Back to resultsPhase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects. (APEX)
Primary Purpose
Gout
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Febuxostat
Febuxostat
Febuxostat
Allopurinol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Gout focused on measuring Uric Acid, gout, xanthine oxidase, febuxostat, tophi
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Placebo Comparator
Arm Label
Febuxostat 80 mg QD
Febuxostat 120 mg QD
Febuxostat 240 mg QD
Allopurinol QD
Placebo QD
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00174915
Brief Title
Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects.
Acronym
APEX
Official Title
A Phase 3, Randomized, Multicenter, Allopurinol and Placebo-Controlled Study Assessing the Safety and Efficacy of Oral Febuxostat in Subjects With Gout.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
February 2003 (undefined)
Primary Completion Date
April 2004 (Actual)
Study Completion Date
April 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout
Keywords
Uric Acid, gout, xanthine oxidase, febuxostat, tophi
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1072 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Febuxostat 80 mg QD
Arm Type
Experimental
Arm Title
Febuxostat 120 mg QD
Arm Type
Experimental
Arm Title
Febuxostat 240 mg QD
Arm Type
Experimental
Arm Title
Allopurinol QD
Arm Type
Active Comparator
Arm Title
Placebo QD
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Febuxostat
Other Intervention Name(s)
TMX-67, Tei-6720, Uloric
Intervention Description
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Intervention Type
Drug
Intervention Name(s)
Febuxostat
Other Intervention Name(s)
TMX-67, Tei-6720, Uloric
Intervention Description
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Intervention Type
Drug
Intervention Name(s)
Febuxostat
Other Intervention Name(s)
TMX-67, Tei-6720, Uloric
Intervention Description
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, orally, once daily for up to 28 weeks.
Primary Outcome Measure Information:
Title
Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
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)
Secondary Outcome Measure Information:
Title
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
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
Title
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
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).
Title
Percent Change From Baseline in Serum Urate Levels at Week 28.
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
Title
Percent Change From Baseline in Serum Urate Levels at Final Visit
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)
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.
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
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.
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)
Title
Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
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
Title
Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
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)
Title
Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Takeda
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
18975369
Citation
Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, Lademacher C, Joseph-Ridge N. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008 Nov 15;59(11):1540-8. doi: 10.1002/art.24209.
Results Reference
result
PubMed Identifier
18600509
Citation
Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph-Ridge N. Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):585-91. doi: 10.1080/15257770802136032.
Results Reference
result
PubMed Identifier
21353107
Citation
Wortmann RL, Macdonald PA, Hunt B, Jackson RL. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. Clin Ther. 2010 Dec;32(14):2386-97. doi: 10.1016/j.clinthera.2011.01.008.
Results Reference
result
PubMed Identifier
22052584
Citation
Chohan S, Becker MA, MacDonald PA, Chefo S, Jackson RL. Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol. Arthritis Care Res (Hoboken). 2012 Feb;64(2):256-61. doi: 10.1002/acr.20680.
Results Reference
result
Links:
URL
http://general.takedapharm.com/content/file.aspx?applicationcode=6C7C39D8-5D09-453B-BF30-696A4AB88E62&fileTypeCode=ULORICPI
Description
Uloric Package Insert
Learn more about this trial
Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects.
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