- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01335997
Efficacy and Safety of Extended-Release Niacin/ Laropiprant/Simvastatin Tablets in Participants With Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-143)
January 17, 2019 updated by: Merck Sharp & Dohme LLC
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
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).
Study Overview
Status
Terminated
Conditions
Study Type
Interventional
Enrollment (Actual)
1139
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 83 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily
Other Names:
ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily
Other Names:
Simvastatin 10 mg oral tablet taken once daily
Other Names:
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
|
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.
|
ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily
Other Names:
ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily
Other Names:
Simvastatin 10 mg oral tablet taken once daily
Other Names:
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline and Week 12 and Week 20
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline and Week 12 and Week 20
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 1, 2011
Primary Completion (Actual)
January 1, 2012
Study Completion (Actual)
January 1, 2012
Study Registration Dates
First Submitted
April 13, 2011
First Submitted That Met QC Criteria
April 14, 2011
First Posted (Estimate)
April 15, 2011
Study Record Updates
Last Update Posted (Actual)
February 6, 2019
Last Update Submitted That Met QC Criteria
January 17, 2019
Last Verified
January 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Lipid Metabolism Disorders
- Hyperlipidemias
- Dyslipidemias
- Hypercholesterolemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Enzyme Inhibitors
- Antimetabolites
- Micronutrients
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Vitamins
- Vitamin B Complex
- Nicotinic Acids
- Simvastatin
- Niacinamide
- Niacin
Other Study ID Numbers
- 0524B-143
- 2011-001007-12 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study Data/Documents
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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