An allopurinol-controlled, randomized, double-dummy, double-blind, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study

J Clin Rheumatol. 2011 Jun;17(4 Suppl 2):S13-8. doi: 10.1097/RHU.0b013e31821d36cc.


Background: Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat is potentially a safe and efficacious alternative.

Objectives: Febuxostat or allopurinol was administered to patients with hyperuricemia including gout for 8 weeks to compare the efficacy and safety of these drugs.

Methods: Doses of febuxostat and allopurinol were 10 and 100 mg/d, respectively, during a 12-day introduction period and were increased to 40 and 200 mg/d for the subsequent treatment period of 44 days.

Results: : The percent changes in serum uric acid levels after 8 weeks were -40.75% for the febuxostat group and -34.41% for the allopurinol group (P < 0.001, analysis of variance, closing testing procedure). The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 82.0% for the febuxostat group and 70.0% for the allopurinol group (P = 0.019, logistic regression analysis). Regarding safety, 213 adverse events were observed in the febuxostat group and 220 events in the allopurinol group. For 10 patients (8.2%) in the febuxostat group and 14 patients (11.6%) in the allopurinol group, association with the study drugs could not be ruled out. There were no severe adverse drug reactions in the febuxostat group other than a high frequency of gout attacks induced by the sudden reduction in blood uric acid levels during the early treatment period.

Conclusions: Febuxostat at 40 mg/d demonstrated more potent hypouricemic effects than allopurinol at 200 mg/d, was efficacious regardless of medical history of gout, and is considered safe for treatment of hyperuricemia.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Allopurinol / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Febuxostat
  • Female
  • Follow-Up Studies
  • Gout / blood
  • Gout / complications
  • Gout / drug therapy*
  • Gout Suppressants / administration & dosage*
  • Humans
  • Hyperuricemia / blood
  • Hyperuricemia / complications
  • Hyperuricemia / drug therapy*
  • Japan
  • Male
  • Middle Aged
  • Thiazoles / administration & dosage*
  • Treatment Outcome
  • Uric Acid / blood*
  • Xanthine Oxidase / antagonists & inhibitors*
  • Xanthine Oxidase / blood


  • Gout Suppressants
  • Thiazoles
  • Febuxostat
  • Uric Acid
  • Allopurinol
  • Xanthine Oxidase