete sections A-E. Attach a MACO label to page 7, Gastroparesis Symptoms Inventory, before separating and giving the questionnaire to the patient for self-administration. The Clinical Coordinator should review the completed questionnaire for missing items or other problems for resolution before the patient leaves the clinical center. Page 7 should be re-attached to the BH form. If a is checked for any item, further review is necessary by the study physician who will determine whether the diagnosis or condition in the Caution item renders the patient ineligible for or unlikely to comply with the requirements of the NORIG trial. If a or is checked for any item, the patient is ineligible for the NORIG trial unless the item can be resolved within the 112 day screening window. The BH form can not be keyed to the data system if there are any Stop or Ineligible items present. The form should be retained in a study file for further evaluation as appropriate.

A. Center, visit, and patient identification d. Other (specify): ( 1)

1. Center ID:

2. Patient ID: specify

9. Does the patient report symptoms of 3. Patient code: gastroparesis of at least 6 months duration (do not have to be contiguous) 4. Visit date (date this form is initiated): with varying degrees of nausea, vomiting, abdominal pain, early satiety, or post-prandial fullness: day mon year Yes No ( 1) ( 2) 5. Visit code: s 1

6. Form & revision: b h 1 C. Medical history ( means Caution; condition is exclusionary if 7. Study: NORIG 2 study physician agrees with diagnosis) 10. Has the patient ever been diagnosed with B. Gastroparesis history diabetes Type 1 or 2: Yes No 8. What is the present understanding of the ( 1) ( 2) reason for patient’s gastroparesis (check all that apply)

a. Idiopathic: ( 1) 11. Does the patient have a G tube, J tube, central catheter or gastric electrical b. Diabetes: ( ) 1 stimulator: Yes No ( ) ( ) c. Post-surgical (includes gastric surgeries such as 1 2 fundoplication, that may disturb the anatomical physiology of gastric emptying, but excludes other organ surgeries that may result with similar gastroparetic symptoms such as appendec- 12. Does the patient have a hypersensitivity or allergy to any tricyclic antidepressant tomy, cholecystectomy, etc): ( 1) drug: Yes No ( 1) ( 2)

Form BH NORIG Revision 1 (10 Mar 09) BH - Baseline Medical History 1 of 8 Patient ID:

13. Has the patient ever been diagnosed with v. Scleroderma: ( 1) or treated for any of the following (check all that w. Malignancy (cancer): ( ) apply; source of information can be interview or 1

chart review) x. Migraine headaches: ( 1)

a. Glaucoma: ( 1) y. Hypertension: ( 1)

z. Coronary artery disease: ( 1) b. History of seizures: ( 1) aa. Cerebrovascular disease: ( 1) ab. Hyperlipidemia (high cholesterol, high triglycerides): ( ) c. Cardiac arrhythmias: ( 1) 1

ac. Pancreatitis: ( 1)

ad. Cholelithiasis: ( 1) d. Pyloric obstruction: ( 1) ae. Gall bladder disease including chronic cholecystitis, gall bladder e. Intestinal obstruction: ( 1) dyskinesia: ( 1)

af. Polycystic ovary syndrome: ( 1) f. Inflammatory bowel disease: ( 1) ag. Myopathy: ( 1)

ah. Multiple sclerosis: ( 1) g. Thyroid disease (hormonal abnormality): ( 1) ai. Eating disorders (anorexia, bulimia): ( 1)

aj. Schizophrenia: ( 1) h. Recent myocardial infarction ak. Bipolar disorder: ( 1) (within past year): ( 1) al. Obsessive compulsive disorder: ( 1) am. Severe anxiety or personality i. Major depression: ( 1) disorder: ( 1) an. Dyslexia or learning problems

j. Advanced liver disease: ( 1) including ADHD (attention deficit hyperactivity disorder): ( 1) k. Peptic ulcer disease: ( 1) ao. Other diagnosis #1 (specify): ( ) l. GERD: Gastroesophageal reflux 1

disease: ( 1) specify m. Interstitial cystitis: ( 1)

ap. Other diagnosis #2 (specify): ( 1) n. Bladder dysfunction: ( 1)

o. Diverticulosis: ( 1) specify p. Endometriosis: ( 1) aq. Other diagnosis #3 (specify): ( 1) q. Blood clots: ( 1) r. Hemophilia (bleeding disorder): ( ) 1 specify s. Systemic lupus erythematosus (SLE) ar. None of the above: ( 1) or collagen vascular disease: ( 1)

t. Rheumatoid arthritis: ( 1)

u. Fibromyalgia: ( 1)

Form BH NORIG Revision 1 (10 Mar 09) BH - Baseline Medical History 2 of 8 Patient ID:

D. Medication use 15. Is the patient currently taking or has the patient used any benzodiazepines in the 14. Is the patient currently taking or has the past month: patient used any proton pump inhibitors, Yes No histamine H2 receptor antagonists or ( 1) ( 2) other similar medications in the past 16. month: (If yes, check all that apply): Yes No ( 1) ( 2) a. Alprazolam (Xanax): ( 1) 15. b. Buspirone (BuSpar): ( 1) (If yes, check all that apply): c. Chlordiazepoxide (Librax): ( 1) a. Antacids, (specify): ( 1) d. Clonazepam (Klonopin): ( 1) e. Diazepam (Valium): ( ) specify 1

f. Halazepam (Paxipam): ( 1) b. Cimetidine (Tagamet): ( 1) g. Lorazepam (Ativan): ( 1) c. Esomeprazole (Nexium): ( 1) h. Oxazepam (Serax): ( 1) d. Famotidine (Pepcid): ( 1) i. Other (specify): ( 1) e. Lansoprazole (Prevacid): ( 1) f. Nizatidine (Axid): ( ) 1 specify

g. Omeprazole (Prilosec, Zegerid): ( 1) 16. Has the patient taken erythromycin in the h. Pantoprazole (Protonix): ( 1) past 6 weeks: i. Rabeprazole (Aciphex): ( 1) Yes No ( *1) ( 2) j. Ranitidine (Zantac): ( 1) k. Other (specify): ( ) 1 *Patient must be off erythromycin for 6 weeks prior to randomization. Use of erythromycin is not specify permitted during the NORIG trial.

17. Is the patient currently taking or has the patient used any prokinetic medications in the past month: Yes No ( 1) ( 2) 18.

(If yes, check all that apply):

a. Azithromycin (Zithromax): ( 1)

b. Bethanechol (Duvoid, Urecholine): ( 1)

c. Botulinum toxin (Botox): ( 1)

d. Cisapride (Propulsid): ( 1)

e. Clarithromycin (Biaxin): ( 1)

f. Domperidone (Motilium): ( 1)

g. Metoclopramide (Reglan): ( 1)

h. Other (specify): ( 1)

specify Form BH NORIG Revision 1 (10 Mar 09) BH - Baseline Medical History 3 of 8 Patient ID:

18. Is the patient currently taking or has the 19. Is the patient currently taking or has the patient used any antiemetic medications patient used any selective serotonin in the past month: reuptake inhibitors (SSRIs) in the past 6 Yes No weeks: ( 1) ( 2) Yes No 19. ( *1) ( 2) (If yes, check all that apply): 20.

a. Aprepitant (Emend): ( 1) *Patient must be on a stable dose for 3 months prior to randomization. b. Dolasetron (Anzemet): ( 1)

c. Dronabinol (Marinol): ( 1) (If yes, check all that apply) d. Granisetron (Kytril): ( 1) a. Citalopram (Celexa): ( 1) e. Meclizine (Antivert): ( 1) b. Escitalopram (Lexapro): ( 1) f. Ondansetron (Zofran): ( 1) c. Fluoxetine (Prozac): ( 1) g. Palonosetron (Aloxi): ( 1) d. Fluvoxamine (Luvox): ( 1) h. Prochlorperazine (Compazine): ( 1) e. Paroxetine (Paxil): ( 1) i. Promethazine (Pentazine, Phenergan): ( 1) f. Sertraline (Zoloft): ( 1) j. Tetrahydrocannabinol (THC, g. Zimelidine (Zelmid): ( 1) marijuana): ( 1) h. Other (specify): ( 1) k. Trimethobenzamide (Benzacot,

Stemetic, Tigan): ( 1) specify l. Tropisetron (Navoban): ( 1)

m. Other (specify): ( 1) 20. Has the patient taken any monoamine oxidase inhibitors (MAOIs) in the past 6 weeks: specify Selegiline (Eldepryl, Emsam, Zelapar) n. Other (specify): ( 1) Isocarboxazid (Marplan) Tranylcypromine (Parnate) specify Yes No ( *1) ( 2)

*Patient must be off MAOIs for 6 weeks prior to randomization. Use of an MAOI is not permitted during the NORIG trial.

Form BH NORIG Revision 1 (10 Mar 09) BH - Baseline Medical History 4 of 8 Patient ID:

21. Has the patient taken any tricyclic 23. Currently or during the past 6 weeks, has antidepressants for refractory symptoms the patient taken the narcotic pain of gastroparesis in the past 6 weeks: medication tramadol (Ultram, Ultracet) on a daily basis or more than 3 times per Amitriptyline (Elavil) week: Amoxapine (Asendin) Yes No Clomipramine (Anafranil) ( *1) ( 2) Desipramine (Norpramin) Doxepin (Sinequan) Imipramine (Tofranil) *Use of tramadol more than 3 days per week is Nortriptyline (Pamelor) not permitted during the NORIG trial. Patient Trimipramine (Surmontil) must be off daily narcotics for 6 weeks prior to Protriptyline (Pliva, Vivactil) randomization. Other tricyclic antidepressants Yes No ( *1) ( 2) 24. Has the patient taken any calcium channel blockers in the past 6 weeks:

*Patient must be off tricyclic antidepressants for Amlodipine (Norvasc) 6 weeks prior to randomization. Diltiazem (Cardizem) Felodipine (Plendil) 22. Has the patient taken any strongly Isradipine (DynaCirc, Prescal) anticholinergic medications in the past Nicardipine (Cardene, Carden SR) 6 weeks: Nifedipine (Adalat, Procardia) Nimodipine (Nimotop) Anisotropine (Valpin 50) Nisoldipine (Sular) Atropine (Atropen) Verapamil (Calan, Isoptin) Belladonna (Donnatal) Other calcium channel blockers Clidinium (Quarzan) Yes No Dicyclomine (Bentyl) ( *1) ( 2) Glycopyrrolate (Robinul) Homatropine (Hycodan) Hyoscyamine (Levsin) *Patient must be off calcium channel blockers for Mepenzolate (Cantil) 6 weeks prior to randomization. Methantheline (Banthine) Methscopolamine (Pamine) Propantheline (Pro-Banthine) Scopolamine (Transderm Scop) Other strongly anticholinergic medications Yes No ( *1) ( 2)

*Patient must be off strongly anticholinergic medications for 6 weeks prior to randomization.

Form BH NORIG Revision 1 (10 Mar 09) BH - Baseline Medical History 5 of 8 Patient ID:

25. Currently or during the past 6 weeks, has 26. Is the patient currently taking or has the the patient taken narcotic pain patient used any of the following medications on a daily basis or more than medications in the past month: 3 times per week: Yes No ( 1) ( 2) Butalbital combinations (Fioricet, Esgic-Plus) 27. Codeine combinations (Tylenol #3, #4) Fentanyl (Duragesic patch) (If yes, check all that apply): Hydrocodone combinations (Lorcet, Lortab) a. Aripiprazole (Abilify): Hydromorphone (Dilaudid) ( 1)

Methadone b. Bupropion (Wellbutrin): ( 1) Oxycodone combinations (Percocet, Percodan, c. Divalproex sodium (Depakote): ( ) Oxycontin, Tylox, Vicodin) 1

Pentazocine (Talacen) d. Duloxetine (Cymbalta): ( 1) Propoxyphene combinations (Darvocet, Wygesic) e. Gabapentin (Neurontin): ( ) Other narcotic pain medications 1

Yes No f. Haloperidol (Haldol): ( 1) ( *1) ( 2) g. Lamotrigine (Lamictal): ( 1) h. Maprotiline (Ludiomil): *Use of narcotics more than 3 days per week is ( 1) not permitted during the NORIG trial. Patient i. Mirtazapine (Remeron): ( 1) must be off daily narcotics for 6 weeks prior to j. Olanzapine (Zyprexa): randomization. ( 1)

k. Pregabalin (Lyrica): ( 1)

l. Venlafaxine (Effexor): ( 1)

m. Ziprasidone (Geodon): ( 1)

n. Other medication #1 (specify): ( 1)

specify

o. Other medication #2 (specify): ( 1)

specify

p. Other medication #3 (specify): ( 1)

specify

Form BH NORIG Revision 1 (10 Mar 09) BH - Baseline Medical History 6 of 8 Patient ID:

E. Administrative information

27. Study Physician PIN:

28. Study Physician signature:

29. Clinical Coordinator PIN:

30. Clinical Coordinator signature:

31. Date form reviewed:

day mon year

Form BH NORIG Revision 1 (10 Mar 09) BH - Baseline Medical History 7 of 8 Affix label here

Patient ID:

Pt code:

Visit code:

F. Gastroparesis Symptoms Inventory

Clinical Global Patient Impression (CGPI): 32. Please consider how you felt this past week in regard to your stomach symptoms. Compared to the way you usually feel, how would you rate your relief of symptoms during the past week (circle one):

3 2 1 0 -1 -2 -3

Completely Considerably Somewhat Unchanged Somewhat Considerably Very Better Better Better Worse Worse Considerably Worse

Directions: This questionnaire asks you about the severity of some symptoms you may have been having. For each symptom, please circle the number that best describes how severe the symptom has been during the prior week. If you have not experienced this symptom, circle 0. If the symptom has been mild, circle 1. If it has been moderate, circle 2. If it has been severe, circle 3. There are no right or wrong answers. Please answer each question as accurately as possible. Please be sure to answer every question.

0 = None 1= Mild 2=Moderate 3=Severe 33. Tiredness/fatigue ...... 0 1 2 3

34. Drowsiness/sedation ...... 0 1 2 3

35. Nervous/jittery ...... 0 1 2 3

36. Sleep disturbance ...... 0 1 2 3

37. Dizziness/light-headedness ...... 0 1 2 3

38. Seizures ...... 0 1 2 3

39. Blurred vision ...... 0 1 2 3

40. Palpitations/fast irregular ...... 0 1 2 3 heartbeat

41. Skin rash ...... 0 1 2 3

42. Headache ...... 0 1 2 3

43. Dry mouth ...... 0 1 2 3

44. Rectal bleeding ...... 0 1 2 3

45. Urinary retention ...... 0 1 2 3

Thank you. Please return this questionnaire to the coordinator.

Form BH BH - Baseline Medical History NORIG Revision 1 (10 Mar 09) 8 of 8 Keyed: ( )

NORIG 8BH - Baseline Medical HistoryBH224 Aug 09 BH - Baseline Medical History Purpose: To collect baseline history information about the patient. When: Screening visit s1. Administered by: Clinical Coordinator, reviewed by Study Physician. Respondent: Patient. Instructions: The Clinical Coordinator should collect the information by either interview or chart review necessary to complete sections A-E. Attach a MACO label to page 8, Gastroparesis Symptoms Inventory, before separating and giving the questionnaire to the patient for self-administration. The Clinical Coordinator should review the completed questionnaire for missing items or other problems for resolution before the patient leaves the clinical center. Page 8 should be re-attached to the BH form. If a is checked for any item, further review is necessary by the study physician who will determine whether the diagnosis or condition in the Caution item renders the patient ineligible for or unlikely to comply with the requirements of the NORIG trial. If a or is checked for any item, the patient is ineligible for the NORIG trial unless the item can be resolved within the 112 day screening window. The BH form can not be keyed to the data system if there are any Stop or Ineligible items present. The form should be retained in a study file for further evaluation as appropriate.

A. Center, visit, and patient identification d. Other (specify): ( 1)

1. Center ID:

2. Patient ID: specify

6. Form & revision: b h 2 C. Medical history ( means Caution; condition is exclusionary if 7. Study: NORIG 2 study physician agrees with diagnosis) 10. Has the patient ever been diagnosed with B. Gastroparesis history diabetes Type 1 or 2: Yes No 8. What is the present understanding of the ( 1) ( 2) reason for patient’s gastroparesis (check all that apply)

a. Idiopathic: ( 1) 11. Does the patient use a G tube, J tube, or a central catheter for nutrition or a gastric b. Diabetes: ( ) 1 electrical stimulator: Yes No ( * ) ( ) c. Post-surgical (includes gastric surgeries such as 1 2 fundoplication, that may disturb the anatomical physiology of gastric emptying, but excludes *Use of a central catheter for medications is other organ surgeries that may result with similar gastroparetic symptoms such as appendec- allowed. tomy, cholecystectomy, etc): ( 1)

Form BH NORIG Revision 2 (24 Aug 09) BH - Baseline Medical History 1 of 8 Patient ID:

12. Does the patient have a hypersensitivity t. Rheumatoid arthritis: ( 1) or allergy to any tricyclic antidepressant u. Fibromyalgia: ( ) drug: 1

Yes No v. Scleroderma: ( 1) ( 1) ( 2) w. Malignancy (cancer): ( 1)

x. Migraine headaches: ( 1) 13. Has the patient ever been diagnosed with y. Hypertension: ( 1) or treated for any of the following (check all that z. Coronary artery disease: apply; source of information can be interview or ( 1) chart review) aa. Cerebrovascular disease: ( 1)

a. Glaucoma: ( 1) ab. Hyperlipidemia

(high cholesterol, high triglycerides): ( 1)

ac. Pancreatitis: ( 1) b. History of seizures: ( 1) ad. Cholelithiasis: ( 1) c. Cardiac arrhythmias: ( ) ae. Gall bladder disease including 1 chronic cholecystitis, gall bladder

dyskinesia: ( 1)

d. Pyloric obstruction: ( 1) af. Polycystic ovary syndrome: ( 1)

ag. Myopathy: ( 1) e. Intestinal obstruction: ( 1) ah. Multiple sclerosis: ( 1)

ai. Eating disorders (anorexia, bulimia): ( 1) f. Inflammatory bowel disease: ( 1) aj. Schizophrenia: ( 1) ak. Bipolar disorder: ( ) g. Thyroid disease 1 (hormonal abnormality): ( 1) al. Obsessive compulsive disorder: ( 1) am. Severe anxiety or personality

h. Recent myocardial infarction disorder: ( 1)

(within past year): ( 1) an. Dyslexia or learning problems including ADHD (attention deficit

hyperactivity disorder): ( 1) i. Major depression: ( 1) ao. Other diagnosis #1 (specify): ( 1)

j. Advanced liver disease: ( 1) specify k. Peptic ulcer disease: ( 1) ap. Other diagnosis #2 (specify): ( 1) l. GERD: Gastroesophageal reflux

disease: ( 1) specify m. Interstitial cystitis: ( 1) aq. Other diagnosis #3 (specify): ( 1) n. Bladder dysfunction: ( 1)

o. Diverticulosis: ( 1) specify

p. Endometriosis: ( 1) ar. None of the above: ( 1) q. Blood clots: ( 1)

r. Hemophilia (bleeding disorder): ( 1) s. Systemic lupus erythematosus (SLE)

or collagen vascular disease: ( 1)

Form BH NORIG Revision 2 (24 Aug 09) BH - Baseline Medical History 2 of 8 Patient ID:

17. Is the patient currently taking or has the patient used any prokinetic medications in the past month: Yes No ( 1) ( 2) 18.

(If yes, check all that apply):

a. Azithromycin (Zithromax): ( 1)

b. Bethanechol (Duvoid, Urecholine): ( 1)

c. Botulinum toxin (Botox): ( 1)

d. Cisapride (Propulsid): ( 1)

e. Clarithromycin (Biaxin): ( 1)

f. Domperidone (Motilium): ( 1)

g. Metoclopramide (Reglan): ( 1)

h. Other (specify): ( 1)

specify Form BH NORIG Revision 2 (24 Aug 09) BH - Baseline Medical History 3 of 8 Patient ID:

a. Aprepitant (Emend): ( 1) *Patient must be on a stable dose for 3 months prior to randomization. b. Dolasetron (Anzemet): ( 1)

Stemetic, Tigan): ( 1) specify l. Tropisetron (Navoban): ( 1)

*Patient must be off MAOIs for 6 weeks prior to randomization. Use of an MAOI is not permitted during the NORIG trial.

Form BH NORIG Revision 2 (24 Aug 09) BH - Baseline Medical History 4 of 8 Patient ID:

*Patient must be off strongly anticholinergic medications for 6 weeks prior to randomization.

Form BH NORIG Revision 2 (24 Aug 09) BH - Baseline Medical History 5 of 8 Patient ID:

Methadone b. Bupropion (Wellbutrin): ( 1) Oxycodone combinations (Percocet, Percodan, c. Divalproex sodium (Depakote): ( ) Oxycontin, Tylox, Vicodin) 1

Pentazocine (Talacen) d. Duloxetine (Cymbalta): ( 1) Propoxyphene combinations (Darvocet, Wygesic) e. Gabapentin (Neurontin): ( ) Other narcotic pain medications 1

k. Pregabalin (Lyrica): ( 1)

l. Venlafaxine (Effexor): ( 1)

m. Ziprasidone (Geodon): ( 1)

n. Other medication #1 (specify): ( 1)

specify

o. Other medication #2 (specify): ( 1)

specify

p. Other medication #3 (specify): ( 1)

specify

Form BH NORIG Revision 2 (24 Aug 09) BH - Baseline Medical History 6 of 8 Patient ID:

E. Administrative information

27. Study Physician PIN:

28. Study Physician signature:

29. Clinical Coordinator PIN:

30. Clinical Coordinator signature:

31. Date form reviewed:

day mon year

Form BH NORIG Revision 2 (24 Aug 09) BH - Baseline Medical History 7 of 8 Affix label here

Patient ID:

Pt code:

Visit code:

F. Gastroparesis Symptoms Inventory

3 2 1 0 -1 -2 -3

Completely Considerably Somewhat Unchanged Somewhat Considerably Very Better Better Better Worse Worse Considerably Worse

0 = None 1= Mild 2=Moderate 3=Severe 33. Tiredness/fatigue ...... 0 1 2 3

34. Drowsiness/sedation ...... 0 1 2 3

35. Nervous/jittery ...... 0 1 2 3

36. Sleep disturbance ...... 0 1 2 3

37. Dizziness/light-headedness ...... 0 1 2 3

38. Seizures ...... 0 1 2 3

39. Blurred vision ...... 0 1 2 3

40. Palpitations/fast irregular ...... 0 1 2 3 heartbeat

41. Skin rash ...... 0 1 2 3

42. Headache ...... 0 1 2 3

43. Dry mouth ...... 0 1 2 3

44. Rectal bleeding ...... 0 1 2 3

45. Urinary retention ...... 0 1 2 3

Thank you. Please return this questionnaire to the coordinator.

Form BH BH - Baseline Medical History NORIG Revision 2 (24 Aug 09) 8 of 8 Keyed: ( )

NORIG2BP - Blood Processing for PlasmaBP119 Mar 09 BP - Blood Processing for Plasma

Purpose: Document collection of fasting blood for separation of plasma in the NORIG trial and shipment to NIDDK Biosample Repository at Fisher BioServices. When: Screening visit s1 or s2 and follow-up visits f03, f06, f09, f12, f15 and f18. By whom: Clinical Coordinator and laboratory personnel responsible for collection and processing of whole blood. Instructions: Apply a MACO label specific for the patient and visit to one 10 mL green top heparin tube; this label is generated by the clinical center upon registration (screening labels) or after randomization (follow-up visit labels). Affix duplicate whole blood tube label in item 10. Choose one of the cryovial label sets provided by the DCC for this patient ID for use with this visit. Label 2.0 mL cryovials with numbered patient-specific plasma (blue) cryovial labels. Affix plasma aliquot #00 label to this form in item 14. For plasma: Fill one 10 mL green top heparin tube with whole blood. Process blood for plasma within two hours according to procedures specified in the NORIG SOP I, section 6.20. After separation, prepare up to 14 aliquots of plasma, depending on volume of plasma obtained: transfer 0.5 mL of plasma to each prelabeled 2.0 mL cryovial. Immediately freeze labeled aliquots of plasma at -70° C. NOTE: Immediately upon completion of plasma aliquot preparation, destroy any leftover cryovial labels including all serum (red) cryovial labels from the label set used at this visit; use of these cryovial labels at any other visit will result in aliquots from both visits being unusable since the visit at which they were collected will not be able to be determined.

A. Center, patient and visit identification B. Processing whole blood Plasma to be separated from whole blood per 1. Center code: instructions in SOP I, section 6.20. Draw fasting blood in the morning.

2. Patient ID: 8. Was blood collected for the NIDDK Biosample Repository:

3. Patient code: Yes ( 1)

No, patient was not fasting for 8 hours ( 2) 4. Date of visit: 19.

No, other reason (specify): ( 3) day mon year 19. 5. Visit code: specify other reason 6. Form & revision: b p 1 9. Date and time of blood draw

7. Study: NORIG 2 a. Date: day mon year b. Time:

: ( 1) ( 2) hour minute am pm

10. Attach matching whole blood tube MACO label:

NORIG Form BP, Plasma Pt: 9999, xyz Visit vvv

Date:

11. Phlebotomist:

print name Form BP NORIG Revision 1 (19 Mar 09) BP - Blood Processing for Plasma 1 of 2 Patient ID:

C. Aliquoting into cryovials E. Administrative information Transfer 0.5 mL plasma into each of up to fourteen 2.0 mL prelabeled cryovials. 19. Clinical Coordinator PIN:

12. Date and time of separation into aliquots 20. Clinical Coordinator signature: a. Date: day mon year b. Time:

: ( 1) ( 2) 21. Date form reviewed: hour minute am pm day mon year 13. Number of aliquots for plasma:

14. Affix duplicate blue plasma aliquot #00 cryovial label (use aliquot #00 label which is lo- cated in the first row of labels in the set): Plasma aliquot #00 label

15. Technician:

print name

D. Freezing cryovials Freeze plasma cryovials immediately at -70 degrees C. Batch ship monthly to the NIDDK Biosample Repository at Fisher BioServices.

16. Date and time cryovials frozen in -70 degrees C a. Date: day mon year b. Time:

: ( 1) ( 2) hour minute am pm

17. Number of cryovials frozen:

18. Technician:

print name

Form BP NORIG Revision 1 (19 Mar 09) BP - Blood Processing for Plasma 2 of 2 Keyed: ( )

NORIG2BP - Blood Processing for PlasmaBP221 Jul 11 BP - Blood Processing for Plasma

Purpose: Document collection of fasting blood for separation of plasma in the NORIG trial and shipment to NIDDK Biosample Repository at Fisher BioServices. When: Screening visit s1 or s2 and follow-up visits f12 and f15. By whom: Clinical Coordinator and laboratory personnel responsible for collection and processing of whole blood. Instructions: Apply a MACO label specific for the patient and visit to one 10 mL green top heparin tube; this label is generated by the clinical center upon registration (screening labels) or after randomization (follow-up visit labels). Affix duplicate whole blood tube label in item 10. Choose one of the cryovial label sets provided by the DCC for this patient ID for use with this visit. Label 2.0 mL cryovials with numbered patient-specific plasma (blue) cryovial labels. Affix plasma aliquot #00 label to this form in item 14. For plasma: Fill one 10 mL green top heparin tube with whole blood. Process blood for plasma within two hours according to procedures specified in the NORIG SOP I, section 6.19. After separation, prepare up to 14 aliquots of plasma, depending on volume of plasma obtained: transfer 0.5 mL of plasma to each prelabeled 2.0 mL cryovial. Immediately freeze labeled aliquots of plasma at -70° C. NOTE: Immediately upon completion of plasma aliquot preparation, destroy any leftover cryovial labels including all serum (red) cryovial labels from the label set used at this visit; use of these cryovial labels at any other visit will result in aliquots from both visits being unusable since the visit at which they were collected will not be able to be determined.

A. Center, patient and visit identification B. Processing whole blood Plasma to be separated from whole blood per 1. Center code: instructions in SOP I, section 6.19. Draw fasting blood in the morning.

2. Patient ID: 8. Was blood collected for the NIDDK Biosample Repository:

3. Patient code: Yes ( 1)

No, patient was not fasting for 8 hours ( 2) 4. Date of visit: 19.

No, other reason (specify): ( 3) day mon year 19. 5. Visit code: specify other reason

6. Form & revision: b p 2 9. Date and time of blood draw a. Date: 7. Study: NORIG 2 day mon year b. Time:

: ( 1) ( 2) hour minute am pm

10. Attach matching whole blood tube MACO label:

NORIG Form BP, Plasma Pt: 9999, xyz Visit vvv

Date:

11. Phlebotomist:

print name

Form BP NORIG Revision 2 (21 Jul 11) BP - Blood Processing for Plasma 1 of 2 Patient ID:

C. Aliquoting into cryovials E. Administrative information Transfer 0.5 mL plasma into each of up to fourteen 2.0 mL prelabeled cryovials. 19. Clinical Coordinator PIN:

12. Date and time of separation into aliquots 20. Clinical Coordinator signature: a. Date: day mon year b. Time: 21. Date form reviewed: : ( 1) ( 2) hour minute am pm day mon year 13. Number of aliquots for plasma:

14. Affix duplicate blue plasma aliquot #00 cryovial label (use aliquot #00 label which is lo- cated in the first row of labels in the set): Plasma aliquot #00 label

15. Technician:

print name

D. Freezing cryovials Freeze plasma cryovials immediately at -70 degrees C. Batch ship monthly to the NIDDK Biosample Repository at Fisher BioServices.

16. Date and time cryovials frozen in -70 degrees C a. Date: day mon year b. Time:

: ( 1) ( 2) hour minute am pm

17. Number of cryovials frozen:

18. Technician:

print name

Form BP NORIG Revision 2 (21 Jul 11) BP - Blood Processing for Plasma 2 of 2 Keyed: ( )

NORIG1CG - Genetic Consent DocumentationCG109 Mar 09 CG - Genetic Consent Documentation

Purpose: To document options selected for use of samples for genetic research. When: Screening visit s1 or s2, or as needed during follow-up. By whom: Study Physician and Clinical Coordinator. Instructions: Complete this form based on the consent document signed by the patient. Do not collect blood if the patient previously provided blood for DNA banking in the Gastroparesis Registry. If the patient changes his/her mind regarding consent for use of DNA samples after the initial form is completed, complete a new CG form using the visit code of the follow-up visit that is open.

A. Center, patient and visit identification 11. Other information related to consent for genetic research that clinic staff feel 1. Center ID: needs to be keyed to the NORIG database (e.g., if your genetic consent had other options that are not covered by the 3 categories of use of DNA samples 2. Patient ID: specified in items 8 through 10):

3. Patient code:

4. Date form completed:

day mon year

5. Visit code: 12. In your judgment, has the patient 6. Form & revision: c g 1 consented to collection of blood for DNA banking (this question is asked in recognition that not all IRBs will have approved consent statements 7. Study: NORIG 2 that include language that can be mapped into the questions in items 8 through 10; a response of "No" to this question (item 12) means that blood B. Consent for collection, storage, and use of DNA should NOT be collected for sending to the samples for current and future genetic research Genetics Repository and if already collected, should be destroyed by the Genetics Repository): 8. Does the patient consent to genetic Yes No research that is currently planned by the ( 1) ( 2) study investigators: Yes No C. Administrative information ( 1) ( 2) 13. Study Physician PIN: 9. Does the patient consent to future genetic research on gastroparesis by this study or 14. Study Physician signature: other study investigators: Yes No ( 1) ( 2) 15. Clinical Coordinator PIN: 10. Does the patient consent to future genetic research not related to gastroparesis by this study or other study investigators: 16. Clinical Coordinator signature: Yes No ( 1) ( 2) 17. Date form reviewed:

day mon year

Form CG NORIG Revision 1 (09 Mar 09) CG - Genetic Consent Documentation 1 of 1 Keyed: ( )

NORIG2EG - Upper Endoscopy DocumentationEG119 Mar 09 EG - Upper Endoscopy Documentation

Purpose: To document the results of the upper gastrointestinal endoscopy (EGD) to determine patient eligibility for the NORIG trial during screening and to document other findings, if any, during follow-up. When: Screening visit s1 or s2. The screening upper gastrointestinal endoscopy procedure must have been performed within 2 years prior to registration into NORIG Trial. Administered by: Study Physician and Clinical Coordinator. Screening visit instructions: This form should be completed using the available reports of the upper gastrointestinal endoscopy procedure. Upper gastrointestinal and Endoscopy with Ultrasound (EUS) reports may be used if all of the required components of the EGD are available. Attach a copy of the available GI procedure reports as the source document. If a is checked for any item, further review is necessary by the study physician who will determine whether the diagnosis or condition in the Caution item renders the patient ineligible for the NORIG trial. If a or is checked for any item, the patient is ineligible for the NORIG trial unless the item can be resolved within the 112 day screening window. The EG form can not be keyed to the data system if there are any Stop or Ineligible items present. The form should be retained in a study file for further evaluation as appropriate or in the file for ineligible patients. Attach a copy of the endoscopy report as the source document. Follow-up visit instructions: If patient has had an endoscopic procedure since the last study visit, results should be recorded on this form using visit code "n". If more than one endoscopy has been performed in the same visit window, use visit code "n1" for the 2nd endoscopy, "n2" for the 3rd endoscopy, etc. This form should be completed using the available reports of the upper gastrointestinal endoscopy procedure. Attach a copy of the available reports as the source document.

A. Center, patient, and visit identification B. Upper endoscopy information

1. Center ID: 8. Date of upper endoscopy:

day mon year 2. Patient ID: a. Is this screening visit s1: Yes No ( 1) ( 2) 3. Patient code: 9. b. Is date of upper endoscopy within 2 4. Date form is initiated: years prior to the NORIG registration date: Yes No day mon year ( 1) ( 2)

5. Visit code: (If STOP, then do not key form. The upper endoscopy must be scheduled). 6. Form & revision: e g 1 9. Reason(s) for the procedure (check all that apply): 7. Study: NORIG 2 a. Gastroparesis symptoms/rule out

obstruction: ( 1)

b. Anemia: ( 1)

c. Abdominal pain: ( 1)

d. Gastrostomy tube: ( 1)

e. GERD: ( 1)

f. Other (specify): ( 1)

specify

Form EG NORIG Revision 1 (19 Mar 09) EG - Upper Endoscopy Documentation 1 of 2 Patient ID:

C. Endoscopic findings D. Other comments

10. Normal stomach: Yes No 12. Other comments concerning upper ( 1) ( 2) endoscopy procedure or results: Yes No 11. ( ) ( ) (If no, check all that apply): 1 2 a. Gastritis: ( ) 13. 1 a. Specify:

b. Ulcer: ( 1)

c. Gastrostomy tube: ( 1)

d. Pyloric stenosis: ( 1) e. Other gastric findings, excluding any gastric surgery (specify): ( 1) E. Eligibility check

13. Is this screening visit (s1): Yes No specify ( 1) ( 2) 15. 11. Surgical change(s) observed in stomach: Yes No 14. Were there any other endoscopic or ( 1) ( 2) histologic findings not recorded above that in the opinion of the Study Physician 12. (If yes, check all that apply): would characterize the patient as ineligible: a. Total resection: ( *1) Yes No ( * 1) ( 2)

b. Billroth I: ( 1) *If Yes, specify:

c. Billroth II: ( 1)

d. Roux-en-Y gastrojejunostomy: ( 1)

e. Other pyloroplasty or antrectomy: ( 1)

F. Administrative information f. Prior fundoplication: ( *1) 15. Study Physician PIN:

g. Other subtotal resection: ( ) 1 16. Study Physician signature:

h. Stapling or banding of the stomach: ( 1) 17. Clinical Coordinator PIN: i. Gastrojejunostomy: ( 1)

18. Clinical Coordinator signature:

j. Other gastric surgery (specify): ( 1)

19. Date form reviewed: specify day mon year * If a participant had these surgical procedures after randomization into the NORIG trial, please record them.

Form EG NORIG Revision 1 (19 Mar 09) EG - Upper Endoscopy Documentation 2 of 2 Keyed: ( )

NORIG 5FH - Follow-up Medical HistoryFH130 Mar 09 FH - Follow-up Medical History Purpose: To collect follow-up medical information about the patient. When: Follow-up visits f03, f06, f09, f12, f15 and f18. Administered by: Clinical Coordinator, reviewed by Study Physician. Respondent: Patient. Instructions: The Clinical Coordinator should collect information by interview and chart review to complete sections A-E. Attach a pre-printed MACO label to page 5, Gastroparesis Symptoms Inventory, before giving to the patient to complete. The Clinical Coordinator should review the completed questionnaire for missing responses and resolve any problems before the patient leaves the clinical center. Page 5 should be re-attached to the FH form.

A. Center, visit, and patient identification C. Medical history

1. Center ID: 10. Since the date in item 8, has the patient been diagnosed with or treated for any of the following (check all that apply; source of in- 2. Patient ID: formation can be interview or chart review. Com- plete the Interim Event Report (IE) form if thought 3. Patient code: to be associated with NORIG study drug.)

a. Pyloric obstruction: ( 1) 4. Visit date (date this form is initiated): b. Intestinal obstruction: ( 1)

day mon year c. Inflammatory bowel disease: ( 1)

d. Advanced liver disease: ( 1) 5. Visit code: f e. Peptic ulcer disease: ( 1) 6. Form & revision: f h 1 f. GERD: Gastroesophageal reflux disease: ( 1)

7. Study: NORIG 2 g. Interstitial cystitis: ( 1)

h. Bladder dysfunction: ( 1) B. Interval identification i. Diverticulosis: ( 1)

8. Date of last Follow-up Medical History j. Endometriosis: ( 1) form (if this is f03, then date of randomization): k. Blood clots: ( 1) l. Hemophilia (bleeding disorder): ( ) day mon year 1

m. Glaucoma: ( 1) 9. Visit code of last Follow-up Medical n. Systemic lupus erythematosus (SLE) History (FH) form (if this is visit f03, then rz): or collagen vascular disease: ( 1)

o. Rheumatoid arthritis: ( 1)

p. Fibromyalgia: ( 1)

q. Scleroderma: ( 1) r. Thyroid disease (hormonal abnormality): ( 1)

s. Malignancy (cancer): ( 1)

t. Migraine headaches: ( 1)

Form FH NORIG Revision 1 (30 Mar 09) FH - Follow-up Medical History 1 of 5 Patient ID:

u. Seizures: ( 1) 11. Since the date in item 8, has the patient had exacerbations of symptoms of v. Hypertension: ( ) 1 gastroparesis:

w. Coronary artery disease: ( 1) Yes No ( *1) ( 2) x. Cardiac arrhythmias: ( ) 1 12.

y. Myocardial infarction: ( 1) a. Number of Emergency Room visits (enter ‘‘00’’ if none): z. Cerebrovascular disease: ( 1) aa. Hyperlipidemia (high cholesterol, high triglycerides): ( ) *Complete the Interim Event Report (IE) form if 1 thought to be associated with NORIG study drug. ab. Pancreatitis: ( 1) ac. Cholelithiasis: ( 1) 12. Since the date in item 8, has the patient ad. Gall bladder disease including been hospitalized: chronic cholecystitis, gall bladder Yes No ( *1) ( 2) dyskinesia: ( 1) 13. ae. Polycystic ovary syndrome: ( ) 1 a. Number of hospitalizations:

af. Myopathy: ( 1)

ag. Multiple sclerosis: ( 1) *Complete the Interim Event Report (IE) form if thought to be associated with NORIG study drug. ah. Eating disorders (anorexia, bulimia): ( 1) ai. Major depression: ( ) 1 D. Medication history aj. Schizophrenia: ( 1) 13. ak. Bipolar disorder: ( ) Since the date in item 8, has the patient 1 taken any proton pump inhibitors,

al. Obsessive compulsive disorder: ( 1) histamine H2 receptor antagonists or other similar medications (check all that apply): am. Severe anxiety or personality

disorder: ( 1) a. Antacids, (specify): ( 1) an. Dyslexia or learning problems including ADHD (attention deficit specify hyperactivity disorder): ( 1) b. Cimetidine (Tagamet): ( 1) ao. Other diagnosis #1 (specify): ( 1) c. Esomeprazole (Nexium): ( 1) d. specify Famotidine (Pepcid): ( 1)

e. Lansoprazole (Prevacid): ( 1) ap. Other diagnosis #2 (specify): ( 1)

f. Nizatidine (Axid): ( 1)

specify g. Omeprazole (Prilosec, Zegerid): ( 1)

aq. Other diagnosis #3 (specify): ( 1) h. Pantoprazole (Protonix): ( 1)

i. Rabeprazole (Aciphex): ( 1) specify j. Ranitidine (Zantac): ( 1)

ar. None of the above: ( 1) k. Other (specify): ( 1)

specify

l. None of the above: ( 1)

Form FH NORIG Revision 1 (30 Mar 09) FH - Follow-up Medical History 2 of 5 Patient ID:

14. Since the date in item 8, has the patient 16. Since the date in item 8, has the patient taken any prokinetic medications taken any of the following (check all that apply): benzodiazepines (check all that apply):

a. Azithromycin (Zithromax): ( 1) a. Alprazolam (Xanax): ( 1)

b. Bethanechol (Duvoid, Urabeth): ( 1) b. Buspirone (BuSpar): ( 1)

c. Botulinum toxin (Botox): ( 1) c. Chlordiazepoxide (Librax): ( 1)

d. Cisapride (Propulsid): ( 1) d. Clonazepam (Klonopin): ( 1)

e. Clarithromycin (Biaxin): ( 1) e. Diazepam (Valium): ( 1)

f. Domperidone (Motilium): ( 1) f. Halazepam (Paxipam): ( 1)

g. Metoclopramide (Reglan): ( 1) g. Lorazepam (Ativan): ( 1)

h. Other (specify): ( 1) h. Oxazepam (Serax): ( 1)

i. Other (specify): ( 1) specify

i. None of the above: ( 1) specify j. None of the above: ( ) 15. Since the date in item 8, has the patient 1 taken any of the following antiemetic 17. Since the date in item 8, has the patient medications (check all that apply): taken any of the following narcotic pain

a. Aprepitant (Emend): ( 1) medications for use 3 times per week or less (check all that apply): b. Dolasetron (Anzemet): ( 1) a. Butalbital combinations (Fioricet, c. Dronabinol (Marinol): ( 1) Esgic-Plus): ( 1) d. Granisetron (Kytril): ( ) 1 b. Codeine combinations

e. Meclizine (Antivert): ( 1) (Tylenol #3, #4): ( 1)

f. Ondansetron (Zofran): ( 1) c. Fentanyl (Duragesic patch): ( 1)

g. Palonosetron (Aloxi): ( 1) d. Hydrocodone combinations (Lorcet, Lortab): ( 1) h. Prochlorperazine (Compazine): ( 1) e. Hydromorphone (Dilaudid): ( 1) i. Promethazine (Pentazine, Phenergan): ( 1) f. Methadone: ( ) j. Tetrahydrocannabinol 1

(THC, marijuana): ( 1) g. Oxycodone combinations (Percocet, Percodan, Oxycontin, Tylox, Vicodin): ( ) k. Trimethobenzamide (Benzacot, 1

Stemetic, Tigan): ( 1) h. Pentazocine (Talacen): ( 1)

l. Tropisetron (Navoban): ( 1) i. Propoxyphene combinations (Darvocet, Wygesic): ( 1) m. Other (specify): ( 1) j. Tramadol (Ultram, Ultracet): ( 1)

specify k. Other (specify): ( 1)

n. None of the above: ( 1) specify

l. None of the above: ( 1)

Form FH NORIG Revision 1 (30 Mar 09) FH - Follow-up Medical History 3 of 5 Patient ID:

18. Since the date in item 8, has the patient E. Administrative information taken any of the following medications (check all that apply): 19. Study Physician PIN:

a. Aripiprazole (Abilify): ( 1) 20. Study Physician signature: b. Bupropion (Wellbutrin): ( 1)

c. Citalopram (Celexa): ( 1)

d. Divalproex sodium (Depakote): ( 1) 21. Clinical Coordinator PIN:

e. Duloxetine (Cymbalta): ( 1) 22. Clinical Coordinator signature: f. Escitalopram (Lexapro): ( 1)

g. Fluoxetine (Prozac): ( 1)

h. Fluvoxamine (Luvox): ( 1) 23. Date form reviewed: i. Gabapentin (Neurontin): ( 1) j. Haloperidol (Haldol): ( ) 1 day mon year

k. Lamotrigine (Lamictal): ( 1)

l. Maprotiline (Ludiomil): ( 1)

m. Mirtazapine (Remeron): ( 1)

n. Olanzapine (Zyprexa): ( 1)

o. Paroxetine (Paxil): ( 1)

p. Pregabalin (Lyrica): ( 1)

q. Sertraline (Zoloft): ( 1)

r. Venlafaxine (Effexor): ( 1)

s. Zimelidine (Zelmid): ( 1)

t. Ziprasidone (Geodon): ( 1)

u. Other medication #1 (specify): ( 1)

specify

v. Other medication #2 (specify): ( 1)

specify

w. Other medication #3 (specify): ( 1)

specify

x. None of the above: ( 1)

Have patient complete section F (page 5).

Form FH NORIG Revision 1 (30 Mar 09) FH - Follow-up Medical History 4 of 5 Affix label here

Patient ID:

Pt code:

Visit code:

F. Gastroparesis Symptoms Inventory

Clinical Global Patient Impression (CGPI): 24. Please consider how you felt this past week in regard to your stomach symptoms, in particular your overall well-being and stomach symptoms. Compared to the way you usually felt before entering the study, how would you rate your relief of symptoms during the past week (circle one): 3 2 1 0 -1 -2 -3

Completely Considerably Somewhat Unchanged Somewhat Considerably Very Better Better Better Worse Worse Considerably Worse

Global Overall Relief of Symptoms:

25. During the past 7 days, have you had adequate relief of your stomach symptoms? Yes No

( 1) ( 2)

Directions: This following questionnaire asks you about the severity of some symptoms you may have been having. For each symptom, please circle the number that best describes how severe the symptom has been during the prior week. If you have not experienced this symptom, circle 0. If the symptom has been mild, circle 1. If it has been moderate, circle 2. If it has been severe, circle 3. There are no right or wrong answers. Please answer each question as accurately as possible. Please be sure to answer every question. 0 = None 1= Mild 2=Moderate 3=Severe 26. Tiredness/fatigue ...... 0 1 2 3

27. Drowsiness/sedation ...... 0 1 2 3

28. Nervous/jittery ...... 0 1 2 3

29. Sleep disturbance ...... 0 1 2 3

30. Dizziness/light-headedness ...... 0 1 2 3

31. Seizures ...... 0 1 2 3

32. Blurred vision ...... 0 1 2 3

33. Palpitations/fast irregular ...... 0 1 2 3 heartbeat

34. Skin rash ...... 0 1 2 3

35. Headache ...... 0 1 2 3

36. Dry mouth ...... 0 1 2 3

37. Rectal bleeding ...... 0 1 2 3

38. Urinary retention ...... 0 1 2 3

Thank you. Please return this questionnaire to the coordinator. Form FH FH - Follow-up Medical History NORIG Revision 1 (30 Mar 09) 5 of 5 Keyed: ( )

NORIG 2GE - Gastric Emptying Scintigraphy DocumentationGE119 Mar 09 GE - Gastric Emptying Scintigraphy Documentation Purpose: Record the results of gastric emptying scintigraphy to determine eligibility for the NORIG trial during screening and to document other findings, if any, during follow-up. When: Screening visit s1: The gastric emptying scintigraphy must have been performed at a GpCRC clinical center within 2 years prior to registration into the NORIG trial. Administered by: Study Physician and Clinical Coordinator. Screening visit instructions: The Study Physician should complete this form using the available gastric emptying scintigraphy report. If the patient has not had a qualifying gastric emptying scintigraphy in the last 2 years, one should be performed. Information not included in the report should be gathered directly from the patient after the test, if possible. If is checked for any item, further review is necessary by the study physician who will determine whether the Caution item renders the patient ineligible for the NORIG trial. If or is reached for any item, the patient is ineligible for the NORIG trial unless the item can be resolved within the 112 day screening window. The GE form can not be keyed to the data system if there are any Stop or Ineligible items present. The form should be retained in a study file for further evaluation as appropriate or in the file for ineligible patients. Follow-up visit instructions: If patient has had a gastric emptying procedure since the last study visit, results should be recorded on this form using visit code ‘‘n’’. Attach a copy of the scintigraphy report to this form as the source document.

A. Identifying information 10. Was the date of gastric emptying scintigraphy during screening or within 2 1. Center ID: years of NORIG registration date: Yes No ( ) ( * ) 2. Patient ID: 1 2

*Test must be rescheduled. 3. Patient code:

11. Meal given for test: 4. Date of form: Egg Beaters: ( 1)

day mon year Generic low-fat egg whites: ( 2)

Other (specify) ( *3) 5. Visit code If report not associated with a visit, fill in ‘‘n.’’

specify 6. Form & revision: g e 1 *Caution: Test may have to be repeated depending on the meal. 7. Study: NORIG 2

B. Gastric Emptying Scintigraphy Test

8. Date of gastric emptying scintigraphy:

day mon year

9. Is this screening visit s1: Yes No ( 1) ( 2) 11.

Form GE NORIG Revision 1 (19 Mar 09) GE - Gastric Emptying Scintigraphy Documentation 1 of 2 Patient ID:

12. Amount of meal and water consumed 14. Interpretation of gastric emptying scintigraphy: a. Meal (check only one):

100% ( 1)

90% ( 2)

75% ( 3)

50% ( 4)

33% ( 5) 15. Comments on the gastric emptying

25% ( 6) scintigraphy:

10% ( 7)

0% ( 8)

Unknown ( 9) b. Water (check only one):

100% ( 1)

90% ( 2)

75% ( 3) C. Eligibility check 50% ( ) 4 16. Is this screening visit s1: 33% ( ) 5 Yes No 25% ( 6) ( 1) ( 2) 10% ( 7) 18.

0% ( 8)

Unknown ( 9) 17. Do the results documented from the gastric emptying scintigraphy qualify this 13. Percent gastric retention patient for randomization in NORIG (Analysis is performed using the geometric mean (Patients must have 2 hour (>60% retention) delay of the anterior and posterior images for each time or 4 hour (>10% retention) delay in gastric emp- point which are then corrected for nucleotide de- tying): cay. Results expressed as percent remaining in the Yes No stomach.) ( 1) ( 2)

a. 0 minutes: · % D. Data Coordinating Center use

b. 30 minutes*: · 18. Study Physician PIN: % 19. Study Physician signature: c. 1 hour: · %

d. 2 hours: · 20. Clinical Coordinator PIN: %

21. Clinical Coordinator signature: e. 3 hours*: · %

f. 4 hours: · 22. Date reviewed: % *The 30 minute and 3 hour time points are op- tional, but should be obtained and recorded, if day mon year available. The 0 minutes, 1, 2, and 4 hour time points are required for NORIG trial randomization.

Form GE NORIG Revision 1 (19 Mar 09) GE - Gastric Emptying Scintigraphy Documentation 2 of 2 Keyed: ( ) NORIG

GS - Gastrointestinal Symptom Rating Scale (GSRS)

Purpose: To collect data on the symptoms the patient has been experiencing in the NORIG trial. When: Screening visit s1 or s2 and follow-up visits f03, f06, f09, f12, f15 and f18. Administered by: Self-administered, but Clinical Coordinator must be available at visit to answer questions and to review completed form. Respondent: Patient. Instructions: The Clinical Coordinator should complete section A and attach a MACO label to each of pages 2-7 before giving the questionnaire to the patient for completion. Follow-up: The Clinical Coordinator should review the completed questionnaire for missing responses and resolve any problems before the patient leaves the clinical center. Page 1 should be reattached to pages 2-7 and the Clinical Coordinator should complete section B.

A. Center, visit, and patient identification B. Administrative information (To be completed by clinical center staff after 1. Center ID: questionnaire is completed.)

2. Patient ID: 8. Clinical Coordinator PIN:

3. Patient code: 9. Clinical Coordinator signature:

4. Visit date:

- - 10. Date form reviewed: day mon year - - 5. Visit code: day mon year

6. Form & revision: g s 1

7. Study: NORIG 2

Form GS NORIG Revision 1 (19 Mar 09) GS - Gastrointestinal Symptom Rating Scale (GSRS) 1 of 7 Affix label here

Patient ID:

Patient code:

Visit code:

DIRECTIONS: This questionnaire asks you about the severity of some symptoms you may have been having. For each symptom, please circle the number that best describes the level of discomfort caused by the symptom during the prior week . If you have had no discomfort at all, circle 1. If you have had slight discomfort, circle 2. If the symptom has caused mild discomfort, circle 3. If you have had moderate discomfort, circle 4. If the symptom has caused moderately severe discomfort, circle 5. If you have had severe discomfort, circle 6. If the symptom has caused very severe discomfort, circle 7. There are no right or wrong answers. Please answer each question as accurately as possible. Please be sure to answer every question.

11. Have you been bothered by stomach ache or pain during the past week? (Stomach ache refers to all kinds of aches or pains in your stomach or belly.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

12. Have you been bothered by heartburn during the past week? (By heartburn we mean a burning pain or discomfort behind the breastbone in your chest.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

Form GS NORIG Revision 1 (19 Mar 09) GS - Gastrointestinal Symptom Rating Scale (GSRS) 2 of 7 Affix label here

Patient ID:

Patient code:

Visit code:

13. Have you been bothered by acid reflux during the past week? (By acid reflux we mean regurgitation or flow of sour or bitter fluid into your mouth.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

14. Have you been bothered by hunger pains in the stomach or belly during the past week? (This hollow feeling in the stomach is associated with the need to eat between meals.):

Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

15. Have you been bothered by nausea during the past week? (By nausea we mean a feeling of wanting to be sick.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

Form GS NORIG Revision 1 (19 Mar 09) GS - Gastrointestinal Symptom Rating Scale (GSRS) 3 of 7 Affix label here

Patient ID:

Patient code:

Visit code:

16. Have you been bothered by rumbling in your stomach or belly during the past week? (Rumbling refers to vibrations or noise in the stomach.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

17. Has your stomach felt bloated during the past week? (Feeling bloated refers to swelling in the stomach or belly.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

18. Have you been bothered by burping during the past week? (Burping refers to bringing air or gas through the mouth.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

Form GS NORIG Revision 1 (19 Mar 09) GS - Gastrointestinal Symptom Rating Scale (GSRS) 4 of 7 Affix label here

Patient ID:

Patient code:

Visit code:

19. Have you been bothered by passing gas or flatus during the past week? (Passing gas or flatus refers to the release of air or gas from the bowel.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

20. Have you been bothered by constipation during the past week? (Constipation refers to a reduced ability to empty the bowels.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

21. Have you been bothered by diarrhea during the past week? (Diarrhea refers to frequent loose or watery stools.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

Form GS NORIG Revision 1 (19 Mar 09) GS - Gastrointestinal Symptom Rating Scale (GSRS) 5 of 7 Affix label here

Patient ID:

Patient code:

Visit code:

22. Have you been bothered by loose stools during the past week? (If your stools have been alternately hard and loose, this question only refers to the extent you have been bothered by the stools being loose.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

23. Have you been bothered by hard stools during the past week? (If your stools have been alternately hard and loose, this question only refers to the extent you have been bothered by the stools being hard.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

24. Have you been bothered by an urgent need to have a bowel movement during the past week? (This urgent need to open your bowels makes you rush to the toilet.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

Form GS NORIG Revision 1 (19 Mar 09) GS - Gastrointestinal Symptom Rating Scale (GSRS) 6 of 7 Affix label here

Patient ID:

Patient code:

Visit code:

25. When going to the toilet during the past week, have you had the feeling of not completely emptying your bowels? (The feeling that after finishing a bowel movement, there is still more stool that needs to be passed.): Circle one No discomfort...... 1 Slight discomfort...... 2 Mild discomfort ...... 3 Moderate discomfort...... 4 Moderately severe discomfort ...... 5 Severe discomfort...... 6 Very severe discomfort...... 7

Thank you. Please return this questionnaire to the coordinator.

Form GS NORIG Revision 1 (19 Mar 09) GS - Gastrointestinal Symptom Rating Scale (GSRS) 7 of 7 Keyed: ( )

NORIG2LR - Laboratory ResultsLR119 Mar 09 LR - Laboratory Results

Purpose: To record laboratory results for tests done during screening and follow-up in the NORIG trial. When: Required at screening (s1 or s2) and follow-up visit f12. Administered by: Study Physician and Clinical Coordinator. Instructions: Laboratory test results may be obtained from chart review. Complete tests as needed (repeat test if results are not within the required time window). The window for each test is specified next to the date of blood draw. Use a calculator if you need to convert units to match the units specified on this form. Please note that the units 103 cells/mL, 1000 cells/mL, and 109/L are equivalent. Call the DCC if you have a question about conver- sion or how to record a value. If is reached in item 34, the patient is NOT eligible and cannot be randomized in the NORIG trial. The form should not be keyed to the data system. Staple the laboratory report to the back of this form. If your laboratory reports are reported electronically, print a copy of the results and staple the report to the back of this form.

A. Center, patient, and visit identification 12. White blood cell count:

1. Center ID: • 103 cells/ μL or 109 cells/L

2. Patient ID: 13. Platelet count: , cells/ μL 3. Patient code: C. Metabolic panel Required at screening and f12 4. Date of visit (date form was initiated): 14. Date of blood draw for metabolic panel:

day mon year day mon year Date must be within 16 weeks of registration for 5. Visit code: the NORIG trial, or in the time window for the 12 week follow-up visit. Check the patient’s NORIG visit window schedule. 6. Form & revision: l r 1 15. Carbon dioxide: • 7. Study: NORIG 2 mEq/L 16. Chloride: B. Hematology mEq/L Required at screening and f12 17. Sodium: 8. Date of blood draw for complete blood mEq/L count: 18. Potassium: • day mon year mEq/L Date must be within 16 weeks of registration, or in the time window for the 12 week follow-up visit. 19. Glucose: Check the patient’s NORIG visit window schedule. mg/dL • 9. Hemoglobin: • 20. Calcium: mg/dL g/dL • 10. Hematocrit: • 21. Magnesium: mg/dL %

11. Red blood cell count: 22. Blood urea nitrogen (BUN): mg/dL • • 106 cells/ μL (million cells/ μL) 23. Creatinine: mg/dL

Form LR NORIG Revision 1 (19 Mar 09) LR - Laboratory Results 1 of 2 Patient ID:

D. Hepatic panel F. Eligibility check Required at screening and f12 Required at s1 or s2 visit

24. Date of blood draw for hepatic panel: 34. Are all screening laboratory results completed on this form: Yes No day mon year ( ) ( * ) Date must be within 16 weeks of registration for 1 2 the NORIG trial, or in the time window for the 12 week follow-up visit. Check the patient’s NORIG visit window schedule. * The patient is ineligible and cannot be randomized into NORIG until all required screening laboratory results are obtained. 25. Bilirubin (total): • mg/dL G. Administrative information

26. Aspartate aminotransferase (AST): 35. Study Physician PIN:

U/L 36. Study Physician signature:

27. Alanine aminotransferase (ALT):

U/L 37. Clinical Coordinator PIN:

28. Alkaline phosphatase: 38. Clinical Coordinator signature: U/L

29. Albumin: • g/dL 39. Date form reviewed:

• 30. Total protein: day mon year g/dL E. Thyroid stimulating hormone

31. Is this a screening visit: Yes No ( 1) ( 2) 35.

32. Date of blood draw for TSH level:

day mon year Date must be within 16 weeks of registration for the NORIG trial (required at s1 or s2 visit).

33. Thyroid stimulating hormone: • μIU/mL or mIU/L

Form LR NORIG Revision 1 (19 Mar 09) LR - Laboratory Results 2 of 2 Keyed: ( )

NORIG3PE - Physical ExaminationPE119 Mar 09 PE - Physical Examination

Purpose: Record physical exam findings in the NORIG trial. When: Screening visit s1 or s2 and follow-up visits f03, f06, f09, f12, f15, and f18. Administered by: Study Physician and Clinical Coordinator. Respondent: Patient. Instructions: Standardized procedures for height, weight, waist and hip measurements are found in NORIG SOP I, sections 6.8-6.11. In brief: Height, weight, waist and hip circumferences should all be measured with the patient standing and wearing light clothing. Shoes should be removed for height and weight measures. Measure the waist around the abdomen horizontally at the midpoint between the highest point of the iliac crest and the lowest part of the costal margin in the mid axillary line. Measure the hips at the fullest part. If a is checked for item 31, further review is necessary. If the physician agrees with the diagnosis, the patient is ineligible for the NORIG trial. If is checked for an item, the patient is ineligible and cannot be randomized in the NORIG trial. The form should not be keyed to the data system, but the form should be retained in the study file for patients who started screening, but were found to be ineligible. Note: ECG is required at screening visit s1 and follow-up visits f09 and f12.

Screening visit instructions: The ECG is required during screening. If a is checked for item 31 ECG findings, further review and confirmation is necessary. If the physician agrees with the diagnosis, the patient is ineligible for the NORIG trial. If the pregnancy test result is positive in item 25, the patient is ineligible and cannot be randomized in the NORIG trial. The form should not be keyed to the data system, but the form should be retained in the study file for patients who started screening, but were found to be ineligible for NORIG.

Follow-up visit instructions: The ECG is required during at follow-up visits f09 and f12. If a is checked for item 31 ECG findings, the Interim Event (IE) form should be completed. If the pregnancy test result is positive in item 25, complete the IE form.

A. Center, patient, and visit identification B. Vital status

1. Center ID: 8. Temperature (oral)

• 2. Patient ID: a. Degrees:

b. Scale: 3. Patient code: Fahrenheit ( 1) Centigrade ( ) 4. Visit date: 2

day mon year 9. Blood pressure

5. Visit code: a. Systolic: mmHg

6. Form & revision: p e 1 b. Diastolic: mmHg

7. Study: NORIG 2 10. Resting radial pulse: beats/minute

11. Respiratory rate: breaths/minute

Form PE NORIG Revision 1 (19 Mar 09) PE - Physical Examination 1 of 3 Patient ID:

C. Measurements 18. Abdomen: Normal ( ) 12. Height (shoes off) 1 a. Height: • 20. Abnormal ( 2) b. Units:

Inches ( 1) 19. Abdomen abnormality (check all that apply) Centimeters ( 2) a. Distention: ( 1) 13. Weight (shoes off) b. Tympany: ( 1) a. Weight: • c. Succussion splash: ( 1) b. Units: d. Tenderness: ( 1) Pounds ( 1) e. Organomegaly: ( 1) Kilograms ( 2) f. Other (specify): ( 1) 14. Waist (standing, at midpoint between highest point of iliac crest and lowest part of costal margin) specify a. Circumference: •

b. Units: specify

Inches ( 1)

Centimeters ( 2) 20. Liver and spleen: Normal ( ) 15. Hip circumference (standing, at fullest part of the 1 hips) 21. • a. Circumference: Abnormal ( 2) b. Units: specify Inches ( 1)

Centimeters ( 2) specify D. Examination findings

16. Chest and lungs: 21. Nervous system: Not performed ( ) Normal ( 1) 0 17. 22. Normal ( ) Abnormal ( 2) 1 22.

specify Abnormal ( 2)

17. Heart: specify

Normal ( 1) 18. specify

Abnormal ( 2)

specify

Form PE NORIG Revision 1 (19 Mar 09) PE - Physical Examination 2 of 3 Patient ID:

22. Other abnormalities noted: 31. Characterize the findings from the resting Yes No ECG. (Use flashcard #7 to review ECG; check ( 1) ( 2) only one): 23. ECG findings are compatible with continued participation in the NORIG

specify other abnormalities trial without further cardiac evaluation ( 1) ECG findings include abnormalities that may be incompatible with participation specify other abnormalities in the NORIG trial ( * 2) E. Pregnancy test (Required at s1 or s2 and at study visits f03, f06, f09, f12, and f15 if applicable) * During follow-up, complete the IE form.

23. Is pregnancy test applicable: Yes No G. Administrative information ( 1) ( 2) 26. 32. Study Physician PIN:

24. Date of pregnancy test: 33. Study Physician signature:

day mon year (Date must be within the visit window)

25. Pregnancy test result 34. Clinical Coordinator PIN: Positive ( * ) 1 35. Clinical Coordinator signature:

Negative ( 2) If pregnancy test is positive during screening, patient is ineligible. If during follow-up, complete the IE form. 36. Date form reviewed:

F. Resting Electrocardiogram day mon year (Required at visits s1 or s2, f09 and f12 only)

26. Is this visit s1 or s2, f09 or f12: Yes No ( 1) ( 2) 32.

27. Date electrocardiogram obtained:

day mon year

28. Record the QTc interval: milliseconds

29. Is the QTc greater than 450 milliseconds: Yes No ( 1) ( 2)

30. Does the patient have a pacemaker: Yes No ( 1) ( 2)

Form PE NORIG Revision 1 (19 Mar 09) PE - Physical Examination 3 of 3 Keyed: ( )

NORIG3PE - Physical ExaminationPE219 Aug 09 PE - Physical Examination

Purpose: Record physical exam findings in the NORIG trial. When: Screening visit s1 or s2 and follow-up visits f09, f12, and f15. Administered by: Study Physician and Clinical Coordinator. Respondent: Patient. Instructions: Standardized procedures for height, weight, waist and hip measurements are found in NORIG SOP I, sections 6.8-6.11. In brief: Height, weight, waist and hip circumferences should all be measured with the patient standing and wearing light clothing. Shoes should be removed for height and weight measures. Measure the waist around the abdomen horizontally at the midpoint between the highest point of the iliac crest and the lowest part of the costal margin in the mid axillary line. Measure the hips at the fullest part. If a is checked for item 31, further review is necessary. If the physician agrees with the diagnosis, the patient is ineligible for the NORIG trial. If is checked for an item, the patient is ineligible and cannot be randomized in the NORIG trial. The form should not be keyed to the data system, but the form should be retained in the study file for patients who started screening, but were found to be ineligible. Note: ECG is required at screening visit s1 and follow-up visits f09 and f12.

Follow-up visit instructions: The ECG is required at follow-up visits f09 and f12. If a is checked for item 31 ECG findings, the Interim Event (IE) form should be completed. If the pregnancy test result is positive in item 25, complete the IE form.

A. Center, patient, and visit identification B. Vital status

1. Center ID: 8. Temperature (oral)

· 2. Patient ID: a. Degrees:

b. Scale: 3. Patient code: Fahrenheit ( 1) Centigrade ( ) 4. Visit date: 2

day mon year 9. Blood pressure

5. Visit code: a. Systolic: mmHg

6. Form & revision: p e 2 b. Diastolic: mmHg

7. Study: NORIG 2 10. Resting radial pulse: beats/minute

11. Respiratory rate: breaths/minute

Form PE NORIG Revision 2 (19 Aug 09) PE - Physical Examination 1 of 3 Patient ID:

C. Measurements 18. Abdomen: Normal 12. Height (shoes off) ( 1) a. Height: · 20. Abnormal ( 2) b. Units:

Inches ( 1) 19. Abdomen abnormality (check all that apply) Centimeters ( 2) a. Distention: ( 1) 13. Weight (shoes off) b. Tympany: ( 1) a. Weight: · c. Succussion splash: ( 1) b. Units: d. Tenderness: ( 1) Pounds ( 1) e. Organomegaly: ( 1) Kilograms ( 2) f. Other (specify): ( 1) 14. Waist (standing, at midpoint between highest point of iliac crest and lowest part of costal margin) specify a. Circumference: · b. Units: specify

Inches ( 1) 20. Liver and spleen: Centimeters ( 2) Normal ( ) 15. Hip circumference (standing, at fullest part of the 1 hips) 21. Abnormal a. Circumference: · ( 2) b. Units: specify Inches ( 1)

Centimeters ( 2) specify D. Examination findings 21. Nervous system: 16. Chest and lungs: Not performed ( 0) Normal ( 1) 22. 17. Normal ( 1) Abnormal ( 2) 22.

Abnormal ( 2) specify

17. Heart: specify Normal ( ) 1 specify 18. Abnormal ( 2) 22. Other abnormalities noted: Yes No specify ( 1) ( 2) 23. specify specify other abnormalities

specify other abnormalities

Form PE NORIG Revision 2 (19 Aug 09) PE - Physical Examination 2 of 3 Patient ID:

E. Pregnancy test 31. Characterize the findings from the resting (Required at s1 or s2 and at study visits f09, f12, ECG. (Use flashcard #7 to review ECG; check and f15 if applicable) only one): ECG findings are compatible with 23. Is pregnancy test applicable: Yes No continued participation in the NORIG ( 1) ( 2) trial without further cardiac evaluation ( 1) 26. ECG findings include abnormalities that may be incompatible with participation 24. Date of pregnancy test: in the NORIG trial ( * ) 2 day mon year (Date must be within the visit window) * Consult a cardiologist to further evaluate the ECG findings. During follow-up, complete the IE 25. Pregnancy test result form.

Positive ( * 1) G. Administrative information

Negative ( 2) 32. Study Physician PIN: If pregnancy test is positive during screening, patient is ineligible. If during follow-up, complete the IE form. 33. Study Physician signature:

F. Resting Electrocardiogram (Required at visits s1 or s2, f09 and f12 only) 34. Clinical Coordinator PIN: 26. Is this visit s1 or s2, f09 or f12: Yes No ( 1) ( 2) 35. Clinical Coordinator signature: 32.

27. Date electrocardiogram obtained:

day mon year 36. Date form reviewed:

28. Record the QTc interval: day mon year milliseconds

29. Is the QTc greater than 450 milliseconds: Yes No ( 1) ( 2)

30. Does the patient have a pacemaker: Yes No ( 1) ( 2)

Form PE NORIG Revision 2 (19 Aug 09) PE - Physical Examination 3 of 3 Keyed: ( ) NORIG PQ – Patient Health Questionnaire

Purpose: To obtain the patient's views of his/her health in the NORIG trial. When: At screening visit s1 or s2 and follow-up visits f09 and f15. Administered by: Self-administered, but Clinical Coordinator must be available at visits to answer questions and to review completed form. Respondent: Patient. Instructions: The Clinical Coordinator should complete section A and attach a MACO label to page 2 before giving the questionnaire to the patient for completion. The Clinical Coordinator should review the completed form questionnaire for missing responses and resolve any problems before the patient leaves the clinical center. Page 1 should be reattached to page 2, and the Clinical Coordinator should complete section B.

A. Center, patient, and visit identification B. Administrative information (To be completed by clinical center staff after 1. Center ID: questionnaire is completed)

2. Patient ID: 8. Clinical Coordinator

3. Patient code: a. PIN:

4. Date of visit (date patient completed the form): b. Signature:

- - day mon year 9. Date form reviewed: 5. Visit code: - - 6. Form & revision: p q 1 day mon year

7. Study: NORIG 2

Form PQ PQ - Patient Health Questionnaire NORIG Revision 1 (30 Mar 09) 1 of 2 Affix label here

PQ - Patient Health Questionnaire Patient ID:

A 15-Item Somatic Symptom Severity Scale Pt code:

Visit code: (Items 1-9 are reserved for clinic use)

10. During the past 4 weeks, how much have you been bothered by any of the following problems? Not bothered Bothered Bothered at all a little a lot

a. Stomach pain ( 1) ( 2) ( 3)

b. Back pain ( 1) ( 2) ( 3)

c. Pain in your arms, legs, or joints ( 1) ( 2) ( 3) (knees, hips, etc)

d. Menstrual cramps or other problems ( 1) ( 2) ( 3) with your periods [Women only; record “n” if male]

e. Headaches ( 1) ( 2) ( 3)

f. Chest pain ( 1) ( 2) ( 3)

g. Dizziness ( 1) ( 2) ( 3)

h. Fainting spells ( 1) ( 2) ( 3)

i. Feeling your heart pound or race ( 1) ( 2) ( 3)

j. Shortness of breath ( 1) ( 2) ( 3)

k. Pain or problems during sexual ( 1) ( 2) ( 3) intercourse

l. Constipation, loose bowels, or ( 1) ( 2) ( 3) diarrhea

m. Nausea, gas, or indigestion ( 1) ( 2) ( 3)

n. Feeling tired or having low energy ( 1) ( 2) ( 3)

o. Trouble sleeping ( 1) ( 2) ( 3)

Thank you. Please return this questionnaire to the Clinical Coordinator.

Form PQ PQ - Patient Health Questionnaire NORIG Revision 1 (30 Mar 09) 2 of 2 Keyed: ( )

NORIG3RG - RegistrationRG127 Jan 09 RG - Registration

Purpose: To register patients as candidates for randomization in Nortriptyline for Idiopathic Gastroparesis (NORIG) Trial and to assign a patient ID number. This is the first form completed for a patient. The Registration Form must be the first form keyed, before any other forms. When: At first screening visit s1. Administered by: Clinical Coordinator. Respondent: Patient. Instructions: Use Flash Cards as instructed. If a condition was checked in Sections B or C, the patient is ineligible and a patient ID should not be assigned and the form should not be keyed. If the patient was previously registered in a GpCRC study, a new ID number should not be assigned.

A. Center, patient and visit identification 11. Age at last birthday: years 1. Center ID: 12. Is the patient at least 25 and less than 66 years old: 2. Patient ID: Yes No ( 1) ( 2) 3. Patient code

4. Visit date: 13. Gender:

Male ( 1) day mon year Female ( 2) 5. Visit code: s 1 14. Ethnic category (show the patient Flash Card #1 and ask to pick the category that describes him/her 6. Form & revision: r g 1 best; check only one):

Hispanic or Latino ( 1)

7. Study: NORIG 2 Not Hispanic, not Latino ( 2)

B. Consent 15. Racial category (show the patient Flash Card #2 and ask him/her to pick the category or categories 8. Has the patient signed the NORIG that describe him/her best; check all that apply)

informed consent statement: a. American Indian or Alaska Native: ( 1) Yes No ( 1) ( 2) b. Asian: ( 1)

c. Black or African American: ( 1) Patient must sign the consent prior to continuing d. Native Hawaiian or other Pacific with screening. Islander: ( 1)

e. White: ( 1) 9. Has the clinical coordinator or study f. physician signed the consent form: Patient refused: ( 1) Yes No ( 1) ( 2)

C. Information about patient

10. Date of birth:

day month year Record 4-digit year for date of birth.

Form RG NORIG Revision 1 (27 Jan 09) RG - Registration 1 of 3 Patient ID:

16. Highest educational level achieved by D. Source of patient patient (show the patient Flash Card #3 and ask (Clinic staff should pick the best description of the him/her to pick the category that describes him/her source of patient) best; check only one): 20. Source of patient (check only one): Never attended school ( 0) Current patient of GpCRC investigator: ( ) Did not complete high school ( 1) 01 Diabetes or endocrine clinic ( ) Completed high school ( 2) 02

Some college or post high school GI clinic ( 03) education or training ( 3) Internal medicine clinic ( 04) Bachelor’s degree or higher ( 4) Neurology clinic ( 05) Nutrition clinic ( ) 17. Which of the following categories best 06 characterizes the patient’s occupational Psychiatry clinic ( 07)

history (show patient Flash Card #4 and ask Self referral ( 08) him/her to pick the category that describes him/her Surgery clinic best; check only one): ( 09) Other, (specify): ( 10) Never employed ( 0)

Laborer ( 1) specify Clerical ( 2)

Professional ( 3) E. Previous registration in a GpCRC study

Homemaker ( 4) Other, (specify): ( ) 21. Has the patient previously been 5 registered in the Gastroparesis Registry: Yes No specify ( 1) ( 2) 24. 18. Marital status of the patient (show patient Flash Card #5 and ask to pick the category that describes 22. ID number previously assigned to patient (record him/her best; check only one): patient ID in item 2):

Single, never married ( 1) Married or living in marriage-like 23. Code previously assigned to patient (record patient code in item 3): relationship ( 2)

Separated, divorced, or annulled ( 3)

Widowed ( 4) 25.

19. Combined annual income before taxes of F. ID assignment all members of patient’s household (show the pa- (If a STOP condition was checked in sections B or tient Flash Card #6 and ask to pick the category C, the patient is ineligible and a patient ID should that describes his/her combined household income not be assigned. If the patient was previously best; check only one): registered in a GpCRC study, a new ID number should not be assigned.) Less than $15,000 ( 1) 24. Place ID label below and record patient $15,000 - $29,999 ( 2) ID in item 2 and patient code in item 3. $30,000 - $49,999 ( 3)

$50,000 or more ( 4) CCCC ####, zzz

Form RG NORIG Revision 1 (27 Jan 09) RG - Registration 2 of 3 Patient ID:

G. Administrative information

25. Clinical Coordinator PIN:

26. Clinical Coordinator signature:

27. Date form reviewed:

day mon year

Form RG NORIG Revision 1 (27 Jan 09) RG - Registration 3 of 3 Keyed: ( )

NORIG3RG - RegistrationRG219 Aug 09 RG - Registration

A. Center, patient and visit identification 11. Age at last birthday: years 1. Center ID: 12. Is the patient at least 21 and less than 66 years old: 2. Patient ID: Yes No ( 1) ( 2) 3. Patient code

4. Visit date: 13. Gender:

Male ( 1) day mon year Female ( 2) 5. Visit code: s 1 14. Ethnic category (show the patient Flash Card #1 and ask to pick the category that describes him/her 6. Form & revision: r g 2 best; check only one):

Hispanic or Latino ( 1) NORIG 2 7. Study: Not Hispanic, not Latino ( 2)

B. Consent 15. Racial category (show the patient Flash Card #2 and ask him/her to pick the category or categories 8. Has the patient signed the NORIG that describe him/her best; check all that apply) informed consent statement: a. American Indian or Alaska Native: ( ) Yes No 1 ( ) ( ) 1 2 b. Asian: ( 1)

c. Black or African American: ( 1) Patient must sign the consent prior to continuing d. Native Hawaiian or other Pacific with screening. Islander: ( 1) e. White: ( ) 9. Has the clinical coordinator or study 1 physician signed the consent form: f. Patient refused: ( 1) Yes No ( ) ( ) 1 2 16. Highest educational level achieved by patient (show the patient Flash Card #3 and ask him/her to pick the category that describes him/her C. Information about patient best; check only one): Never attended school ( ) 10. Date of birth: 0 Did not complete high school ( 1)

Completed high school ( 2) day month year Some college or post high school Record 4-digit year for date of birth. education or training ( 3)

Bachelor’s degree or higher ( 4) Form RG NORIG Revision 2 (19 Aug 09) RG - Registration 1 of 3 Patient

17. Which of the following categories best D. Source of patient characterizes the patient’s occupational (Clinic staff should pick the best description of the history (show patient Flash Card #4 and ask source of patient) him/her to pick the category that describes him/her best; check only one): 20. Source of patient (check only one): Never employed ( 0) Current patient of GpCRC investigator: ( 01) Laborer ( 1) Diabetes or endocrine clinic ( 02) Clerical ( 2) GI clinic ( 03) Professional ( 3) Internal medicine clinic ( 04) Homemaker ( 4) Neurology clinic ( 05) Other, (specify): ( 5) Nutrition clinic ( 06)

Psychiatry clinic ( 07) specify Self referral ( 08) Surgery clinic ( ) 18. Marital status of the patient (show patient Flash 09 Card #5 and ask to pick the category that describes Other, (specify): ( 10) him/her best; check only one): Single, never married ( ) 1 specify Married or living in marriage-like

relationship ( 2) E. Previous registration in a GpCRC study Separated, divorced, or annulled ( ) 3 21. Has the patient previously been Widowed ( 4) registered in the Gastroparesis Registry: Yes No 19. Combined annual income before taxes of ( 1) ( 2) all members of patient’s household (show the pa- 24. tient Flash Card #6 and ask to pick the category that describes his/her combined household income best; check only one): 22. ID number previously assigned to patient (record patient ID in item 2): Less than $15,000 ( 1) $15,000 - $29,999 ( ) 2 23. Code previously assigned to patient (record pa- $30,000 - $49,999 ( 3) tient code in item 3):

$50,000 or more ( 4) 25. F. ID assignment (If a STOP condition was checked in sections B or C, the patient is ineligible and a patient ID should not be assigned. If the patient was previously registered in a GpCRC study, a new ID number should not be assigned.)

24. Place ID label below and record patient ID in item 2 and patient code in item 3.

CCCC ####, zzz

Form RG NORIG Revision 2 (19 Aug 09) RG - Registration 2 of 3 Patient

G. Administrative information

25. Clinical Coordinator PIN:

26. Clinical Coordinator signature:

27. Date form reviewed:

day mon year

Form RG NORIG Revision 2 (19 Aug 09) RG - Registration 3 of 3 Keyed: ( )

NORIG4RZ - RandomizationRZ119 Feb 09 RZ - Randomization

Purpose: • Check eligibility for the NORIG trial. • Record reasons for ineligibility for patients found to be ineligible. When: After completion of screening, randomization visit (rz). Administered by: Study Physician and Clinical Coordinator. Respondent: Patient and Clinical Coordinator. Instructions: This form (RZ) must be completed and keyed for all patients registered into formal screening for the NORIG trial earlier as indicated by keying the Registration Form (RG) into the data system. Even if an is checked for any item on Form RZ (i.e., patient cannot be randomized into the NORIG trial), all items on Form RZ must be completed, which may require writing "m" (missing) next to items relating to procedures that were not done once the patient was found to be ineligible.

A. Center, patient, and visit identification 9. Gastric emptying scintigraphy: a. Date of most recent gastric emptying 1. Center ID: scintigraphy:

2. Patient ID: day mon year b. Was patient able to complete gastric 3. Patient code: emptying scintigraphy: Yes No ( 1) ( 2) 4. Visit date (date this form is initiated):

day mon year c. Did patient have abnormal 2-hr or 4-hr values on gastric emptying 5. Visit code: r z scintigraphy: Yes No ( 1) ( 2) 6. Form & revision: r z 1

d. Was 2-hour value greater than 60%: 7. Study: NORIG 2 Yes No ( 1) ( 2) B. Check on criteria for inclusion in the NORIG e. Was 4-hour value greater than 10%: trial Yes No ( 1) ( 2) 8. Does the patient report symptoms of gastroparesis of at least 6 months f. Did patient have a Gastroparesis duration (do not have to be contiguous) Cardinal Symptom Index (GCSI) score with varying degrees of nausea, of 21 or greater as calculated on vomiting, abdominal pain, early satiety, PAGI-SYM (GD form): Yes No or post-prandial fullness: ( 1) ( 2) Yes No ( 1) ( 2)

Form RZ NORIG Revision 1 (19 Feb 09) RZ - Randomization 1 of 4 Patient ID:

C. Exclusion 11. Does the patient have any of the following medication-related exclusions: 10. Do any of the patient’s assessments show a. Hypersensitivity or allergy to any evidence of these exclusions: tricyclic antidepressant drug: a. Gastroparesis from diabetic, Yes No post-surgical, or other etiologies ( 1) ( 2) including fundoplication: Yes No ( 1) ( 2) b. Clear history of a failed trial of nortriptyline use for gastroparetic b. Glaucoma: Yes No symptoms: Yes No ( 1) ( 2) ( 1) ( 2)

h. Any active disorder other than f. Use of strongly anticholinergic gastroparesis which could explain medications: Yes No symptoms in the opinion of the ( 1) ( 2) investigator: Yes No ( 1) ( 2) 13. Is there any other condition or issue that, in the opinion of the investigator, would i. Symptoms of primary depression or interfere with the patient’s adherence or suicidal ideation: hinder completion of study requirements: Yes No Yes No ( 1) ( 2) ( * 1) ( 2)

*If Yes, specify reason:

specify reason

Form RZ NORIG Revision 1 (19 Feb 09) RZ - Randomization 2 of 4 Patient ID:

D. Eligibility check on day of randomization 20. Were any STOP’s or ineligible conditions other than “missing Form 14. Was an ineligibility condition checked or RZ” identified by the Randomization an eligibility not ascertained in items Task: 8-13: Yes No Yes ( ) ( ) ( * ) 1 1 2 22.

22. No ( 2) *Verify all screening visit forms RG, BH, BC, BD, Task not run because patient is known BP, BT, CG, EG, GD, GE, GS, LR, PE, PI, PQ, to be ineligible ( * 3) QF, SE, ST have been keyed into the data system by running the Randomization Task for NORIG on 22. your clinic data system. * You can skip running the Randomization Task if you already know that the patient is ineligible; you must run the task to randomize the patient. 15. Is the patient male: Yes No ( 1) ( 2) 21. Does the patient still consent to 20. participate (you should ask the patient to orally affirm his/her consent): 16. Is the patient of childbearing potential: Yes No Yes No ( * 1) ( 2) ( ) ( ) 1 2 23. 19. * Go to item 23 and complete this form. Then key this form and run the Randomization Task on your 17. Was the patient’s screening pregnancy clinic data system to randomize the patient. test positive: Yes No E. Reasons for ineligibility for ineligible patients ( *1) ( 2) NOTE: Complete this section for ineligible patients only and key the form. The form must be *Go to item 22. keyed to document the reasons for ineligibility for NORIG.

18. Is the patient currently breast feeding: 22. Reason for ineligibility (check all that apply) Yes No ( *1) ( 2) a. Reason covered in items 8-13 or 17-19: ( 1) b. Tests are outside time window and

*Go to item 22. clinic chose not to repeat tests: ( 1) c. Other reason not covered on this form 19. In the judgment of the Study Physician (specify): ( 1) and Clinical Coordinator, is the patient (female of childbearing potential) willing specify reason to use effective birth control methods to avoid pregnancy during the NORIG trial (check "yes" if patient is not of childbearing potential): Yes No ( 1) ( *2)

Form RZ NORIG Revision 1 (19 Feb 09) RZ - Randomization 3 of 4 Patient ID:

F. Administrative information

23. Study Physician PIN:

24. Study Physician signature:

25. Clinical Coordinator PIN:

26. Clinical Coordinator signature:

27. Date form reviewed:

day mon year

Form RZ NORIG Revision 1 (19 Feb 09) RZ - Randomization 4 of 4 Keyed: ( )

NORIG4RZ - RandomizationRZ219 Aug 09 RZ - Randomization

Purpose: · Check eligibility for the NORIG trial. · Record reasons for ineligibility for patients found to be ineligible. When: After completion of screening, randomization visit (rz). Administered by: Study Physician and Clinical Coordinator. Respondent: Patient and Clinical Coordinator. Instructions: This form (RZ) must be completed and keyed for all patients registered into formal screening for the NORIG trial earlier as indicated by keying the Registration Form (RG) into the data system. Even if an is checked for any item on Form RZ (i.e., patient cannot be randomized into the NORIG trial), all items on Form RZ must be completed, which may require writing "m" (missing) next to items relating to procedures that were not done once the patient was found to be ineligible.

A. Center, patient, and visit identification 9. Gastric emptying scintigraphy: a. Date of most recent gastric emptying 1. Center ID: scintigraphy:

2. Patient ID: day mon year b. Was patient able to complete gastric 3. Patient code: emptying scintigraphy: Yes No ( 1) ( 2) 4. Visit date (date this form is initiated):

day mon year c. Did patient have abnormal 2-hr or 4-hr values on gastric emptying 5. Visit code: r z scintigraphy: Yes No ( 1) ( 2) 6. Form & revision: r z 2

NORIG 2 d. Was 2-hour value greater than 60%: 7. Study: Yes No ( 1) ( 2) B. Check on criteria for inclusion in the NORIG e. Was 4-hour value greater than 10%: trial Yes No ( 1) ( 2) 8. Does the patient report symptoms of gastroparesis of at least 6 months f. Did patient have a Gastroparesis duration (do not have to be contiguous) Cardinal Symptom Index (GCSI) score with varying degrees of nausea, of 21 or greater as calculated on vomiting, abdominal pain, early satiety, PAGI-SYM (GD form): Yes No or post-prandial fullness: ( 1) ( 2) Yes No ( 1) ( 2)

Form RZ NORIG Revision 2 (19 Aug 09) RZ - Randomization 1 of 4 Patient ID:

c. Recent myocardial infarction (within 1 year): Yes No 12. Has the patient used any of the following ( 1) ( 2) medications in the past 6 weeks: a. Use of narcotics more than 3 days per week including fentanyl d. History of significant cardiac patches: Yes No arrhythmias and/or prolonged QTc: ( 1) ( 2) Yes No ( 1) ( 2) b. Use of calcium channel blockers: Yes No e. History of seizures: ( 1) ( 2) Yes No ( 1) ( 2) c. Use of erythromycin: Yes No ( ) ( ) f. Hypersensitivity or allergy to wheat, 1 2 algae or egg: Yes No d. Use of a monoamine oxidase ( 1) ( 2) inhibitor (MAOI): Yes No ( 1) ( 2) g. Use of a G-tube, J-tube, central catheter for nutrition, or a gastric e. Use of any tricyclic electrical stimulator (central catheter antidepressant: Yes No for medications is allowed): ( 1) ( 2) Yes No ( 1) ( 2) f. Use of strongly anticholinergic medications: Yes No h. Any active disorder other than ( 1) ( 2) gastroparesis which could explain symptoms in the opinion of the investigator: Yes No 13. Is there any other condition or issue that, ( 1) ( 2) in the opinion of the investigator, would interfere with the patient’s adherence or hinder completion of study requirements: i. Symptoms of primary depression or Yes No suicidal ideation: ( * 1) ( 2) Yes No ( 1) ( 2) *If Yes, specify reason:

specify reason

Form RZ NORIG Revision 2 (19 Aug 09) RZ - Randomization 2 of 4 Patient ID:

D. Eligibility check on day of randomization 20. Were any STOP’s or ineligible conditions other than ‘‘missing Form 14. Was an ineligibility condition checked or RZ’’ identified by the Randomization an eligibility not ascertained in items Task: 8-13: Yes No Yes ( 1) ( ) ( * ) 1 2 22.

18. Is the patient currently breast feeding: 22. Reason for ineligibility (check all that apply) Yes No ( *1) ( 2) a. Reason covered in items 8-13 or 17-19: ( 1) b. Tests are outside time window and *Go to item 22. clinic chose not to repeat tests: ( 1) c. Other reason not covered on this form 19. In the judgment of the Study Physician (specify): ( 1) and Clinical Coordinator, is the patient (female of childbearing potential) willing specify reason to use effective birth control methods to avoid pregnancy during the NORIG trial (check "yes" if patient is not of childbearing potential): Yes No ( 1) ( *2)

Form RZ NORIG Revision 2 (19 Aug 09) RZ - Randomization 3 of 4 Patient ID:

F. Administrative information

23. Study Physician PIN:

24. Study Physician signature:

25. Clinical Coordinator PIN:

26. Clinical Coordinator signature:

27. Date form reviewed:

day mon year

Form RZ NORIG Revision 2 (19 Aug 09) RZ - Randomization 4 of 4 Keyed: ( )

NORIG4RZ - RandomizationRZ311 Nov 10 RZ - Randomization

A. Center, patient, and visit identification 9. Gastric emptying scintigraphy: a. Date of most recent gastric emptying 1. Center ID: scintigraphy:

2. Patient ID: day mon year b. Was patient able to complete gastric 3. Patient code: emptying scintigraphy: Yes No ( 1) ( 2) 4. Visit date (date this form is initiated):

day mon year c. Did patient have abnormal 2-hr or 4-hr values on gastric emptying 5. Visit code: r z scintigraphy: Yes No ( 1) ( 2) 6. Form & revision: r z 3 d. Was 2-hour value greater than 60%: 7. Study: NORIG 2 Yes No ( 1) ( 2) B. Check on criteria for inclusion in the NORIG e. Was 4-hour value greater than 10%: trial Yes No ( 1) ( 2) 8. Does the patient report symptoms of gastroparesis of at least 6 months f. Did patient have a Gastroparesis duration (do not have to be contiguous) Cardinal Symptom Index (GCSI) score with varying degrees of nausea, of 21 or greater as calculated on PAGI-SYM (GD form): vomiting, abdominal pain, early satiety, Yes No or post-prandial fullness: ( 1) ( 2) Yes No ( 1) ( 2)

Form RZ NORIG Revision 3 (11 Nov 10) RZ - Randomization 1 of 4 Patient ID:

c. Recent myocardial infarction (within 1 year): Yes No 12. Has the patient used any of the following ( 1) ( 2) medications in the past 6 weeks: a. Use of narcotics more than 3 days per d. History of significant cardiac week including fentanyl patches: Yes No arrhythmias and/or prolonged QTc: ( ) ( ) Yes No 1 2 ( 1) ( 2) b. Use of calcium channel blockers: Yes No e. History of seizures: ( ) ( ) Yes No 1 2 ( 1) ( 2) c. Use of erythromycin: Yes No ( ) ( ) f. Use of a G-tube, J-tube, central 1 2 catheter for nutrition, or a gastric electrical stimulator (central catheter d. Use of a monoamine oxidase for medications is allowed): inhibitor (MAOI): Yes No Yes No ( 1) ( 2) ( 1) ( 2)

e. Use of any tricyclic g. Any active disorder other than antidepressant: Yes No gastroparesis which could explain ( 1) ( 2) symptoms in the opinion of the investigator: Yes No f. Use of strongly anticholinergic ( 1) ( 2) medications: Yes No ( 1) ( 2) h. Symptoms of primary depression or suicidal ideation: Yes No 13. Is there any other condition or issue that, in the opinion of the investigator, would ( 1) ( 2) interfere with the patient’s adherence or hinder completion of study requirements: Yes No ( * 1) ( 2)

*If Yes, specify reason:

specify reason

Form RZ NORIG Revision 3 (11 Nov 10) RZ - Randomization 2 of 4 Patient ID:

D. Eligibility check on day of randomization 20. Were any STOP’s or ineligible conditions other than “missing Form RZ” 14. Was an ineligibility condition checked or identified by the Randomization Task: an eligibility not ascertained in items Yes ( ) 8-13: 1 Yes No 22. ( 1) ( *2) No ( 2) 22. Task not run because patient is known

*Verify all screening visit forms RG, BH, BC, BD, to be ineligible ( * 3) BP, CG, EG, GD, GE, GS, LR, PE, PI, PQ, QF, 22. SE, ST have been keyed into the data system by running the Randomization Task for NORIG on * You can skip running the Randomization Task if your clinic data system. you already know that the patient is ineligible; you must run the task to randomize the patient.

15. Is the patient male: Yes No 21. Does the patient still consent to ( 1) ( 2) participate (you should ask the patient to orally 20. affirm his/her consent): Yes No 16. Is the patient of childbearing potential: ( * 1) ( 2) Yes No 23. ( 1) ( 2) 19. * Go to item 23 and complete this form. Then key this form and run the Randomization Task on your clinic data system to randomize the patient. 17. Was the patient’s screening pregnancy test positive: E. Reasons for ineligibility for ineligible patients Yes No ( * ) ( ) NOTE: Complete this section for ineligible pa- 1 2 tients only and key the form. The form must be keyed to document the reasons for ineligibility for *Go to item 22. NORIG. 22. Reason for ineligibility (check all that apply) 18. Is the patient currently breast feeding: Yes No a. Reason covered in items 8-13 or 17-19: ( 1) ( *1) ( 2) b. Tests are outside time window and

clinic chose not to repeat tests: ( 1) *Go to item 22. c. Other reason not covered on this form (specify): ( 1) 19. In the judgment of the Study Physician and Clinical Coordinator, is the patient specify reason (female of childbearing potential) willing to use effective birth control methods to avoid pregnancy during the NORIG trial (check "yes" if patient is not of childbearing potential): Yes No ( 1) ( *2)

Form RZ NORIG Revision 3 (11 Nov 10) RZ - Randomization 3 of 4 Patient ID:

F. Administrative information

23. Study Physician PIN:

24. Study Physician signature:

25. Clinical Coordinator PIN:

26. Clinical Coordinator signature:

27. Date form reviewed:

day mon year

Form RZ NORIG Revision 3 (11 Nov 10) RZ - Randomization 4 of 4 NORIG Keyed: ( )

ST - EGG and Satiety Test

Purpose: To document symptoms and results of the satiety test and electrogastrogram in patients with gastroparesis. When: Screening visit s1 or s2 and follow-up visits, f03, f06, f09, f12, and f18. Administered by: Study Physician and Clinical Coordinator. Respondent: Patient will respond to symptom evaluations on pages 2-7. Instructions: The Clinical Coordinator should complete section A. The Clinical Coordinator will use pages 2-7 to obtain patient’s responses during the test procedure. The visual analog scales on pages 2, 3, 5, 6, and 7 are 100 mm in length and should be measured from left to right with a metric (SI) ruler. Enter the value closest to the patient’s vertical line in millimeters (0-100 mm) in items 9, 10, 14, 15, and 16. Using the EGG report, complete section E. The Study Physician and Clinical Coordinator should complete Section F. Attach a copy of the EGG report to this form. Save the raw digital EGG data to a CD and place it in the patient’s study file.

A. Clinic, visit, and patient identification

1. Center ID:

2. Patient ID:

3. Patient code:

4. Date of form: - - day mon year

5. Visit code: (If report not associated with a visit, fill in “n”.)

6. Form & revision: s t 1

7. Study: NORIG 2

8. Has the patient fasted since midnight: Yes No

( 1) ( * 2)

* Patient must be fasting; test must be re-scheduled.

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 1 of 9 Patient ID:

B. Baseline Symptom Scores

9. BASELINE SYMPTOMS - - at the START of the EGG recording ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 2 of 9 Patient ID:

10. BASELINE SYMPTOMS - - just BEFORE satiety test begins ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 3 of 9 Patient ID:

C. SATIETY TEST VOLUMES

11. Time Satiety Test Started: : (24-hour)

Do not key data recorded in this box.

Subject drinks Ensure 150 mL from a cup every 5 minutes until he/she is completely full.

After each cup, record amount ingested, wait 15 seconds, then ask the subject to rate their feeling of fullness on a 0, 1, 2, 3, 4, 5 scale. 0 = not full at all and 5 is completely full. The satiety test ends when the patient is completely full.

1 Start Time: : Completed: mL: Fullness:

2 Start Time: : Completed: mL: Fullness:

3 Start Time: : Completed: mL: Fullness:

4 Start Time: : Completed: mL: Fullness:

5 Start Time: : Completed: mL: Fullness:

6 Start Time: : Completed: mL: Fullness:

7 Start Time: : Completed: mL: Fullness:

8 Start Time: : Completed: mL: Fullness:

9 Start Time: : Completed: mL: Fullness:

10 Start Time: : Completed: mL: Fullness:

11 Start Time: : Completed: mL: Fullness:

12 Start Time: : Completed: mL: Fullness:

12. Time Satiety Test Ended: : 13. Total Ensure Volume Consumed: (24-hour) mL

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 4 of 9 Patient ID:

D. Post prandial Symptom Scores

14. SYMPTOMS -- IMMEDIATELY AFTER finishing Ensure ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 5 of 9 Patient ID:

15. SYMPTOMS -- 15 MINUTES AFTER finishing Ensure ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 6 of 9 Patient ID:

16. SYMPTOMS -- 30 MINUTES AFTER finishing Ensure (At end of EGG) ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 7 of 9 Patient ID:

E. EGG data: (Note: The EGG signal analysis must be performed on a minimum of 8 consecutive, artifact-free minutes per 15 minute period.)

17. What was the duration of the baseline 0-15 minute time period analyzed: (min)

18. What was the duration of the post satiety test 0-15 minute time period analyzed: (min)

19. What was the duration of the post satiety test 16-30 minute time period analyzed: (min)

20. Distribution of average power by frequency region (as % of power in the 0-15 cpm range):

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. . % b. . % c. . % d. . %

0-15 post satiety: e. . % f. . % g. . % h. . %

16-30 post satiety: i. . % j. . % k. . % l. . %

21. Ratios of average power (POSTprandial/PREprandial) by frequency range:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

0-15 post satiety: a. . b. . c. . d. .

16-30 post satiety: e. . f. . g. . h. .

22. Distribution of average power by frequency range:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. . e+ b. . e+ c. . e+ d. . e+

0-15 post satiety: e. . e+ f. . e+ g. . e+ h. . e+

16-30 post satiety: i. . e+ j. . e+ k. . e+ l. . e+

23. Average dominant frequency:

a. Baseline: . cpm

b. 0-15 post satiety: . cpm

c. 16-30 post satiety: . cpm

24. Percentage of time with the dominant EGG frequencies in the four frequency ranges:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. % b. % c. % d. %

0-15 post satiety: e. % f. % g. % h. %

16-30 post satiety: i. % j. % k. % l. %

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 8 of 9 Patient ID:

F. Administrative information

25. Study Physician PIN:

26. Study Physician signature:

27. Clinical Coordinator PIN:

28. Clinical Coordinator signature:

29. Date form reviewed: - - day mon year

Form ST NORIG Revision 1 (21 May 09) ST - EGG and Satiety Test 9 of 9 NORIG Keyed: ( )

ST - EGG and Satiety Test

Purpose: To document symptoms and results of the satiety test and electrogastrogram in patients with gastroparesis. When: Screening visit s1 or s2 and follow-up visit f12. Administered by: Study Physician and Clinical Coordinator. Respondent: Patient will respond to symptom evaluations on pages 2-7. Instructions: The Clinical Coordinator should complete section A. The Clinical Coordinator will use pages 2-7 to obtain patient’s responses during the test procedure. The visual analog scales on pages 2, 3, 5, 6, and 7 are 100 mm in length and should be measured from left to right with a metric (SI) ruler. Enter the value closest to the patient’s vertical line in millimeters (0-100 mm) in items 9, 10, 14, 15, and 16. Using the EGG report, complete section E. The Study Physician and Clinical Coordinator should complete Section F. Attach a copy of the EGG report to this form. Save the raw digital EGG data to a USB flash drive.

A. Clinic, visit, and patient identification

1. Center ID:

2. Patient ID:

3. Patient code:

4. Date of form: - - day mon year

5. Visit code: (If report not associated with a visit, fill in “n”.)

6. Form & revision: s t 2

7. Study: NORIG 2

8. Has the patient fasted since midnight: Yes No

( 1) ( * 2)

* Patient must be fasting; test must be re-scheduled.

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 1 of 9 Patient ID:

B. Baseline Symptom Scores

9. BASELINE SYMPTOMS - - at the START of the EGG recording : (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 2 of 9 Patient ID:

10. BASELINE SYMPTOMS - - just BEFORE satiety test begins : (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 3 of 9 Patient ID:

C. SATIETY TEST VOLUMES

11. Time Satiety Test Started: : (24-hour)

Do not key data recorded in this box.

Subject drinks Ensure 150 mL from a cup every 5 minutes until he/she is completely full.

1 Start Time: : Completed: mL: Fullness:

2 Start Time: : Completed: mL: Fullness:

3 Start Time: : Completed: mL: Fullness:

4 Start Time: : Completed: mL: Fullness:

5 Start Time: : Completed: mL: Fullness:

6 Start Time: : Completed: mL: Fullness:

7 Start Time: : Completed: mL: Fullness:

8 Start Time: : Completed: mL: Fullness:

9 Start Time: : Completed: mL: Fullness:

10 Start Time: : Completed: mL: Fullness:

11 Start Time: : Completed: mL: Fullness:

12 Start Time: : Completed: mL: Fullness:

12. Time Satiety Test Ended: : 13. Total Ensure Volume Consumed: (24-hour) mL

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 4 of 9 Patient ID:

D. Post prandial Symptom Scores

14. SYMPTOMS -- IMMEDIATELY AFTER finishing Ensure : (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 5 of 9 Patient ID:

15. SYMPTOMS -- 15 MINUTES AFTER finishing Ensure : (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 6 of 9 Patient ID:

16. SYMPTOMS -- 30 MINUTES AFTER finishing Ensure (At end of EGG) : (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 7 of 9 Patient ID:

E. EGG data: (Note: The EGG signal analysis must be performed on a minimum of 8 consecutive, artifact-free minutes per 15 minute period.)

17. What was the duration of the baseline 0-15 minute time period analyzed: (min)

18. What was the duration of the post satiety test 0-15 minute time period analyzed: (min)

19. What was the duration of the post satiety test 16-30 minute time period analyzed: (min)

20. Distribution of average power by frequency region (as % of power in the 0-15 cpm range):

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. . % b. . % c. . % d. . %

0-15 post satiety: e. . % f. . % g. . % h. . %

16-30 post satiety: i. . % j. . % k. . % l. . %

21. Ratios of average power (POSTprandial/PREprandial) by frequency range:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

0-15 post satiety: a. . b. . c. . d. .

16-30 post satiety: e. . f. . g. . h. .

22. Distribution of average power by frequency range:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. . e+ b. . e+ c. . e+ d. . e+

0-15 post satiety: e. . e+ f. . e+ g. . e+ h. . e+

16-30 post satiety: i. . e+ j. . e+ k. . e+ l. . e+

23. Average dominant frequency:

a. Baseline: . cpm

b. 0-15 post satiety: . cpm

c. 16-30 post satiety: . cpm

24. Percentage of time with the dominant EGG frequencies in the four frequency ranges:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. % b. % c. % d. %

0-15 post satiety: e. % f. % g. % h. %

16-30 post satiety: i. % j. % k. % l. %

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 8 of 9 Patient ID:

F. Administrative information

25. Study Physician PIN:

26. Study Physician signature:

27. Clinical Coordinator PIN:

28. Clinical Coordinator signature:

29. Date form reviewed: - - day mon year

Form ST NORIG Revision 2 (19 Aug 09) ST - EGG and Satiety Test 9 of 9 NORIG Keyed: ( )

ST - EGG and Satiety Test

Purpose: To document symptoms and results of the satiety test and electrogastrogram in patients with gastroparesis. When: Screening visit s1 or s2 and follow-up visit f12. Administered by: Study Physician and Clinical Coordinator. Respondent: Patient will respond to symptom evaluations on pages 2-7. Instructions: The Clinical Coordinator should complete section A. The Clinical Coordinator will use pages 2-7 to obtain patient’s responses during the test procedure. The visual analog scales on pages 2, 3, 5, 6, and 7 should be measured from left to right with a metric (SI) ruler. Enter the value closest to the patient’s vertical line in millimeters (0-100 mm) in items 9, 10, 14, 15, and 16. Choose only whole minutes and do not select more than 15 minutes for any recording period. Using the EGG report, complete section E. The Study Physician and Clinical Coordinator should complete Section F. Attach a copy of the EGG report to this form. Save the raw digital EGG data to a USB flash drive.

A. Clinic, visit, and patient identification

1. Center ID:

2. Patient ID:

3. Patient code:

4. Date of form: - - day mon year

5. Visit code: (If report not associated with a visit, fill in “n”.)

6. Form & revision: s t 3

7. Study: NORIG 2

8. Has the patient fasted since midnight: Yes No

( 1) ( * 2)

* Patient must be fasting; test must be re-scheduled.

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 1 of 9 Patient ID:

B. Baseline Symptom Scores

9. BASELINE SYMPTOMS - - at the START of the EGG recording ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 2 of 9 Patient ID:

10. BASELINE SYMPTOMS - - just BEFORE satiety test begins ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 3 of 9 Patient ID:

C. SATIETY TEST VOLUMES

11. Time Satiety Test Started: : (24-hour)

Do not key data recorded in this box.

Subject drinks Ensure 150 mL from a cup every 5 minutes until he/she is completely full.

1 Start Time: : Completed: mL: Fullness:

2 Start Time: : Completed: mL: Fullness:

3 Start Time: : Completed: mL: Fullness:

4 Start Time: : Completed: mL: Fullness:

5 Start Time: : Completed: mL: Fullness:

6 Start Time: : Completed: mL: Fullness:

7 Start Time: : Completed: mL: Fullness:

8 Start Time: : Completed: mL: Fullness:

9 Start Time: : Completed: mL: Fullness:

10 Start Time: : Completed: mL: Fullness:

11 Start Time: : Completed: mL: Fullness:

12 Start Time: : Completed: mL: Fullness:

12. Time Satiety Test Ended: : 13. Total Ensure Volume Consumed: (24-hour) mL

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 4 of 9 Patient ID:

D. Post prandial Symptom Scores

14. SYMPTOMS -- IMMEDIATELY AFTER finishing Ensure ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 5 of 9 Patient ID:

15. SYMPTOMS -- 15 MINUTES AFTER finishing Ensure ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 6 of 9 Patient ID:

16. SYMPTOMS -- 30 MINUTES AFTER finishing Ensure (At end of EGG) ~~ : ~~ (24-Hour clock)

Mark each symptom line with a vertical line where you believe each of the following words best describes how you currently feel (PLEASE make ONLY ONE VERTICAL LINE for each symptom).

a. STOMACH FULLNESS mm

NOT FULL AT ALL COMPLETELY FULL

b. HUNGER mm

NONE EXTREME

c. NAUSEA mm

NONE SEVERE

d. BLOATING mm

NONE SEVERE

e. ABDOMINAL DISCOMFORT mm

NONE SEVERE

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 7 of 9 Patient ID:

E. EGG data: (Note: The EGG signal analysis must be performed on a minimum of 8 consecutive, artifact-free minutes per 15 minute period.)

17. What was the duration of the baseline 0-15 minute time period analyzed: (min)

18. What was the duration of the post satiety test 0-15 minute time period analyzed: (min)

19. What was the duration of the post satiety test 16-30 minute time period analyzed: (min)

20. Distribution of average power by frequency region (as % of power in the 0-15 cpm range):

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. . % b. . % c. . % d. . %

0-15 post satiety: e. . % f. . % g. . % h. . %

16-30 post satiety: i. . % j. . % k. . % l. . %

21. Ratios of average power (POSTprandial/PREprandial) by frequency range:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

0-15 post satiety: a. . b. . c. . d. .

16-30 post satiety: e. . f. . g. . h. .

22. Distribution of average power by frequency range:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. . e+ b. . e+ c. . e+ d. . e+

0-15 post satiety: e. . e+ f. . e+ g. . e+ h. . e+

16-30 post satiety: i. . e+ j. . e+ k. . e+ l. . e+

23. Average dominant frequency:

a. Baseline: . cpm

b. 0-15 post satiety: . cpm

c. 16-30 post satiety: . cpm

24. Percentage of time with the dominant EGG frequencies in the four frequency ranges:

Period Bradygastria Normal Tachygastria Duodenal (minutes) (1 - <2.5 cpm) (2.5 - <3.8 cpm) (3.8-10 cpm) (>10-15 cpm)

Baseline: a. % b. % c. % d. %

0-15 post satiety: e. % f. % g. % h. %

16-30 post satiety: i. % j. % k. % l. %

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 8 of 9 Patient ID:

F. Administrative information

25. Measure the length of the line below and enter the total length in millimeters:

26. Study Physician PIN:

27. Study Physician signature:

28. Clinical Coordinator PIN:

29. Clinical Coordinator signature:

30. Date form reviewed: - - day mon year

Form ST NORIG Revision 3 (24 Feb 10) ST - EGG and Satiety Test 9 of 9 Keyed: ( ) NORIG DD – Drug Dosing Determination and Dispensing

Purpose: To determine correct dosage of study drug and to dispense study drug. When: Visits rz, f03, f06, f09, f12, and f15. Use visit code “n” if a change in the dosage of study drug occurs at a time other than a study visit. Administered by: Study Physician or Clinical Coordinator. Instructions: This form will be used to document the dosage the patient is currently taking and the new dosage prescribed at this visit. The Randomization task must be completed and the patient randomized in NORIG before keying this form.

IMPORTANT: This form must be entered into the data system to obtain the study drug bottle number(s) for dispensing to the participant.

If the patient tolerates the study drug, study drugs should be dispensed in the quantities specified below:

Scheduled No. of Visit dose # bottles Comment rz 10 mg 1 3 week supply 1 10 mg capsule each day f03 25 mg 1 3 week supply 1 25 mg capsule each day f06 50 mg 2 3 week supply 2 25 mg capsules each day f09 75 mg 3 3 week supply 3 25 mg capsules each day f12 75 mg 3 3 week supply 3 25 mg capsules each day f15 -- As needed, per tapering protocol

A. Center, patient, and visit identification B. Drug dosing

1. Center ID: 8. Is this the Randomization visit: Yes No ( * ) ( ) 2. Patient ID: 1 2 15. 3. Patient code: *Dispense 1 bottle of 10 mg capsules. 4. Visit date (date this form is initiated): 9. - - What dose has the patient been taking since the day mon year last study visit:

5. Visit code: mg If the patient is not taking study drug, enter “00” 6. Form & revision: d d 1 and skip to 12. 7. Study: NORIG 2 10. Was this the dose according to the dose escalation schedule: Yes No

( 1) ( 2)

11. Was the dose tolerated by the patient:

Yes No

( 1) ( 2)

Form DD DD - Drug Dosing Determination and Dispensing NORIG Revision 1 (18 Aug 11) 1 of 2 Patient ID:

12. Is this the f15 visit: Yes No 13. Will the patient move up to the next dose ( 1) ( 2) according to the dose escalation schedule: 13. Yes ( 1) No, patient is at the highest dose of 75 mg ( ) a. How many capsules does the patient have 2 No, patient experienced side effects and will remaining from the previous visit: not dose-escalate ( * 3)

*If patient experienced severe and unanticipated side effects, complete the SR form. Complete Enter “000” if patient does not return NORIG IE and/or LR forms as needed. bottles. 14. The new prescribed dose will be: b. What is the patient's current daily dose:

75 mg (patient should be tapered mg to a 50 mg dose for one week then If 0 mg, go to item 16. tapered to the 25 mg dose for one

week) ( 1) 12c. 15. Study drug required (see dosing schedule in Instructions) 50 mg (patient should be tapered to the 25 a. Number of bottle(s) of study drug required: mg dose for one week) ( 2)

12d. (1-3) 25 mg (patient should be tapered to the 10 b. Strength of study drug: mg dose for one week) ( 3) 15. 10 mg ( 1) 25 mg ( 2) 10 mg (no tapering required, stop study drug) ( ) 4 C. Administrative information 16. 16. Study Physician PIN:

0 mg ( 5) 17. Study Physician signature: 16.

c. Does patient have 21 or more 25 mg capsules: Yes No 18. Clinical Coordinator PIN:

( 1) ( 2) 19. Clinical Coordinator signature: 16. 15.

d. Does patient have 7 or more 25 mg capsules: Yes No 20. Date form reviewed: ( 1) ( 2) 16. 15. - - day mon year

IMPORTANT: This form must be keyed into the data system to obtain the study drug bottle number(s) for dispensing to the participant. Once study drug is dispensed complete and key the RD - Study Drug Dispensing and Return form within 1 hour.

Form DD DD - Drug Dosing Determination and Dispensing NORIG Revision 1 (18 Aug 11) 2 of 2 Keyed: ( )

NORIG3IE - Interim Event ReportIE111 Mar 09 IE - Interim Event Report

Purpose: To document (1) events that impact on the patient’s treatment or participation in NORIG (e.g., temporary interruption or permanent cessation of study medication), or (2) adverse events thought to be associated with study drug that do not meet the criteria for Serious Adverse Event/IND Safety Report (SR) form, or (3) other event that clinical center staff feel should be reported now rather than wait until the next follow-up visit and that is not recorded on another NORIG form. Adverse events associated with NORIG study medication that are both serious and unexpected should not be reported on this (IE) form, but should be recorded on the IND Safety Re- port (SR) form. When: As needed; use visit code n even if reporting an event discovered during a regular follow-up visit. If more than one event is reported on the same calendar day (i.e., same date in item 4 for all events), use visit code n for first event, n1 for second event, etc. Administered by: Study Physician and Clinical Coordinator. Instructions: Complete and key this form for any event that meets the criteria above. The short name (item 21) and the severity code (item 22) are to be obtained from the NCI’s Common Terminology Criteria for Adverse Events v3.0 (CTCAE). The CTCAE document is available at www.gpcrc.us under Documents. Fax the DCC (Atten- tion: Mika Green) (1) a copy of this form; (2) A narrative description of the event; (3) A copy of your report to your IRB) if severity grade is 3 or higher (Fax 410-955-0932). GpCRC Data Coordinating Center telephone number: (410) 955-8175.

A. Center, patient, and visit identification 10. Gender: Male ( ) 1. Center ID: 1

Female ( 2) 2. Patient ID: 11. Age at time of event: years 3. Patient code: 12. Is the patient currently taking the NORIG study drug at the prescribed dose: 4. Date of report: Yes No

( 1) ( 2) day mon year 13. Summarize the patient’s history of 5. Visit code: n treatment with NORIG study drug (e.g., how long has patient been on study drug, have there been any treatment interruptions): 6. Form & revision: i e 1

7. Study: NORIG 2

B. Visit interval identification

8. Most recently completed study visit (screening or follow-up): D. Event description a. Date: day mon year 14. Is the event due to gastroparesis symptom exacerbation or increased severity of gastroparesis symptoms, such b. Visit code: as excessive nausea, vomiting, or pain: C. Patient information Yes No ( 1) ( 2) 9. Date randomized in NORIG (enter "n" if patient is not yet randomized): 15. Date event started:

day mon year day mon year

Form IE NORIG Revision 1 (11 Mar 09) IE - Interim Event Report 1 of 3 Patient ID:

16. Is the event associated with NORIG 20. As a result of this event, are there any study drug (check only one): changes to the study drug dose: Yes No

Definitely yes ( 1) ( 1) ( 2) If yes, specify: Probably yes ( 2)

Possible yes ( 3)

Probably no ( 4)

Definitely no ( 5)

17. Describe event:

21. Short name for event if applicable (short names for AEs are listed in the CTCAE v3.0 document available at www.gpcrc.us; click on Documents):

Not applicable ( 0)

22. Severity grade (severity grades are listed in the CTCAE v3.0 document available at 18. Nature of event (check all that apply) www.gpcrc.us; click on Documents). For events grade 3 and up, key this form and send the DCC a. Drug dispensing mixup: ( 1) (Attn: Mika Green; (1) A copy of this form; (2) A b. Study procedure related event: ( ) narrative description of the event; (3) A copy of 1 your report to your IRB.) c. Medication related event: ( 1) Not applicable ( 0) d. Severe allergic reaction: ( 1) Grade 1 - Mild ( 1) e. Drug interactions: ( 1) Grade 2 - Moderate ( 2) f. Arrhythmias: ( 1) Grade 3 - Severe ( 3) g. Electrolyte imbalance: ( ) 1 Grade 4 - Life threatening or disabling ( 4) h. Enzyme elevation: ( ) 1 Grade 5 - Death ( * 5)

i. Thrombocytopenia: ( 1) *Complete and key Death Report (DR) form. j. Worsening of co-morbid illness: ( 1) k. Pregnancy: ( ) 1 23. Date event resolved (enter "n" if event is not yet resolved): l. Other (specify): ( 1)

day mon year

24. What action was taken: 19. Did the event lead to (check all that apply):

a. Emergency Room visit: ( 1)

b. Hospitalization: ( 1)

c. Other doctor visit: ( 1)

d. Other (specify): ( 1)

Form IE NORIG Revision 1 (11 Mar 09) IE - Interim Event Report 2 of 3 Patient ID:

25. Other comments on event:

E. Administrative information

26. Clinical Coordinator PIN:

27. Clinical Coordinator signature:

28. Study Physician PIN:

29. Study Physician signature:

30. Date form reviewed:

day mon year

Key this form. If the severity grade is 3 or higher, fax the form to the DCC (Attention: Mika Green) for review by Linda Lee, the Safety Officer. Re- ports will be distributed for further review by the Steering Committee and Data and Safety Monitor- ing Board.

Form IE NORIG Revision 1 (11 Mar 09) IE - Interim Event Report 3 of 3 Keyed: ( ) NORIG RD – Study Drug Dispensing and Return

Purpose: To record dispensing and return of study drugs. When: Visits rz, f03, f06, f09, f12, f15 and f18. Use visit code “n” if drugs are dispensed or returned at a time other than a regular study visit or if a second form is needed at a visit to document returned study drugs. Administered by: Pharmacist or Clinical Coordinator, reviewed by Study Physician. Instructions: This form documents dispensing of study drug, return of unused study drug, and return of empty study drug bottles. This form is required at visit rz and every scheduled follow-up visit. It may be used at unscheduled visits as needed (use visit code n).

IMPORTANT: This form must be keyed into the data system within one hour of dispensing study drug to a participant.

If the patient tolerates study drug, study drugs are dispensed in the quantities specified below:

No. of Visit Scheduled dose bottles Comment

rz 10 mg q.d. 1 3 week supply: 1 10 mg capsule each day f03 25 mg q.d. 1 3 week supply: 1 25 mg capsule each day f06 50 mg q.d. 2 3 week supply: 2 25 mg capsules each day f09 75 mg q.d. 3 3 week supply: 3 25 mg capsules each day f12 75 mg q.d. 3 3 week supply: 3 25 mg capsules each day f15 - - As needed, per tapering protocol

The patient should be queried about return of empty study drug bottles at all study visits. Each time a patient returns a used study drug bottle to the clinical center, the pharmacist or the clinical coordinator should count and record the remaining number of capsules in study drug bottles. This form allows recording of the return of up to three bottles. If more than three bottles are returned at a time, complete a second form (using visit code “n”) to record the information for the remaining bottles.

A. Center, patient, and visit identification B. Study drug dispensing

1. Center ID: 8. Is this a second form for returning additional drug bottles at this visit: Yes No

2. Patient ID: ( * 1) ( 2) 16. 3. Patient code: * Key first form before this form. 4. Date of visit: 9. Will study drug be dispensed today: - - Yes No day mon year ( 1) ( 2) 5. Visit code: 11.

6. Form & revision: r d 1 10. Reason for not dispensing study drug (check all that apply) 7. Study: NORIG 2 a. Not a scheduled study drug

dispensing visit: ( 1) b. Study physician-directed treatment

interruption/termination: ( 1) c. Unwillingness of the patient to

take study drugs: ( 1) d. Other (specify): ( 1)

specify

16.

Form RD NORIG Revision 1 (18 Aug 11) RD – Study Drug Dispensing and Return 1 of 2 Patient ID:

11. How many bottles were dispensed: C. Study drug return

(1-3) 16. Were any bottles returned at this visit: Yes No Bottle tear-off label ( 1) ( 2) 12. 22.

17. Number of bottles returned (if more than 3 bottles are Affix label here returned, complete a second RD form):

(1-3)

13. a. b. Bottle No. Number of capsules returned Affix label here

18. ______- ______(00-50)

14. 19. ______- ______(00-50)

Affix label here 20. ______- ______(00-50)

D. Remaining bottles

21. Are any additional bottles being returned: 15. How were the study drugs dispensed to the patient Yes No

(check only one) : ( * 1) ( 2)

In person ( 1) *If yes, complete a second RD form using visit Mail ( 2) code “n.” Other (specify) ( 3) E. Administrative information

specify 22. Clinical Coordinator PIN:

23. Clinical Coordinator signature: IMPORTANT: You must enter this form into the data system within one hour of dispensing study drug to the participant. 24. Date form reviewed:

- - day mon year

Form RD NORIG Revision 1 (18 Aug 11) RD – Study Drug Dispensing and Return 2 of 2