A Study of Danoprevir in Combination With Low-Dose Ritonavir in Healthy Subjects

A Single-center, Single-dose, Randomized, Double-blind, Double-dummy, Placebo-controlled, Positive-controlled, Four-way Crossover Study to Investigate the Effect of Danoprevir With Low Dose Ritonavir (DNV/r) on the QT/QTc Interval in Healthy Subjects

This single-dose, randomized, double-blind, double-dummy, placebo-controlled, positive-controlled four-way crossover study will evaluate the effect of a single dose of danoprevir with low-dose ritonavir on the QC/QTc interval in healthy volunteers. Subjects will be randomly assigned to one of four sequences with treatments of A: therapeutic dose of danoprevir plus ritonavir (DNV/r), B: supratherapeutic dose of DNV/r, C: moxifloxacin and D: placebo, with a washout period of at least 7 days between treatments.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67064

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult healthy volunteers, 18 - 60 years of age
• Female subjects must be surgically sterile or post-menopausal
• Male subjects and their partners of child-bearing potential must use to methods of contraception for the duration of the study and for three months after the last drug administration
• Agree to abstain from strenuous exercise for three days before dosing and throughout the study (including washout period and follow-up visit)

Exclusion Criteria:

• History or evidence of any clinically significant disease or disorder
• Pregnant or lactating women
• Male partners of women who are lactating or trying to become pregnant
• Current smokers or subjects who have discontinued smoking less than six months prior to first dosing
• Positive alcohol breath test; suspicion of regular consumption of drugs of abuse
• Positive for hepatitis B, hepatitis C or HIV infection
• Participation in an investigational drug, biologic, or device study within three months before first study drug administration

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: danoprevir; 100 mg single dose orally; Drug: danoprevir; 400 mg single dose orally; Drug: moxifloxacin placebo; single oral dose; Drug: ritonavir; 100 mg single dose orally
Experimental: B	Drug: danoprevir; 100 mg single dose orally; Drug: danoprevir; 400 mg single dose orally; Drug: moxifloxacin placebo; single oral dose; Drug: ritonavir; 100 mg single dose orally
Active Comparator: C	Drug: danoprevir placebo; single oral dose; Drug: moxifloxacin; 400 mg single dose orally; Drug: ritonavir placebo; single oral dose
Placebo Comparator: D	Drug: moxifloxacin placebo; single oral dose; Drug: danoprevir placebo; single oral dose; Drug: ritonavir placebo; single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Threshold pharmacological effect on cardiac repolarization as detected by changes in the QT/QTc interval following single dose	approximately 9 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Plasma concentrations	approximately 9 weeks
Safety: Incidence of adverse events	approximately 9 weeks
Cardiac response: Electrocardiogram (ECG)	approximately 9 weeks
Correlation between pharmacokinetics (plasma concentrations) and QT/QTc interval changes	approximately 9 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 20, 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; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Protease Inhibitors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; HIV Protease Inhibitors; Viral Protease Inhibitors; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Ritonavir; Lactams
• Other Study ID Numbers: NP25298; 2011-001413-13 (EudraCT Number)