A Phase Ib, Randomized, Double-Blind, Placebo-Controlled Trial in Caucasian 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
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Chronic Hepatitis C Infection
- Sponsor
- Janssen R&D Ireland
- Enrollment
- 11
- Primary Endpoint
- Determination of pharmacokinetics of JNJ-47910382
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study is to determine the safety, tolerability, pharmacokinetics (what the body does to the medication) and antiviral activity of JNJ-47910382 when administered in different dosing regimens in Caucasian genotype-1 chronic HCV-infected patients.
Detailed Description
This is a Phase Ib, double-blind (neither physician nor patient knows the treatment that the patient receives), randomized (the study drug is assigned by chance), placebo-controlled study in treatment-naïve (someone who has never used drugs for HCV infection), Caucasian genotype 1 chronic HCV-infected patients. The study consists of a screening period, a 9-day treatment period (with 5 days of actual medication intake) and a 4-week follow-up period. The patients will be divided over 4 panels of 10 patients each that will be initiated sequentially. In each panel patients will receive JNJ-47910382 or placebo during 5 consecutive days. JNJ-47910382 or placebo will be administered once daily or twice daily. Within each panel, 5 patients of genotype-1a and 5 patients of genotype-1b will be enrolled. Patients will be randomly assigned to receive active treatment or placebo in such a way that 4 patients of each genotype receive active treatment and 1 subject of each genotype receives placebo. The pharmacokinetic profile of JNJ-47910382 will be assessed in each panel. HCV RNA kinetics (HCV RNA level) and HCV resistance will be studied and biomarkers at the messenger RNA (mRNA), protein and cell level will be explored. The entire study duration for each participant will be approximately four weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Chronic (diagnosis of hepatitis C more than or 6 months before the screening period) HCV infection. Geno- and subtype should be determined or confirmed at screening, and should be 1a or 1b
- •Never received (Peg) IFN, RBV or any other approved or investigational antiviral treatment for chronic HCV infection
- •HCV RNA level of \>100,000 IU/mL at screening (as assessed by standard quantitative in vitro nucleic acid amplification assay)
- •Patients having good accessible veins
Exclusion Criteria
- •Evidence of liver cirrhosis or decompensated liver disease
- •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, or medical history or physical examination findings during screening
- •Patient having uncontrolled/unstable disease such as diabetes, epilepsy, a manifest psychiatric disease, thyroid disease or disorders
Arms & Interventions
Panel I
Patients will be randomized to receive JNJ-47910382 at a dose of 30 mg or placebo as monotherapy once daily for 5 days.
Intervention: Placebo
Panel I
Patients will be randomized to receive JNJ-47910382 at a dose of 30 mg or placebo as monotherapy once daily for 5 days.
Intervention: JNJ-47910382
Panel II
Patients will be randomized to receive JNJ-47910382 at a dose of 90 mg or placebo as monotherapy once daily for 5 days.
Intervention: Placebo
Panel II
Patients will be randomized to receive JNJ-47910382 at a dose of 90 mg or placebo as monotherapy once daily for 5 days.
Intervention: JNJ-47910382
Panel III
Patients will be randomized to receive JNJ-47910382 at a dose of 300 mg or placebo as monotherapy once daily for 5 days.
Intervention: Placebo
Panel III
Patients will be randomized to receive JNJ-47910382 at a dose of 300 mg or placebo as monotherapy once daily for 5 days.
Intervention: JNJ-47910382
Panel IV
Patients will be randomized to receive JNJ-47910382 at a dose of 400 or 450 mg once daily or 300 mg twice daily (morning dose only on Day 5) or placebo as monotherapy for 5 days.
Intervention: Placebo
Panel IV
Patients will be randomized to receive JNJ-47910382 at a dose of 400 or 450 mg once daily or 300 mg twice daily (morning dose only on Day 5) or placebo as monotherapy for 5 days.
Intervention: JNJ-47910382
Outcomes
Primary Outcomes
Determination of pharmacokinetics of JNJ-47910382
Time Frame: Up to 9 Days
The pharmacokinetics of JNJ-47910382 after 5 consecutive days of administration in chronic HCV-genotype-1 infected patients in different doses and dose regimens will be determined.
Number of participants with adverse events as a measure of safety and tolerability
Time Frame: Up to 4 weeks
Evaluation of the intrinsic antiviral activity of JNJ-47910382
Time Frame: Up to 4 weeks
Evaluation of the intrinsic antiviral activity of different doses and dose regimens of JNJ-47910382 in chronic HCV-genotype-1 infected subjects, as measured by the HCV RNA decrease from baseline (Day 1) over time.