Arisaph Pharmaceuticals, Inc. announced today during an oral presentation at the American Heart Association (AHA) meeting in Los Angeles, CA that its niacin analog, ARI-3037MO, was extremely well tolerated in a single-ascending dose (SAD) and a multiple-ascending dose (MAD) trial in healthy male and female volunteers. The results showed that ARI-3037MO did not provoke flushing or any other adverse skin changes, nor did it cause increases in liver enzymes or blood glucose at doses up to 6 grams per day. In both clinical trials, ARI-3037MO also demonstrated encouraging lipid effects. Based on these promising results, ARI-3037MO potentially represents a transformational, new niacin-like option for treatment of patients with dyslipidemia, especially in the setting of metabolic syndrome, a disorder that afflicts as many as 70 million Americans.
"The absence of flushing and other niacin induced adverse events highlights a differentiated safety profile for our novel niacin analog," said Christopher P. Kiritsy, Co-Founder, President and Chief Executive Officer of Arisaph Pharmaceuticals. "Moreover, the evidence of lipid changes in such short duration trials in healthy volunteers shows that our preclinical efficacy data are translating and breeds optimism for the development of our best-in-class niacin analog."
In two placebo controlled, safety and pharmacokinetic trials (SAD and MAD), 58 healthy male and female volunteers were given either single escalating doses of ARI-3037MO (up to 6 grams per day) or repeat escalating doses of ARI-3037MO (up to 3.5 grams per day) for 14 days. In both trials, ARI-3037MO was given once daily without a titration scheme. The results showed that ARI-3037MO was extremely well tolerated with no treatment-related adverse events. Specifically, treatment with ARI-3037MO did not show any evidence of flushing or adverse skin changes, such as itching or rash, using a validated visual-analog scale. Additionally, no deleterious changes in liver enzymes or blood glucose were observed with ARI-3037MO, even when given at high doses in a repeat-dose setting.
The pharmacokinetics of ARI-3037MO revealed that the drug was well absorbed orally and showed good dose proportionality. In both clinical trials, ARI-3037MO produced encouraging lipid signals. For example, a single dose of 6 grams of ARI-3037MO produced a 15% increase in HDL and attenuated the postprandial increase in serum triglycerides (TGs). In the MAD trial, the 2g and 3.5g doses of ARI-3037MO decreased LDL-cholesterol (LDL-C) from baseline and improved post-prandial triglycerides by more than 30% compared with placebo. Such lipid trends are encouraging considering that the trials were short-duration, safety and pharmacokinetic studies in healthy volunteers and would not be expected to show pharmacodynamic effects.