Ardea Biosciences, Inc. has announced positive results from a Phase 1 study in normal, healthy volunteers of RDEA594, its lead product candidate for the treatment of hyperuricemia and gout, and a pilot Phase 2a proof-of-concept study in gout patients of RDEA594's prodrug, RDEA806 (RDEA806 is converted to RDEA594 in the body).
RDEA594 is an inhibitor of URAT1, a transporter in the kidney that regulates uric acid excretion. These data, as well as future development plans for RDEA594, are being presented today at an investor and analyst event hosted by the Company in New York, NY. The Company intends to present further data from RDEA594 studies at an upcoming scientific conference.
Phase 1
Over 60 normal, healthy volunteers have been administered RDEA594 in Phase 1 single-dose and multiple-dose studies at doses ranging from 5 to 600 mg. Results from the randomized, double-blind, placebo-controlled, multiple-ascending-dose study of RDEA594 that evaluated 100, 200 and 400 mg, oral, once-daily doses of RDEA594 or placebo over a 10-day dosing period are being presented. Statistically significant reductions in uric acid were dose-dependent and seen in all dose groups. A reduction of 45% from baseline (corrected for placebo) was observed after 10 days at the highest dose evaluated. In Phase 1 studies, RDEA594 has been well-tolerated, with no serious adverse events or drug-related discontinuations due to adverse events. Adverse events were infrequent, transient and of mild to moderate severity, with no imbalance between placebo and drug groups.
Following is a summary of uric acid percentage reductions from baseline observed in the multiple-ascending-dose study of RDEA594:
|
RDEA594 Dose |
|
Placebo-Corrected Change
from Baseline (%) |
|
p-value vs. Placebo |
|
100 mg QD |
|
16 |
|
< 0.05 |
|
200 mg QD |
|
31 |
|
< 0.01 |
|
400 mg QD |
|
45 |
|
< 0.001 |
Ardea is initiating a comprehensive Phase 2 program to demonstrate the broad clinical utility of RDEA594 in the treatment of hyperuricemia and gout. This program includes a Phase 2 dose-ranging study of RDEA594 in gout patients, as well as a number of additional studies, including a combination study with RDEA594 added on to allopurinol, currently the most prescribed medication for the treatment of hyperuricemia and gout, a drug-drug interaction study of RDEA594 in combination with febuxostat (ULORIC® from Takeda Pharmaceuticals North America, Inc.), and a renal impairment and pharmacodynamic study of RDEA594 in subjects with varying degrees of renal insufficiency. The Phase 2 program will be initiated in the second quarter of this year and is designed to further assess the safety, pharmacodynamics and efficacy of RDEA594 as a single agent and in combination with other agents that lower uric acid via a different, and potentially complementary, mechanism. Initial results from this program are expected in the fourth quarter of 2009.
Phase 2a