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

NCT00143663 | Completed Phase 3

• 2 other identifiers: 01-04-TL-475-008U1111-1122-7722
• Study Type: interventional
• Target: 361
• Locations: 1 country
• Sites: 47

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).

Conditions

Dyslipidemia

Keywords

Hypercholesterolemia; Hyperlipidemia; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Low-Density Lipoprotein cholesterol

  Week 12 or Final Visit

Secondary Outcomes (12)

• Change from Baseline in Calculated Low-Density Lipoprotein cholesterol

  Week 12 or Final Visit

• Change from Baseline in High-Density Lipoprotein cholesterol

  Week 12 or Final Visit

• Change from Baseline in the ratio of Low-Density Lipoprotein cholesterol/ High-Density Lipoprotein cholesterol

  Week 12 or Final Visit

• Change from Baseline in Very Low-Density Lipoprotein cholesterol

  Week 12 or Final Visit

• Change from Baseline in non- High-Density Lipoprotein cholesterol

  Week 12 or Final Visit

Study Arms (2)

Lapaquistat Acetate 100 mg QD

EXPERIMENTAL

Drug: Lapaquistat Acetate

Placebo QD

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Lapaquistat Acetate DRUG

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

Also known as: TAK-475

Lapaquistat Acetate 100 mg QD

Placebo DRUG

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

Placebo QD

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (47)

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Northport, Alabama, United States

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Mesa, Arizona, United States

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Chula Vista, California, United States

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Encinitas, California, United States

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Long Beach, California, United States

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Pismo 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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Golden, Colorado, United States

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Aventura, Florida, United States

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Clearwater, Florida, United States

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Daytona Beach, Florida, United States

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Hollywood, Florida, United States

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Jacksonville, Florida, United States

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Jupiter, Florida, United States

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New Port Richy, Florida, United States

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Pembroke Pines, Florida, United States

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Elk Grove Village, Illinois, United States

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Peoria, Illinois, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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Arkansas City, Kansas, United States

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Wichita, Kansas, United States

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Louisville, Kentucky, United States

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Livonia, Michigan, United States

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Las Vegas, Nevada, United States

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Margate City, New Jersey, United States

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New Hyde Park, New York, United States

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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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Medford, Oregon, United States

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Downingtown, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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Tipton, Pennsylvania, United States

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Warwick, Rhode Island, United States

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Charleston, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Bristol, Tennessee, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Ogden, Utah, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Madison, Wisconsin, United States

Location

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

Dyslipidemias; 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

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

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: August 31, 2005
• First Posted: September 2, 2005
• Study Start: September 1, 2005
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2006
• Last Updated: May 24, 2012

Record last verified: 2012-05

Locations

US (47)