Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study

Arthritis Rheumatol. 2019 Jan;71(1):143-153. doi: 10.1002/art.40685.


Objective: To assess the efficacy and safety of febuxostat extended release (XR) and immediate release (IR) in patients with gout and normal or impaired renal function.

Methods: This was a 3-month, phase III, multicenter, double-blind, placebo-controlled study. Patients (n = 1,790) with a history of gout and normal or impaired (mild-to-severe) renal function were randomized to receive placebo, febuxostat IR 40 or 80 mg, or febuxostat XR 40 or 80 mg once daily (1:1:1:1:1 ratio). End points included proportions of patients with a serum urate (UA) level of <5.0 mg/dl at month 3 (primary end point), a serum UA level of <6.0 mg/dl at month 3, and ≥1 gout flare requiring treatment over 3 months (secondary end points).

Results: Both febuxostat formulations led to significantly greater proportions of patients achieving a serum UA level of <5.0 mg/dl or <6.0 mg/dl at month 3 (P < 0.001 for all comparisons versus placebo). Equivalent doses of febuxostat XR and IR had similar treatment effects on serum UA level end points; however, a significantly greater proportion of patients achieved a serum UA level of <5.0 mg/dl with XR 40 mg versus IR 40 mg. Similar proportions of patients experienced ≥1 gout flare across treatment groups. Rates of treatment-emergent adverse events were low and evenly distributed between treatment arms. A preplanned subgroup analysis demonstrated that febuxostat formulations were well tolerated and generally effective on serum UA level end points (versus placebo) across all renal function subgroups.

Conclusion: Both formulations of febuxostat (XR and IR) were well tolerated and effective in patients with gout and normal or impaired renal function, including patients with severe renal impairment.

Trial registration: ClinicalTrials.gov NCT02139046.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Colchicine / therapeutic use
  • Cough / chemically induced
  • Creatinine / blood
  • Delayed-Action Preparations
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Drug Therapy, Combination
  • Febuxostat / administration & dosage*
  • Febuxostat / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • Gout / blood
  • Gout / complications
  • Gout / drug therapy*
  • Gout Suppressants / administration & dosage*
  • Gout Suppressants / therapeutic use
  • Headache / chemically induced
  • Humans
  • Hypertension / chemically induced
  • Male
  • Middle Aged
  • Naproxen / therapeutic use
  • Nasopharyngitis / chemically induced
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / metabolism*
  • Respiratory Tract Infections / chemically induced
  • Severity of Illness Index
  • Treatment Outcome
  • Uric Acid / blood
  • gamma-Glutamyltransferase / blood


  • Delayed-Action Preparations
  • Gout Suppressants
  • Febuxostat
  • Uric Acid
  • Naproxen
  • Creatinine
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Colchicine

Associated data

  • ClinicalTrials.gov/NCT02139046