A Study of Potential Drug-Drug Interaction Between Efavirenz and Danoprevir With Low Dose Ritonavir in Healthy Volunteers

A Study to Evaluate the Potential Drug-Drug Interaction Between Efavirenz and Danoprevir With Low Dose Ritonavir When Administered Together in Healthy Adult Volunteers

This phase 1, randomized, open-label, multiple-dose, 2-sequence, 2-period crossover study will evaluate potential drug-drug interaction between efavirenz and danoprevir with low-dose ritonavir in healthy volunteers. In Period 1. subjects will be randomized to receive multiple oral doses of either danoprevir with ritonavir or efavirenz for 14 days. In Period 2, all subjects will receive multiple oral doses of the combination danoprevir with ritonavir and efavirenz for 14 days. Anticipated time on study treatment is 28 days.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female non-smoking subjects, 18 to 55 years of age
• Healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history and a complete physical examination
• Medical history without major, recent or ongoing pathology
• Weight >/= 50.0 kg
• Body mass index (BMI) 18.0 - 32.0 kg/m2

Exclusion Criteria:

• Pregnant or lactating women or males with female partners who are pregnant or lactating
• History of any clinically significant medical condition which may impact the safety of the participant
• Positive results for drugs of abuse at screening or prior to admission to the clinical site during any study period
• Positive for hepatitis B, hepatitis C or HIV infection
• Current smokers or subjects who have discontinued smoking less than 6 months prior to first dose of study medication
• Use of hormonal contraceptives (e.g. birth control pill, patches, or injectable, implantable devices) within 30 days before the first dose of study medication
• Use of investigational drug or device within 30 days of the first dose of study medication (6 months for biologic therapies) or 5 half-lives of the investigational drug, whichever is longer
• History of drug-related allergic reaction
• History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average; alcohol consumption will be prohibited 72 hours prior to entry in the clinical site center and throughout the entire study

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A danoprevir+ritonavir	Drug: danoprevir; multiple oral doses; Drug: ritonavir; multiple oral doses
Active Comparator: B efavirenz	Drug: efavirenz; multiple oral doses
Experimental: C combination	Drug: danoprevir; multiple oral doses; Drug: ritonavir; multiple oral doses; Drug: efavirenz; multiple oral doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of efavirenz, danoprevir and ritonavir in coadministration: Cmax	Pre-dose and up to 24 hours post-dose on Days 14 and 28
Pharmacokinetics of efavirenz, danoprevir and ritonavir in coadministration: Area under the concentration-time curve (AUC)	Pre-dose and up to 24 hours post-dose on Days 14 and 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 2 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 19, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 30, 2012

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: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Ritonavir; Efavirenz
• Other Study ID Numbers: NP28103