Efficacy of Lapaquistat Acetate Alone or Combined With Simvastatin in Subjects With Hypercholesterolemia

Exclusion Criteria

• •Has an alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
• •Has a serum creatinine of greater than 133 μmol/L.
• •Has a creatine kinase greater than 3 times the upper limit of normal.
• •Has type 1 or 2 diabetes mellitus.
• •Has a previous history of cancer that had 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, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal aortic aneurysm, coronary revascularization or multiple factors that conferred a 10-year risk for coronary heart 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 was taking antiretroviral medications, as determined by medical history.
• •Has exposure to lapaquistat acetate in other studies, was participating in another investigational study, or had participated in an investigational study within the past 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 known hypersensitivity or history of adverse reaction to simvastatin.
• •Has a known hypersensitivity or history of adverse reaction to simvastatin.
• •Has a history or presence of clinically significant food allergy that would prevent adherence to the recommended 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, any other malabsorption syndrome, or had gastric bypass or any other surgical procedure for weight loss.
• •Is unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments.
• •Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
• •Has any other serious disease or condition that might reduced life expectancy, impaired successful management according to the protocol, or make the participant an unsuitable candidate to receive study medication.