A Study of Potential Drug-Drug Interaction Between Efavirenz and Danoprevir With Low Dose Ritonavir in Healthy Volunteers

Study Overview
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Brief Summary
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This phase 1, randomized, open-label, multiple-dose, 2-sequence, 2-period crossover study will evaluate potential drug-drug interaction between efavirenz and danoprevir with low-dose ritonavir in healthy volunteers. In Period 1. subjects will be randomized to receive multiple oral doses of either danoprevir with ritonavir or efavirenz for 14 days. In Period 2, all subjects will receive multiple oral doses of the combination danoprevir with ritonavir and efavirenz for 14 days. Anticipated time on study treatment is 28 days.

Official Title
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A Study to Evaluate the Potential Drug-Drug Interaction Between Efavirenz and Danoprevir With Low Dose Ritonavir When Administered Together in Healthy Adult Volunteers

Conditions
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Healthy Volunteer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female non-smoking subjects, 18 to 55 years of age 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 Weight >/= 50.0 kg Body mass index (BMI) 18.0 - 32.0 kg/m2 Exclusion Criteria: Pregnant or lactating women or males with female partners who are pregnant or lactating History of any clinically significant medical condition which may impact the safety of the participant 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 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 pill, patches, or injectable, implantable devices) within 30 days before the first dose of study medication Use of 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 reaction History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average; alcohol consumption will be prohibited 72 hours prior to entry in the clinical site center and throughout the entire study

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: A danoprevir+ritonavir<br> | Drug: danoprevir<br>* multiple oral doses<br>Drug: ritonavir<br>* multiple oral doses<br>|
| Active Comparator: B efavirenz<br> | Drug: efavirenz<br>* multiple oral doses<br>|
| Experimental: C combination<br> | Drug: danoprevir<br>* multiple oral doses<br>Drug: efavirenz<br>* multiple oral doses<br>Drug: ritonavir<br>* multiple oral doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of efavirenz, danoprevir and ritonavir in coadministration: Cmax |  | Pre-dose and up to 24 hours post-dose on Days 14 and 28 | 
| Pharmacokinetics of efavirenz, danoprevir and ritonavir in coadministration: Area under the concentration-time curve (AUC) |  | Pre-dose and up to 24 hours post-dose on Days 14 and 28 | 

Secondary Outcome Measures

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