NCT01335997

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).

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,139

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2011

Shorter than P25 for phase_3

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 13, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 15, 2011

Completed
16 days until next milestone

Study Start

First participant enrolled

May 1, 2011

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
4.5 years until next milestone

Results Posted

Study results publicly available

June 21, 2016

Completed
Last Updated

February 6, 2019

Status Verified

January 1, 2019

Enrollment Period

8 months

First QC Date

April 13, 2011

Results QC Date

January 13, 2016

Last Update Submit

January 17, 2019

Conditions

Keywords

Low-density lipoproteinLDLHigh-density lipoproteinHDLNiacinLipid modifying therapyCholesterolHigh cholesterolTriglycerides

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Blood Levels

    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 Outcomes (1)

  • Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) Blood Levels

    Baseline and Week 12 and Week 20

Study Arms (2)

ERN/LRPT/SIM → ERN/LRPT+SIM

EXPERIMENTAL

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)Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)Drug: Simvastatin (SIM)Drug: Placebo Run-InDrug: SIM-matching placebo

ERN/LRPT+SIM → ERN/LRPT/SIM

ACTIVE COMPARATOR

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)Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)Drug: Simvastatin (SIM)Drug: Placebo Run-InDrug: SIM-matching placebo

Interventions

ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily

Also known as: MK-0524B
ERN/LRPT+SIM → ERN/LRPT/SIMERN/LRPT/SIM → ERN/LRPT+SIM

ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily

Also known as: MK-0524A, Tredaptive™
ERN/LRPT+SIM → ERN/LRPT/SIMERN/LRPT/SIM → ERN/LRPT+SIM

Simvastatin 10 mg oral tablet taken once daily

Also known as: Zocor®
ERN/LRPT+SIM → ERN/LRPT/SIMERN/LRPT/SIM → ERN/LRPT+SIM

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

ERN/LRPT+SIM → ERN/LRPT/SIMERN/LRPT/SIM → ERN/LRPT+SIM

Placebo for simvastatin 10 mg oral tablet taken once daily

ERN/LRPT+SIM → ERN/LRPT/SIMERN/LRPT/SIM → ERN/LRPT+SIM

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

MK-0524Simvastatin

Condition Hierarchy (Ancestors)

HyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Limitations and Caveats

Study was terminated for business reasons.

Results Point of Contact

Title
Senior Vice President, Global Clinical Development
Organization
Merck Sharp & Dohme Corp.

Study Officials

  • Medical Director

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 13, 2011

First Posted

April 15, 2011

Study Start

May 1, 2011

Primary Completion

January 1, 2012

Study Completion

January 1, 2012

Last Updated

February 6, 2019

Results First Posted

June 21, 2016

Record last verified: 2019-01

Data Sharing

IPD Sharing
Will share

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

More information

Available IPD Datasets

CSR Synsopsi Link Access