Ardea Biosciences, Inc 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 seven days or 40 mg of febuxostat QD for seven days, and then the combination of the two regimens for seven 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 per cent from baseline. When administered in combination for seven days, the two agents produced a mean reduction in serum urate of approximately 60 per cent from baseline, with intraday reductions of almost 75 per cent. No clinically relevant adverse effects or laboratory abnormalities were observed during administration of RDEA594. Two subjects experienced grade two 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.
"The substantial reduction in serum uric acid observed when RDEA594 and febuxostat are co-administered indicate that these two oral agents with complementary mechanisms may be able to accelerate improvement in tophaceous gout compared to single agent therapy," commented John S Sundy MD, associate professor of medicine and head of the Section of Allergy and Clinical Immunology in the Division of Pulmonary, Allergy and Critical Care Medicine at Duke University Medical Center and a member of Ardea's scientific advisory board. "I look forward to studying this combination in patients with advanced disease."
"Similar reductions in serum urate produced when RDEA594 and febuxostat were administered alone, and the substantial reduction produced when these agents were administered in combination supports our strategy to develop RDEA594 as both monotherapy and in combination with xanthine oxidase inhibitors, such as febuxostat or allopurinol," added Barry D Quart, Ardea's president and chief executive officer. "With the dramatic reduction in serum uric acid observed when RDEA594 and febuxostat are administered in combination, together these agents may be able to produce reductions in tophaceous gout previously achieved only with intravenous therapy."
In addition to this study, RDEA594 is currently being administered in a phase-2b single-agent dose-response study evaluating the safety and urate-lowering effects of 200, 400 and 600 mg of RDEA594, a phase-2b study evaluating RDEA594 as an add-on to allopurinol in patients that do not respond adequately to allopurinol alone, and a study in gout patients with renal impairment.
Ardea Biosciences is a biotechnology company focused on the development of small-molecule therapeutics for the treatment of gout, cancer and human immunodeficiency virus (HIV).