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)

NCT00769132 | Completed Phase 1 Results

• 2 other identifiers: 0524A-0752008_561
• Study Type: interventional
• Target: 26
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Prostaglandin I Metabolite (PGI-M)

  On Day 7 across the 24-hour urinary collection period.

Study Arms (4)

A

EXPERIMENTAL

ER niacin/laropiprant + Placebo to laropiprant

Drug: Comparator: niacin + laropiprant

B

ACTIVE COMPARATOR

ER niacin + Placebo to laropiprant

Drug: Comparator: niacin

C

EXPERIMENTAL

laropiprant + Placebo to ER niacin/laropiprant

Drug: Comparator: laropiprant

D

PLACEBO COMPARATOR

Placebo

Drug: Comparator: placebo

Interventions

Comparator: niacin + laropiprant DRUG

ER niacin 2 g/laropiprant 40 mg tablet once daily for 7 days

A

Comparator: niacin DRUG

ER niacin 2 g tablet once daily for 7 days

Also known as: Niaspan

B

Comparator: laropiprant DRUG

laropiprant 40 mg once daily for 7 days

C

Comparator: placebo DRUG

matching placebo tablets for each of the interventions once daily for 7 days

D

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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 healthy, hypercholesterolemic, and diabetic subjects. J Clin Pharmacol. 2009 Dec;49(12):1426-35. doi: 10.1177/0091270009339593. Epub 2009 Oct 15.

  PMID: 19833861 RESULT

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

MK-0524; Niacin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Study Start: August 3, 2007
• Primary Completion: October 13, 2007
• Study Completion: November 6, 2007
• Last Updated: November 21, 2019
• Results First Posted: November 27, 2008

Record last verified: 2019-11