Clinical trial NCT01185873: A Study of Danoprevir in Healthy Volunteers And Patients With Hepatic Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-08-20
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics (plasma concentration) of danoprevir in patients with hepatic impairment
timeFrame: From baseline to day 10
Secondary outcomes:
measure: Safety and tolerability (incidence of adverse events) of danoprevir in patients with hepatic impairment
timeFrame: From baseline to day 10
Other outcomes:
Locations:
city: Lenexa
country: United States
state: Kansas
city: Prague 8
country: Czech Republic
city: Praha 7
country: Czech Republic
city: Bratislava
country: Slovakia
city: Bratislava
country: Slovakia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: