Efficacy and Safety of Extended Release (ER) Niacin/Laropiprant When Added to Ongoing Lipid-Modifying Therapy in Patients With High Cholesterol or Abnormal Lipid Levels (MK-0524A-133)

NCT01274559 | Terminated Phase 3 Results

• 3 other identifiers: 0524A-133CTRI/2012/08/0028572010-021627-27
• Study Type: interventional
• Target: 1,173
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled study in participants with primary hypercholesterolemia or mixed dyslipidemia, and elevated low density lipoprotein-cholesterol (LDL-C) to assess the efficacy and safety of extended release (ER) niacin/laropiprant \[ERN/LRPT (MK-0524A)\] when added to the following ongoing lipid-modifying therapy (LMT): simvastatin, atorvastatin, rosuvastatin monotherapy, ezetimibe/simvastatin fixed dose combination (FDC), or any statin co-administered with ezetimibe. The study is based on the hypothesis that ERN/LRPT 2 g daily will be superior to placebo at lowering LDL-C at Week 12 of treatment.

Conditions

Primary Hypercholesterolemia; Mixed Dyslipidemia

Keywords

MK-0524A/ER; Hypercholesterolemia; Dyslipidemia; Niacin; Laropiprant

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline at Week 12 in Low Density Lipoprotein-Cholesterol (LDL-C)

  Baseline and Week 12

Secondary Outcomes (22)

• Percent Change From Baseline in LDL-C:High-density Lipoprotein Cholesterol (HDL-C) at Week 12

  Baseline and Week 12

• Percent Change From Baseline in HDL-C at Week 12

  Baseline and Week 12

• Percent Change From Baseline in Triglyceride (TG) at Week 12

  Baseline and Week 12

• Percent Change From Baseline in Non-HDL-C at Week 12

  Baseline and Week 12

• Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 12

  Baseline and Week 12

Study Arms (2)

Extended-release niacin/laropiprant

EXPERIMENTAL

ERN/LRPT 1 g (1 tablet for 4 wks) followed by ERN/LRPT 2 g (2 tablets for 8 wks); Each 1-g tablet contains 1 g of ER niacin and 20 mg of laropiprant.

Drug: Extended-release niacin/laropiprant (ERN/LRPT)

Placebo

PLACEBO COMPARATOR

Matching 1 g Placebo (1 tablet for 4 wks) followed by 2 g placebo (2 tablets for 8 weeks)

Drug: Placebo

Interventions

Extended-release niacin/laropiprant (ERN/LRPT) DRUG

1 oral 1 g tablet of ERN/LRPT to be taken with food in the evening or at bedtime for the first 4 weeks of treatment; then 2 oral 1g tablets of ERN/LRPT to be taken together in the evening or at bedtime with food for the next 8 weeks. Each 1g tablet contains 1g ERN and 20 mg LRPT

Extended-release niacin/laropiprant

Placebo DRUG

1 oral 1 g tablet of placebo to be taken with food in the evening or at bedtime for the first 4 weeks of treatment; then 2 oral 1g tablets of placebo to be taken together in the evening or at bedtime with food for the next 8 weeks.

Placebo

Eligibility Criteria

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

You may qualify if:

• Has a history of primary hypercholesterolemia or mixed dyslipidemia.
• Must meet one of the risk categories (very high, high or moderate and corresponding LDL-C criteria at Visit 2.
• Has TG levels \<500 mg/dL (\<5.65 mmol/L).
• Has been on a stable dose of one of the following lipid-modifying therapies (LMTs)for at least 6 weeks prior to Visit 1, and agrees to remain on the same type and dose of LMT for the duration of the study:
• Monotherapy: any statin
• Combination Therapy: ezetimibe/simvastatin in the same tablet
• Co-administration Therapy: any statin co-administered with ezetimibe
• Is male or female and ≥18 years of age on day of signing informed consent.
• A female must meet ONE of the following:
• Of reproductive potential and agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control for the study duration.
• Not of reproductive potential is eligible without requiring the use of contraception. Definition of "not of reproductive potential": one who has either of the following:
• reached natural menopause, defined as: 6 months of spontaneous amenorrhea with serum FSH levels (at Visit 1) in the postmenopausal range (per central lab) or 12 months of spontaneous amenorrhea.Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g., anorexia nervosa).
• weeks post surgical hysterectomy, or bilateral oophorectomy with or without hysterectomy.
• Bilateral tubal ligation without subsequent restorative procedure.
• Understands the study's procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.

You may not qualify if:

• \- Has taken a prohibited LMT within 6 weeks of Visit 1. Examples of
• prohibited LMT include bile acid sequestrants, fibrates (monotherapy, coadministration or combination with other LMT), niacin \>50 mg, and red yeast rice products.
• Has had a change to the type or dose of acceptable LMT regimen within 6 weeks of Visit 1.
• Is pregnant, breastfeeding, or expecting to conceive during the study including the 14-day poststudy follow-up.
• Has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Female who is expecting to donate eggs during the study, including the 14-day follow-up.
• Is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
• Has participated in a study, including post-study follow-up, with an investigational compound (non-lipid-modifying) within 30 days of Visit 1 or a lipid-modifying compound (investigational or marketed), within 6 weeks of Visit 1.
• Has donated and/or received blood as follows:
• donated blood products or has had phlebotomy of \>300 mL within 8 weeks prior to signing informed consent.
• intends to give or receive blood products during the study.
• intends to donate more than 250 mL of blood products within 8 weeks following the last study visit.
• Creatinine clearance (eGFR) \<30 mL/min (0.50 mL/s)
• ALT (SGPT) \>1.5 x ULN
• AST (SGOT) \>1.5 x ULN

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypercholesterolemia; Dyslipidemias

Interventions

MK-0524

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

MK-0524A-133 was stopped prior to completion. Raw individual efficacy data were obtained but none of planned efficacy outcomes were summarized or analyzed. Only safety data were summarized.

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2010
• First Posted: January 11, 2011
• Study Start: March 1, 2011
• Primary Completion: February 26, 2013
• Study Completion: February 26, 2013
• Last Updated: May 22, 2024
• Results First Posted: March 14, 2014

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share