GoutPhase 3EXCELNCT00175019
Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010
A Phase 3 study testing Febuxostat and Allopurinol in people with Gout, run by Takeda.
Trial summary
The purpose of this study is to determine the long-term safety of febuxostat, once daily (QD), compared to allopurinol in reducing serum urate levels 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?
- No, everyone receives an active treatment
- How many people
- 1,086 participants
- Where
- No sites listed yet
- Study dates
- Jul 2003to Feb 2007
- 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
- Is receiving thiazide diuretic therapy (only to subjects randomized to or receiving febuxostat).
- Has a serum urate level less than 8.0 mg/dL and is not taking uric acid-lowering therapy (other than allopurinol or febuxostat).
- Has participated in a clinical study in which febuxostat was administered.
- Is completing Phase 3 Studies C02-009 or C02-010.
- Must not have experienced any serious study drug-related adverse events in the previous study.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study
Who cannot join
- Has had any other significant medical condition as defined by the investigator that would interfere with the treatment, safety, or compliance with the protocol.
- Is intolerant of allopurinol.
About this study
Official title: A Phase 3, Open-Label, Randomized, Allopurinol-Controlled Study to Assess the Long-Term Safety of Oral Febuxostat in Subjects With Gout
The purpose of this study is to determine the long-term safety of febuxostat, once daily (QD), compared to allopurinol in reducing serum urate levels in subjects with gout.
Read the detailed description
Uric acid is the end product of purine degradation in humans. Hyperuricemia, a urate concentration in serum exceeding the limit of urate solubility (approximately 7.0 mg/dL), is a common biochemical abnormality. Aberrations in any of the multiple mechanisms involved in the production and/or excretion of uric acid may increase serum urate concentrations, with persistent hyperuricemia as a marker for extracellular fluid monosodium urate supersaturation. As such, hyperuricemia is a necessary (but often insufficient) risk factor for monosodium urate crystal deposition in tissues and is the fundamental pathophysiological process underlying the clinical manifestations of gout, which is a chronic disease characterized by urate crystal formation and deposition in joints and bones. Gout may progress from episodic attacks of acute inflammatory arthritis to a disabling chronic disorder characterized by deforming arthropathy; destructive deposits of urate crystals (tophi) in bones, joints, and other organs; structural and functional renal impairment due to interstitial urate crystal deposition; and urinary tract stones composed entirely or partially of uric acid crystals. Management of gout requires chronic treatment aimed at lowering serum urate levels into a subsaturating range (usually <6.0 mg/dL) in which crystal formation and deposition are prevented or reversed.
Febuxostat (TMX-67) is a non-purine selective xanthine oxidase inhibitor being developed as an orally administered agent for the management of hyperuricemia in patients with gout.
This study was originally designed and initiated having all subjects initially assigned to 80 mg febuxostat provided as an 80 mg tablet, to be administered orally. Subjects could be titrated to 120 mg, provided as one 40 and 80 mg tablet, between Months 2 and 6, if their serum uric acid rose > 6.0 mg/dL; the dose could be down-titrated to 80 mg if the serum uric acid decreased to < 3.0 mg/dL.
The protocol was amended to add a comparator arm, and to have subjects randomized to 80 or 120 mg febuxostat or allopurinol (100 or 300 mg, dependent on renal function). The information below reflects the treatments following the implementation of the revised protocol.
- Conditions
- Gout
- Being tested
- Febuxostat, Allopurinol
- Keywords
- uric acid, xanthine oxidase, hyperuricemia, tophi, Drug Therapy
- Medical subject headings
- Gout, Hyperuricemia
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, tablets, orally, once daily.
FebuxostatDrug
Also called TMX-67, Tei-6720, Uloric
Febuxostat 120 mg, tablets, orally, once daily.
AllopurinolDrug
Also called Zyloprim
Allopurinol 100 mg or 300 mg, tablets, orally, once daily.
| 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 |
| Allopurinol QD | Active comparator | Not described Receives: Drug: Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 1.
Serum urate values were obtained at the Month 1 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 1 visit was summarized.
Measured: Month 1
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 12.
Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 12 visit was summarized.
Measured: Month 12
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 24.
Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 24 visit was summarized.
Measured: Month 24
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 36.
Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 36 visit was summarized.
Measured: Month 36
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Last Visit on Treatment.
The percentage of subjects whose serum urate was <6.0 mg/dL at the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.
Measured: Last Visit on treatment (up to 40 months).
Secondary outcomes (8)
Percent Change in Serum Urate Levels From Baseline to the Last Visit on Treatment.
The percent change in serum urate from baseline to the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.
Measured: Last Visit on treatment (up to 40 months).
Percent Change From Baseline in Primary Tophus Size at Month 12 for Subjects With Palpable Tophi Measured at Baseline.
The area of the primary tophus was calculated based on the length and width of the tophus measured at the Month 12 visit. The percent change from baseline in primary tophus size to the Month 12 visit was summarized.
Measured: Month 12
Percent Change From Baseline in Primary Tophus Size at Month 24 for Subjects With Palpable Tophi Measured at Baseline.
The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and Month 24 visit. The percent change from baseline in primary tophus size to the Month 24 visit was summarized.
Measured: Month 24
Percent Change From Baseline in Primary Tophus Size at Month 36 for Subjects With Palpable Tophi Measured at Baseline.
The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and Month 36 visit. The percent change from baseline in primary tophus size to the Month 36 visit was summarized.
Measured: Month 36
Percent Change From Baseline in Primary Tophus Size at Final Visit for Subjects With Palpable Tophi Measured at Baseline.
The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and final visit. The percent change from baseline in primary tophus size to the final visit was summarized.
Measured: Final Visit (up to 40 months).
Percent Change From Baseline in the Total Number of Tophi for Subjects With Palpable Tophi at Final Visit.
The number of tophi were counted at baseline and final visits. The percent change from baseline in the number of tophi to the final visit was summarized.
Measured: Final Visit (up to 40 months).
Percentage of Subjects Requiring Treatment for Gout Flare up to Month 12.
The percentage of subjects requiring treatment for gout flare during the first twelve months of final stable treatment was summarized.
Measured: Month 12
Percentage of Subjects Requiring Treatment for Gout Flare After Month 12.
The percentage of subjects requiring treatment for gout flare after the first 12 months of final stable treatment was summarized.
Measured: After Month 12 to Final Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startJul 2003
- Primary completionFeb 2007
- Study completionFeb 2007
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 (1)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
- None (open label)
- Enrolment
- 1,086 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Director, Study chair, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00175019
- Sponsor's protocol ID
- C02-021
- Other IDs
- U1111-1113-9814
- Acronym
- EXCEL
- Status last verified
- Jul 2010
- First submitted
- 12 Sep 2005
- Last updated
- 27 Jul 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol. 2009 Jun;36(6):1273-82. doi: 10.3899/jrheum.080814. Epub 2009 Mar 13.
PubMed 19286847
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Open-Label, Randomized, Allopurinol-Controlled Study to Assess the Long-Term Safety of Oral Febuxostat in Subjects With Gout
- ClinicalTrials.gov ID
- NCT00175019
- Acronym / sponsor ID
- EXCEL / C02-021
- Conditions
- Gout
- Keywords
- uric acid, xanthine oxidase, hyperuricemia, tophi, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,086 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jul 2003
- Primary completion
- Feb 2007 (actual)
- Study completion
- Feb 2007 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 7 Sep 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 determine the long-term safety of febuxostat, once daily (QD), compared to allopurinol in reducing serum urate levels in subjects with gout.
Detailed description
Uric acid is the end product of purine degradation in humans. Hyperuricemia, a urate concentration in serum exceeding the limit of urate solubility (approximately 7.0 mg/dL), is a common biochemical abnormality. Aberrations in any of the multiple mechanisms involved in the production and/or excretion of uric acid may increase serum urate concentrations, with persistent hyperuricemia as a marker for extracellular fluid monosodium urate supersaturation. As such, hyperuricemia is a necessary (but often insufficient) risk factor for monosodium urate crystal deposition in tissues and is the fundamental pathophysiological process underlying the clinical manifestations of gout, which is a chronic disease characterized by urate crystal formation and deposition in joints and bones. Gout may progress from episodic attacks of acute inflammatory arthritis to a disabling chronic disorder characterized by deforming arthropathy; destructive deposits of urate crystals (tophi) in bones, joints, and other organs; structural and functional renal impairment due to interstitial urate crystal deposition; and urinary tract stones composed entirely or partially of uric acid crystals. Management of gout requires chronic treatment aimed at lowering serum urate levels into a subsaturating range (usually <6.0 mg/dL) in which crystal formation and deposition are prevented or reversed.
Febuxostat (TMX-67) is a non-purine selective xanthine oxidase inhibitor being developed as an orally administered agent for the management of hyperuricemia in patients with gout.
This study was originally designed and initiated having all subjects initially assigned to 80 mg febuxostat provided as an 80 mg tablet, to be administered orally. Subjects could be titrated to 120 mg, provided as one 40 and 80 mg tablet, between Months 2 and 6, if their serum uric acid rose > 6.0 mg/dL; the dose could be down-titrated to 80 mg if the serum uric acid decreased to < 3.0 mg/dL.
The protocol was amended to add a comparator arm, and to have subjects randomized to 80 or 120 mg febuxostat or allopurinol (100 or 300 mg, dependent on renal function). The information below reflects the treatments following the implementation of the revised protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Febuxostat 80 mg QD | Experimental | Drug: Febuxostat |
| Febuxostat 120 mg QD | Experimental | Drug: Febuxostat |
| Allopurinol QD | Active comparator | Drug: Allopurinol |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Is receiving thiazide diuretic therapy (only to subjects randomized to or receiving febuxostat).
- Has a serum urate level less than 8.0 mg/dL and is not taking uric acid-lowering therapy (other than allopurinol or febuxostat).
- Has participated in a clinical study in which febuxostat was administered.
- Is completing Phase 3 Studies C02-009 or C02-010.
- Must not have experienced any serious study drug-related adverse events in the previous study.
Key exclusion criteria (2 listed)
- Has had any other significant medical condition as defined by the investigator that would interfere with the treatment, safety, or compliance with the protocol.
- Is intolerant of allopurinol.
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, tablets, orally, once daily. | Drug | Febuxostat 80 mg QD |
| FebuxostatAlso: TMX-67, Tei-6720, UloricFebuxostat 120 mg, tablets, orally, once daily. | Drug | Febuxostat 120 mg QD |
| AllopurinolAlso: ZyloprimAllopurinol 100 mg or 300 mg, tablets, orally, once daily. | Drug | Allopurinol QD |
Primary outcome
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 1.
Time frame: Month 1
Serum urate values were obtained at the Month 1 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 1 visit was summarized.
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 12.
Time frame: Month 12
Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 12 visit was summarized.
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 24.
Time frame: Month 24
Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 24 visit was summarized.
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 36.
Time frame: Month 36
Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 36 visit was summarized.
Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Last Visit on Treatment.
Time frame: Last Visit on treatment (up to 40 months).
The percentage of subjects whose serum urate was <6.0 mg/dL at the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.
8 secondary outcomes
Percent Change in Serum Urate Levels From Baseline to the Last Visit on Treatment.
Time frame: Last Visit on treatment (up to 40 months).
Percent Change From Baseline in Primary Tophus Size at Month 12 for Subjects With Palpable Tophi Measured at Baseline.
Time frame: Month 12
Percent Change From Baseline in Primary Tophus Size at Month 24 for Subjects With Palpable Tophi Measured at Baseline.
Time frame: Month 24
Percent Change From Baseline in Primary Tophus Size at Month 36 for Subjects With Palpable Tophi Measured at Baseline.
Time frame: Month 36
Percent Change From Baseline in Primary Tophus Size at Final Visit for Subjects With Palpable Tophi Measured at Baseline.
Time frame: Final Visit (up to 40 months).
Percent Change From Baseline in the Total Number of Tophi for Subjects With Palpable Tophi at Final Visit.
Time frame: Final Visit (up to 40 months).
Percentage of Subjects Requiring Treatment for Gout Flare up to Month 12.
Time frame: Month 12
Percentage of Subjects Requiring Treatment for Gout Flare After Month 12.
Time frame: After Month 12 to Final Visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19286847Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol. 2009 Jun;36(6):1273-82. doi: 10.3899/jrheum.080814. Epub 2009 Mar 13.
- Uloric Package InsertLink provided by the sponsor.
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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 chair
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 6 inclusion and 2 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 27 Jul 2010. 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. 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 7 Sep 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 Serum Urate Level Decreases to < 6.0 mg/dL at Month 1. (time frame: Month 1). The study lists 5 primary outcomes in all. 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 NCT00175019, which also lists 1 linked publication.
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 27 Jul 2010.