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J Clin Lipidol. 2008 Oct;2(5):375-83. doi: 10.1016/j.jacl.2008.08.445. Epub 2008 Aug 23.

Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans.

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1
Merck & Co., Inc., 126 East Lincoln Avenue, PO Box 2000, Rahway, NJ 07065-0900, USA.

Abstract

BACKGROUND:

Development of niacin-like agents that favorably affect lipids with an improved flushing profile would be beneficial.

OBJECTIVE:

To evaluate a niacin receptor partial agonist, MK-0354, in Phase I and II studies.

METHODS:

The pharmacokinetic/pharmacodynamic effects of single and multiple doses (7 days) of MK-0354 (300-4000 mg) were evaluated in two Phase I studies conducted in healthy men. A Phase II study assessed the effects of MK-0354 2.5 g once daily on lipids during 4 weeks in 66 dyslipidemic patients.

RESULTS:

MK-0354 single doses up to 4000 mg and multiple doses (7 days) up to 3600 mg produced robust dose-related reductions in free fatty acid (FFA) over 5 hours. Single doses of MK-0354 300 mg and extended release-niacin (Niaspan) 1 g produced comparable reductions in FFA. Suppression of FFA following 7 daily doses of MK-0354 was similar to that after a single dose. In the Phase II study, MK-0354 2.5 g produced little flushing but no clinically meaningful effects on lipids (placebo-adjusted percent change: high-density lipoprotein cholesterol, 0.4%, 95% confidence interval -5.2 to 6.0; low-density lipoprotein cholesterol, -9.8%, 95% confidence interval -16.8 to -2.7; triglyceride, -5.8%, 95% confidence interval -22.6 to 11.9).

CONCLUSION:

Treatment with MK-0354 for 7 days resulted in plasma FFA suppression with minimal cutaneous flushing. However, 4 weeks of treatment with MK-0354 failed to produce changes in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or triglycerides.

PMID:
21291763
DOI:
10.1016/j.jacl.2008.08.445

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