Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects. (APEX)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00174915
First received: September 9, 2005
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to compare febuxostat, allopurinol and placebo, once daily (QD), in subjects with gout.


Condition Intervention Phase
Gout
Drug: Febuxostat
Drug: Allopurinol
Drug: Placebo
Phase 3

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: Treatment
Official Title: A Phase 3, Randomized, Multicenter, Allopurinol and Placebo-Controlled Study Assessing the Safety and Efficacy of Oral Febuxostat in Subjects With Gout.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). [ Time Frame: Last 3 visits (any last 3 visits up to week 28) ] [ Designated as safety issue: No ]
    Each subject's serum urate at the last 3 visits determined the subject's response for the primary efficacy variable. A subject who prematurely discontinued without least 3 postbaseline serum urate levels was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used. The last 3 visits used may have differed for each subject.


Secondary Outcome Measures:
  • Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Week 28 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Week 28 visit was summarized.

  • Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit [ Time Frame: Final Visit (up to 28 weeks). ] [ Designated as safety issue: No ]
    The percentage of subjects whose serum urate was <6.0 mg/dL at the final visit was summarized. The final visit was the last visit at which a serum urate value was collected and may have differed by subject.

  • Percent Change From Baseline in Serum Urate Levels at Week 28. [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
    Serum urate values were obtained at the Week 28 visit. The percent change in serum urate was calculated as [(Week 28 - baseline levels)/baseline]*100 and summarized.

  • Percent Change From Baseline in Serum Urate Levels at Final Visit [ Time Frame: Baseline and Final Visit (up to 28 weeks) ] [ Designated as safety issue: No ]
    The percent change in serum urate from baseline to the Final visit was summarized. The percent change in serum urate was calculated as [(Final visit - baseline levels)/baseline]*100. The final visit was the last visit at which a serum urate value was collected. The timing of the final visit may have differed for each subject.

  • Percent Change in Primary Tophus Size at Week 28, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit. [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
    The percent change from baseline in primary tophus size as determined by physical measurement was calculated as [(Week 28 - baseline sizes)/baseline]*100 for the subset of subjects with a primary palpable tophus at the Screening Visit. If the primary tophus was no longer palpable at the Week 28 visit, the size was assumed to be zero.

  • Percent Change in Primary Tophus Size at Final Visit, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit. [ Time Frame: Baseline and Final Visit (up to 28 weeks) ] [ Designated as safety issue: No ]
    Percent change in primary tophus size was calculated as [(Final Visit - baseline sizes)/baseline]*100 for the subset of subjects with a primary palpable tophus at Screening. If tophus was not palpable at Final visit, the size was assumed to be 0. The timing of the final visit may have differed for each subject.

  • Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit. [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]
    Change from baseline at Week 28 in the total number of tophi per subject was calculated for the subset of subjects with palpable tophi at the Screening Visit. If the tophi were not palpable at the Week 28 visit, the total count was assumed to be 0.

  • Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit [ Time Frame: Final Visit (up to 28 weeks) ] [ Designated as safety issue: No ]
    Change in number of tophi/subject was calculated for the subset of subjects with palpable tophi at the Screening. If the tophi were not palpable at the Final Visit, total count was assumed to be 0. The timing of the final visit may have differed for each subject.

  • Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. [ Time Frame: Weeks 8 through 28 ] [ Designated as safety issue: No ]
    Percentage of subjects requiring treatment for a gout flare between Weeks 8 and 28 of the double-blind treatment period was summarized. A subject who reported more than 1 gout flare during this period was counted only once.


Enrollment: 1072
Study Start Date: February 2003
Study Completion Date: April 2004
Primary Completion Date: April 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Febuxostat 80 mg QD Drug: Febuxostat
Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric
Experimental: Febuxostat 120 mg QD Drug: Febuxostat
Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric
Experimental: Febuxostat 240 mg QD Drug: Febuxostat
Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric
Active Comparator: Allopurinol QD Drug: Allopurinol
Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine >1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.
Placebo Comparator: Placebo QD Drug: Placebo
Placebo, orally, once daily for up to 28 weeks.

Detailed Description:

A Phase 3 Study comparing 80 mg, 120 mg or 240 mg of febuxostat, allopurinol (300 mg for those with normal renal function and 100 mg for those with impaired renal function) and placebo administered once daily in subjects with gout.

Subjects will receive treatment for 28 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hyperuricemia (serum urate ≥8.0 mg/dL and gout by American Rheumatism Association Criteria
  • Renal function defined as a serum creatinine level of < 2.0 mg/dL and creatinine clearance of > 20 milliliters per minute (mL/min) by Cockroft and Gault formula.

Exclusion Criteria:

  • History of xanthinuria
  • Intolerance to allopurinol
  • Presence of renal calculi,
  • Alcohol intake of ≥ 14 drinks/week
  • Clinically significant medical condition
  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: NCT00174915

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

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00174915     History of Changes
Other Study ID Numbers: C02-009, U1111-1113-9740
Study First Received: September 9, 2005
Results First Received: March 12, 2009
Last Updated: January 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Uric Acid, gout, xanthine oxidase, febuxostat, tophi

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
Allopurinol
Febuxostat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Antimetabolites
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014