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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)

Information source: Merck Sharp & Dohme Corp.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Primary Hypercholesterolemia; Mixed Dyslipidemia

Intervention: Extended-release niacin/laropiprant (ERN/LRPT) (Drug); Placebo (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Merck Sharp & Dohme Corp.

Summary

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.

Clinical Details

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Percent Change From Baseline at Week 12 in Low Density Lipoprotein-Cholesterol (LDL-C)

Secondary outcome:

Percent Change From Baseline in LDL-C:High-density Lipoprotein Cholesterol (HDL-C) at Week 12

Percent Change From Baseline in HDL-C at Week 12

Percent Change From Baseline in Triglyceride (TG) at Week 12

Percent Change From Baseline in Non-HDL-C at Week 12

Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 12

Percent Change From Baseline in Apo B:Apolipoprotein A-I (Apo A-I) at Week 12

Percent Change From Baseline in Total Cholesterol (TC):HDL-C at Week 12

Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 12

Percent Change From Baseline in Apo A-I at Week 12

Percent Change From Baseline in TC at Week 12

Percent Change From Baseline in LDL-C at Week 4

Percent Change From Baseline in LDL-C:HDL-C at Week 4

Percent Change From Baseline in HDL-C at Week 4

Percent Change From Baseline in TG at Week 4

Percent Change From Baseline in Non-HDL-C at Week 4

Percent Change From Baseline in Apo B at Week 4

Percent Change From Baseline in Apo B:Apo A-I at Week 4

Percent Change From Baseline in TC:HDL-C at Week 4

Percent Change From Baseline in Lp(a) at Week 4

Percent Change From Baseline in Apo A-I at Week 4

Percent Change From Baseline in TC at Week 4

Number of Participants Who Achieve LDL-C Target Levels at Week 12 of Treatment

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

Additional Information

Starting date: March 2011
Last updated: April 27, 2015

Page last updated: August 23, 2015

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