GoutPhase 3APEXNCT00174915

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

A Phase 3 study testing Febuxostat and Allopurinol in people with Gout, run by Takeda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to compare febuxostat, allopurinol and placebo, once daily (QD), in subjects with gout. Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Gout
What is being tested?: Febuxostat and Allopurinol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,072 participants
Where: No sites listed yet
Study dates: Feb 2003to Apr 2004
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

History of xanthinuria
Intolerance to allopurinol
Presence of renal calculi,
Alcohol intake of ≥ 14 drinks/week
Clinically significant medical condition

About this study

Official title: A Phase 3, Randomized, Multicenter, Allopurinol and Placebo-Controlled Study Assessing the Safety and Efficacy of Oral Febuxostat in Subjects With Gout.

The purpose of this study is to compare febuxostat, allopurinol and placebo, once daily (QD), in subjects with gout.

Read the 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.

Conditions: Gout
Being tested: Febuxostat, Allopurinol, Placebo
Keywords: Uric Acid, gout, xanthine oxidase, febuxostat, tophi
Medical subject headings: Gout

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FebuxostatDrug
Also called TMX-67, Tei-6720, Uloric
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
FebuxostatDrug
Also called TMX-67, Tei-6720, Uloric
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
FebuxostatDrug
Also called TMX-67, Tei-6720, Uloric
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
AllopurinolDrug
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.
PlaceboDrug
Placebo, orally, once daily for up to 28 weeks.

Study groups in NCT00174915
Study group	Role	What they receive
Febuxostat 80 mg QD	Experimental	Not described Receives: Drug: Febuxostat
Febuxostat 120 mg QD	Experimental	Not described Receives: Drug: Febuxostat
Febuxostat 240 mg QD	Experimental	Not described Receives: Drug: Febuxostat
Allopurinol QD	Active comparator	Not described Receives: Drug: Allopurinol
Placebo QD	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Last 3 visits (any last 3 visits up to week 28)

Secondary outcomes (9)

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.
Measured: Week 28
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.
Measured: Final Visit (up to 28 weeks).
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.
Measured: Baseline and Week 28
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.
Measured: Baseline and Final Visit (up to 28 weeks)
Percent Change in Primary Tophus Size at Week 28, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit.
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.
Measured: Baseline and Week 28
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.
Measured: Baseline and Final Visit (up to 28 weeks)
Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
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.
Measured: Baseline and Week 28
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.
Measured: Final Visit (up to 28 weeks)
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.
Measured: Weeks 8 through 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2003Apr 2004

First posted15 Sep 2005 (estimated)
Study startFeb 2003
Primary completionApr 2004
Study completionApr 2004

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for GoutStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 1,072 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00174915
Sponsor's protocol ID: C02-009
Other IDs: U1111-1113-9740
Acronym: APEX
Status last verified: Jan 2012
First submitted: 9 Sep 2005
Last updated: 2 Feb 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 18975369
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.
PubMed 18600509
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.
PubMed 21353107
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.
PubMed 22052584

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 4
Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout
Gout
RecruitingPhase 3
A Study of Dotinurad Versus Allopurinol in Participants With Gout
Gout
RecruitingPhase 3
A Study of Dotinurad Versus Allopurinol in Tophaceous Gout
Tophaceous Gout
Not yet recruitingPhase 3
Combined Metabolic Activator Supplementation in Subjects Diagnosed With Gout
Gout Disease
Enrolling by invitation
The Remote Monitoring of Gout Study
Gout Initiating Urate-loweringUrate-lowering Therapy

All Gout trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Randomized, Multicenter, Allopurinol and Placebo-Controlled Study Assessing the Safety and Efficacy of Oral Febuxostat in Subjects With Gout.
ClinicalTrials.gov ID: NCT00174915
Acronym / sponsor ID: APEX / C02-009
Conditions: Gout
Keywords: Uric Acid, gout, xanthine oxidase, febuxostat, tophi
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,072 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: Feb 2003
Primary completion: Apr 2004 (actual)
Study completion: Apr 2004 (actual)
First posted: 15 Sep 2005 (estimated)
Results: Posted 16 Jul 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to compare febuxostat, allopurinol and placebo, once daily (QD), in subjects with gout.

Detailed description

Subjects will receive treatment for 28 weeks.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Febuxostat 80 mg QD	Experimental	Drug: Febuxostat
Febuxostat 120 mg QD	Experimental	Drug: Febuxostat
Febuxostat 240 mg QD	Experimental	Drug: Febuxostat
Allopurinol QD	Active comparator	Drug: Allopurinol
Placebo QD	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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.

Key exclusion criteria (5 listed)

History of xanthinuria
Intolerance to allopurinol
Presence of renal calculi,
Alcohol intake of ≥ 14 drinks/week
Clinically significant medical condition

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FebuxostatAlso: TMX-67, Tei-6720, UloricFebuxostat 80 mg, orally, once daily for up to 28 weeks.	Drug	Febuxostat 80 mg QD
FebuxostatAlso: TMX-67, Tei-6720, UloricFebuxostat 120 mg, orally, once daily for up to 28 weeks.	Drug	Febuxostat 120 mg QD
FebuxostatAlso: TMX-67, Tei-6720, UloricFebuxostat 240 mg, orally, once daily for up to 28 weeks.	Drug	Febuxostat 240 mg QD
AllopurinolAllopurinol, 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.	Drug	Allopurinol QD
PlaceboPlacebo, orally, once daily for up to 28 weeks.	Drug	Placebo QD

Primary outcome

Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Time frame: 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.

9 secondary outcomes

Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Time frame: Week 28
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Time frame: Final Visit (up to 28 weeks).
Percent Change From Baseline in Serum Urate Levels at Week 28.
Time frame: Baseline and Week 28
Percent Change From Baseline in Serum Urate Levels at Final Visit
Time frame: Baseline and Final Visit (up to 28 weeks)
Percent Change in Primary Tophus Size at Week 28, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Time frame: Baseline and Week 28
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.
Time frame: Baseline and Final Visit (up to 28 weeks)
Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Time frame: Baseline and Week 28
Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Time frame: Final Visit (up to 28 weeks)
Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Time frame: Weeks 8 through 28

Results and safety

Results posted to the registry on 16 Jul 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Febuxostat 80 mg QD	267	174
Febuxostat 120 mg QD	269	200
Febuxostat 240 mg QD	134	86
Allopurinol QD	268	211
Placebo QD	134	101

Primary outcome: Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).

Time frame: Last 3 visits (any last 3 visits up to week 28). Number. Unit: Percentage of subjects

Measure	Febuxostat 80 mg QD n = 262	Febuxostat 120 mg QD n = 269	Febuxostat 240 mg QD n = 134	Allopurinol QD n = 268	Placebo QD n = 134
Value	48	65	69	22	0

Febuxostat 80 mg QD vs Placebo QD: p <0.001, Cochran-Mantel-Haenszel
Febuxostat 120 mg QD vs Placebo QD: p <0.001, Cochran-Mantel-Haenszel
Febuxostat 240 mg QD vs Placebo QD: p <0.001, Cochran-Mantel-Haenszel

Population analysed: 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.

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Febuxostat 80 mg QD	11 of 267 (4.1%)	122 of 267 (45.7%)	Not reported
Febuxostat 120 mg QD	9 of 269 (3.3%)	123 of 269 (45.7%)	Not reported
Febuxostat 240 mg QD	5 of 134 (3.7%)	72 of 134 (53.7%)	Not reported
Allopurinol QD	7 of 268 (2.6%)	133 of 268 (49.6%)	Not reported
Placebo QD	2 of 134 (1.5%)	61 of 134 (45.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 18975369Schumacher 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 publication: PubMed 18600509Becker 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 publication: PubMed 21353107Wortmann 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 publication: PubMed 22052584Chohan 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.
Uloric Package InsertLink provided by the sponsor.

Related trials for Gout

RecruitingPhase 4
Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout
Gout
RecruitingPhase 3
A Study of Dotinurad Versus Allopurinol in Participants With Gout
Gout
RecruitingPhase 3
A Study of Dotinurad Versus Allopurinol in Tophaceous Gout
Tophaceous Gout
Not yet recruitingPhase 3
Combined Metabolic Activator Supplementation in Subjects Diagnosed With Gout
Gout Disease
Enrolling by invitation
The Remote Monitoring of Gout Study
Gout Initiating Urate-loweringUrate-lowering Therapy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Takeda

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Febuxostat and Allopurinol in people with Gout, run by Takeda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jul 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). (time frame: Last 3 visits (any last 3 visits up to week 28)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00174915, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2012; AzTrials last refreshed its copy on 8 Nov 2026.