A Study of Drug-Drug Interaction Between Danoprevir/Low-Dose Ritonavir and Raltegravir in Healthy Volunteers

Study Overview
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Brief Summary
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This open-label, multiple dose, single sequence crossover study will evaluate the drug-drug interaction between danoprevir/low-dose ritonavir and raltegravir in healthy volunteers. Subjects will receive raltegravir on Days 1-4 and, after a washout period of 3 days, danoprevir and low-dose ritonavir on Days 8-21, in combination with raltegravir on Days 18-21.

Official Title
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A Study to Evaluate the Potential Drug-Drug Interaction Between Danoprevir/Low-Dose Ritonavir When Given With Raltegravir in Healthy Adult Volunteers

Conditions
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Healthy Volunteer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy non-smoking male and female adults, 18 - 55 years of age, inclusive Healthy status defined by absence of evidence of any active or chronic disease Medical history without major, recent, or ongoing pathology Weight >/= 50.0 kg Body mass index (BMI) 18.0 - 32-0 kg/m2 Willingness to abstain from alcohol, xanthine-containing beverages or food (e.g. coffee, tea, cola, chocolate, energy drinks) from 48 hours prior to entry in the clinical site until discharge Females of child-bearing potential and males and their female partners of child-bearing potential must agree to use 2 forms of contraception, one of which must be a barrier method, during the study and for 90 days after the last drug administration. Acceptable barrier forms of contraception are condom and diaphragm; acceptable non-barrier forms of contraception for this study are non-hormonal intrauterine device (IUD) and/or spermicide Exclusion Criteria: Pregnant or lactating females or males with female partners who are pregnant or lactating Any history of clinically significant cardiovascular or cerebrovascular disease, hypertension, and/or infections Positive test 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 within 30 days before the first dose of study medication History of clinically significant drug-related allergy (such as anaphylaxis) or hepatotoxicity

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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Period 1 Control<br> | Drug: raltegravir<br>* 400 mg q12h Days 1-4 and 18-21<br>|
| Experimental: Period 2 danoprevir/ritonavir<br> | Drug: danoprevir<br>* 100 mg q12h Days 8-21<br>Drug: raltegravir<br>* 400 mg q12h Days 1-4 and 18-21<br>Drug: ritonavir<br>* 100 mg q12h Days 8-21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of steady-state ritonavir-boosted danoprevir on steady-state raltegravir pharmacokinetics: Area under the concentration-time curve (AUC) |  | approximately 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of steady-state raltegravir on danoprevir/ritonavir pharmacokinetics: Area under the concentration-time curve (AUC) |  | Pre-dose Days 8. 14, 15, 16 and 20, pre-and up to 24 h post-dose Days 17 and 21 | 
| Safety: Incidence of adverse events |  | approximately 2 months |