A Study to Evaluate Efficacy and Safety of Extended-Release Niacin + Laropiprant + Simvastatin in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-118)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 3

Conditions: Primary Hypercholesterolemia; Dyslipidemia

Treatments: Drug: Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM); Drug: Placebo; Drug: Simvastatin; Drug: Extended Release (ER) niacin/laropiprant (N/LRPT)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01294683

0524B-118

2010-023939-42 (EudraCT Number)

Details and patient eligibility

About

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/40 mg is equivalent to ERN/LRPT 2 g co-administered with simvastatin 40 mg in reducing low-density lipoprotein cholesterol (LDL-C).

Enrollment: 977 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Participant has a history of primary hypercholesterolemia or mixed dyslipidemia and meets LDL-C and triglyceride criteria.
• Visit 2:
• Participant is high risk coronary heart disease (CHD) or CHD risk-equivalent.

Exclusion Criteria

• Participant is pregnant or breast-feeding, or expecting to conceive during the study.

• Participant has a history of malignancy.

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

• Participant is high risk CHD patient on statin therapy or any patient on statin therapy equivalent to 80 mg simvastatin.

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

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

• Participant 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.

• Participant is human immunodeficiency virus (HIV) positive.

• Participant has taken niacin >50 mg/day, bile-acid sequestrants, hydroxymethyl glutaryl 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.

• Participant 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.

• Participant is taking prohibited medications such as systemic corticosteroids, itraconazole or ketoconazole, erythromycin, clarithromycin, or telithromycin, nefazodone, HIV protease inhibitors, verapamil, amiodarone, cyclosporine, danazol, diltiazem or fusidic acid.

• Participant consumes >1 quart of grapefruit juice/day.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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977 participants in 2 patient groups

Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg

Experimental group

Description:

After a 2-week placebo run-in, participants received extended release (ER) niacin/laropiprant (N/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.

Treatment:

Drug: Placebo

Drug: Extended Release (ER) niacin/laropiprant (N/LRPT)

Drug: Simvastatin

Drug: Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM)

Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g

Experimental group

Description:

After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.

Treatment:

Drug: Placebo

Drug: Extended Release (ER) niacin/laropiprant (N/LRPT)

Drug: Simvastatin

Drug: Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM)