Document Name Clinical Protocol 204930 Type Version Document Identifier Effective Date eldo_clinical_doc 6.0; Most-Recent; Effective; CURRENT 090032d580c189ed 12-Sep-2016 05:12:55 Reason For Issue Auto Issue The Clinical Protocol 204930 Copy ri ght: Gl axoSmit hKlin e. An unpublished work subject to trade secret protecti on. Thi s work contains confident ial and propri etary i nformat io n of Gl axoSmi th Kline and should not be copied, circulated, or distributed to persons not em pl oy ed by GlaxoSmi th Kline unless specifically authori zed. Unauthorized di scl osure of this work is expressly prohibi ted. Page 1 of 108 Document Name Clinical Protocol 204930 Type Version Document Identifier Effective Date eldo_clinical_doc 6.0; Most-Recent; Effective; CURRENT 090032d580c189ed 12-Sep-2016 05:12:55 Reason For Issue Auto Issue CONFIDENTIAL SUMMARY INFORMATION Title: Study to Investigate the Impact on Oral Health Related Quality of Life of Managing Dentine Hypersensitivity with a Daily Use Anti -Sensitivity Tooth paste Protocol Number: 204930 Sponsor: GlaxoSmithKline Consumer Healthcare (GSKCH) UK Trading Limited St Georges Avenue, Weybridge, Surrey, KT13 0DE, United Kingdom (UK) Tel: PPD Product Name: Dentifrice containing 0.454% w/w stannous fluo ride (1100ppm fluoride) Development Phase: N/A Tel: PPD Expert Advice Outside of Normal Working Hours: PRIMARY CONTACT PPD BSC HONS Clinical Study Manager : PPD BSC, MSC Protocol Authors: Clinical Research: PPD , MSC Tel: PPD Biostatistician: PPD PPD , B.Sc, M.Sc Clinical Supplies: PPD Principal Investigator: Robert M aclure , BSc, BDS Study Site Name & Address: SITE 1. Intertek Clinical Research Services (CRS), 2Frederick Street, Wid nes, Cheshire, WA8 6PG Page 2 of 108 Document Name Clinical Protocol 204930 Type Version Document Identifier Effective Date eldo_clinical_doc 6.0; Most-Recent; Effective; CURRENT 090032d580c189ed 12-Sep-2016 05:12:55 Reason For Issue Auto Issue SITE 2. INTERTEK CLINICAL RESEARCH SERVICES (CRS), 119 STATION ROAD, ELLESMERE PORT, CHESHIRE, CH65 4BW, UK Study Site Telephone Number: + PPD Study Examiner : PPD , BSc, BDS PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT PAGE I confirm agreement to conduct the study i n co mp liance wit h the protocol and any amendments and according to the current ICH GCP guidelines. I acknowl edge that I am responsible for overall study conduct. I agree to personally conduct or supervise the described study. I agree to ensure that all associates, colleagues and emplo yees assist ing in the conduct of the study are inform ed about thei r obligati ons. Mechanisms are in pl ace to en sure si te staff receives all appropriate informat io n throughout the study . I agree to conduct this study i n full conformance wit h the l aws and regulations of the country i n which the research is conducted and the Declaration of Helsinki. Invest igator Name: Dr Robert Maclure Invest igator Qualificat io ns: BSc, BDS Invest igator Signature: PPD Date of Si gnature/ Agreement: Page 3 of 108 Document Name Clinical Protocol 204930 Type Version Document Identifier Effective Date eldo_clinical_doc 6.0; Most-Recent; Effective; CURRENT 090032d580c189ed 12-Sep-2016 05:12:55 Reason For Issue Auto Issue Table of Content SUMMARY INFORMATION ............................................... 2 PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT PAGE ................................ .............................................. 3 Table of Content ................................ ...................................... 4 PROCESS FOR AMENDING TH E PROTOCOL ............... 8 PROTOCOL AMENDMENT PAGE .................................... 9 PROTOCOL SYNOPSIS FOR STUDY 204930 ................... 15 1. INTRODUCTION ............................................................... 19 2. OBJECTIVES AND ENDPOINTS .................................... 21 3. STUDY PLAN ................................ ..................................... 21 3.1. Study Design ................................ ............................................ 21 3.2. Subject Restrictions ................................ ................................ 23 3.3. Type and Planned Number of Subjects ................................ .24 3.4. Study Design and Dose Justification ...................................... 25 4. SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA ........................................ 26 4.1. Inclusion Criteria ................................ .................................... 26 4.2. Exclusion Criteria ................................ ................................... 28 4.3. Screening/ Baseline Failures ................................................... 29 4.4. Withdrawal/ Stopping Criteria .............................................. 30 4.5. Subject Replacement ............................................................... 32 4.6. Subject and Study Completion ............................................... 32 5. PRODUCT INFORMATION ............................................. 32 5.1. Study Product ................................ .......................................... 32 5.2. Dose Schedule ................................ .......................................... 33 Page 4 of 108 Document Name Clinical Protocol 204930 Type Version Document Identifier Effective Date eldo_clinical_doc 6.0; Most-Recent; Effective; CURRENT 090032d580c189ed 12-Sep-2016 05:12:55 Reason For Issue Auto Issue 5.3. Dose Modification ................................ ................................... 33 5.4. Product Compliance ............................................................... 33 5.5. Precautions ................................ .............................................. 33 5.6. Overdose ................................ .................................................. 33 5.7. Rescue Therapy ................................ ....................................... 34 5.8. Product Assignment ................................ ................................ 34 5.8.1 Randomisation ................................ .......................................... 34 5.8.2 Blinding ................................ ..................................................... 34 5.9. Pack aging and Labelling ........................................................ 34 5.9.1. Accountability of Product ....................................................... 35 5.9.2. Storage of Product ................................ .................................. 35 6. STUDY ASSESSMENTS AND PROCEDURES .............. 35 6.1. Visit 1 -Screening Visit ........................................................... 35 6.1 .1 Telephone Screening ................................ ................................ 35 6.1.2. Informed Consent ................................ ................................... 36 6.1.3. Demographics ................................ .......................................... 36 6.1.4. Medical History and Concomitant Medication ..................... 36 6.1.5. Oral Hard Tissue (OHT) Examination .................................. 36 6.1.6. Oral Soft T issue (OST) Examination ..................................... 36 6.1.7. Eligible Tooth Assessment ...................................................... 37 6.2. Visit 2 to Visit 8 ................................ ....................................... 38 6.2.1. Dentine Hyersensitivity Experience Questionnaire (DHEQ) ................................ ................................................... 38 6.2.2 Labelled Magnitude Scales (LMS) Training Exercise ........... 39 6.2.3. Oral Soft Tissue (OST) Examination ..................................... 39 6.2.4. Evaporative Air Sensitivity Assessments ............................... 39 6.2.5. Stu dy Conclusion ................................ ..................................... 41 7. SAFETY ASSESSMENTS .................................................. 41 7.1. Definitions of an Adverse Event and Serious Adverse Event ................................ ...................................................... 41 Page 5 of 108 Document Name Clinical Protocol 204930 Type Version Document Identifier Effective Date eldo_clinical_doc 6.0; Most-Recent; Effective; CURRENT 090032d580c189ed 12-Sep-2016 05:12:55 Reason For Issue Auto Issue 7.1.1. Adverse Events ................................ ........................................ 41 7.1.2. Serious Adverse Events ........................................................... 42 7.2. Recording Adverse Eve nts and Serious Adverse Events ...... 43 7.3. Evaluating Adverse Events and Serious Adverse Events ..... 44 7.4. Reporting Adverse Events and Serious Adverse Events ....... 45 7.5. Follow -up of Adverse Events and Serious Adverse Events .. 46 7.6. Definition of and Procedure for Reporting Medical Device Incidents ................................ ................................................ 47 7.6.1. Definition of an Incident ......................................................... 48 7.6.2. Reporting of Incidents and Malfunctions .............................. 48 7.6.3. Follow -up of Incidents ............................................................ 49 7.7. Collection of Pregnancy Information ..................................... 50 7.7.1. Time Period for Collecting of Pregnancy Information ......... 50 7.7.2. Action to be Taken if Pregnancy Occurs ............................... 50 8. DATA M ANAGEMENT .................................................... 51 8.1. Source Documents/ Data ......................................................... 51 8.2. Electronic