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

Gout Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00174967
• Other study ID #: TMX-00-004
• Secondary ID: U1111-1114-1992
• Status: Completed
• Phase: Phase 2
• First received: September 9, 2005
• Last updated: July 27, 2011
• Start date: January 2001
• Est. completion date: July 2001

Study information

• Verified date: July 2011
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: July 2001
• Est. primary completion date: July 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• Placebo
Febuxostat placebo-matching tablets, orally, once daily for up to 4 weeks.
• Febuxostat
Febuxostat 40 mg, tablets, orally, once daily for up to 4 weeks.
• Febuxostat
Febuxostat 80 mg, tablets, orally, once daily for up to 4 weeks.
• Febuxostat
Febuxostat 120 mg, tablets, orally, once daily for up to 4 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

References & Publications (3)

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-co — View 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. Epub 2006 Aug 15. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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)	No
Secondary	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.	No

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