n"lar?ipa! MospiilalsINsPIHEo BY IIFF MospiilalsINsPIHEo

Ethics Committee of Manipal Hospitals os, HAL Airport Road, Bangalore-560017

Date: 14/JuV2011 ~i6~fs~ To, Dr. B. G. Dbarmanand 7.7 jUL 2011 Consultant R~Logiq Manipal Hospital, Bangalore-560017 R~GEIVh~D ON Dear Dr. Dharmanand,

7be institutional Ethics Committee i independent Ethics Committee Ethics Committee of MuoipaI HospitPb, Bangnlorr reviewed and discussed your application to conduct the clinical trial AW81245 entitled Re: "A Phase i I)uuble-Btind, Randomized, PIPceb~Coatrolled, Safety pod RfnePcy Study of Once Daily Coetmlkd Release Pregabolin in the treatment of Patients with FibromynlgiP (Protocol A0081245~ on 14N~VZOll.

The following documents submitted for the above-mentioned clinical project were reviewed &

approved:

PmtocolAmendment 1 version 19 October 2010.

~2·· Molecular Proftling Stlppl~t version 26 Fe~ 2010.

,3. Informed Consent Document Part i version 02 June 2011 in English.

4; E-Yposure in Utem Partner Release oFInfanna(ioo form customized for imih on 31 Jul 2008 and for A0081245 study on 08 March 2011 in English, Tamil and sloop witft translation certificate dated 12 Apr 2011.

5. A0081245 pwstioonPires venioa 1 in Ena$sb. TnnTt lad ICalmada along with the t~wlatioa certificate in Kaaaada

· FIBROMYALGIA IMPACT QUESTIONNAIRE - NRS FORMA1' · HOSPITAL ANXIETY AND DEPRESSION SCALE (~IADS) · BENEFIT, SATISFACTION, AND WILLINGNESS TO CONTINUE · MFI ~ MULTID~SIONAL FATIGUE INVENTORY (MFI) · MEDICAL OUTCOMES STUDY SLEEP SCALE (MOS)- ACII~~ · PATIENT GLOBAL IMPRESSION OF CHANCE (PGIC) a PATTENT HEALTCI UUESnONNAnt~ (PHQ-II1 a SF-36v2 TM HEAL·I-tl SURVEY QUESTIONNAIRE - ACUTE · SHEEflAN - SUICLDALITY TRACKING SCALE (LIFETLME ASSESSMENT) · SHEEHAN - SUICIDALI'TY TRACK~G SCALE (SINCE I,AST VISIT) · WORK PRODUCTIVITY AND ACTIVITY IMPAIR~T QUESTIONNAIRE - F1BROMYALGIA SYNDROME (WPAI-FMS) · NUMERIC RATING SCALE FOR PAIN (ONE WEEK RECALL)

:n~painosi;ita; SB,HALAirport Road,Bengalore-56W17 Phone:0802502 4444/3344 Fax:0802526 6757 a-mail: infa(6~manipalhospitalS.Com i:ui;ol'dte & ReyistcFcii Oliice: Menlpal nes4h Entorprloec hn. Ltd. ~t~nlTowsre. Sg,Fbor. 14. KAL Ai~on Road. BanRalore - 560 008 Ph: +91 80 4078 9199. WWw.manipBlhoSpi(BI~Mm

------~-~ Manipal Hospitals INSPIRED RY LIFE 6. Investigator's Bmch~ne dated July 2010.

,7. Case Report Form version 3 1 January 201 I. ,S· Insurance certificate dated 21 February 2011 for the period 46 February 2011 to 3Td February 2012.

9. A0081245 Subject ID Canl_l9 Oct 2010_Ver 1_US in English

,ill. A0081245 ~ppoiotment Canf_l9 Oct 2010_va I_US in English

:~ 11. A0081245 Poster_l9 Oct 2010_Ver IYS in English

,.12. A0081245 Dosing Diary_l9 Oct 2010_ver I_US in English

13. Prizer ICON IVRS_Subject User Guide version 0.2 draft in English and version 2.0 in Tamil and Kannada along with translation certificate

~. 14. Acti Watch-Spechum Study Guide.

15. Tote Rag: large non-woven guesseted event tote will help ensure that patients will bring their study medication and cards to and from their study visits.

16. Proposed method of patient accrual as mentioned below:

· Patients visiting our hospital/lnstiMe OPD's · Referred patients from primary health can centre/private practitioners or other institutesi Hospitals through verbal communication and discussion · Patient Database

17. Principal investigator's current CV. 18. Investigator's Undertaking (As required by Appendix Vn as per Schedule Y 20 Jan 2005 amendment)

19. Study work order template from sponsor. ,O. Additionally, we note your proposal to enroll a maximum of 10 subjects at this site. 21. Patient travel expense reimbursement at the rate oflll~for patients within the city and Rs, Ifor patients outside the city. 22. We will be using the below mentioned labs as the central lab for all protocol specified investigations in the study and local labs at our institute will be used in emergency.

Central Labs:

Quintiles .~echnologies () Private Limited, Lab Division (PMUM) 301-A-2. Leela Business Park M V Road Andheri (East) 400 059 India

~a-;isli Wospilai: 98, HAL Airport Road, Bangalore -560017 Phone: 080 2502 4444 i 3344 Far: 080 2526 6757 e-mail: [email protected] eorporato & Ragrstoled Onice: ManiDal Heath Enterprises Pvt, Ltd. Manipal Towers, 516 Floor, 14, HAL Airport Road, B~ - 560 008. Ph· +9~ no 4078 Y100. WWW.manlpBlhospitals.c~om ~ ~a~~··Ds·~·

Quintiles Laboratories Americas Global Headquarters 1600 Terrell Mill Rd Suite 100 Mariet(a GA 30067 USA

Uuintiles Laboratories-Asia puiadles East Asia Pte. Ltd 79 Science Pa~ Drive #0648 Cinbech IV Singapore Science Park 1 Singapore 118264

WuX;AppTBch 288 Fute Zhong Road Waigaoqiao Free Trade 7nne Shanghai 200131, P.R, China

Kings Heights DNA and Bionuids GoE Pfcrer Global Research 6t Development Kings Heights Technology Center 23 Kings Highway Groton, CT 06340

Local Lab:

Manipal Hospital Diagnostic Services 98, HAL Airport Road, Bangalo~B560017 K~ India

23, Profonaa for the Approval afthe Research Project

1124. Conflict oflnterest

25. Scientific Committee letter

i·"an:i??~ *8':;·i;,i: 98, HAL Airport Road, Bangalore -560017 Phone: 080 2502 4444 i 3344 Fax: 080 2526 6757 e-mail: [email protected] ,:o-\;:;: i a iiL1Llt;tr?Te(i OrfiCE: Menipal Health Enterprises Pvt. Ltd, ManipalTowerr, 51h Floor, 14, HAL Airport Road, Bangalore - 560 008. Ph:+91 80 4078 9100. www.manipalhospitals.com nospitais INSPIRED BY LIFEManipail

The following Safety Letters and SUSAR Line listingwere reviewed:

i. Safety Letters and SUSAR Line Listing for the period Aug 2010 till 20 May 201 i:

Safety Letter-a:

2010046603 10 Post ileus FU:1 2010115247 21 0 Concussion initial 2010121)72 witMrawaI synbmme, &-Oa-lo initial 2010115247

9-Nov-lO Concussion~~------FU:I 2010147757 22-Dec-1D Cellulitis left foot initial 2010181915 Cholecystectomy-gall stones Initial 2011007515 I~yponatremia Thrombocytolwnia I~-Feb-l I Acute tM1SillitiS Initial 2011007515 HyponabPmia, Thrombocytopenla 22-Feb-11 Acute tonsillitis FU: I 2010115247 05-Apr-ii Concussion 1Concussion] FU: 2 I6-May- 2009290481 suicidal thoughts [Suicidal ideation] 2011 depression [Depression] PU:2 2011090661 Status epilepticus [Status 20 May 2011 epilepticus] Initial

SUSAR Line LiPting:

5-Aug- 2010 to Period: 01 feb 2010 31 Jul 2010 and Brief dated 11

25-Jan- 11 dated 29 Oct 2009 th~o~p~L25~

i·l-Feb- Clinical Trisl Safety Update report freporting period: 01 Aug 2010 through 3 1 Jan 11 2011

;.i!::li:ai i"ospill:: 98, HAL Airport Road, Bangalore -560017 Phone: 080 25M 4444 / 3344 Fax: 080 2526 6757 a-mail. info((i~manipalhospitals.com i~!~iurate & Registiiiud C)Rice: Manipal Health Enterprlse· Pvt, Ltd. ManipalTowers. 5th Floor, 14, HAL Airport Road, Bangalore - 560 008, Ph: +91 80 4078 9100, www.manipalhospitals.com L-isspl~Uis s INSPllltD BYIIFE~arr;r·-~:

The following members of the Ethics C~ittee were present at the meeting held on 14/07/201 1 at 3:00 pm, at Manipal Hospital Bangalore-560017

Name QualilEEltion Desigantmn/ Title I Affiliation s as to the

Institution

Yes/No Justice S. R. B.A.B.L C~anNoting No Bannurmath Member

Dr. Ananya MD Voting Memberl I~o Chskrsborthy fPharmacology) Cli~

Ms. Hasitha S Vikram MA,M.S.W.. Voting Member/ No Social Work

Mrs. Rekha. K M.C.S Voting Member/ No Social Work

Dr. Marina N. Rehera PhD Voting Memheri No

Mr. Vasanth Krishna.K BA (Law) L.I,.B Voting Memberi Yes

Dr. S. S. lyengar DM (Cardiology) Member Secretary Yes Non-Voting Member MD Radio- Voting Member/ Yes Dr. Pumima Clinician MD Voting Membed Yes Dr. C. S. Na~araja (Anesthesia) Clinician Prabhakar U. Ci. I)harmansnd MD Voting~ Yes (Rheumatology) Clinician

Dr.Vishwanath Siddini MD Voting Msmberl Yes OJephrology) Clinician

MD Voting Mambed Yes Dr. ~agdish Chinnappa (Pediatrics) Clinician

I)r. Suresh Chandm MD Voting Memberi Yes ) Clinician MD IIRPPI Yes Dr. Malathi Non-Voting Member

,,-._ ·:I ·-I; ·:ils;:98,HAL Airport Road, Bangalore -560017 Phone: 080 2502 4444 i 3344 Fax: 080 2526 6757 a-mail : into~~manipalhospitaIs.com :i~y;sieied On,;~ Manipal Health Enterprises Pvt. Ltd. Manipal Towers, 5th Floor, 14, HAL AirpoR Road. Banqaiore - 560 008 Ph: +918040789100, www.manipalhospitals.com Manipal Hospitals INSPIRED RY IIFE

Dr. B. G. I)hannanand who is participating in the study and is also the member of the Ethics Committee is abstained from voting during this meeting.

Pharmacoyenomics study is not permitted by the EC and hence the informed Consent Document Part II is not approved by the Ethics Committee.

Pending Documents are:

i. Dccl Approval Letter 2. Clinical Trial Agreement & Financial Agreement 3. Clinical Trial RelTistration of the Study the CTR~

The trial can be started only after the above said pending documents are submitted to the Ethics Committee.

We hereby confirm that the Ethics Com~ of MnnipPI Hospit·h, B8slplsre is ~zed and operates as per the GCP and applicable regulations.

Yours sincerely, ----7 "i '--" Dr. S. S. lyenRnr Member Secretary, Ethics Committee of Manipsl HospitoLs

YB. HAL Atrpon Road. Banyaiote -560017 Phone: 080 2~j02 4444 i 3344 Fax: 080 2526 6757 e-muli : intoiamanipaihuspifaIs.cam

2222222222 Menipal Health Enterprises Pvt. Ltd. Manipai Towers, 5th Floor. 14. HAL Airpo~t Road. Banqalore - 560008 Ph: ,91 8040789100 w~lv~manipaihospitaiscom