- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00865228
Efficacy of Lapaquistat Acetate in Subjects With Hypercholesterolemia
A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 100 mg in the Morning vs Lapaquistat Acetate 100 mg in the Evening vs Lapaquistat Acetate 50 mg Twice Daily vs Placebo in Subjects With Hypercholesterolemia
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 the lipoprotein that transports endogenous cholesterol from the liver to the peripheral tissues. Increased cholesterol and triglyceride levels lead to an increased risk of arteriosclerosis, 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.
Lapaquistat acetate is being developed by Takeda for the treatment of hypercholesterolemia.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Long Beach, California, United States
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Sacramento, California, United States
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San Diego, California, United States
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Florida
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Hollywood, Florida, United States
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Jacksonville, Florida, United States
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New Port Richey, Florida, United States
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Illinois
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Chicago, Illinois, United States
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Kansas
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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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New Jersey
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Margate, New Jersey, United States
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North Carolina
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Charlotte, North Carolina, United States
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Raleigh, 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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Oregon
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Medford, Oregon, United States
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Pennsylvania
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Perkasie, Pennsylvania, United States
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Sellerville, Pennsylvania, United States
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Tennessee
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Bristol, Tennessee, United States
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Virginia
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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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Madison, 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 a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
- Has prior to Randomization a mean low-density lipoprotein cholesterol greater than or equal to 130 mg/dL and less than or equal to 220 mg/dL for 2 consecutive samples.
- Has prior to Randomization mean triglycerides less than 400 mg/dL for 2 consecutive samples.
- Is willing and able to comply with a standardized, therapeutic lifestyle change diet or equivalent.
Exclusion Criteria:
- Has an alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of normal during the screening period.
- Has a serum creatinine greater than133 mmol/L during the screening period.
- Has a creatine phosphokinase greater than 3 times the upper limit of normal, identified during the screening period.
- Has active liver disease or jaundice.
- Has a 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 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, abdomin al aorticaneurysm, coronary angioplasty, coronary or peripheral arterial surgery or multiple risk factors that confer a 10-year risk for cardiovascular 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 is taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
- Has received any investigational compound within 30 days prior to screening Visit 1, or is currently participating in another 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.
- Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.
- Has uncontrolled hypertension despite treatment at Screening Visit 1.
- Has had inflammatory bowel 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 alcohol abuse within the past 2 years.
- Has stage I squamous cell carcinoma of the skin.
- Has type 1 or type 2 diabetes mellitus.
Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- Fluvastatin
- Lovastatin
- bile acid sequestrants (eg, cholestyramine)
- intestinal cholesterol uptake inhibitors (eg, ezetimibe)
- Fibrates (eg, fenofibrate, gemfibrozil)
- Niacin
- Cholestin
- red yeast rice
- fish oils
- plant sterols and stanols
- orlistat
- sibutramine
- isotretinoin
- tacrolimus
- Probucol
- Systemic corticosteroids and androgens
- Potent CYP3A4 inhibitors
- Cyclosporine
- Erythromycin
- Clarithromycin
- Telithromycin
- human immunodeficiency virus protease inhibitors
- amiodarone
- diltiazem
- verapamil
- nefazodone
- grapefruit juice
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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Placebo Comparator: Placebo BID
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Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.
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Experimental: Lapaquistat Acetate 100 mg QD (morning)
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Lapaquistat acetate 100 mg, tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.
Other Names:
Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate 100 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Names:
Lapaquistat acetate 50 mg, tablets, orally, once daily in the morning and Lapaquistat acetate 50 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Names:
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Experimental: Lapaquistat Acetate 100 mg QD (evening)
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Lapaquistat acetate 100 mg, tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.
Other Names:
Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate 100 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Names:
Lapaquistat acetate 50 mg, tablets, orally, once daily in the morning and Lapaquistat acetate 50 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Names:
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Experimental: Lapaquistat Acetate 50 mg BID
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Lapaquistat acetate 100 mg, tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.
Other Names:
Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate 100 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Names:
Lapaquistat acetate 50 mg, tablets, orally, once daily in the morning and Lapaquistat acetate 50 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Percent change from Baseline in the Fasting Plasma Low-Density Lipoprotein Cholesterol concentration
Time Frame: Week 6
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Week 6
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Percent change from Baseline in High-Density Lipoprotein Cholesterol
Time Frame: Week 6
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Week 6
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Change from Baseline in Total Cholesterol
Time Frame: Week 6
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Week 6
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Percent change from Baseline in apolipoprotein B
Time Frame: Week 6
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Week 6
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Percent change from Baseline in apolipoprotein A1
Time Frame: Week 6
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Week 6
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Change from Baseline in Triglycerides
Time Frame: Week 6
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Week 6
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Percent change from Baseline in Very Low-Density Lipoprotein Cholesterol
Time Frame: Week 6
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Week 6
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Percent change from Baseline in non- High-Density Lipoprotein Cholesterol
Time Frame: Week 6
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Week 6
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Percent change from Baseline in derived ratio of Low-Density Lipoprotein Cholesterol / High-Density Lipoprotein Cholesterol
Time Frame: Week 6
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Week 6
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Percent change from Baseline in derived ratio of Total Cholesterol / High-Density Lipoprotein Cholesterol
Time Frame: Week 6
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Week 6
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Percent change from Baseline in derived ratio of apolipoprotein B / apolipoprotein A1
Time Frame: Week 6
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Week 6
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Change from Baseline in high sensitivity C-Reactive Protein.
Time Frame: Week 6
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Week 6
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: VP, Clinical Science, Takeda
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
Additional Relevant MeSH Terms
Other Study ID Numbers
- TAK-475_201
- U1111-1122-8404 (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.
Clinical Trials on Hypercholesterolemia
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Direct PlantesUnknownHYPERCHOLESTEROLEMIAFrance
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Chong Kun Dang PharmaceuticalRecruitingPrimary HypercholesterolemiaKorea, Republic of
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Addpharma Inc.CompletedPrimary HypercholesterolemiaKorea, Republic of
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JW PharmaceuticalCompletedPrimary HypercholesterolemiaKorea, Republic of
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Hanmi Pharmaceutical Company LimitedCompletedPrimary HypercholesterolemiaKorea, Republic of
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Organon and CoCompletedPrimary Hypercholesterolemia | Homozygous Familial Hypercholesterolemia
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Ahn-Gook Pharmaceuticals Co.,LtdRecruitingPrimary HypercholesterolemiaKorea, Republic of
Clinical Trials on Lapaquistat acetate
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TakedaTerminatedHypercholesterolemiaUkraine, Spain, Israel, Netherlands, Estonia, Russian Federation, Hungary, Norway, United Kingdom, Slovakia, Latvia
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TakedaCompletedDyslipidemiaUnited States
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TakedaCompletedHypercholesterolemia
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TakedaTerminatedHypercholesterolemiaFrance, United Kingdom, United States, Israel, Poland, Canada
-
TakedaCompletedHypercholesterolemiaSerbia, Estonia, Russian Federation, Latvia
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TakedaCompletedDyslipidemiaUnited States, Germany, Argentina, Mexico, Poland, South Africa, Chile, Netherlands, Peru, Estonia, Russian Federation, Czech Republic, Hungary, Lithuania, Latvia, Slovakia, United Kingdom
-
TakedaCompleted
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TakedaCompletedHyperlipidemiasUnited States, Canada
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TakedaCompletedHypercholesterolemiaPoland, United Kingdom, Germany, South Africa, Finland, Estonia, Czech Republic
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TakedaCompletedHypercholesterolemiaUnited States