Long-Term Safety of Febuxostat in Subjects With Gout.

Study Overview
=================
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.

Official Title
-----------------
Phase II, Open-Label Study, to Assess the Long-Term Safety of Oral TMX-67 in Subjects With Gout

Conditions
-----------------
Gout

Intervention / Treatment
-----------------
* Drug: Febuxostat
* Drug: Febuxostat
* Drug: Febuxostat


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Febuxostat<br>* Febuxostat 40 mg, tablets, orally, once daily, based on serum urate level.<br>* Other names: Uloric;|
| Experimental: 2<br> | Drug: Febuxostat<br>* Febuxostat 80 mg, tablets, orally, once daily, based on serum urate level.<br>* Other names: Uloric;|
| Experimental: 3<br> | Drug: Febuxostat<br>* Febuxostat 120 mg, tablets, orally, once daily, based on serum urate level.<br>* Other names: Uloric;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit. | 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. | Month 6 | 
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit. | 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. | Month 12 | 
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit. | 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. | Month 18 | 
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit. | 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. | Month 24 | 
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit. | 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. | Month 36 | 
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit. | 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. | Month 48 | 
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit. | 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. | Month 60 | 
| Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Final Visit. | 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. | Last Visit on treatment (up to 66 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Serum Urate Levels From Baseline at Month 6 Visit. | 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. | Baseline and Month 6 | 
| Percent Change in Serum Urate Levels From Baseline at Month 12 Visit. | 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. | Baseline and Month 12 | 
| Percent Change in Serum Urate Levels From Baseline at Month 18 Visit. | 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. | Baseline and Month 18 | 
| Percent Change in Serum Urate Levels From Baseline at Month 24 Visit. | 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. | Baseline and Month 24 | 
| Percent Change in Serum Urate Levels From Baseline at Month 36 Visit. | 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. | Baseline and Month 36 | 
| Percent Change in Serum Urate Levels From Baseline at Month 48 Visit. | 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. | Baseline and Month 48 | 
| Percent Change in Serum Urate Levels From Baseline at Month 60 Visit. | 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. | Baseline and Month 60 | 
| Percent Change in Serum Urate Levels From Baseline at Final Visit. | 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. | Baseline and Last Visit on treatment (up to 66 months). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Uric acid, xanthine oxidase, tophi, Drug Therapy