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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00618995
First received: February 8, 2008
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Comparator: ER niacin (+) laropiprant
Drug: Comparator: ER niacin
Drug: Comparator: laropiprant
Drug: Comparator: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Urinary 11-Dehydrothromboxane B2 (11-dTxB2) [ Time Frame: On Day 7 across the 24-hour urinary collection period. ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Prostaglandin I Metabolite (PGI-M) [ Time Frame: On Day 7 across the 24-hour urinary collection period. ] [ Designated as safety issue: No ]
    PGI-M in the Overall 24 Hour Collection Interval Following Administration on Day 7


Enrollment: 26
Study Start Date: September 2007
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618995

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00618995     History of Changes
Other Study ID Numbers: 0524A-079, 2008_508
Study First Received: February 8, 2008
Results First Received: December 5, 2008
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Niacin
Nicotinic Acids
Niacinamide
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014