Phase II Clinical Trial of Febuxostat for Gout
Title: Febuxostat, a novel nonpurine selective
inhibitor of xanthine oxidase: a twenty-eight-day, multicenter,
phase II, randomized, double-blind, placebo-controlled, dose-response
clinical trial examining safety and efficacy in patients with
gout.
Authors: Becker MA, et al
Publication: Arthritis Rheum. 2005 Mar;52(3):916-23.
Gout affects approximately 1 to 2% of the American population,
and has limited treatment options. The purpose of this study was
to examine the safety and efficacy of febuxostat, an inhibitor
of the enzyme xanthine oxidase, in establishing normal levels
of uric acid (urate) in the blood of gout patients with hyperuricemia
(high levels of uric acid in the blood, defined as 8.0mg/dl or
greater).
A double-blind, randomized, placebo-controlled trial of 153 patients
ages 23 to 80 years was conducted. These subjects were divided
into groups receiving 3 different levels of febuxostat (40, 80,
or 120 mg) or placebo daily for 28 days. They also received colchicines
as additional treatment for 14 days before and after the trial.
The authors then examined the number of subjects that have reduced
uric acid levels of 0.6 mg/dl or less.
The authors found that subjects that took febuxostat had lower
uric acid levels:
Febuxostat Dose |
% of patients with reduced uric
acid |
0 mg (placebo) |
0 |
40 mg |
56 |
80 mg |
76 |
120 mg |
94 |
This table showed that no subject taking placebo had reduced
uric acid levels and almost all (94%) of patients taking 120 mg
of febuxostat daily for 28 days had lower uric acid levels.
When the uric acid levels were measured after 28 days, the authors
noted that uric acid levels in the blood of the patients were
lowered in the following proportion:
Febuxostat Dose |
% of decrease in uric acid level |
0 mg (placebo) |
2 |
40 mg |
37 |
80 mg |
44 |
120 mg |
59 |
This showed that more percentage of people had successfully decreased
uric acid level with higher doses of febuxostat, and the size
of the decrease was greater with higher doses.
However, when the authors examined the rate of gouty flares,
they found:
Febuxostat Dose |
% of patients with gouty flares |
0 mg (placebo) |
37 |
40 mg |
35 |
80 mg |
44 |
120 mg |
59 |
This table showed that people taking higher doses of febuxostat
had higher frequency of gout flares.
When taking colchicines as additional medication, the gout flares
occurred less frequently (8 to 13%). The incidence of other side
effects were similar in those receiving febuxostat and placebo.
