Gout
Conditions
Keywords
uric Acid, xanthine oxidase, tophi, Drug Therapy
Brief summary
The purpose of this study is to evaluate the safety and efficacy of febuxostat, once daily (QD), versus allopurinol in subjects with gout.
Detailed description
This was a randomized, controlled, double-blind study of 52 weeks duration. Subjects receiving prior urate-lowering therapy underwent a 2-week washout period prior to randomization. Subjects were then randomized to one of three treatment groups: febuxostat 80 milligram (mg), febuxostat 120 mg, or allopurinol 300 mg. Naproxen (250 mg twice daily) or colchicine (0.6 mg once daily) was provided for prophylaxis of acute gout flares during the washout period and the first 8 weeks of double-blind treatment.
Interventions
DRUGFebuxostat
Febuxostat 80 mg, orally, once daily for up to 52 weeks.
DRUGAllopurinol
Allopurinol 300 mg, capsules, orally, once daily for up to 52 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
* Meeting the preliminary criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout. * Serum uric acid ≥ 8.0 milligrams per deciliter (mg/dL) at Baseline
Exclusion criteria
* Serum creatinine \>1.5 mg/dL * Calculated creatinine clearance of \<50 milliliters per minutes (mL/min) * Pregnancy or lactation; * Concurrent therapy with urate lowering agents, azathioprine, 6-mercaptopurine, thiazide diuretics, or medications containing aspirin (\>325 mg) or other salicylates; * Body Mass Index (BMI) \>50 kilogram per meter²(kg/m²); * A history of xanthinuria, active liver disease, or hepatic dysfunction; * A history of alcohol abuse or intake of 14 or more alcohol-containing drinks/week.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) | Last 3 Visits (up to 52 weeks) | 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 With Serum Urate <6.0 mg/dL at Week 52 Visit | Week 52 | Serum urate values were obtained at the Week 52 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Week 52 visit was summarized. |
| Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit | Final Visit (up to 52 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. The timing of the final visit may have differed for each 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 Week 52. | Baseline and Week 52 | Serum urate values were obtained at the Week 52 visit. The percent change in serum urate was calculated as \[(week 52 - baseline levels/baseline)\]\*100 and summarized. |
| Percent Change From Baseline in Serum Urate Levels at Final Visit | Baseline and Final Visit (up to 52 weeks) | The percent change in serum urate from baseline to the Final visit was calculated as \[(Final Visit - baseline levels/baseline)\]\*100 and summarized. The Final visit was the last visit with a serum urate value. The timing of the final visit may have differed for each subject. |
| Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | 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 With Serum Urate <6.0 mg/dL at Week 28 Visit | 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. |
| Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | Baseline and Final Visit (up to 52 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. |
| Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. | Baseline and Week 28 | The 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 no longer palpable at the Week 28 visit, the total count was assumed to be zero. |
| Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. | Baseline and Week 52 | The change from baseline at Week 52 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 no longer palpable at the Week 52 visit, the total count was assumed to be zero. |
| Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. | Baseline and Final Visit (up to 52 weeks) | Change in number of tophi/subject calculated for the subset of subjects with palpable tophi at 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 Gout Flares Between Weeks 8 and 52. | Weeks 8 through 52 | The percentage of subjects requiring treatment for a gout flare between Weeks 8 and 52 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 From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | Baseline and Week 52 | The percent change from baseline in primary tophus size as determined by physical measurement was calculated as \[(Week 52 - baseline sizes)/baseline\]\*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 52 visit, the size was assumed to be zero. |
Participant flow
Recruitment details
Subjects were enrolled at 112 investigative sites, 106 in the United States and 6 in Canada, from 11 July 2002 to 20 February 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 52 weeks. | 256 |
| Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 52 weeks. | 251 |
| Allopurinol 300 mg QD Allopurinol 300 mg, orally, once daily for up to 52 weeks. | 253 |
| Total | 760 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 23 | 8 |
| Overall Study | Gout Flare | 10 | 28 | 9 |
| Overall Study | Lost to Follow-up | 25 | 18 | 21 |
| Overall Study | Other | 11 | 14 | 14 |
| Overall Study | Personal Reason(s) | 19 | 13 | 13 |
| Overall Study | Protocol Violation | 7 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Febuxostat 80 mg QD | Febuxostat 120 mg QD | Allopurinol 300 mg QD |
|---|---|---|---|---|
| Age Continuous | 51.8 years STANDARD_DEVIATION 12.13 | 51.8 years STANDARD_DEVIATION 11.69 | 52.0 years STANDARD_DEVIATION 12.12 | 51.6 years STANDARD_DEVIATION 12.63 |
| Age, Customized <45 years | 230 subjects | 75 subjects | 71 subjects | 84 subjects |
| Age, Customized 45 years to <65 years | 398 subjects | 140 subjects | 133 subjects | 125 subjects |
| Age, Customized ≥65 years | 132 subjects | 41 subjects | 47 subjects | 44 subjects |
| Body Mass Index 18.5 kg/m² to <25 kg/m² | 34 subjects | 15 subjects | 12 subjects | 7 subjects |
| Body Mass Index <18.5 kilogram per meter² (kg/m²) | 0 subjects | 0 subjects | 0 subjects | 0 subjects |
| Body Mass Index 25 kg/m² to <30 kg/m² | 251 subjects | 75 subjects | 87 subjects | 89 subjects |
| Body Mass Index ≥30 kg/m² | 472 subjects | 166 subjects | 152 subjects | 154 subjects |
| Body Mass Index missing | 3 subjects | 0 subjects | 0 subjects | 3 subjects |
| Calculated Creatinine Clearance ≥120 mL/min | 80 subjects | 28 subjects | 23 subjects | 29 subjects |
| Calculated Creatinine Clearance <50 milliliters per minute (mL/min) | 34 subjects | 13 subjects | 8 subjects | 13 subjects |
| Calculated Creatinine Clearance 50 mL/min to <80 mL/min | 235 subjects | 77 subjects | 90 subjects | 68 subjects |
| Calculated Creatinine Clearance 80 mL/min to <120 mL/min | 408 subjects | 138 subjects | 130 subjects | 140 subjects |
| Calculated Creatinine Clearance missing | 3 subjects | 0 subjects | 0 subjects | 3 subjects |
| Presence of Primary Palpable Tophus No and no other tophi present | 603 subjects | 203 subjects | 196 subjects | 204 subjects |
| Presence of Primary Palpable Tophus No, but other tophi present | 6 subjects | 1 subjects | 2 subjects | 3 subjects |
| Presence of Primary Palpable Tophus Yes | 151 subjects | 52 subjects | 53 subjects | 46 subjects |
| Race/Ethnicity Asian | 25 subjects | 10 subjects | 9 subjects | 6 subjects |
| Race/Ethnicity Black or African American | 62 subjects | 24 subjects | 20 subjects | 18 subjects |
| Race/Ethnicity Hispanic | 58 subjects | 22 subjects | 17 subjects | 19 subjects |
| Race/Ethnicity Other | 28 subjects | 7 subjects | 6 subjects | 15 subjects |
| Race/Ethnicity White | 587 subjects | 193 subjects | 199 subjects | 195 subjects |
| Sex: Female, Male Female | 31 Participants | 13 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Male | 729 Participants | 243 Participants | 243 Participants | 243 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 164 / 256 | 145 / 251 | 167 / 253 |
| serious Total, serious adverse events | 10 / 256 | 19 / 251 | 18 / 253 |
Outcome results
Primary
Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams 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 (up to 52 weeks)
Population: Analysis was performed on the intent-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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat 80 mg QD | Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) | 53 Percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) | 62 Percentage of subjects |
| Allopurinol 300 mg QD | Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) | 21 Percentage of subjects |
97.5% CI: [23.1, 41.3]
97.5% CI: [31.5, 49.5]
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.072Fisher Exact
Secondary
Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening.
Change in number of tophi/subject calculated for the subset of subjects with palpable tophi at 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: Baseline and Final Visit (up to 52 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 baseline. Missing data were not imputed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
| Febuxostat 120 mg QD | Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
| Allopurinol 300 mg QD | Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
p-value: 0.657Wilcoxon (Mann-Whitney)
p-value: 0.444Wilcoxon (Mann-Whitney)
p-value: 0.719Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening.
The 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 no longer palpable at the Week 28 visit, the total count 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, had a baseline serum urate ≥8.0 mg/dL, and had palpable tophi at baseline. Missing data were not imputed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
| Febuxostat 120 mg QD | Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
| Allopurinol 300 mg QD | Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
p-value: 0.674Wilcoxon (Mann-Whitney)
p-value: 0.32Wilcoxon (Mann-Whitney)
p-value: 0.411Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening.
The change from baseline at Week 52 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 no longer palpable at the Week 52 visit, the total count was assumed to be zero.
Time frame: Baseline and Week 52
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 baseline. Missing data were not imputed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
| Febuxostat 120 mg QD | Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. | -1.0 number of tophi |
| Allopurinol 300 mg QD | Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. | 0.0 number of tophi |
p-value: 0.507Wilcoxon (Mann-Whitney)
p-value: 0.188Wilcoxon (Mann-Whitney)
p-value: 0.362Wilcoxon (Mann-Whitney)
Secondary
Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52.
The percentage of subjects requiring treatment for a gout flare between Weeks 8 and 52 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 52
Population: Analysis was performed on the ITT subjects who had at least one dose of study drug between Weeks 8 and 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat 80 mg QD | Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52. | 64 percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52. | 70 percentage of subjects |
| Allopurinol 300 mg QD | Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52. | 64 percentage of subjects |
p-value: >0.999Fisher Exact
p-value: 0.229Fisher Exact
p-value: 0.266Fisher Exact
Secondary
Percentage of Subjects With Serum Urate <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. The timing of the final visit may have differed for each subject.
Time frame: Final Visit (up to 52 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 With Serum Urate <6.0 mg/dL at Final Visit | 74 Percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit | 80 Percentage of subjects |
| Allopurinol 300 mg QD | Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit | 36 Percentage of subjects |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.164Fisher Exact
Secondary
Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit
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 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 With Serum Urate <6.0 mg/dL at Week 28 Visit | 72 Percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit | 82 Percentage of subjects |
| Allopurinol 300 mg QD | Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit | 42 Percentage of subjects |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.031Fisher Exact
Secondary
Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit
Serum urate values were obtained at the Week 52 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Week 52 visit was summarized.
Time frame: Week 52
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 With Serum Urate <6.0 mg/dL at Week 52 Visit | 81 Percentage of subjects |
| Febuxostat 120 mg QD | Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit | 82 Percentage of subjects |
| Allopurinol 300 mg QD | Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit | 39 Percentage of subjects |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.883Fisher Exact
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 calculated as \[(Final Visit - baseline levels/baseline)\]\*100 and summarized. The Final visit was the last visit with a serum urate value. The timing of the final visit may have differed for each subject.
Time frame: Baseline and Final Visit (up to 52 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 | -44.7 percent change from baseline | Standard Deviation 19.1 |
| Febuxostat 120 mg QD | Percent Change From Baseline in Serum Urate Levels at Final Visit | -51.5 percent change from baseline | Standard Deviation 19.91 |
| Allopurinol 300 mg QD | Percent Change From Baseline in Serum Urate Levels at Final Visit | -33.0 percent change from baseline | Standard Deviation 15.33 |
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. | -46.3 percent change from baseline | Standard Deviation 15.76 |
| Febuxostat 120 mg QD | Percent Change From Baseline in Serum Urate Levels at Week 28. | -53.5 percent change from baseline | Standard Deviation 18.2 |
| Allopurinol 300 mg QD | Percent Change From Baseline in Serum Urate Levels at Week 28. | -34.8 percent change from baseline | Standard Deviation 12.92 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: <0.001ANOVA
Secondary
Percent Change From Baseline in Serum Urate Levels at Week 52.
Serum urate values were obtained at the Week 52 visit. The percent change in serum urate was calculated as \[(week 52 - baseline levels/baseline)\]\*100 and summarized.
Time frame: Baseline and Week 52
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 52. | -47.7 percent change from baseline | Standard Deviation 17.5 |
| Febuxostat 120 mg QD | Percent Change From Baseline in Serum Urate Levels at Week 52. | -53.0 percent change from baseline | Standard Deviation 19.31 |
| Allopurinol 300 mg QD | Percent Change From Baseline in Serum Urate Levels at Week 52. | -34.8 percent change from baseline | Standard Deviation 13.56 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
p-value: 0.006ANOVA
Secondary
Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.
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 52 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 a palpable primary tophus measured at baseline. Missing data were not imputed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -51.7 percent change from baseline |
| Febuxostat 120 mg QD | Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -43.8 percent change from baseline |
| Allopurinol 300 mg QD | Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -39.6 percent change from baseline |
p-value: 0.08Wilcoxon (Mann-Whitney)
p-value: 0.372Wilcoxon (Mann-Whitney)
p-value: 0.246Wilcoxon (Mann-Whitney)
Secondary
Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.
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, had a baseline serum urate ≥8.0 mg/dL, and had a palpable primary tophus measured at baseline. Missing data were not imputed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -29.5 percent change from baseline |
| Febuxostat 120 mg QD | Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -49.5 percent change from baseline |
| Allopurinol 300 mg QD | Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -28.6 percent change from baseline |
p-value: 0.011Wilcoxon (Mann-Whitney)
p-value: >0.999Wilcoxon (Mann-Whitney)
p-value: 0.024Wilcoxon (Mann-Whitney)
Secondary
Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.
The percent change from baseline in primary tophus size as determined by physical measurement was calculated as \[(Week 52 - baseline sizes)/baseline\]\*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 52 visit, the size was assumed to be zero.
Time frame: Baseline and Week 52
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 a palpable primary tophus measured at baseline. Missing data were not imputed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Febuxostat 80 mg QD | Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -83.4 percent change from baseline |
| Febuxostat 120 mg QD | Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -65.5 percent change from baseline |
| Allopurinol 300 mg QD | Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | -49.7 percent change from baseline |
p-value: 0.083Wilcoxon (Mann-Whitney)
p-value: 0.164Wilcoxon (Mann-Whitney)
p-value: 0.619Wilcoxon (Mann-Whitney)