Efficacy of Lapaquistat Acetate Alone or Combined With High-Dose Statin Therapy in Subjects With Hypercholesterolemia

NCT00249899 | Terminated Phase 3

• 3 other identifiers: 01-05-TL-475-0212005-004876-19U1111-1122-8008
• Study Type: interventional
• Target: 649
• Locations: 3 countries
• Sites: 23

Brief Summary

The purpose of this study is to evaluate lapaquistat acetate, once daily (QD), taken alone or with additional statin therapy 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 (2)

Lapaquistat Acetate 100 mg QD

EXPERIMENTAL

(and stable statin therapy)

Drug: Lapaquistat acetate and stable statin therapy

Stable statin therapy

ACTIVE COMPARATOR

Drug: Stable statin therapy

Interventions

Lapaquistat acetate and stable statin therapy DRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily and stable statin therapy for up to 24 weeks.

Also known as: TAK-475, Atorvastatin, Rosuvastatin, Simvastatin

Lapaquistat Acetate 100 mg QD

Stable statin therapy DRUG

Lapaquistat acetate placebo-matching, tablets, orally, once daily and stable statin therapy for up to 24 weeks.

Also known as: Atorvastatin, Rosuvastatin, Simvastatin

Stable statin therapy

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.
• The subject had taken the highest recommended dose of a statin for at least 4 weeks prior to Visit 1.

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 to atorvastatin, simvastatin or 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 (23)

Unknown Facility

Santa Ana, California, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Iowa City, Iowa, United States

Location

Unknown Facility

Kansas City, Kansas, United States

Location

Unknown Facility

Auburn, Maine, United States

Location

Unknown Facility

Scarborough, Maine, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Concord, New Hampshire, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Calgary, Alberta, Canada

Location

Unknown Facility

Vancouver, British Columbia, Canada

Location

Unknown Facility

Chicoutimi, Quebec, Canada

Location

Unknown Facility

Laval, Quebec, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Unknown Facility

Ste-Foy, Quebec, Canada

Location

Unknown Facility

Bellville, South Africa

Location

Unknown Facility

Johannesburg, South Africa

Location

Unknown Facility

Parow, South Africa

Location

Unknown Facility

Pretoria, South Africa

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

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; Atorvastatin; Rosuvastatin Calcium; Simvastatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic 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: November 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2007
• Last Updated: May 24, 2012

Record last verified: 2012-05

Locations

ZA (4); CA (6); US (13)