A Blinded, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Pharmacokinetics, and Antiviral Activity of ABT-267 in Combination With Peginterferon Alpha-2a and Ribavirin (pegIFN/RBV) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 11
- 主要终点
- Time to Maximum Plasma Concentration (Tmax) of ABT-267
研究概览
简要总结
The purpose of this study was to assess the safety, pharmacokinetics, and 4-week rapid virologic response (RVR) of 3 different doses of ABT-267 (also known as ombitasvir) in combination with pegylated interferon/ribavirin (pegIFN/RBV) compared with pegIFN/RBV alone (ABT-267 placebo) in treatment naïve, hepatitis C virus (HCV), genotype 1-infected participants.
详细描述
The study was a randomized, double blind, placebo controlled study consisting of 2 substudies. In substudy 1, participants received 1 of 3 doses of ABT-267 or placebo + pegIFN/RBV for 12 weeks. In substudy 2, participants received pegIFN/RBV for 36 weeks. Participants were followed for 48 weeks post ABT-267 treatment for evaluation of efficacy and safety.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Treatment naïve participants
- •Females must be either postmenopausal for at least 2 years or surgically sterile
- •Males must be surgically sterile or practicing specific forms of birth control
- •Chronic hepatitis C virus (HCV), genotype-1 infected participants
- •Documented FibroTest score in combination with an Aspartate Aminotransferase to Platelet Ratio Index (APRI), or a liver biopsy within the last 12 months to document absence of cirrhosis
排除标准
- •Pregnant or breastfeeding female
- •Use of any medications contraindicated for use with pegylated interferon(pegIFN) or ribavirin (RBV) 2 weeks prior to study drug administration or 10 half-lives, whichever is longer
- •Clinically significant cardiac, respiratory (except mild asthma), renal, gastrointestinal, hematologic, neurologic disease, or any uncontrolled medical illness or psychiatric disease or disorder
- •Current or past clinical evidence of cirrhosis or bridging fibrosis
- •Abnormal screening laboratory results
研究组 & 干预措施
ABT-267 (5 mg) once daily + pegIFN/RBV
Participants were given 5 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: ABT-267 (Drug)
ABT-267 (5 mg) once daily + pegIFN/RBV
Participants were given 5 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Pegylated interferon (pegIFN) (Drug)
ABT-267 (5 mg) once daily + pegIFN/RBV
Participants were given 5 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Ribavirin (RBV) (Drug)
ABT-267 (50 mg) once daily + pegIFN/RBV
Participants were given 50 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: ABT-267 (Drug)
ABT-267 (50 mg) once daily + pegIFN/RBV
Participants were given 50 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Pegylated interferon (pegIFN) (Drug)
ABT-267 (50 mg) once daily + pegIFN/RBV
Participants were given 50 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Ribavirin (RBV) (Drug)
ABT-267 (200 mg) once daily + pegIFN/RBV
Participants were given 200 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: ABT-267 (Drug)
ABT-267 (200 mg) once daily + pegIFN/RBV
Participants were given 200 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Pegylated interferon (pegIFN) (Drug)
ABT-267 (200 mg) once daily + pegIFN/RBV
Participants were given 200 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Ribavirin (RBV) (Drug)
Placebo + pegIFN/RBV
Participants were given matching placebo to ABT-267 once daily in combination with pegIFN/RBV for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Pegylated interferon (pegIFN) (Drug)
Placebo + pegIFN/RBV
Participants were given matching placebo to ABT-267 once daily in combination with pegIFN/RBV for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Ribavirin (RBV) (Drug)
Placebo + pegIFN/RBV
Participants were given matching placebo to ABT-267 once daily in combination with pegIFN/RBV for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
干预措施: Placebo for ABT-267 (Other)
结局指标
主要结局
Time to Maximum Plasma Concentration (Tmax) of ABT-267
时间窗: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267
时间窗: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; prior to dose on Day 2 (24 hours after Day 1 dose); and at each subsequent study visit up to Week 12
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; prior to dose on Day 2 (24 hours after Day 1 dose); and at each subsequent study visit. The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The area under the plasma concentration -time curve (AUC; measured in ng\*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma. The AUC24 of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Percentage of Participants With 4-week Rapid Virologic Response (RVR)
时间窗: Week 4
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Rapid virologic response was defined as HCV RNA levels \< the lower limit of detection (\< 15 IU/mL) at Week 4. Data are reported as percentage of participants with RVR.
Plasma Concentrations of Ribavirin (RBV)
时间窗: At each study visit from Week 1 to Week 12
Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and RBV concentrations in plasma were summarized at each visit. Data are reported as the median (range).
Serum Concentrations of Pegylated Interferon (pegIFN)
时间窗: At each study visit from Week 1 to Week 12
Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and pegIFN concentrations in serum were summarized at each visit. Data are reported as the median (range).
Maximum Plasma Concentration (Cmax) of ABT-267
时间窗: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the plasma after administration in a dosing interval. The Cmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
次要结局
- Percentage of Participants With Partial Early Virologic Response (pEVR)(Baseline and Week 12)
- Percentage of Participants With Complete Early Virologic Response (cEVR)(Week 12)
- Median Time to Suppression of Hepatitis C Virus Ribonucleic Acid (HCV RNA)(Approximately 12 weeks)
- Percentage of Participants With Extended Rapid Virologic Response (eRVR)(Week 4 through Week 12)
- Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing(12 weeks after the last dose of pegIFN/RBV)
- Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing(24 weeks after the last dose of pegIFN/RBV)