- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00532311
Efficacy of Lapaquistat Acetate Co-Administered With Statins in Subjects With Hypercholesterolemia
A Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 50 mg or Placebo When Co-administered With Statins in Subjects With Hypercholesterolemia, With an Optional Open-Label Extension
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Dyslipidemias are a group of metabolic disorders produced by raised concentrations of lipoproteins, especially low-density lipoprotein cholesterol, which is the lipoprotein that transports endogenous cholesterol from the liver to the peripheral tissues. Increased cholesterol and triglycerides levels lead to an increased risk of arteriosclerosis, which is the underlying cause of heart attack, strokes and peripheral vascular disease.
Despite changes in lifestyle and the availability of potent lipid-lowering agents, cardiovascular disease continues to be the major cause of death in Western Europe and North America. Serum cholesterol levels exceeding 5 mmol/L (193 mg/dL) are common in adults in Britain and much of Europe, the United States, Australia and New Zealand.
This study will evaluate the efficacy and safety of lapaquistat acetate taken with either torvastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin or lovastatin (stable statin therapy) in subjects with hypercholesterolemia. Total participation time in this study is expected to be up to 12 weeks, with an optional, 48-week, open-label extension period for participants who qualify.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States
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Huntsville, Alabama, United States
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Mobile, Alabama, United States
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Tuscaloosa, Alabama, United States
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Arizona
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Chandler, Arizona, United States
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Gilbert, Arizona, United States
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Glendale, Arizona, United States
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Tucson, Arizona, United States
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California
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Artesia, California, United States
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Long Beach, California, United States
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Santa Ana, California, United States
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Santa Rosa, California, United States
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Tustin, California, United States
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Walnut Creek, California, United States
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Colorado
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Colorado Springs, Colorado, United States
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Golden, Colorado, United States
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District of Columbia
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Washington, District of Columbia, United States
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Florida
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Coral Gables, Florida, United States
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Ft. Meyers, Florida, United States
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Hollywood, Florida, United States
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Jacksonville, Florida, United States
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Miami, Florida, United States
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New Port Richey, Florida, United States
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Pembroke Pines, Florida, United States
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Pensacola, Florida, United States
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Pinellas Park, Florida, United States
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Sarasota, Florida, United States
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St. Petersburg, Florida, United States
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West Palm Beach, Florida, United States
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Georgia
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Dunwoody, Georgia, United States
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Idaho
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Idaho Falls, Idaho, United States
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Illinois
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Aurora, Illinois, United States
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Chicago, Illinois, United States
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Indiana
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Evansville, Indiana, United States
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Indianapolis, Indiana, United States
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Iowa
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Iowa City, Iowa, United States
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Kansas
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Overland Park, Kansas, United States
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Wichita, Kansas, United States
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Kentucky
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Louisville, Kentucky, United States
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Maine
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CantonAuburn, Maine, United States
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Scarborough, Maine, United States
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Maryland
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Baltimore, Maryland, United States
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Massachusetts
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Haverhill, Massachusetts, United States
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Michigan
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Ann Arbor, Michigan, United States
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Minnesota
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Brooklyn Center, Minnesota, United States
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Edina, Minnesota, United States
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Mississippi
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Olive Branch, Mississippi, United States
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Missouri
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St. Louis, Missouri, United States
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Montana
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Billings, Montana, United States
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New Jersey
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Margate, New Jersey, United States
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Wilwood, New Jersey, United States
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North Carolina
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Asheville, North Carolina, United States
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Charlotte, North Carolina, United States
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Durham, North Carolina, United States
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Hickory, North Carolina, United States
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Raleigh, North Carolina, United States
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Salisbury, North Carolina, United States
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Statesville, North Carolina, United States
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Wilmington, North Carolina, United States
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Winston Salem, North Carolina, United States
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Ohio
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Cincinnati, Ohio, United States
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Kettering, Ohio, United States
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Mentor, Ohio, United States
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Zanesville, Ohio, United States
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Oklahoma
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Oklahoma City, Oklahoma, United States
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Oregon
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Portland, Oregon, United States
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Pennsylvania
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Altoona, Pennsylvania, United States
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Dowington, Pennsylvania, United States
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Sellerville, Pennsylvania, United States
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Rhode Island
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Warwick, Rhode Island, United States
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South Carolina
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Goose Creek, South Carolina, United States
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Greer, South Carolina, United States
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Mt Pleasant, South Carolina, United States
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Mt. Pleasant, South Carolina, United States
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Simpsonville, South Carolina, United States
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Tennessee
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Bristol, Tennessee, United States
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Texas
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Austin, Texas, United States
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Corpus Christi, Texas, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Irving, Texas, United States
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San Antonio, Texas, United States
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Utah
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Salt Lake City, Utah, United States
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Virginia
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Burke, Virginia, United States
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Norfolk, Virginia, United States
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Richmond, Virginia, United States
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Wisconsin
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Wauwatosa, Wisconsin, United States
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Females of childbearing potential who are sexually active must agree to use adequate contraception from screening throughout the duration of the study and for 30 days following the last dose.
- Has been on a stable dose of statin for at least 3 months prior to Screening. Participants enrolled in Canada, Latin America, and South Africa must be on the maximum approved dose of statin (atorvastatin 80 mg, simvastatin 80 mg, rosuvastatin 40 mg, pravastatin 80 mg, fluvastatin 80 mg, or lovastatin 80 mg).
- Prior to Randomization, the participant has a mean low density lipoprotein cholesterol level greater than or equal to 100 mg/dL and less than or equal to 190 mg/dL for 2 consecutive samples.
- Prior to Randomization, the subject has mean triglyceride level greater than or equal to 400 mg/dL for 2 consecutive samples.
- Is willing and able to comply with the recommended, standardized diet.
Exclusion Criteria:
- Has an nine aminotransferase or aspartate aminotransferase level greater than 1.5 times the upper limit of normal, identified during screening.
- Has a serum creatinine greater than 133 mmol/L, identified during screening.
- Has a creatine kinase greater than 3 times the upper limit of normal, identified during screening.
- Has active liver disease or jaundice.
- Has taken any bile acid sequestrants [eg, cholestyramine], and intestinal cholesterol uptake inhibitors [eg, ezetimibe]) from 30 days before Screening until study completion or any fibrates for 6 weeks before Visit 1.
- Has a previous history of cancer that has been in remission for less than 5 years prior to the first dose of study medication.
- Has an endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism affecting lipid metabolism.
- Has a history of myocardial infarction, angina pectoris, unstable angina, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal aortic aneurysm, coronary angioplasty, coronary or peripheral arterial surgery, or multiple risk factors that confer a 10-year risk for cardiovascular heart disease greater than 20% based on Framingham risk scoring.
- Has a positive hepatitis B surface antigen or hepatitis C virus antibody test, as determined by medical history.
- Has a positive human immunodeficiency virus status or is taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
- Has received any investigational medication 30 days prior to screening, (for drugs with a long half-life, within a period of less than 5 times the drug's half-life) or is participating in an investigational study.
- Has received lapaquistat acetate in a previous clinical study or as a therapeutic agent.
- Has a history or presence of clinically significant food allergy that would prevent adherence to the specialized 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 had inflammatory bowel disease or any other malabsorption syndrome, or has had gastric bypass or any other surgical procedure for weight loss.
- Has a history of drug abuse or a history of high alcohol intake within the previous 2 years.
- Has type 1 or 2 diabetes mellitus.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Stable statin therapy
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Lapaquistat acetate placebo-matching tablets, orally, once daily and stable statin therapy for up to 12 weeks.
Other Names:
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Experimental: Lapaquistat Acetate 50 mg QD
(and stable statin therapy)
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Lapaquistat acetate 50 mg, tablets, orally, once daily and stable statin therapy for up to 12 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Change from Baseline in Triglycerides
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in Total Cholesterol
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in apolipoprotein A1
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in apolipoprotein B
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in non- High Density Lipoprotein cholesterol
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in High Density Lipoprotein cholesterol
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in Very Low Density Lipoprotein cholesterol
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in high-sensitivity C-reactive protein
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Change from Baseline in the ratio of Low Density Lipoprotein cholesterol/High Density Lipoprotein cholesterol
Time Frame: 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 1.81 mmol/L (70 mg/dL)
Time Frame: 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 2.59 mmol/L (100 mg/dL)
Time Frame: 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 3.37 mmol/L (130 mg/dL)
Time Frame: Week 12 or Final Visit
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Week 12 or Final Visit
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Lipid Metabolism Disorders
- Hyperlipidemias
- Dyslipidemias
- Hypercholesterolemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Atorvastatin
- Rosuvastatin Calcium
- Pravastatin
- Simvastatin
- Lovastatin
- L 647318
- Dihydromevinolin
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
Other Study ID Numbers
- TAK-475_307
- U1111-1122-8479 (Registry Identifier: WHO)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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