Trial Outcomes & Findings for Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects. (NCT NCT00174915)
NCT ID: NCT00174915
Last Updated: 2012-02-02
Results Overview
Each subject's serum urate at the last 3 visits determined the subject's response for the primary efficacy variable. A subject who prematurely discontinued without least 3 postbaseline serum urate levels was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used. The last 3 visits used may have differed for each subject.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1072 participants
Primary outcome timeframe
Last 3 visits (any last 3 visits up to week 28)
Results posted on
2012-02-02
Participant Flow
Subjects were enrolled at 167 investigative sites in the United States from 21 February 2003 to 07 April 2004.
Subjects currently receiving urate-lowering therapy discontinued those urate-lowering therapies and initiated prophylactic medications before enrollment in once daily (QD) treatment groups.
Participant milestones
| Measure |
Febuxostat 80 mg QD
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
267
|
269
|
134
|
268
|
134
|
|
Overall Study
COMPLETED
|
174
|
200
|
86
|
211
|
101
|
|
Overall Study
NOT COMPLETED
|
93
|
69
|
48
|
57
|
33
|
Reasons for withdrawal
| Measure |
Febuxostat 80 mg QD
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
19
|
17
|
9
|
17
|
10
|
|
Overall Study
Adverse Event
|
18
|
16
|
11
|
18
|
5
|
|
Overall Study
Personal Reason(s)
|
16
|
16
|
9
|
9
|
9
|
|
Overall Study
Other
|
15
|
8
|
6
|
5
|
3
|
|
Overall Study
Gout Flare
|
13
|
6
|
8
|
1
|
0
|
|
Overall Study
Protocol Violation
|
6
|
3
|
3
|
6
|
3
|
|
Overall Study
Therapeutic Failure
|
6
|
3
|
2
|
1
|
3
|
Baseline Characteristics
Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects.
Baseline characteristics by cohort
| Measure |
Febuxostat 80 mg QD
n=267 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=269 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=134 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=268 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=134 Participants
Placebo, orally, once daily for up to 28 weeks.
|
Total
n=1072 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Customized
<45 years
|
82 subjects
n=5 Participants
|
79 subjects
n=7 Participants
|
33 subjects
n=5 Participants
|
82 subjects
n=4 Participants
|
36 subjects
n=21 Participants
|
312 subjects
n=8 Participants
|
|
Age, Customized
45 years to <65 years
|
146 subjects
n=5 Participants
|
154 subjects
n=7 Participants
|
71 subjects
n=5 Participants
|
147 subjects
n=4 Participants
|
79 subjects
n=21 Participants
|
597 subjects
n=8 Participants
|
|
Age, Customized
≥65 years
|
39 subjects
n=5 Participants
|
36 subjects
n=7 Participants
|
30 subjects
n=5 Participants
|
39 subjects
n=4 Participants
|
19 subjects
n=21 Participants
|
163 subjects
n=8 Participants
|
|
Age Continuous
|
50.6 years
STANDARD_DEVIATION 12.24 • n=5 Participants
|
51.2 years
STANDARD_DEVIATION 11.57 • n=7 Participants
|
54.3 years
STANDARD_DEVIATION 12.83 • n=5 Participants
|
51.8 years
STANDARD_DEVIATION 12.25 • n=4 Participants
|
51.5 years
STANDARD_DEVIATION 12.18 • n=21 Participants
|
51.6 years
STANDARD_DEVIATION 12.17 • n=8 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
67 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
251 Participants
n=5 Participants
|
256 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
249 Participants
n=4 Participants
|
123 Participants
n=21 Participants
|
1005 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
200 subjects
n=5 Participants
|
214 subjects
n=7 Participants
|
107 subjects
n=5 Participants
|
206 subjects
n=4 Participants
|
108 subjects
n=21 Participants
|
835 subjects
n=8 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
38 subjects
n=5 Participants
|
27 subjects
n=7 Participants
|
13 subjects
n=5 Participants
|
33 subjects
n=4 Participants
|
9 subjects
n=21 Participants
|
120 subjects
n=8 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
13 subjects
n=5 Participants
|
16 subjects
n=7 Participants
|
8 subjects
n=5 Participants
|
17 subjects
n=4 Participants
|
10 subjects
n=21 Participants
|
64 subjects
n=8 Participants
|
|
Race/Ethnicity, Customized
Asian
|
8 subjects
n=5 Participants
|
8 subjects
n=7 Participants
|
1 subjects
n=5 Participants
|
6 subjects
n=4 Participants
|
3 subjects
n=21 Participants
|
26 subjects
n=8 Participants
|
|
Race/Ethnicity, Customized
Other
|
8 subjects
n=5 Participants
|
4 subjects
n=7 Participants
|
5 subjects
n=5 Participants
|
6 subjects
n=4 Participants
|
4 subjects
n=21 Participants
|
27 subjects
n=8 Participants
|
|
Body Mass Index
<18.5 kilogram per meter² (kg/m²)
|
0 subjects
n=5 Participants
|
0 subjects
n=7 Participants
|
0 subjects
n=5 Participants
|
0 subjects
n=4 Participants
|
0 subjects
n=21 Participants
|
0 subjects
n=8 Participants
|
|
Body Mass Index
18.5 kg/m² to <25 kg/m²
|
10 subjects
n=5 Participants
|
11 subjects
n=7 Participants
|
9 subjects
n=5 Participants
|
15 subjects
n=4 Participants
|
16 subjects
n=21 Participants
|
61 subjects
n=8 Participants
|
|
Body Mass Index
25 kg/m² to <30 kg/m²
|
85 subjects
n=5 Participants
|
81 subjects
n=7 Participants
|
42 subjects
n=5 Participants
|
91 subjects
n=4 Participants
|
48 subjects
n=21 Participants
|
347 subjects
n=8 Participants
|
|
Body Mass Index
≥30 kg/m²
|
172 subjects
n=5 Participants
|
176 subjects
n=7 Participants
|
83 subjects
n=5 Participants
|
161 subjects
n=4 Participants
|
70 subjects
n=21 Participants
|
662 subjects
n=8 Participants
|
|
Body Mass Index
missing
|
0 subjects
n=5 Participants
|
1 subjects
n=7 Participants
|
0 subjects
n=5 Participants
|
1 subjects
n=4 Participants
|
0 subjects
n=21 Participants
|
2 subjects
n=8 Participants
|
|
Presence of a Primary PalpableTophus
Yes
|
48 subjects
n=5 Participants
|
53 subjects
n=7 Participants
|
25 subjects
n=5 Participants
|
64 subjects
n=4 Participants
|
29 subjects
n=21 Participants
|
219 subjects
n=8 Participants
|
|
Presence of a Primary PalpableTophus
No, but other tophi present
|
0 subjects
n=5 Participants
|
3 subjects
n=7 Participants
|
1 subjects
n=5 Participants
|
1 subjects
n=4 Participants
|
1 subjects
n=21 Participants
|
6 subjects
n=8 Participants
|
|
Presence of a Primary PalpableTophus
No, and no other tophi present
|
219 subjects
n=5 Participants
|
213 subjects
n=7 Participants
|
108 subjects
n=5 Participants
|
203 subjects
n=4 Participants
|
104 subjects
n=21 Participants
|
847 subjects
n=8 Participants
|
|
Serum Creatinine
≤1.5 milligram per deciliter (mg/dL)
|
258 subjects
n=5 Participants
|
258 subjects
n=7 Participants
|
129 subjects
n=5 Participants
|
258 subjects
n=4 Participants
|
129 subjects
n=21 Participants
|
1032 subjects
n=8 Participants
|
|
Serum Creatinine
>1.5 mg/dL
|
9 subjects
n=5 Participants
|
11 subjects
n=7 Participants
|
5 subjects
n=5 Participants
|
10 subjects
n=4 Participants
|
5 subjects
n=21 Participants
|
40 subjects
n=8 Participants
|
PRIMARY outcome
Timeframe: Last 3 visits (any last 3 visits up to week 28)Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug and had a baseline serum urate ≥8.0 mg/dL. If subject prematurely discontinued from study before at least 3 serum urate levels were obtained, subject was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used.
Each subject's serum urate at the last 3 visits determined the subject's response for the primary efficacy variable. A subject who prematurely discontinued without least 3 postbaseline serum urate levels was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used. The last 3 visits used may have differed for each subject.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=262 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=269 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=134 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=268 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=134 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
|
48 Percentage of subjects
|
65 Percentage of subjects
|
69 Percentage of subjects
|
22 Percentage of subjects
|
0 Percentage of subjects
|
SECONDARY outcome
Timeframe: Week 28Population: Analysis was performed on intend to treat (ITT) subjects, which were defined as all randomized subjects who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.
Serum urate values were obtained at the Week 28 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Week 28 visit was summarized.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=161 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=188 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=83 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=208 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=99 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
|
76 Percentage of subjects
|
87 Percentage of subjects
|
94 Percentage of subjects
|
41 Percentage of subjects
|
1 Percentage of subjects
|
SECONDARY outcome
Timeframe: Final Visit (up to 28 weeks).Population: Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.
The percentage of subjects whose serum urate was \<6.0 mg/dL at the final visit was summarized. The final visit was the last visit at which a serum urate value was collected and may have differed by subject.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=253 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=265 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=126 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=263 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=127 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
|
72 Percentage of subjects
|
79 Percentage of subjects
|
92 Percentage of subjects
|
39 Percentage of subjects
|
1 Percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline and Week 28Population: Analysis was performed on the ITT subjects, which were defined as all randomized subjects. who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.
Serum urate values were obtained at the Week 28 visit. The percent change in serum urate was calculated as \[(Week 28 - baseline levels)/baseline\]\*100 and summarized.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=161 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=188 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=83 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=208 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=99 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Serum Urate Levels at Week 28.
|
-47.6 Percent change
Standard Deviation 15.86
|
-54.9 Percent change
Standard Deviation 14.97
|
-67.8 Percent change
Standard Deviation 18.18
|
-34.4 Percent change
Standard Deviation 14.21
|
-3.6 Percent change
Standard Deviation 13.85
|
SECONDARY outcome
Timeframe: Baseline and Final Visit (up to 28 weeks)Population: Analysis was performed on the ITT subjects, which were defined as all randomized subjects. who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.
The percent change in serum urate from baseline to the Final visit was summarized. The percent change in serum urate was calculated as \[(Final visit - baseline levels)/baseline\]\*100. The final visit was the last visit at which a serum urate value was collected. The timing of the final visit may have differed for each subject.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=253 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=265 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=126 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=263 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=127 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percent Change From Baseline in Serum Urate Levels at Final Visit
|
-45.2 Percent change
Standard Deviation 18.16
|
-51.9 Percent change
Standard Deviation 17.99
|
-66.3 Percent change
Standard Deviation 20.62
|
-33.7 Percent change
Standard Deviation 14.75
|
-3.0 Percent change
Standard Deviation 13.28
|
SECONDARY outcome
Timeframe: Baseline and Week 28Population: Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug, who had a baseline serum urate ≥8.0 mg/dL, and who had a palpable primary tophus measured at baseline. Missing data were not imputed.
The percent change from baseline in primary tophus size as determined by physical measurement was calculated as \[(Week 28 - baseline sizes)/baseline\]\*100 for the subset of subjects with a primary palpable tophus at the Screening Visit. If the primary tophus was no longer palpable at the Week 28 visit, the size was assumed to be zero.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=26 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=35 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=14 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=46 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=21 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percent Change in Primary Tophus Size at Week 28, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit.
|
-45.6 percent change from baseline
Interval -85.9 to 3.0
|
-54.2 percent change from baseline
Interval -100.0 to -16.7
|
-53.2 percent change from baseline
Interval -77.8 to -22.1
|
-31.5 percent change from baseline
Interval -95.0 to 5.6
|
-52.0 percent change from baseline
Interval -62.5 to -21.4
|
SECONDARY outcome
Timeframe: Baseline and Final Visit (up to 28 weeks)Population: Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug, who had a baseline serum urate ≥8.0 mg/dL, and who had a palpable primary tophus measured at baseline. Missing data were not imputed.
Percent change in primary tophus size was calculated as \[(Final Visit - baseline sizes)/baseline\]\*100 for the subset of subjects with a primary palpable tophus at Screening. If tophus was not palpable at Final visit, the size was assumed to be 0. The timing of the final visit may have differed for each subject.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=42 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=50 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=24 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=61 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=26 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percent Change in Primary Tophus Size at Final Visit, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit.
|
-33.8 percent change from baseline
Interval -85.4 to 0.0
|
-42.4 percent change from baseline
Interval -90.3 to 0.0
|
-47.0 percent change from baseline
Interval -80.0 to -13.8
|
-22.6 percent change from baseline
Interval -66.7 to 0.0
|
-40.3 percent change from baseline
Interval -62.5 to -16.7
|
SECONDARY outcome
Timeframe: Baseline and Week 28Population: Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug,had a baseline serum urate ≥8.0 mg/dL, and had palpable tophi at the screening visit. Missing data were not imputed.
Change from baseline at Week 28 in the total number of tophi per subject was calculated for the subset of subjects with palpable tophi at the Screening Visit. If the tophi were not palpable at the Week 28 visit, the total count was assumed to be 0.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=28 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=38 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=16 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=47 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=22 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
|
0.0 number of tophi
Interval -0.5 to 0.0
|
0.0 number of tophi
Interval -2.0 to 0.0
|
0.0 number of tophi
Interval -1.0 to 0.0
|
0.0 number of tophi
Interval -1.0 to 0.0
|
0.0 number of tophi
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Final Visit (up to 28 weeks)Population: Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug,had a baseline serum urate ≥8.0 mg/dL, and had palpable tophi at the screening visit. Missing data were not imputed.
Change in number of tophi/subject was calculated for the subset of subjects with palpable tophi at the Screening. If the tophi were not palpable at the Final Visit, total count was assumed to be 0. The timing of the final visit may have differed for each subject.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=42 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=53 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=25 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=62 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=27 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
|
0.0 number of tophi
Interval 0.0 to 0.0
|
0.0 number of tophi
Interval -1.0 to 0.0
|
0.0 number of tophi
Interval -1.0 to 0.0
|
0.0 number of tophi
Interval 0.0 to 0.0
|
0.0 number of tophi
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Weeks 8 through 28Population: Analysis was performed on the ITT subjects who had at least one dose of study drug between Weeks 8 and 28.
Percentage of subjects requiring treatment for a gout flare between Weeks 8 and 28 of the double-blind treatment period was summarized. A subject who reported more than 1 gout flare during this period was counted only once.
Outcome measures
| Measure |
Febuxostat 80 mg QD
n=223 Participants
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=240 Participants
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=106 Participants
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=237 Participants
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=119 Participants
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
|
55 percentage of subjects
|
54 percentage of subjects
|
57 percentage of subjects
|
46 percentage of subjects
|
52 percentage of subjects
|
Adverse Events
Febuxostat 80 mg QD
Serious events: 11 serious events
Other events: 122 other events
Deaths: 0 deaths
Febuxostat 120 mg QD
Serious events: 9 serious events
Other events: 123 other events
Deaths: 0 deaths
Febuxostat 240 mg QD
Serious events: 5 serious events
Other events: 72 other events
Deaths: 0 deaths
Allopurinol QD
Serious events: 7 serious events
Other events: 133 other events
Deaths: 0 deaths
Placebo QD
Serious events: 2 serious events
Other events: 61 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Febuxostat 80 mg QD
n=267 participants at risk
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=269 participants at risk
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=134 participants at risk
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=268 participants at risk
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=134 participants at risk
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemias not elsewhere classified (NEC)
|
0.00%
0/267
|
0.37%
1/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Cardiac disorders
Cardiomyopathies
|
0.00%
0/267
|
0.37%
1/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Cardiac disorders
Coronary Artery Disorders NEC
|
0.75%
2/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.75%
1/134
|
|
Cardiac disorders
Ischaemic Coronary Artery Disorders
|
0.37%
1/267
|
0.74%
2/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Cardiac disorders
Supraventricular Arrhythmias
|
0.00%
0/267
|
0.37%
1/269
|
0.75%
1/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Gastrointestinal disorders
Abdominal Hernias, Site Unspecified
|
0.00%
0/267
|
0.00%
0/269
|
0.75%
1/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Gastrointestinal disorders
Duodenal and Small Intestinal Stenosis and Obstruction
|
0.00%
0/267
|
0.00%
0/269
|
0.75%
1/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Gastrointestinal disorders
Gastrointestinal & Abdominal Pain, Excluding Oral,Throat
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Gastrointestinal disorders
Intestinal Ulcers and Perforation NEC
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.37%
1/268
|
0.00%
0/134
|
|
Gastrointestinal disorders
Nausea and Vomiting Symptoms
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
General disorders
Pain and Discomfort NEC
|
0.75%
2/267
|
0.37%
1/269
|
0.00%
0/134
|
0.37%
1/268
|
0.00%
0/134
|
|
Hepatobiliary disorders
Cholecystitis and Cholelithiasis
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.37%
1/268
|
0.00%
0/134
|
|
Infections and infestations
Abdominal and Gastrointestinal Infections
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.37%
1/268
|
0.00%
0/134
|
|
Injury, poisoning and procedural complications
Device Failure and Malfunction
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Injury, poisoning and procedural complications
Device Related Complications
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.75%
1/134
|
|
Injury, poisoning and procedural complications
Non-Site Specific Procedural Complications
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.75%
1/134
|
|
Metabolism and nutrition disorders
Hypoglycaemic Conditions NEC
|
0.00%
0/267
|
0.37%
1/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Metabolism and nutrition disorders
Total Fluid Volume Decreased
|
0.00%
0/267
|
0.00%
0/269
|
0.75%
1/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness Conditions
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Musculoskeletal and connective tissue disorders
Osteoarthropathies
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.37%
1/268
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colonic Neoplasms Malignant
|
0.00%
0/267
|
0.37%
1/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endocrine Neoplasms Benign NEC
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.37%
1/268
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endocrine Neoplasms Malignant and Unspecified NEC
|
0.00%
0/267
|
0.37%
1/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's Disease NEC
|
0.00%
0/267
|
0.00%
0/269
|
0.00%
0/134
|
0.37%
1/268
|
0.00%
0/134
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic Neoplasms Malignant
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Nervous system disorders
Seizures and Seizure Disorders NEC
|
0.00%
0/267
|
0.00%
0/269
|
0.75%
1/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Nervous system disorders
Transient Cerebrovascular Events
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Renal and urinary disorders
Renal Failure and Impairment
|
0.00%
0/267
|
0.00%
0/269
|
0.75%
1/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm and Obstruction
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
|
Respiratory, thoracic and mediastinal disorders
Lower Respiratory Tract Signs and Symptoms
|
0.37%
1/267
|
0.00%
0/269
|
0.00%
0/134
|
0.00%
0/268
|
0.00%
0/134
|
Other adverse events
| Measure |
Febuxostat 80 mg QD
n=267 participants at risk
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 120 mg QD
n=269 participants at risk
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
|
Febuxostat 240 mg QD
n=134 participants at risk
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
|
Allopurinol QD
n=268 participants at risk
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine \>1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
|
Placebo QD
n=134 participants at risk
Placebo, orally, once daily for up to 28 weeks.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea (Excluding Infective)
|
6.0%
16/267
|
7.1%
19/269
|
13.4%
18/134
|
6.3%
17/268
|
8.2%
11/134
|
|
Gastrointestinal disorders
Gastrointestinal & Abdominal Pains, Excluding Oral,Throat
|
1.9%
5/267
|
2.6%
7/269
|
6.0%
8/134
|
2.2%
6/268
|
2.2%
3/134
|
|
Gastrointestinal disorders
Nausea and Vomiting Symptoms
|
4.1%
11/267
|
3.7%
10/269
|
6.0%
8/134
|
2.2%
6/268
|
3.7%
5/134
|
|
Infections and infestations
Influenza Viral Infections
|
4.1%
11/267
|
4.8%
13/269
|
5.2%
7/134
|
3.7%
10/268
|
4.5%
6/134
|
|
Infections and infestations
Upper Respiratory Tract Infections
|
14.6%
39/267
|
19.3%
52/269
|
20.1%
27/134
|
19.4%
52/268
|
15.7%
21/134
|
|
Injury, poisoning and procedural complications
Non-Site Specific Injuries NEC
|
4.1%
11/267
|
3.3%
9/269
|
6.7%
9/134
|
3.0%
8/268
|
2.2%
3/134
|
|
Investigations
Liver Function Analyses
|
6.4%
17/267
|
3.7%
10/269
|
4.5%
6/134
|
5.6%
15/268
|
2.2%
3/134
|
|
Musculoskeletal and connective tissue disorders
Joint Related Signs and Symptoms
|
6.4%
17/267
|
8.6%
23/269
|
5.2%
7/134
|
7.5%
20/268
|
5.2%
7/134
|
|
Musculoskeletal and connective tissue disorders
Muscle Related Signs and Symptoms NEC
|
1.1%
3/267
|
0.74%
2/269
|
1.5%
2/134
|
0.37%
1/268
|
5.2%
7/134
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and Connective Tissues Signs and Symptoms NEC
|
8.6%
23/267
|
8.9%
24/269
|
10.4%
14/134
|
10.1%
27/268
|
9.7%
13/134
|
|
Nervous system disorders
Headache NEC
|
5.2%
14/267
|
5.2%
14/269
|
9.0%
12/134
|
7.1%
19/268
|
5.2%
7/134
|
|
Nervous system disorders
Neurological Signs and Symptoms NEC
|
1.9%
5/267
|
1.9%
5/269
|
6.7%
9/134
|
2.2%
6/268
|
1.5%
2/134
|
|
Vascular disorders
Vascular Hypertensive Disorders NEC
|
4.9%
13/267
|
2.2%
6/269
|
4.5%
6/134
|
1.1%
3/268
|
6.0%
8/134
|
Additional Information
Sr. VP, Clinical Science
Takeda Global Research & Development Center, Inc.
Phone: 800-778-2860
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER