Long-Term Safety of Febuxostat in Subjects With Gout. - Full Text View

Sponsored by:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00174941

Purpose

The purpose of this study is to evaluate the long-term safety of febuxostat in maintaining serum urate levels within clinically acceptable levels in subjects with gout.

Condition	Intervention	Phase
Gout	Drug: Febuxostat	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II, Open-Label Study, to Assess the Long-Term Safety of Oral TMX-67 in Subjects With Gout

Resource links provided by NLM:

MedlinePlus related topics: Gout

Drug Information available for: Tei 6720

U.S. FDA Resources

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

Primary Outcome Measures:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit. [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit. [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit. [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit. [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit. [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit. [ Time Frame: Month 48 ] [ Designated as safety issue: No ]
Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit. [ Time Frame: Month 60 ] [ Designated as safety issue: No ]
Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Final Visit. [ Time Frame: Last Visit on treatment (up to 66 months). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent Change in Serum Urate Levels From Baseline at Month 6 Visit. [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
Percent Change in Serum Urate Levels From Baseline at Month 12 Visit. [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
Percent Change in Serum Urate Levels From Baseline at Month 18 Visit. [ Time Frame: Baseline and Month 18 ] [ Designated as safety issue: No ]
Percent Change in Serum Urate Levels From Baseline at Month 24 Visit. [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
Percent Change in Serum Urate Levels From Baseline at Month 36 Visit. [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
Percent Change in Serum Urate Levels From Baseline at Month 48 Visit. [ Time Frame: Baseline and Month 48 ] [ Designated as safety issue: No ]
Percent Change in Serum Urate Levels From Baseline at Month 60 Visit. [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
Percent Change in Serum Urate Levels From Baseline at Final Visit. [ Time Frame: Baseline and Last Visit on treatment (up to 66 months). ] [ Designated as safety issue: No ]

Enrollment:	116
Study Start Date:	March 2001
Study Completion Date:	December 2006
Primary Completion Date:	December 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Febuxostat Febuxostat 40 mg, tablets, orally, once daily, based on serum urate level.
2: Experimental	Drug: Febuxostat Febuxostat 80 mg, tablets, orally, once daily, based on serum urate level.
3: Experimental	Drug: Febuxostat Febuxostat 120 mg, tablets, orally, once daily, based on serum urate level.

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 milligrams per deciliter [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 not sufficient) 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 in part of uric acid crystals. Management of gout requires chronic treatment aimed at lowering serum urate 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 management of hyperuricemia in patients with gout.

Subjects who want to participate in this study will have successfully completed study TMX-00-004 (NCT00174967).

All participants will initially receive an 80 mg dose. Dose titrations will occur in order to obtain and maintain clinically acceptable serum urate levels.

Eligibility

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

Criteria

Inclusion Criteria:

Hyperuricemia (serum uric acid ≥8.0 mg/dL upon entering parent study TMX-00-004).
Must meet American College of Rheumatology criteria for gout.
Must have adequate renal function (serum creatinine <1.5 mg/dL).
Must have completed four weeks of double-blind dosing in Study TMX-00-004.
Must not have experienced any serious study drug-related Adverse Events in Study TMX 00-004.
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.

Exclusion Criteria:

History of xanthinuria
Alcohol consumption >14/week
Has a History of significant concomitant illness
Has active liver disease.
Has a body mass index greater than 50 kg/m2
Any other significant medical condition that would interfere with the treatment, safety or compliance with the protocol, as defined by the investigator.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00174941

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Chair:

Medical Director

Takeda Global Research & Development Center, Inc.

More Information

Additional Information:

Uloric Package Insert This link exits the ClinicalTrials.gov site

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

Publications:

Colwell HH, Hunt BJ, Pasta DJ, Palo WA, Mathias SD, Joseph-Ridge N. Gout Assessment Questionnaire: Initial results of reliability, validity and responsiveness. Int J Clin Pract. 2006 Oct;60(10):1210-7. Epub 2006 Aug 15.

Schumacher HR Jr, Becker MA, Lloyd E, MacDonald PA, Lademacher C. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology. 2009 Feb;48(2):188-194.

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	TMX-01-005
Study First Received:	September 12, 2005
Results First Received:	March 12, 2009
Last Updated:	August 13, 2009
ClinicalTrials.gov Identifier:	NCT00174941 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Uric acid
xanthine oxidase
tophi
Drug Therapy

Study placed in the following topic categories:

Metabolic Diseases
Joint Diseases
Febuxostat
Rheumatic Diseases
Gout
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors

Uric Acid
Musculoskeletal Diseases
Genetic Diseases, Inborn
Arthritis
Antirheumatic Agents
Metabolic Disorder

Additional relevant MeSH terms:

Metabolic Diseases
Joint Diseases
Febuxostat
Rheumatic Diseases
Gout Suppressants
Pharmacologic Actions
Gout

Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Musculoskeletal Diseases
Genetic Diseases, Inborn
Arthritis
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 02, 2009