title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Japan. kamatani@msb.biglobe.ne.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Shin
authors.initials: S
authors.lastname: Fujimori
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hada
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000284:Administration, Oral; D000493:Allopurinol / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000069465:Febuxostat; D005260:Female; D005500:Follow-Up Studies; D006073:Gout / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007564:Japan; D008297:Male; D008875:Middle Aged; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase