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

NCT ID: NCT01335997

Last Updated: 2019-02-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-01
• Study Completion Date: 2012-01-01

Brief 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).

Conditions

Primary Hypercholesterolemia; Mixed Dyslipidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ERN/LRPT/SIM → ERN/LRPT+SIM

Weeks 0-4 (Period 1): Participants will take ERN/LRPT/SIM 1 g/10 mg and SIM-matching placebo tablets daily; Weeks 5-12 (Period 2): Participants will be advanced to ERN/LRPT/SIM 2 g/20 mg and SIM-matching placebo tablets daily; Weeks 13-20 (Period III): Participants will crossover to ERN/LRPT 2 g + SIM 20 mg coadministration treatment.

Group Type: EXPERIMENTAL

ER niacin/laropiprant (ERN/LRPT)

Intervention Type: DRUG

ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily

ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)

Intervention Type: DRUG

ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily

Simvastatin (SIM)

Intervention Type: DRUG

Simvastatin 10 mg oral tablet taken once daily

Placebo Run-In

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo for simvastatin 10 mg oral tablet taken once daily

ERN/LRPT+SIM → ERN/LRPT/SIM

Weeks 0-4 (Period I): Participants will take ERN/LRPT co-administered with SIM (ERN/LRPT 1g + SIM 10 mg tablets) daily; Weeks 5-12 (Period II): Participants will be advanced to ERN/LRPT 2 g + SIM 20 mg daily; Weeks 13-20 (Period III): Participants will crossover to the ERN/LRPT/SIM 2 g/20 mg combination treatment and SIM-matching placebo tablets.

Group Type: ACTIVE_COMPARATOR

ER niacin/laropiprant (ERN/LRPT)

Intervention Type: DRUG

ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily

ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)

Intervention Type: DRUG

ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily

Simvastatin (SIM)

Intervention Type: DRUG

Simvastatin 10 mg oral tablet taken once daily

Placebo Run-In

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo for simvastatin 10 mg oral tablet taken once daily

Interventions

ER niacin/laropiprant (ERN/LRPT)

ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily

Intervention Type: DRUG

ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)

ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily

Intervention Type: DRUG

Simvastatin (SIM)

Simvastatin 10 mg oral tablet taken once daily

Intervention Type: DRUG

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

Intervention Type: DRUG

SIM-matching placebo

Placebo for simvastatin 10 mg oral tablet taken once daily

Intervention Type: DRUG

Other Intervention Names

MK-0524B; MK-0524A, Tredaptive™; Zocor®

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Documents

Document Type: CSR Synsopsi Link

View Document

Other Identifiers

2011-001007-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0524B-143

Identifier Type: -

Identifier Source: org_study_id