Efficacy and Safety of Oral Febuxostat in Participants With Gout (CONFIRMS)

Study Description

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Brief Summary:

The purpose of this study is to compare the efficacy and safety of febuxostat, once Daily (QD), to allopurinol in subjects with hyperuricemia and gout.

Condition or disease	Intervention/treatment	Phase
Gout	Drug: Febuxostat; Drug: Allopurinol	Phase 3

Detailed Description:

Renal impairment is common in subjects with gout, with the prevalence ranging from 50% to 70%. This population represents an unmet medical need as uricosuric drugs are contraindicated in these patients, and the only available treatment, allopurinol, may have to be dose reduced to avoid overt side effects.

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.

Treatment duration will be 6 months.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	2269 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase 3, Randomized, Multicenter, Double-Blind, Allopurinol-Controlled Study Assessing the Efficacy and Safety of Oral Febuxostat in Subjects With Gout.
Study Start Date :	February 2007
Actual Primary Completion Date :	March 2008
Actual Study Completion Date :	March 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Febuxostat 40 mg QD	Drug: Febuxostat; Febuxostat 40 mg, capsules, orally, once daily for up to 6 months.; Other Names: TMX-67; Tei-6720; Uloric
Experimental: Febuxostat 80 mg QD	Drug: Febuxostat; Febuxostat 80 mg, capsules, orally, once daily for up to 6 months.; Other Names: TMX-67; Tei-6720; Uloric
Active Comparator: Allopurinol 200 mg or 300 mg QD; (dependent on renal function)	Drug: Allopurinol; Allopurinol 200 mg or 300 mg, capsules, orally, once daily for up to 6 months. Dose is dependent on the subject's renal function. Subjects with normal renal function or mild renal impairment received 300 mg once daily; subjects with moderate renal impairment received 200 mg once daily.; Other Name: Zyloprim

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Subjects Whose Serum Urate Level is <6.0 Milligrams Per Deciliter (mg/dL) at the Final Visit. [ Time Frame: Last Visit on treatment (up to 6 months) ]
   The percentage of subjects whose serum urate level 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.

Secondary Outcome Measures :

1. Percentage of Renal Impairment Subjects Whose Final Visit Serum Urate Level is <6.0 mg/dl [ Time Frame: Last Visit on treatment (up to 6 months) ]
   The percentage of subjects with mild-to-moderate renal impairment 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.
2. Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 2 Visit. [ Time Frame: Month 2 ]
   Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 2 visit was summarized.
3. Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 4 Visit. [ Time Frame: Month 4 ]
   Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 4 visit was summarized.
4. Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 6 Visit. [ Time Frame: Month 6 ]
   Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.
5. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 2 Visit. [ Time Frame: Month 2 ]
   Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 2 visit was summarized.
6. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 4 Visit. [ Time Frame: Month 4 ]
   Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 4 visit was summarized.
7. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit. [ Time Frame: Month 6 ]
   Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 6 visit was summarized.
8. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Final Visit. [ Time Frame: Last Visit on treatment (up to 6 months) ]
   The percentage of subjects whose serum urate level was <5.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected.
9. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 2 Visit [ Time Frame: Month 2 ]
   Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 2 visit was summarized.
10. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 4 Visit [ Time Frame: Month 4 ]
    Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 4 visit was summarized.
11. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 6 Visit [ Time Frame: Month 6 ]
    Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 6 visit was summarized.
12. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Final Visit [ Time Frame: Last Visit on treatment (up to 6 months) ]
    The percentage of subjects whose serum urate level was <4.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected.
13. Mean Percent Change From Baseline in Serum Urate Levels at Month 2 Visit. [ Time Frame: Baseline and Month 2 ]
    Serum urate values were obtained at the Month 2 visit. The percent change in serum urate from baseline to the Month 2 visit was summarized.
14. Mean Percent Change From Baseline in Serum Urate Levels at Month 4 Visit [ Time Frame: Baseline and Month 4 ]
    Serum urate values were obtained at the Month 4 visit. The percent change in serum urate from baseline to the Month 4 visit was summarized.
15. Mean Percent Change From Baseline in Serum Urate Levels at Month 6 Visit. [ Time Frame: Baseline and Month 6 ]
    Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.
16. Mean Percent Change From Baseline in Serum Urate Levels at Final Visit. [ Time Frame: Baseline and Last Visit on treatment (up to 6 months) ]
    The percent change in serum urate from baseline to the Final visit was summarized. The final visit was the last visit at which a serum urate value was collected.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Has one or more of the American Rheumatism Association criteria for the diagnosis of gout.
• 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.
• Must have a serum urate level greater than or equal to 8.0 milligram per deciliter (mg/dL).

Exclusion Criteria:

• Have a severe, unstable, or life threatening medical condition that would likely prevent them from completing this study.
• Has a known body reaction to febuxostat, allopurinol, naproxen, any other non-steroidal anti-inflammatory drug (NSAID), aspirin, lansoprazole, colchicine, or any components in their formulation.
• History of xanthinuria.
• Alcohol consumption greater than 14/week.
• History of significant concomitant illness.
• Active liver or peptic ulcer disease.
• Has rheumatoid arthritis requiring treatment.
• Has estimated creatinine clearance less than 30 milliliter per minute (mL/min) calculated using the Cockcroft-Gault formula corrected for ideal body weight.
• Requires therapy with any other urate-lowering drug other than the study drug; long-term use of NSAIDs and COX-2 inhibitors; salicylates; thiazide diuretics; losartan; azathioprine; mercaptopurine; theophylline; intravenous (IV) colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole;trimethoprim.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 258 Study Locations

Sponsors and Collaborators

Takeda

Investigators

Study Chair:	Medical Director	Takeda

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Uloric Package Insert 

FDA Safety Alerts and Recalls 

Publications of Results:

Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E, Lademacher C. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 2010;12(2):R63. doi: 10.1186/ar2978. Epub 2010 Apr 6.

Wortmann RL, Macdonald PA, Hunt B, Jackson RL. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials. Clin Ther. 2010 Dec;32(14):2386-97. doi: 10.1016/j.clinthera.2011.01.008.

Becker MA, MacDonald PA, Hunt B, Gunawardhana L. Treating hyperuricemia of gout: safety and efficacy of febuxostat and allopurinol in older versus younger subjects. Nucleosides Nucleotides Nucleic Acids. 2011 Dec;30(12):1011-7. doi: 10.1080/15257770.2011.603715.

Chohan S, Becker MA, MacDonald PA, Chefo S, Jackson RL. Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol. Arthritis Care Res (Hoboken). 2012 Feb;64(2):256-61. doi: 10.1002/acr.20680.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Becker MA, MacDonald PA, Hunt BJ, Jackson RL. Diabetes and gout: efficacy and safety of febuxostat and allopurinol. Diabetes Obes Metab. 2013 Nov;15(11):1049-55. doi: 10.1111/dom.12135. Epub 2013 Jun 12.

Jackson RL, Hunt B, MacDonald PA. The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age. BMC Geriatr. 2012 Mar 21;12:11. doi: 10.1186/1471-2318-12-11.

Wells AF, MacDonald PA, Chefo S, Jackson RL. African American patients with gout: efficacy and safety of febuxostat vs allopurinol. BMC Musculoskelet Disord. 2012 Feb 9;13:15. doi: 10.1186/1471-2474-13-15.

Responsible Party:	Takeda
ClinicalTrials.gov Identifier:	NCT00430248 History of Changes
Other Study ID Numbers:	F-GT06-153; U1111-1114-0226 ( Registry Identifier: WHO )
First Posted:	February 1, 2007
Results First Posted:	July 16, 2009
Last Update Posted:	February 2, 2012
Last Verified:	January 2012

Keywords provided by Takeda:

tophi; hyperuricemia; uric acid; Drug Therapy

Additional relevant MeSH terms:

Gout; Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Allopurinol	Febuxostat; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Free Radical Scavengers; Antioxidants; Protective Agents; Physiological Effects of Drugs