• Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  

• Change from Baseline in Triglycerides [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in Total Cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in High Density Lipoprotein cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in Very Low Density Lipoprotein cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in apolipoprotein A1 [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in apolipoprotein B [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in non- High Density Lipoprotein cholesterol [ Time Frame: Week 24 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 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Change from Baseline in high-sensitivity C-reactive protein [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 2.59 mmol/L (100 mg/dL) [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 3.37 mmol/L (130 mg/dL) [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]
  
• Best corrected visual acuity [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: Yes ]
  
• Adverse Events [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 or Final Visit ] [ Designated as safety issue: Yes ]
  
• Clinical Laboratory Tests [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 or Final Visit ] [ Designated as safety issue: Yes ]
  
• Vital Signs [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 or Final Visit ] [ Designated as safety issue: Yes ]
  
• 12-lead Electrocardiogram [ Time Frame: Weeks 12 and 24 or Final Visit ] [ Designated as safety issue: Yes ]
  
• Physical Examination [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: Yes ]
  

In humans, cholesterol is acquired from dietary sources and is produced de novo in the liver, intestine, and various other tissues. Normally, the balance among cholesterol synthesis, dietary intake, and degradation is adequate to maintain healthy cholesterol plasma levels; however, in subjects with hypercholesterolemia, elevation in low-density lipoprotein cholesterol leads to atherosclerotic deposition of cholesterol in the arterial walls (atherosclerosis) and subsequent coronary heart disease. Thus, it has been established that lowering the low-density lipoprotein cholesterol plasma concentrations effectively reduces cardiovascular morbidity and mortality. Additional lipid risk factors for coronary heart disease include elevated triglyceride, very low-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels, and low levels of high-density lipoprotein cholesterol.

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, representing a serious public health concern.

Currently, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) are the first-line monotherapies prescribed for the treatment of dyslipidemia, after diet and therapeutic lifestyle changes alone fail to reduce low-density lipoprotein cholesterol to desired levels. Statins reduce low-density lipoprotein cholesterol and triglycerides, increase high-density lipoprotein cholesterol, and improve endothelial function. Treatment with statins reduces the risk of a vascular event by about 30% in subjects with and without symptoms of arteriosclerosis; however, many subjects fail to reach recommended levels of low-density lipoprotein cholesterol reduction after receiving low-dose statins as a monotherapy. Consequently, the dosage of statins is often increased or an additional treatment is added; the latter has become an important therapeutic option for achieving increasingly stringent lipid targets set forth by international therapeutic guidelines.

Ezetimibe is a lipid-lowering compound that selectively inhibits intestinal absorption of cholesterol at the brush border of the small intestine, leading to a decrease in the delivery of intestinal cholesterol to the liver. Ezetimibe does not affect the absorption of triglycerides, fatty acids, bile acids, progesterone, ethinylestradiol, or fat-soluble vitamins A and D.

TAK-475 (lapaquistat acetate) is a squalene synthase inhibitor currently under development at Takeda for the treatment of dyslipidemia. This study will evaluate the efficacy and safety of lapaquistat acetate taken with ezetimibe in subjects with hypercholesterolemia. Total participation time in this study is expected to be up to 24 weeks.