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Protocol Ptk0796-Absi-16301 Omadacycline (PTK 0796) PTK0796-ABSI-16301 – Version 3.0 IND 73,431 22-NOV-2016 IND 75,928 PROTOCOL PTK0796-ABSI-16301 Study Title A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare the Safety and Efficacy of Oral Omadacycline to Oral Linezolid for Treating Adult Subjects with Acute Bacterial Skin and Skin Structure Infection (ABSSSI) IND Number: 73,431 and 75,928 Protocol Number: PTK0796-ABSI-16301 Indication: Acute Bacterial Skin and Skin Structure Infection Phase: 3 Investigational Omadacycline (PTK 0796) Product: Dose Form: Oral Sponsor: Paratek Pharma, LLC A wholly-owned subsidiary of Paratek Pharmaceuticals, Inc. 75 Park Plaza, 4th Floor Boston, MA 02116 USA 1000 First Ave Suite 400 King of Prussia, PA, 19406 P.O. Box 120828 Boston, MA 02111 Tel: +1 617-275-0040 Protocol Version: Version 3.0 Date: 22-NOV-2016 NCT02877927 Confidential and Proprietary Page 1 of 79 Paratek Pharma, LLC Omadacycline (PTK 0796) PTK0796-ABSI-16301 – Version 3.0 IND 73,431 22-NOV-2016 IND 75,928 TABLE OF CONTENTS TABLE OF CONTENTS .....................................................................................................2 LIST OF IN-TEXT TABLES ..............................................................................................6 LIST OF APPENDICES ......................................................................................................6 1 DISCLOSURE STATEMENT ..........................................................................................7 2 CONTACTS ......................................................................................................................8 2.1 Emergency Contacts ................................................................................................8 2.2 Additional Contacts .................................................................................................8 3 SPONSOR SIGNATURE ..................................................................................................9 4 INVESTIGATOR AGREEMENT...................................................................................10 5 LIST OF ABBREVIATIONS ..........................................................................................11 6 DEFINITIONS .................................................................................................................14 7 PROTOCOL SYNOPSIS.................................................................................................15 8 STUDY FLOWCHART ..................................................................................................23 9 INTRODUCTION ...........................................................................................................26 9.1 Background ............................................................................................................26 10 STUDY OBJECTIVES ....................................................................................................28 10.1 Primary Objectives .................................................................................................28 10.2 Secondary Objectives .............................................................................................28 11 STUDY DESIGN.............................................................................................................29 11.1 Description .............................................................................................................29 11.2 Rationale of Study Design .....................................................................................29 11.3 Rationale for Choice of Comparator ......................................................................29 11.4 Approximate Duration of Subject Participation ....................................................29 11.5 Approximate Duration of Study .............................................................................30 11.6 Approximate Number of Subjects .........................................................................30 12 SELECTION OF SUBJECTS..........................................................................................30 12.1 Inclusion Criteria ...................................................................................................30 12.2 Exclusion Criteria ..................................................................................................31 12.3 Screen Failures .......................................................................................................33 13 PRIOR AND CONCOMITANT TREATMENT ............................................................33 13.1 Prohibited Treatment .............................................................................................34 13.1.1 Concomitant Medications That May Interact With Linezolid .....................34 13.2 Permitted Treatments .............................................................................................35 13.2.1 Dressings ......................................................................................................35 13.2.2 Topical Solutions .........................................................................................35 13.2.3 Surgical Procedures .....................................................................................35 Confidential and Proprietary Page 2 of 79 Paratek Pharma, LLC Omadacycline (PTK 0796) PTK0796-ABSI-16301 – Version 3.0 IND 73,431 22-NOV-2016 IND 75,928 14 PROCEDURES................................................................................................................35 14.1 Visit Schedule and Assessments ............................................................................36 14.2 Screening Phase .....................................................................................................36 14.2.1 Subject Demographics/Other Baseline Characteristics ...............................37 14.2.1.1 Medical History Relating to the Infection Under Study ....................37 14.2.2 Physical Examination...................................................................................37 14.2.3 Diagnosis of ABSSSI and Clinical Assessment of the Site of Infection .....37 14.2.4 Assessment of Lesion Size...........................................................................38 14.2.5 Subject Reported Outcomes .........................................................................38 14.2.5.1 Numerical Rating Scale for Pain ........................................................38 14.2.5.2 SF-36v2® Health Survey ....................................................................39 14.2.6 Urine Tests ...................................................................................................39 14.3 Double-blind Treatment Phase ..............................................................................39 14.3.1 Assessments While on Test Article .............................................................39 14.3.1.1 Treatment Phase .................................................................................40 14.3.1.2 Management While on Oral Test Article ...........................................41 14.3.2 Permitted Dose Adjustments and Interruptions of Test Article ...................42 14.4 Follow-up Phase.....................................................................................................42 14.5 Total Volume of Blood Collected ..........................................................................42 15 TEST ARTICLE AND ADMINISTRATION .................................................................42 15.1 Test Article Administration ...................................................................................42 15.1.1 Identity of the Investigational Product .........................................................43 15.2 Investigational and Comparator Test Article .........................................................43 15.2.1 Investigational Test Article: Omadacycline ................................................43 15.2.2 Comparator Test Article: Linezolid ............................................................43 15.3 Dose Selection Rationale .......................................................................................43 15.4 Subject Compliance ...............................................................................................44 16 SAFETY ..........................................................................................................................45 16.1 Physical Examinations ...........................................................................................45 16.1.1 Vital Signs ....................................................................................................45 16.1.2 Laboratory Evaluations ................................................................................46 16.1.2.1 Hematology ........................................................................................46 16.1.2.2 Clinical Chemistry .............................................................................47 16.1.2.3 Other Laboratory Tests ......................................................................47 16.1.3 Safety Studies to be Performed Locally .......................................................47 16.1.3.1 Electrocardiogram (ECG) ..................................................................47 16.1.3.2 Pregnancy and Assessments of Fertility ............................................48 16.1.3.3 Blood Cultures ...................................................................................48
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