CTN-0030 Protocol Book

1 NIDA-CTN-0030A Two-Phase Randomized Controlled Clinical Trial of Buprenorphine/Naloxone treatment Plus Individual Drug Counseling for Opioid Analgesic DependenceNATIONAL INSTITUTE ON DRUG ABUSECLINICAL TRIALS NETWORKP rotocol ( 2007)CONTACT INFORMATION FOR INVESTIGATORS/COLLABORATORST itleNameAffiliationLead Investigator for Protocol Implementation(LI)Roger Weiss, New England NodeLead Investigator for Protocol DevelopmentWalter Ling, NodeProject DirectorJennifer Sharpe Potter, , MPHN orthern New England NodeProject Co-DirectorAl Hasson, Pacific NodeProject ManagerKristi Prather, New England NodeMedical MonitorHilary Connery, , New England NodeSafety MonitorRobert Lindblad, Coordinating CenterBiostatisticiansEva Petkova, Island NodeJanet Levy, CCTNR egulatory SpecialistScott Provost, , New England NodeTraining DirectorMarc Copersino.

2 New England NodeNIDA LiaisonsJack Blaine, CCTNP etra Jacobs, CCTNE xecutive CommitteeFranklin Ingram, Carolina Node Carmen Masson, NodeMichael Bogenschutz, NodeJeff Selzer, Island NodeNathaniel Katz, New England NodeMichele Straus, , Coordinating CenterTable of ContentsCTN-0030 Protocolpage iVersion Study Synopsis and Study Objectives .. Study Design .. PHASE 1 .. Research Questions - Phase 1 .. Hypothesis - Phase 1 .. Primary Outcome Measure for Phase 1 .. Phase 1 Study Design .. PHASE 2.

3 Research Questions - Phase 2 .. Hypothesis - Phase 2 .. Primary Outcome Measure - Phase 2 .. Phase 2 Study Design .. Study Population .. Eligibility Criteria .. Study Intervention .. Induction and Post-Induction treatment Schedules .. Induction Schedule - Day 1 of treatment .. Post-Induction .. Duration of Study .. Safety Assessments .. Outcome Assessments .. Study Timetable .. Introduction .. Background .. Clinical Profile .. Clinical Efficacy .. Pharmacokinetics (Drug Studies).

4 Clinical Safety .. Study Rationale .. Rationale for the Choice of the Specific Enhanced treatment in Phase 1 and 2 Rationale for Pain Assessment and Intervention .. Study Objectives .. Primary Objective .. Secondary Objectives .. Study Overview of Study Design .. Phase 1 Induction and treatment .. 4-1 Table of ContentsCTN-0030 Protocolpage iiVersion Induction .. Phase 1 treatment .. Phase 2 Induction and treatment .. Data Collection Phase 1 and Phase 2 .. Duration of Study and Visit Schedule.

5 Feasibility Review .. Study Population .. Subject Recruitment .. Eligibility Criteria .. Inclusion Criteria .. Exclusion Criteria .. Community treatment Programs (CTPs) .. Number of CTP Sites .. CTP Characteristics .. Outcome Measures .. Primary Outcome Measures .. Success in Phase 1 .. Failure in Phase 1 .. Substantial Improvement in Phase 2 .. Secondary Outcome Measures .. Study Procedures .. Recruitment and Enrollment .. Recruitment Plan .. Projected Recruitment Rate.

6 Initial Subject Screening .. Testing Completed .. Informed Consent Procedures .. Comprehension Assessment .. Other Procedures for Vulnerable Populations .. Baseline Assessment .. Randomization .. Method .. treatment Discontinuation & Study Termination .. Participant-Initiated Discontinuation .. Investigator-Initiated Discontinuation .. treatment Discontinuation .. Procedures for Discontinuation .. Replacement of Subjects .. Study Termination .. Follow-Up .. Binding.

7 Prevention of Study Dropouts .. Study Treatments .. 8-1 Table of ContentsCTN-0030 Protocolpage iiiVersion treatment by Phase .. PHASE 1 .. Induction Schedule .. Post-Induction .. PHASE 2 .. Behavioral Therapies .. Standard Medical Management (SMM) .. Enhanced Medical Management (EMM) .. Study Intervention .. Dosing During Taper .. Dispensing of Study Medication .. Drug Packaging/Handling/Storage/Accountabilit y .. Training Procedures .. Concomitant Therapy .. General Considerations.

8 Medications Allowed During the Trial .. Ancillary Detoxification Comfort Medications .. Study Assessments .. Study Timetable .. Protocol Specific Assessments .. Laboratory Tests ( , Pregnancy Test, Liver Profile) .. Clinical Assessments ( Medical History and Physical Exam) .. Efficacy Assessments .. Urine Drug Testing .. Substance Use Report .. Clinical Opiate Withdrawal Scale (COWS) .. Visual Analog Scales (VAS) .. Safety Assessments .. Pain and Other Assessments .. Brief Pain Inventory.

9 Beck Depression Inventory II .. Pain and Opioid Analgesics Use History .. CIDI Section E and Section K .. SF-36 .. Fagerstrom Test for Nicotine Dependence .. Locator Information .. treatment Compliance .. Process Measures .. Projected Timetable for Assessments .. Common Assessment Battery (CAB) .. Brief Demographics Form .. Addiction Severity Index (ASI) - Lite .. Risk Behavior Survey .. Composite International Diagnostic Interview (CIDI) .. Statistical Analysis ..11-1 Table of ContentsCTN-0030 Protocolpage ivVersion Overview of Study Design.

10 General Analytic Strategy .. Significance Testing .. Preliminary Analysis .. Intent to Treat (ITT) and Completer Samples .. Missing Data and Dropouts .. Demographic and Baseline Characteristics .. Adjusting for Covariates .. Modeling of Site Effects .. Phase 1: Initial treatment Study .. Overview .. Outcome Measures and Predictors of Response .. Primary Outcome Measures .. Secondary Outcome Measures .. Covariates and Predictors of Outcome .. Statistical Considerations .. Randomization.