Febuxostat Versus Allopurinol Control Trial in Subjects With Gout

Gout Clinical Trial

— FACT  

Official title:

A Phase 3, Randomized, Multicenter Study Comparing the Safety and Efficacy of Oral Febuxostat Versus Allopurinol in Subjects With Gout

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00102440
• Other study ID #: C02-010
• Secondary ID: U1111-1114-0184
• Status: Completed
• Phase: Phase 3
• First received: January 29, 2005
• Last updated: January 31, 2012
• Start date: July 2002
• Est. completion date: February 2004

Study information

• Verified date: January 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of febuxostat, once daily (QD), versus allopurinol in subjects with gout.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 760
• Est. completion date: February 2004
• Est. primary completion date: February 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• Febuxostat
Febuxostat 80 mg, orally, once daily for up to 52 weeks.
• Febuxostat
Febuxostat 120 mg, orally, once daily for up to 52 weeks.
• Allopurinol
Allopurinol 300 mg, capsules, orally, once daily for up to 52 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

References & Publications (4)

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. — View Citation

Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005 Dec 8;353(23):2450-61. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Last 3 Visits (up to 52 weeks)	No
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.	Week 28	No
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.	Week 52	No
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.	Final Visit (up to 52 weeks)	No
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.	Baseline and Week 28	No
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.	Baseline and Week 52	No
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.	Baseline and Final Visit (up to 52 weeks)	No
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.	Baseline and Week 28	No
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.	Baseline and Week 52	No
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.	Baseline and Final Visit (up to 52 weeks)	No
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.	Baseline and Week 28	No
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.	Baseline and Week 52	No
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.	Baseline and Final Visit (up to 52 weeks)	No
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.	Weeks 8 through 52	No

External Links

•   American College of Rheumatology
•   FDA Safety Alerts and Recalls
•   Uloric Package Insert