A Multi-Center, Randomized, Double-Blind, Multiple Ascending Dose, Placebo-Controlled, Parallel Group 2-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic of the HCV Nucleoside Inhibitor RO5428029 in Healthy Subjects (Part A), and in Chronic Hepatitis C Genotype 1 Infected Patients (Part B).
- Conditions
- 10047438chronic hepatitis C
- Registration Number
- NL-OMON36081
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 50
- Healthy subjects (Part A) or patients with chronic hepatitis C infection (Part B), 18 to 60 years of age, inclusive
- Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a minimum weight of 45 kg
- Female subjects/patients must be surgically sterile or post-menopausal
- Male subjects/patients and their partners of childbearing potential must use 2 methods of contraception
- For HCV patients:
- Hepatitis C genotype 1 of >/= 6 months duration at screening
- HCV RNA quantifiable (Roche COBAS TaqMan HCV Test) at screening
- HCV treatment-naïve
- Liver biopsy or non-invasive procedure within the past 2 years showing absence of cirrhosis
- Pregnant or lactating women, and male partners of women who are pregnant or lactating
- Women with reproductive potential
- Positive test for drugs of abuse
- History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams or 1 unit of alcohol
- History or symptoms of any significant disease or disorder
- History of active malignancy within the last 5 years, except for localized or in situ carcinoma (e.g. basal or squamous cell carcinoma of the skin)
- Positive for hepatitis B or HIV infection, and/ or HCV for healthy volunteers (Part A)
- For HCV patients:
- Decompensated liver disease or impaired liver function as defined by any history of ascites, hepatic encephalopathy, hepatocellular carcinoma or bleeding esophageal varices, or prothrombin international normalized ratio (PTINR) >/= 2.0 at screening
- Evidence of cirrhosis and/or incomplete transition to cirrhosis
- Presence or history of non-hepatitis C liver disease
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Safety and tolerability: AEs, 12-lead ECGs, vital signs and laboratory tests<br /><br>- PK parameters: Cmax, AUC, Tmax and Cmin of RO1080713<br /><br>- HCV RNA levels<br /><br>- Resistance emergence</p><br>
- Secondary Outcome Measures
Name Time Method <p>- PK: Other pharmacokinetic parameters of RO1080713<br /><br>- PK: Pharmacokinetic parameters of RO5428029 and/or other metabolites as<br /><br>needed</p><br>