Effect of Febuxostat on Renal Function in Patients With Gout and Moderate to Severe Renal Impairment
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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|
- Change From Baseline to Month 12 in Serum Creatinine [ Time Frame: Baseline and Month 12 ]Renal function was assessed by measuring the change from Baseline in serum creatinine. Analyses were conducted by the Central Laboratory.
- Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline and Month 12 ]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 [ Time Frame: 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 [ 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. ]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 [ 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. ]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.
|Study Start Date:||April 2010|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Placebo-matching capsules, orally, twice daily for up to 12 months.
Febuxostat placebo-matching capsules
Experimental: Febuxostat 30 mg BID
Febuxostat 30 mg, capsules, orally, twice daily (BID) for up to 12 months.
Experimental: Febuxostat 40/80 mg QD
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.
Other Names:Drug: Placebo
Febuxostat placebo-matching capsules
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01082640
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|Study Director:||Medical Director||Takeda|