Febuxostat Versus Allopurinol Control Trial in Subjects With Gout - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment
Condition:	Gout
Interventions:	Drug: Febuxostat Drug: Allopurinol

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled at 112 investigative sites, 106 in the United States and 6 in Canada, from 11 July 2002 to 20 February 2004.

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.

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
STARTED	256	251	253
COMPLETED	168	153	187
NOT COMPLETED	88	98	66
Lost to Follow-up	25	18	21
Adverse Event	16	23	8
Gout Flare	10	28	9
Personal Reason(s)	19	13	13
Other	11	14	14
Protocol Violation	7	2	1

Baseline Characteristics

Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Baseline Measures

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD	Total
Number of Participants [units: participants]	256	251	253	760
Age, Customized [units: subjects]
<45 years	75	71	84	230
45 years to <65 years	140	133	125	398
≥65 years	41	47	44	132
Age [units: years] Mean ± Standard Deviation	51.8 ± 11.69	52.0 ± 12.12	51.6 ± 12.63	51.8 ± 12.13
Gender [units: subjects]
Female	13	8	10	31
Male	243	243	243	729
Body Mass Index [units: subjects]
<18.5 kilogram per meter² (kg/m²)	0	0	0	0
18.5 kg/m² to <25 kg/m²	15	12	7	34
25 kg/m² to <30 kg/m²	75	87	89	251
≥30 kg/m²	166	152	154	472
missing	0	0	3	3
Calculated Creatinine Clearance^[1] [units: subjects]
<50 milliliters per minute (mL/min)	13	8	13	34
50 mL/min to <80 mL/min	77	90	68	235
80 mL/min to <120 mL/min	138	130	140	408
≥120 mL/min	28	23	29	80
missing	0	0	3	3
Presence of Primary Palpable Tophus [units: subjects]
Yes	52	53	46	151
No, but other tophi present	1	2	3	6
No and no other tophi present	203	196	204	603
Race/Ethnicity [units: subjects]
White	193	199	195	587
Black or African American	24	20	18	62
Hispanic	22	17	19	58
Asian	10	9	6	25
Other	7	6	15	28

[1]	Calculated creatinine clearance based on the Cockcroft-Gault equation using ideal body weight.

Outcome Measures

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1. Primary:

Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) [ Last 3 Visits (up to 52 weeks) ]

Show Outcome Measure 1

2. Secondary:

Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit [ Week 28 ]

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3. Secondary:

Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit [ Week 52 ]

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4. Secondary:

Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit [ Final Visit (up to 52 weeks) ]

Show Outcome Measure 4

5. Secondary:

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

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6. Secondary:

Percent Change From Baseline in Serum Urate Levels at Week 52. [ Baseline and Week 52 ]

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7. Secondary:

Percent Change From Baseline in Serum Urate Levels at Final Visit [ Baseline and Final Visit (up to 52 weeks) ]

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8. Secondary:

Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [ Baseline and Week 28 ]

Show Outcome Measure 8

9. Secondary:

Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [ Baseline and Week 52 ]

Show Outcome Measure 9

10. Secondary:

Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [ Baseline and Final Visit (up to 52 weeks) ]

Show Outcome Measure 10

11. Secondary:

Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. [ Baseline and Week 28 ]

Show Outcome Measure 11

12. Secondary:

Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. [ Baseline and Week 52 ]

Show Outcome Measure 12

13. Secondary:

Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. [ Baseline and Final Visit (up to 52 weeks) ]

Show Outcome Measure 13

14. Secondary:

Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52. [ Weeks 8 through 52 ]

Show Outcome Measure 14

Serious Adverse Events

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Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Serious Adverse Events

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Total, serious adverse events
# participants affected	10	19	18
Cardiac disorders
Cardiac Disorders not elsewhere classified (NEC) ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Coronary Artery Disorders NEC ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	4/253 (1.58%)
Heart Failures NEC ^†^A # participants affected / at risk	3/256 (1.17%)	1/251 (0.40%)	0/253 (0.00%)
Ischaemic Coronary Artery Disorders NEC ^†^A # participants affected / at risk	3/256 (1.17%)	2/251 (0.80%)	2/253 (0.79%)
Rate and Rhythm Disorders NEC ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Supraventricular Arrhythmias ^†^A # participants affected / at risk	1/256 (0.39%)	1/251 (0.40%)	0/253 (0.00%)
Ventricular Arrhythmias and Cardiac Arrest ^†^A # participants affected / at risk	0/256 (0.00%)	2/251 (0.80%)	1/253 (0.40%)
Gastrointestinal disorders
Acute and Chronic Pancreatitis ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Gastrointestinal Fistulae ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Gastrointestinal Ulcers and Perforation, Site Unspecified ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Intestinal Haemorrhages ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Intestinal Ulcers and Perforation NEC ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Peritoneal and Retroperitoneal Haemorrhages ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Umbilical Hernias ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
General disorders
Febrile Disorders ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Immune system disorders
Allergies to Food, Food Additives, Drugs and Other Chemicals ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Infections and infestations
Abdominal and Gastrointestinal Infections ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	2/253 (0.79%)
Infections NEC ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Lower Respiratory Tract and Lung Infections ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Skin Structures and Soft Tissue Infections ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Staphylococcal Infections ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Urinary Tract Infections ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Viral Infections NEC ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Injury, poisoning and procedural complications
Chest and Lung Injuries NEC ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Non-Site Specific Injuries NEC ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Site Specific Injuries NEC ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Investigations
Coagulation and Bleeding Analyses ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Musculoskeletal and connective tissue disorders
Joint Related Signs and Symptoms ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Musculoskeletal and Connective Tissue Signs and Symptoms NEC ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Osteoarthropathies ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Spine and Neck Deformities ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colonic Neoplasms Malignant ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Prostatic Neoplasms Malignant ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Testicular Neoplasms Malignant ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Nervous system disorders
Central Nervous System Vascular Disorders NEC ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Central nervous system Hemorrhages & Cerebrovascular Accidents ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Cervical Spinal Cord and Nerve Root Disorders ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Disturbances in Consciousness NEC ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	1/253 (0.40%)
Encephalopathies NEC ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Renal and urinary disorders
Renal Failure and Impairment ^†^A # participants affected / at risk	2/256 (0.78%)	0/251 (0.00%)	0/253 (0.00%)
Renal Lithiasis ^†^A # participants affected / at risk	0/256 (0.00%)	0/251 (0.00%)	1/253 (0.40%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm and Obstruction ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Pneumothorax and Pleural Effusions NEC ^†^A # participants affected / at risk	1/256 (0.39%)	0/251 (0.00%)	0/253 (0.00%)
Pulmonary Thrombotic and Embolic Conditions ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)
Respiratory Failures (Excluding [Excl] Neonatal) ^†^A # participants affected / at risk	1/256 (0.39%)	1/251 (0.40%)	0/253 (0.00%)
Vascular disorders
Peripheral Embolism and Thrombosis ^†^A # participants affected / at risk	0/256 (0.00%)	1/251 (0.40%)	0/253 (0.00%)

^†	Indicates events were collected by systematic assessment.
^A	Term from vocabulary, MedDRA 7.0

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:

Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005 Dec 8;353(23):2450-61.

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.

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	C02-010
Study First Received:	January 29, 2005
Results First Received:	March 12, 2009
Last Updated:	August 17, 2009
ClinicalTrials.gov Identifier:	NCT00102440 History of Changes
Health Authority:	United States: Food and Drug Administration