Clinical trial NCT00430248: Efficacy and Safety of Oral Febuxostat in Participants With Gout
Official title: A Phase 3, Randomized, Multicenter, Double-Blind, Allopurinol-Controlled Study Assessing the Efficacy and Safety of Oral Febuxostat in Subjects With Gout.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gout
Keywords: tophi
hyperuricemia
uric acid
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-02-01
Enrollment: 2269
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy and safety of febuxostat, once Daily (QD), to allopurinol in subjects with hyperuricemia and gout.

Detailed description: Renal impairment is common in subjects with gout, with the prevalence ranging from 50% to 70%. This population represents an unmet medical need as uricosuric drugs are contraindicated in these patients, and the only available treatment, allopurinol, may have to be dose reduced to avoid overt side effects.

Febuxostat (TMX-67) is a non-purine selective xanthine oxidase inhibitor being developed as an orally administered agent for management of hyperuricemia in patients with gout.

Treatment duration will be 6 months.

Eligibility criteria: Inclusion Criteria:

* Has one or more of the American Rheumatism Association criteria for the diagnosis of gout.
* 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.
* Must have a serum urate level greater than or equal to 8.0 milligram per deciliter (mg/dL).

Exclusion Criteria:

* Have a severe, unstable, or life threatening medical condition that would likely prevent them from completing this study.
* Has a known body reaction to febuxostat, allopurinol, naproxen, any other non-steroidal anti-inflammatory drug (NSAID), aspirin, lansoprazole, colchicine, or any components in their formulation.
* History of xanthinuria.
* Alcohol consumption greater than 14/week.
* History of significant concomitant illness.
* Active liver or peptic ulcer disease.
* Has rheumatoid arthritis requiring treatment.
* Has estimated creatinine clearance less than 30 milliliter per minute (mL/min) calculated using the Cockcroft-Gault formula corrected for ideal body weight.
* Requires therapy with any other urate-lowering drug other than the study drug; long-term use of NSAIDs and COX-2 inhibitors; salicylates; thiazide diuretics; losartan; azathioprine; mercaptopurine; theophylline; intravenous (IV) colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole;trimethoprim.

Primary outcomes:
measure: Percentage of Subjects Whose Serum Urate Level is <6.0 Milligrams Per Deciliter (mg/dL) at the Final Visit.
timeFrame: Last Visit on treatment (up to 6 months)
Secondary outcomes:
measure: Percentage of Renal Impairment Subjects Whose Final Visit Serum Urate Level is <6.0 mg/dl
timeFrame: Last Visit on treatment (up to 6 months)
measure: Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 2 Visit.
timeFrame: Month 2
measure: Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 4 Visit.
timeFrame: Month 4
measure: Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 6 Visit.
timeFrame: Month 6
measure: Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 2 Visit.
timeFrame: Month 2
measure: Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 4 Visit.
timeFrame: Month 4
measure: Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit.
timeFrame: Month 6
measure: Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Final Visit.
timeFrame: Last Visit on treatment (up to 6 months)
measure: Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 2 Visit
timeFrame: Month 2
measure: Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 4 Visit
timeFrame: Month 4
measure: Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 6 Visit
timeFrame: Month 6
measure: Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Final Visit
timeFrame: Last Visit on treatment (up to 6 months)
measure: Mean Percent Change From Baseline in Serum Urate Levels at Month 2 Visit.
timeFrame: Baseline and Month 2
measure: Mean Percent Change From Baseline in Serum Urate Levels at Month 4 Visit
timeFrame: Baseline and Month 4
measure: Mean Percent Change From Baseline in Serum Urate Levels at Month 6 Visit.
timeFrame: Baseline and Month 6
measure: Mean Percent Change From Baseline in Serum Urate Levels at Final Visit.
timeFrame: Baseline and Last Visit on treatment (up to 6 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Hoover
country: United States
state: Alabama
city: Hueytown
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Montgomery
country: United States
state: Alabama
city: Northport
country: United States
state: Alabama
city: Ozark
country: United States
state: Alabama
city: Tuscaloosa
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Gilbert
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Sierra Vista
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Fort Smith
country: United States
state: Arkansas
city: Jonesboro
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Carmichael
country: United States
state: California
city: Clovis
country: United States
state: California
city: Concord
country: United States
state: California
city: El Centro
country: United States
state: California
city: Fair Oaks
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: Irvine
country: United States
state: California
city: Laguna Hills
country: United States
state: California
city: LaJolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Rancho Cucamonga
country: United States
state: California
city: Riverside
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Torrance
country: United States
state: California
city: Tustin
country: United States
state: California
city: Vallejo
country: United States
state: California
city: Vista
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: West Covina
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Whittier
country: United States
state: California
city: Boulder
country: United States
state: Colorado
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Highlands Ranch
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Longmont
country: United States
state: Colorado
city: Wheat Ridge
country: United States
state: Colorado
city: Danbury
country: United States
state: Connecticut
city: Trumbull
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Aventura
country: United States
state: Florida
city: Boynton Beach
country: United States
state: Florida
city: Brandon
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Delray Beach
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Gainsville
country: United States
state: Florida
city: Hallandale
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Holly Hill
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Largo
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: New Smyrna Beach
country: United States
state: Florida
city: Opa Locka
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: St. Petersburg
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Winter Haven
country: United States
state: Florida
city: Zephyrhills
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Conyers
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Dunwoody
country: United States
state: Georgia
city: Gainesville
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Stockbridge
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Boise
country: United States
state: Idaho
city: Coeur d'Alene
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Nampa
country: United States
state: Idaho
city: Arlington Heights
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Evanston
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Vernon Hills
country: United States
state: Illinois
city: Elkhart
country: United States
state: Indiana
city: Evansville
country: United States
state: Indiana
city: Mishawaka
country: United States
state: Indiana
city: Clive
country: United States
state: Iowa
city: Des Moines
country: United States
state: Iowa
city: Dubuque
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Elizabethtown
country: United States
state: Kentucky
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Ruston
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Slidell
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Frederick
country: United States
state: Maryland
city: Owings Mills
country: United States
state: Maryland
city: Prince Frederick
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Fall River
country: United States
state: Massachusetts
city: New Bedford
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Flint
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Stevensville
country: United States
state: Michigan
city: Troy
country: United States
state: Michigan
city: Chaska
country: United States
state: Minnesota
city: Flowood
country: United States
state: Mississippi
city: Jackson
country: United States
state: Mississippi
city: Olive Branch
country: United States
state: Mississippi
city: Florissant
country: United States
state: Missouri
city: Jefferson City
country: United States
state: Missouri
city: Manchester
country: United States
state: Missouri
city: Mexico
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Butte
country: United States
state: Montana
city: Grand Island
country: United States
state: Nebraska
city: Lincoln
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Reno
country: United States
state: Nevada
city: Dover
country: United States
state: New Hampshire
city: Blackwood
country: United States
state: New Jersey
city: Edison
country: United States
state: New Jersey
city: Flemington
country: United States
state: New Jersey
city: Manalapan
country: United States
state: New Jersey
city: Medford
country: United States
state: New Jersey
city: Midland Park
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Endwell
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: New York
country: United States
state: New York
city: Smithtown
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Harrisburg
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Lenoir
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Austintown
country: United States
state: Ohio
city: Beachwood
country: United States
state: Ohio
city: Chardon
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Hudson
country: United States
state: Ohio
city: Kettering
country: United States
state: Ohio
city: Lyndhurst
country: United States
state: Ohio
city: Perrysburg
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Willoughby Hills
country: United States
state: Ohio
city: Youngstown
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Bend
country: United States
state: Oregon
city: Eugene
country: United States
state: Oregon
city: Lake Oswego
country: United States
state: Oregon
city: Medford
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Bethlehem
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: East Norriton
country: United States
state: Pennsylvania
city: Feasterville Trevose
country: United States
state: Pennsylvania
city: Harrisburg
country: United States
state: Pennsylvania
city: Lansdale
country: United States
state: Pennsylvania
city: Mechanicsburg
country: United States
state: Pennsylvania
city: Morrisville
country: United States
state: Pennsylvania
city: Penndel
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Reading
country: United States
state: Pennsylvania
city: Scotland
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Cranston
country: United States
state: Rhode Island
city: East Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Mount Pleasant
country: United States
state: South Carolina
city: Orangeburg
country: United States
state: South Carolina
city: Simpsonville
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Bristol
country: United States
state: Tennessee
city: Chattanooga
country: United States
state: Tennessee
city: Clarksville
country: United States
state: Tennessee
city: Collierville
country: United States
state: Tennessee
city: Jackson
country: United States
state: Tennessee
city: Johnson City
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: New Tazewell
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Beaumont
country: United States
state: Texas
city: Bellaire
country: United States
state: Texas
city: Bryan
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Killeen
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Layton
country: United States
state: Utah
city: Midvale
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: St. George
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Chesapeake
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Everett
country: United States
state: Washington
city: Gig Harbor
country: United States
state: Washington
city: Lakewood
country: United States
state: Washington
city: Olympia
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Vancouver
country: United States
state: Washington
city: Monroe
country: United States
state: Wisconsin
city: Oregon
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_CHAIR
References:
citation: Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E, Lademacher C. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 2010;12(2):R63. doi: 10.1186/ar2978. Epub 2010 Apr 6.
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.
citation: Becker MA, MacDonald PA, Hunt B, Gunawardhana L. Treating hyperuricemia of gout: safety and efficacy of febuxostat and allopurinol in older versus younger subjects. Nucleosides Nucleotides Nucleic Acids. 2011 Dec;30(12):1011-7. doi: 10.1080/15257770.2011.603715.
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.
citation: Becker MA, MacDonald PA, Hunt BJ, Jackson RL. Diabetes and gout: efficacy and safety of febuxostat and allopurinol. Diabetes Obes Metab. 2013 Nov;15(11):1049-55. doi: 10.1111/dom.12135. Epub 2013 Jun 12.
citation: Jackson RL, Hunt B, MacDonald PA. The efficacy and safety of febuxostat for urate lowering in gout patients >/=65 years of age. BMC Geriatr. 2012 Mar 21;12:11. doi: 10.1186/1471-2318-12-11.
citation: Wells AF, MacDonald PA, Chefo S, Jackson RL. African American patients with gout: efficacy and safety of febuxostat vs allopurinol. BMC Musculoskelet Disord. 2012 Feb 9;13:15. doi: 10.1186/1471-2474-13-15.