title: An allopurinol-controlled, multicenter, randomized, open-label, 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 2 exploratory clinical study.
abstract: BACKGROUND
  Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative.
  
  
  OBJECTIVE
  Febuxostat was administered to patients with hyperuricemia including gout in Japan to compare its efficacy and safety with those of allopurinol.
  
  
  METHODS
  The starting dose of febuxostat and allopurinol was 10 and 100 mg/d, respectively, and was increased to the fixed maintenance dose of 40 or 60 mg/d for febuxostat and 300 mg/d for allopurinol for 16 weeks.
  
  
  RESULTS
  : The percent change in the serum uric acid level at 16 weeks compared with the baseline serum uric acid level was -42.96% ± 13.33% and -52.47% ± 9.79% for the febuxostat 40- and 60-mg/d groups, respectively, and -36.55% ± 18.59% for the allopurinol group, indicating that the hypouricemic effects of febuxostat increased in a dose-dependent manner and equaled to or surpassed those of allopurinol (P = 0.0239, 2-sample t test). The percentage of patients with serum uric acid levels of 6.0 mg/dL or less at 16 weeks was 88.9% and 100% for the febuxostat 40- and 60-mg/d groups, respectively, and 68.8% for the allopurinol group, showing higher achievements for the febuxostat groups compared with the allopurinol group. All adverse drug reactions were mild to moderate in severity, and there were no severe symptoms or reactions leading to drug discontinuation.
  
  
  CONCLUSIONS
  These results suggest that febuxostat is safe at doses of 40 and 60 mg/d and has equal or greater efficacy than 300 mg/d allopurinol.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Teikyo University, Tokyo, Japan. kamatani@msb.biglobe.ne.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Kamatani
authors.initials: K
authors.lastname: Naoyuki
authors.forename: Shin
authors.initials: S
authors.lastname: Fujimori
authors.forename: Fujimori
authors.initials: F
authors.lastname: Shin
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hada
authors.forename: Hada
authors.initials: H
authors.lastname: Toshikazu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Hosoya
authors.initials: H
authors.lastname: Tatsuo
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.forename: Kohri
authors.initials: K
authors.lastname: Kenjiro
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Nakamura
authors.initials: N
authors.lastname: Toshitaka
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
authors.forename: Ueda
authors.initials: U
authors.lastname: Takanori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yamamoto
authors.initials: Y
authors.lastname: Tetsuya
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Yamanaka
authors.initials: Y
authors.lastname: Hisashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Matsuzawa
authors.initials: M
authors.lastname: Yuji
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*; D013997:Time Factors; 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