Drug-Drug Interaction Study Between Telaprevir and Buprenorphine

Study Overview
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Brief Summary
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The purpose of this study is to investigate the drug-drug interaction potential between telaprevir and buprenorphine/naloxone. An understanding of the interaction potential will help to determine whether buprenorphine dose adjustments are necessary for patients who are concomitantly treated with telaprevir. Telaprevir, in combination with other antiviral agents, is being investigated for the treatment of chronic hepatitis C virus infection. Buprenorphine/naloxone is used for maintainance therapy in patients with opioid dependence.

Official Title
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A Phase 1, Open-Label, Single-Sequence Study to Examine the Effect of Telaprevir on the Pharmacokinetics of Buprenorphine in Subjects on Stable Buprenorphine/Naloxone Maintenance Therapy

Conditions
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Hepatitis C, Opioid-Related Disorders

Intervention / Treatment
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* Drug: telaprevir
* Drug: buprenorphine/naloxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between the ages of 18 and 64 years, inclusive. Females must be of non-childbearing potential. Receiving once daily buprenorphine/naloxone maintenance therapy at a stable dose not exceeding 24 mg/6 mg, respectively, for at least 2 weeks prior to screening. Exclusion Criteria: Illicit use of drugs such as cocaine, amphetamines and methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines, tricyclic antidepressants, methadone or opiates/opioids (apart from buprenorphine). Treatment with any investigational drug within the last 30 days, or 5 half-lives, whichever is longer. Blood donation of 500 mL or more within the last 56 days. Infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label Arm<br>The treatment period will include 3 phases: 14 day run-in period 7 day co-administration period 31 day follow-up period | Drug: telaprevir<br>* Two 375 mg tablets administered every 8 hours on Day 1 through Day 7, inclusive.<br>Drug: buprenorphine/naloxone<br>* Buprenorphine/naloxone sublingual tablets or films contain buprenorphine HCl and naloxone HCl dihydrate at a ratio of 4:1 buprenorphine:naloxone (ratio of free bases). In this study buprenorphine/naloxone will be dosed from Day -14 through Day 38, inclusive. From Day -14 through Day -1 all subjects will receive a maximum of 24 mg/6 mg of buprenorphine/naloxone. Subjects will not be permitted to change their dose during the telaprevir co-administration period (Day 1 through Day 7) unless warranted by the investigator's clinical judgment of subject safety. After Day 8, the dose of buprenorphine/naloxone may be adjusted if deemed necessary by the investigator.<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood levels of buprenorphine | Measured by maximum observed concentration (Cmax), minimum observed concentration (Cmin), time of the maximum concentration (tmax), area under the time curve (AUC) from the time of study drug administration, zero to tau, where tau is the dosing interval. | Day -4 through Day 38 | 
| Blood levels of norbuprenorphine | Measured by maximum observed concentration (Cmax), minimum observed concentration (Cmin), time of the maximum concentration (tmax), area under the time curve (AUC) from the time of study drug administration, zero to tau, where tau is the dosing interval. | Day -4 through Day 38 | 
| Blood levels of naloxone | Measured by maximum observed concentration (Cmax) | Day -1 and Day 7 | 
| Blood levels of telaprevir | Measured by maximum observed concentration (Cmax), minimum observed concentration (Cmin), time of the maximum concentration (tmax), area under the time curve (AUC) from the time of study drug administration, zero to tau, where tau is the dosing interval. | Day 1 through Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Measured by incidence of treatment-emergent adverse events, clinical laboratory assessments, electrocardiogram outcomes, and vital signs. | Day -14 through Day 38 | 
| Buprenorphine withdrawal symtoms | Measured by Clinical Opiate Withdrawal Scale (COWS), Desires for Drug Questionnaire (DDQ), and pupillometry. | Day -2 through Day 38 |