Efficacy and Safety of Extended Release (ER) Niacin/Laropiprant When Added to Ongoing Lipid-Modifying Therapy in Patients With High Cholesterol or Abnormal Lipid Levels (MK-0524A-133)

A Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo-Controlled 12-Week Study to Evaluate the Efficacy and Safety of Extended Release (ER) Niacin/Laropiprant When Added to Ongoing Lipid-Modifying Therapy in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia

This is a multicenter, randomized, double-blind, placebo-controlled study in participants with primary hypercholesterolemia or mixed dyslipidemia, and elevated low density lipoprotein-cholesterol (LDL-C) to assess the efficacy and safety of extended release (ER) niacin/laropiprant [ERN/LRPT (MK-0524A)] when added to the following ongoing lipid-modifying therapy (LMT): simvastatin,

atorvastatin, rosuvastatin monotherapy, ezetimibe/simvastatin fixed dose combination (FDC), or any statin co-administered with ezetimibe. The study is based on the hypothesis that ERN/LRPT 2 g daily will be superior to placebo at lowering LDL-C at Week 12 of treatment.

Inclusion Criteria:

• Has a history of primary hypercholesterolemia or mixed dyslipidemia.

• Must meet one of the risk categories (very high, high or moderate and corresponding LDL-C criteria at Visit 2.

• Has TG levels <500 mg/dL (<5.65 mmol/L).

• Has been on a stable dose of one of the following lipid-modifying therapies (LMTs)for at least 6 weeks prior to Visit 1, and agrees to remain on the same type and dose of LMT for the duration of the study:

  • Monotherapy: any statin
  • Combination Therapy: ezetimibe/simvastatin in the same tablet
  • Co-administration Therapy: any statin co-administered with ezetimibe

• Is male or female and ≥18 years of age on day of signing informed consent.

• A female must meet ONE of the following:

  • Of reproductive potential and agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control for the study duration.

  • Not of reproductive potential is eligible without requiring the use of contraception. Definition of "not of reproductive potential": one who has either of the following:

    • reached natural menopause, defined as: 6 months of spontaneous amenorrhea with serum FSH levels (at Visit 1) in the postmenopausal range (per central lab) or 12 months of spontaneous amenorrhea.Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g., anorexia nervosa).
    • 6 weeks post surgical hysterectomy, or bilateral oophorectomy with or without hysterectomy.
    • Bilateral tubal ligation without subsequent restorative procedure.

• Understands the study's procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.

Exclusion Criteria

- Has taken a prohibited LMT within 6 weeks of Visit 1. Examples of

prohibited LMT include bile acid sequestrants, fibrates (monotherapy, coadministration or combination with other LMT), niacin >50 mg, and red yeast rice products.

• Has had a change to the type or dose of acceptable LMT regimen within 6 weeks of Visit 1.

• Is pregnant, breastfeeding, or expecting to conceive during the study including the 14-day poststudy follow-up.

• Has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

• Female who is expecting to donate eggs during the study, including the 14-day follow-up.

• Is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.

• Has participated in a study, including post-study follow-up, with an investigational compound (non-lipid-modifying) within 30 days of Visit 1 or a lipid-modifying compound (investigational or marketed), within 6 weeks of Visit 1.

• Has donated and/or received blood as follows:

  • donated blood products or has had phlebotomy of >300 mL within 8 weeks prior to signing informed consent.
  • intends to give or receive blood products during the study.
  • intends to donate more than 250 mL of blood products within 8 weeks following the last study visit.

• Has the following exclusionary laboratory values at Visit 2

  • Creatinine clearance (eGFR) <30 mL/min (0.50 mL/s)
  • ALT (SGPT) >1.5 x ULN
  • AST (SGOT) >1.5 x ULN
  • CK >2 x ULN

• Has used recreational or illicit drugs within 1 year of signing informed consent.

• Was <80% compliant with LMT or placebo at Visit 2, AND in the opinion of the investigator, is believed to be unable to maintain at least 80% compliance with dosing during the active treatment period.

• Has chronic heart failure defined by the New York Heart Association (NYHA) Classes III or IV, uncontrolled cardiac arrhythmias, or poorly controlled hypertension (systolic blood pressure >160 mm Hg or diastolic >100 mm Hg).

• Has Type 1 or Type 2 diabetes mellitus and meets one or more of the following criteria:

  • Is poorly controlled (HbA1C >8.0% at Visit 1)
  • Is newly diagnosed (within 3 months of Visit 1)
  • Has recently experienced repeated hypoglycemia or unstable glycemic control (within 3 months of Visit 1).
  • Is taking new or recently adjusted antidiabetic pharmacotherapy (with the exception of ± ≤ 10 units of insulin) within 3 months of Visit 1.

• Has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia such as hyper- or hypothyroidism.

• Has nephrotic syndrome or other clinically significant renal disease.

• Has active peptic ulcer disease within 3 months of Visit 1.

• Has a history of hypersensitivity or allergic reaction to niacin or niacin containing products.

• Has history of myocardial infarction, stroke, coronary artery bypass surgery or other revascularization procedure, unstable angina or angioplasty within 3 months of Visit 1.

• Has arterial bleeding.

• Has a history of ileal bypass, gastric bypass or other significant condition associated with malabsorption or rapid weight loss within 18 months of Visit 1.

• Has active or chronic hepatobiliary or hepatic disease.

• Is Chinese and is on simvastatin 80 mg or a product containing simvastatin 80 mg at Visit 1.

• Is receiving treatment with systemic steroids (intravenous, injected, and oral steroids) OR systemic anabolic agents.

• Consumes more than 3 alcoholic drinks on any given day or more than 14 drinks per week.

• Is taking the following antioxidant vitamins each day:

  • Vitamin C in excess of 1500 mg
  • Vitamin E in excess of 45 IU for men, 36 IU for women
  • Beta Carotene 15000 IU for men, 12000 IU for women