A Study of Drug-Drug Interaction Between Danoprevir Coadministered With Low-Dose Ritonavir and Tenofovir Disoproxil Fumarate or Atazanavir
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: S1 P1 TDF + DNV/r
|
Drug: danoprevir
multiple oral doses
Drug: ritonavir
multiple oral doses
Drug: tenofovir disoproxil fumarate
single oral doses
|
| Experimental: S1/S2 P2 DNV/r + ATZ
|
Drug: atazanavir
multiple oral doses
Drug: danoprevir
multiple oral doses
Drug: ritonavir
multiple oral doses
|
| Experimental: S2 P1 ATZ/r
|
Drug: atazanavir
multiple oral doses
Drug: ritonavir
multiple oral doses
|
Outcome Measures
Primary Outcome Measures
- 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
- Safety: Incidence of adverse events [approximately 2 months]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lenexa | Kansas | United States | 66219 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NP28104