Clinical trial NCT01082640: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Impairment
Keywords: Gout
physiology
Hyperuricemia
Uric Acid
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-03-08
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline to Month 12 in Serum Creatinine
timeFrame: Baseline and Month 12
Secondary outcomes:
measure: Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline and Month 12
measure: Percentage of Participants With Serum Urate (sUA) Less Than 6 mg/dL at Month 12
timeFrame: Month 12
measure: Mean Clearance (CL/F) of Febuxostat at Steady State
timeFrame: 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.
measure: Mean Area Under the Concentration-Time Curve During the Dosing Interval (AUC[0-τ]) of Febuxostat at Steady State
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
city: Sierra Vista
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Huntington Park
country: United States
state: California
city: Irvine
country: United States
state: California
city: Lakewood
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Jose
country: United States
state: California
city: Tustin
country: United States
state: California
city: Arvada
country: United States
state: Colorado
city: Westminster
country: United States
state: Colorado
city: Wheat Ridge
country: United States
state: Colorado
city: Middlebury
country: United States
state: Connecticut
city: Brandon
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: Port Charlotte
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Conyers
country: United States
state: Georgia
city: Dunwoody
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Boise
country: United States
state: Idaho
city: Evergreen Park
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Valparaiso
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Elizabethtown
country: United States
state: Kentucky
city: Paducah
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Brooklyn Center
country: United States
state: Minnesota
city: Neptune City
country: United States
state: New Jersey
city: Morganton
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Bethlehem
country: United States
state: Pennsylvania
city: Anderson
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Danville
country: United States
state: Virginia
city: Fairfax
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Williamsburg
country: United States
state: Virginia
city: Clarksburg
country: United States
state: West Virginia
city: Wauwatosa
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
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.