A Safety And Pharmacokinetic Study of Setrobuvir Alone and In Combination With Ritonavir-Boosted Danoprevir in Subjects With Mild Hepatic Impairment Compared to Healthy Controls

Roche

Status and phase

Completed

Phase 1

Conditions

Healthy Volunteer

Treatments

Drug: danoprevir

Drug: setrobuvir

Drug: ritonavir

Study type

Interventional

Funder types

Industry

Identifiers

NCT01714154

NP28326

2012-002283-28 (EudraCT Number)

Details and patient eligibility

About

This multi-center, fixed-sequence, open-label, multiple-dose, 2-period study will evaluate the safety, tolerability and pharmacokinetics of setrobuvir alone or in combination with ritonavir-boosted danoprevir in subjects with mild hepatic impairment compared to healthy controls. All subjects will receive multiple doses of setrobuvir orally for 10 days in Period 1 and multiple doses of setrobuvir plus ritonavir-boosted danoprevir orally for 10 days in Period 2, with a washout phase of at least 9 days between treatments.

Enrollment

18 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Male and female adults, 18-65 years of age, inclusive
Weight >/= 45.0 kg
Body mass index (BMI) 18.0 - 35.0 kg/m2, inclusive
Females of childbearing potential and males and their female partners of childbearing potential must agree to use two forms of non-hormonal contraception as defined by protocol
Subjects with a history of substance abuse may be enrolled provided they have not abused drugs or alcohol for at least 6 months
Healthy subjects only:

Medical history without major recent or ongoing pathology Laboratory values at screening and Day -1 within the normal range or showing no clinically relevant deviations

Subjects with hepatic impairment only:

Stable mild liver disease (Child-Pugh A) of cryptogenic, post-hepatic, hepatitis B/C, or alcoholic origin Stable hepatic impairment defined as no clinically significant change in disease status within the last 30 days Must be on stable dose of medication and/or treatment regimen at least 2 weeks before dosing of study medication

Exclusion criteria

Pregnant or lactating women or males with female partners who are pregnant or lactating
Active infection or febrile illness </= 10 days prior to the first dose of study medication
Uncontrolled/untreated hypertension
Inadequate renal function
Positive urine drug screen or positive breath alcohol test at screening and on Day -1 of each period
An average alcohol intake of more than 2 units per day or 14 units per week until 48 hours prior to enrollment
History of any significant drug-related allergy or hepatotoxicity
Participation in other clinical studies with an investigational drug or new chemical entity within 3 months (6 months for biologic therapies) prior to the first dose of study medication
Positive for HIV infection
Any clinically significant cardiovascular or cerebrovascular disease
Healthy subjects only:

Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, absorption of medication, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study Positive screening test for HBsAg or HCV antibody

Subjects with hepatic impairment only:

Severe ascites at screening or Day -1 History of or current severe hepatic encephalopathy (Grade 3 or higher) Biliary liver cirrhosis or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver Positive screening test for HCV antigen