Gout
Conditions
Keywords
Uric Acid, gout, xanthine oxidase, febuxostat, tophi
Brief summary
The purpose of this study is to compare febuxostat, allopurinol and placebo, once daily (QD), in subjects with gout.
Detailed description
A Phase 3 Study comparing 80 mg, 120 mg or 240 mg of febuxostat, allopurinol (300 mg for those with normal renal function and 100 mg for those with impaired renal function) and placebo administered once daily in subjects with gout. Subjects will receive treatment for 28 weeks.
Interventions
DRUGFebuxostat
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
DRUGAllopurinol
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.
DRUGPlacebo
Placebo, orally, once daily for up to 28 weeks.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Hyperuricemia (serum urate ≥8.0 mg/dL and gout by American Rheumatism Association Criteria * Renal function defined as a serum creatinine level of \< 2.0 mg/dL and creatinine clearance of \> 20 milliliters per minute (mL/min) by Cockroft and Gault formula.
Exclusion criteria
* History of xanthinuria * Intolerance to allopurinol * Presence of renal calculi, * Alcohol intake of ≥ 14 drinks/week * Clinically significant medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). | Last 3 visits (any last 3 visits up to week 28) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit | Final Visit (up to 28 weeks). | 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. |
| Percent Change From Baseline in Serum Urate Levels at Week 28. | Baseline and Week 28 | 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. |
| Percent Change From Baseline in Serum Urate Levels at Final Visit | Baseline and Final Visit (up to 28 weeks) | 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. |
| 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. | Baseline and Week 28 | 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. |
| Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 | Week 28 | 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. |
| Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit. | Baseline and Week 28 | 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. |
| Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit | Final Visit (up to 28 weeks) | 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. |
| Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. | Weeks 8 through 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. |
| 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. | Baseline and Final Visit (up to 28 weeks) | 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. |
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks. | 267 |
| Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks. | 269 |
| Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks. | 134 |
| 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. | 268 |
| Placebo QD Placebo, orally, once daily for up to 28 weeks. | 134 |
| Total | 1,072 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 18 | 16 | 11 | 18 | 5 |
| Overall Study | Gout Flare | 13 | 6 | 8 | 1 | 0 |
| Overall Study | Lost to Follow-up | 19 | 17 | 9 | 17 | 10 |
| Overall Study | Other | 15 | 8 | 6 | 5 | 3 |
| Overall Study | Personal Reason(s) | 16 | 16 | 9 | 9 | 9 |
| Overall Study | Protocol Violation | 6 | 3 | 3 | 6 | 3 |
| Overall Study | Therapeutic Failure | 6 | 3 | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo QD | Allopurinol QD | Febuxostat 240 mg QD | Febuxostat 120 mg QD | Febuxostat 80 mg QD |
|---|---|---|---|---|---|---|
| Age Continuous | 51.6 years STANDARD_DEVIATION 12.17 | 51.5 years STANDARD_DEVIATION 12.18 | 51.8 years STANDARD_DEVIATION 12.25 | 54.3 years STANDARD_DEVIATION 12.83 | 51.2 years STANDARD_DEVIATION 11.57 | 50.6 years STANDARD_DEVIATION 12.24 |
| Age, Customized <45 years | 312 subjects | 36 subjects | 82 subjects | 33 subjects | 79 subjects | 82 subjects |
| Age, Customized 45 years to <65 years | 597 subjects | 79 subjects | 147 subjects | 71 subjects | 154 subjects | 146 subjects |
| Age, Customized ≥65 years | 163 subjects | 19 subjects | 39 subjects | 30 subjects | 36 subjects | 39 subjects |
| Body Mass Index 18.5 kg/m² to <25 kg/m² | 61 subjects | 16 subjects | 15 subjects | 9 subjects | 11 subjects | 10 subjects |
| Body Mass Index <18.5 kilogram per meter² (kg/m²) | 0 subjects | 0 subjects | 0 subjects | 0 subjects | 0 subjects | 0 subjects |
| Body Mass Index 25 kg/m² to <30 kg/m² | 347 subjects | 48 subjects | 91 subjects | 42 subjects | 81 subjects | 85 subjects |
| Body Mass Index ≥30 kg/m² | 662 subjects | 70 subjects | 161 subjects | 83 subjects | 176 subjects | 172 subjects |
| Body Mass Index missing | 2 subjects | 0 subjects | 1 subjects | 0 subjects | 1 subjects | 0 subjects |
| Presence of a Primary PalpableTophus No, and no other tophi present | 847 subjects | 104 subjects | 203 subjects | 108 subjects | 213 subjects | 219 subjects |
| Presence of a Primary PalpableTophus No, but other tophi present | 6 subjects | 1 subjects | 1 subjects | 1 subjects | 3 subjects | 0 subjects |
| Presence of a Primary PalpableTophus Yes | 219 subjects | 29 subjects | 64 subjects | 25 subjects | 53 subjects | 48 subjects |
| Race/Ethnicity, Customized Asian | 26 subjects | 3 subjects | 6 subjects | 1 subjects | 8 subjects | 8 subjects |
| Race/Ethnicity, Customized Black or African American | 120 subjects | 9 subjects | 33 subjects | 13 subjects | 27 subjects | 38 subjects |
| Race/Ethnicity, Customized Hispanic | 64 subjects | 10 subjects | 17 subjects | 8 subjects | 16 subjects | 13 subjects |
| Race/Ethnicity, Customized Other | 27 subjects | 4 subjects | 6 subjects | 5 subjects | 4 subjects | 8 subjects |
| Race/Ethnicity, Customized White | 835 subjects | 108 subjects | 206 subjects | 107 subjects | 214 subjects | 200 subjects |
| Serum Creatinine >1.5 mg/dL | 40 subjects | 5 subjects | 10 subjects | 5 subjects | 11 subjects | 9 subjects |
| Serum Creatinine ≤1.5 milligram per deciliter (mg/dL) | 1032 subjects | 129 subjects | 258 subjects | 129 subjects | 258 subjects | 258 subjects |
| Sex: Female, Male Female | 67 Participants | 11 Participants | 19 Participants | 8 Participants | 13 Participants | 16 Participants |
| Sex: Female, Male Male | 1005 Participants | 123 Participants | 249 Participants | 126 Participants | 256 Participants | 251 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 122 / 267 | 123 / 269 | 72 / 134 | 133 / 268 | 61 / 134 |
| serious Total, serious adverse events | 11 / 267 | 9 / 269 | 5 / 134 | 7 / 268 | 2 / 134 |
Outcome results
Primary
Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
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)
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat 80 mg QD | Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). | 48 Percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). | 65 Percentage of subjects |
| Febuxostat 240 mg QD | Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). | 69 Percentage of subjects |
| Allopurinol QD | Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). | 22 Percentage of subjects |
| Placebo QD | Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). | 0 Percentage of subjects |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.479Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
97.5% CI: [16.7, 34.7]
97.5% CI: [34, 51.3]
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
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)
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | 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 |
| Febuxostat 120 mg QD | 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 |
| Febuxostat 240 mg QD | 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 |
| Allopurinol QD | 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 |
| Placebo QD | 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 |
p-value: 0.683Wilcoxon (Mann-Whitney)
p-value: 0.078Wilcoxon (Mann-Whitney)
p-value: 0.442Wilcoxon (Mann-Whitney)
p-value: 0.99Wilcoxon (Mann-Whitney)
p-value: 0.077Wilcoxon (Mann-Whitney)
p-value: 0.662Wilcoxon (Mann-Whitney)
p-value: 0.139Wilcoxon (Mann-Whitney)
p-value: 0.705Wilcoxon (Mann-Whitney)
p-value: 0.337Wilcoxon (Mann-Whitney)
p-value: 0.643Wilcoxon (Mann-Whitney)
Secondary
Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
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
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | 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 |
| Febuxostat 120 mg QD | 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 |
| Febuxostat 240 mg QD | 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 |
| Allopurinol QD | 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 |
| Placebo QD | 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 |
p-value: 0.949Wilcoxon (Mann-Whitney)
p-value: 0.05Wilcoxon (Mann-Whitney)
p-value: 0.577Wilcoxon (Mann-Whitney)
p-value: 0.598Wilcoxon (Mann-Whitney)
p-value: 0.062Wilcoxon (Mann-Whitney)
p-value: 0.969Wilcoxon (Mann-Whitney)
p-value: 0.056Wilcoxon (Mann-Whitney)
p-value: 0.659Wilcoxon (Mann-Whitney)
p-value: 0.197Wilcoxon (Mann-Whitney)
p-value: 0.521Wilcoxon (Mann-Whitney)
Secondary
Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
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
Population: Analysis was performed on the ITT subjects who had at least one dose of study drug between Weeks 8 and 28.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat 80 mg QD | Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. | 55 percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. | 54 percentage of subjects |
| Febuxostat 240 mg QD | Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. | 57 percentage of subjects |
| Allopurinol QD | Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. | 46 percentage of subjects |
| Placebo QD | Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. | 52 percentage of subjects |
p-value: 0.645Cochran-Mantel-Haenszel
p-value: 0.756Cochran-Mantel-Haenszel
p-value: 0.428Cochran-Mantel-Haenszel
p-value: 0.076Cochran-Mantel-Haenszel
p-value: 0.106Cochran-Mantel-Haenszel
p-value: 0.069Cochran-Mantel-Haenszel
p-value: 0.837Cochran-Mantel-Haenszel
p-value: 0.749Cochran-Mantel-Haenszel
p-value: 0.581Cochran-Mantel-Haenszel
p-value: 0.311Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
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).
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat 80 mg QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit | 72 Percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit | 79 Percentage of subjects |
| Febuxostat 240 mg QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit | 92 Percentage of subjects |
| Allopurinol QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit | 39 Percentage of subjects |
| Placebo QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit | 1 Percentage of subjects |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.074Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat 80 mg QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 | 76 Percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 | 87 Percentage of subjects |
| Febuxostat 240 mg QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 | 94 Percentage of subjects |
| Allopurinol QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 | 41 Percentage of subjects |
| Placebo QD | Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 | 1 Percentage of subjects |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.011Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.091Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Serum Urate Levels at Final Visit
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)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Febuxostat 80 mg QD | Percent Change From Baseline in Serum Urate Levels at Final Visit | -45.2 Percent change | Standard Deviation 18.16 |
| Febuxostat 120 mg QD | Percent Change From Baseline in Serum Urate Levels at Final Visit | -51.9 Percent change | Standard Deviation 17.99 |
| Febuxostat 240 mg QD | Percent Change From Baseline in Serum Urate Levels at Final Visit | -66.3 Percent change | Standard Deviation 20.62 |
| Allopurinol QD | Percent Change From Baseline in Serum Urate Levels at Final Visit | -33.7 Percent change | Standard Deviation 14.75 |
| Placebo QD | Percent Change From Baseline in Serum Urate Levels at Final Visit | -3.0 Percent change | Standard Deviation 13.28 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
Secondary
Percent Change From Baseline in Serum Urate Levels at Week 28.
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
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Febuxostat 80 mg QD | Percent Change From Baseline in Serum Urate Levels at Week 28. | -47.6 Percent change | Standard Deviation 15.86 |
| Febuxostat 120 mg QD | Percent Change From Baseline in Serum Urate Levels at Week 28. | -54.9 Percent change | Standard Deviation 14.97 |
| Febuxostat 240 mg QD | Percent Change From Baseline in Serum Urate Levels at Week 28. | -67.8 Percent change | Standard Deviation 18.18 |
| Allopurinol QD | Percent Change From Baseline in Serum Urate Levels at Week 28. | -34.4 Percent change | Standard Deviation 14.21 |
| Placebo QD | Percent Change From Baseline in Serum Urate Levels at Week 28. | -3.6 Percent change | Standard Deviation 13.85 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
Secondary
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.
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)
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | 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 |
| Febuxostat 120 mg QD | 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. | -42.4 percent change from baseline |
| Febuxostat 240 mg QD | 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. | -47.0 percent change from baseline |
| Allopurinol QD | 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. | -22.6 percent change from baseline |
| Placebo QD | 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. | -40.3 percent change from baseline |
p-value: 0.699Wilcoxon (Mann-Whitney)
p-value: 0.822Wilcoxon (Mann-Whitney)
p-value: 0.579Wilcoxon (Mann-Whitney)
p-value: 0.679Wilcoxon (Mann-Whitney)
p-value: 0.278Wilcoxon (Mann-Whitney)
p-value: 0.104Wilcoxon (Mann-Whitney)
p-value: 0.56Wilcoxon (Mann-Whitney)
p-value: 0.309Wilcoxon (Mann-Whitney)
p-value: 0.759Wilcoxon (Mann-Whitney)
p-value: 0.385Wilcoxon (Mann-Whitney)
Secondary
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.
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
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | 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 |
| Febuxostat 120 mg QD | 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. | -54.2 percent change from baseline |
| Febuxostat 240 mg QD | 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. | -53.2 percent change from baseline |
| Allopurinol QD | 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. | -31.5 percent change from baseline |
| Placebo QD | 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. | -52.0 percent change from baseline |
p-value: 0.789Wilcoxon (Mann-Whitney)
p-value: 0.32Wilcoxon (Mann-Whitney)
p-value: 0.381Wilcoxon (Mann-Whitney)
p-value: 0.809Wilcoxon (Mann-Whitney)
p-value: 0.154Wilcoxon (Mann-Whitney)
p-value: 0.247Wilcoxon (Mann-Whitney)
p-value: 0.415Wilcoxon (Mann-Whitney)
p-value: 0.649Wilcoxon (Mann-Whitney)
p-value: 0.807Wilcoxon (Mann-Whitney)
p-value: 0.844Wilcoxon (Mann-Whitney)