Efficacy and Safety of Extended-Release Niacin/ Laropiprant/Simvastatin Tablets in Participants With Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-143)

This study has been terminated.
(Business Reasons)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01335997
First received: April 13, 2011
Last updated: May 12, 2016
Last verified: May 2016
  Purpose
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).

Condition Intervention Phase
Primary Hypercholesterolemia
Mixed Dyslipidemia
Drug: ER niacin/laropiprant (ERN/LRPT)
Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)
Drug: Simvastatin (SIM)
Drug: Placebo Run-In
Drug: SIM-matching placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Multicenter, Double-Blind, Crossover Design Study to Evaluate Lipid-Altering Efficacy and Safety of 1 g/10 mg Extended-Release Niacin/Laropiprant/Simvastatin Combination Tablets in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Blood Levels [ Time Frame: Baseline and Week 12 and Week 20 ] [ Designated as safety issue: No ]
    Due to study termination caused by the decision to stop the development of the combination tablet, sufficient data were not available to perform the planned efficacy analysis, which is based on the cross-over data collected in period II and III.


Secondary Outcome Measures:
  • Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) Blood Levels [ Time Frame: Baseline and Week 12 and Week 20 ] [ Designated as safety issue: No ]
    Due to study termination caused by the decision to stop the development of the combination tablet, sufficient data were not available to perform the planned efficacy analysis, which is based on the cross-over data collected in period II and III.


Enrollment: 1139
Study Start Date: May 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ERN/LRPT/SIM → ERN/LRPT+SIM
Weeks 0-4 (Period 1): Participants will take ERN/LRPT/SIM 1 g/10 mg and SIM-matching placebo tablets daily; Weeks 5-12 (Period 2): Participants will be advanced to ERN/LRPT/SIM 2 g/20 mg and SIM-matching placebo tablets daily; Weeks 13-20 (Period III): Participants will crossover to ERN/LRPT 2 g + SIM 20 mg coadministration treatment.
Drug: ER niacin/laropiprant (ERN/LRPT)
ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily
Other Name: MK-0524B
Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)
ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily
Other Name: MK-0524A, Tredaptive™
Drug: Simvastatin (SIM)
Simvastatin 10 mg oral tablet taken once daily
Other Name: Zocor®
Drug: Placebo Run-In
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
Drug: SIM-matching placebo
Placebo for simvastatin 10 mg oral tablet taken once daily
Active Comparator: ERN/LRPT+SIM → ERN/LRPT/SIM
Weeks 0-4 (Period I): Participants will take ERN/LRPT co-administered with SIM (ERN/LRPT 1g + SIM 10 mg tablets) daily; Weeks 5-12 (Period II): Participants will be advanced to ERN/LRPT 2 g + SIM 20 mg daily; Weeks 13-20 (Period III): Participants will crossover to the ERN/LRPT/SIM 2 g/20 mg combination treatment and SIM-matching placebo tablets.
Drug: ER niacin/laropiprant (ERN/LRPT)
ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily
Other Name: MK-0524B
Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)
ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily
Other Name: MK-0524A, Tredaptive™
Drug: Simvastatin (SIM)
Simvastatin 10 mg oral tablet taken once daily
Other Name: Zocor®
Drug: Placebo Run-In
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
Drug: SIM-matching placebo
Placebo for simvastatin 10 mg oral tablet taken once daily

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01335997

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01335997     History of Changes
Other Study ID Numbers: 0524B-143  2011-001007-12 
Study First Received: April 13, 2011
Results First Received: January 13, 2016
Last Updated: May 12, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Low-density lipoprotein
LDL
High-density lipoprotein
HDL
Niacin
Lipid modifying therapy
Cholesterol
High cholesterol
Triglycerides

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Simvastatin
Niacin
Niacinamide
Nicotinic Acids
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Vasodilator Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2016