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- Title
The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout.
- Authors
Steinberg, Alexandra S.; Vince, Bradley D.; Yun-Jung Choi; Martin, Robert L.; McWherter, Charles A.; Boudes, Pol F.; Choi, Yun-Jung
- Abstract
<bold>Objective: </bold>Arhalofenate (ARH), in development for gout, has uricosuric and anti-flare activities. ARH plus febuxostat (FBX) were evaluated in subjects with gout for serum uric acid (SUA) lowering, drug interaction, and safety.<bold>Methods: </bold>Open phase II trial in gout volunteers (NCT02252835). Cohort 1 received ARH 600 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 80 mg followed by 40 mg. FBX 40 mg was continued alone for 2 weeks. Cohort 2 received ARH 800 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 40 mg followed by 80 mg. FBX 80 mg was continued alone for 2 weeks. SUA, its fractional excretion (FEUA), and plasma oxypurines were assessed. Pharmacokinetics of FBX and ARH were determined alone and in combination for cohort 2.<bold>Results: </bold>Baseline mean SUA was 9.4 mg/dl for cohort 1 (n = 16) and 9.2 mg/dl for cohort 2 (n = 16). The largest SUA decrease (63%) was observed with ARH 800 mg + FBX 80 mg, with all subjects reaching SUA < 6 mg/dl and 93% < 5 mg/dl. The area under the curve (AUC)(0-t) of ARH acid + FBX/ARH acid was 108%. The AUC(0-t) of FBX + ARH acid/FBX was 87%. As expected, FBX increased oxypurines and increases were unaffected by ARH co-administration. Baseline FEUA were low (3.5%-4.6%) and ARH increased them toward normal without overexcretion of UA. ARH was well tolerated and appeared safe.<bold>Conclusion: </bold>ARH and FBX lowered SUA by complementary mechanisms. The combination provided greater decreases than each drug alone. The combination was well tolerated and appeared safe.<bold>Trial Registration: </bold>NCT02252835.
- Publication
Journal of Rheumatology, 2017, Vol 44, Issue 3, p374
- ISSN
0315-162X
- Publication type
journal article
- DOI
10.3899/jrheum.161062