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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: danoprevir
* Drug: danoprevir
* Drug: danoprevir placebo
* Drug: moxifloxacin
* Drug: moxifloxacin placebo
* Drug: ritonavir
* Drug: ritonavir placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: danoprevir<br>* 100 mg single dose orally<br>Drug: moxifloxacin placebo<br>* single oral dose<br>Drug: ritonavir<br>* 100 mg single dose orally<br>|
| Experimental: B<br> | Drug: danoprevir<br>* 400 mg single dose orally<br>Drug: moxifloxacin placebo<br>* single oral dose<br>Drug: ritonavir<br>* 100 mg single dose orally<br>|
| Active Comparator: C<br> | Drug: danoprevir placebo<br>* single oral dose<br>Drug: moxifloxacin<br>* 400 mg single dose orally<br>Drug: ritonavir placebo<br>* single oral dose<br>|
| Placebo Comparator: D<br> | Drug: danoprevir placebo<br>* single oral dose<br>Drug: moxifloxacin placebo<br>* single oral dose<br>Drug: ritonavir placebo<br>* single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |