A Study of Drug-Drug Interaction Between Danoprevir Coadministered With Low-Dose Ritonavir and Tenofovir Disoproxil Fumarate or Atazanavir

Study Overview
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Brief Summary
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This randomized, open-label, multiple-treatment multiple-dose, 2-period, 2-sequence study will evaluate potential drug-drug interactions between danoprevir (DNV) when coadministered with low-dose ritonavir (r) and tenofovir disoproxil fumarate (TDF) or atazanavir (ATZ) in healthy volunteers. Subjects will be randomized to receive in Period 1 either single oral doses of TDF and multiple oral doses of DNV/r or multiple oral doses of ATZ/r. In Period 2, all subjects will receive multiple oral doses of DNV/r plus ATZ. Anticipated time on study treatment is up to 20 days.

Official Title
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A Study to Evaluate the Potential Drug-Drug Interaction Between Danoprevir When Coadministered With Low-Dose Ritonavir and Tenofovir Disoproxil Fumarate or Atazanavir in Healthy Adult Volunteers

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: atazanavir
* Drug: danoprevir
* Drug: ritonavir
* Drug: tenofovir disoproxil fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female volunteers, 18 to 55 years of age, inclusive Body weight >/= 55 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 disease or condition Positive for drugs of abuse at screening or prior to admission to the clinical site 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 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 allergy reaction 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

Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S1 P1 TDF + DNV/r<br> | Drug: danoprevir<br>* multiple oral doses<br>Drug: ritonavir<br>* multiple oral doses<br>Drug: tenofovir disoproxil fumarate<br>* single oral doses<br>|
| Experimental: S1/S2 P2 DNV/r + ATZ<br> | Drug: atazanavir<br>* multiple oral doses<br>Drug: danoprevir<br>* multiple oral doses<br>Drug: ritonavir<br>* multiple oral doses<br>|
| Experimental: S2 P1 ATZ/r<br> | Drug: atazanavir<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 tenofovir disoproxil fumarate and atazanavir when coadministered with danoprevir/ritonavir: Area under the concentration-time curve (AUC) |  | Pre-dose, and up to 48 hours post-dose Days 1, 8, 11, 16, 20 | 
| Pharmacokinetics of danoprevir and ritonavir when coadministered with tenofovir disoproxil fumarate and atazanavir: Area under the concentration-time curve (AUC) |  | Pre-dose, and up to 24 hours post-dose Days 10, 11, 16, 20 | 

Secondary Outcome Measures

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