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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: cyclosporine
* Drug: danoprevir
* Drug: ritonavir


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DNV/r+cyclosporine<br> | Drug: cyclosporine<br>* Single oral dose<br>Drug: danoprevir<br>* Single oral dose<br>Drug: ritonavir<br>* Single oral dose<br>|
| Active Comparator: cyclosporine<br> | Drug: cyclosporine<br>* Single oral dose<br>|
| Active Comparator: danoprevir+ritonavir<br> | Drug: danoprevir<br>* Single oral dose<br>Drug: ritonavir<br>* Single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |