A Relative Bioavailability Study of Danoprevir and Ritonavir in Healthy Volunteers - Full Text View

Purpose

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.

Condition	Intervention	Phase
Healthy Volunteer	Drug: danoprevir Drug: ritonavir	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-availability Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

Drug Information available for: Ritonavir

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Part 1: Danoprevir bioavailabilty (Tablet Formulation 1) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Part 1: Danoprevir bioavailability (Tablet Formulation 2) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Part 2: Ritonavir bioavailability (Test Formulation 1) in combination with danoprevir (refernce formulation): Area under the concentration-time curve (AUC) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Part 2: Ritonavir bioavailability (Test Formulation 2) in combination with danoprevir (reference formulation): Area under the concentration-time curve (AUC) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety: Incidence of adverse events [ Time Frame: approximately 4 months ] [ Designated as safety issue: No ]

Enrollment:	36
Study Start Date:	December 2011
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Part 1 A	Drug: danoprevir Reference Phase 2 Tablet Formulation, 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: ritonavir Reference Formulation, single oral dose
Experimental: Part 1 C	Drug: danoprevir Phase 3 Tablet Formulation 2, single oral dose Drug: ritonavir Reference Formulation, single oral dose
Active Comparator: Part 2 D	Drug: danoprevir Reference Phase 2 Tablet Formulation, single oral dose Drug: ritonavir Reference Formulation, single oral dose
Experimental: Part 2 E	Drug: danoprevir Reference Phase 2 Tablet Formulation, single oral dose Drug: ritonavir Test Formulation 1, single oral dose
Experimental: Part 2 F	Drug: danoprevir Reference Phase 2 Tablet Formulation, single oral dose Drug: ritonavir Test Formulation 2, single oral dose

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01483729

Locations

New Zealand

Christchurch, New Zealand

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01483729 History of Changes
Other Study ID Numbers:	NP27945, RPU425UD-114254
Study First Received:	November 30, 2011
Last Updated:	March 4, 2013
Health Authority:	New Zealand: Medsafe

Additional relevant MeSH terms:

Ritonavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013