A Phase III Multicenter, Double-Blind, Crossover Design Study to Evaluate Lipid-Altering Efficacy and Safety of Extended-Release Niacin/Laropiprant/Simvastatin Combination Tablet in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 977
- 主要终点
- Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
研究概览
简要总结
This study is being done to find out if tablets containing extended release (ER) niacin, laropiprant, and simvastatin (ERN/LRPT/SIM) are as effective as tablets containing ER niacin and laropiprant taken with simvastatin tablets (ERN/LRPT + SIM) for lowering high cholesterol and high lipid levels in the blood. The primary hypothesis is that ERN/LRPT/SIM 2 g/40 mg is equivalent to ERN/LRPT 2 g co-administered with simvastatin 40 mg in reducing low-density lipoprotein cholesterol (LDL-C).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg
After a 2-week placebo run-in, participants received extended release (ER) niacin/laropiprant (N/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.
干预措施: Simvastatin (Drug)
Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg
After a 2-week placebo run-in, participants received extended release (ER) niacin/laropiprant (N/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.
干预措施: Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM) (Drug)
Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg
After a 2-week placebo run-in, participants received extended release (ER) niacin/laropiprant (N/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.
干预措施: Extended Release (ER) niacin/laropiprant (N/LRPT) (Drug)
Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg
After a 2-week placebo run-in, participants received extended release (ER) niacin/laropiprant (N/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.
干预措施: Placebo (Drug)
Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g
After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.
干预措施: Simvastatin (Drug)
Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g
After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.
干预措施: Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM) (Drug)
Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g
After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.
干预措施: Extended Release (ER) niacin/laropiprant (N/LRPT) (Drug)
Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g
After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
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 (Week 12 for Period II and Week 20 for Period III)
Blood samples were taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III) to determine the LDL-C levels. The change from baseline after 8 weeks of treatment was recorded. Results from recent studies indicated that the combination tablet formulations used in the study did not meet the pre-specified pharmacokinetic bounds used to establish the equivalence of the combination tablet (MK-0524B; ERN/LRPT/SIM) to the coadministration of MK-0524A (ERN/LRPT) and SIM. Therefore, efficacy data were not analyzed, as the study was stopped early. Only safety data were evaluated.
次要结局
- 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 Elevations in ALT and/or AST of >=10 x ULN(up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III))
- 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 Periods I/II and 8 weeks in Period III))
- Percentage of Participants With Elevations in ALT and/or AST of >=5 x ULN(up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III))
- Percentage of Participants With Creatine Kinase (CK) >=10 x ULN(up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III))
- Percentage of Participants With CK >=10 x ULN With Muscle Symptoms - Drug Related(up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III))
- Percentage of Participants Who Experienced at Least 1 Hepatitis-related Adverse Event (AE)(up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III))
- Percentage of Participants With New Onset of Diabetes(up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III))
- Percentage of Participants With a Confirmed Adjudicated Cardiovascular Event(up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III))
- Percentage of Participants Who Experienced at Least 1 AE(up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III))
- Percentage of Participants Who Were Discontinued From the Study Due to an AE(up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III))