Efficacy and Safety of Extended-Release Niacin/ Laropiprant/Simvastatin Tablets in Participants With Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-143)

Primary Hypercholesterolemia Clinical Trial

Official title:

A Phase III Multicenter, Double-Blind, Crossover Design Study to Evaluate Lipid-Altering Efficacy and Safety of 1 g/10 mg Extended-Release Niacin/Laropiprant/Simvastatin Combination Tablets in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01335997
• Other study ID #: 0524B-143
• Secondary ID: 2011-001007-12
• Status: Terminated
• Phase: Phase 3
• Start date: May 1, 2011
• Est. completion date: January 1, 2012

Study information

• Verified date: January 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to find out if tablets containing extended release (ER) niacin, laropiprant, and simvastatin (ERN/LRPT/SIM) are as effective as tablets containing ER niacin and laropiprant taken with simvastatin tablets (ERN/LRPT + SIM) for lowering high cholesterol and high lipid levels in the blood. The primary hypothesis is that ERN/LRPT/SIM 2 g /20 mg is equivalent to ERN/LRPT 2 g coadministered with simvastatin 20 mg in reducing low-density lipoprotein cholestrol (LDL-C).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1139
• Est. completion date: January 1, 2012
• Est. primary completion date: January 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion criteria:

• Has a history of primary hypercholesterolemia or mixed dyslipidemia and meets LDL-C and triglyceride criteria.

• Is high risk coronary heart disease (CHD) and has LDL-C =190 mg/dL (=4.91 mmol/L).

• Is not high risk CHD and has LDL-C =240 mg/dL (=6.21 mmol/L).

Exclusion criteria:

• Is pregnant or breast-feeding, or expecting to conceive or donate eggs or sperm during the study.

• Has a history of malignancy within =5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

• Consumes more than 3 alcoholic drinks per day (14 per week).

• Is a high risk CHD patient on lipid modifying therapy (LMT).

• Is on any LMT with equivalent or greater LDL-C-lowering efficacy than simvastatin 40 mg.

• Has Type 1 or Type 2 diabetes mellitus that is poorly controlled, or on statin therapy.

• Currently engages in vigorous exercise or is on an aggressive diet regimen.

• Has uncontrolled endocrine or metabolic disease, uncontrolled gout, kidney or hepatic disease, heart failure, recent peptic ulcer disease, hypersensitivity or allergic reaction to niacin or simvastatin, recent heart attack, stroke or heart surgery.

• Is human immunodeficiency virus (HIV) positive.

• Has taken niacin >50 mg/day, bile-acid sequestrants, 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA) reductase inhibitors, ezetimibe, Cholestin™ [red yeast rice] and other red yeast products within 6 weeks, or fibrates within 8 weeks of randomization visit (Visit 3).

Note: Fish oils, phytosterol margarines and other non-prescribed therapies are allowed provided participant has been on a stable dose for 6 weeks prior to Visit 2 and agrees to remain on this dose for the duration of the study.

• Is currently receiving cyclical hormonal contraceptives or intermittent use of hormone replacement therapies (HRTs) (e.g., estradiol, medroxyprogesterone, progesterone). Note: Participants who have been on a stable dose of non-cyclical HRT or hormonal contraceptive for greater than 6 weeks prior to Visit 1 are eligible if they agree to remain on the same regimen for the duration of the study.

• Is taking prohibited medications such as systemic corticosteroids, potent inhibitors of Cytochrome P450 3A4 (CYP3A4), cyclosporine, danazol, or fusidic acid.

• Consumes >1 quart of grapefruit juice/day.

• Requires warfarin treatment and has not been on a stable dose with a stable International Normalized Ratio (INR) for at least 6 weeks prior to Visit 1.

Related Conditions & MeSH terms

• Dyslipidemias
• Hypercholesterolemia
• Mixed Dyslipidemia
• Primary Hypercholesterolemia

Intervention

Drug:
• ER niacin/laropiprant (ERN/LRPT)
ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily
• ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)
ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily
• Simvastatin (SIM)
Simvastatin 10 mg oral tablet taken once daily
• Placebo Run-In
Placebo matches both ER niacin 1 g/laropiprant 20 mg oral tablet and ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet; placebo is taken once daily
• SIM-matching placebo
Placebo for simvastatin 10 mg oral tablet taken once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Blood Levels	Due to study termination caused by the decision to stop the development of the combination tablet, sufficient data were not available to perform the planned efficacy analysis, which is based on the cross-over data collected in period II and III.	Baseline and Week 12 and Week 20
Secondary	Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) Blood Levels	Due to study termination caused by the decision to stop the development of the combination tablet, sufficient data were not available to perform the planned efficacy analysis, which is based on the cross-over data collected in period II and III.	Baseline and Week 12 and Week 20