A Relative Bioavailability Study of Danoprevir and Ritonavir in Healthy Volunteers

Study Overview
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Brief Summary
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This single dose, randomized, open-label, 6 sequence, 3-period, crossover study will evaluate the relative bioavailability of danoprevir and ritonavir in healthy volunteers. In Part 1, subjects will be randomized to receive single oral doses of one of three tablet formulations of danoprevir plus the reference ritonavir formulation, with an at least 7-day washout between periods. In Part 2, subjects will be randomized to receive single oral doses of one of three tablet formulations of ritonavir plus the reference formulation of danoprevir, with at least a 7-day washout betwen periods. The anticipated time on study is up to 30 days.

Conditions
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Healthy Volunteer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers, 18 to 45 years of age inclusive Body mass index 18.0 - 32.0 kg/m2, weight >/= 50 kg Healthy status will be defined as absence of evidence of any active or chronic disease following a detailed medical and surgical history and a complete physical examination Non-smoker 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 (barrier form plus intrauterine device and spemicide) 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 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 Use of hormonal contraceptives (birth control pills, injectable, implantable devices) within 30 days before the first dose of study medication Routine use of more than 2 g of acetaminophen daily History of clinically significant drug allergy (such as anaphylaxis) or hepatotoxicity History of hypersensitivity to danoptevir, ritonavir, or other protease inhibitors History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average Current enrollment or participation in a clinical trial of an experimental medication or medical device within 3 months of screening unless agreed upon by the Sponsor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part 1 A<br> | Drug: danoprevir<br>* Reference Phase 2 Tablet Formulation, single oral dose<br>Drug: ritonavir<br>* Reference Formulation, single oral dose<br>|
| Experimental: Part 1 B<br> | Drug: danoprevir<br>* Phase 3 Tablet Formulation 1, single oral dose<br>Drug: ritonavir<br>* Reference Formulation, single oral dose<br>|
| Experimental: Part 1 C<br> | Drug: danoprevir<br>* Phase 3 Tablet Formulation 2, single oral dose<br>Drug: ritonavir<br>* Reference Formulation, single oral dose<br>|
| Active Comparator: Part 2 D<br> | Drug: danoprevir<br>* Reference Phase 2 Tablet Formulation, single oral dose<br>Drug: ritonavir<br>* Reference Formulation, single oral dose<br>|
| Experimental: Part 2 E<br> | Drug: danoprevir<br>* Reference Phase 2 Tablet Formulation, single oral dose<br>Drug: ritonavir<br>* Test Formulation 1, single oral dose<br>|
| Experimental: Part 2 F<br> | Drug: danoprevir<br>* Reference Phase 2 Tablet Formulation, single oral dose<br>Drug: ritonavir<br>* Test Formulation 2, single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Danoprevir bioavailabilty (Tablet Formulation 1) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC) |  | 24 hours | 
| Part 1: Danoprevir bioavailability (Tablet Formulation 2) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC) |  | 24 hours | 
| Part 2: Ritonavir bioavailability (Test Formulation 1) in combination with danoprevir (refernce formulation): Area under the concentration-time curve (AUC) |  | 24 hours | 
| Part 2: Ritonavir bioavailability (Test Formulation 2) in combination with danoprevir (reference formulation): Area under the concentration-time curve (AUC) |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | approximately 4 months |