A Pharmacokinetic And Bioavailability Study of Intravenous Danoprevir in Healthy Volunteers

Study Overview
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Brief Summary
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This three-part study will evaluate the pharmacokinetics and bioavailability of intravenous danoprevir with and without low-dose oral ritonavir, and the effect of oral cyclosporine on the pharmacokinetics of intravenous danoprevir with ritonavir in healthy volunteers.

Official Title
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A Three-Part Study Evaluating the Pharmacokinetics of Intravenous (IV) Danoprevir (DNV)/Oral Low-Dose Ritonavir (RTV), the Absolute Bioavailability of DNV With and Without Oral Low-Dose RTV, and the Effect of Oral Cyclosporine on IV DNV/Oral Low-Dose RTV in Healthy Adult Volunteers

Conditions
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Healthy Volunteer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult healthy male and female nonsmoking volunteers, 18 to 55 years of age inclusive; 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 Exclusion Criteria: Pregnant or lactating women or males with female partners who are pregnant or lactating 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: iv danoprevir<br> | Drug: danoprevir<br>* single iv infusion<br>Drug: ritonavir<br>* oral doses<br>|
| Placebo Comparator: Part 1: placebo<br> | Drug: placebo<br>* single iv infusion<br>Drug: ritonavir<br>* oral doses<br>|
| Experimental: Part 2 A: iv danoprevir<br> | Drug: danoprevir<br>* single iv infusion<br>Drug: ritonavir<br>* oral doses<br>|
| Active Comparator: Part 2 B: oral danoprevir<br> | Drug: danoprevir<br>* single oral dose<br>Drug: ritonavir<br>* oral doses<br>|
| Active Comparator: Part 2 C: ritonavir<br> | Drug: ritonavir<br>* oral doses<br>|
| Experimental: Part 3 D: iv danoprevir<br> | Drug: danoprevir<br>* single iv infusion<br>Drug: ritonavir<br>* oral doses<br>|
| Experimental: Part 3 E: iv danoprevir + cyclosporine<br> | Drug: danoprevir<br>* single iv infusion<br>Drug: ritonavir<br>* oral doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area under the concentration-time curve (AUC) |  | Pre-dose and up to 12 hours post-dose | 
| Safety: Incidence of adverse events |  | approximately 7 months |