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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00143663
First received: August 31, 2005
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

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).


Condition Intervention Phase
Dyslipidemia
Drug: Lapaquistat Acetate
Drug: Placebo
Phase 3

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 TAK-475 100 mg Versus Placebo in Subjects With Primary Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change from Baseline in Low-Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Calculated Low-Density Lipoprotein 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 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 Very Low-Density Lipoprotein cholesterol [ 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 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 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 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 the ratio of apolipoprotein B/ apolipoprotein A1 [ 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 ]

Enrollment: 361
Study Start Date: September 2005
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapaquistat Acetate 100 mg QD Drug: Lapaquistat Acetate
Lapaquistat acetate 100 mg, tablets, orally, once daily for up to 12 weeks
Other Name: TAK-475
Placebo Comparator: Placebo QD Drug: Placebo
Lapaquistat acetate placebo-matching tablets, orally, once daily for up to 12 weeks

Detailed Description:

This study will evaluate the efficacy and safety of TAK-475 (lapaquistat acetate) compared to placebo in subjects with primary hypercholesterolemia. Subjects who have signed the informed consent will undergo necessary evaluations to determine eligibility for a dietary run-in phase. Subjects who meet randomization criteria will enter treatment with one of the following randomized treatments: lapaquistat acetate or placebo.

  Eligibility

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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Has inflammatory bowel disease or any other malabsorption syndrome or 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 any other serious disease or condition at Run-In or at Randomization that might reduce life expectancy, impair successful management according to the protocol, or make the subject an unsuitable candidate to receive study drug.
  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: NCT00143663

  Show 47 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00143663     History of Changes
Other Study ID Numbers: 01-04-TL-475-008, U1111-1122-7722
Study First Received: August 31, 2005
Last Updated: May 23, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Hypercholesterolemia
Hyperlipidemia
Drug Therapy

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

ClinicalTrials.gov processed this record on August 28, 2014