A Study to Evaluate the Effects of Extended Release (ER) Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites in Subjects With High Cholesterol (0524A-075)(COMPLETED)

A Randomized, Double-Blind, Placebo-Controlled, 4-Period, Crossover Study to Evaluate the Effects of ER Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites in Subjects With Hypercholesterolemia

The purpose of this study is to evaluate the potential effects of ER niacin/laropiprant, ER niacin, laropiprant, and placebo over the course of seven days on urinary levels of a metabolite of thromboxane A2 (TxA2), as a marker of in vivo platelet reactivity.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Comparator: niacin + laropiprant; Drug: Comparator: niacin; Drug: Comparator: laropiprant; Drug: Comparator: placebo

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female subjects may not be pregnant and/or will agree to use appropriate method of contraception beginning at least 2 weeks prior to administration of the first dose of study drug in the first treatment period, throughout the study and until at least 2 weeks after administration of the last dose of study drug in the last treatment period.
• Subject is judged to be in good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug.
• Subject has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug.
• Subject has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months; subjects who have discontinued smoking or the use of nicotine/nicotine containing products for at least approximately 3 months may be enrolled in the study at the discretion of the investigator

Exclusion Criteria:

• Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 to 10 years. - Subjects who have had situational depression may be enrolled in the study at the discretion of the investigator.
• Subject has a history of stroke, chronic seizures, or major neurological disorder.
• Subject has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.
• Subject has a history of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment.
• Subject has history of a thrombotic or platelet related disorder including prior deep venous thrombosis. Subject is being treated with coumadin, heparin, clopidogrel has used these agents within 2 weeks of screening. Subject is being treated with aspirin or has used this agent within 3 weeks prior to administration of screening.
• Subject is unable to refrain from or anticipates the use of any medication, including prescription and non- prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of study drug, throughout the study until the poststudy visit.
• Subject consumes excessive amounts of alcohol, defined as greater than 3 glasses, of alcoholic beverages or distilled spirits per day.
• Subject consumes excessive amounts, defined as greater than 6 servings, of coffee, tea, cola, or other caffeinated beverages per day.
• Subject has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the prestudy (screening) visit.
• Subject has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
• Subject is currently a regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; ER niacin/laropiprant + Placebo to laropiprant	Drug: Comparator: niacin + laropiprant; ER niacin 2 g/laropiprant 40 mg tablet once daily for 7 days
ACTIVE_COMPARATOR: B; ER niacin + Placebo to laropiprant	Drug: Comparator: niacin; ER niacin 2 g tablet once daily for 7 days; Other Names: Niaspan
EXPERIMENTAL: C; laropiprant + Placebo to ER niacin/laropiprant	Drug: Comparator: laropiprant; laropiprant 40 mg once daily for 7 days
PLACEBO_COMPARATOR: D; Placebo	Drug: Comparator: placebo; matching placebo tablets for each of the interventions once daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary 11-dehydrothromboxane B2 (11-dTxB2)	The creatinine-normalized urine levels of 11-dTxB2 on Day 7 following a 7 day course of daily dosing in the overall 24 hour collection interval.	On Day 7 across the 24-hour urinary collection period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostaglandin I Metabolite (PGI-M)	The creatinine-normalized urine levels of PGI-M in the overall 24 hour collection interval following administration on Day 7.	On Day 7 across the 24-hour urinary collection period.

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Lauring B, Dishy V, Luo WL, Laterza O, Patterson J, Cote J, Chao A, Larson P, Gutierrez M, Wagner JA, Lai E. Laropiprant in combination with extended-release niacin does not alter urine 11-dehydrothromboxane B2, a marker of in vivo platelet function, in healthy, hypercholesterolemic, and diabetic subjects. J Clin Pharmacol. 2009 Dec;49(12):1426-35. doi: 10.1177/0091270009339593. Epub 2009 Oct 15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2007
• Primary Completion (ACTUAL): October 13, 2007
• Study Completion (ACTUAL): November 6, 2007

Study Registration Dates

• First Submitted: October 7, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (ESTIMATE): October 8, 2008

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 0524A-075; 2008_561