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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 主要终点
- Change from baseline in HCV RNA levels over time during the 5-day treatment regimen
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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).
干预措施: JNJ-47910382 30 mg (Drug)
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).
干预措施: Placebo (Drug)
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.
干预措施: JNJ-47910382 90 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: JNJ-47910382 200 mg (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in HCV RNA levels over time during the 5-day treatment regimen
时间窗: Up to 4 weeks after the last dose of study medication.
Number of participants with HCV RNA levels below the limit of detection
时间窗: Up to 4 weeks after the last dose of study medication.
次要结局
- Mean plasma concentrations 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.)
- The number of participants affected by an adverse event(Up to 30 days after the last dose of study medication)
- Minimum observed plasma concentration 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.)
- Time to reach the maximum plasma concentration 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.)