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

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Drug: cyclosporine; Drug: danoprevir; Drug: ritonavir

• Registration Number: NCT01514968
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2012-01-16
• Study First Submitted QC: 2012-01-18
• Study First Posted: 2012-01-23
• Primary Completion: 2012-02
• Study Completion: 2012-02
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
DNV/r+cyclosporine	cyclosporine	-
DNV/r+cyclosporine	danoprevir	-
DNV/r+cyclosporine	ritonavir	-
cyclosporine	cyclosporine	-
danoprevir+ritonavir	danoprevir	-
danoprevir+ritonavir	ritonavir	-

Primary Outcome Measures

Name	Time	Method
Effect of single dose of cyclosporine on pharmacokinetics of ritonavir-boosted danoprevir: maximum plasma concentration (Cmax)/area under the concentration-time curve (AUC)	16 time points up to 96 hours

Secondary Outcome Measures

Name	Time	Method
Effect of single dose of ritonavir-boosted danoprevir on pharmacokinetics of cyclosporine	16 time points up to 96 hours
Safety: Incidence of adverse events	approximately 50 days