A Study of Drug-Drug Interaction Between Danoprevir Coadministered With Low-Dose Ritonavir and Tenofovir Disoproxil Fumarate or Atazanavir

A Study to Evaluate the Potential Drug-Drug Interaction Between Danoprevir When Coadministered With Low-Dose Ritonavir and Tenofovir Disoproxil Fumarate or Atazanavir in Healthy Adult Volunteers

This randomized, open-label, multiple-treatment multiple-dose, 2-period, 2-sequence study will evaluate potential drug-drug interactions between danoprevir (DNV) when coadministered with low-dose ritonavir (r) and tenofovir disoproxil fumarate (TDF) or atazanavir (ATZ) in healthy volunteers. Subjects will be randomized to receive in Period 1 either single oral doses of TDF and multiple oral doses of DNV/r or multiple oral doses of ATZ/r. In Period 2, all subjects will receive multiple oral doses of DNV/r plus ATZ. Anticipated time on study treatment is up to 20 days.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: danoprevir; Drug: ritonavir; Drug: tenofovir disoproxil fumarate; Drug: atazanavir

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219

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, inclusive
• Body weight >/= 55 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 disease or condition
• Positive for drugs of abuse at screening or prior to admission to the clinical site
• 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 pill, patches, or 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 allergy reaction
• 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

• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S1 P1 TDF + DNV/r	Drug: danoprevir; multiple oral doses; Drug: ritonavir; multiple oral doses; Drug: tenofovir disoproxil fumarate; single oral doses
Experimental: S1/S2 P2 DNV/r + ATZ	Drug: danoprevir; multiple oral doses; Drug: ritonavir; multiple oral doses; Drug: atazanavir; multiple oral doses
Experimental: S2 P1 ATZ/r	Drug: ritonavir; multiple oral doses; Drug: atazanavir; multiple oral doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of tenofovir disoproxil fumarate and atazanavir when coadministered with danoprevir/ritonavir: Area under the concentration-time curve (AUC)	Pre-dose, and up to 48 hours post-dose Days 1, 8, 11, 16, 20
Pharmacokinetics of danoprevir and ritonavir when coadministered with tenofovir disoproxil fumarate and atazanavir: Area under the concentration-time curve (AUC)	Pre-dose, and up to 24 hours post-dose Days 10, 11, 16, 20

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; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Ritonavir; Atazanavir Sulfate
• Other Study ID Numbers: NP28104