This study evaluates the safety and efficacy of lesinurad administered with an XOI versus a placebo plus an XOI in gout participants who have moderate renal impairment and who are not at target level of serum urate (sUA).
This postmarketing study is a randomized, double-blind, placebo-controlled study to evaluate safety (with particular focus on renal and cardiovascular events) and efficacy of lesinurad 200 mg once daily (QD) in combination with an XOI for up to 24 months compared with XOI monotherapy, in participants with gout and moderate renal impairment who have not reached target sUA levels (\<6.0 mg/dL) on an XOI alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
242
200 mg oral tablet
All participants must be on a stable, medically appropriate dose of XOI as their sole urate-lowering therapy (ULT) indicated for the treatment of gout for at least 4 weeks prior to Screening and throughout the Screening Period. This stable dose of XOI will be maintained throughout the study period.
matching placebo oral tablet
Percentage of Participants Who Achieve Serum Urate (sUA) < 6.0 mg/dL at Month 6
Time frame: Month 6
Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Change From Baseline in Estimated Creatinine Clearance (eCrCl) at Month 24
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, 24 months
Percent Change From Baseline in eCrCl at Month 24
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, 24 months
Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment
The eCrCl was calculated by the Cockcroft-Gault formula using ideal body weight.
Time frame: Baseline, Months 1, 3, 6, 9, 12, 15, 18
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Gout flare prophylaxis: commercially available colchicine is provided through the Month 6 study visit. Actual colchicine dose (0.5 or 0.6 mg qd) and frequency were adjusted based on the local label, subject medical history, and clinical judgement.
Gout flare prophylaxis: Participants unable to take colchicine are permitted to take a short course of low-dose oral corticosteroids up to the Month 3 study visit
Central Alabama Research
Birmingham, Alabama, United States
Southern Arizona VA Health Care System
Tucson, Arizona, United States
Medvin Clinical Research
Covina, California, United States
Northern California Research
Sacramento, California, United States
Capital Nephrology Medical Group
Sacramento, California, United States
Inland Rheumatology Clinical Trials, Inc
Upland, California, United States
Medvin Clinical Research - Whittier
Whittier, California, United States
Western Nephrology-Westminster
Westminster, Colorado, United States
New England Research Associates, Llc
Trumbull, Connecticut, United States
Arthritis, Autoimmune, & Allergy LLC
Daytona Beach, Florida, United States
...and 106 more locations
Percentage of Participants With Serum Creatinine (sCr) Elevations (≥1.5 × Baseline) Over the Study Period
Time frame: up to 18 months
Percentage of Participants Meeting Criteria (eg, Based on sCr or eCrCl Criteria) for Treatment Discontinuations Over the Study Period
Kidney function was monitored throughout the study by measuring sCr and calculating eCrCl by Cockcroft-Gault formula using ideal body weight. Treatment discontinuations were required if a participant experienced an absolute sCr ≥4.0 mg/dL or an eCrCl \<20 mL/min (based on central laboratory results).
Time frame: up to 18 months
Percentage of Participants Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Renal-related and kidney stone events were based on Medical Dictionary for Regulatory Activities (MedDRA) "Renal and Urinary Disorders" system organ classification. AEs that started on or after the first dose of study drug in this study, or those AEs with onset prior to the first dose of study drug but worsened after the first dose of study drug, were considered treatment emergent.
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.
Percentage of Participants With Contributing Factors to Renal SAEs as Adjudicated by the Renal Event Adjudication Committee (REAC)
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.
Percentage of Participants With Cardiac Event Adjudication Committee (CEAC)-Adjudicated Major Adverse Cardiovascular Events (MACEs)
MACEs are defined as Cardiovascular Death, Nonfatal Myocardial Infarction, and Nonfatal Stroke.
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.
Incidence of CEAC-Adjudicated MACEs or Hospitalization for Unstable Angina (MACE+)
MACEs are defined as Cardiovascular Death, Nonfatal Myocardial Infarction, and Nonfatal Stroke.
Time frame: From first dose of study drug through each participant's study duration, up to approximately 18 months.