Drug Interaction & Methadone & Buprenorphine

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of steady state DCV/ASV/BMS-791325 fixed dose combination (FDC) + 75mg BMS-791325 on the Pharmacokinetics (PK) of Methadone in subjects with the stable dose of Methadone and on the PK of Buprenorphine in subjects with the stable dose of Buprenorphine.

Detailed Description
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IND number: 101,943 Primary purpose: Other: Phase 1 Clinical Pharmacology drug interaction study in healthy subjects

Official Title
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A Phase1, Open-Label, Drug-Drug Interaction Study Between Methadone and Daclatasvir/Asunaprevir/BMS-791325 3 DAA FDC + 75mg BMS-791325 and Between Buprenorphine/Naloxone and Daclatasvir/Asunaprevir/BMS-791325 3 DAA FDC +75mg BMS-791325

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Methadone
* Drug: DCV 3DAA FDC
* Drug: BMS-791325
* Drug: Buprenorphine
* Drug: Naloxone


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Subject must be on stable Methadone or Buprenorphine regimens for at least 28 days prior to screening Exclusion Criteria: Subjects must be healthy except for history of Methadone or Buprenorphine treatment regimens Prior exposure to DCV, ASV or BMS-791325 within 3 months of screening or any other investigational drug or placebo within 4 weeks of study drug administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Methadone + DCV 3DAA FDC + BMS-791325<br>Methadone 40-120 mg tablet or solution orally once on Day 1 Methadone 40-120 mg tablet or solution orally once daily + DCV 3DAA FDC (Daclatasvir 30 mg/Asunaprevir 200 mg/BMS-791325 75 mg 3 direct-acting antiviral (3DAA) fixed dose combination tablet) orally twice daily + BMS-791325 75 mg tablet orally twice daily on Days 2 through 12 | Drug: Methadone<br> <br> Drug: DCV 3DAA FDC<br> <br> Drug: BMS-791325<br> <br> |
| Active Comparator: Part 2: Buprenorphine/Naloxone + DCV 3DAA FDC + BMS-791325<br>Buprenorphine/Naloxone 8/2 - 24/6 mg tablet or sublingual film orally once on Day 1 Buprenorphine/Naloxone 8/2 - 24/6 mg tablet or sublingual film orally once + DCV 3DAA FDC (Daclatasvir 30 mg/Asunaprevir 200 mg/BMS-791325 75 mg 3DAA fixed dose combination tablet) orally twice daily + BMS-791325 75 mg tablet orally twice daily on Days 2 through 12 | Drug: DCV 3DAA FDC<br> <br> Drug: BMS-791325<br> <br> Drug: Buprenorphine<br> <br> Drug: Naloxone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) of R-Methadone for Part 1 |  | 24 timepoints up to Day 13 | 
| Area under the concentration-time curve in one dosing interval (AUC(TAU)) of R-Methadone for Part 1 |  | 24 timepoints up to Day 13 | 
| Cmax of Buprenorphine and Norbuprenorphine for Part 2 |  | 24 timepoints up to Day 13 | 
| AUC(TAU) of Buprenorphine and Norbuprenorphine for Part 2 |  | 24 timepoints up to Day 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of S-Methadone and Total Methadone for Part 1 |  | 24 timepoints up to 13 days | 
| AUC(TAU) of S-Methadone and Total Methadone for Part 1 |  | 24 timepoints up to 13 days | 
| Concentration at 24 hours (C24) of S-Methadone, Total Methadone and R-Methadone for Part 1 |  | 24 timepoints up to 13 days | 
| Time of maximum observed concentration (Tmax) of S-Methadone, Total Methadone and R-Methadone for Part 1 |  | 24 timepoints up to 13 days | 
| C24 of Buprenorphine and Norbuprenorphine for Part 2 |  | 24 timepoints up to 13 days | 
| Tmax of Buprenorphine and Norbuprenorphine for Part 2 |  | 24 timepoints up to 13 days | 
| Ratio of metabolite AUC(TAU) to parent AUC(TAU) (MR_AUC(TAU)) of Norbuprenorphine to Buprenorphine |  | 24 timepoints up to 13 days | 
| Cmax of of Daclatasvir (DCV) , Asunaprevir (ASV) , BMS-791325, and BMS-794712 |  | 10 timepoints on Day 12 | 
| AUC(TAU) of DCV, ASV, BMS-791325, and BMS-794712 |  | 10 timepoints on Day 12 | 
| Concentration at 12 hours (C12) of DCV, ASV, BMS-791325, and BMS-794712 |  | 10 timepoints on Day 12 | 
| Tmax of DCV, ASV, BMS-791325, and BMS-794712 |  | 10 timepoints on Day 12 | 
| MR_AUC(TAU) for BMS-794712 to BMS-791325 |  | 10 timepoints on Day 12 | 
| Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), death and AEs leading to discontinuation |  | Up to day 13 | 
| Results of vital signs, Electrocardiograms (ECGs), Physical Examinations (PEs) and clinical labs |  | Up to day 13 | 
| Scores of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), Objective Opiate Withdrawal Scale (OOWS), and Opiate Overdose Assessment (OOA) |  | Up to day 13 |