Clinical trial NCT01294683: A Study to Evaluate Efficacy and Safety of Extended-Release Niacin + Laropiprant + Simvastatin in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-118)
Official title: A Phase III Multicenter, Double-Blind, Crossover Design Study to Evaluate Lipid-Altering Efficacy and Safety of Extended-Release Niacin/Laropiprant/Simvastatin Combination Tablet in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Primary Hypercholesterolemia
Dyslipidemia
Keywords: Low-density lipoprotein
LDL
High-density lipoprotein
HDL
Niacin
Lipid modifying therapy
Cholesterol
High cholesterol
Triglycerides
Mixed Dyslipidemia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-02-11
Enrollment: 977
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion criteria

* 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.

Exclusion Criteria

* 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.

Primary outcomes:
measure: Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: 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:
measure: Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
timeFrame: 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)
measure: Percentage of Participants With Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x Upper Limit of Normal (ULN)
timeFrame: Up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants With Elevations in ALT and/or AST of >=5 x ULN
timeFrame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants With Elevations in ALT and/or AST of >=10 x ULN
timeFrame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants With Creatine Kinase (CK) >=10 x ULN
timeFrame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants With CK >=10 x ULN With Muscle Symptoms - Drug Related
timeFrame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants Who Experienced at Least 1 Hepatitis-related Adverse Event (AE)
timeFrame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants With New Onset of Diabetes
timeFrame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants With a Confirmed Adjudicated Cardiovascular Event
timeFrame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)
measure: Percentage of Participants Who Experienced at Least 1 AE
timeFrame: up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
measure: Percentage of Participants Who Were Discontinued From the Study Due to an AE
timeFrame: up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: