A Drug-Drug Interaction Study Between Danoprevir/Low-Dose Ritonavir and Cyclosporine in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01514968
First received: January 16, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

This single-dose, randomized, open-label, 2-sequence, 3-period study will evaluate the effect of cyclosporine on the pharmacokinetics of ritonavir-boosted danoprevir (DNV/r) in healthy volunteers. Subjects will be randomized to one of two treatment sequences to receive a single oral dose of DNV/r or cyclosporine. In treatment period 3, subjects will receive a single oral dose of DNV/r plus cyclosporine. Anticipated time on study is 33 days.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Drug-Drug Interaction Study Between Danoprevir/Low-dose Ritonavir and Cyclosporine, a Potent Inhibitor of OATP, in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Effect of single dose of cyclosporine on pharmacokinetics of ritonavir-boosted danoprevir: maximum plasma concentration (Cmax)/area under the concentration-time curve (AUC) [ Time Frame: 16 time points up to 96 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of single dose of ritonavir-boosted danoprevir on pharmacokinetics of cyclosporine [ Time Frame: 16 time points up to 96 hours ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 50 days ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: December 2011
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: danoprevir+ritonavir Drug: danoprevir
Single oral dose
Drug: ritonavir
Single oral dose
Active Comparator: cyclosporine Drug: cyclosporine
Single oral dose
Experimental: DNV/r+cyclosporine Drug: danoprevir
Single oral dose
Drug: ritonavir
Single oral dose
Drug: cyclosporine
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:

  • Male and female healthy volunteers, 18 to 45 years of age inclusive
  • Body mass index (BMI) 18.0 to 32.0 kg/m2
  • Weight >/= 50 kg
  • Healthy status defined by absence of evidence of any active or chronic disease following detailed medical and surgical history and a complete physical examination
  • Nonsmoker
  • Females of childbearing potential and males and their female partner(s) 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 (acceptable barrier forms are condom and diaphragm, acceptable non-barrier forms of contraception for this study are non-hormonal intrauterine device and/or spemicide)

Exclusion Criteria:

  • Pregnant or lactating females
  • Positive results for drugs of abuse in the urine 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 the first dose of study medication
  • Use of hormonal contraceptives (birth control pills, patches or injectable, implantable devices) within 30 days before the first dose of study medication
  • Routine chronic use of more than 2 g acetaminophen daily
  • Use of any investigational drug or device within 30 days of screening (6 months for biologic therapies) or 5 half-lives of the investigational drug, whichever is longer
  • History of clinically significant disease or disorder
  • History of clinically significant drug-related allergy (such as anaphylaxis) or hepatotoxicity
  • History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01514968

Locations
United States, Kansas
Lenexa, Kansas, United States, 66219
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01514968     History of Changes
Other Study ID Numbers: NP27947
Study First Received: January 16, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Ritonavir
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on April 22, 2014