A Study of The Relative Bioavailability of Ritonavir-Boosted Danoprevir Fixed Dose Combination Tablets in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Drug: danoprevir; Drug: ritonavir

• Registration Number: NCT01592318
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-04-24
• Study Start: 2012-05
• Study First Submitted QC: 2012-05-03
• Study First Posted: 2012-05-07
• Primary Completion: 2012-06
• Study Completion: 2012-06
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
DNV + r reference	danoprevir	-
DNV + r reference	ritonavir	-
DNV/r fixed dose combination	danoprevir	-
DNV/r fixed dose combination	ritonavir	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Safety: Incidence of adverse events	approximately 2 months