Efficacy of Lapaquistat Acetate Alone or Combined With Simvastatin in Subjects With Hypercholesterolemia
A Double-Blind, Randomized, Placebo-Controlled Factorial Study to Evaluate the Efficacy and Safety of Lapaquistat and Simvastatin Alone and in Combination in Subjects With Hypercholesterolemia
研究概览
地位
条件
详细说明
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. Patients with hypercholesterolemia have elevated low-density lipoprotein cholesterol, which leads to atherosclerotic deposition of cholesterol in the arterial walls. As identified by the National Cholesterol Education Program Adult Treatment Panel III, lowering the low-density lipoprotein cholesterol plasma concentration effectively reduces cardiovascular morbidity and mortality and is essential for the prevention and management of coronary heart disease.
Currently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are the first-line monotherapies prescribed to reduce low-density lipoprotein cholesterol, after diet and therapeutic lifestyle change. However, low doses of statins often fail to produce the ATP III-recommended levels of low-density lipoprotein cholesterol reduction, making it necessary to increase the dose or add an additional treatment. Dose increases of statins in turn may result in decreased tolerability and potential safety concerns which contribute to the high discontinuation rates of statins and their prescription at low, and often ineffective, doses.
The purpose of this study is to determine whether administration of lapaquistat acetate co-administered with simvastatin will be more efficacious in lowering low-density lipoprotein cholesterol, compared to lapaquistat or simvastatin alone. Total participation time in this study is anticipated to be 19 weeks.
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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British Columbia
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Abbotsford、British Columbia、加拿大
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Coquitlam、British Columbia、加拿大
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Victoria、British Columbia、加拿大
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Manitoba
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Winnipeg、Manitoba、加拿大
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Newfoundland and Labrador
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Mount Pearl、Newfoundland and Labrador、加拿大
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St. John's、Newfoundland and Labrador、加拿大
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Ontario
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Cornwall、Ontario、加拿大
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London、Ontario、加拿大
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Oakville、Ontario、加拿大
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Oshawa、Ontario、加拿大
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Thornhill、Ontario、加拿大
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Toronto、Ontario、加拿大
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Prince Edward Island
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Cornwall、Prince Edward Island、加拿大
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Quebec
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Mirabel、Quebec、加拿大
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Sherbrooke、Quebec、加拿大
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St. Lambert、Quebec、加拿大
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Ste-Foy、Quebec、加拿大
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Alabama
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Huntsville、Alabama、美国
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Arizona
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Chandler、Arizona、美国
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Scottsdale、Arizona、美国
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Sierra Vista、Arizona、美国
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Tucson、Arizona、美国
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California
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Beverly Hills、California、美国
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Long Beach、California、美国
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Sacramento、California、美国
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Spring Valley、California、美国
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Colorado
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Colorado Springs、Colorado、美国
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Florida
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Hialeah、Florida、美国
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Hollywood、Florida、美国
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Jacksonville、Florida、美国
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Jupiter、Florida、美国
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Kissimmee、Florida、美国
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Miami、Florida、美国
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Ocala、Florida、美国
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Pembroke Pines、Florida、美国
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Pinellas Park、Florida、美国
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Stuart、Florida、美国
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West Palm Beach、Florida、美国
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Illinois
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Arlington Heights、Illinois、美国
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Chicago、Illinois、美国
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Peoria、Illinois、美国
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Indiana
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Indianapolis、Indiana、美国
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Kansas
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Overland Park、Kansas、美国
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Wichita、Kansas、美国
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Kentucky
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Louisville、Kentucky、美国
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Minnesota
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Edina、Minnesota、美国
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Missouri
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St. Louis、Missouri、美国
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Nevada
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Las Vegas、Nevada、美国
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New Jersey
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Margate City、New Jersey、美国
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North Carolina
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Raleigh、North Carolina、美国
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Statesville、North Carolina、美国
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Winston-Salem、North Carolina、美国
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Ohio
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Cincinnati、Ohio、美国
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Columbus、Ohio、美国
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Kettering、Ohio、美国
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Oklahoma
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Bartlesville、Oklahoma、美国
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Oregon
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Portland、Oregon、美国
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Pennsylvania
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Beaver、Pennsylvania、美国
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Downingtown、Pennsylvania、美国
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Tipton、Pennsylvania、美国
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South Carolina
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Goose Creek、South Carolina、美国
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Tennessee
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Jackson、Tennessee、美国
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Nashville、Tennessee、美国
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Texas
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San Antonio、Texas、美国
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Virginia
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Norfolk、Virginia、美国
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Richmond、Virginia、美国
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Washington
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Lakewood、Washington、美国
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Woman of childbearing potential can not to be pregnant, lactating, not planning on becoming pregnant, and agree to use acceptable forms of contraception throughout the course of the study.
- Prior to Randomization, has a low-density lipoprotein cholesterol level mean greater than or equal to 3.37 mmol/L and less than or equal to 5.70 mmol/L.
- Prior to Randomization, has a mean triglyceride level less than or equal to 4.52 mmol/L (400 mg/dL).
- Has clinical laboratory evaluations including clinical chemistry, hematology, and urinalysis within the defined reference range.
Exclusion Criteria:
- Has an alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
- Has a serum creatinine of greater than 133 μmol/L.
- Has a creatine kinase greater than 3 times the upper limit of normal.
- Has type 1 or 2 diabetes mellitus.
- Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication.
- Has an endocrine disorder, such as Cushing syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism.
- Has a history of myocardial infarction, angina pectoris, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal aortic aneurysm, coronary revascularization or multiple factors that conferred a 10-year risk for coronary heart disease greater than 20% based on Framingham risk scoring.
- Has a positive hepatitis B surface antigen, or antibody to hepatitis C virus, as determined by medical history and/or subject's verbal report.
- Has a positive human immunodeficiency virus status or was taking antiretroviral medications, as determined by medical history.
- Has exposure to lapaquistat acetate in other studies, was participating in another investigational study, or had participated in an investigational study within the past 30 days or, for drugs with a long half-life, within a period of less than 5 times the drug's half-life. Has a known hypersensitivity or history of adverse reaction to simvastatin.
- Has a known hypersensitivity or history of adverse reaction to simvastatin.
- Has a history or presence of clinically significant food allergy that would prevent adherence to the recommended diet.
- Has a known heterozygous or homozygous familial hypercholesterolemia or known Type III hyperlipoproteinemia (familial dysbetalipoproteinemia).
- Has fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain.
- Has uncontrolled hypertension
- Has inflammatory bowel disease, any other malabsorption syndrome, or had gastric bypass or any other surgical procedure for weight loss.
- Is unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
- Has any other serious disease or condition that might reduced life expectancy, impaired successful management according to the protocol, or make the participant an unsuitable candidate to receive study medication.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:阶乘赋值
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器:辛伐他汀
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Lapaquistat acetate placebo-matching tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
其他名称:
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实验性的:Lapaquistat Acetate 50 mg QD + 辛伐他汀
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Lapaquistat acetate 50 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
其他名称:
Lapaquistat acetate 100 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
其他名称:
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实验性的:Lapaquistat Acetate 100 mg QD + 辛伐他汀
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Lapaquistat acetate 50 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
其他名称:
Lapaquistat acetate 100 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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低密度脂蛋白胆固醇相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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次要结果测量
结果测量 |
大体时间 |
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甘油三酯基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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总胆固醇的基线变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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载脂蛋白 A1 相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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载脂蛋白 B 相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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非高密度脂蛋白胆固醇相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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高密度脂蛋白胆固醇相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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极低密度脂蛋白胆固醇相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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总胆固醇/高密度脂蛋白胆固醇比值相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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载脂蛋白 A1/载脂蛋白 B 比值相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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高敏 C 反应蛋白相对于基线的变化
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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低密度脂蛋白胆固醇浓度低于 2.59 毫摩尔/升(100 毫克/分升)的受试者百分比
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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低密度脂蛋白胆固醇浓度低于 3.37 毫摩尔/升(130 毫克/分升)的受试者百分比
大体时间:第 12 周或最后一次访问
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第 12 周或最后一次访问
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Adverse Events
大体时间:Weeks: 2, 4, 8, and 12 or Final Visit
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Weeks: 2, 4, 8, and 12 or Final Visit
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Physical Examination
大体时间:Week 12 or Final Visit
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Week 12 or Final Visit
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Safety Laboratory Tests
大体时间:Weeks: 2, 4, 8, and 12 or Final Visit
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Weeks: 2, 4, 8, and 12 or Final Visit
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12- lead Electrocardiogram assessments
大体时间:Week 12 or Final Visit
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Week 12 or Final Visit
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Best Corrected Visual Acuity results
大体时间:Week 12 or Final Visit
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Week 12 or Final Visit
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Vital Signs
大体时间:Weeks: 2, 4, 8, and 12 or Final Visit
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Weeks: 2, 4, 8, and 12 or Final Visit
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Change from Baseline in the ratio of Low Density Lipoprotein cholesterol/High Density
大体时间:Week 12 or Final Visit
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Week 12 or Final Visit
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Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 4.14 mmol/L (160 mg/dL)
大体时间:Week 12 or Final Visit
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Week 12 or Final Visit
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合作者和调查者
赞助
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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