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

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

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).

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic, Healthy Volunteer
• Intervention / Treatment: Drug: RO5428029; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34094
  • Strasbourg, France, 67064
• Netherlands
  • Leiden, Netherlands, 2333
• Poland
  • Chorzow, Poland, 41-500
  • Warsaw, Poland, 01-201
  • Wrocław, Poland, 50-349

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: A2	Drug: placebo; multiple doses
Placebo Comparator: B2	Drug: placebo; multiple doses
Experimental: A1 Healthy Volunteers	Drug: RO5428029; Multiple ascending doses
Experimental: B1 HCV Infection	Drug: RO5428029; Multiple ascending doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: June 6, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimate): June 10, 2011

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: NP25733