A Study on Safety, Tolerability and Pharmacokinetics of RO5303253 in Healthy Volunteers and Patients With Chronic Hepatitis C Genotype 1

Study Overview
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Brief Summary
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This randomized, double-blind, placebo controlled, 3 part study will assess the safety, tolerability and pharmacokinetics of RO5303253 in healthy volunteers and patients with chronic hepatitis C genotype 1. In Part A, cohorts of healthy volunteers will be randomized to receive single ascending doses of RO5303253 or placebo. In Part 2, healthy volunteers will receive a single dose of RO5303253 or placebo in a cross-over design (with a washout period of at least 7 days) to assess food effects on pharmacokinetics. In Part 3, patients with chronic hepatitis C will be randomized ro receive either RO5303253 or placebo for 5 days.

Official Title
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A Single Ascending Dose Tolerability and Pharmacokinetic Study of RO5303253 With a Pilot Food-effect Investigation in Healthy Subjects and Exploratory Pharmacokinetic, Pharmacodynamic, and Safety Assessments in Chronic Hepatitis C Genotype 1 Patients Following 5 Days of Oral Administration

Conditions
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Hepatitis C, Chronic, Healthy Volunteer

Intervention / Treatment
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* Drug: Placebo
* Drug: RO5303253
* Drug: RO5303253
* Drug: RO5303253


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers or patients with chronic hepatitis C genotype 1, 18 to 60 years of age Patients must be treatment-naïve for antiviral therapy for chronic hepatitis C with interferon based therapy Body mass index (BMI) 18 - 32 kg/m2 inclusive, minimum weight 45 kg Females must be surgically sterile or menopausal Male subjects and their partners of childbearing potential must use 2 methods of contraception throughout the study and for 70 days after the last dose Exclusion Criteria: Pregnant or lactating women and male partners of women who are pregnant or lactating Women with reproductive potential Positive for hepatitis B or HIV (or hepatitis C for healthy volunteers) at screening For hepatitis C patients: decompensated liver disease or impaired liver function, evidence of cirrhosis documented at any time, presence or history of non-hepatitis C chronic 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: A: HV ascending dose<br> | Drug: Placebo<br>* matching RO5303253 placebo, administered as single dose (Parts A + B) or multiple dose (Part C)<br>Drug: RO5303253<br>* Cohorts receiving single ascending doses<br>|
| Experimental: B: HV food effect<br> | Drug: Placebo<br>* matching RO5303253 placebo, administered as single dose (Parts A + B) or multiple dose (Part C)<br>Drug: RO5303253<br>* Single dose<br>|
| Experimental: C: Hepatitis C<br> | Drug: Placebo<br>* matching RO5303253 placebo, administered as single dose (Parts A + B) or multiple dose (Part C)<br>Drug: RO5303253<br>* Multiple doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Adverse events, laboratory parameters, ECG, blood pressure |  | approximately 6 months | 
| Pharmacokinetics: Plasma and urine concentrations of RO5303253 and its main metabolite RO1080713 |  | approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of food intake on pharmacokinetics in healthy volunteers |  | Days 1-4 | 
| Pharmacodynamics (viral responses) and drug resistance profiling in chronic hepatitis C patients |  | From baseline to Day 15 |