A Study on the Interaction Between Danoprevir/Ritonavir and Methadone

Study Overview
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Brief Summary
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This multicenter, open-label study will assess the effect of multiple doses of danoprevir/ritonavir on steady-state pharmacokinetics of methadone. Subjects on stable methadone maintenance therapy (20 - 120 mg daily as single oral morning dose) will receive danoprevir 100 mg orally twice daily and ritonavir 100 mg orally twice daily for 10 days.

Official Title
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Investigation of the Effect of Multiple Doses of Danoprevir/Ritonavir on Methadone in Subjects on Stable Methadone Maintenance Therapy (MMT)

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: danoprevir
* Drug: methadone
* Drug: ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults, 18 - 65 years of age, inclusive Subjects must be on a stable methadone maintenance regimen (20 to 120 mg/day) for the treatment of opiate addiction for at least 30 days prior to screening and should be on a stable dose for at least 14 days prior to Day -1 Body weight >/= 50 kg Body mass index (BMI) 18.0 - 32.0 kg/m2 Females of childbearing potential and males with female partners of childbearing potential must agree to use 2 forms of non-hormonal contraception during the study and for 90 days after the last study drug administration Exclusion Criteria: Pregnant or lactating women and male partners of women who are pregnant or lactating Symptoms of methadone withdrawal at screening, on Day -2 or Day -1 Inadequate venous access History or evidence of any clinically significant disease or disorder, except for drug abuse or dependence Positive test for alcohol or drugs of abuse at screening and up to Day -2 (with the exception of methadone) History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol); alcohol consumption will be prohibited during study confinement and for at least 48 hours before screening, dosing and each scheduled visit Positive for hepatitis B, hepatitis C or HIV infection

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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: danoprevir<br>* 200 mg daily (100 mg q12h) orally, Days 1-10<br>Drug: methadone<br>* stable maintenance therapy: 20-120 mg daily single oral morning dose<br>Drug: ritonavir<br>* 200 mg daily (100 mg q12h) orally, Days 1-10<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of danoprevir/ritonavir on steady state pharmacokinetics (area under the concentration - time curve (AUC)) of methadone |  | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | approximately 4 weeks |