A Study of Danoprevir in Healthy Volunteers And Patients With Hepatic Impairment

Study Overview
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Brief Summary
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This non-randomized, multi-center, open-label study will evaluate the pharmacokinetics and the safety and tolerability of danoprevir (RO5190591) and ritonavir in healthy volunteers and patients with mild, moderate or severe hepatic impairment. Participants will be administered repeated daily doses of danoprevir and ritonavir. The anticipated time on study treatment is 10 days.

Official Title
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The Effect of Hepatic Impairment on the Pharmacokinetics of RO5190591/Ritonavir: A Multiple-Center, Open-Label Study Following Multiple Oral Doses of RO5190591/Ritonavir to Subjects With Mild, Moderate, or Severe Hepatic Impairment and Healthy Subjects With Normal Hepatic Function

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: danoprevir
* Drug: ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Volunteers: Adult healthy volunteers, 18-70 years of age Weight >/=50.0 kg Body Mass Index (BMI) 18.0-40.0 kg/m2 Ability and willingness to abstain from alcohol-containing beverages or food from 48 hours prior to entry in the clinical study center until discharge Ability and willingness to abstain from grapefruit or grapefruit juice, star fruit, and Seville oranges from 7 days prior to entry in the clinical study center until discharge Medical history without major recent or ongoing pathology Patients with hepatic impairment: Adult patients, 18-70 years of age Weight >/=50.0 kg Body Mass Index (BMI) 18.0-40.0 kg/m2 Ability and willingness to abstain from alcohol-containing beverages or food from 48 hours prior to entry in the clinical study center until discharge Ability and willingness to abstain from grapefruit or grapefruit juice, star fruit, and Seville oranges from 7 days prior to entry in the clinical study center until discharge Stable, mild, moderate, or severe liver disease of cryptogenic, post-hepatic, hepatitis B or alcoholic origin Exclusion Criteria: Healthy Volunteers: Pregnant or lactating women and male partners of women who are pregnant or lactating Uncontrolled treated/untreated hypertension (systolic blood pressure >/=160 mmHg and /or diastolic blood pressure >/=105 mmHg Any history of clinically significant cardiovascular or cerebrovascular disease Creatinine clearance </=60 mL/min Positive test results for drugs or alcohol Donation or loss of blood over 450 ml within 60 days prior to screening Patients with hepatic impairment: Pregnant or lactating women and male partners of women who are pregnant or lactating Uncontrolled treated/untreated hypertension (systolic blood pressure >/=160 mmHg and /or diastolic blood pressure >/=105 mmHg Any history of clinically significant cardiovascular or cerebrovascular disease Severe ascites at screening or admission to the clinic History of or current severe hepatic encephalopathy (grade 3 or higher) Any evidence of progressive liver disease within the last 4 weeks History of liver transplantation Creatinine clearance </=60 mL/min Positive test results for drugs or alcohol Donation or loss of blood over 450 ml within 60 days prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: danoprevir<br>* Repeated oral doses<br>Drug: ritonavir<br>* Repeated oral doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (plasma concentration) of danoprevir in patients with hepatic impairment |  | From baseline to day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability (incidence of adverse events) of danoprevir in patients with hepatic impairment |  | From baseline to day 10 |