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

Phase 3TerminatedNCT01294683

Merck Sharp & Dohme LLC977 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

977

Conditions

Primary Hypercholesterolemia Dyslipidemia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)

Blood samples were taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III) to determine the LDL-C levels. The change from baseline after 8 weeks of treatment was recorded. Results from recent studies indicated that the combination tablet formulations used in the study did not meet the pre-specified pharmacokinetic bounds used to establish the equivalence of the combination tablet (MK-0524B; ERN/LRPT/SIM) to the coadministration of MK-0524A (ERN/LRPT) and SIM. Therefore, efficacy data were not analyzed, as the study was stopped early. Only safety data were evaluated.

Time frame: Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III)

Secondary Outcomes

Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)

Blood samples were taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III) to determine the HDL-C levels. The change from baseline after 8 weeks of treatment was recorded. Results from recent studies indicated that the combination tablet formulations used in the study did not meet the pre-specified pharmacokinetic bounds used to establish the equivalence of the combination tablet (MK-0524B; ERN/LRPT/SIM) to the coadministration of MK-0524A (ERN/LRPT) and SIM. Therefore, efficacy data were not analyzed, as the study was stopped early. Only safety data were evaluated.

Time frame: Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment during each period (Week 12 for Period II and Week 20 for Period III)

Percentage of Participants With Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x Upper Limit of Normal (ULN)

Participants had AST and ALT levels assessed during Period I (4 weeks ) and throughout each 8 week treatment period (20 weeks total). Participants who had an assessment of either AST or ALT that was 3 x ULN or greater were recorded. The AST UNLs for males and females were 43 U/L and 36 U/L, respectively. The ALT UNLs for males and females were 40 U/L and 33 U/L, respectively.

Time frame: Up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Percentage of Participants With Elevations in ALT and/or AST of >=5 x ULN

Participants had AST and ALT levels assessed during Period I (4 weeks ) throughout each 8 week treatment period (20 weeks total). Participants who had an assessment of either AST or ALT that was 5 x ULN or greater were recorded. The AST UNLs for males and females were 43 U/L and 36 U/L, respectively. The ALT UNLs for males and females were 40 U/L and 33 U/L, respectively.