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

NCT00249912 | Completed Phase 3

• 2 other identifiers: 01-05-TL-475-022U1111-1122-8106
• Study Type: interventional
• Target: 415
• Locations: 2 countries
• Sites: 92

Brief Summary

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.

Conditions

Hypercholesterolemia

Keywords

Hyperlipidemia; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Low Density Lipoprotein cholesterol

  Week 24 or Final Visit

Secondary Outcomes (20)

• Adverse Events

  Weeks: 2, 4, 8, 12, 16, 20, and 24 or Final Visit

• Physical Examination

  Week 24 or Final Visit

• Safety Laboratory Tests

  Weeks: 2, 4, 8, 12, 16, 20, and 24 or Final Visit

• 12- lead Electrocardiogram assessments

  Week 24 or Final Visit

• Best Corrected Visual Acuity results

  Week 24 or Final Visit

Study Arms (3)

Lapaquistat Acetate 50 mg QD + Rosuvastatin

EXPERIMENTAL

Drug: Lapaquistat acetate and rosuvastatin

Lapaquistat Acetate 100 mg QD + Rosuvastatin

EXPERIMENTAL

Drug: Lapaquistat acetate and rosuvastatin

Rosuvastatin

ACTIVE COMPARATOR

Drug: Rosuvastatin

Interventions

Lapaquistat acetate and rosuvastatin DRUG

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

Also known as: TAK-475, Crestor

Lapaquistat Acetate 50 mg QD + Rosuvastatin

Rosuvastatin DRUG

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

Also known as: Crestor

Rosuvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Takeda: lead

Study Sites (92)

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Birmingham, Alabama, United States

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Haleyville, Alabama, United States

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Mobile, Alabama, United States

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Scottsdale, Arizona, United States

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Long Beach, California, United States

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Mission Viejo, California, United States

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Orange, California, United States

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Redondo Beach, California, United States

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Rolling Hills Estates, California, United States

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San Diego, California, United States

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Torrance, California, United States

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Tustin, California, United States

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Avon, Connecticut, United States

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Bristol, Connecticut, United States

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DeLand, Florida, United States

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Fort Lauderdale, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Jupiter, Florida, United States

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Melbourne, Florida, United States

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Miami, Florida, United States

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Naples, Florida, United States

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Ocala, Florida, United States

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Pembroke Pines, Florida, United States

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Plantation, Florida, United States

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Hayden Lake, Idaho, United States

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Meridian, Idaho, United States

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Arlington Heights, Illinois, United States

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Aurora, Illinois, United States

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Chicago, Illinois, United States

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Peoria, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Kansas City, Kansas, United States

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Witchita, Kansas, United States

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Louisville, Kentucky, United States

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Thibodaux, Louisiana, United States

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Auburn, Maine, United States

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Haverhill, Massachusetts, United States

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Benzonia, Michigan, United States

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Detroit, Michigan, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Missoula, Montana, United States

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Concord, New Hampshire, United States

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West Seneca, New York, United States

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Raleigh, North Carolina, United States

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Statesville, North Carolina, United States

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Winstom-Salem, North Carolina, United States

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Grand Forks, North Dakota, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Kettering, Ohio, United States

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Tulsa, Oklahoma, United States

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Eugene, Oregon, United States

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Portland, Oregon, United States

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Lansdale, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Scotland, Pennsylvania, United States

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Cranston, Rhode Island, United States

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Anderson, South Carolina, United States

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Bristol, Tennessee, United States

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Cordova, Tennessee, United States

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Kingsport, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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McKinney, Texas, United States

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Midland, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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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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Weber City, Virginia, United States

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Bellevue, Washington, United States

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Burien, Washington, United States

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Edmonds, Washington, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Calgary, Alberta, Canada

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Portage la Prairie, Manitoba, Canada

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London, Ontario, Canada

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Oakville, Ontario, Canada

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Oshawa, Ontario, Canada

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Thornhill, Ontario, Canada

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Toronto, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Saint-Jérôme, Quebec, Canada

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Ste-Foy, Quebec, Canada

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Related Publications (1)

• 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.

  PMID: 21518985 RESULT

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipidemias

Interventions

1-((1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)acetyl)piperidine-4-acetic acid; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2005
• First Posted: November 7, 2005
• Study Start: October 1, 2005
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2007
• Last Updated: May 24, 2012

Record last verified: 2012-05

Locations

CA (10); US (82)