A Randomized, Open-label Study of the Effect of PEGASYS ® Plus COPEGUS® With or Without Concomitant Pioglitazone (Actos®) on Early Viral Kinetics in Treatment-naive Patients With Chronic Hepatitis C, Genotype-1, and Insulin Resistance
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 155
- 主要终点
- Change From Initiation of Pegasys Plus Copegus in log10 Hepatitis C Virus Ribonucleic Acid (HCV RNA) Viral Load to Week 12 of Anti-HCV Therapy
研究概览
简要总结
This 2 arm study will assess the efficacy and safety of PEGASYS plus COPEGUS, with or without concomitant pioglitazone, on hepatitis C virus titers in treatment-naive patients with genotype 1 chronic hepatitis C, and insulin resistance. Patients will be randomized to receive either a)PEGASYS 180 micrograms/week + Copegus 1000-1600 mg/day (according to body weight) for 48 weeks or b)16 weeks of pioglitazone (30 mg daily for 8 weeks, then 45 mg daily for 8 weeks), followed by PEGASYS 180 micrograms/week + Copegus 1000-1600 mg/day + pioglitazone 45 mg daily for 48 weeks. The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult patients, >=18 years of age;
- •chronic hepatitis C, genotype 1;
- •insulin resistance.
排除标准
- •other forms of liver disease;
- •cirrhosis;
- •previous treatment for chronic hepatitis C;
- •insulin treatment during prior 2 weeks;
- •type 1 diabetes.
研究组 & 干预措施
PEG-INF alpha-2a + ribavirin+ pioglitazone
Participants received pioglitazone in a 16 week run-in period (30 mg per day orally for 8 weeks followed by 45 mg per day orally for 8 weeks). Participants then received piogliatzone 45 mg daily orally plus 18 μg of Peginterferon Alfa-2a (PEG-INF alpha-2a) subcutaneous (sc) once a week plus ribavirin (1000 - 1600 mg/day orally as a split dose in the morning and the evening based on the participant's body weight) for 48 weeks in the anti-HCV treatment phase. Participants received 45 mg of pioglitazone per day orally in the 24 week follow-up period.
干预措施: peginterferon alfa-2a [Pegasys] (Drug)
PEG-INF alpha-2a + ribavirin+ pioglitazone
Participants received pioglitazone in a 16 week run-in period (30 mg per day orally for 8 weeks followed by 45 mg per day orally for 8 weeks). Participants then received piogliatzone 45 mg daily orally plus 18 μg of Peginterferon Alfa-2a (PEG-INF alpha-2a) subcutaneous (sc) once a week plus ribavirin (1000 - 1600 mg/day orally as a split dose in the morning and the evening based on the participant's body weight) for 48 weeks in the anti-HCV treatment phase. Participants received 45 mg of pioglitazone per day orally in the 24 week follow-up period.
干预措施: ribavirin [Copegus] (Drug)
PEG-INF alpha-2a + ribavirin+ pioglitazone
Participants received pioglitazone in a 16 week run-in period (30 mg per day orally for 8 weeks followed by 45 mg per day orally for 8 weeks). Participants then received piogliatzone 45 mg daily orally plus 18 μg of Peginterferon Alfa-2a (PEG-INF alpha-2a) subcutaneous (sc) once a week plus ribavirin (1000 - 1600 mg/day orally as a split dose in the morning and the evening based on the participant's body weight) for 48 weeks in the anti-HCV treatment phase. Participants received 45 mg of pioglitazone per day orally in the 24 week follow-up period.
干预措施: Pioglitazone (Drug)
PEG-INF alpha-2a + ribavirin
Participants received 18 μg of Peginterferon Alfa-2a (PEG-INF alpha-2a) subcutaneous (sc) once a week plus ribavirin (1000 - 1600 mg/day orally as a split dose in the morning and the evening based on the participant's body weight) for 48 weeks in the anti-HCV treatment phase followed by a treatment free 24 week follow-up period.
干预措施: peginterferon alfa-2a [Pegasys] (Drug)
PEG-INF alpha-2a + ribavirin
Participants received 18 μg of Peginterferon Alfa-2a (PEG-INF alpha-2a) subcutaneous (sc) once a week plus ribavirin (1000 - 1600 mg/day orally as a split dose in the morning and the evening based on the participant's body weight) for 48 weeks in the anti-HCV treatment phase followed by a treatment free 24 week follow-up period.
干预措施: ribavirin [Copegus] (Drug)
结局指标
主要结局
Change From Initiation of Pegasys Plus Copegus in log10 Hepatitis C Virus Ribonucleic Acid (HCV RNA) Viral Load to Week 12 of Anti-HCV Therapy
时间窗: Initiation of Pegasys plus Copegus, Week 12 of anti-HCV treatment
Serum samples were collected for HCV RNA. The change from initiation of Pegasys plus Copegus to Week 12 in HCV RNA titers were calculated. Randomization for the with Pioglitazone arm occurred prior to the 16 week run-in period and randomization for the without Pioglitazone arm occurred prior to the start of anti-HCV treatment.
次要结局
- Change From Initiation of Pegasys Plus Copegus in log10 HCV RNA Viral Load to Week 24 and Week 48 of Anti-HCV Therapy(Initiation of Pegasys Plus Copegus, Week 24 and Week 48 of anti-HCV therapy)
- Percentage of Participants Achieving Virologic Response(Weeks 4, 12, 24, 48, 60, 72)
- Percentage of Participants With a ≥ 2 log10 Decrease in HCV RNA From Initiation of Pegasys Plus Copegus to Weeks 4, 12, 24, 48, 60, 72(Initiation of Pegasys plus Copegus, Weeks 4, 12, 24, 48, 60, 72)
- Percentage of Participants With a Virological Relapse at Week 72 (24 Weeks After the End of Anti-HCV Treatment)(Week 72)
- Percentage of Participants With a Confirmed Virological Breakthrough up to 48 Weeks(Up to 48 Weeks)
- Percentage of Nonresponders During the 48 Week Anti-HCV Treatment Period(Up to 48 Weeks)
- Change in Log10 HCV RNA Viral Load at Assessments From Randomization to 16 Weeks of Pioglitazone Pretreatment Run-In Period for the Pioglitazone Arm Only(Randomization (Week-16),Weeks -12, -8, -4 and 0)
- Change From Baseline in Fasting Plasma Glucose Levels at Each Time Point Assessed(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Fasting Insulin Levels at Each Time Point Assessed.(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Fasting Hemoglobin A1C (HbA1c) Concentrations at Each Time Point Assessed(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Homeostasis Model Assessment (HOMA) Scores at Each Time Point Assessed(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Serum Triglyceride Concentrations at Each Time-point Assessed(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60, 72)
- Change From Baseline in Total Cholesterol Levels at Each Time-point Assessed(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Low-density Lipoprotein (LDL-cholesterol) Levels at Each Time-point Assessed(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in High-density Lipoprotein (HDL-cholesterol) Levels at Each Time-point Assessed(Baseline, Weeks 4,8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Tumor Necrosis Factor Alpha (TNF-α) at Each Time Point Assessed(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Transforming Growth Factor Beta (TGF-β) Levels at Each Time Point Assessed(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Adiponectin Levels at Each Time Point Assessed(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Leptin Levels at Each Time Point Assessed(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)
- Change From Baseline in Free Fatty Acid Levels at Each Time Point Assessed(Baseline, Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)
- Percentage of Participants With Beck Depression Inventory Fast Screen (BDI-FS) Score ≥ 4 at Each Time Point Assessed(Weeks 4, 8,12,16,20,24,28,32,36,40,44,48,60,72)