Clinical trial NCT00174941: Long-Term Safety of Febuxostat in Subjects With Gout.
Official title: Phase II, Open-Label Study, to Assess the Long-Term Safety of Oral TMX-67 in Subjects With Gout
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gout
Keywords: Uric acid
xanthine oxidase
tophi
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit.
timeFrame: Month 6
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit.
timeFrame: Month 12
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit.
timeFrame: Month 18
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit.
timeFrame: Month 24
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit.
timeFrame: Month 36
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit.
timeFrame: Month 48
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit.
timeFrame: Month 60
measure: Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Final Visit.
timeFrame: Last Visit on treatment (up to 66 months).
Secondary outcomes:
measure: Percent Change in Serum Urate Levels From Baseline at Month 6 Visit.
timeFrame: Baseline and Month 6
measure: Percent Change in Serum Urate Levels From Baseline at Month 12 Visit.
timeFrame: Baseline and Month 12
measure: Percent Change in Serum Urate Levels From Baseline at Month 18 Visit.
timeFrame: Baseline and Month 18
measure: Percent Change in Serum Urate Levels From Baseline at Month 24 Visit.
timeFrame: Baseline and Month 24
measure: Percent Change in Serum Urate Levels From Baseline at Month 36 Visit.
timeFrame: Baseline and Month 36
measure: Percent Change in Serum Urate Levels From Baseline at Month 48 Visit.
timeFrame: Baseline and Month 48
measure: Percent Change in Serum Urate Levels From Baseline at Month 60 Visit.
timeFrame: Baseline and Month 60
measure: Percent Change in Serum Urate Levels From Baseline at Final Visit.
timeFrame: Baseline and Last Visit on treatment (up to 66 months).
Other outcomes:
Locations:
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1111/j.1742-1241.2006.01104.x. Epub 2006 Aug 15.
citation: 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 (Oxford). 2009 Feb;48(2):188-94. doi: 10.1093/rheumatology/ken457.
citation: Whelton A, Macdonald PA, Zhao L, Hunt B, Gunawardhana L. Renal function in gout: long-term treatment effects of febuxostat. J Clin Rheumatol. 2011 Jan;17(1):7-13. doi: 10.1097/RHU.0b013e318204aab4.