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

Phase 1

Completed

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

• Registration Number: NCT01185873
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-08-17
• Study First Submitted QC: 2010-08-19
• Study First Posted: 2010-08-20
• Study Start: 2011-02
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 81

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	ritonavir	-
1	danoprevir	-

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (plasma concentration) of danoprevir in patients with hepatic impairment	From baseline to day 10

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability (incidence of adverse events) of danoprevir in patients with hepatic impairment	From baseline to day 10