A Study to Evaluate the Effects of ER Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites (0524A-079)(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 Type 2 Diabetes

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 specific metabolite (which is a marker of in vivo platelet reactivity).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Comparator: placebo; Drug: Comparator: ER niacin (+) laropiprant; Drug: Comparator: ER niacin; Drug: Comparator: laropiprant

Detailed Description

Subjects will receive 1 of 4 treatments per period and will eventually receive all 4 treatments:

Treatment A: ER niacin 2g/laropiprant 40 mg daily + Placebo to laropiprant for 7 days

Treatment B: ER niacin 2 g daily + Placebo to laropiprant for 7

days

Treatment C: laropiprant 40 mg daily + Placebo to ER niacin/laropiprant for 7 days

Treatment D: placebo daily for 7 days. There will be at least a 7-day interval between dosing on Day 7 of a period and dosing on Day 1 of the subsequent period

• 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 has a history of T2DM either treated with diet and exercise alone or with metformin or a sulfonylurea
• Subject is judged to be in good health (other than history of Type 2 diabetes mellitus) 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
• Subject has a history of stroke, chronic seizures, or major neurological disorder
• Subject has a history of clinically significant endocrine (except for Type 2 diabetes mellitus), 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 blood or platelet related disorder including prior deep venous thrombosis. Subject is being treated with coumadin, heparin, clopidogrel or 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 (with the exception of metformin or sulfonylurea agents), including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks until the post-study visit. No concomitant medications may be taken during the study
• Subject consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages, per day
• Subject consumes excessive amounts, defined as greater than 6, 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 uses insulin, PPAR gamma agonists (rosiglitazone or pioglitazone), exenatide (Byetta), acarbose (Prandase, Precose) or dipeptidyl-peptidase 4 (DPP-4) inhibitors (JANUVIA™1)

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; Arm A: ER niacin/laropiprant + Placebo to laropiprant	Drug: Comparator: ER niacin (+) laropiprant; ER niacin 2 g/ laropiprant 40 mg daily for 7 days.
EXPERIMENTAL: B; Arm B: ER niacin + Placebo to laropiprant	Drug: Comparator: ER niacin; ER niacin 2 g daily for 7 days.
EXPERIMENTAL: C; Arm C: laropiprant + Placebo to ER Niacin/laropiprant	Drug: Comparator: laropiprant; laropiprant 40 mg daily for 7 days.
PLACEBO_COMPARATOR: D; Arm 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)	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: August 1, 2007
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: February 8, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (ESTIMATE): February 20, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): September 7, 2015
• Last Update Submitted That Met QC Criteria: August 25, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; 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-079; 2008_508