Clinical trial NCT00143663: Effect of Lapaquistat Acetate on Blood Cholesterol Levels in Subjects With Elevated Cholesterol
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dyslipidemia
Keywords: Hypercholesterolemia
Hyperlipidemia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2005-09-02
Enrollment: 361
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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 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.

Primary outcomes:
measure: Change from Baseline in Low-Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
Secondary outcomes:
measure: Change from Baseline in Calculated Low-Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in High-Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in the ratio of Low-Density Lipoprotein cholesterol/ High-Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in Very Low-Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in non- High-Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in Triglycerides
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in Total Cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in the ratio of Total Cholesterol/High-Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in apolipoprotein A1
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in apolipoprotein B
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in the ratio of apolipoprotein B/ apolipoprotein A1
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in High-Sensitivity C-reactive Protein
timeFrame: Week 12 or Final Visit
Other outcomes:
Locations:
city: Northport
country: United States
state: Alabama
city: Mesa
country: United States
state: Arizona
city: Chula Vista
country: United States
state: California
city: Encinitas
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Pismo Beach
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Golden
country: United States
state: Colorado
city: Aventura
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: New Port Richy
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Elk Grove Village
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Arkansas City
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Livonia
country: United States
state: Michigan
city: Las Vegas
country: United States
state: Nevada
city: Margate
country: United States
state: New Jersey
city: New Hyde Park
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Medford
country: United States
state: Oregon
city: Downingtown
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: Tipton
country: United States
state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Mt. Pleasant
country: United States
state: South Carolina
city: Bristol
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.