Long-Term Safety of Febuxostat in Subjects With Gout. - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Gout
Intervention:	Drug: Febuxostat

Participant Flow

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 23 investigational sites in the United States from 21 March 2001 to 29 December 2006

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were to have completed 4 weeks of double-blind dosing in Study TMX-00-004 (NCT00174967) before enrollment in once daily (QD) treatment groups. Dose titrations will occur in order to obtain and maintain clinically acceptable serum urate levels.

Reporting Groups

	Description
Febuxostat 40 mg QD	Febuxostat 40 mg, orally, once daily, based on serum urate level.
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily, based on serum urate level.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Total Febuxostat	No text entered.

Participant Flow: Overall Study

	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
STARTED	8 ^[1]	79 ^[1]	29 ^[1]	116
COMPLETED	6	41	11	58
NOT COMPLETED	2	38	18	58
Adverse Event	1	10	2	13
Protocol Violation	0	1	0	1
Lost to Follow-up	0	3	2	5
Personal Reason(s)	0	14	8	22
Gout Flare	0	4	4	8
Reason Not Specified	1	6	2	9

[1]	Subjects started on febuxostat 80mg. Number of subjects based on Final Stable Dose after titration.

Baseline Characteristics

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Reporting Groups

	Description
Febuxostat 40 mg QD	Febuxostat 40 mg orally, once daily, based on serum urate level.
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily, based on serum urate level
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily, based on serum urate level

Baseline Measures

	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total
Number of Participants [units: participants]	8	79	29	116
Age, Customized [units: Subjects]
<45 years	2	20	9	31
45 to <65 years	4	40	15	59
≥65 years	2	19	5	26
Age [units: years] Mean ± Standard Deviation	54.5 ± 11.44	53.9 ± 12.85	51.3 ± 13.01	53.3 ± 12.74
Gender [units: subjects]
Female	0	9	2	11
Male	8	70	27	105
History of Kidney Stone [units: Subjects]
Yes	0	11	3	14
No	8	68	26	102
Presence of Tophus [units: Subjects]
Yes	1	13	12	26
No	7	66	17	90
Race/Ethnicity [units: Subjects]
Asian	0	0	2	2
Black or African American	1	5	3	9
White	7	71	21	99
Hispanic	0	2	1	3
Other	0	1	2	3
Renal Function ^[1] [units: Subjects]
Normal	3	33	12	48
Impaired	5	46	17	68
Urine Uric Acid [units: Subjects]
Underexcretor	5	62	21	88
Overproducer	3	16	7	26
Missing	0	1	1	2
Body Mass Index [units: kiligram per meter² (kg/m²)] Mean ± Standard Deviation	28.4 ± 2.78	32.9 ± 5.28	33.9 ± 6.82	32.9 ± 5.69
Serum Urate [units: mg/dL] Mean ± Standard Deviation	9.58 ± 1.18	9.48 ± 1.04	10.23 ± 1.74	9.7 ± 1.30

[1]	Impaired renal function was defined as serum creatinine >1.5 milligrams per deciliter (mg/dL) or a creatinine clearance of ≤80 milliliters per minute (mL/min)

Outcome Measures

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1. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit. [ Time Frame: Month 6 ]

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2. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit. [ Time Frame: Month 12 ]

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3. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit. [ Time Frame: Month 18 ]

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4. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit. [ Time Frame: Month 24 ]

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5. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit. [ Time Frame: Month 36 ]

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6. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit. [ Time Frame: Month 48 ]

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7. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit. [ Time Frame: Month 60 ]

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8. Primary:

Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Final Visit. [ Time Frame: Last Visit on treatment (up to 66 months). ]

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9. Secondary:

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

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10. Secondary:

Percent Change in Serum Urate Levels From Baseline at Month 12 Visit. [ Time Frame: Baseline and Month 12 ]

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11. Secondary:

Percent Change in Serum Urate Levels From Baseline at Month 18 Visit. [ Time Frame: Baseline and Month 18 ]

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12. Secondary:

Percent Change in Serum Urate Levels From Baseline at Month 24 Visit. [ Time Frame: Baseline and Month 24 ]

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13. Secondary:

Percent Change in Serum Urate Levels From Baseline at Month 36 Visit. [ Time Frame: Baseline and Month 36 ]

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14. Secondary:

Percent Change in Serum Urate Levels From Baseline at Month 48 Visit. [ Time Frame: Baseline and Month 48 ]

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15. Secondary:

Percent Change in Serum Urate Levels From Baseline at Month 60 Visit. [ Time Frame: Baseline and Month 60 ]

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16. Secondary:

Percent Change in Serum Urate Levels From Baseline at Final Visit. [ Time Frame: Baseline and Last Visit on treatment (up to 66 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 Science
Organization: Takeda Global Research & Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com

Publications of Results:

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.

Schumacher HR Jr, Becker MA, Lloyd E, MacDonald PA, Lademacher C. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology. 2009 Feb;48(2):188-194.

Whelton A, Macdonald PA, Zhao L, Hunt B, Gunawardhana L. Renal function in gout: long-term treatment effects of febuxostat. J Clin Rheumatol. 2011 Jan;17(1):7-13.

Responsible Party:	Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00174941 History of Changes
Other Study ID Numbers:	TMX-01-005, U1111-1114-2039
Study First Received:	September 12, 2005
Results First Received:	March 12, 2009
Last Updated:	January 25, 2011
Health Authority:	United States: Food and Drug Administration