A Study of the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of JNJ-47910382 at Different Doses and Dose Regimens in Asian Genotype-1, Chronic, HCV-Infected Patients

Sponsor

Janssen R&D Ireland (Industry)

Overall Status

Terminated

CT.gov ID

NCT01586325

Collaborator

(none)

Enrollment

Locations

Arms

22.9

Actual Duration (Months)

1.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety, tolerability, pharmacokinetics (how a drug is absorbed and distributed in the body), and intrinsic antiviral activity of JNJ-47910382 after 5 consecutive days of administration in chronic, hepatitis C virus (HCV)-genotype-1-infected patients at different doses and dose regimens.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection	Drug: JNJ-47910382 30 mg Drug: JNJ-47910382 90 mg Drug: JNJ-47910382 200 mg Drug: Placebo	Phase 1

Detailed Description

This is a double-blind (neither physician nor patient knows the name of the assigned drug), randomized (patients are assigned by chance to treatment groups) placebo-controlled study. A placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect. The study population will consist of Asian treatment-naive genotype-1, chronic HCV-infected patients. The trial will involve a screening period at a maximum of 6 weeks before baseline, a 9-day treatment period (with 5 days of actual medication intake) and a 4-week follow-up period. Patients will be divided into 3 panels of 8 patients (Panel 1) or 5 patients (Panels 2 and 3). Treatment will be initiated in each panel of patients sequentially. In each panel, patients will receive JNJ-47910382 or placebo during 5 consecutive days. JNJ-47910382, or placebo, will be administered once daily. Treatments will be taken by mouth and with standardized meals in all dosing regimens. Patient safety will be monitored.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase Ib, Randomized, Double-Blind, Placebo-Controlled Trial in Asian Genotype 1 Chronic HCV-Infected Subjects to Determine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Repeated Doses of JNJ-47910382 Given in Different Doses and Dose Regimens

Actual Study Start Date :

May 25, 2012

Actual Primary Completion Date :

Apr 21, 2014

Actual Study Completion Date :

Apr 21, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panel 1 Study participants will receive double-blind treatment with JNJ-47910382 30 mg or matching placebo. Participants in each of Panel will be treated sequentially (ie, participants in Panel 1 will be treated before participants in Panel 2, participants in Panel 2 will be treated before participants in Panel 3).	Drug: JNJ-47910382 30 mg JNJ-47910382 30 mg (0.6 mL of an oral suspension of 50 mg/mL of JNJ-47910382) administered once daily as monotherapy for 5 days. Drug: Placebo Matching Placebo administered once daily as monotherapy for 5 days.
Experimental: Panel 2 Study participants will receive double-blind treatment with JNJ-47910382 90 mg or matching placebo. Participants in each of Panel will be treated sequentially.	Drug: JNJ-47910382 90 mg JNJ-47910382 90 mg (1.8 mL of an oral suspension of 50 mg/mL of JNJ-47910382) administered once daily as monotherapy for 5 days. Drug: Placebo Matching Placebo administered once daily as monotherapy for 5 days.
Experimental: Panel 3 Study participants will receive double-blind treatment with JNJ-47910382 200 mg (maxiumum dose) or matching placebo. Participants in each of Panel will be treated sequentially.	Drug: JNJ-47910382 200 mg JNJ-47910382 200 mg (4 mL of an oral suspension of 50 mg/mL of JNJ-47910382) administered once daily as monotherapy for 5 days. Drug: Placebo Matching Placebo administered once daily as monotherapy for 5 days.

Arm

Intervention/Treatment

Experimental: Panel 1

Study participants will receive double-blind treatment with JNJ-47910382 30 mg or matching placebo. Participants in each of Panel will be treated sequentially (ie, participants in Panel 1 will be treated before participants in Panel 2, participants in Panel 2 will be treated before participants in Panel 3).

Drug: JNJ-47910382 30 mg

JNJ-47910382 30 mg (0.6 mL of an oral suspension of 50 mg/mL of JNJ-47910382) administered once daily as monotherapy for 5 days.

Drug: Placebo

Matching Placebo administered once daily as monotherapy for 5 days.

Experimental: Panel 2

Study participants will receive double-blind treatment with JNJ-47910382 90 mg or matching placebo. Participants in each of Panel will be treated sequentially.

Drug: JNJ-47910382 90 mg

JNJ-47910382 90 mg (1.8 mL of an oral suspension of 50 mg/mL of JNJ-47910382) administered once daily as monotherapy for 5 days.

Drug: Placebo

Matching Placebo administered once daily as monotherapy for 5 days.

Experimental: Panel 3

Study participants will receive double-blind treatment with JNJ-47910382 200 mg (maxiumum dose) or matching placebo. Participants in each of Panel will be treated sequentially.

Drug: JNJ-47910382 200 mg

JNJ-47910382 200 mg (4 mL of an oral suspension of 50 mg/mL of JNJ-47910382) administered once daily as monotherapy for 5 days.

Drug: Placebo

Matching Placebo administered once daily as monotherapy for 5 days.

Outcome Measures

Primary Outcome Measures

Change from baseline in HCV RNA levels over time during the 5-day treatment regimen [Up to 4 weeks after the last dose of study medication.]
Number of participants with HCV RNA levels below the limit of detection [Up to 4 weeks after the last dose of study medication.]

Secondary Outcome Measures

Mean plasma concentrations of JNJ-47910382 [Up to Day 9 of each treatment period.]
Maximum observed plasma concentration of JNJ-47910382 [Up to Day 9 of each treatment period.]
Minimum observed plasma concentration of JNJ-47910382 [Up to Day 9 of each treatment period]
Time to reach the maximum plasma concentration of JNJ-47910382 [Up to Day 9 of each treatment period.]
Area under the plasma concentration-time curve from time 0 to 24 hours of JNJ-47910382 [Up to Day 9 of each treatment period.]
Average steady-state plasma concentration of JNJ-47910382 [Up to Day 9 of each treatment period.]
Terminal elimination half life of JNJ-47910382 [Up to Day 9 of each treatment period.]
The number of participants affected by an adverse event [Up to 30 days after the last dose of study medication]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Documented chronic HCV infection (diagnosis of hepatitis C >= 6 months before the screening period)
HCV geno- and subtype of 1a or 1b (Panel 1) or 1b (Panels 2 and 3)
Patient has never received pegylated interferon, ribavirin, or any other approved or investigational antiviral treatment for chronic HCV infection
Patient with HCV ribonucleic acid (RNA) level of >100,000 IU/mL at screening (as assessed by standard quantitative in vitro nucleic acid amplification assay)
A Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, extremes included
A body weight above 50 kg
Normal 12-lead electrocardiogram (ECG) at screening

Exclusion Criteria:

Evidence of or documented liver cirrhosis
Evidence of decompensated liver disease
Evidence of any other cause of significant liver disease in addition to hepatitis C
History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the Investigator's opinion would compromise patient's safety and/or compliance with the study procedures
A positive urine drug (with exclusion of methadone or equivalent) test at study screening
Patient with protocol-defined laboratory abnormalities at screening
Patient coinfected with HIV-1 or HIV-2, or hepatitis A or B virus infection, or active tuberculosis at study screening
Patient infected/coinfected with non-genotype 1 HCV at study screening
Patient with any cardiac disease at screening, or any active clinically significant disease (eg, cardiac dysfunction, cardio(myo)pathy, cardiac insufficiency), or medical history or physical examination findings during screening that, in the Investigator's opinion, would compromise the outcome of the trial
Patient having uncontrolled/unstable disease such as diabetes, epilepsy, a manifest psychiatric disease, or thyroid disease or disorders
Patient with non-stable methadone (or equivalent drug) use