Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SCH 900518 in Naive or Treatment-Experienced Subjects Infected With Hepatitis C Virus Genotype 1 (Protocol No. P04695)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 主要终点
- Safety and tolerability were to be assessed by collecting adverse events (AEs), vital signs, electrocardiograms (ECGs), physical examinations, urinalysis, and safety laboratory tests.
研究概览
简要总结
Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SCH 900518 in Naive or Treatment-Experienced Subjects Infected With Hepatitis C Virus Genotype 1 (Protocol No. P04695)
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject infected with HCV genotype 1 (any sub-type) virus who is:
- •treatment naïve (eg. to interferon and ribavirin); or
- •treatment experienced (non-responder and relapser): subject who received interferon based therapy and continued to have detectable HCV RNA levels at the end of follow-up, a subject who did not attain a 2 log decline in HCV RNA levels at ~12 weeks and discontinued treatment, or subject who had no detectable viral load while on treatment but had a detectable viral load post treatment.
- •Subject with acceptable medical history, physical examination, and clinical laboratory evaluations consistent with CHC, compensated liver disease, and any associated diseases (diabetes, hypertension, etc).
- •Subjects with an HCV RNA viral load of >10^5 copies/mL or equivalent international units
- •BMI of 18 to 40 kg/m^2, men and women, ages 18-65 years inclusive
- •Female must be non-lactating and have a negative pregnancy test at Screening and Day -1 and either be of nonchildbearing potential or if of childbearing potential, must be practicing effective double-barrier contraceptive methods from at least 2 weeks prior to Day -1 until 30 days after study completion.
- •Male must be willing to practice barrier contraception from Day 1 through 3 months following treatment with SCH
- •Subject must have an ECG recording showing no clinically significant findings at Screening.
- •Subject with chronic stable hemophilia may enroll
- •Subject on stable methadone treatment may enroll in this study (evaluation by investigator includes history of stable clinical management for >3 months).
排除标准
- •Subject has a significant acute or chronic medical illness which is not stable or is not controlled with medication (excluding prohibited medications).
- •Subject has received an organ transplant.
- •Subject has evidence of decompensated liver disease by physical exam (encephalopathy, ascites, caput medusae, etc).
- •Subject has at anytime received an HCV NS3-specific protease inhibitor.
- •Subject has a platelet count <80,000/mm^3 (confirmed by repeat analysis) at Screening.
- •Subject has a serum hemoglobin of <10.0 g/dL (confirmed by repeat analysis) at Screening.
- •Subject has a serum AST /ALT value >5 x ULN (confirmed by repeat analysis) at Screening.
- •Subject has a serum alkaline phosphatase value >2 x ULN (confirmed by repeat analysis) at Screening.
- •Two or more of the following criteria (confirmed by repeat analysis) at Screening:
- •Total serum bilirubin >2.0 mg/dL.
- •Serum albumin <3.5 g/dL.
- •INR >1.7 (with the exception of hemophiliacs).
- •Subject has a neutrophil count <1,000/mm^3 (confirmed by repeat analysis) at Screening.
- •Creatinine clearance (as estimated by method of Cockcroft and Gault) less than 50 mL/min at Screening.
- •Subject who has a history of any clinically significant local or systemic infectious disease within 1 week prior to screening (other than HCV-infection).
- •Male subject whose female partner intends on becoming pregnant within 3 months of the study.
- •Subject is positive for HIV antibodies or hepatitis B surface antigen.
- •Subject has a clinically significant allergy or intolerance to foods or drugs, or is known or suspected to have hypersensitivity to any ingredient in the investigational product.
- •Subject has a clinically significant history of auto-immune hepatitis.
- •Subject has used any investigational drugs or donated blood within 30 days prior to study drug administration.
- •Subject who received any of the following treatments: known inhibitor of CYP3A4 metabolism (2 weeks of prior to randomization), known inducer of CYP3A4 metabolism (2 weeks prior to randomization) and treatment for HCV infection (1 month prior to randomization)
研究组 & 干预措施
Treatment-naïve 800 mg TID
Period 1: SCH 900518 (800 mg TID) or placebo for 7 days
Period 2: SCH 900518 (800 mg TID) + PegIntron (1.5 µg/kg QW) or placebo + PegIntron for 14 days.
干预措施: Drug: SCH 900518 Biologic: Peginterferon alfa-2b(PegIntron) (Drug)
Treatment-experienced: 800 mg TID
Period 1: SCH 900518 (800 mg TID) or placebo for 7 days
Period 2: SCH 900518 (800 mg TID) + PegIntron (1.5 ug/kg QW) or placebo + PegIntron for 14 days
干预措施: Drug: SCH 900518 Biologic: Peginterferon alfa-2b (Drug)
Treatment-naïve: 400 mg + RTV BID
Period 1: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) for 7 days.
Period 2: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) +PegIntron (1.5 µg/kg QW) for 14 days.
干预措施: Drug: SCH 900518 Drug: Ritonavir (RTV) Biologic: Peginterferon alfa-2b (PegIntron) (Drug)
Treatment-experienced: 400 mg + RTV BID
Period 1: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) for 7 days.
Period 2: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) +PegIntron (1.5 µg/kg QW) for 14 days.
干预措施: Drug: SCH 900518 Drug: Ritonavir (RTV) Drug: Ritonavir (RTV) Biologic: Peginterferon alfa-2b (PegIntron) (Drug)
结局指标
主要结局
Safety and tolerability were to be assessed by collecting adverse events (AEs), vital signs, electrocardiograms (ECGs), physical examinations, urinalysis, and safety laboratory tests.
时间窗: Screening Period: 90 days, Period 1: 7 days, Washout: 4 weeks, Period 2: 14 days, Standard of Care with PegIntron and ribavirin: 84 days
次要结局
- Log change in HCV-RNA from baseline. Ctrough of SCH 900518 resulting in mean HCV RNA decrease > 2 log10 IU/mL. Ctrough of SCH 900518+PEG resulting in HCV-RNA < LOQ. SCH 900518 PK: Cmax, Tmax, AUC, Ctrough, t½, R, CL/F, Vd/F. PEG and RTV: Ctrough(Period 1: 7 days, Washout: 4 weeks, Period 2: 14 Days)