A Randomized, Placebo-Controlled Trial to Assess the Effects of 8 Weeks of Administration of GSK256073, a Selective GPR109A Agonist, on High-Density Lipoprotein Cholesterol in Subjects With Dyslipidemia

Autor:	John J. Lepore, Kelly M. Mahar, Anne-Charlotte de Gouville, Thomas F Haws, Dennis L. Sprecher, Feng Gao, Michael J. Fossler, Eric Olson
Rok vydání:	2019
Předmět:	Agonist Male medicine.medical_specialty medicine.drug_class Placebo-controlled study Pharmaceutical Science Placebo 030226 pharmacology & pharmacy Niacin Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein Internal medicine medicine Flushing Humans Pharmacology (medical) Aged Dyslipidemias business.industry Cholesterol Drug Administration Routes Cholesterol HDL Middle Aged medicine.disease Endocrinology Treatment Outcome chemistry 030220 oncology & carcinogenesis Xanthines Female business Dyslipidemia Lipoprotein
Zdroj:	Clinical pharmacology in drug developmentReferences. 8(7)
ISSN:	2160-7648
Popis:	GPR109A (HM74A), a G-protein-coupled receptor, is hypothesized to mediate lipid and lipoprotein changes and dermal flushing associated with niacin administration. GSK256073 (8-chloro-3-pentyl-1H-purine-2,6[3H,7H]-dione) is a selective GPR109A agonist shown to suppress fatty acid levels and produce mild flushing in short-term clinical studies. This study evaluated the effects of GSK256073 on lipids in subjects with low high-density lipoprotein cholesterol (HDLc). Subjects (n = 80) were randomized (1:1:1:1) to receive GSK256073 5, 50, or 150 mg/day or matching placebo for 8 weeks. The primary end point was determining the GSK256073 exposure-response relationship for change from baseline in HDLc. No significant exposure response was observed between GSK256073 and HDLc levels. GSK256073 did not significantly alter HDLc levels versus placebo, but rather revealed a trend at the 150-mg dose for a nonsignificant decrease in HDLc (-6.31%; P = .12) and an increase in triglycerides (median, 24.4%; 95% confidence interval, 7.3%-41.6%). Flushing was reported in 21%, 25%, and 60% of subjects (5, 50, and 150 mg, respectively) versus 24% for placebo. Results indicated that selective activation of the GPR109A receptor with GSK256073 did not produce niacin-like lipid effects. These findings add to the increasing evidence that niacin-mediated lipoprotein changes occur predominantly via GPR109A-independent pathways.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e131573b4df54b8b6cc9db4bd9cabe3e https://pubmed.ncbi.nlm.nih.gov/31268250 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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