A Study of Danoprevir in Combination With Low-Dose Ritonavir in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01398293
Recruitment Status : Completed
First Posted : July 20, 2011
Last Update Posted : November 2, 2016
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This single-dose, randomized, double-blind, double-dummy, placebo-controlled, positive-controlled four-way crossover study will evaluate the effect of a single dose of danoprevir with low-dose ritonavir on the QC/QTc interval in healthy volunteers. Subjects will be randomly assigned to one of four sequences with treatments of A: therapeutic dose of danoprevir plus ritonavir (DNV/r), B: supratherapeutic dose of DNV/r, C: moxifloxacin and D: placebo, with a washout period of at least 7 days between treatments.

Condition or disease Intervention/treatment Phase
Healthy Volunteer Drug: danoprevir Drug: danoprevir placebo Drug: moxifloxacin Drug: moxifloxacin placebo Drug: ritonavir Drug: ritonavir placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Official Title: A Single-center, Single-dose, Randomized, Double-blind, Double-dummy, Placebo-controlled, Positive-controlled, Four-way Crossover Study to Investigate the Effect of Danoprevir With Low Dose Ritonavir (DNV/r) on the QT/QTc Interval in Healthy Subjects
Study Start Date : August 2011
Actual Primary Completion Date : November 2011
Actual Study Completion Date : November 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Ritonavir

Arm Intervention/treatment
Experimental: A Drug: danoprevir
100 mg single dose orally

Drug: moxifloxacin placebo
single oral dose

Drug: ritonavir
100 mg single dose orally

Experimental: B Drug: danoprevir
400 mg single dose orally

Drug: moxifloxacin placebo
single oral dose

Drug: ritonavir
100 mg single dose orally

Active Comparator: C Drug: danoprevir placebo
single oral dose

Drug: moxifloxacin
400 mg single dose orally

Drug: ritonavir placebo
single oral dose

Placebo Comparator: D Drug: danoprevir placebo
single oral dose

Drug: moxifloxacin placebo
single oral dose

Drug: ritonavir placebo
single oral dose

Primary Outcome Measures :
  1. Threshold pharmacological effect on cardiac repolarization as detected by changes in the QT/QTc interval following single dose [ Time Frame: approximately 9 weeks ]

Secondary Outcome Measures :
  1. Pharmacokinetics: Plasma concentrations [ Time Frame: approximately 9 weeks ]
  2. Safety: Incidence of adverse events [ Time Frame: approximately 9 weeks ]
  3. Cardiac response: Electrocardiogram (ECG) [ Time Frame: approximately 9 weeks ]
  4. Correlation between pharmacokinetics (plasma concentrations) and QT/QTc interval changes [ Time Frame: approximately 9 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Adult healthy volunteers, 18 - 60 years of age
  • Female subjects must be surgically sterile or post-menopausal
  • Male subjects and their partners of child-bearing potential must use to methods of contraception for the duration of the study and for three months after the last drug administration
  • Agree to abstain from strenuous exercise for three days before dosing and throughout the study (including washout period and follow-up visit)

Exclusion Criteria:

  • History or evidence of any clinically significant disease or disorder
  • Pregnant or lactating women
  • Male partners of women who are lactating or trying to become pregnant
  • Current smokers or subjects who have discontinued smoking less than six months prior to first dosing
  • Positive alcohol breath test; suspicion of regular consumption of drugs of abuse
  • Positive for hepatitis B, hepatitis C or HIV infection
  • Participation in an investigational drug, biologic, or device study within three months before first study drug administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01398293

Strasbourg, France, 67064
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche Identifier: NCT01398293     History of Changes
Other Study ID Numbers: NP25298
2011-001413-13 ( EudraCT Number )
First Posted: July 20, 2011    Key Record Dates
Last Update Posted: November 2, 2016
Last Verified: November 2016

Additional relevant MeSH terms:
Norgestimate, ethinyl estradiol drug combination
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors