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

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ClinicalTrials.gov Identifier: NCT01335997
Recruitment Status : Terminated (Business Reasons)
First Posted : April 15, 2011
Results First Posted : June 21, 2016
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief 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).

Condition or disease Intervention/treatment 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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1139 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, 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
Actual Study Start Date : May 1, 2011
Actual Primary Completion Date : January 1, 2012
Actual Study Completion Date : January 1, 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Blood Levels [ Time Frame: Baseline and Week 12 and Week 20 ]
    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 :
  1. Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) Blood Levels [ Time Frame: Baseline and Week 12 and Week 20 ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01335997


Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Study Data/Documents: CSR Synsopsi Link  This link exits the ClinicalTrials.gov site

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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT01335997    
Other Study ID Numbers: 0524B-143
2011-001007-12 ( EudraCT Number )
First Posted: April 15, 2011    Key Record Dates
Results First Posted: June 21, 2016
Last Update Posted: February 6, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Keywords provided by Merck Sharp & Dohme LLC:
Low-density lipoprotein
LDL
High-density lipoprotein
HDL
Niacin
 Lipid modifying therapy
Cholesterol
High cholesterol
Triglycerides
Additional relevant MeSH terms:
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Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Niacin
Niacinamide
Nicotinic Acids
Simvastatin
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
Physiological Effects of Drugs