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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1139

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 81 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • MK-0524A, Tredaptive™
Drug: Simvastatin (SIM)
Simvastatin 10 mg oral tablet taken once daily
Other Names:
  • 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 Names:
  • 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 Names:
  • MK-0524A, Tredaptive™
Drug: Simvastatin (SIM)
Simvastatin 10 mg oral tablet taken once daily
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 14, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 15, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 17, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

  1. CSR Synsopsi Link

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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