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: July 7, 2014
Last verified: July 2014
  Purpose

This single-dose, randomized, open-label, 2-sequence, 3-period study will evalua te the effect of cyclosporine on the pharmacokinetics of ritonavir-boosted danop revir (DNV/r) in healthy volunteers. Subjects will be randomized to one of two t reatment sequences to receive a single oral dose of DNV/r or cyclosporine. In tr eatment period 3, subjects will receive a single oral dose of DNV/r plus cyclosp orine. 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 spermicide)

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: July 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 July 23, 2014