Febuxostat Versus Allopurinol Control Trial in Subjects With Gout - Full Text View

Sponsor:	Takeda Global Research & Development Center, Inc.
Information provided by (Responsible Party):	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00102440

Purpose

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

Condition	Intervention	Phase
Gout	Drug: Febuxostat Drug: Allopurinol	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3, Randomized, Multicenter Study Comparing the Safety and Efficacy of Oral Febuxostat Versus Allopurinol in Subjects With Gout

Resource links provided by NLM:

MedlinePlus related topics: Gout

Drug Information available for: Allopurinol sodium Tei 6720 Allopurinol

U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) [ Time Frame: Last 3 Visits (up to 52 weeks) ] [ Designated as safety issue: No ]
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 With Serum Urate <6.0 mg/dL at Week 28 Visit [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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 With Serum Urate <6.0 mg/dL at Week 52 Visit [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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 [ Time Frame: Final Visit (up to 52 weeks) ] [ Designated as safety issue: No ]
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. [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
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. [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and Final Visit (up to 52 weeks) ] [ Designated as safety issue: No ]
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. [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
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 From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
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.
Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [ Time Frame: Baseline and Final Visit (up to 52 weeks) ] [ Designated as safety issue: No ]
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. [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
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. [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
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. [ Time Frame: Baseline and Final Visit (up to 52 weeks) ] [ Designated as safety issue: No ]
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. [ Time Frame: Weeks 8 through 52 ] [ Designated as safety issue: No ]
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.

Enrollment:	760
Study Start Date:	July 2002
Study Completion Date:	February 2004
Primary Completion Date:	February 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Febuxostat 80 mg QD	Drug: Febuxostat Febuxostat 80 mg, orally, once daily for up to 52 weeks. Other Names: TMX-67 Tei-6720 Uloric
Experimental: Febuxostat 120 mg QD	Drug: Febuxostat Febuxostat 120 mg, orally, once daily for up to 52 weeks. Other Names: TMX-67 Tei-6720 Uloric
Active Comparator: Allopurinol 300 mg QD	Drug: Allopurinol Allopurinol 300 mg, capsules, orally, once daily for up to 52 weeks.

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.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00102440

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

Medical Director

Takeda Global Research & Development Center, Inc.

More Information

Additional Information:

American College of Rheumatology This link exits the ClinicalTrials.gov site

Uloric Package Insert This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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.

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.

Responsible Party:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00102440 History of Changes
Other Study ID Numbers:	C02-010, U1111-1114-0184
Study First Received:	January 29, 2005
Results First Received:	March 12, 2009
Last Updated:	January 31, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

uric Acid
xanthine oxidase
tophi
Drug Therapy

Additional relevant MeSH terms:

Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Allopurinol
Febuxostat

Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Antimetabolites
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012