Niacin/Laropiprant Tablet for South and Southeast Asians With Low High-Density Lipoprotein Cholesterol (LDL-C) at Risk for Cardiovascular Disease (MK-0524A-108)

A 16-Week, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Extended Release Niacin/Laropiprant in South and Southeast Asians Not on a Lipid Modulating Agent, With Decreased High-Density Lipoprotein Cholesterol and Low- Density Lipoprotein Cholesterol at or Below NCEP ATP III Goal

The study will evaluate the use of extended release niacin/laropiprant (ERN/LRPT) combination tablets in a primary prevention population currently not taking or eligible for lipid-modifying therapy (LMT); the population will comprise participants with low to moderate risk for coronary heart disease (CHD), low high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) at or below goal level, and normal or mildly elevated triglyceride (TG) levels.

Study Overview

• Status: Terminated
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: ERN/LRPT; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• LMT ineligible
• Participants must meet the lipid criteria of "low to moderate CHD risk" as defined by National Cholesterol Education Program Adult Treatment Panel III Framingham Point Scores (NCEP ATP III)
• HDL-C <40 mg/dL (1.03 mmol/L) in males and <50 mg/dL (1.29 mmol/L) in females
• Triglyceride (TG) level <300 mg/dL (3.39 mmol/L).
• Fasting serum glucose (FSG) at Visit 1 AND Visit 2 <126 mg/dL (<7 mmol/L)
• Hemoglobin A1c (HbA1c) level <6.5%
• Participant willing to use acceptable method of contraception during the study, including the 14-day follow-up period

Exclusion criteria:

• 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
• Participation in a study with an investigational compound (non-lipid-modifying) within 30 days
• Pregnant, breastfeeding, or expecting to conceive, or father a child during the study, including the 14-day follow-up period
• Consumption of more than 3 alcoholic drinks on any given day or more than 14 drinks per week
• Engages in or plans to engage in vigorous exercise or an aggressive diet regimen during the study
• Diabetes mellitus, based on medical history, FSG ≥126 mg/dL (7 mmol/L), and HbA1c ≥6.5%
• Risk factors for coronary heart disease
• Active or chronic hepatobiliary or hepatic disease
• Active peptic ulcer disease within 3 months of Visit 1
• History of hypersensitivity or allergic reaction to niacin or niacin-containing products
• Episode of gout within 1 year of Visit 1, unless currently stable on allopurinol
• Taking an LMT (including statins, bile acid sequestrants, fibrates and niacin >50 mg as monotherapy or coadministered with other LMTs)
• Use of over-the- counter or traditional medicine (e.g. red yeast rice products) for lipid-lowering
• Receiving treatment with systemic corticosteroids (unless on stable therapy for at lest 6 weeks for replacement for pituitary/adrenal/hypogonadal disease)
• Uncontrolled illness or infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ERN/LRPT group; All participants will begin with a screening period of 1 week, followed by a placebo run-in period of 2 weeks before being randomized to receive ERN/LRPT for 16 weeks.	Drug: ERN/LRPT; ERN/LRPT combination tablets (each containing 1 g of extended release niacin and 20 mg of laropiprant), orally, one tablet once per day for 4 weeks, then 2 tablets once per day for 12 weeks; Other Names: Tredaptive™
PLACEBO_COMPARATOR: Placebo group; All participants will begin with a screening period of 1 week, followed by a placebo run-in period of 2 weeks before being randomized to receive placebo for 16 weeks.	Drug: placebo; ERN/LRPT-matched placebo, orally, one tablet once per day for 4 weeks, then 2 tablets once per day for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) Averaged Across Week 12 and Week 16	The percentage change from baseline in the participants' LDL-C was to be evaluated and averaged across treatment Week 12 and Week 16.	Baseline and Weeks 12 to 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in the Ratio of LDL-C to High-Desity Lipoprotein Cholesterol (HDL-C) at Week 16	The percentage from baseline in the participants' ration of LDL-C to HDL-C was to be evaluated at study Week 16.	Baseline and Week 16
Percent Change From Baseline in HDL-C at Week 16	The percentage change from baseline in the participants' HDL-C was to be evaluated at study Week 16.	Baseline and Week 16
Percent Change From Baseline in Triglycerides (TG) at Week 16	The percentage change from baseline in participants' TG level was to be evaluated at study Week 16.	Baseline and Week 16
Percent Change From Baseline in Non-HDL-C at Week 16	The percentage change from baseline in participants' non-HDL-C was to be calculated at study Week 16.	Baseline and Week 16
Percent Change From Baseline in the Ratio of Total Cholesterol (TC) to HDL-C at Week 16	The percentage change from baseline in the ratio of TC to HDL-C was to be evaluated at study Week 16.	Baseline and Week 16
Percent Change From Baseline in Lipoprotein(a) (LP[a]) at Week 16	The pecentage change from baseline in participants LP(a) was to be evaluated at study Week 16.	Baseline and Week 16
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16	The percentage change from baseline in participants' Apo B was to be evaluated at study Week 16.	Baseline and Week 16
Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) at Week 16	The percentage change from baseline in participants' Apo A-I was to be evaluated at study Week 16.	Baseline and Week 16

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: August 9, 2011
• First Submitted That Met QC Criteria: August 9, 2011
• First Posted (ESTIMATE): August 11, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 13, 2015
• Last Update Submitted That Met QC Criteria: April 27, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias
• Other Study ID Numbers: 0524A-108; CTRI/2012/08/002873 (REGISTRY: CTRI)