Effect of Lapaquistat Acetate on Blood Cholesterol Levels in Subjects With Elevated Cholesterol

NCT ID: NCT00143663

Last Updated: 2012-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 361 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2006-04-30

Brief Summary

The purpose of this study is to determine if patients with elevated cholesterol, but not taking any other lipid medication, could lower their cholesterol with administration of lapaquistat acetate, once daily (QD).

Detailed Description

This study will evaluate the efficacy and safety of TAK-475 (lapaquistat acetate) compared to placebo in subjects with primary hypercholesterolemia. Subjects who have signed the informed consent will undergo necessary evaluations to determine eligibility for a dietary run-in phase. Subjects who meet randomization criteria will enter treatment with one of the following randomized treatments: lapaquistat acetate or placebo.

Conditions

Dyslipidemia

Study Design

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

Study Groups

Lapaquistat Acetate 100 mg QD

Group Type: EXPERIMENTAL

Lapaquistat Acetate

Intervention Type: DRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily for up to 12 weeks

Placebo QD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Lapaquistat acetate placebo-matching tablets, orally, once daily for up to 12 weeks

Interventions

Lapaquistat Acetate

Lapaquistat acetate 100 mg, tablets, orally, once daily for up to 12 weeks

Intervention Type: DRUG

Placebo

Lapaquistat acetate placebo-matching tablets, orally, once daily for up to 12 weeks

Intervention Type: DRUG

Other Intervention Names

TAK-475

Eligibility Criteria

Inclusion Criteria

• Female participants of childbearing potential cannot be been pregnant, lactating and are not planning on becoming pregnant and agrees to use acceptable forms of contraception throughout the course of this study.
• Must have a mean low-density lipoprotein cholesterol values between 3.367 and 5.689 mmol/L, inclusive, from 2 consecutive samples taken at least 1 week apart with the difference between the 2 values not exceeding 15% of the higher value.
• Must have a triglyceride value of 4.516 mmol/L or less from 2 consecutive samples taken at least 1 week apart with the upper value from either sample being 5.081 mmol/L or less.
• Has clinical laboratory evaluations within the reference ranges for the testing laboratory unless the results were deemed not clinically significant by the investigator or sponsor.
• Is willing and able to maintain a standardized low-cholesterol diet.

Exclusion Criteria

• Has an alanine aminotransferase or aspartate aminotransferase level greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
• Has a serum creatinine level greater than 135 μmol/L.
• Has a creatine phosphokinase value greater than three times the upper limit of normal.
• Has diabetes mellitus type 1 or 2.
• Has a history of cancer that had been in remission for less than 5 years prior to the first dose of study drug. This criterion did not include subjects with basal cell or stage I squamous cell carcinoma of the skin.
• 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 risk factors that present a 10-year risk for CHD of greater than 20%, based on Framingham risk scoring.
• Has a positive hepatitis B surface antigen or hepatitis C virus antibody, as determined by medical history and/or participant's verbal report.
• Has a positive human immunodeficiency virus test result or was taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
• Is unable or unwilling to discontinue excluded medications or to continue stable doses of "stable dose" medications or would require treatment with any excluded medication during the study.
• Has had exposure to lapaquistat acetate in other studies or was participating or enrolled in another investigational study within the previous 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 history or presence of a clinically significant food allergy that would prevent adherence to the therapeutic lifestyle change (or equivalent) 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 or any other malabsorption syndrome or 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 any other serious disease or condition at Run-In or at Randomization that might reduce life expectancy, impair successful management according to the protocol, or make the subject an unsuitable candidate to receive study drug.

• 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

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Northport, Alabama, United States

Mesa, Arizona, United States

Chula Vista, California, United States

Encinitas, California, United States

Long Beach, California, United States

Pismo Beach, California, United States

Sacramento, California, United States

San Diego, California, United States

Golden, Colorado, United States

Aventura, Florida, United States

Clearwater, Florida, United States

Daytona Beach, Florida, United States

Hollywood, Florida, United States

Jacksonville, Florida, United States

Jupiter, Florida, United States

New Port Richy, Florida, United States

Pembroke Pines, Florida, United States

Elk Grove Village, Illinois, United States

Peoria, Illinois, United States

Evansville, Indiana, United States

Indianapolis, Indiana, United States

Arkansas City, Kansas, United States

Wichita, Kansas, United States

Louisville, Kentucky, United States

Livonia, Michigan, United States

Las Vegas, Nevada, United States

Margate City, New Jersey, United States

New Hyde Park, New York, 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

Downingtown, Pennsylvania, United States

Sellersville, Pennsylvania, United States

Tipton, Pennsylvania, United States

Warwick, Rhode Island, United States

Charleston, South Carolina, United States

Mt. Pleasant, South Carolina, United States

Bristol, Tennessee, United States

Dallas, Texas, United States

San Antonio, Texas, United States

Ogden, Utah, United States

Norfolk, Virginia, United States

Richmond, Virginia, United States

Madison, Wisconsin, United States

Countries

United States

References

Stein EA, Bays H, O'Brien D, Pedicano J, Piper E, Spezzi A. Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia. Circulation. 2011 May 10;123(18):1974-85. doi: 10.1161/CIRCULATIONAHA.110.975284. Epub 2011 Apr 25.

Reference Type: RESULT

PMID: 21518985 (View on PubMed)

Other Identifiers

U1111-1122-7722

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-04-TL-475-008

Identifier Type: -

Identifier Source: org_study_id