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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00618995
• Other study ID #: 0524A-079
• Secondary ID: 2008_508
• Status: Completed
• Phase: Phase 1
• First received: February 8, 2008
• Last updated: August 25, 2015
• Start date: August 2007
• Est. completion date: December 2007

Study information

• Verified date: August 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Comparator: ER niacin (+) laropiprant
ER niacin 2 g/ laropiprant 40 mg daily for 7 days.
• Comparator: ER niacin
ER niacin 2 g daily for 7 days.
• Comparator: laropiprant
laropiprant 40 mg daily for 7 days.
• Comparator: placebo
matching placebo tablets for each of the interventions once daily for 7 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 h — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No