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.

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.

• Authors: Naoyuki Kamatani, Shin Fujimori, Toshikazu Hada, Tatsuo Hosoya, Kenjiro Kohri, Toshitaka Nakamura, Takanori Ueda, Tetsuya Yamamoto, Hisashi Yamanaka, Yuji Matsuzawa
• Journal: Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases (J Clin Rheumatol) Vol. 17 Issue 4 Suppl 2 Pg. S13-8 (Jun 2011) ISSN: 1536-7355 [Electronic] United States
• PMID: 21654265 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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