Clinical trial NCT00532311: Efficacy of Lapaquistat Acetate Co-Administered With Statins in Subjects With Hypercholesterolemia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: Hyperlipidemia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-09-20
Enrollment: 411
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 the study is to determine the efficacy of lapaquistat acetate, once daily (QD), taken with statins on cholesterol levels in subjects with hypercholesterolemia

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 acetate 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 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.

Primary outcomes:
measure: Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
Secondary outcomes:
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 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 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 non- 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 the ratio of Total Cholesterol/High Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in high-sensitivity C-reactive protein
timeFrame: Week 12 or Final Visit
measure: Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 1.81 mmol/L (70 mg/dL)
timeFrame: Week 12 or Final Visit
measure: Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 2.59 mmol/L (100 mg/dL)
timeFrame: Week 12 or Final Visit
measure: Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 3.37 mmol/L (130 mg/dL)
timeFrame: Week 12 or Final Visit
Other outcomes:
Locations:
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state: Alabama
city: Huntsville
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state: Alabama
city: Mobile
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city: Tuscaloosa
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state: Alabama
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city: Gilbert
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state: California
city: Long Beach
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city: Santa Rosa
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city: Golden
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state: Colorado
city: Washington
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city: Ft. Meyers
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city: New Port Richey
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city: Pembroke Pines
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city: Dunwoody
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state: Georgia
city: Idaho Falls
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state: Idaho
city: Aurora
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state: Illinois
city: Chicago
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state: Illinois
city: Evansville
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state: Indiana
city: Indianapolis
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city: Iowa City
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state: Iowa
city: Overland Park
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state: Kansas
city: Wichita
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state: Kansas
city: Louisville
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state: Kentucky
city: CantonAuburn
country: United States
state: Maine
city: Scarborough
country: United States
state: Maine
city: Baltimore
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state: Maryland
city: Haverhill
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Brooklyn Center
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state: Minnesota
city: Edina
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state: Minnesota
city: Olive Branch
country: United States
state: Mississippi
city: St. Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Margate
country: United States
state: New Jersey
city: Wilwood
country: United States
state: New Jersey
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Raleigh
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state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Statesville
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state: North Carolina
city: Wilmington
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state: North Carolina
city: Winston Salem
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Kettering
country: United States
state: Ohio
city: Mentor
country: United States
state: Ohio
city: Zanesville
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Altoona
country: United States
state: Pennsylvania
city: Dowington
country: United States
state: Pennsylvania
city: Sellerville
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state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Goose Creek
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state: South Carolina
city: Greer
country: United States
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city: Mt Pleasant
country: United States
state: South Carolina
city: Mt. Pleasant
country: United States
state: South Carolina
city: Simpsonville
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state: South Carolina
city: Bristol
country: United States
state: Tennessee
city: Austin
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state: Texas
city: Corpus Christi
country: United States
state: Texas
city: Dallas
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state: Texas
city: Houston
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city: Irving
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state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Burke
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Wauwatosa
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: