Long-Term Safety of Febuxostat in Subjects With Gout. (FOCUS)

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00174941
First received: September 12, 2005
Last updated: January 25, 2011
Last verified: January 2011
  Purpose

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


Condition Intervention Phase
Gout
Drug: Febuxostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


Further study details as provided by Takeda:

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 ]
    Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.

  • 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 ]
    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 or is Maintained at <6.0 mg/dL at Month 18 Visit. [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Month 18 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 18 visit was summarized.

  • 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 ]
    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 or is Maintained at <6.0 mg/dL at Month 36 Visit. [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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 or is Maintained at <6.0 mg/dL at Month 48 Visit. [ Time Frame: Month 48 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Month 48 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 48 visit was summarized.

  • 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 ]
    Serum urate values were obtained at the Month 60 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 60 visit was summarized.

  • 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 ]
    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.


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 ]
    Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.

  • Percent Change in Serum Urate Levels From Baseline at Month 12 Visit. [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Month 12 visit. The percent change in serum urate from baseline to the Month 12 visit was summarized.

  • Percent Change in Serum Urate Levels From Baseline at Month 18 Visit. [ Time Frame: Baseline and Month 18 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Month 18 visit. The percent change in serum urate from baseline to the Month 18 visit was summarized.

  • Percent Change in Serum Urate Levels From Baseline at Month 24 Visit. [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Month 24 visit. The percent change in serum urate from baseline to the Month 24 visit was summarized.

  • Percent Change in Serum Urate Levels From Baseline at Month 36 Visit. [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Month 36 visit. The percent change in serum urate from baseline to the Month 36 visit was summarized.

  • Percent Change in Serum Urate Levels From Baseline at Month 48 Visit. [ Time Frame: Baseline and Month 48 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Month 48 visit. The percent change in serum urate from baseline to the Month 48 visit was summarized.

  • Percent Change in Serum Urate Levels From Baseline at Month 60 Visit. [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    The secondary outcome was the mean percent change from baseline to Month 60 visit as assessed by serum urate levels collected at baseline and at the Month 60 visit by dose at observation.

  • 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 ]
    The percent change in serum urate from baseline to the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.


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
Experimental: 1 Drug: Febuxostat
Febuxostat 40 mg, tablets, orally, once daily, based on serum urate level.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric
Experimental: 2 Drug: Febuxostat
Febuxostat 80 mg, tablets, orally, once daily, based on serum urate level.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric
Experimental: 3 Drug: Febuxostat
Febuxostat 120 mg, tablets, orally, once daily, based on serum urate level.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Sponsors and Collaborators
Takeda
Investigators
Study Chair: Medical Director Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00174941     History of Changes
Other Study ID Numbers: TMX-01-005, U1111-1114-2039
Study First Received: September 12, 2005
Results First Received: March 12, 2009
Last Updated: January 25, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
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
Febuxostat
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014