Efficacy and Safety of Extended-Release Niacin/ Laropiprant/Simvastatin Tablets in Participants With Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-143)
Condition: Primary Hypercholesterolemia; Mixed Dyslipidemia
MeSH terms: Hypercholesterolemia; Dyslipidemias
Intervention: ER niacin/laropiprant (ERN/LRPT); ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM); Simvastatin (SIM); Placebo Run-In; SIM-matching placebo
Intervention description: ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily; ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily; Simvastatin 10 mg oral tablet taken once daily; 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; Placebo for simvastatin 10 mg oral tablet taken once daily
Intervention MeSH terms: Niacin; Niacinamide; Nicotinic Acids; Simvastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 1139.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Low-density lipoprotein; LDL; High-density lipoprotein; HDL; Niacin; Lipid modifying therapy; Cholesterol; High cholesterol; Triglycerides

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).
    

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.