Abstract 1634: Effects of the DP1-receptor Antagonist MK-0524 on Nicotinic Acid-Induced Flushing in Lipid Clinic Patients
OBJECTIVES: Niacin (nicotinic acid) is not optimally utilized because of flushing, a process mediated by PGD2, leading to poor patient compliance and inadequate dosing. This Phase IIB study assessed the benefit of the DP1-receptor antagonist, MK-0524, on extended-release niacin (ERN)-induced flushing.
METHODS: Patients (N=412) were randomized to ERN 1g (given as NIASPAN®, with no prior titration) + MK-0524 placebo, 18.75, 37.5, 75, or 150 mg, or double-placebo for 4 wks (acute phase), with doubling of the respective doses for the remaining 4 wks (chronic phase). Patients reported flushing intensity using the validated Global Flushing Severity Score (GFSS; none/mild [0–3], moderate [4 – 6], severe [7–9], extreme ) in a daily eDiary. A subset of patients was randomized to MK-0524 150 mg versus placebo in a 4-week crossover safety study.
RESULTS: Patients on MK-0524 + ERN reported significantly lower acute (dose-response p<0.001) and chronic phase (dose-response p=0.021) flushing intensity compared to ERN alone. At each coadministered MK-0524 dose, there was a significantly (p<0.05) lower flushing intensity versus ERN alone (figure⇓: data from first week of acute phase, all MK-0524 doses pooled). MK-0524 150 mg had no meaningful effect on lipids, nor did it impact the lipid-altering effects of ERN. There was a low incidence of adverse experiences with MK-0524, either alone or coadministered with ERN.
CONCLUSIONS: Patients receiving MK-0524 had significantly lower flushing intensity associated with ERN treatment. MK-0524 could significantly improve both tolerability and achievement of optimal therapeutic dosing of niacin, a therapy proven to reduce cardiovascular risk.