Primary HypercholesterolemiaPhase 3NCT01335997

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

A Phase 3 study testing ER niacin/laropiprant (ERN/LRPT), ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM) and Simvastatin (SIM) in people with Primary Hypercholesterolemia and Mixed Dyslipidemia, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Primary Hypercholesterolemia, Mixed Dyslipidemia
What is being tested?: ER niacin/laropiprant (ERN/LRPT), ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM) and Simvastatin (SIM)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,139 participants
Where: No sites listed yet
Study dates: 1 May 2011to 1 Jan 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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).

Who cannot join

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.

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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.

About this study

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

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).

Conditions: Primary Hypercholesterolemia, Mixed Dyslipidemia
Being tested: ER niacin/laropiprant (ERN/LRPT), ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM), Simvastatin (SIM), Placebo Run-In, SIM-matching placebo
Keywords: Low-density lipoprotein, LDL, High-density lipoprotein, HDL, Niacin, Lipid modifying therapy, Cholesterol, High cholesterol, Triglycerides
Medical subject headings: Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ER niacin/laropiprant (ERN/LRPT)Drug
Also called MK-0524B
ER niacin 1 g/laropiprant 20 mg oral tablet taken once daily
ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)Drug
Also called MK-0524A, Tredaptive™
ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily
Simvastatin (SIM)Drug
Also called Zocor®
Simvastatin 10 mg oral tablet taken once daily
Placebo Run-InDrug
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
SIM-matching placeboDrug
Placebo for simvastatin 10 mg oral tablet taken once daily

Study groups in NCT01335997
Study group	Role	What they receive
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. Receives: 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
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. Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Week 12 and Week 20

Secondary outcomes (1)

Change From Baseline in High Density Lipoprotein Cholesterol (HDL-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.
Measured: Baseline and Week 12 and Week 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 May 20111 Jan 2012

First posted15 Apr 2011 (estimated)
Study start1 May 2011
Primary completion1 Jan 2012
Study completion1 Jan 2012

Why it stopped: Business Reasons

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Primary HypercholesterolemiaStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 1,139 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01335997
Sponsor's protocol ID: 0524B-143
Other IDs: 2011-001007-12
Status last verified: Jan 2019
First submitted: 13 Apr 2011
Last updated: 6 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
Recruiting
Food Supplement for Individuals With Polygenic Hypercholesterolaemia
Polygenic Hypercholesterolaemia
Active, not recruiting
Italian Digital Primary Cardiovascular Prevention Study
Healthy Population
RecruitingObservational study
A Study of Bempedoic Acid or Its Single-pill Combination Therapy With Ezetimibe in Patients With Primary Hypercholesterolaemia or Mixed Dyslipidaemia
Primary Hypercholesterolaemia, Mixed Dyslipidemia

All Primary Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01335997
Acronym / sponsor ID: 0524B-143
Conditions: Primary Hypercholesterolemia, Mixed Dyslipidemia
Keywords: Low-density lipoprotein, LDL, High-density lipoprotein, HDL, Niacin, Lipid modifying therapy, Cholesterol, High cholesterol
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Business Reasons
Enrolment: 1,139 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 1 May 2011 (actual)
Primary completion: 1 Jan 2012 (actual)
Study completion: 1 Jan 2012 (actual)
First posted: 15 Apr 2011 (estimated)
Results: Posted 21 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
ERN/LRPT/SIM → ERN/LRPT+SIM	Experimental	Drug: ER niacin/laropiprant (ERN/LRPT), Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM), Drug: Simvastatin (SIM), Drug: Placebo Run-In, Drug: SIM-matching placeboWeeks 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.
ERN/LRPT+SIM → ERN/LRPT/SIM	Active comparator	Drug: ER niacin/laropiprant (ERN/LRPT), Drug: ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM), Drug: Simvastatin (SIM), Drug: Placebo Run-In, Drug: SIM-matching placeboWeeks 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.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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).

Key exclusion criteria (15 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ER niacin/laropiprant (ERN/LRPT)Also: MK-0524BER niacin 1 g/laropiprant 20 mg oral tablet taken once daily	Drug	ERN/LRPT+SIM → ERN/LRPT/SIM, ERN/LRPT/SIM → ERN/LRPT+SIM
ER niacin/laropiprant/simvastatin (ERN/LRPT/SIM)Also: MK-0524A, Tredaptive™ER niacin 1 g/laropiprant 20 mg/simvastatin 10 mg oral tablet taken once daily	Drug	ERN/LRPT+SIM → ERN/LRPT/SIM, ERN/LRPT/SIM → ERN/LRPT+SIM
Simvastatin (SIM)Also: Zocor®Simvastatin 10 mg oral tablet taken once daily	Drug	ERN/LRPT+SIM → ERN/LRPT/SIM, ERN/LRPT/SIM → ERN/LRPT+SIM
Placebo Run-InPlacebo 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	ERN/LRPT+SIM → ERN/LRPT/SIM, ERN/LRPT/SIM → ERN/LRPT+SIM
SIM-matching placeboPlacebo for simvastatin 10 mg oral tablet taken once daily	Drug	ERN/LRPT+SIM → ERN/LRPT/SIM, ERN/LRPT/SIM → ERN/LRPT+SIM

Primary outcome

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.

1 secondary outcome

Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) Blood Levels
Time frame: Baseline and Week 12 and Week 20

Results and safety

Results posted to the registry on 21 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ERN/LRPT/SIM → ERN/LRPT+SIM (Sequence 1)	577	84
ERN/LRPT+SIM → ERN/LRPT/SIM (Sequence 2)	562	83

Primary outcome: Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Blood Levels

Time frame: Baseline and Week 12 and Week 20

Population analysed: Completers Population - participants that completed the study, have respective endpoint data available at baseline, end of period II and end of period III and were not off study drug more than 3 days prior to their period II and period III observations.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 22 weeks, including 14 days after last dose of study drug (non-serious adverse events up to 20 weeks and serious adverse events up to 22 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Seq 1 (Periods I+II): ERN/LRPT/SIMVA → ERN/LRPT+SIMVA	11 of 567 (1.9%)	103 of 567 (18.2%)	Not reported
Seq 2 (Periods I+II): ERN/LRPT+SIM → ERN/LRPT/SIM	5 of 554 (0.9%)	95 of 554 (17.1%)	Not reported
Seq 1 (Period III): ERN/LRPT/SIMVA → ERN/LRPT+SIMVA	0 of 83 (0%)	0 of 83 (0%)	Not reported
Seq 2 (Period III): ERN/LRPT+SIM → ERN/LRPT/SIM	1 of 82 (1.2%)	0 of 82 (0%)	Not reported

Limitations and caveats (from the sponsor): Study was terminated for business reasons.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Primary Hypercholesterolemia

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
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Recruiting
Food Supplement for Individuals With Polygenic Hypercholesterolaemia
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Active, not recruiting
Italian Digital Primary Cardiovascular Prevention Study
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RecruitingObservational study
A Study of Bempedoic Acid or Its Single-pill Combination Therapy With Ezetimibe in Patients With Primary Hypercholesterolaemia or Mixed Dyslipidaemia
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Blood Levels (time frame: Baseline and Week 12 and Week 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01335997.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2019.