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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic, Healthy Volunteer
• Intervention / Treatment: Drug: Placebo; Drug: RO5303253; Drug: RO5303253; Drug: RO5303253

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Grafton, New Zealand, 1010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: HV ascending dose	Drug: Placebo; matching RO5303253 placebo, administered as single dose (Parts A + B) or multiple dose (Part C); Drug: RO5303253; Cohorts receiving single ascending doses; Drug: RO5303253; Single dose; Drug: RO5303253; Multiple doses
Experimental: B: HV food effect	Drug: Placebo; matching RO5303253 placebo, administered as single dose (Parts A + B) or multiple dose (Part C); Drug: RO5303253; Cohorts receiving single ascending doses; Drug: RO5303253; Single dose; Drug: RO5303253; Multiple doses
Experimental: C: Hepatitis C	Drug: Placebo; matching RO5303253 placebo, administered as single dose (Parts A + B) or multiple dose (Part C); Drug: RO5303253; Cohorts receiving single ascending doses; Drug: RO5303253; Single dose; Drug: RO5303253; Multiple doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: August 12, 2010
• First Submitted That Met QC Criteria: August 12, 2010
• First Posted (Estimate): August 13, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: PP25195; 2009-018183-96