Back to resultsEffect of Febuxostat on Renal Function in Patients With Gout and Moderate to Severe Renal Impairment
Primary Purpose
Renal Impairment
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Febuxostat
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Renal Impairment focused on measuring Gout, physiology, Hyperuricemia, Uric Acid, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Must have a serum urate greater than 7 mg/dL and a serum creatinine greater than or equal to 1.5 mg at Day -21
- Must have a history or presence of gout defined as having one or more of the American Rheumatism Association criteria for the diagnosis of gout (the criteria related to tophi have been excluded for the purpose of the study)
- Must have an estimated Glomerular Filtration Rate (eGFR) of 15 or greater, or less than or equal to 50 mL/min, AND a serum creatinine greater than 1.5 mg/dL at Screening Visit Day -21
Exclusion Criteria:
- Has secondary hyperuricemia (eg, due to myeloproliferative disorder, or organ transplant)
- Has tophaceous gout
- Has a history of xanthinuria
- Has received aspirin greater than 325 mg/day within 35 days prior to Day 1/Randomization Visit
- Has known hypersensitivity or allergy to allopurinol or any component in its formulation
- Has known hypersensitivity to febuxostat or colchicine or any components in their formulation
- Has myocardial infarction or stroke within the 90 days prior to the Screening Visit
- Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0 times the upper limit of normal
- Has end stage renal disease or is likely to be a candidate for dialysis over the 1 year study period
- Has a serum creatinine less than or equal to 1.5 mg/dL, or an estimated Glomerular Filtration Rate at Day -21 Screening Visit less than 15 mL/min or greater than 50 mL/min as calculated by the central laboratory
- Is required to take excluded medications
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Febuxostat 30 mg BID
Febuxostat 40/80 mg QD
Arm Description
Placebo-matching capsules, orally, twice daily for up to 12 months.
Febuxostat 30 mg, capsules, orally, twice daily (BID) for up to 12 months.
Participants initially received febuxostat 40 mg, capsules, once daily (QD) and one placebo-matching capsule QD and remained on this dose for up to 12 months if their serum urate (sUA) was <6.0 mg/dL at the Day 14 visit. Participants whose sUA was ≥6.0 mg/dL at the Day 14 visit received febuxostat 80 mg, capsule, QD, and one placebo-matching capsule QD at the Month 1 visit, and for the remainder of the study.
Outcomes
Primary Outcome Measures
Change From Baseline to Month 12 in Serum Creatinine
Renal function was assessed by measuring the change from Baseline in serum creatinine. Analyses were conducted by the Central Laboratory.
Secondary Outcome Measures
Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
Change from baseline to Month 12 in estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula (as calculated by the central laboratory).
Percentage of Participants With Serum Urate (sUA) Less Than 6 mg/dL at Month 12
Serum urate concentrations were determined using the enzymatic method as performed by the Central Laboratory.
Mean Clearance (CL/F) of Febuxostat at Steady State
Mean CL/F at steady state were estimated using a population pharmacokinetic (PK) approach, based on 2 PK samples collected prior to dosing, and 4 PK samples collected postdose.
Mean Area Under the Concentration-Time Curve During the Dosing Interval (AUC[0-τ]) of Febuxostat at Steady State
Mean AUC during the dosing interval at steady state was estimated using a population pharmacokinetic (PK) approach, based on 2 PK samples collected prior to dosing, and 4 PK samples collected postdose.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01082640
Brief Title
Effect of Febuxostat on Renal Function in Patients With Gout and Moderate to Severe Renal Impairment
Official Title
A Multicenter, Randomized, Double-Blind, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo on Renal Function in Gout Subjects With Hyperuricemia and Moderate to Severe Renal Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the effect of febuxostat, once daily (QD) or twice daily (BID), on renal function in gout patients with elevated serum urate levels and who have moderate to severe renal impairment.
Detailed Description
Gout is caused by high levels of uric acid in the body, and is associated with a broad range of conditions including heart disease, chronic kidney disease and high blood pressure. Hyperuricemia, which is defined as an elevation in serum urate levels, develops into gout when urate crystals form in the body and settle in joints and other organs.
Approximately 40-60% of patients with hyperuricemia and gout have some degree of renal impairment. Hyperuricemia has long been associated with renal disease, and chronic hyperuricemia as seen in gout can lead to deposition of urate crystals resulting in diminished renal function.
This study will evaluate the effect of febuxostat on the renal function of patients with hyperuricemia and gout and moderate to severe renal impairment.
All participants must have an average sitting blood pressure measurement less than 160 mmHg systolic and less than 95 mmHg diastolic. All participants must meet the American Rheumatism Association (ARA) diagnostic criteria for gout (subjects with tophi were excluded). Participants are expected to return to the site for approximately 10 visits.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment
Keywords
Gout, physiology, Hyperuricemia, Uric Acid, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo-matching capsules, orally, twice daily for up to 12 months.
Arm Title
Febuxostat 30 mg BID
Arm Type
Experimental
Arm Description
Febuxostat 30 mg, capsules, orally, twice daily (BID) for up to 12 months.
Arm Title
Febuxostat 40/80 mg QD
Arm Type
Experimental
Arm Description
Participants initially received febuxostat 40 mg, capsules, once daily (QD) and one placebo-matching capsule QD and remained on this dose for up to 12 months if their serum urate (sUA) was <6.0 mg/dL at the Day 14 visit. Participants whose sUA was ≥6.0 mg/dL at the Day 14 visit received febuxostat 80 mg, capsule, QD, and one placebo-matching capsule QD at the Month 1 visit, and for the remainder of the study.
Intervention Type
Drug
Intervention Name(s)
Febuxostat
Other Intervention Name(s)
Uloric, TMX-67
Intervention Description
Febuxostat capsules
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Febuxostat placebo-matching capsules
Primary Outcome Measure Information:
Title
Change From Baseline to Month 12 in Serum Creatinine
Description
Renal function was assessed by measuring the change from Baseline in serum creatinine. Analyses were conducted by the Central Laboratory.
Time Frame
Baseline and Month 12
Secondary Outcome Measure Information:
Title
Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
Description
Change from baseline to Month 12 in estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula (as calculated by the central laboratory).
Time Frame
Baseline and Month 12
Title
Percentage of Participants With Serum Urate (sUA) Less Than 6 mg/dL at Month 12
Description
Serum urate concentrations were determined using the enzymatic method as performed by the Central Laboratory.
Time Frame
Month 12
Title
Mean Clearance (CL/F) of Febuxostat at Steady State
Description
Mean CL/F at steady state were estimated using a population pharmacokinetic (PK) approach, based on 2 PK samples collected prior to dosing, and 4 PK samples collected postdose.
Time Frame
The 2 pre-dose PK samples collected were collected at any 2 of the following visits: Months 3, 6, 9, and/or 12, at -0.25 to 0 hours. The 4 postdose PK samples were collected at Months 3, 6, and/or 9, at 0.25; 0.75 to 2.0; 2.5 to 4.0; and 5 to 12 hours.
Title
Mean Area Under the Concentration-Time Curve During the Dosing Interval (AUC[0-τ]) of Febuxostat at Steady State
Description
Mean AUC during the dosing interval at steady state was estimated using a population pharmacokinetic (PK) approach, based on 2 PK samples collected prior to dosing, and 4 PK samples collected postdose.
Time Frame
The 2 pre-dose PK samples collected were collected at any 2 of the following visits: Months 3, 6, 9, and/or 12, at -0.25 to 0 hours. The 4 postdose PK samples were collected at Months 3, 6, and/or 9, at 0.25; 0.75 to 2.0; 2.5 to 4.0; and 5 to 12 hours.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have a serum urate greater than 7 mg/dL and a serum creatinine greater than or equal to 1.5 mg at Day -21
Must have a history or presence of gout defined as having one or more of the American Rheumatism Association criteria for the diagnosis of gout (the criteria related to tophi have been excluded for the purpose of the study)
Must have an estimated Glomerular Filtration Rate (eGFR) of 15 or greater, or less than or equal to 50 mL/min, AND a serum creatinine greater than 1.5 mg/dL at Screening Visit Day -21
Exclusion Criteria:
Has secondary hyperuricemia (eg, due to myeloproliferative disorder, or organ transplant)
Has tophaceous gout
Has a history of xanthinuria
Has received aspirin greater than 325 mg/day within 35 days prior to Day 1/Randomization Visit
Has known hypersensitivity or allergy to allopurinol or any component in its formulation
Has known hypersensitivity to febuxostat or colchicine or any components in their formulation
Has myocardial infarction or stroke within the 90 days prior to the Screening Visit
Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0 times the upper limit of normal
Has end stage renal disease or is likely to be a candidate for dialysis over the 1 year study period
Has a serum creatinine less than or equal to 1.5 mg/dL, or an estimated Glomerular Filtration Rate at Day -21 Screening Visit less than 15 mL/min or greater than 50 mL/min as calculated by the central laboratory
Is required to take excluded medications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Birmingham
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Alabama
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United States
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Peoria
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United States
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Sierra Vista
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Tucson
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Little Rock
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Huntington Park
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Irvine
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Lakewood
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United States
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Long Beach
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Sacramento
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San Diego
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San Jose
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Tustin
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Arvada
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Colorado
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Westminster
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Wheat Ridge
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Middlebury
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Connecticut
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Brandon
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Daytona Beach
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Jacksonville
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Miami
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Pinellas Park
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Port Charlotte
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Port Orange
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Augusta
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Conyers
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Dunwoody
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Honolulu
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Boise
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United States
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Evergreen Park
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Springfield
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Valparaiso
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Wichita
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United States
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Elizabethtown
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Paducah
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Baltimore
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Detroit
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United States
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Kalamazoo
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United States
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Brooklyn Center
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United States
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Neptune City
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United States
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Morganton
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United States
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Wilmington
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Fargo
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United States
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Oklahoma City
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Portland
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Bethlehem
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Anderson
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Greer
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Chattanooga
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United States
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Houston
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United States
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Odessa
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United States
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San Antonio
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Texas
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Danville
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Virginia
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United States
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Fairfax
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Virginia
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United States
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Richmond
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Virginia
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United States
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Williamsburg
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Virginia
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United States
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Clarksburg
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West Virginia
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United States
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Wauwatosa
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Wisconsin
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United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26894653
Citation
Saag KG, Whelton A, Becker MA, MacDonald P, Hunt B, Gunawardhana L. Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment. Arthritis Rheumatol. 2016 Aug;68(8):2035-43. doi: 10.1002/art.39654.
Results Reference
derived
Links:
URL
http://general.takedapharm.com/content/file.aspx?applicationcode=6C7C39D8-5D09-453B-BF30-696A4AB88E62&fileTypeCode=ULORICPI
Description
Uloric Package Insert
Learn more about this trial
Effect of Febuxostat on Renal Function in Patients With Gout and Moderate to Severe Renal Impairment
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