Efficacy of Lapaquistat Co-Administered With Statins in Subjects With Hypercholesterolemia - Full Text View

Sponsor:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00532311

Purpose

The purpose of the study is to determine the efficacy of lapaquistat taken with statins on cholesterol levels in subjects with hypercholesterolemia

Condition	Intervention	Phase
Hypercholesterolemia	Drug: Lapaquistat and stable statin therapy Drug: Stable statin therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 50 mg or Placebo When Co-Administered With Statins in Subjects With Hypercholesterolemia, With an Optional Open-Label Extension

Resource links provided by NLM:

Genetics Home Reference related topics: hypercholesterolemia

MedlinePlus related topics: Cholesterol Statins

Drug Information available for: Lovastatin Simvastatin Pravastatin Pravastatin sodium Fluvastatin Atorvastatin Atorvastatin calcium Rosuvastatin calcium Rosuvastatin

U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from Baseline in Triglycerides [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in Total Cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in High Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in Very Low Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in apolipoprotein A1 [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in apolipoprotein B [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in non- High Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in the ratio of Low Density Lipoprotein cholesterol/High Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in high-sensitivity C-reactive protein [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 1.81 mmol/L (70 mg/dL) [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 2.59 mmol/L (100 mg/dL) [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 3.37 mmol/L (130 mg/dL) [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]

Enrollment:	411
Study Start Date:	July 2007
Study Completion Date:	April 2008
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Lapaquistat and stable statin therapy Lapaquistat 50 mg, tablets, orally, once daily and stable statin therapy for up to 12 weeks.
2: Placebo Comparator	Drug: Stable statin therapy Lapaquistat placebo-matching tablets, orally, once daily and stable statin therapy for up to 12 weeks.

Detailed Description:

Dyslipidemias are a group of metabolic disorders produced by raised concentrations of lipoproteins, especially low-density lipoprotein cholesterol, which is the lipoprotein that transports endogenous cholesterol from the liver to the peripheral tissues. Increased cholesterol and triglycerides levels lead to an increased risk of arteriosclerosis, which is the underlying cause of heart attack, strokes and peripheral vascular disease.

Despite changes in lifestyle and the availability of potent lipid-lowering agents, cardiovascular disease continues to be the major cause of death in Western Europe and North America. Serum cholesterol levels exceeding 5 mmol/L (193 mg/dL) are common in adults in Britain and much of Europe, the United States, Australia and New Zealand.

This study will evaluate the efficacy and safety of lapaquistat taken with either torvastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin or lovastatin (stable statin therapy) in subjects with hypercholesterolemia. Total participation time in this study is expected to be up to 12 weeks, with an optional, 48-week, open-label extension period for participants who qualify.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Females of childbearing potential who are sexually active must agree to use adequate contraception from screening throughout the duration of the study and for 30 days following the last dose.
Has been on a stable dose of statin for at least 3 months prior to Screening. Participants enrolled in Canada, Latin America, and South Africa must be on the maximum approved dose of statin (atorvastatin 80 mg, simvastatin 80 mg, rosuvastatin 40 mg, pravastatin 80 mg, fluvastatin 80 mg, or lovastatin 80 mg).
Prior to Randomization, the participant has a mean low density lipoprotein cholesterol level greater than or equal to 100 mg/dL and less than or equal to 190 mg/dL for 2 consecutive samples.
Prior to Randomization, the subject has mean triglyceride level greater than or equal to 400 mg/dL for 2 consecutive samples.
Is willing and able to comply with the recommended, standardized diet.

Exclusion Criteria:

Has an nine aminotransferase or aspartate aminotransferase level greater than 1.5 times the upper limit of normal, identified during screening.
Has a serum creatinine greater than 133 mmol/L, identified during screening.
Has a creatine kinase greater than 3 times the upper limit of normal, identified during screening.
Has active liver disease or jaundice.
Has taken any bile acid sequestrants [eg, cholestyramine], and intestinal cholesterol uptake inhibitors [eg, ezetimibe]) from 30 days before Screening until study completion or any fibrates for 6 weeks before Visit 1.
Has a previous history of cancer that has been in remission for less than 5 years prior to the first dose of study medication.
Has an endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism affecting lipid metabolism.
Has a history of myocardial infarction, angina pectoris, unstable angina, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal aortic aneurysm, coronary angioplasty, coronary or peripheral arterial surgery, or multiple risk factors that confer a 10-year risk for cardiovascular heart disease greater than 20% based on Framingham risk scoring.
Has a positive hepatitis B surface antigen or hepatitis C virus antibody test, as determined by medical history.
Has a positive human immunodeficiency virus status or is taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
Has received any investigational medication 30 days prior to screening, (for drugs with a long half-life, within a period of less than 5 times the drug's half-life) or is participating in an investigational study.
Has received lapaquistat acetate in a previous clinical study or as a therapeutic agent.
Has a history or presence of clinically significant food allergy that would prevent adherence to the specialized 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 had inflammatory bowel disease or any other malabsorption syndrome, or has had gastric bypass or any other surgical procedure for weight loss.
Has a history of drug abuse or a history of high alcohol intake within the previous 2 years.
Has type 1 or 2 diabetes mellitus.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532311

Hide Study Locations

Locations

United States, Alabama

Tuscaloosa, Alabama, United States

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Mobile, Alabama, United States
United States, Arizona

Tucson, Arizona, United States

Chandler, Arizona, United States

Gilbert, Arizona, United States

Glendale, Arizona, United States
United States, California

Walnut Creek, California, United States

Santa Rosa, California, United States

Tustin, California, United States

Long Beach, California, United States

Santa Ana, California, United States

Artesia, California, United States
United States, Colorado

Colorado Springs, Colorado, United States

Golden, Colorado, United States
United States, District of Columbia

Washington, District of Columbia, United States
United States, Florida

Jacksonville, Florida, United States

Miami, Florida, United States

Sarasota, Florida, United States

West Palm Beach, Florida, United States

St. Petersburg, Florida, United States

Hollywood, Florida, United States

Pinellas Park, Florida, United States

Pembroke Pines, Florida, United States

Pensacola, Florida, United States

Ft. Meyers, Florida, United States

Coral Gables, Florida, United States

New Port Richey, Florida, United States
United States, Georgia

Dunwoody, Georgia, United States
United States, Idaho

Idaho Falls, Idaho, United States
United States, Illinois

Aurora, Illinois, United States

Chicago, Illinois, United States
United States, Indiana

Evansville, Indiana, United States

Indianapolis, Indiana, United States
United States, Iowa

Iowa City, Iowa, United States
United States, Kansas

Wichita, Kansas, United States

Overland Park, Kansas, United States
United States, Kentucky

Louisville, Kentucky, United States
United States, Maine

CantonAuburn, Maine, United States

Scarborough, Maine, United States
United States, Maryland

Baltimore, Maryland, United States
United States, Massachusetts

Haverhill, Massachusetts, United States
United States, Michigan

Ann Arbor, Michigan, United States
United States, Minnesota

Brooklyn Center, Minnesota, United States

Edina, Minnesota, United States
United States, Mississippi

Olive Branch, Mississippi, United States
United States, Missouri

St. Louis, Missouri, United States
United States, Montana

Billings, Montana, United States
United States, New Jersey

Wilwood, New Jersey, United States

Margate, New Jersey, United States
United States, North Carolina

Asheville, North Carolina, United States

Charlotte, North Carolina, United States

Salisbury, North Carolina, United States

Durham, North Carolina, United States

Wilmington, North Carolina, United States

Winston Salem, North Carolina, United States

Hickory, North Carolina, United States

Raleigh, North Carolina, United States

Statesville, North Carolina, United States
United States, Ohio

Cincinnati, Ohio, United States

Mentor, Ohio, United States

Kettering, Ohio, United States

Zanesville, Ohio, United States
United States, Oklahoma

Oklahoma City, Oklahoma, United States
United States, Oregon

Portland, Oregon, United States
United States, Pennsylvania

Dowington, Pennsylvania, United States

Altoona, Pennsylvania, United States

Sellerville, Pennsylvania, United States
United States, Rhode Island

Warwick, Rhode Island, United States
United States, South Carolina

Simpsonville, South Carolina, United States

Goose Creek, South Carolina, United States

Greer, South Carolina, United States

Mt. Pleasant, South Carolina, United States

Mt Pleasant, South Carolina, United States
United States, Tennessee

Bristol, Tennessee, United States
United States, Texas

Houston, Texas, United States

Dallas, Texas, United States

Austin, Texas, United States

Corpus Christi, Texas, United States

Irving, Texas, United States

San Antonio, Texas, United States
United States, Utah

Salt Lake City, Utah, United States
United States, Virginia

Richmond, Virginia, United States

Norfolk, Virginia, United States

Burke, Virginia, United States
United States, Wisconsin

Wauwatosa, Wisconsin, United States

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

Medical Director

Takeda Global Research & Development Center, Inc.

More Information

No publications provided

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	TAK-475-307
Study First Received:	September 18, 2007
Last Updated:	January 14, 2009
ClinicalTrials.gov Identifier:	NCT00532311 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

Hyperlipidemia
Drug Therapy

Additional relevant MeSH terms:

Antimetabolites
Hyperlipidemias
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Enzyme Inhibitors
Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Pravastatin
Therapeutic Uses
Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on November 27, 2009