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

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 prima ry 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.

Source: Clinical Pharmacology in Drug Development - July 2, 2019 Category: Drugs & Pharmacology Authors: Eric J. Olson, Kelly M. Mahar, Thomas F. Haws, Feng Gao, Anne ‐Charlotte Gouville, Dennis L. Sprecher, John J. Lepore Tags: Original Manuscript Source Type: research