A Study of The Relative Bioavailability of Ritonavir-Boosted Danoprevir Fixed Dose Combination Tablets in Healthy Volunteers

Study Overview
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Brief Summary
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This randomized, open-label, crossover study will evaluate the relative bioavailability of ritonavir-boosted danoprevir fixed dose combination tablets (FDC) as compared to ad hoc combination of reference tablets of danoprevir and ritonavir in healthy volunteers. Subjects will be randomized to 1 of 6 treatment sequences to receive single oral doses of either an FDC of danoprevir and ritonavir or danoprevir and ritonavir as separate tablets. In a crossover design, subjects will participate in 3 study periods with at least a 7-day washout between periods. In Part 2, single dose administration of film-coated FDCs will be compared to reference tablets.

Official Title
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An Up to Two-Part Relative Bioavailability Study of Ritonavir-Boosted Danoprevir Fixed Dose Combination Tablets as Compared to the Reference Phase 2 Ad Hoc Combination Tablets in Healthy Adult Volunteers

Conditions
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Healthy Volunteer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female volunteers, 18 to 55 years of age Body weight >/= 50.0 kg Body mass index (BMI) 18.0 - 32.0 kg/m2 Healthy non-smoking subjects. 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 Females of childbearing potential and males and their female partners of childbearing potential must agree to use 2 forms of contraception, 1 of which must be a barrier method, during the study and for 90 days after the last drug administration Exclusion Criteria: Pregnant or lactating women or males with female partners who are pregnant or lactating Any history of clinically significant cardiovascular or cerebrovascular disease, hypertension, and/or infections Positive result 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 pills, patches, injectable, implantable devices) within 30 days before the first dose of study medication Use of an 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 reactions or hepatotoxicity History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DNV + r reference<br> | Drug: danoprevir<br>* Reference tablet, single oral dose<br>Drug: ritonavir<br>* Reference tablet, single oral dose<br>|
| Experimental: DNV/r fixed dose combination<br> | Drug: danoprevir<br>* Fixed dose combination tablet with ritonavir, single oral dose<br>Drug: ritonavir<br>* Fixed dose combination tablet with danoprevir, single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative bioavailability of danoprevir: Area under the concentration-time curve (AUC) |  | Pre-dose and up to 24 hours post-dose Days 1, 8 and 15 | 
| Pharmacokinetics of ritonavir: Area under the concentration-time curve (AUC) |  | Pre-dose and up to 24 hours post-dose Days 1, 8 and 15 | 

Secondary Outcome Measures

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