Session Type: Poster Session D
Session Time: 8:30AM-10:30AM
Background/Purpose: AR882 is a novel, potent and selective uric acid transporter 1 (URAT1) inhibitor in Phase 2 development for the treatment of hyperuricemia and gout. In Phase 1 and Phase 2a studies AR882 exhibited good dose proportionality, long effective half-life and dose-dependent serum urate (sUA) lowering effect and was well tolerated in healthy subjects or gout patients.
Methods: AR882 had been evaluated in healthy subjects with normal renal function, mild or moderate impairment (estimated creatinine clearance ≥ 90, 60 to < 90, 30 to < 60 mL/min, respectively), or in gout patients with normal renal function or mild renal impairment. Subjects with severe renal impairment (15 to < 30 mL/min) are currently being enrolled for evaluation. AR882 was given as an oral capsule at 50 mg (multiple doses) or 100 mg (single dose). Serial blood and urine samples were collected for measurement of AR882 concentration and sUA levels for PK/PD assessment. Adverse events, laboratory safety tests, vital signs, and electrocardiograms were collected throughout the study.
Results: Following a single oral dose of AR882 at 100 mg, only mild increases in plasma exposure to AR882 was noted in subjects with mild (n=8) or moderate (n=8) impairment when compared to subjects with normal renal function (n=8). The sUA lowering effect of AR882 was not affected in subjects with mild or moderate impairment. Maximal reduction in sUA levels was approximately 50-60% in subjects with renal impairment, similar to those observed in subjects with normal renal function.
In 28 gout patients receiving 50 mg multiple doses for one week in a phase 2a study, similar AR882 plasma exposure was observed between patients with normal renal function (n=18) and those with mild renal impairment (n=10). At steady state, reduction of sUA levels was approximately 53% in both renal function groups. Response rate at target sUA levels were also similar.
Conclusion: AR882 sUA lowering effect is similar in subjects with mild or moderate renal impairment compared to subjects/patients with normal renal function. No clinically relevant serum creatinine elevation was observed in either the phase 2a gout patient study or the phase 1 renal impairment study.
To cite this abstract in AMA style:shen z, Polvent E, hingorani v, Yan R, Yan S, Yeh L. AR882, a Potent and Selective Uricosuric Agent, Showed Effectiveness in Patients with Various Degrees of Renal Impairment [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/ar882-a-potent-and-selective-uricosuric-agent-showed-effectiveness-in-patients-with-various-degrees-of-renal-impairment/. Accessed December 7, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ar882-a-potent-and-selective-uricosuric-agent-showed-effectiveness-in-patients-with-various-degrees-of-renal-impairment/