A Study of The Relative Bioavailability of Ritonavir-Boosted Danoprevir Fixed Dose Combination Tablets in Healthy Volunteers
Study Details
Study Description
Brief Summary
This randomized, open-label, crossover study will evaluate the relative bioavailability of ritonavir-boosted danoprevir fixed dose combination tablets (FDC) as compared to ad hoc combination of reference tablets of danoprevir and ritonavir in healthy volunteers. Subjects will be randomized to 1 of 6 treatment sequences to receive single oral doses of either an FDC of danoprevir and ritonavir or danoprevir and ritonavir as separate tablets. In a crossover design, subjects will participate in 3 study periods with at least a 7-day washout between periods. In Part 2, single dose administration of film-coated FDCs will be compared to reference tablets.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: DNV + r reference
|
Drug: danoprevir
Reference tablet, single oral dose
Drug: ritonavir
Reference tablet, single oral dose
|
| Experimental: DNV/r fixed dose combination
|
Drug: danoprevir
Fixed dose combination tablet with ritonavir, single oral dose
Drug: ritonavir
Fixed dose combination tablet with danoprevir, single oral dose
|
Outcome Measures
Primary Outcome Measures
- Relative bioavailability of danoprevir: Area under the concentration-time curve (AUC) [Pre-dose and up to 24 hours post-dose Days 1, 8 and 15]
- Pharmacokinetics of ritonavir: Area under the concentration-time curve (AUC) [Pre-dose and up to 24 hours post-dose Days 1, 8 and 15]
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
-
Body weight >/= 50.0 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 cardiovascular or cerebrovascular disease, hypertension, and/or infections
-
Positive result 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
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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 pills, patches, 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 allergic reactions or hepatotoxicity
-
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 | Christchurch | New Zealand | 8011 |
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.- NP28136