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

Healthy Volunteer Clinical Trial

Official title:

A Drug-Drug Interaction Study Between Danoprevir/Low-dose Ritonavir and Cyclosporine, a Potent Inhibitor of OATP, in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01514968
• Other study ID #: NP27947
• Status: Completed
• Phase: Phase 1
• First received: January 16, 2012
• Last updated: November 1, 2016
• Start date: December 2011
• Est. completion date: February 2012

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• cyclosporine
Single oral dose
• danoprevir
Single oral dose
• ritonavir
Single oral dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Effect of single dose of ritonavir-boosted danoprevir on pharmacokinetics of cyclosporine		16 time points up to 96 hours	No
Secondary	Safety: Incidence of adverse events		approximately 50 days	No