A Multicenter, Randomized, Double-Blind, "Crossover" Design Study to Evaluate the Lipid-Altering Efficacy and Safety of MK-0524B Combination Tablet Compared to MK-0524A + Simvastatin Coadministration in Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,414
- 主要终点
- Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
研究概览
简要总结
This is a 20-week clinical trial in participants with primary hypercholesterolemia or mixed dyslipidemia to demonstrate the effect of MK-0524B compared to MK-0524A + Simvastatin on lipid values.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •has primary hypercholesterolemia or mixed dyslipidemia based on medical history (previous diagnosis), historic lipid values, or as otherwise determined through optional lipid measurements at screening visit
- •meets one of the following triglyceride (TG) criteria:
- •is on niacin, statin, or fibrate and has TG <500 mg/dL at or within 6 months of washout
- •is not on any lipid altering therapy or is on lipid altering therapy other than niacin, statin, or fibrate and has TG <600 mg/dL at or within 6 months of screening
排除标准
- •is high risk (coronary heart disease [CHD] or CHD risk equivalent) AND is on a statin
- •is pregnant or breast-feeding, or expecting to conceive during the study including the 14-day post study follow-up
- •has Type 1 or Type 2 diabetes mellitus and is on statin therapy, is poorly controlled, is newly diagnosed (within 3 months of Visit 1), has recently experienced repeated hypoglycemia or unstable glycemic control or is taking new or recently adjusted anti-diabetic medications (with the exception of +/- 10 units of insulin) within 3 months of Visit 1
- •has the following conditions: chronic heart failure, uncontrolled/unstable cardiac arrhythmias, unstable hypertension, active or chronic hepatobiliary disorder or hepatic disease, human immunodeficiency virus (HIV) positive, gout (within 1 year)
研究组 & 干预措施
Sequence 1: MK-0524B 1.8g/20mg→MK-0524A 2g+Simvastatin 20mg
After a 2-week placebo run-in, participants will receive MK-0524B (0.9 g/simvastatin 10 mg) for 4 weeks, then MK-0524B 1.8g /20 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 20 mg for 8 weeks.
干预措施: MK-0524A (Drug)
Sequence 1: MK-0524B 1.8g/20mg→MK-0524A 2g+Simvastatin 20mg
After a 2-week placebo run-in, participants will receive MK-0524B (0.9 g/simvastatin 10 mg) for 4 weeks, then MK-0524B 1.8g /20 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 20 mg for 8 weeks.
干预措施: Placebo (Drug)
Sequence 1: MK-0524B 1.8g/20mg→MK-0524A 2g+Simvastatin 20mg
After a 2-week placebo run-in, participants will receive MK-0524B (0.9 g/simvastatin 10 mg) for 4 weeks, then MK-0524B 1.8g /20 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 20 mg for 8 weeks.
干预措施: MK-0524B (Drug)
Sequence 2: MK-0524A 2g+Simvastatin 20mg →MK-0524B 1.8g/20mg
After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 10 mg for 4 weeks, then co-administered MK-0524A 2g +simvastatin 20 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/20 mg combination tablet for 8 weeks.
干预措施: MK-0524A (Drug)
Sequence 2: MK-0524A 2g+Simvastatin 20mg →MK-0524B 1.8g/20mg
After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 10 mg for 4 weeks, then co-administered MK-0524A 2g +simvastatin 20 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/20 mg combination tablet for 8 weeks.
干预措施: Placebo (Drug)
Sequence 2: MK-0524A 2g+Simvastatin 20mg →MK-0524B 1.8g/20mg
After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 10 mg for 4 weeks, then co-administered MK-0524A 2g +simvastatin 20 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/20 mg combination tablet for 8 weeks.
干预措施: MK-0524B (Drug)
Sequence 3: MK-0524B 1.8g/40mg→MK-0524A 2g+Simvastatin 40mg
After a 2-week placebo run-in, participants will receive MK-0524B 0.9g/40 mg combination tablet for 4 weeks, then MK-0524B 1.8g /40 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 40 mg for 8 weeks.
干预措施: MK-0524A (Drug)
Sequence 3: MK-0524B 1.8g/40mg→MK-0524A 2g+Simvastatin 40mg
After a 2-week placebo run-in, participants will receive MK-0524B 0.9g/40 mg combination tablet for 4 weeks, then MK-0524B 1.8g /40 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 40 mg for 8 weeks.
干预措施: Placebo (Drug)
Sequence 3: MK-0524B 1.8g/40mg→MK-0524A 2g+Simvastatin 40mg
After a 2-week placebo run-in, participants will receive MK-0524B 0.9g/40 mg combination tablet for 4 weeks, then MK-0524B 1.8g /40 mg combination tablet for 8 weeks. Participant is then co-administered MK-0524A 2 g + simvastatin 40 mg for 8 weeks.
干预措施: MK-0524B (Drug)
Sequence 4: MK-0524A 2g+Simvastatin 40mg →MK-0524B 1.8g/40mg
After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 40 mg for 4 weeks, then co-administration MK-0524A 2g +simvastatin 40 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/40 mg combination tablet for 8 weeks.
干预措施: MK-0524A (Drug)
Sequence 4: MK-0524A 2g+Simvastatin 40mg →MK-0524B 1.8g/40mg
After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 40 mg for 4 weeks, then co-administration MK-0524A 2g +simvastatin 40 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/40 mg combination tablet for 8 weeks.
干预措施: Placebo (Drug)
Sequence 4: MK-0524A 2g+Simvastatin 40mg →MK-0524B 1.8g/40mg
After a 2-week placebo run-in, participants will be co-administered MK-0524A 1g + simvastatin 40 mg for 4 weeks, then co-administration MK-0524A 2g +simvastatin 40 mg for 8 weeks. Participant then receives MK-0524B 1.8 g/40 mg combination tablet for 8 weeks.
干预措施: MK-0524B (Drug)
结局指标
主要结局
Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
时间窗: Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment during each period (Week 12 for Period II and Week 20 for Period III)
Blood samples taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment during each period to determine the LDL-C levels. The change from baseline after 8 weeks of treatment was recorded.
次要结局
- Percentage of Participants With a Confirmed Adjudicated Cardiovascular Event(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants Who Experience at Least 1 Laboratory AE(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants With Creatine Kinase (CK) >=10 x ULN(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)(Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment during each period (Week 12 for Period II and Week 20 for Period III))
- Percentage of Participants With CK >=10 x ULN With Muscle Symptoms - Drug Related(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants With Worsening of the Pre-existing Conditions of Diabetes in Participants With Diabetes at Baseline(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants Who Experience at Least 1 Hepatitis-related Non-serious Clinical AE(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage Change From Baseline in LDL-C at Week 4(Baseline (Day1 of Period I) and Week 4)
- Percentage of Participants With Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x Upper Limit of Normal (ULN)(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants With CK >=10 x ULN With Muscle Symptoms(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants With New Diagnosis of Impaired Fasting Blood Glucose(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants With New Diagnosis of Diabetes(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants Who Experience at Least 1 Clinical Adverse Event (AE)(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants Who Were Discontinued From the Study Due to a Laboratory AE(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage of Participants Who Were Discontinued From the Study Due to a Clinical AE(up 20 weeks (12 weeks in Period I/II and 8 weeks in Period III))
- Percentage Change From Baseline in HDL-C at Week 4(Baseline (Day1 of Period I) and Week 4)