Rheumatology and Therapy (Sep 2019)

A Randomized, Double-Blind, Non-Inferiority Study of Febuxostat Versus Allopurinol in Hyperuricemic Chinese Subjects With or Without Gout

  • Fengchun Zhang,
  • Zhichun Liu,
  • Lindi Jiang,
  • Hao Zhang,
  • Dongbao Zhao,
  • Yang Li,
  • Hejian Zou,
  • Xiaoyue Wang,
  • Xiangpei Li,
  • Bingyin Shi,
  • Jianhua Xu,
  • Hongjie Yang,
  • Shaoxian Hu,
  • Shen Qu

DOI
https://doi.org/10.1007/s40744-019-00173-8
Journal volume & issue
Vol. 6, no. 4
pp. 543 – 557

Abstract

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Abstract Introduction This 24-week randomized, double-blind, non-inferiority study compared the efficacy and safety of febuxostat, a xanthine oxidase inhibitor, with allopurinol using an up-titration method in hyperuricemic Chinese subjects with or without gout. Methods Eligible adults (serum uric acid [SUA] > 7.0 mg/dl with a history of gout, SUA ≥ 8.0 mg/dl with complications or SUA ≥ 9.0 mg/dl without complications) were randomized (1:1:1) to febuxostat 40 mg/day, 80 mg/day, or allopurinol 300 mg/day. Starting doses of febuxostat 20 mg/day and allopurinol 100 mg/day were up-titrated, up to 16 weeks, to the randomized doses and maintained to week 24. Primary endpoint was non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day based on the percentage of subjects with SUA ≤ 6.0 mg/dl at week 24. The same comparison was made between febuxostat 60 mg/day or 80 mg/day versus allopurinol 300 mg/day. Safety assessments included measurement of treatment-emergent adverse events (TEAEs). Results The per-protocol population comprised 472 subjects. Non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not demonstrated based on the protocol-defined margin of − 10% (44.7 vs. 50.0%; − 5.3% difference; 95% confidence interval [CI]: − 16.4%, 5.8%); however, superiority over allopurinol 300 mg/day was demonstrated for febuxostat 60 mg/day at week 16 (66.3 vs. 51.2%; a 15.0% difference; 95% CI: 4.2%, 25.9%) and febuxostat 80 mg/day at week 24 (70.0 vs. 50.0%; a 20.0% difference; 95% CI: 9.3%, 30.7%). The frequency of TEAEs was similar across groups, with gout flares occurring frequently. Conclusions Using a novel dose-titration method, although the primary endpoint of non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not reached, non-inferiority and superiority of febuxostat 60 mg/day and 80 mg/day versus allopurinol 300 mg/day was demonstrated at weeks 16 and 24, respectively. Febuxostat demonstrated an acceptable tolerability profile in the treatment of hyperuricemia in Chinese subjects with or without gout. Trial Registration JapicCTI-132106. Funding Astellas Pharma Global Development, Inc.

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