Efficacy of Lapaquistat Acetate Alone or Combined With Rosuvastatin in Subjects With Hypercholesterolemia

NCT ID: NCT00249912

Last Updated: 2012-05-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

415 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2007-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to evaluate lapaquistat acetate, once daily (QD), taken alone or with rosuvastatin on cholesterol levels in treating patients with elevated cholesterol.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 rosuvastatin will be more efficacious in lowering low-density lipoprotein cholesterol, compared to lapaquistat or rosuvastatin alone. Total participation time in this study is anticipated to be 24 weeks.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hypercholesterolemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lapaquistat Acetate 50 mg QD + Rosuvastatin

Group Type EXPERIMENTAL

Lapaquistat acetate and rosuvastatin

Intervention Type DRUG

Lapaquistat acetate 50 mg, tablets, orally, once daily and stable Rosuvastatin therapy (10 or 20 mg) for up to 24 weeks.

Lapaquistat Acetate 100 mg QD + Rosuvastatin

Group Type EXPERIMENTAL

Lapaquistat acetate and rosuvastatin

Intervention Type DRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily and stable Rosuvastatin therapy (10 or 20 mg) for up to 24 weeks.

Rosuvastatin

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Lapaquistat acetate placebo-matching tablets, orally, once daily and stable Rosuvastatin therapy (10 or 20 mg) for up to 24 weeks.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Lapaquistat acetate and rosuvastatin

Lapaquistat acetate 50 mg, tablets, orally, once daily and stable Rosuvastatin therapy (10 or 20 mg) for up to 24 weeks.

Intervention Type DRUG

Lapaquistat acetate and rosuvastatin

Lapaquistat acetate 100 mg, tablets, orally, once daily and stable Rosuvastatin therapy (10 or 20 mg) for up to 24 weeks.

Intervention Type DRUG

Rosuvastatin

Lapaquistat acetate placebo-matching tablets, orally, once daily and stable Rosuvastatin therapy (10 or 20 mg) for up to 24 weeks.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

TAK-475 Crestor TAK-475 Crestor Crestor

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
* Participant is taking a stable dose of rosuvastatin (10 or 20 mg) for at least 4 weeks prior to Screening.

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.
* The subject had a known hypersensitivity or history of adverse reaction rosuvastatin.
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Birmingham, Alabama, United States

Site Status

Haleyville, Alabama, United States

Site Status

Mobile, Alabama, United States

Site Status

Scottsdale, Arizona, United States

Site Status

Long Beach, California, United States

Site Status

Mission Viejo, California, United States

Site Status

Orange, California, United States

Site Status

Redondo Beach, California, United States

Site Status

Rolling Hills Estates, California, United States

Site Status

San Diego, California, United States

Site Status

Torrance, California, United States

Site Status

Tustin, California, United States

Site Status

Avon, Connecticut, United States

Site Status

Bristol, Connecticut, United States

Site Status

DeLand, Florida, United States

Site Status

Fort Lauderdale, Florida, United States

Site Status

Hialeah, Florida, United States

Site Status

Jacksonville, Florida, United States

Site Status

Jupiter, Florida, United States

Site Status

Melbourne, Florida, United States

Site Status

Miami, Florida, United States

Site Status

Naples, Florida, United States

Site Status

Ocala, Florida, United States

Site Status

Pembroke Pines, Florida, United States

Site Status

Plantation, Florida, United States

Site Status

Hayden Lake, Idaho, United States

Site Status

Meridian, Idaho, United States

Site Status

Arlington Heights, Illinois, United States

Site Status

Aurora, Illinois, United States

Site Status

Chicago, Illinois, United States

Site Status

Peoria, Illinois, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Iowa City, Iowa, United States

Site Status

Kansas City, Kansas, United States

Site Status

Witchita, Kansas, United States

Site Status

Louisville, Kentucky, United States

Site Status

Thibodaux, Louisiana, United States

Site Status

Auburn, Maine, United States

Site Status

Haverhill, Massachusetts, United States

Site Status

Benzonia, Michigan, United States

Site Status

Detroit, Michigan, United States

Site Status

Kansas City, Missouri, United States

Site Status

St Louis, Missouri, United States

Site Status

Missoula, Montana, United States

Site Status

Concord, New Hampshire, United States

Site Status

West Seneca, New York, United States

Site Status

Raleigh, North Carolina, United States

Site Status

Statesville, North Carolina, United States

Site Status

Winstom-Salem, North Carolina, United States

Site Status

Grand Forks, North Dakota, United States

Site Status

Akron, Ohio, United States

Site Status

Cincinnati, Ohio, United States

Site Status

Columbus, Ohio, United States

Site Status

Kettering, Ohio, United States

Site Status

Tulsa, Oklahoma, United States

Site Status

Eugene, Oregon, United States

Site Status

Portland, Oregon, United States

Site Status

Lansdale, Pennsylvania, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Pittsburgh, Pennsylvania, United States

Site Status

Scotland, Pennsylvania, United States

Site Status

Cranston, Rhode Island, United States

Site Status

Anderson, South Carolina, United States

Site Status

Bristol, Tennessee, United States

Site Status

Cordova, Tennessee, United States

Site Status

Kingsport, Tennessee, United States

Site Status

Austin, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

Houston, Texas, United States

Site Status

McKinney, Texas, United States

Site Status

Midland, Texas, United States

Site Status

San Antonio, Texas, United States

Site Status

Salt Lake City, Utah, United States

Site Status

Burke, Virginia, United States

Site Status

Norfolk, Virginia, United States

Site Status

Richmond, Virginia, United States

Site Status

Weber City, Virginia, United States

Site Status

Bellevue, Washington, United States

Site Status

Burien, Washington, United States

Site Status

Edmonds, Washington, United States

Site Status

Seattle, Washington, United States

Site Status

Spokane, Washington, United States

Site Status

Calgary, Alberta, Canada

Site Status

Portage la Prairie, Manitoba, Canada

Site Status

London, Ontario, Canada

Site Status

Oakville, Ontario, Canada

Site Status

Oshawa, Ontario, Canada

Site Status

Thornhill, Ontario, Canada

Site Status

Toronto, Ontario, Canada

Site Status

Chicoutimi, Quebec, Canada

Site Status

Saint-Jérôme, Quebec, Canada

Site Status

Ste-Foy, Quebec, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada

References

Explore related publications, articles, or registry entries linked to this study.

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

Review additional registry numbers or institutional identifiers associated with this trial.

U1111-1122-8106

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-05-TL-475-022

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.