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Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects. (APEX)

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ClinicalTrials.gov Identifier: NCT00174915
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : July 16, 2009
Last Update Posted : February 2, 2012
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Gout
Interventions Drug: Febuxostat
Drug: Allopurinol
Drug: Placebo
Enrollment 1072

Recruitment Details Subjects were enrolled at 167 investigative sites in the United States from 21 February 2003 to 07 April 2004.
Pre-assignment Details Subjects currently receiving urate-lowering therapy discontinued those urate-lowering therapies and initiated prophylactic medications before enrollment in once daily (QD) treatment groups.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description Febuxostat 80 mg, orally, once daily for up to 28 weeks. Febuxostat 120 mg, orally, once daily for up to 28 weeks. Febuxostat 240 mg, orally, once daily for up to 28 weeks. 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, orally, once daily for up to 28 weeks.
Period Title: Overall Study
Started 267 269 134 268 134
Completed 174 200 86 211 101
Not Completed 93 69 48 57 33
Reason Not Completed
Lost to Follow-up             19             17             9             17             10
Adverse Event             18             16             11             18             5
Personal Reason(s)             16             16             9             9             9
Other             15             8             6             5             3
Gout Flare             13             6             8             1             0
Protocol Violation             6             3             3             6             3
Therapeutic Failure             6             3             2             1             3
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD Total
Hide Arm/Group Description Febuxostat 80 mg, orally, once daily for up to 28 weeks. Febuxostat 120 mg, orally, once daily for up to 28 weeks. Febuxostat 240 mg, orally, once daily for up to 28 weeks. 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, orally, once daily for up to 28 weeks. Total of all reporting groups
Overall Number of Baseline Participants 267 269 134 268 134 1072
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 267 participants 269 participants 134 participants 268 participants 134 participants 1072 participants
<45 years 82 79 33 82 36 312
45 years to <65 years 146 154 71 147 79 597
≥65 years 39 36 30 39 19 163
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 267 participants 269 participants 134 participants 268 participants 134 participants 1072 participants
50.6  (12.24) 51.2  (11.57) 54.3  (12.83) 51.8  (12.25) 51.5  (12.18) 51.6  (12.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 267 participants 269 participants 134 participants 268 participants 134 participants 1072 participants
Female
16
   6.0%
13
   4.8%
8
   6.0%
19
   7.1%
11
   8.2%
67
   6.3%
Male
251
  94.0%
256
  95.2%
126
  94.0%
249
  92.9%
123
  91.8%
1005
  93.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 267 participants 269 participants 134 participants 268 participants 134 participants 1072 participants
White 200 214 107 206 108 835
Black or African American 38 27 13 33 9 120
Hispanic 13 16 8 17 10 64
Asian 8 8 1 6 3 26
Other 8 4 5 6 4 27
Body Mass Index  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 267 participants 269 participants 134 participants 268 participants 134 participants 1072 participants
<18.5 kilogram per meter² (kg/m²) 0 0 0 0 0 0
18.5 kg/m² to <25 kg/m² 10 11 9 15 16 61
25 kg/m² to <30 kg/m² 85 81 42 91 48 347
≥30 kg/m² 172 176 83 161 70 662
missing 0 1 0 1 0 2
Presence of a Primary PalpableTophus  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 267 participants 269 participants 134 participants 268 participants 134 participants 1072 participants
Yes 48 53 25 64 29 219
No, but other tophi present 0 3 1 1 1 6
No, and no other tophi present 219 213 108 203 104 847
Serum Creatinine  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 267 participants 269 participants 134 participants 268 participants 134 participants 1072 participants
≤1.5 milligram per deciliter (mg/dL) 258 258 129 258 129 1032
>1.5 mg/dL 9 11 5 10 5 40
1.Primary Outcome
Title Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Hide Description 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.
Time Frame Last 3 visits (any last 3 visits up to week 28)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 262 269 134 268 134
Measure Type: Number
Unit of Measure: Percentage of subjects
48 65 69 22 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The overall 0.05 level of significance for the multiple comparisons of each febuxostat dose to placebo was controlled using Hochberg's method. The p-value was statistically significant.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL versus [v.] >1.5 mg/dL).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The overall 0.05 level of significance for the multiple comparisons of each febuxostat dose to placebo was controlled using Hochberg's method. The p-value was statistically significant.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The overall 0.05 level of significance for the multiple comparisons of each febuxostat dose to placebo was controlled using Hochberg's method. The p-value was statistically significant.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority of febuxostat 80 mg to allopurinol was declared if the value of the lower bound of the 97.5% confidence interval is > -10%.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 25.7
Confidence Interval 97.5%
16.7 to 34.7
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority of febuxostat 120 mg to allopurinol was declared if the value of the lower bound of the 97.5% confidence interval is > -10%.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 42.7
Confidence Interval 97.5%
34.0 to 51.3
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Comparisons of each febuxostat dose to allopurinol were adjusted to control the overall 0.05 level of significance for superiority by using Hochberg's method. The p-value was statistically significant.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Comparisons of each febuxostat dose to allopurinol were adjusted to control the overall 0.05 level of significance for superiority by using Hochberg's method. The p-value was statistically significant.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.479
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
2.Secondary Outcome
Title Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Hide Description 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.
Time Frame Week 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 161 188 83 208 99
Measure Type: Number
Unit of Measure: Percentage of subjects
76 87 94 41 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
3.Secondary Outcome
Title Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Hide Description 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.
Time Frame Final Visit (up to 28 weeks).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 253 265 126 263 127
Measure Type: Number
Unit of Measure: Percentage of subjects
72 79 92 39 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
4.Secondary Outcome
Title Percent Change From Baseline in Serum Urate Levels at Week 28.
Hide Description 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.
Time Frame Baseline and Week 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 161 188 83 208 99
Mean (Standard Deviation)
Unit of Measure: Percent change
-47.6  (15.86) -54.9  (14.97) -67.8  (18.18) -34.4  (14.21) -3.6  (13.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in Serum Urate Levels at Final Visit
Hide Description 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.
Time Frame Baseline and Final Visit (up to 28 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 253 265 126 263 127
Mean (Standard Deviation)
Unit of Measure: Percent change
-45.2  (18.16) -51.9  (17.99) -66.3  (20.62) -33.7  (14.75) -3.0  (13.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.
Method ANOVA
Comments [Not Specified]
6.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame Baseline and Week 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 26 35 14 46 21
Median (Inter-Quartile Range)
Unit of Measure: percent change from baseline
-45.6
(-85.9 to 3.0)
-54.2
(-100.0 to -16.7)
-53.2
(-77.8 to -22.1)
-31.5
(-95.0 to 5.6)
-52.0
(-62.5 to -21.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.789
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.320
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.381
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.809
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.154
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.247
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.415
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.649
Comments Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.807
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.844
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame Baseline and Final Visit (up to 28 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 42 50 24 61 26
Median (Inter-Quartile Range)
Unit of Measure: percent change from baseline
-33.8
(-85.4 to 0.0)
-42.4
(-90.3 to 0.0)
-47.0
(-80.0 to -13.8)
-22.6
(-66.7 to 0)
-40.3
(-62.5 to -16.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.699
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.822
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.579
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.679
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.104
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.560
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.309
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.759
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.385
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Hide Description 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.
Time Frame Baseline and Week 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 28 38 16 47 22
Median (Inter-Quartile Range)
Unit of Measure: number of tophi
0.0
(-0.5 to 0.0)
0.0
(-2.0 to 0.0)
0.0
(-1.0 to 0.0)
0.0
(-1.0 to 0.0)
0.0
(0.0 to 0.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.949
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.577
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.598
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.062
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.969
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.056
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.659
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.197
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.521
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Hide Description 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.
Time Frame Final Visit (up to 28 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 42 53 25 62 27
Median (Inter-Quartile Range)
Unit of Measure: number of tophi
0.0
(0.0 to 0.0)
0.0
(-1.0 to 0.0)
0.0
(-1.0 to 0.0)
0.0
(0.0 to 0.0)
0.0
(0.0 to 0.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.683
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.442
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.990
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.662
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.705
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.337
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.643
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Hide Description 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.
Time Frame Weeks 8 through 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT subjects who had at least one dose of study drug between Weeks 8 and 28.
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description:
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
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, orally, once daily for up to 28 weeks.
Overall Number of Participants Analyzed 223 240 106 237 119
Measure Type: Number
Unit of Measure: percentage of subjects
55 54 57 46 52
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.645
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.756
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.428
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.076
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons..
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL)
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.106
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Febuxostat 240 mg QD, Allopurinol QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 120 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.837
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.749
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Febuxostat 120 mg QD, Febuxostat 240 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.581
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Allopurinol QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.311
Comments Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Hide Arm/Group Description Febuxostat 80 mg, orally, once daily for up to 28 weeks. Febuxostat 120 mg, orally, once daily for up to 28 weeks. Febuxostat 240 mg, orally, once daily for up to 28 weeks. 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, orally, once daily for up to 28 weeks.
All-Cause Mortality
Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/267 (4.12%)   9/269 (3.35%)   5/134 (3.73%)   7/268 (2.61%)   2/134 (1.49%) 
Blood and lymphatic system disorders           
Anaemias not elsewhere classified (NEC)  1  0/267 (0.00%)  1/269 (0.37%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Cardiac disorders           
Cardiomyopathies  1  0/267 (0.00%)  1/269 (0.37%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Coronary Artery Disorders NEC  1  2/267 (0.75%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  1/134 (0.75%) 
Ischaemic Coronary Artery Disorders  1  1/267 (0.37%)  2/269 (0.74%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Supraventricular Arrhythmias  1  0/267 (0.00%)  1/269 (0.37%)  1/134 (0.75%)  0/268 (0.00%)  0/134 (0.00%) 
Gastrointestinal disorders           
Abdominal Hernias, Site Unspecified  1  0/267 (0.00%)  0/269 (0.00%)  1/134 (0.75%)  0/268 (0.00%)  0/134 (0.00%) 
Duodenal and Small Intestinal Stenosis and Obstruction  1  0/267 (0.00%)  0/269 (0.00%)  1/134 (0.75%)  0/268 (0.00%)  0/134 (0.00%) 
Gastrointestinal & Abdominal Pain, Excluding Oral,Throat  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Intestinal Ulcers and Perforation NEC  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  1/268 (0.37%)  0/134 (0.00%) 
Nausea and Vomiting Symptoms  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
General disorders           
Pain and Discomfort NEC  1  2/267 (0.75%)  1/269 (0.37%)  0/134 (0.00%)  1/268 (0.37%)  0/134 (0.00%) 
Hepatobiliary disorders           
Cholecystitis and Cholelithiasis  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  1/268 (0.37%)  0/134 (0.00%) 
Infections and infestations           
Abdominal and Gastrointestinal Infections  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  1/268 (0.37%)  0/134 (0.00%) 
Injury, poisoning and procedural complications           
Device Failure and Malfunction  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Device Related Complications  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  1/134 (0.75%) 
Non-Site Specific Procedural Complications  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  1/134 (0.75%) 
Metabolism and nutrition disorders           
Hypoglycaemic Conditions NEC  1  0/267 (0.00%)  1/269 (0.37%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Total Fluid Volume Decreased  1  0/267 (0.00%)  0/269 (0.00%)  1/134 (0.75%)  0/268 (0.00%)  0/134 (0.00%) 
Musculoskeletal and connective tissue disorders           
Muscle Weakness Conditions  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Osteoarthropathies  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  1/268 (0.37%)  0/134 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Colonic Neoplasms Malignant  1  0/267 (0.00%)  1/269 (0.37%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Endocrine Neoplasms Benign NEC  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  1/268 (0.37%)  0/134 (0.00%) 
Endocrine Neoplasms Malignant and Unspecified NEC  1  0/267 (0.00%)  1/269 (0.37%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Hodgkin's Disease NEC  1  0/267 (0.00%)  0/269 (0.00%)  0/134 (0.00%)  1/268 (0.37%)  0/134 (0.00%) 
Prostatic Neoplasms Malignant  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Nervous system disorders           
Seizures and Seizure Disorders NEC  1  0/267 (0.00%)  0/269 (0.00%)  1/134 (0.75%)  0/268 (0.00%)  0/134 (0.00%) 
Transient Cerebrovascular Events  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Renal and urinary disorders           
Renal Failure and Impairment  1  0/267 (0.00%)  0/269 (0.00%)  1/134 (0.75%)  0/268 (0.00%)  0/134 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Bronchospasm and Obstruction  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Lower Respiratory Tract Signs and Symptoms  1  1/267 (0.37%)  0/269 (0.00%)  0/134 (0.00%)  0/268 (0.00%)  0/134 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 7.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   122/267 (45.69%)   123/269 (45.72%)   72/134 (53.73%)   133/268 (49.63%)   61/134 (45.52%) 
Gastrointestinal disorders           
Diarrhoea (Excluding Infective)  1  16/267 (5.99%)  19/269 (7.06%)  18/134 (13.43%)  17/268 (6.34%)  11/134 (8.21%) 
Gastrointestinal & Abdominal Pains, Excluding Oral,Throat  1  5/267 (1.87%)  7/269 (2.60%)  8/134 (5.97%)  6/268 (2.24%)  3/134 (2.24%) 
Nausea and Vomiting Symptoms  1  11/267 (4.12%)  10/269 (3.72%)  8/134 (5.97%)  6/268 (2.24%)  5/134 (3.73%) 
Infections and infestations           
Influenza Viral Infections  1  11/267 (4.12%)  13/269 (4.83%)  7/134 (5.22%)  10/268 (3.73%)  6/134 (4.48%) 
Upper Respiratory Tract Infections  1  39/267 (14.61%)  52/269 (19.33%)  27/134 (20.15%)  52/268 (19.40%)  21/134 (15.67%) 
Injury, poisoning and procedural complications           
Non-Site Specific Injuries NEC  1  11/267 (4.12%)  9/269 (3.35%)  9/134 (6.72%)  8/268 (2.99%)  3/134 (2.24%) 
Investigations           
Liver Function Analyses  1  17/267 (6.37%)  10/269 (3.72%)  6/134 (4.48%)  15/268 (5.60%)  3/134 (2.24%) 
Musculoskeletal and connective tissue disorders           
Joint Related Signs and Symptoms  1  17/267 (6.37%)  23/269 (8.55%)  7/134 (5.22%)  20/268 (7.46%)  7/134 (5.22%) 
Muscle Related Signs and Symptoms NEC  1  3/267 (1.12%)  2/269 (0.74%)  2/134 (1.49%)  1/268 (0.37%)  7/134 (5.22%) 
Musculoskeletal and Connective Tissues Signs and Symptoms NEC  1  23/267 (8.61%)  24/269 (8.92%)  14/134 (10.45%)  27/268 (10.07%)  13/134 (9.70%) 
Nervous system disorders           
Headache NEC  1  14/267 (5.24%)  14/269 (5.20%)  12/134 (8.96%)  19/268 (7.09%)  7/134 (5.22%) 
Neurological Signs and Symptoms NEC  1  5/267 (1.87%)  5/269 (1.86%)  9/134 (6.72%)  6/268 (2.24%)  2/134 (1.49%) 
Vascular disorders           
Vascular Hypertensive Disorders NEC  1  13/267 (4.87%)  6/269 (2.23%)  6/134 (4.48%)  3/268 (1.12%)  8/134 (5.97%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 7.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research & Development Center, Inc.
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00174915     History of Changes
Other Study ID Numbers: C02-009
U1111-1113-9740 ( Registry Identifier: WHO )
First Submitted: September 9, 2005
First Posted: September 15, 2005
Results First Submitted: March 12, 2009
Results First Posted: July 16, 2009
Last Update Posted: February 2, 2012