NCT00813527

Effect of Lapaquistat Acetate Combined With Fenofibrate on Blood Cholesterol Levels

A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 or Placebo When Coadministered With Fenofibrate in Subjects With Combined Hyperlipidemia

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 213 (actual)
• Sponsor: Takeda · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to compare changes in cholesterol levels in patients with elevated blood cholesterol with administration of lapaquistat acetate, once daily (QD), and fenofibrate.

Detailed description

Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. It has been established that lowering the low-density lipoprotein cholesterol plasma concentration effectively reduces cardiovascular morbidity and mortality. As a result of this finding, the National Cholesterol Education Program Adult Treatment Panel III identifies control of low-density lipoprotein cholesterol as essential in the prevention and management of coronary heart disease. Currently, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line monotherapies prescribed to reduce low-density lipoprotein cholesterol, after diet and therapeutic lifestyle change. However, low doses of statins often fail to produce the Adult Treatment Panel III-recommended levels of low-density lipoprotein cholesterol reduction, making it necessary to increase the dose or add an additional treatment. This in turn may result in decreased tolerability and potential safety concerns. At higher doses, statins are associated with various myopathies ranging from rare occurrences of rhabdomyolysis and myositis to more frequent symptoms of muscle weakness, cramps, or pain; these can occur with mild or no increases in creatine kinase. Statin use also is associated with increases in liver transaminase levels. These tolerability and safety concerns may contribute to the high discontinuation rates of statins and their prescription at low, and often ineffective, doses. TAK-475 (lapaquistat acetate) inhibits the cholesterol synthesis pathway at a different step than statins (acting on squalene synthase rather than 3-hydroxy-3-methylglutaryl coenzyme A); it does not reduce concentrations of isoprenylated intermediates believed to be responsible for the myopathies associated with statin use. This study was conducted to determine whether lapaquistat acetate with fenofibrate has the potential to be more effective than fenofibrate by itself in lowering low-density lipoprotein cholesterol.

Conditions

• Hyperlipidemias

Interventions

Type	Name	Description
DRUG	Lapaquistat acetate and fenofibrate	Lapaquistat acetate 100 mg, tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.
DRUG	Fenofibrate	Lapaquistat acetate placebo-matching tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.

Timeline

• Start date: 2006-02-01
• Primary completion: 2007-01-01
• Completion: 2007-01-01
• First posted: 2008-12-23
• Last updated: 2012-05-24

Locations

36 sites across 2 countries: United States, Canada