Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
RDEA594, a Novel Uricosuric Agent, Significantly Reduced Serum Urate Levels and Was Well Tolerated in a Phase 2a Pilot Study in Hyperuricemic Gout Patients
Lasko1, Ben, Sheedy2, Beth, Hingorani2, Vijay, Tellier3, Guy, Manhard2, Kimberly, Yeh2, Li-Tain, Miner2, Jeffrey N.
RDEA594 is in development for the management of hyperuricemia in gout patients. It is a uricosuric agent that acts through inhibition of the uric acid transporter (URAT1) in the proximal tubule of the kidney. RDEA594 was safe and well tolerated and demonstrated dose-dependent reductions in serum urate (sUA) in over 100 healthy volunteers in Phase I studies of up to 10 days duration. The primary objective of this pilot study was to compare the proportion of patients whose sUA level was <6.0 mg/dL following 2 weeks of continuous treatment with RDEA594 compared to allopurinol and placebo in gout patients
Twenty-one gout patients with hyperuricemia (sUA >= 8.0 mg/dL) were enrolled. Patients were randomized in a 2:1:1 ratio to the following treatment groups: RDEA594 200 mg once daily (qd) for 1 week followed by 400 mg qd for 1 week, RDEA594 matching placebo qd for 2 weeks, or open-label allopurinol 300 mg qd for 2 weeks. The study included a 2-week run-in period, a 2-week treatment period, and a 1 week follow-up period. To reduce the incidence of gout flares, colchicine (0.6 mg qd) was administered to all patients throughout the 5-week study. An immediate release (IR) capsule formulation was administered under fed conditions. Serum urate levels were assessed at baseline, Days 1, 8, 9, 14 and 15, and at the end of the follow-up period. Safety was assessed by adverse events (AEs), clinical laboratory test results, vital signs, 12-lead ECGs, and physical examinations. Drug exposure was assessed by measuring concentrations of RDEA594 in plasma and urine.
Preliminary results suggest that RDEA594 plasma levels in gout patients were generally consistent with those observed in Phase 1 healthy volunteer studies. A large majority of the patients achieved target sUA concentrations of less than 6 mg/dL after the first week of treatment, which was comparable to patients receiving allopurinol and significantly better than placebo. On average, RDEA594-treated patients achieved a 40% reduction in serum urate levels by this early time point. RDEA594 was well tolerated in this study, with no serious adverse events and no premature discontinuations due to adverse events at the time of this assessment
Preliminary results in this pilot study show that RDEA594 lowers sUA and is well tolerated after dosing in gout patients with hyperuricemia
To cite this abstract, please use the following information:
Lasko, Ben, Sheedy, Beth, Hingorani, Vijay, Tellier, Guy, Manhard, Kimberly, Yeh, Li-Tain, et al; RDEA594, a Novel Uricosuric Agent, Significantly Reduced Serum Urate Levels and Was Well Tolerated in a Phase 2a Pilot Study in Hyperuricemic Gout Patients [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1105