Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010
Condition: Gout
MeSH terms: Gout
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to determine the long-term safety of febuxostat, once daily
      (QD), compared to allopurinol in reducing serum urate levels in subjects with gout.
    

Detailed description: 
      Uric acid is the end product of purine degradation in humans. Hyperuricemia, a urate
      concentration in serum exceeding the limit of urate solubility (approximately 7.0 mg/dL), is
      a common biochemical abnormality. Aberrations in any of the multiple mechanisms involved in
      the production and/or excretion of uric acid may increase serum urate concentrations, with
      persistent hyperuricemia as a marker for extracellular fluid monosodium urate
      supersaturation. As such, hyperuricemia is a necessary (but often insufficient) risk factor
      for monosodium urate crystal deposition in tissues and is the fundamental pathophysiological
      process underlying the clinical manifestations of gout, which is a chronic disease
      characterized by urate crystal formation and deposition in joints and bones. Gout may
      progress from episodic attacks of acute inflammatory arthritis to a disabling chronic
      disorder characterized by deforming arthropathy; destructive deposits of urate crystals
      (tophi) in bones, joints, and other organs; structural and functional renal impairment due to
      interstitial urate crystal deposition; and urinary tract stones composed entirely or
      partially of uric acid crystals. Management of gout requires chronic treatment aimed at
      lowering serum urate levels into a subsaturating range (usually <6.0 mg/dL) in which crystal
      formation and deposition are prevented or reversed.

      Febuxostat (TMX-67) is a non-purine selective xanthine oxidase inhibitor being developed as
      an orally administered agent for the management of hyperuricemia in patients with gout.

      This study was originally designed and initiated having all subjects initially assigned to 80
      mg febuxostat provided as an 80 mg tablet, to be administered orally. Subjects could be
      titrated to 120 mg, provided as one 40 and 80 mg tablet, between Months 2 and 6, if their
      serum uric acid rose > 6.0 mg/dL; the dose could be down-titrated to 80 mg if the serum uric
      acid decreased to < 3.0 mg/dL.

      The protocol was amended to add a comparator arm, and to have subjects randomized to 80 or
      120 mg febuxostat or allopurinol (100 or 300 mg, dependent on renal function). The
      information below reflects the treatments following the implementation of the revised
      protocol.
    

Intervention name(s): Febuxostat; Febuxostat; Allopurinol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Febuxostat 80 mg, tablets, orally, once daily.; Febuxostat 120 mg, tablets, orally, once daily.; Allopurinol 100 mg or 300 mg, tablets, orally, once daily.
Other intervention name(s): TMX-67; Tei-6720; Uloric; TMX-67; Tei-6720; Uloric; Zyloprim
Intervention MeSH terms: Allopurinol; Febuxostat
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: uric acid; xanthine oxidase; hyperuricemia; tophi; Drug Therapy