Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects. - Study Results

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 Drug: Placebo

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 167 investigative sites in the United States from 21 February 2003 to 07 April 2004.

Pre-Assignment Details

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

Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD	Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD	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 QD	Placebo, orally, once daily for up to 28 weeks.

Participant Flow: Overall Study

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Febuxostat 240 mg QD	Allopurinol QD	Placebo QD
STARTED	267	269	134	268	134
COMPLETED	174	200	86	211	101
NOT COMPLETED	93	69	48	57	33
Lost to Follow-up	19	17	9	17	10
Adverse Event	18	16	11	18	5
Personal Reason(s)	16	16	9	9	9
Other	15	8	6	5	3
Gout Flare	13	6	8	1	0
Protocol Violation	6	3	3	6	3
Therapeutic Failure	6	3	2	1	3

Baseline Characteristics

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Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD	Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD	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 QD	Placebo, orally, once daily for up to 28 weeks.

Baseline Measures

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Febuxostat 240 mg QD	Allopurinol QD	Placebo QD	Total
Number of Participants [units: participants]	267	269	134	268	134	1072
Age, Customized [units: subjects]
<45 years	82	79	33	82	36	312
45 years to <65 years	146	154	71	147	79	597
≥65 years	39	36	30	39	19	163
Age [units: years] Mean ± Standard Deviation	50.6 ± 12.24	51.2 ± 11.57	54.3 ± 12.83	51.8 ± 12.25	51.5 ± 12.18	51.6 ± 12.17
Gender [units: subjects]
Female	16	13	8	19	11	67
Male	251	256	126	249	123	1005
Race/Ethnicity, Customized [units: subjects]
White	200	214	107	206	108	835
Black or African American	38	27	13	33	9	120
Hispanic	13	16	8	17	10	64
Asian	8	8	1	6	3	26
Other	8	4	5	6	4	27
Body Mass Index [units: subjects]
<18.5 kilogram per meter² (kg/m²)	0	0	0	0	0	0
18.5 kg/m² to <25 kg/m²	10	11	9	15	16	61
25 kg/m² to <30 kg/m²	85	81	42	91	48	347
≥30 kg/m²	172	176	83	161	70	662
missing	0	1	0	1	0	2
Presence of a Primary PalpableTophus [units: subjects]
Yes	48	53	25	64	29	219
No, but other tophi present	0	3	1	1	1	6
No, and no other tophi present	219	213	108	203	104	847
Serum Creatinine [units: subjects]
≤1.5 milligram per deciliter (mg/dL)	258	258	129	258	129	1032
>1.5 mg/dL	9	11	5	10	5	40

Outcome Measures

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1. Primary:

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) ]

Show Outcome Measure 1

2. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 [ Time Frame: Week 28 ]

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3. Secondary:

Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit [ Time Frame: Final Visit (up to 28 weeks). ]

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4. Secondary:

Percent Change From Baseline in Serum Urate Levels at Week 28. [ Time Frame: Baseline and Week 28 ]

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5. Secondary:

Percent Change From Baseline in Serum Urate Levels at Final Visit [ Time Frame: Baseline and Final Visit (up to 28 weeks) ]

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6. Secondary:

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 ]

Show Outcome Measure 6

7. Secondary:

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) ]

Show Outcome Measure 7

8. Secondary:

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 ]

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9. Secondary:

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) ]

Show Outcome Measure 9

10. Secondary:

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 ]

Show Outcome Measure 10

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
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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:

Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, Lademacher C, Joseph-Ridge N. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008 Nov 15;59(11):1540-8.

Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph-Ridge N. Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):585-91.

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.

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.

Responsible Party:	Takeda Global Research & Development Center, Inc.
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