Controlled, Parallel Group, Multi-Center Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Older Adult Subjects with Overactive Bladder (OAB)
Total Page：16
File Type：pdf, Size：1020Kb
A Phase 4, Double-Blind, Randomized, Placebo- Controlled, Parallel Group, Multi-Center Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Older Adult Subjects with Overactive Bladder (OAB) ISN/Protocol 178-MA-1005 ClinicalTrials.gov Identifier: NCT02216214 Date of Protocol: Version 3.0 10 Sep 2015 Sponsor: Astellas Pharma Global Development, Inc. Medical Affairs, Americas 1 Astellas Way Northbrook, IL 60062 Sponsor APGD, Medical Affairs, Americas ISN/Protocol 178-MA-1005 - CONFIDENTIAL - A Phase 4, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multi-Center Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Older Adult Subjects with Overactive Bladder (OAB) PILLAR Protocol for Phase 4 Study of Mirabegron ISN/Protocol 178-MA-1005 Version 3.0 Incorporating Substantial Amendment 2 September 10, 2015 IND 69,416 Sponsor: Astellas Pharma Global Development, Inc. Medical Affairs, Americas 1 Astellas Way Northbrook, IL 60062 This confidential document is the property of the Sponsor. No unpublished information contained in this document may be disclosed without prior written approval of the Sponsor. 10 Sep 2015 Astellas Page 1 of 105 Version 3.0 Incorporating Substantial Amendment 2 Sponsor APGD, Medical Affairs, Americas ISN/Protocol 178-MA-1005 - CONFIDENTIAL - Table of Contents I. SIGNATURES ······················································································ 8 II. CONTACT DETAILS OF KEY SPONSOR'S PERSONNEL····························10 III. LIST OF ABBREVIATIONS AND KEY TERMS··········································11 IV. SYNOPSIS··························································································16 V. FLOW CHART AND SCHEDULE OF ASSESSMENTS ·································25 1 INTRODUCTION·················································································28 1.1 Background ····················································································28 1.2 Non-clinical and Clinical Data ······························································31 1.2.1 Summary of Non-clinical Safety Data with Mirabegron ···························31 1.2.2 Summary of the Pharmacokinetics of Mirabegron ··································31 1.2.3 Summary of Clinical Data with Mirabegron ·········································32 1.3 Summary of Key Safety Information for Study Drugs ···································33 1.3.1 Summary of Key Safety Information for Mirabegron ······························33 1.4 Risk-Benefit Assessment·····································································34 2 STUDY OBJECTIVE(S), DESIGN AND VARIABLES···································35 2.1 Study Objectives ··············································································35 2.2 Study Design and Dose Rationale···························································35 2.2.1 Study Design·············································································35 2.2.2 Dose Rationale···········································································36 2.3 Variables ·······················································································36 2.3.1 Primary Variable ········································································36 2.3.2 Secondary Variables ····································································36 2.3.3 Other Variables ··········································································37 3 STUDY POPULATION··········································································37 3.1 Selection of Study Population ·······························································37 3.2 Inclusion Criteria··············································································37 3.3 Exclusion Criteria ·············································································38 4 TREATMENTS····················································································39 4.1 Identification of Investigational Product(s) ················································39 4.1.1 Test Drug ·················································································39 4.1.2 Placebo ···················································································40 10 Sep 2015 Astellas Page 2 of 105 Version 3.0 Incorporating Substantial Amendment 2 Sponsor APGD, Medical Affairs, Americas ISN/Protocol 178-MA-1005 - CONFIDENTIAL - 4.2 Packaging and Labeling ······································································40 4.3 Study Drug Handling ·········································································40 4.4 Blinding ························································································41 4.4.1 Blinding Method·········································································41 4.4.2 Confirmation of the Indistinguishability of the Study Drugs ······················41 4.4.3 Retention of the Assignment Schedule and Procedures for Treatment Code Breaking ··················································································41 4.4.4 Breaking the Treatment Code for Emergency ·······································42 4.4.5 Breaking the Treatment Code by the Sponsor ·······································42 4.5 Assignment and Allocation ··································································42 5 TREATMENTS AND EVALUATION························································43 5.1 Dosing and Administration of Study Drugs and Other Medications····················43 5.1.1 Dose/Dose Regimen and Administration Period ····································43 5.1.2 Previous and Concomitant Medication (Drugs and Therapies)····················43 5.1.2.1 Previous Medication (Drugs and Therapies) ···································43 5.1.2.2 Concomitant Medication (Drugs and Therapies) ······························43 5.1.3 Treatment Compliance··································································44 5.1.4 Emergency Procedures and Management of Overdose ·····························44 5.2 Demographics and Baseline Characteristics ···············································44 5.2.1 Demographics············································································44 5.2.2 Medical History··········································································44 5.2.3 Diagnosis of the Target Disease, Severity, and Duration of Disease··············44 5.3 Efficacy·························································································45 5.3.1 Patient Diary - Micturition and Incontinence ········································45 5.3.2 Barthel Index of Activities of Daily Living ··········································45 5.3.3 Vulnerable Elders Survey ······························································45 5.3.4 Patient Perception of Intensity of Urgency Scale····································46 5.3.5 OAB Symptoms, Quality of Life, Bladder Health and Treatment Benefit ·······46 5.3.5.1 Overactive Bladder-questionnaire ···············································46 5.3.5.2 Patient Perception of Bladder Condition········································47 5.3.5.3 Treatment Satisfaction – Visual Analog Scale ·································47 5.3.5.4 University of Alabama, Birmingham Life Space Assessment···············47 5.4 Safety Assessment ············································································48 5.4.1 Vital Signs················································································48 10 Sep 2015 Astellas Page 3 of 105 Version 3.0 Incorporating Substantial Amendment 2 Sponsor APGD, Medical Affairs, Americas ISN/Protocol 178-MA-1005 - CONFIDENTIAL - 5.4.2 Patient Diary - Subject Measurement Vital Signs ···································48 5.4.3 Montreal Cognitive Assessment ·······················································49 5.4.4 Adverse Events ··········································································49 5.4.4.1 Adverse Events of Possible Hepatic Origin ····································50 5.4.5 Laboratory Assessments································································50 5.4.6 Physical Examination ···································································50 5.4.7 Electrocardiogram (ECG) ······························································51 5.4.8 Post-Void Residual Volume···························································51 5.4.9 Cough Provocation Test ································································51 5.4.10 Follow-up Phone Calls to Patient······················································51 5.5 Adverse Events and Other Safety Aspects ·················································51 5.5.1 Definition of Adverse Events (AEs) ··················································51 5.5.2 Definition of Serious Adverse Events (SAEs) ·······································52 5.5.3 Criteria for Causal Relationship to the Study Drug ·································53 5.5.4 Criteria for Defining the Severity of an Adverse Event ····························53 5.5.5 Reporting of Serious Adverse Events (SAEs) ·······································53 5.5.6 Follow-up to Adverse Events ··························································54 5.5.7 Monitoring of Common Serious Adverse Events (SAEs) ··························55 5.5.8 Procedure in Case of Pregnancy·······················································55 5.5.9 Emergency Procedures