Efficacy of Lapaquistat Acetate in Subjects With Hypercholesterolemia

This study has been terminated.
(Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents)
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00865228
First received: March 18, 2009
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to determine the role of time of dosing on the lipid-lowering effects of lapaquistat acetate, once daily (QD) or twice daily (BID), in subjects with hypercholesterolemia.


Condition Intervention Phase
Hypercholesterolemia
Drug: Lapaquistat acetate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 100 mg in the Morning vs Lapaquistat Acetate 100 mg in the Evening vs Lapaquistat Acetate 50 mg Twice Daily vs Placebo in Subjects With Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percent change from Baseline in the Fasting Plasma Low-Density Lipoprotein Cholesterol concentration [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Total Cholesterol [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in apolipoprotein B [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in apolipoprotein A1 [ Time Frame: Week 6 ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Triglycerides [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in High-Density Lipoprotein Cholesterol [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in Very Low-Density Lipoprotein Cholesterol [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in non- High-Density Lipoprotein Cholesterol [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in derived ratio of Low-Density Lipoprotein Cholesterol / High-Density Lipoprotein Cholesterol [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in derived ratio of Total Cholesterol / High-Density Lipoprotein Cholesterol [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent change from Baseline in derived ratio of apolipoprotein B / apolipoprotein A1 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Change from Baseline in high sensitivity C-Reactive Protein. [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

Enrollment: 224
Study Start Date: July 2007
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapaquistat Acetate 100 mg QD (morning) Drug: Lapaquistat acetate
Lapaquistat acetate 100 mg, tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.
Other Name: TAK-475
Experimental: Lapaquistat Acetate 100 mg QD (evening) Drug: Lapaquistat acetate
Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate 100 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Name: TAK-475
Experimental: Lapaquistat Acetate 50 mg BID Drug: Lapaquistat acetate
Lapaquistat acetate 50 mg, tablets, orally, once daily in the morning and Lapaquistat acetate 50 mg, tablets, orally, once daily in the evening for up to six weeks.
Other Name: TAK-475
Placebo Comparator: Placebo BID Drug: Placebo
Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.

Detailed Description:

Dyslipidemias are a group of metabolic disorders produced by raised concentrations of lipoproteins, especially low-density lipoprotein cholesterol the lipoprotein that transports endogenous cholesterol from the liver to the peripheral tissues. Increased cholesterol and triglyceride levels lead to an increased risk of arteriosclerosis, 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.

Lapaquistat acetate is being developed by Takeda for the treatment of hypercholesterolemia.

  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 a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
  • Has prior to Randomization a mean low-density lipoprotein cholesterol greater than or equal to 130 mg/dL and less than or equal to 220 mg/dL for 2 consecutive samples.
  • Has prior to Randomization mean triglycerides less than 400 mg/dL for 2 consecutive samples.
  • Is willing and able to comply with a standardized, therapeutic lifestyle change diet or equivalent.

Exclusion Criteria:

  • Has an alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of normal during the screening period.
  • Has a serum creatinine greater than133 mmol/L during the screening period.
  • Has a creatine phosphokinase greater than 3 times the upper limit of normal, identified during the screening period.
  • Has active liver disease or jaundice.
  • Has a 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 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, abdomin al aorticaneurysm, coronary angioplasty, coronary or peripheral arterial surgery or multiple risk factors that confer a 10-year risk for cardiovascular 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 is taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
  • Has received any investigational compound within 30 days prior to screening Visit 1, or is currently participating in another 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.
  • Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.
  • Has uncontrolled hypertension despite treatment at Screening Visit 1.
  • Has had inflammatory bowel 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 alcohol abuse within the past 2 years.
  • Has stage I squamous cell carcinoma of the skin.
  • Has type 1 or type 2 diabetes mellitus.
  • Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • Fluvastatin
    • Lovastatin
    • bile acid sequestrants (eg, cholestyramine)
    • intestinal cholesterol uptake inhibitors (eg, ezetimibe)
    • Fibrates (eg, fenofibrate, gemfibrozil)
    • Niacin
    • Cholestin
    • red yeast rice
    • fish oils
    • plant sterols and stanols
    • orlistat
    • sibutramine
    • isotretinoin
    • tacrolimus
    • Probucol
    • Systemic corticosteroids and androgens
    • Potent CYP3A4 inhibitors
    • Cyclosporine
    • Erythromycin
    • Clarithromycin
    • Telithromycin
    • human immunodeficiency virus protease inhibitors
    • amiodarone
    • diltiazem
    • verapamil
    • nefazodone
    • grapefruit juice
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00865228

Locations
United States, California
Long Beach, California, United States
Sacramento, California, United States
San Diego, California, United States
United States, Florida
Hollywood, Florida, United States
Jacksonville, Florida, United States
New Port Richey, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Kansas
Wichita, Kansas, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, New Jersey
Margate, New Jersey, United States
United States, North Carolina
Charlotte, North Carolina, United States
Raleigh, North Carolina, United States
Statesville, North Carolina, United States
Wilmington, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Oregon
Medford, Oregon, United States
United States, Pennsylvania
Perkasie, Pennsylvania, United States
Sellerville, Pennsylvania, United States
United States, Tennessee
Bristol, Tennessee, United States
United States, Virginia
Norfolk, Virginia, United States
Richmond, Virginia, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP, Clinical Science Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00865228     History of Changes
Other Study ID Numbers: TAK-475_201, U1111-1122-8404
Study First Received: March 18, 2009
Last Updated: May 23, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Hyperlipidemia
Dyslipidemia
High Cholesterol
Drug Therapy

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 01, 2014