A Relative Bioavailability Study of Danoprevir and Ritonavir in Healthy Volunteers

This single dose, randomized, open-label, 6 sequence, 3-period, crossover study will evaluate the relative bioavailability of danoprevir and ritonavir in healthy volunteers. In Part 1, subjects will be randomized to receive single oral doses of one of three tablet formulations of danoprevir plus the reference ritonavir formulation, with an at least 7-day washout between periods. In Part 2, subjects will be randomized to receive single oral doses of one of three tablet formulations of ritonavir plus the reference formulation of danoprevir, with at least a 7-day washout betwen periods. The anticipated time on study is up to 30 days.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 36
• 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 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers, 18 to 45 years of age inclusive
• Body mass index 18.0 - 32.0 kg/m2, weight >/= 50 kg
• Healthy status will be defined as absence of evidence of any active or chronic disease following a detailed medical and surgical history and a complete physical examination
• Non-smoker
• 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 (barrier form plus intrauterine device and spemicide) 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
• Positive results 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
• Use of hormonal contraceptives (birth control pills, injectable, implantable devices) within 30 days before the first dose of study medication
• Routine use of more than 2 g of acetaminophen daily
• History of clinically significant drug allergy (such as anaphylaxis) or hepatotoxicity
• History of hypersensitivity to danoptevir, ritonavir, or other protease inhibitors
• History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average
• Current enrollment or participation in a clinical trial of an experimental medication or medical device within 3 months of screening unless agreed upon by the Sponsor

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part 1 A	Drug: danoprevir; Phase 3 Tablet Formulation 1, single oral dose; Drug: danoprevir; Phase 3 Tablet Formulation 2, single oral dose; Drug: danoprevir; Reference Phase 2 Tablet Formulation, single oral dose; Drug: ritonavir; Test Formulation 1, single oral dose; Drug: ritonavir; Test Formulation 2, single oral dose; Drug: ritonavir; Reference Formulation, single oral dose
Experimental: Part 1 B	Drug: danoprevir; Phase 3 Tablet Formulation 1, single oral dose; Drug: danoprevir; Phase 3 Tablet Formulation 2, single oral dose; Drug: danoprevir; Reference Phase 2 Tablet Formulation, single oral dose; Drug: ritonavir; Test Formulation 1, single oral dose; Drug: ritonavir; Test Formulation 2, single oral dose; Drug: ritonavir; Reference Formulation, single oral dose
Experimental: Part 1 C	Drug: danoprevir; Phase 3 Tablet Formulation 1, single oral dose; Drug: danoprevir; Phase 3 Tablet Formulation 2, single oral dose; Drug: danoprevir; Reference Phase 2 Tablet Formulation, single oral dose; Drug: ritonavir; Test Formulation 1, single oral dose; Drug: ritonavir; Test Formulation 2, single oral dose; Drug: ritonavir; Reference Formulation, single oral dose
Active Comparator: Part 2 D	Drug: danoprevir; Phase 3 Tablet Formulation 1, single oral dose; Drug: danoprevir; Phase 3 Tablet Formulation 2, single oral dose; Drug: danoprevir; Reference Phase 2 Tablet Formulation, single oral dose; Drug: ritonavir; Test Formulation 1, single oral dose; Drug: ritonavir; Test Formulation 2, single oral dose; Drug: ritonavir; Reference Formulation, single oral dose
Experimental: Part 2 E	Drug: danoprevir; Phase 3 Tablet Formulation 1, single oral dose; Drug: danoprevir; Phase 3 Tablet Formulation 2, single oral dose; Drug: danoprevir; Reference Phase 2 Tablet Formulation, single oral dose; Drug: ritonavir; Test Formulation 1, single oral dose; Drug: ritonavir; Test Formulation 2, single oral dose; Drug: ritonavir; Reference Formulation, single oral dose
Experimental: Part 2 F	Drug: danoprevir; Phase 3 Tablet Formulation 1, single oral dose; Drug: danoprevir; Phase 3 Tablet Formulation 2, single oral dose; Drug: danoprevir; Reference Phase 2 Tablet Formulation, single oral dose; Drug: ritonavir; Test Formulation 1, single oral dose; Drug: ritonavir; Test Formulation 2, single oral dose; Drug: ritonavir; Reference Formulation, single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Danoprevir bioavailabilty (Tablet Formulation 1) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC)	24 hours
Part 1: Danoprevir bioavailability (Tablet Formulation 2) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC)	24 hours
Part 2: Ritonavir bioavailability (Test Formulation 1) in combination with danoprevir (refernce formulation): Area under the concentration-time curve (AUC)	24 hours
Part 2: Ritonavir bioavailability (Test Formulation 2) in combination with danoprevir (reference formulation): Area under the concentration-time curve (AUC)	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 4 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 30, 2011
• First Submitted That Met QC Criteria: November 30, 2011
• First Posted (Estimate): December 1, 2011

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: NP27945; RPU425UD-114254 (Other Identifier: PRA International)