Ignite Creation Date:
2024-05-05 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00143676
Status:
COMPLETED
Last Update Posted:
2012-05-24
First Post:
2005-08-31
Brief Title:
Efficacy of Lapaquistat Acetate and Atorvastatin on Blood Cholesterol Levels in Subjects With Primary Hypercholesterolemia
Sponsor:
Takeda
Organization:
Takeda
Study Overview
Official Title:
A Double-blind Randomized Placebo-controlled Study to Evaluate the Efficacy and Safety of TAK-475 50 mg 100 mg or Placebo When Co-administered With Atorvastatin 10 mg to 40 mg in Subjects With Primary Hypercholesterolemia
Status:
COMPLETED
Status Verified Date:
2012-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine the efficacy of lapaquistat acetate once daily QD on lowering cholesterol in subjects already taking atorvastatin
Detailed Description:
According to the World Health Organization CHD is now the leading cause of death worldwide In 2001 CHD caused 72 million deaths and estimates for 2020 indicate that annual CHD deaths will increase to 111 million These statistics suggest that improved options are needed to treat hypercholesterolemia and dyslipidemia
The balance among cholesterol synthesis dietary intake and degradation is normally adequate to maintain healthy cholesterol plasma levels However in patients with hypercholesterolemia elevated low-density lipoprotein cholesterol leads to atherosclerotic deposition of cholesterol in the arterial walls Consequently in this population it has been established that lowering low-density lipoprotein cholesterol plasma concentrations effectively reduces cardiovascular morbidity and mortality The National Cholesterol Education Program Adult Treatment Panel III has therefore identified control of low-density lipoprotein cholesterol as essential in the prevention and management of CHD Additional lipid risk factors designated by National Cholesterol Education Program Adult Treatment Panel III include elevated triglycerides elevated non-high-density lipoprotein cholesterol atherogenic lipoproteins and low levels of high-density lipoprotein cholesterol Lipoproteins rich in triglycerides such as very-low-density lipoprotein cholesterol appear to contribute to atherosclerosis whereas the apparent protective effect of high-density lipoprotein cholesterol which is likely related to high-density lipoprotein cholesterol-facilitated transport of cholesterol away from atherosclerotic deposits may be limited at low high-density lipoprotein cholesterol concentrations
Initial dietary and lifestyle measures taken to control dyslipidemia are often inadequate and most patients require pharmacologic intervention Currently 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors statins are the first-line monotherapies most often prescribed to reduce low-density lipoprotein cholesterol after diet and therapeutic lifestyle change However with statin monotherapy many patients fail to reach National Cholesterol Education Program Adult Treatment Panel III recommended levels of low-density lipoprotein cholesterol reduction As a result the statin dosage must be increased or an additional treatment added to achieve treatment goals Increasing the statin dosage may result in decreased tolerability and potential safety concerns contributing to the high discontinuation rates of statins and their prescription at low and often ineffective doses Further although the effectiveness of increasing the dose varies among the statins in general doubling of the dose above the minimum effective dose has been found to decrease serum low-density lipoprotein cholesterol by only an additional 6 percent
TGRD is developing an orally active squalene synthase inhibitor TAK-475 lapaquistat acetate for the treatment of dyslipidemia Lapaquistat acetate inhibits the biosynthesis of cholesterol by inhibiting the enzyme squalene synthase which catalyzes the conversion of farnesyl diphosphate to squalene-a precursor in the final steps of cholesterol production
This study will assess the effects of co-administration of lapaquistat acetate with atorvastatin the most commonly prescribed statin in the United States on LDL-C and associated lipid variables in subjects with hypercholesterolemia Study Participation is anticipated to be up to 24 weeks
The balance among cholesterol synthesis dietary intake and degradation is normally adequate to maintain healthy cholesterol plasma levels However in patients with hypercholesterolemia elevated low-density lipoprotein cholesterol leads to atherosclerotic deposition of cholesterol in the arterial walls Consequently in this population it has been established that lowering low-density lipoprotein cholesterol plasma concentrations effectively reduces cardiovascular morbidity and mortality The National Cholesterol Education Program Adult Treatment Panel III has therefore identified control of low-density lipoprotein cholesterol as essential in the prevention and management of CHD Additional lipid risk factors designated by National Cholesterol Education Program Adult Treatment Panel III include elevated triglycerides elevated non-high-density lipoprotein cholesterol atherogenic lipoproteins and low levels of high-density lipoprotein cholesterol Lipoproteins rich in triglycerides such as very-low-density lipoprotein cholesterol appear to contribute to atherosclerosis whereas the apparent protective effect of high-density lipoprotein cholesterol which is likely related to high-density lipoprotein cholesterol-facilitated transport of cholesterol away from atherosclerotic deposits may be limited at low high-density lipoprotein cholesterol concentrations
Initial dietary and lifestyle measures taken to control dyslipidemia are often inadequate and most patients require pharmacologic intervention Currently 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors statins are the first-line monotherapies most often prescribed to reduce low-density lipoprotein cholesterol after diet and therapeutic lifestyle change However with statin monotherapy many patients fail to reach National Cholesterol Education Program Adult Treatment Panel III recommended levels of low-density lipoprotein cholesterol reduction As a result the statin dosage must be increased or an additional treatment added to achieve treatment goals Increasing the statin dosage may result in decreased tolerability and potential safety concerns contributing to the high discontinuation rates of statins and their prescription at low and often ineffective doses Further although the effectiveness of increasing the dose varies among the statins in general doubling of the dose above the minimum effective dose has been found to decrease serum low-density lipoprotein cholesterol by only an additional 6 percent
TGRD is developing an orally active squalene synthase inhibitor TAK-475 lapaquistat acetate for the treatment of dyslipidemia Lapaquistat acetate inhibits the biosynthesis of cholesterol by inhibiting the enzyme squalene synthase which catalyzes the conversion of farnesyl diphosphate to squalene-a precursor in the final steps of cholesterol production
This study will assess the effects of co-administration of lapaquistat acetate with atorvastatin the most commonly prescribed statin in the United States on LDL-C and associated lipid variables in subjects with hypercholesterolemia Study Participation is anticipated to be up to 24 weeks
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U1111-1122-7783 | REGISTRY | WHO | None |