A Study to Evaluate Efficacy and Safety of Extended-Release Niacin + Laropiprant + Simvastatin in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-118)

NCT01294683 | Terminated Phase 3 Results

• 2 other identifiers: 0524B-1182010-023939-42
• Study Type: interventional
• Target: 977
• Locations: 0 countries
• Sites: N/A

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/40 mg is equivalent to ERN/LRPT 2 g co-administered with simvastatin 40 mg in reducing low-density lipoprotein cholesterol (LDL-C).

Conditions

Primary Hypercholesterolemia; Dyslipidemia

Keywords

Low-density lipoprotein; LDL; High-density lipoprotein; HDL; Niacin; Lipid modifying therapy; Cholesterol; High cholesterol; Triglycerides; Mixed Dyslipidemia

Outcome Measures

Primary Outcomes (1)

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

  Blood samples were taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III) to determine the LDL-C levels. The change from baseline after 8 weeks of treatment was recorded. Results from recent studies indicated that the combination tablet formulations used in the study did not meet the pre-specified pharmacokinetic bounds used to establish the equivalence of the combination tablet (MK-0524B; ERN/LRPT/SIM) to the coadministration of MK-0524A (ERN/LRPT) and SIM. Therefore, efficacy data were not analyzed, as the study was stopped early. Only safety data were evaluated.

  Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III)

Secondary Outcomes (11)

• Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)

  Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment during each period (Week 12 for Period II and Week 20 for Period III)

• Percentage of Participants With Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x Upper Limit of Normal (ULN)

  Up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

• Percentage of Participants With Elevations in ALT and/or AST of >=5 x ULN

  up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

• Percentage of Participants With Elevations in ALT and/or AST of >=10 x ULN

  up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

• Percentage of Participants With Creatine Kinase (CK) >=10 x ULN

  up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Study Arms (2)

Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg

EXPERIMENTAL

After a 2-week placebo run-in, participants received extended release (ER) niacin/laropiprant (N/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.

Drug: Simvastatin; Drug: Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM); Drug: Extended Release (ER) niacin/laropiprant (N/LRPT); Drug: Placebo

Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g

EXPERIMENTAL

After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.

Drug: Simvastatin; Drug: Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM); Drug: Extended Release (ER) niacin/laropiprant (N/LRPT); Drug: Placebo

Interventions

Simvastatin DRUG

Also known as: Zocor

Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg; Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g

Extended Release (ER) niacin/laropiprant/simvastatin (N/LRPT/SIM) DRUG

Also known as: MK-0524B

Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg; Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g

Extended Release (ER) niacin/laropiprant (N/LRPT) DRUG

Also known as: MK-0524A

Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg; Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g

Placebo DRUG

Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg; Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has a history of primary hypercholesterolemia or mixed dyslipidemia and meets LDL-C and triglyceride criteria.
• Visit 2:
• Participant is high risk coronary heart disease (CHD) or CHD risk-equivalent.

You may not qualify if:

• Participant is pregnant or breast-feeding, or expecting to conceive during the study.
• Participant has a history of malignancy.
• Participant consumes more than 3 alcoholic drinks per day (14 per week).
• Participant is high risk CHD patient on statin therapy or any patient on statin therapy equivalent to 80 mg simvastatin.
• Participant with Type 1 or Type 2 diabetes mellitus that is poorly controlled, or on statin therapy.
• Participant currently engages in vigorous exercise or is on an aggressive diet regimen.
• Participant 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.
• Participant is human immunodeficiency virus (HIV) positive.
• Participant has taken niacin \>50 mg/day, bile-acid sequestrants, hydroxymethyl glutaryl 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.
• Participant 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.
• Participant is taking prohibited medications such as systemic corticosteroids, itraconazole or ketoconazole, erythromycin, clarithromycin, or telithromycin, nefazodone, HIV protease inhibitors, verapamil, amiodarone, cyclosporine, danazol, diltiazem or fusidic acid.
• Participant consumes \>1 quart of grapefruit juice/day.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Dyslipidemias; Hypercholesterolemia

Interventions

Simvastatin; Niacin; MK-0524

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperlipidemias

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

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, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2011
• First Posted: February 11, 2011
• Study Start: February 4, 2011
• Primary Completion: January 17, 2012
• Study Completion: January 17, 2012
• Last Updated: August 16, 2018
• Results First Posted: December 13, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share