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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: danoprevir; Drug: ritonavir

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czech Republic
  • Prague 8, Czech Republic, 180 00
  • Praha 7, Czech Republic, 170 00
• Slovakia
  • Bratislava, Slovakia, 831 01
  • Bratislava, Slovakia, 83305
• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: danoprevir; Repeated oral doses; Drug: ritonavir; Repeated oral doses

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: August 17, 2010
• First Submitted That Met QC Criteria: August 19, 2010
• First Posted (Estimate): August 20, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: NP25290; 2010-020314-29