Clinical trial NCT01592318: A Study of The Relative Bioavailability of Ritonavir-Boosted Danoprevir Fixed Dose Combination Tablets in Healthy Volunteers
Official title: An Up to Two-Part Relative Bioavailability Study of Ritonavir-Boosted Danoprevir Fixed Dose Combination Tablets as Compared to the Reference Phase 2 Ad Hoc Combination Tablets in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-05-07
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.


Eligibility 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
* 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

Primary outcomes:
measure: Relative bioavailability of danoprevir: Area under the concentration-time curve (AUC)
timeFrame: Pre-dose and up to 24 hours post-dose Days 1, 8 and 15
measure: Pharmacokinetics of ritonavir: Area under the concentration-time curve (AUC)
timeFrame: Pre-dose and up to 24 hours post-dose Days 1, 8 and 15
Secondary outcomes:
measure: Safety: Incidence of adverse events
timeFrame: approximately 2 months
Other outcomes:
Locations:
city: Christchurch
country: New Zealand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: