PMID- 26989892 OWN - NLM STAT- MEDLINE DCOM- 20170707 LR - 20220409 IS - 2326-5205 (Electronic) IS - 2326-5191 (Print) IS - 2326-5191 (Linking) VI - 68 IP - 8 DP - 2016 Aug TI - A Randomized, Double-Blind, Active- and Placebo-Controlled Efficacy and Safety Study of Arhalofenate for Reducing Flare in Patients With Gout. PG - 2027-34 LID - 10.1002/art.39684 [doi] AB - OBJECTIVE: Arhalofenate is a novel antiinflammatory uricosuric agent. The objective of this study was to evaluate its antiflare activity in patients with gout. METHODS: This was a 12-week, randomized, double-blind, controlled phase IIb study. Eligible patients had had >/=3 flares of gout during the previous year, had discontinued urate-lowering therapy and colchicine, and had a serum uric acid (UA) level of 7.5-12 mg/dl. Patients were randomly assigned at a 2:2:2:2:1 ratio to receive 600 mg arhalofenate, 800 mg arhalofenate, 300 mg allopurinol, 300 mg allopurinol plus 0.6 mg colchicine, or placebo once a day. The primary outcome measure was the flare incidence (number of flares divided by time of exposure). The serum UA level was a secondary outcome measure. RESULTS: A total of 239 gout patients were randomized and took at least 1 dose of study medication. The primary outcome measure comparing flare incidence between 800 mg arhalofenate and 300 mg allopurinol was achieved, with a 46% decrease in the 800 mg arhalofenate group (0.66 versus 1.24; P = 0.0056). Treatment with 800 mg arhalofenate was also significantly better than placebo (P = 0.049) and not significantly different from treatment with 300 mg allopurinol plus 0.6 mg colchicine (P = 0.091). Mean changes in serum UA level were -12.5% with 600 mg arhalofenate and -16.5% with 800 mg arhalofenate (P = 0.001 and P = 0.0001, respectively, versus -0.9% with placebo). There were no meaningful differences in adverse events (AEs) between groups, and there were no serious AEs related to arhalofenate. Urinary calculus occurred in 1 patient receiving 300 mg allopurinol. No abnormal serum creatinine values >1.5-fold the baseline value were observed in the arhalofenate-treated groups. CONCLUSION: Arhalofenate at a dosage of 800 mg decreased gout flares significantly compared to allopurinol at a dosage of 300 mg. Arhalofenate was well tolerated and appeared safe. Arhalofenate is the first urate-lowering antiflare therapy. CI - (c) 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. FAU - Poiley, Jeffrey AU - Poiley J AD - Arthritis Associates, Orlando, Florida. FAU - Steinberg, Alexandra S AU - Steinberg AS AD - CymaBay Therapeutics, Newark, California. FAU - Choi, Yun-Jung AU - Choi YJ AD - CymaBay Therapeutics, Newark, California. FAU - Davis, Charles S AU - Davis CS AD - CSD Biostatistics, Tucson, Arizona. FAU - Martin, Robert L AU - Martin RL AD - CymaBay Therapeutics, Newark, California. FAU - McWherter, Charles A AU - McWherter CA AD - CymaBay Therapeutics, Newark, California. FAU - Boudes, Pol F AU - Boudes PF AD - CymaBay Therapeutics, Newark, California. CN - Arhalofenate Flare Study Investigators LA - eng SI - ClinicalTrials.gov/NCT02063997 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Acetamides) RN - 0 (Gout Suppressants) RN - 0 (Phenylacetates) RN - 1P01UJR9X1 (arhalofenate) RN - 63CZ7GJN5I (Allopurinol) SB - IM CIN - Arthritis Rheumatol. 2016 Aug;68(8):1793-6. PMID: 26990165 CIN - Nat Rev Rheumatol. 2016 May;12 (5):252. PMID: 27052485 MH - Acetamides/adverse effects/*therapeutic use MH - Allopurinol/adverse effects/*therapeutic use MH - Double-Blind Method MH - Female MH - Gout/*drug therapy MH - Gout Suppressants/adverse effects/*therapeutic use MH - Humans MH - Male MH - Middle Aged MH - Phenylacetates/adverse effects/*therapeutic use MH - Treatment Outcome PMC - PMC5129473 FIR - Bays, H IR - Bays H FIR - Bolshoun, D IR - Bolshoun D FIR - Bolster, E IR - Bolster E FIR - Cheung, D IR - Cheung D FIR - Cone, C IR - Cone C FIR - DeGarmo, R IR - DeGarmo R FIR - Earl, J IR - Earl J FIR - El Asmar, I IR - El Asmar I FIR - Felber, D IR - Felber D FIR - Fitz-Patrick, D IR - Fitz-Patrick D FIR - Gaffo, A IR - Gaffo A FIR - Gottschlich, G IR - Gottschlich G FIR - Greenwald, J IR - Greenwald J FIR - Griffin, C IR - Griffin C FIR - Guice, M IR - Guice M FIR - Harper, W IR - Harper W FIR - Hill, J IR - Hill J FIR - Huffman, C IR - Huffman C FIR - Huling, R Jr IR - Huling R Jr FIR - Johnson, F IR - Johnson F FIR - Kafka, S IR - Kafka S FIR - Keane, J IR - Keane J FIR - Kirby, W IR - Kirby W FIR - Kirstein, J IR - Kirstein J FIR - Kolettis, E IR - Kolettis E FIR - Lefebvre, G IR - Lefebvre G FIR - Mabaquiao, A IR - Mabaquiao A FIR - Maynard, K IR - Maynard K FIR - McIlwain, H IR - McIlwain H FIR - McNeill, R IR - McNeill R FIR - Mehta, D IR - Mehta D FIR - Montgomery, R IR - Montgomery R FIR - Morgan, C IR - Morgan C FIR - Poiley, J IR - Poiley J FIR - Powell, S IR - Powell S FIR - Radbill, K IR - Radbill K FIR - Reschak, M IR - Reschak M FIR - Surowitz, R IR - Surowitz R FIR - Tarro, J IR - Tarro J FIR - Turner, M IR - Turner M FIR - Velazquez, F IR - Velazquez F FIR - Watkins, L IR - Watkins L FIR - White, J IR - White J FIR - Williams, H IR - Williams H FIR - Wilson, J IR - Wilson J FIR - Zaidi, F IR - Zaidi F FIR - Henein, S IR - Henein S FIR - Toma, A IR - Toma A FIR - Burtchuladze, T IR - Burtchuladze T FIR - Kartvelishvili, E IR - Kartvelishvili E FIR - Kilasonia, L IR - Kilasonia L FIR - Lagvilava, L IR - Lagvilava L FIR - Shalamberidze, L IR - Shalamberidze L FIR - Tsiskarishvili, N IR - Tsiskarishvili N EDAT- 2016/03/19 06:00 MHDA- 2017/07/08 06:00 PMCR- 2016/11/30 CRDT- 2016/03/19 06:00 PHST- 2015/10/18 00:00 [received] PHST- 2016/03/15 00:00 [accepted] PHST- 2016/03/19 06:00 [entrez] PHST- 2016/03/19 06:00 [pubmed] PHST- 2017/07/08 06:00 [medline] PHST- 2016/11/30 00:00 [pmc-release] AID - ART39684 [pii] AID - 10.1002/art.39684 [doi] PST - ppublish SO - Arthritis Rheumatol. 2016 Aug;68(8):2027-34. doi: 10.1002/art.39684.