1. A Randomized, Double‐Blind, Active‐ and Placebo‐Controlled Efficacy and Safety Study of Arhalofenate for Reducing Flare in Patients With Gout
- Author
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Poiley, Jeffrey, Steinberg, Alexandra S., Choi, Yun‐Jung, Davis, Charles S., Martin, Robert L., McWherter, Charles A., Boudes, Pol F., Bays, H., Bolshoun, D., Bolster, E., Cheung, D., Cone, C., DeGarmo, R., Earl, J., El Asmar, I., Felber, D., Fitz‐Patrick, D., Gaffo, A., Gottschlich, G., Greenwald, J., Griffin, C., Guice, M., Harper, W., Hill, J., Huffman, C., Huling, R., Johnson, F., Kafka, S., Keane, J., Kirby, W., Kirstein, J., Kolettis, E., Lefebvre, G., Mabaquiao, A., Maynard, K., McIlwain, H., McNeill, R., Mehta, D., Montgomery, R., Morgan, C., Poiley, J., Powell, S., Radbill, K., Reschak, M., Surowitz, R., Tarro, J., Turner, M., Velazquez, F., Watkins, L., White, J., Williams, H., Wilson, J., Zaidi, F., Henein, S., Toma, A., Burtchuladze, T., Kartvelishvili, E., Kilasonia, L., Lagvilava, L., Shalamberidze, L., and Tsiskarishvili, N.
- Subjects
Male ,medicine.medical_specialty ,Gout ,Allopurinol ,Immunology ,Placebo ,Gastroenterology ,Gout Suppressants ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Rheumatology ,Randomized controlled trial ,law ,Internal medicine ,Acetamides ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Adverse effect ,Phenylacetates ,030203 arthritis & rheumatology ,Creatinine ,business.industry ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,Surgery ,Clinical trial ,Treatment Outcome ,chemistry ,Female ,business ,medicine.drug - Abstract
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.
- Published
- 2016