Clinical trial NCT01586325: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Hepatitis C Infection
Keywords: Chronic hepatitis C infection
Asian genotype 1 chronic hepatitis C infection
JNJ-47910382
Non-structural protein 5A (NS5A) inhibitor
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2012-04-26
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in HCV RNA levels over time during the 5-day treatment regimen
timeFrame: Up to 4 weeks after the last dose of study medication.
measure: Number of participants with HCV RNA levels below the limit of detection
timeFrame: Up to 4 weeks after the last dose of study medication.
Secondary outcomes:
measure: Mean plasma concentrations of JNJ-47910382
timeFrame: Up to Day 9 of each treatment period.
measure: Maximum observed plasma concentration of JNJ-47910382
timeFrame: Up to Day 9 of each treatment period.
measure: Minimum observed plasma concentration of JNJ-47910382
timeFrame: Up to Day 9 of each treatment period
measure: Time to reach the maximum plasma concentration of JNJ-47910382
timeFrame: Up to Day 9 of each treatment period.
measure: Area under the plasma concentration-time curve from time 0 to 24 hours of JNJ-47910382
timeFrame: Up to Day 9 of each treatment period.
measure: Average steady-state plasma concentration of JNJ-47910382
timeFrame: Up to Day 9 of each treatment period.
measure: Terminal elimination half life of JNJ-47910382
timeFrame: Up to Day 9 of each treatment period.
measure: The number of participants affected by an adverse event
timeFrame: Up to 30 days after the last dose of study medication
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
city: Niaosung, Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References: