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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: danoprevir; Drug: danoprevir; Drug: ritonavir; Drug: ritonavir

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DNV + r reference	Drug: danoprevir; Fixed dose combination tablet with ritonavir, single oral dose; Drug: danoprevir; Reference tablet, single oral dose; Drug: ritonavir; Fixed dose combination tablet with danoprevir, 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: danoprevir; Reference tablet, single oral dose; Drug: ritonavir; Fixed dose combination tablet with danoprevir, single oral dose; Drug: ritonavir; Reference tablet, single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 2 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 24, 2012
• First Submitted That Met QC Criteria: May 3, 2012
• First Posted (Estimate): May 7, 2012

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lactams
• Other Study ID Numbers: NP28136