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Clinical Trial Protocol Clinical Trial Protocol - Clinical effectiveness of the newer antipsychotic compounds olanzapine, quetiapine and aripiprazole in comparison with low dose conventional antipsychotics (haloperidol and flupentixol) in patients with schizophrenia - NeSSy (Neuroleptic Strategy Study) ------------------------------------------------------------------------------------------------------------------------------------------------------- - Confidential - Confidential - Confidential - Confidential - Clinical Trial Protocol Clinical Effectiveness Of The Newer Antipsychotic Compounds Olanzapine, Quetiapine And Aripiprazole In Comparison With Low Dose Conventional Antipsychotics (Haloperidol And Flupentixol) In Patients With Schizophrenia The Neuroleptic Strategy Study – NeSSy Protocol-ID.: NeSSy_200901 EudraCT Number 2009-010966-47 ---------------------------------------------------------------------------------------------------------------------------------------------------------- Protocol Authors: Prof. Dr. med. Mühlbauer, Dr. med. Bobis Seidenschwanz, Department of Pharmacology, Klinikum Bremen-Mitte; Prof. Dr. rer. nat. Dr. h.c. Timm, Competence Center for Clinical Trials Bremen, Version 04, 05 December 2012 Page 1 of 44 Clinical Trial Protocol - Clinical effectiveness of the newer antipsychotic compounds olanzapine, quetiapine and aripiprazole in comparison with low dose conventional antipsychotics (haloperidol and flupentixol) in patients with schizophrenia - NeSSy (Neuroleptic Strategy Study) ------------------------------------------------------------------------------------------------------------------------------------------------------- Table of contents 1 Abbreviations .................................................................................................................. 4 2 Synopsis.......................................................................................................................... 5 3 General Information ..................................................................................................... 10 3.1 Protocol Title, Protocol Identifying Number, Date ................................................... 10 3.2 Sponsor and Monitor .............................................................................................. 10 3.3 Persons Authorized to Sign the Protocol (Amendments) for the Sponsor .............. 10 3.4 Sponsors’ Medical Experts ..................................................................................... 10 3.5 Coordinating Investigator ........................................................................................ 10 3.6 Qualified Physician ................................................................................................. 11 3.7 Other Medical Departments Involved in the Trial .................................................... 11 4 Background Information .............................................................................................. 11 4.1 The Investigational Products .................................................................................. 11 4.2 Findings from Clinical Trials.................................................................................... 11 4.3 Risks of the Investigational Products ...................................................................... 13 4.3.1 Olanzapine .......................................................................................................... 13 4.3.2 Quetiapine .......................................................................................................... 13 4.3.3 Aripiprazole ......................................................................................................... 13 4.3.4 Haloperidol .......................................................................................................... 13 4.3.5 Flupentixol .......................................................................................................... 13 4.4 Route of Administration, Dosage (Regimen), Treatment Period ............................ 14 4.5 Protocol, Good Clinical Practice (GCP) and Applicable Regulatory Requirements 14 4.6 Description of the Population to be Studied............................................................ 14 5 Trial Objectives and Purpose ...................................................................................... 15 6 Trial Design ................................................................................................................... 15 6.1 Endpoints ................................................................................................................ 15 6.1.1 Primary Endpoints .............................................................................................. 15 6.1.2 Secondary Endpoints .......................................................................................... 15 6.1.3 Adjunctive Secondary Outcome Measures (Efficacy Analyses) ......................... 15 6.1.4 Secondary Criteria for Safety Analyses .............................................................. 15 6.2 Type and Design of the Trial .................................................................................. 16 6.3 Minimizing / Avoiding of Bias .................................................................................. 18 6.3.1 Randomization .................................................................................................... 18 6.3.2 Blinding ............................................................................................................... 19 6.4 Trial Treatments ..................................................................................................... 19 6.5 Description and Duration of Trial Periods ............................................................... 20 6.6 Study Drug Discontinuation, Early Termination, Drop-outs .................................... 20 6.7 Accountability Procedures for Investigational Products .......................................... 21 6.8 Unmasking of Treatment Assignment..................................................................... 21 6.9 Subsequent Treatment after Study Termination ..................................................... 22 6.10 Patients’ Data Collected in the CRF ....................................................................... 22 7 Selection and Withdrawal of Subjects ........................................................................ 22 7.1 Subject Inclusion Criteria ........................................................................................ 22 7.2 Subject Exclusion Criteria ....................................................................................... 23 7.3 Withdrawal Procedures .......................................................................................... 24 7.3.1 Subject Withdrawal Criteria ................................................................................ 24 7.3.2 Data of Withdrawn Subjects ............................................................................... 24 7.3.3 Replacement of Withdrawn Subjects .................................................................. 25 7.3.4 Follow-up for Withdrawn Subjects ...................................................................... 25 8 Treatment of Subjects .................................................................................................. 25 8.1 Trial Drugs and Dosage .......................................................................................... 25 8.2 Concomitant Psychotropic and Non-psychotropic Medication and Treatment .. 25 8.3 Procedures for Monitoring Subject Compliance ..................................................... 26 ---------------------------------------------------------------------------------------------------------------------------------------------------------- Protocol Authors: Prof. Dr. med. Mühlbauer, Dr. med. Bobis Seidenschwanz, Department of Pharmacology, Klinikum Bremen-Mitte; Prof. Dr. rer. nat. Dr. h.c. Timm, Competence Center for Clinical Trials Bremen, Version 04, 05 December 2012 Page 2 of 44 Clinical Trial Protocol - Clinical effectiveness of the newer antipsychotic compounds olanzapine, quetiapine and aripiprazole in comparison with low dose conventional antipsychotics (haloperidol and flupentixol) in patients with schizophrenia - NeSSy (Neuroleptic Strategy Study) ------------------------------------------------------------------------------------------------------------------------------------------------------- 9 Assessment of Efficacy ............................................................................................... 26 9.1 Specification of the Efficacy Parameters ................................................................ 26 9.1.1 Primary Endpoints .............................................................................................. 26 9.1.2 Secondary Endpoints .......................................................................................... 26 9.1.3 Adjunctive Secondary Outcome Measures (Efficacy Analyses) ......................... 26 9.2 Assessing, Recording and Analyzing of Efficacy Parameters ................................ 27 10 Assessment of Safety .................................................................................................. 27 10.1 Specification of Safety Parameters......................................................................... 27 10.2 Assessing, Recording and Analyzing of Safety Parameters ..................................
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