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

Study Overview
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Brief Summary
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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).

Detailed Description
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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

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Comparator: ER niacin (+) laropiprant
* Drug: Comparator: ER niacin
* Drug: Comparator: laropiprant
* Drug: Comparator: placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Arm A: ER niacin/laropiprant + Placebo to laropiprant | Drug: Comparator: ER niacin (+) laropiprant<br>* ER niacin 2 g/ laropiprant 40 mg daily for 7 days.<br>|
| Experimental: B<br>Arm B: ER niacin + Placebo to laropiprant | Drug: Comparator: ER niacin<br>* ER niacin 2 g daily for 7 days.<br>|
| Experimental: C<br>Arm C: laropiprant + Placebo to ER Niacin/laropiprant | Drug: Comparator: laropiprant<br>* laropiprant 40 mg daily for 7 days.<br>|
| Placebo Comparator: D<br>Arm D: Placebo | Drug: Comparator: placebo<br>* matching placebo tablets for each of the interventions once daily for 7 days<br>|

What is the study measuring?
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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. |