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
Overview
- Phase
- Phase 1
- Intervention
- danoprevir
- Conditions
- Healthy Volunteer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 40
- Primary Endpoint
- Pharmacokinetics of tenofovir disoproxil fumarate and atazanavir when coadministered with danoprevir/ritonavir: Area under the concentration-time curve (AUC)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
S1/S2 P2 DNV/r + ATZ
Intervention: danoprevir
S1/S2 P2 DNV/r + ATZ
Intervention: ritonavir
S2 P1 ATZ/r
Intervention: atazanavir
S1 P1 TDF + DNV/r
Intervention: danoprevir
S2 P1 ATZ/r
Intervention: ritonavir
S1 P1 TDF + DNV/r
Intervention: ritonavir
S1 P1 TDF + DNV/r
Intervention: tenofovir disoproxil fumarate
S1/S2 P2 DNV/r + ATZ
Intervention: atazanavir
Outcomes
Primary Outcomes
Pharmacokinetics of tenofovir disoproxil fumarate and atazanavir when coadministered with danoprevir/ritonavir: Area under the concentration-time curve (AUC)
Time Frame: 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)
Time Frame: Pre-dose, and up to 24 hours post-dose Days 10, 11, 16, 20
Secondary Outcomes
- Safety: Incidence of adverse events(approximately 2 months)