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Study Protocol Is Strictly Adhered to Throughout, and That All Data Are Collected and Recorded Correctly on the CRF

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Study Protocol Is Strictly Adhered to Throughout, and That All Data Are Collected and Recorded Correctly on the CRF CLINICAL TRIAL PROTOCOL A Phase 1, Randomized, Open-Label, Parallel-Group, Relative Bioavailability Study to Investigate the Pharmacokinetics, including Food Effect, as well as the Safety and Tolerability of Single Doses of New Immediate Release Tablet Formulations of Emodepside (BAY 44-4400), compared to Oral Solution, in Healthy Male Subjects Short title Relative Bioavailability Study of Emodepside IR-tablets and Solution Name of product(s) Emodepside (BAY 44-4400) Drug Class Anthelmintic cyclooctadepsipeptide Phase 1 Indication Treatment of onchocerciasis (river blindness) and potentially other filarial diseases including lymphatic filariasis Clinical Trial Protocol DNDI-EMO-03 Number EudraCT 2017-003091-31 Sponsor DNDi, Chemin Louis Dunant, 15, 1202 Geneva Switzerland Phone: +41 22 906 9230 Principal Investigator Dr Jeremy Dennison, Hammersmith Medicines Research (HMR), Cumberland Avenue, Park Royal, London, NW10 7EW, United Kingdom Phone : +44 (0) 20 8961 4130 Clinical Trial Protocol Version 3, 01 February 2018 Version / Date Protocol Amendment N/A Number / Date The information contained in this document is confidential. It is to be used by Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is understood that this information will not be disclosed to others without written authorisation from DNDi, except where required by applicable local laws Confidential Page 1 of 69 Protocol template_Version 1.2_24 April 2014 Protocol number (DNDI-EMO-03) Emodepside (BAY 44-4400) Protocol Version/Date: Version 3, 01 February 2018 CONTACT DETAILS Principal Investigator: Dr Jeremy Dennison Senior Research Physician and Principal Investigator Hammersmith Medicines Research (HMR) Limited Cumberland Avenue, Park Royal, London, NW10 7EW, United Kingdom Investigator Site 24-Hour Medical Contact: On-call physician tel: +44 (0) 7930 323 244 Co-Investigators: (See Study Reference Manual) Name and address of Monitor (if other than the Sponsor) Niche Science & Technology Unit 26, Falstaff House, Bardolph Road, Richmond TW9 2LH, United Kingdom Tel.: + 44 (0)20 8332 2588 Name, title, address, and telephone number(s) of the Sponsor's medical expert for the trial (24 h) Nathalie Strub-Wourgaft MD, Medical Director, 15 Chemin Louis Dunant, 1211 Geneva, Switzerland Switchboard: +41 22 906 92 30 Mobile: +41 79 874 05 39 Name, Title, Address, and Telephone Number(s) of the Sponsor's Clinical Project Manager for the Trial Sophie Delhomme, Translation Manager, 15 Chemin Louis Dunant, 1211 Geneva, Switzerland Switchboard: +41 22 906 92 30 Direct: +41 22 9026 92 79 Name, Title, Address, and Telephone Number(s) of other Sponsor Representatives Frédéric Monnot PharmD, Acting Head of Filariasis, 15 Chemin Louis Dunant, 1211 Geneva, Switzerland Switchboard: +41 22 906 92 30 Mobile: +41 79 219 52 59 Jean-Yves Gillon PharmD, PhD, Head of Translational Sciences, Confidential Page 2 of 69 Clinical Trial Protocol template_Version 1.2_02 June 2014 Protocol number (DNDI-EMO-03) Emodepside (BAY 44-4400) Protocol Version/Date: Version 3, 01 February 2018 15 Chemin Louis Dunant, 1211 Geneva, Switzerland Switchboard: +41 22 906 92 30 Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical department(s) and/or Institutions involved in the trial (See Study Procedures Manual) Phase 1 Unit Hammersmith Medicines Research (HMR) Limited Cumberland Avenue, Park Royal, London, NW10 7EW, United Kingdom Switchboard: +44 (0) 20 8961 4130 Clinical Laboratory The HMR Analytical Laboratory Cumberland Avenue, Park Royal, London, NW10 7EW, United Kingdom Switchboard: +44 (0) 20 8961 4130 Bioanalytic Laboratory Analytical Services International Ltd St. George’s, University of London, Cranmer Terrace, London, SW17 0RE, United Kingdom Switchboard: +44 (0) 20 8725 2845 Confidential Page 3 of 69 Clinical Trial Protocol template_Version 1.2_02 June 2014 Protocol number (DNDI-EMO-03) Emodepside (BAY 44-4400) Protocol Version/Date: Version 3, 01 February 2018 TABLE OF CONTENTS ABBREVIATIONS – GLOSSARY OF TERMS ........................................................ 10 PROTOCOL SUMMARY .......................................................................................... 13 1. BACKGROUND AND STUDY RATIONALE ................................................. 19 2. STUDY OBJECTIVES AND ENDPOINTS .................................................... 28 2.1. Objectives ........................................................................................................................... 28 2.1.1. Primary Objective .................................................................................................. 28 2.1.2. Secondary Objectives........................................................................................... 28 2.2. Study Endpoints ................................................................................................................. 28 2.2.1. Primary Endpoint .................................................................................................. 29 2.2.2. Secondary Endpoints ........................................................................................... 29 3. STUDY DESIGN AND STUDY DESIGN RATIONALE .................................. 29 3.1. Study design ....................................................................................................................... 29 3.2. Study duration and duration of subject participation .................................................... 30 3.3. Definition of the end of trial .............................................................................................. 31 3.4. Rationale of study design ................................................................................................. 31 4. SELECTION OF SUBJECTS ........................................................................ 32 4.1. Inclusion criteria ................................................................................................................ 32 4.2. Exclusion criteria ............................................................................................................... 33 4.3. Dietary and lifestyle guidance .......................................................................................... 35 5. SCHEDULE OF ASSESSMENTS ................................................................. 36 6. ENROLMENT PROCEDURES ...................................................................... 38 7. STUDY TREATMENTS ................................................................................. 38 7.1. Doses and treatment regimens ........................................................................................ 38 7.2. Emodepside Liquid Service Formulation ........................................................................ 39 7.3. Emodepside Immediate Release Tablets ......................................................................... 40 7.4. IMP supply and handling ................................................................................................... 40 7.5. Dose decision ..................................................................................................................... 41 7.6. Trial stopping criteria ........................................................................................................ 41 7.7. Study treatment labelling, packaging .............................................................................. 41 7.8. Accountability .................................................................................................................... 41 7.9. Storage ................................................................................................................................ 42 7.10. Blinding and procedures for unblinding ......................................................................... 42 7.11. Concomitant treatments .................................................................................................... 42 8. STUDY ASSESSMENTS ............................................................................... 43 8.1. Subject Information and Consent Form .......................................................................... 43 8.2. Timing of Assessments ..................................................................................................... 43 8.3. Screening Visit ................................................................................................................... 44 8.4. Admission to Ward (Day 1) ............................................................................................. 44 Confidential Page 7 of 69 Clinical Trial Protocol template_Version 1.2_02 June 2014 Protocol number (DNDI-EMO-03) Emodepside (BAY 44-4400) Protocol Version/Date: Version 3, 01 February 2018 8.5. Profile day (Day 0) .............................................................................................................. 45 8.6. Post-dosing days (Days 1–3) ............................................................................................ 45 8.7. Outpatient (ambulatory) visit (Day 5) and Follow-up visit (Day 7) ................................ 45 8.8. Sampling time points and additional tests ...................................................................... 46 8.9. PK assessments ................................................................................................................. 47 8.10. Total blood volume ...........................................................................................................
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