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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Takeda Global Research & Development Center, Inc.

ClinicalTrials.gov Identifier:

NCT00430248

First received: January 25, 2007

Last updated: January 31, 2012

Last verified: January 2012

History of Changes

Results First Received: March 12, 2009

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
Condition:	Gout
Interventions:	Drug: Febuxostat Drug: Allopurinol

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled at 324 sites in the United States from 16 February 2007 to 12 March 2008.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects who were currently receiving urate-lowering therapy discontinued those urate-lowering therapies and initiated prophylactic medications before enrollemnt in once daily (QD) treatment groups.

Reporting Groups

	Description
Febuxostat 40 mg QD	Febuxostat 40 mg, orally, once daily for up to 6 months.
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 6 months.
Allopurinol 200 mg or 300 mg QD	Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.

Participant Flow: Overall Study

	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 200 mg or 300 mg QD
STARTED	757	756	756
COMPLETED	632	598	621
NOT COMPLETED	125	158	135
Adverse Event	49	61	64
Protocol Violation	10	2	4
Personal Reasons	12	24	9
Lost to Follow-up	28	33	28
Therapeutic Failure	1	1	1
Withdrawal by Subject	14	20	16
Inclusion/Exclusion Criteria Not Met	0	2	0
Gout Flare	3	7	2
Reason Not Specified	8	8	11

Baseline Characteristics

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Reporting Groups

	Description
Febuxostat 40 mg QD	Febuxostat 40 mg, orally, once daily for up to 6 months.
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 6 months.
Allopurinol 200 mg or 300 mg QD	Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
Total	Total of all reporting groups

Baseline Measures

	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 200 mg or 300 mg QD	Total
Number of Participants [units: participants]	757	756	756	2269
Age, Customized [units: subjects]
<45 years of age	192	196	180	568
45 to <65 years of age	450	432	445	1327
≥65 years of age	115	128	131	374
Age [units: years] Mean ± Standard Deviation	52.5 ± 11.68	53.0 ± 11.79	52.9 ± 11.73	52.8 ± 11.73
Gender [units: subjects]
Female	35	46	47	128
Male	722	710	709	2141
Ethnicity (NIH/OMB) [units: subjects]
Hispanic or Latino	47	49	53	149
Not Hispanic or Latino	710	707	702	2119
Unknown or Not Reported	0	0	1	1
Race (NIH/OMB) [units: subjects]
American Indian or Alaska Native	6	10	6	22
Asian	26	25	37	88
Native Hawaiian or Other Pacific Islander	11	10	11	32
Black or African American	83	78	67	228
White	620	618	625	1863
More than one race	11	15	8	34
Unknown or Not Reported	0	0	2	2
Body Mass Index [units: subjects]
<18.5 kilograms per meter² (kg/m²)	0	1	1	2
18.5 kg/m² to <25 kg/m²	50	46	42	138
25 kg/m² to <30 kg/m²	215	232	236	683
≥30 kg/m²	490	476	476	1442
Missing	2	1	1	4
Cardiovascular Disease [units: subjects]
No	336	316	320	972
Yes	421	440	436	1297
Renal Function ^[1] [units: subjects]
Moderate Renal Impairment	130	136	136	402
Mild Renal Impairment	349	367	365	1081
Normal Renal Function	278	253	255	786
Mean Body Mass Index [units: kg/m²] Mean ± Standard Deviation	32.9 ± 6.37	32.9 ± 6.39	32.7 ± 6.23	32.8 ± 6.33
Serum Urate [units: milligrams per deciliter (mg/dL)] Mean ± Standard Deviation	9.6 ± 1.15	9.6 ± 1.20	9.5 ± 1.19	9.6 ± 1.18

[1]	Moderate renal impairment - baseline estimated creatinine clearance (CLcr) 30 milliliters per minute (mL/min) to 59 mL/min; Mild renal impairment - baseline estimated CLcr 60 mL/min to 89 mL/min; Normal renal function - estimated CLcr ≥90 mL/min. CLcr calculated using the Cockroft-Gault formula corrected for ideal body weight.

[1]

Moderate renal impairment - baseline estimated creatinine clearance (CLcr) 30 milliliters per minute (mL/min) to 59 mL/min; Mild renal impairment - baseline estimated CLcr 60 mL/min to 89 mL/min; Normal renal function - estimated CLcr ≥90 mL/min.

CLcr calculated using the Cockroft-Gault formula corrected for ideal body weight.

Outcome Measures

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1. Primary:

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) ]

Show Outcome Measure 1

2. Secondary:

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) ]

Show Outcome Measure 2

3. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 2 Visit. [ Time Frame: Month 2 ]

Show Outcome Measure 3

4. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 4 Visit. [ Time Frame: Month 4 ]

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5. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 6 Visit. [ Time Frame: Month 6 ]

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6. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 2 Visit. [ Time Frame: Month 2 ]

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7. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 4 Visit. [ Time Frame: Month 4 ]

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8. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit. [ Time Frame: Month 6 ]

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Measure Type	Secondary
Measure Title	Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit.
Measure Description	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.
Time Frame	Month 6
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects with a serum urate value at Month 6 visit.

Reporting Groups

	Description
Febuxostat 40 mg QD	Febuxostat 40 mg, orally, once daily for up to 6 months.
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 6 months.
Allopurinol 200 mg or 300 mg QD	Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.

Measured Values

	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 200 mg or 300 mg QD
Number of Participants Analyzed [units: participants]	618	596	616
Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit. [units: percentage of subjects]	19.3	49.7	14.8

Statistical Analysis 1 for Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit.

Groups ^[1]	Febuxostat 40 mg QD vs. Allopurinol 200 mg or 300 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	0.041

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The a priori threshold for statistical significance was 0.05 (two-tailed).

Statistical Analysis 2 for Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 200 mg or 300 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The a priori threshold for statistical significance was 0.05 (two-tailed).

Statistical Analysis 3 for Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit.

Groups ^[1]	Febuxostat 40 mg QD vs. Febuxostat 80 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The a priori threshold for statistical significance was 0.05 (two-tailed).

9. Secondary:

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) ]

Show Outcome Measure 9

10. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 2 Visit [ Time Frame: Month 2 ]

Show Outcome Measure 10

11. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 4 Visit [ Time Frame: Month 4 ]

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12. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 6 Visit [ Time Frame: Month 6 ]

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13. Secondary:

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) ]

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14. Secondary:

Mean Percent Change From Baseline in Serum Urate Levels at Month 2 Visit. [ Time Frame: Baseline and Month 2 ]

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15. Secondary:

Mean Percent Change From Baseline in Serum Urate Levels at Month 4 Visit [ Time Frame: Baseline and Month 4 ]

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16. Secondary:

Mean Percent Change From Baseline in Serum Urate Levels at Month 6 Visit. [ Time Frame: Baseline and Month 6 ]

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17. Secondary:

Mean Percent Change From Baseline in Serum Urate Levels at Final Visit. [ Time Frame: Baseline and Last Visit on treatment (up to 6 months) ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Sr. VP, Clinical Sciences
Organization: Takeda Global Research and Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com

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 Apr 6;12(2):R63 [Epub ahead of print]

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.

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.

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.

Publications automatically indexed to this study:

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.

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.

Responsible Party:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00430248 History of Changes
Other Study ID Numbers:	F-GT06-153, U1111-1114-0226
Study First Received:	January 25, 2007
Results First Received:	March 12, 2009
Last Updated:	January 31, 2012
Health Authority:	United States: Food and Drug Administration

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