Dose-Response, Safety and Efficacy of Febuxostat in Subjects With Gout

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of febuxostat, once daily (QD), in reducing serum urate levels in subjects with gout.

Detailed Description
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Gout is a chronic urate crystal deposition disorder, which if left untreated may result in progressive disease characterized by joint and bone destruction from tophaceous deposits and renal impairment due to gouty nephropathy. Hyperuricemia, defined as a serum urate concentration of >7.0 milligrams per deciliter (mg/dL), is the underlying metabolic aberration leading to urate crystal deposition in gout. Gout has several clinical presentations, including: recurrent acute attacks of inflammatory arthritis; deposition of monosodium urate monohydrate crystals in joints, bones and even parenchymal organs (tophaceous gout); renal impairment; and uric acid nephrolithiasis. As serum urate levels increase beyond >7.0 mg/dL, the risks for gouty arthritis or for renal calculi increase. Currently allopurinol is the only xanthine oxidase inhibitor available. Allopurinol is the agent of choice for reduction of serum urate levels in patients with: uric acid overproduction; unresponsive or intolerant to uricosuric agents; impaired renal function; uric acid urolithiasis; or tophi. 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.

Official Title
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Phase II, Dose-Response, Safety and Efficacy Study of Oral TMX-67 in Subjects With Gout.

Conditions
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Gout

Intervention / Treatment
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* Drug: Placebo
* Drug: Febuxostat
* Drug: Febuxostat
* Drug: Febuxostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hyperuricemia (serum uric acid ≥8.0 mg/dL). Must meet American College of Rheumatology criteria for gout. Must have adequate renal function (serum creatinine <1.5 mg/dL). 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 kilogram per meter² (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
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo QD<br> | Drug: Placebo<br>* Febuxostat placebo-matching tablets, orally, once daily for up to 4 weeks.<br>|
| Experimental: Febuxostat 40 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 40 mg, tablets, orally, once daily for up to 4 weeks.<br>* Other names: Uloric;|
| Experimental: Febuxostat 80 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 80 mg, tablets, orally, once daily for up to 4 weeks.<br>* Other names: Uloric;|
| Experimental: Febuxostat 120 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 120 mg, tablets, orally, once daily for up to 4 weeks.<br>* Other names: Uloric;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 Milligram Per Deciliter (mg/dL) at the Day 28 Visit. | Serum urate values were obtained at the Day 28 visit. The percentage of subjects whose serum urate decreased to <6.0 mg/dL at the Day 28 visit was summarized. | Day 28. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 7 Visit. | Serum urate values were obtained at the Day 7 visit. The percentage of subjects whose serum urate decreased to <6.0 mg/dL at the Day 7 visit was summarized. | Day 7. | 
| Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 14 Visit. | Serum urate values were obtained at the Day 14 visit. The percentage of subjects whose serum urate decreased to <6.0 mg/dL at the Day 14 visit was summarized. | Day 14. | 
| Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 21 Visit. | Serum urate values were obtained at the Day 21 visit. The percentage of subjects whose serum urate decreased to <6.0 mg/dL at the Day 21 visit was summarized. | Day 21. | 
| Percent Change in Serum Urate Levels From Baseline to the Day 7 Visit. | Serum urate values were obtained at the Day 7 visit. The percent change in serum urate from baseline to the Day 7 visit was summarized. | Baseline and Day 7. | 
| Percent Change in Serum Urate Levels From Baseline to the Day 14 Visit. | Serum urate values were obtained at the Day 14 visit. The percent change in serum urate from baseline to the Day 14 visit was summarized. | Baseline and Day 14. | 
| Percent Change in Serum Urate Levels From Baseline to the Day 21 Visit | Serum urate values were obtained at the Day 21 visit. The percent change in serum urate from baseline to the Day 21 visit was summarized. | Baseline and Day 21. | 
| Percent Change in Serum Urate Levels From Baseline to the Day 28 Visit. | Serum urate values were obtained at the Day 28 visit. The percent change in serum urate from baseline to the Day 28 visit was summarized. | Baseline and Day 28. | 
| Maximum Percent Change in Serum Urate Level From Baseline During the Entire Treatment Period. | Serum urate values were obtained at the Day 7, 14, 21,and 28 visits. The maximum percent change in serum urate levels obtained at any visit was summarized. | Baseline and Any visit (Day 7, 14, 21,or 28) | 
| Percent Change in 24-hour Urine Uric Acid Level From Baseline to Day 28. | 24-hour urine uric acid levels were obtained at the Day 28 visit. The percent change in 24-hour urine uric acid level from baseline to the Day 28 visit was summarized. | Baseline and Day 28. | 

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