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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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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.

Goldfarb DS, MacDonald PA, Hunt B, Gunawardhana L. Febuxostat in gout: serum urate response in uric acid overproducers and underexcretors. J Rheumatol. 2011 Jul;38(7):1385-9. doi: 10.3899/jrheum.101156. Epub 2011 May 15.

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