Clinical trial NCT00174967: Dose-Response, Safety and Efficacy of Febuxostat in Subjects With Gout
Official title: Phase II, Dose-Response, Safety and Efficacy Study 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: 153
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 Milligram Per Deciliter (mg/dL) at the Day 28 Visit.
timeFrame: Day 28.
Secondary outcomes:
measure: Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 7 Visit.
timeFrame: Day 7.
measure: Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 14 Visit.
timeFrame: Day 14.
measure: Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 21 Visit.
timeFrame: Day 21.
measure: Percent Change in Serum Urate Levels From Baseline to the Day 7 Visit.
timeFrame: Baseline and Day 7.
measure: Percent Change in Serum Urate Levels From Baseline to the Day 14 Visit.
timeFrame: Baseline and Day 14.
measure: Percent Change in Serum Urate Levels From Baseline to the Day 21 Visit
timeFrame: Baseline and Day 21.
measure: Percent Change in Serum Urate Levels From Baseline to the Day 28 Visit.
timeFrame: Baseline and Day 28.
measure: Maximum Percent Change in Serum Urate Level From Baseline During the Entire Treatment Period.
timeFrame: Baseline and Any visit (Day 7, 14, 21,or 28)
measure: Percent Change in 24-hour Urine Uric Acid Level From Baseline to Day 28.
timeFrame: Baseline and Day 28.
Other outcomes:
Locations:
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_CHAIR
References:
citation: Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Palo WA, Eustace D, Vernillet L, Joseph-Ridge N. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout. Arthritis Rheum. 2005 Mar;52(3):916-23. doi: 10.1002/art.20935.
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: 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.