Ardea Biosciences, Inc. (Nasdaq: RDEA) today announced positive results from the first dosing group of an ongoing drug-drug interaction and pharmacodynamic study of RDEA594, its lead product candidate for the treatment of hyperuricemia and gout, and febuxostat (Uloric®, Takeda Pharmaceutical Company Limited; Adenuric®, Ipsen). This randomized, placebo-controlled study in normal healthy volunteers with baseline serum urate levels of greater than 5 mg/dL is designed to evaluate the potential for pharmacokinetic drug interactions, as well as the serum urate-lowering effect, safety and tolerability of escalating doses of RDEA594, administered once-daily (QD) in combination with 40 mg febuxostat.
In the first two periods of the initial dosing group, 18 subjects received either 200 mg of RDEA594 QD or matching placebo for 7 days or 40 mg of febuxostat QD for 7 days, and then the combination of the two regimens for 7 days. The combination of RDEA594 and febuxostat in this first dosing group was well tolerated and no pharmacokinetic drug interactions were observed. After one week of dosing as monotherapy, both RDEA594 and febuxostat produced a mean reduction in serum urate of approximately 40% from baseline. When administered in combination for 7 days, the two agents produced a mean reduction in serum urate of approximately 60% from baseline, with intraday reductions of almost 75%. No clinically relevant adverse effects or laboratory abnormalities were observed during administration of RDEA594. Two subjects experienced grade 2 increases in a liver enzyme while receiving febuxostat alone. Based on these positive results, we have initiated a second dosing group evaluating 400 mg of RDEA594 QD in combination with 40 mg of febuxostat QD.