{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:40:38Z","timestamp":1788435638887,"version":"build-2803163510"},"reference-count":25,"publisher":"The Journal of Rheumatology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Open phase II trial in gout volunteers (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02252835\">NCT02252835<\/jats:ext-link>). 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>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 &lt; 6 mg\/dl and 93% &lt; 5 mg\/dl. The area under the curve (AUC)<jats:sub>(0-t)<\/jats:sub>of ARH acid + FBX\/ARH acid was 108%. The AUC<jats:sub>(0-t)<\/jats:sub>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%\u20134.6%) and ARH increased them toward normal without overexcretion of UA. ARH was well tolerated and appeared safe.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>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. Trial registration:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02252835\">NCT02252835<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.161062","type":"journal-article","created":{"date-parts":[[2016,12,16]],"date-time":"2016-12-16T01:38:06Z","timestamp":1481852286000},"page":"374-379","source":"Crossref","is-referenced-by-count":34,"title":["The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout"],"prefix":"10.3899","volume":"44","author":[{"given":"Alexandra S.","family":"Steinberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley D.","family":"Vince","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Jung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"McWherter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pol F.","family":"Boudes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"2018112909364730000_44.3.374.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.curtheres.2013.04.003"},{"key":"2018112909364730000_44.3.374.2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21772"},{"key":"2018112909364730000_44.3.374.3","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.055269"},{"key":"2018112909364730000_44.3.374.4","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/33.1.104"},{"key":"2018112909364730000_44.3.374.5","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204463"},{"key":"2018112909364730000_44.3.374.6","first-page":"2429","article-title":"Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis","volume":"31","author":"Borstad","year":"2004","journal-title":"J Rheumatol"},{"key":"2018112909364730000_44.3.374.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050373"},{"key":"2018112909364730000_44.3.374.8","doi-asserted-by":"publisher","DOI":"10.1002\/art.24209"},{"key":"2018112909364730000_44.3.374.9","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.semarthrit.2012.03.010","article-title":"Treatment of chronic gouty arthritis: it is not just about urate-lowering therapy","volume":"42","author":"Schlesinger","year":"2012","journal-title":"Semin Arthritis Rheum"},{"key":"2018112909364730000_44.3.374.10","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21773"},{"key":"2018112909364730000_44.3.374.11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1097\/BOR.0000000000000031","article-title":"Safety profile of anti-gout agents: an update","volume":"26","author":"Stamp","year":"2014","journal-title":"Curr Opin Rheumatol"},{"issue":"Suppl 3","key":"2018112909364730000_44.3.374.12","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1136\/annrheumdis-2012-eular.2860","article-title":"FRI0403 Arhalofenate, a novel uricosuric agent, is an inhibitor of human uric acid transporters","volume":"71","author":"Lavan","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"2018112909364730000_44.3.374.13","doi-asserted-by":"publisher","DOI":"10.1002\/art.33484"},{"key":"2018112909364730000_44.3.374.14","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1002\/art.39684","article-title":"A randomized, double-blind, active- and placebo-controlled efficacy and safety study of arhalofenate for reducing flare in patients with gout","volume":"68","author":"Poiley","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2018112909364730000_44.3.374.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00860.x"},{"key":"2018112909364730000_44.3.374.16","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket114"},{"key":"2018112909364730000_44.3.374.17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1159\/000167564","article-title":"Suprofen-induced uricosuria. 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