PASS information Title Post-Authorisation Safety Study (PASS) for Flupirtine – Effect of Risk Minimisation Measures in Germany Protocol version identifier Version 3.0 Date of last version of protocol July 01, 2015 EU PAS register number Study not registered; registration planned after approval of the protocol by BfArM Active substance Flupirtine (INN) Pharmacotherapeutic group: non- opioid, non-NSAID, non-steroidal analgesic ATC code: N02BG07 Medicinal product Flupirtine-containing medicinal products Product reference Not applicable Procedure number DE/H/3428/001/DC DE/H/3430/001/DC Marketing authorisation holder(s) Lupin (Europe) Limited responsible for this study Victoria Court, Bexton Road Knutsford, Cheshire, WA16 OPF UK Hormosan Pharma GmbH – a Lupin Group Company Wilhelmshoeherstr. 106 60389 Frankfurt Germany Joint PASS No Research question and objectives Evaluation of the impact of the introduction of risk minimisation measures (DHPC and updated SmPC) for flupirtine on the prescription behaviour of physicians Country(-ies) of study Germany Authors Birgit Ehlken, MSc Director RWES, Epidemiology and Safety IMS Health GmbH & Co. OHG, Germany Dr. Deepa Arora MD Vice President & Global Head- Drug Safety & Risk Management Lupin Ltd PASS Flupirtine Germany Version: September 24, 2015 Katja Gleisner Head of Pharmacovigilance/ EU QPPV Hormosan Pharma GmbH – a Lupin Group Company Dr. Abdus Samad Manager - Drug Safety and Risk Management Lupin Ltd 2 PASS Flupirtine Germany Version: September 24, 2015 Marketing authorisation holder(s) Marketing authorisation holder(s) Lupin (Europe) Limited Victoria Court, Bexton Road Knutsford, Cheshire, WA16 OPF UK Hormosan Pharma GmbH – a Lupin Group Company Wilhelmshöher Straße 106 60389 Frankfurt Germany MAH contact person Katja Gleisner Head of Pharmacovigilance / EU Qualified Person for Pharmacovigilance Hormosan Pharma GmbH – a Lupin Group Company Wilhelmshöher Straße 106 60389 Frankfurt/Main - Germany Phone: +49 (0) 69 - 47 87 343 Fax: +49 (0) 69 - 47 87 316 E-Mail: [email protected] 3 PASS Flupirtine Germany Version: September 24, 2015 1. Table of contents PASS INFORMATION ..................................................................................................................... 1 MARKETING AUTHORISATION HOLDER(S) ............................................................................... 3 1. TABLE OF CONTENTS .............................................................................................................. 4 2. LIST OF ABBREVIATIONS ........................................................................................................ 5 3. RESPONSIBLE PARTIES .......................................................................................................... 7 4. ABSTRACT ...............................................................................................................................10 5. AMENDMENTS AND UPDATES ..............................................................................................13 6. MILESTONES ............................................................................................................................14 7. RATIONALE AND BACKGROUND..........................................................................................15 8. RESEARCH QUESTION AND OBJECTIVES ..........................................................................17 9. RESEARCH METHODS ............................................................................................................18 9.1. STUDY DESIGN .....................................................................................................................18 9.2. SETTING ................................................................................................................................18 9.3. VARIABLES ...........................................................................................................................19 9.4. DATA SOURCES ...................................................................................................................21 9.5. STUDY SIZE ...........................................................................................................................22 9.6. DATA MANAGEMENT ...........................................................................................................23 9.7. DATA ANALYSIS ...................................................................................................................23 9.8. QUALITY CONTROL .............................................................................................................32 9.9. LIMITATIONS OF THE RESEARCH METHODS ..................................................................33 9.10. OTHER ASPECTS ...............................................................................................................34 10. PROTECTION OF HUMAN SUBJECTS ................................................................................34 11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS .........................................................................................................................35 12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS ......................35 13. REFERENCES ........................................................................................................................36 ANNEX 1. LIST OF STAND-ALONE DOCUMENTS ....................................................................38 ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS ...................................................39 ANNEX 3. ADDITIONAL INFORMATION ....................................................................................46 4 PASS Flupirtine Germany Version: September 24, 2015 2. List of abbreviations AE Adverse Event ATC Anatomical Therapeutic Chemical Classification ALAT Alanine Aminotransaminase AP Alkaline Phosphatase ASAT Aspartate Aminotransaminase BfArM Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte) CMDh Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human COE Center of Excellence DA IMS® Disease Analyzer DDD Defined Daily Dose DHPC Direct Healthcare Professional Communication DUS Drug Utilisation Study EC European Commission EMA European Medicines Agency EMR Electronic Medical Record ENCePP European Network of Centres for Pharmacoepidemiology and Pharmacovigilance EU-PAS European Post Authorisation Study GGT Gamma-Glutamyl Transpeptidase, Gamma-Glutamyl- Transferase GLDH Glutamate Dehydrogenase GP General Practitioner GVP Good Pharmacovigilance Practices ICD International Statistical Classification of Diseases and Related Health Problems, Version 2014, German Modification INN International Nonproprietary Name LFT Liver Function Test LRx IMS® Longitudinal Prescription database MAH Marketing authorization holder NSAID Non-Steroidal Anti-Inflammatory Drug OTC Over The Counter PASS Post-Authorization Safety Study PCP Primary Care Physician QPPV Qualified Person for Pharmacovigilance PRAC Pharmacovigilance Risk Assessment Committee RMM Risk Minimisation Measures RMP Risk Management Plan RMS Reference Member State RWES Real World Evidence Solutions SAS Statistical Analysis Systems SHI Statutory Health Insurance SmPC Summary of Product Characteristics SNEPCO Selective Neuronal Potassium Channel Opener SOP Standard Operating Procedure 5 PASS Flupirtine Germany Version: September 24, 2015 STROBE Strengthening the Reporting of Observational Studies in Epidemiology WHO World Health Organization 6 PASS Flupirtine Germany Version: September 24, 2015 3. Responsible parties Sponsor Lupin Atlantis Holdings SA Durachweg 13 8200 Schaffhausen Switzerland Project Team Dr. Deepa Arora Vice President & Global Head of Drug Safety and Risk Management Lupin Limited Lupin Ltd 159 CST Road, Kalina, Santacruz East Mumbai 400 098 India Phone: +91 22 6640 2348 e-mail: [email protected] Dr. Abdus Samad Manager - Drug Safety and Risk Management Lupin Limited Lupin Ltd 159 CST Road, Kalina, Santacruz East Mumbai 400 098 India Phone: +91 22 6640 2601 e-mail: [email protected] Katja Gleisner Head of Pharmacovigilance / EU Qualified Person for Pharmacovigilance Hormosan Pharma GmbH – a Lupin Group Company Wilhelmshöher Straße 106 60389 Frankfurt/Main - Germany Phone: +49 69 - 47 87 343 Fax: +49 69 - 47 87 316 e-mail: [email protected] 7 PASS Flupirtine Germany Version: September 24, 2015 Subcontractor IMS Health GmbH & Co. OHG Erika-Mann-Str. 5 80636 München, Germany IMS Health is a partner centre of the ENCePP scientific network which is coordinated by the European Medicines Agency. IMS is dedicated to excellence in research by adhering to the ENCePP Guide on Methodological Standards and promoting scientific independence and transparency. Project Team Massoud Toussi, MD, PhD, MBA (Scientific Director) Principal, Europe Pharmacoepidemiology and Drug Safety IMS Real-World Evidence Solutions Tour Ariane, 5-7 Place de la Pyramide, 92088 Paris La Défense, France Phone: +33 (0)1 4135 1335 Fax: +33 (0)1-41 35 13 49 e-mail: [email protected] Birgit Ehlken, MSc (Protocol) Director Real World Evidence Solutions Pharmacoepidemiology and Drug Safety IMS Health GmbH & Co. OHG Erika-Mann-Str. 5 80636 München, Germany Phone: +49-(0)89-4579126430 Fax: +49-(0)89-4579127400 e-mail: [email protected] Silvia Dombrowski, MSc (Statistical Evaluation) Consultant CES LifeLink – Epidemiology & Pharmacovigilance IMS Health GmbH & Co. OHG