Efficacy of Lapaquistat Acetate in Subjects With Hypercholesterolemia

NCT ID: NCT00865228

Last Updated: 2012-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2007-11-30

Brief Summary

The purpose of this study is to determine the role of time of dosing on the lipid-lowering effects of lapaquistat acetate, once daily (QD) or twice daily (BID), in subjects with hypercholesterolemia.

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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lapaquistat Acetate 100 mg QD (morning)

Group Type: EXPERIMENTAL

Lapaquistat acetate

Intervention Type: DRUG

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.

Lapaquistat Acetate 100 mg QD (evening)

Group Type: EXPERIMENTAL

Lapaquistat acetate

Intervention Type: DRUG

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.

Lapaquistat Acetate 50 mg BID

Group Type: EXPERIMENTAL

Lapaquistat acetate

Intervention Type: DRUG

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.

Placebo BID

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Lapaquistat acetate

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.

Intervention Type: DRUG

Lapaquistat acetate

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.

Intervention Type: DRUG

Lapaquistat acetate

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

TAK-475; TAK-475; TAK-475

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VP, Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Long Beach, California, United States

Sacramento, California, United States

San Diego, California, United States

Hollywood, Florida, United States

Jacksonville, Florida, United States

New Port Richey, Florida, United States

Chicago, Illinois, United States

Wichita, Kansas, United States

Louisville, Kentucky, United States

Margate City, New Jersey, United States

Charlotte, North Carolina, United States

Raleigh, North Carolina, United States

Statesville, North Carolina, United States

Wilmington, North Carolina, United States

Winston-Salem, North Carolina, United States

Medford, Oregon, United States

Perkasie, Pennsylvania, United States

Sellerville, Pennsylvania, United States

Bristol, Tennessee, United States

Norfolk, Virginia, United States

Richmond, Virginia, United States

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

U1111-1122-8404

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-475_201

Identifier Type: -

Identifier Source: org_study_id