Safety and Efficacy of Oral Febuxostat in Subjects With Gout

• Sponsor: Xijing Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02082769
• Collaborator: Qingdao Shengbang Pharmaceutical Co., Ltd. (Industry)
• Enrollment: 504
• Arms: 3
• Duration (Months): 27

Study Details

Study Description

Brief Summary

The purpose of this study is to compare febuxostat allopurinol in subjects with gout.

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: Febuxostat; Drug: Allopurinol	Phase 3

Detailed Description

A randomized, double-blind, multicenter, allopurinol-controlled and parallel-assigned study comparing 40 mg, 80 mg of febuxostat, and allopurinol 300 mg in subjects with gout. Subjects will receive treatment for 24 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 504 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Multicenter, Allopurinol-Controlled Study Assessing the Safety and Efficacy of Oral Febuxostat in Subjects With Gout
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Febuxostat 40 mg QD Febuxostat 40 mg, orally, once daily for up to 24 weeks	Drug: Febuxostat
Experimental: Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 24 weeks	Drug: Febuxostat
Active Comparator: Allopurinol 100mg QD Allopurinol 100mg, orally, three times daily for up to 24 weeks	Drug: Allopurinol

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL) [Last 3 visits (any last 3 visits up to week 26)]

Secondary Outcome Measures

1. Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit [Final Visit (up to 26 weeks)]

Other Outcome Measures

1. Absolute Change in the Serum Urate Level at the Final Visit Relative to Baseline [Baseline and Final Visit (up to 26 weeks)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Hyperuricemia (serum urate ≥8.0 mg/dL) and gout by Chinese Rheumatism Association Criteria;

• Renal function defined as a serum creatinine level of < 2.0 mg/dL and creatinine clearance of > 20 milliliters per minute (mL/min) by Cockcroft and Gault formula;

• No gout flare 2 weeks beforehand during 2-week screening period.

Exclusion Criteria:

• Pregnancy or lactation;

• Concurrent therapy with urate lowering agents, azathioprine, 6-mercaptopurine, thiazide diuretics, or medications containing aspirin (>325 mg) or other salicylates;

• Body Mass Index (BMI) >50 kilogram per meter²(kg/m²);

• A history of active liver disease, or hepatic dysfunction;

• A history of bronchial asthma;

• A history of renal calculi or thyroid disease;

• Secondary gout Joint diseases induced by rheumatoid arthritis, psoriatic arthritis and bone tumor;

• Intolerance to allopurinol and Ibuprofen;

• Alcohol intake of ≥ 14 drinks/week;

• Clinically significant medical condition.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Xijing Hospital
• Qingdao Shengbang Pharmaceutical Co., Ltd.

Investigators

• Principal Investigator: Shenren Chen, M.D., The Second Affiliated Hospital of Shantou University Medical College
• Principal Investigator: Yangang Wang, M.D., The Affiliated Hospital of Qingdao University
• Principal Investigator: Xiumei Liu, M.D., The First Affiliated Hospital of Shanxi Medical University
• Principal Investigator: Hong Liu, M.D., First Affiliated Hospital of Guangxi Medical University
• Principal Investigator: Yongde Peng, M.D., Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Principal Investigator: Jianqin Wang, M.D., LanZhou University
• Principal Investigator: Jinying Lin, M.D., People's Hospital of Guangxi
• Principal Investigator: Haiwang Ji, M.D., Shaanxi Provincial People's Hospital
• Principal Investigator: Bin Liu, M.D., The First Hospital of Jilin University
• Principal Investigator: Ying Lu, M.D., Zhejiang Provincial Tongde Hospital
• Principal Investigator: Peng Liu, M.D., Guangxi Ruikang Hospital
• Principal Investigator: Yonghong Zhang, M.D., Luoyang Orthopedic-Traumatological Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Xijing Hospital
• ClinicalTrials.gov Identifier: NCT02082769
• Other Study ID Numbers: SFDA2010L04287
• First Posted: Mar 10, 2014
• Last Update Posted: Feb 3, 2016
• Last Verified: Mar 1, 2014

• Keywords provided by Xijing Hospital: Gout; Uric Acid; Xanthine oxidase; Febuxostat
• Additional relevant MeSH terms: Gout; Allopurinol; Febuxostat

Study Results

Participant Flow

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 100mg QD
Arm/Group Description	Febuxostat 40 mg, orally, once daily for up to 24 weeks Febuxostat	Febuxostat 80 mg, orally, once daily for up to 24 weeks Febuxostat	Allopurinol 100mg, orally, three times daily for up to 24 weeks Allopurinol
Period Title: Overall Study
STARTED	168	168	168
COMPLETED	144	141	132
NOT COMPLETED	24	27	36

Baseline Characteristics

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 100mg QD	Total
Arm/Group Description	Febuxostat 40 mg, orally, once daily for up to 24 weeks Febuxostat	Febuxostat 80 mg, orally, once daily for up to 24 weeks Febuxostat	Allopurinol 100mg, orally, three times daily for up to 24 weeks Allopurinol	Total of all reporting groups
Overall Participants	160	158	159	477
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	160 100%	158 100%	159 100%	477 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (11.9)	48.2 (12.0)	46.5 (10.7)	46.7 (11.2)
Sex: Female, Male (Count of Participants)
Female	158 98.8%	146 92.4%	149 93.7%	453 95%
Male	2 1.3%	12 7.6%	10 6.3%	24 5%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.2 (2.7)	25.1 (2.6)	25.4 (3.3)	25.2 (2.8)
Systolic blood pressure (SBP) (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	126.2 (10.0)	126.4 (11.0)	124.8 (10.1)	126.4 (10.4)
Diastolic blood pressure (DBP) (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	79.1 (8.2)	77.6 (8.1)	78.7 (7.9)	78.5 (8.1)
Baseline serum urate level units (umol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [umol/l]	560.8 (73.3)	565.1 (75.5)	574.2 (77.8)	566.7 (75.2)

Outcome Measures

1. Primary Outcome

Title	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 26)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 100mg QD
Arm/Group Description	Febuxostat 40 mg, orally, once daily for up to 24 weeks Febuxostat	Febuxostat 80 mg, orally, once daily for up to 24 weeks Febuxostat	Allopurinol 100mg, orally, three times daily for up to 24 weeks Allopurinol
Measure Participants	160	158	159
Number [percentage of participants]	22.5 14.1%	33.5 21.2%	17.0 10.7%

2. Secondary Outcome

Title	Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Time Frame	Final Visit (up to 26 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 100mg QD
Arm/Group Description	Febuxostat 40 mg, orally, once daily for up to 24 weeks Febuxostat	Febuxostat 80 mg, orally, once daily for up to 24 weeks Febuxostat	Allopurinol 100mg, orally, three times daily for up to 24 weeks Allopurinol
Measure Participants	160	158	159
Number [percentage of participants]	45.0 28.1%	58.9 37.3%	34.6 21.8%

3. Other Pre-specified Outcome

Title	Absolute Change in the Serum Urate Level at the Final Visit Relative to Baseline
Time Frame	Baseline and Final Visit (up to 26 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Allopurinol 100mg QD
Arm/Group Description	Febuxostat 40 mg, orally, once daily for up to 24 weeks Febuxostat	Febuxostat 80 mg, orally, once daily for up to 24 weeks Febuxostat	Allopurinol 100mg, orally, three times daily for up to 24 weeks Allopurinol
Measure Participants	160	158	159
Mean (Standard Deviation) [umol/l]	182.2 (115.6)	216.0 (137.2)	170.4 (132.6)

Adverse Events

Arm/Group Title	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Allopurinol 100mg QD
Arm/Group Description	Febuxostat 40 mg, orally, once daily for up to 24 weeks Febuxostat		Febuxostat 80 mg, orally, once daily for up to 24 weeks Febuxostat		Allopurinol 100mg, orally, three times daily for up to 24 weeks Allopurinol
All Cause Mortality
	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Allopurinol 100mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Allopurinol 100mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/168 (0%)		1/168 (0.6%)		0/168 (0%)
Renal and urinary disorders
hydronephrosis	0/168 (0%)	0	1/168 (0.6%)	1	0/168 (0%)	0
Other (Not Including Serious) Adverse Events
	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Allopurinol 100mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/168 (26.8%)		46/168 (27.4%)		41/168 (24.4%)
Cardiac disorders
Abnormal electrocardiogram	4/168 (2.4%)	4	0/168 (0%)	0	1/168 (0.6%)	1
Gastrointestinal disorders
Gastrointestinal disorders	3/168 (1.8%)	3	2/168 (1.2%)	2	4/168 (2.4%)	4
General disorders
Others	12/168 (7.1%)	12	10/168 (6%)	10	10/168 (6%)	10
Hepatobiliary disorders
Liver function test abnormalities	17/168 (10.1%)	17	22/168 (13.1%)	22	18/168 (10.7%)	18
Renal and urinary disorders
Renal function test abnormalities	2/168 (1.2%)	2	7/168 (4.2%)	7	2/168 (1.2%)	2
Abnormal urine protein	4/168 (2.4%)	4	4/168 (2.4%)	4	1/168 (0.6%)	1
Skin and subcutaneous tissue disorders
Drug allergy	3/168 (1.8%)	3	1/168 (0.6%)	1	5/168 (3%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.