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)

Hypercholesterolemia 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 Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00769132
• Other study ID #: 0524A-075
• Secondary ID: 2008_561
• Status: Completed
• Phase: Phase 1
• Start date: August 3, 2007
• Est. completion date: November 6, 2007

Study information

• Verified date: November 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• 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 metabolite of thromboxane A2 (TxA2), as a marker of in vivo platelet reactivity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 6, 2007
• Est. primary completion date: October 13, 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• 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 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.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Comparator: niacin + laropiprant
ER niacin 2 g/laropiprant 40 mg tablet once daily for 7 days
• Comparator: niacin
ER niacin 2 g tablet once daily for 7 days
• Comparator: laropiprant
laropiprant 40 mg once 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.
Secondary	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.