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

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00174967
First received: September 9, 2005
Last updated: July 27, 2011
Last verified: July 2011
  Purpose

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


Condition Intervention Phase
Gout
Drug: Placebo
Drug: Febuxostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Phase II, Dose-Response, Safety and Efficacy Study of Oral TMX-67 in Subjects With Gout.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 Milligram Per Deciliter (mg/dL) at the Day 28 Visit. [ Time Frame: Day 28. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 7 Visit. [ Time Frame: Day 7. ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 14 Visit. [ Time Frame: Day 14. ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 21 Visit. [ Time Frame: Day 21. ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Serum Urate Levels From Baseline to the Day 7 Visit. [ Time Frame: Baseline and Day 7. ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Serum Urate Levels From Baseline to the Day 14 Visit. [ Time Frame: Baseline and Day 14. ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Serum Urate Levels From Baseline to the Day 21 Visit [ Time Frame: Baseline and Day 21. ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Serum Urate Levels From Baseline to the Day 28 Visit. [ Time Frame: Baseline and Day 28. ] [ Designated as safety issue: No ]
    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.

  • Maximum Percent Change in Serum Urate Level From Baseline During the Entire Treatment Period. [ Time Frame: Baseline and Any visit (Day 7, 14, 21,or 28) ] [ Designated as safety issue: No ]
    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.

  • Percent Change in 24-hour Urine Uric Acid Level From Baseline to Day 28. [ Time Frame: Baseline and Day 28. ] [ Designated as safety issue: No ]
    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.


Enrollment: 153
Study Start Date: January 2001
Study Completion Date: July 2001
Primary Completion Date: July 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo QD Drug: Placebo
Febuxostat placebo-matching tablets, orally, once daily for up to 4 weeks.
Experimental: Febuxostat 40 mg QD Drug: Febuxostat
Febuxostat 40 mg, tablets, orally, once daily for up to 4 weeks.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric
Experimental: Febuxostat 80 mg QD Drug: Febuxostat
Febuxostat 80 mg, tablets, orally, once daily for up to 4 weeks.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric
Experimental: Febuxostat 120 mg QD Drug: Febuxostat
Febuxostat 120 mg, tablets, orally, once daily for up to 4 weeks.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric

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

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00174967

Sponsors and Collaborators
Takeda
Investigators
Study Chair: Medical Director Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00174967     History of Changes
Other Study ID Numbers: TMX-00-004, U1111-1114-1992
Study First Received: September 9, 2005
Results First Received: March 12, 2009
Last Updated: July 27, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Uric Acid
xanthine oxidase
tophi
Drug Therapy

Additional relevant MeSH terms:
Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Febuxostat
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014