A Study on the Interaction Between Danoprevir/Ritonavir and Methadone

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: danoprevir; Drug: methadone; Drug: ritonavir

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
  • Kansas
    • Overland Park, Kansas, United States, 66211

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: July 6, 2011
• First Submitted That Met QC Criteria: July 6, 2011
• First Posted (Estimate): July 8, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Protease Inhibitors; Analgesics, Opioid; Narcotics; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Respiratory System Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitussive Agents; Ritonavir; Methadone
• Other Study ID Numbers: NP25644