A Study of RO5428029 in Healthy Volunteers and Patients With Chronic Hepatitis C

Study Overview
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Brief Summary
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This 2-part, randomized, double-blind, placebo-controlled study will assess the safety, pharmacokinetics and pharmacodynamics of RO5428029 in healthy volunteers and patients with hepatitis C infection. Cohorts will be randomized to receive either RO5428029 in ascending doses or placebo for up to 7 days (patients) or up to 14 days (healthy volunteers).

Official Title
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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 and in CHC Genotype 1 Infected Patients

Conditions
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Hepatitis C, Chronic, Healthy Volunteer

Intervention / Treatment
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* Drug: RO5428029
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 (no prior antiviral therapy for chronic hepatitis C with interferon-based therapy) Liver biopsy or non-invasive procedure within the past 2 years showing absence of cirrhosis Exclusion Criteria: Pregnant or lactating women, and male partners of women who are pregnant or lactating 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 for 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1 Healthy Volunteers<br> | Drug: RO5428029<br>* Multiple ascending doses<br>|
| Placebo Comparator: A2<br> | Drug: placebo<br>* multiple doses<br>|
| Experimental: B1 HCV Infection<br> | Drug: RO5428029<br>* Multiple ascending doses<br>|
| Placebo Comparator: B2<br> | Drug: placebo<br>* multiple doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Viral load response: HCV RNA (assessed by Roche COBAS Taqman HCV Test) |  | up to 17 days | 
| Parts A + B: Safety: Incidence of adverse events |  | up to 24 days | 
| Parts A + B: Pharmacokinetics: Area under the concentration - time curve (AUC) |  | up to 24 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Viral resistance (viral breakthrough/non-response/partial response) HCV RNA assessed by Roche COBAS Paqman HCV Test |  | up to 17 days |