Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated febuxostat, a nonpurine xanthine oxidase inhibitor, those allopurinol, purine base analogue gout and disease.We conducted multicenter, double-blind, noninferiority trial involving disease; were randomly assigned to receive febuxostat or allopurinol stratified according kidney function. The had prespecified margin of 1.3 for the hazard ratio primary end point (a composite death, nonfatal...

In Brief Background: The association between hyperuricemia, gout, and impaired renal function has long been recognized. Recent data provide evidence for the causal relationship elevated serum urate (sUA) changes, leading to declines in glomerular filtration rates. healthy adults, rate wanes with age. Urate-lowering therapy (ULT) allopurinol shown stabilize or reverse this. Objective: Here we examine long-term effects of ULT febuxostat on estimated (eGFR). Methods: This is a post hoc analysis...

Renal impairment is a risk factor for gout and barrier to optimal management. We undertook this exploratory study obtain data that have been heretofore limited regarding the safety efficacy of febuxostat in patients with moderate-to-severe renal (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ).Ninety-six were enrolled 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients randomly assigned at 1:1:1 ratio receive 30 mg twice daily, 40/80 once...

To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects early gout (1 or 2 flares).In this double-blind, placebo-controlled study, 314 hyperuricemia (serum uric acid [UA] level ≥7.0 mg/dl) and were randomized 1:1 to receive once-daily 40 mg (increased 80 if serum UA was ≥6.0 mg/dl day 14) placebo. The primary efficacy end point mean change from baseline month 24 modified Sharp/van der Heijde erosion score for single affected joint....

Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation. Febuxostat, xanthine oxidoreductase inhibitor, effective in lowering serum urate concentration and healthy volunteers people with gout. This work studied whether febuxostat, compared allopurinol placebo, would reduce 24-hour prevent growth or new formation.In this 6-month, double-blind, multicenter, randomized controlled trial, hyperuricosuric participants recent history of stones one more...

Background Hyperuricemia is associated with hypertension, elevated serum uric acid levels postulated to have a causal role in the development of hypertension. Consequently, reduction may help lower blood pressure ( BP ). A Phase 2, double‐blind, placebo‐controlled trial was conducted assess potential ‐lowering effects xanthine oxidase inhibitor febuxostat subjects hypertension and hyperuricemia (serum ≥0.42 mmol/L [≥7.0 mg/dL]). Methods Results Subjects (n=121) were randomized 1:1 80 mg once...

Hyperuricemia can accelerate renal decline associated with aging. Chronic kidney disease is frequently seen in patients hyperuricemia and gout.Assess the impact of urate-lowering therapy on function subjects gout who were treated febuxostat for ≤ 48 months.Subjects from 2 phase 3 clinical studies enrolled 3, long-term, open-label Febuxostat/Allopurinol Comparative Extension Long-Term (EXCEL) study. In EXCEL study, 1086 initially 80 or 120 mg daily, allopurinol 300 daily. The permitted to...

Objective. Hyperuricemia of gout can arise due to either overproduction or underexcretion uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective this post-hoc analysis was determine the effectiveness xanthine oxidase inhibitor febuxostat reducing serum urate (sUA) levels gouty who were overproducers underexcretors. Methods. Gouty subjects 18 85 years age sUA ≥ 8.0 mg/dl at baseline enrolled a Phase 2, 28-day,...

To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients the Cardiovascular Safety Febuxostat Allopurinol Patients With Gout Comorbidities (CARES) trial.Patients were randomly assigned receive (40 mg 80 once daily, according levels at week 2) titrated 100-mg increments 200-400 300-600 (with dose determined kidney function). Changes baseline level, tophus...

Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended (XR) formulation febuxostat was developed to provide equal or superior efficacy on compared IR and potentially lower risk treatment-initiated flares due an altered pattern drug exposure. The present study evaluated safety XR formulations moderate renal impairment (estimated glomerular filtrate rate ≥ 30 < 60 ml/min).This...

To assess the efficacy and safety of febuxostat extended release (XR) immediate (IR) in patients with gout normal or impaired renal function.This was a 3-month, phase III, multicenter, double-blind, placebo-controlled study. Patients (n = 1,790) history (mild-to-severe) function were randomized to receive placebo, IR 40 80 mg, XR mg once daily (1:1:1:1:1 ratio). End points included proportions serum urate (UA) level <5.0 mg/dl at month 3 (primary end point), UA <6.0 3, ≥1 flare requiring...

N-Acetyltransferase (NAT) polymorphism has been implicated in differences the susceptibility of individuals to toxicity chemicals metabolized by this enzyme system. Investigation into toxicological consequences acetylator and mechanism these effects humans, however, greatly hindered due lack a suitable human tissue culture system for determination hepatic NAT activity status individuals. An vitro developed study using liver slices dynamic organ culture. Acetylation para-aminobenzoic acid...

Despite an increasing incidence of gout in older age patients with multiple metabolic and cardiovascular comorbidities, there are limited data addressing whether currently available urate-lowering therapy is comparably effective safe (≥65 years age) versus younger (<65 patients. In this secondary analysis from the CONFIRMS trial, we found that among 374 subjects, approved doses febuxostat or commonly prescribed allopurinol was at least comparable to 1894 subjects well tolerated despite high...

Febuxostat, a non-purine selective xanthine oxidase (XO) inhibitor, may affect the metabolism of theophylline as XO hydroxylates 1-methylxanthine to 1-methyluric acid. The objective this study was examine effects febuxostat on pharmacokinetics and its metabolites.24 healthy subjects received 80 mg (Regimen A) or matching placebo B) daily for 7 days along with single oral dose 400 Day 5 in double-blind, randomized, cross-over fashion (≥ day washout between periods) followed by collection...

This drug utilization study evaluated the impact of 2019 label changes on real-world febuxostat among patients with gout. We describe numbers and proportions initiating as new users (allopurinol-naïve) or prevalent (prior allopurinol use) data established cardiovascular disease (CVD) morbidities before, during, after changes.This descriptive, non-interventional, cross-sectional used from two large administrative claims databases in United States, IQVIA PharMetrics Plus database Optum...

Objective: To evaluate the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in preschool-aged children (4–5 years age inclusive) diagnosed with attention-deficit/hyperactivity disorder (ADHD). Methods: This phase 3 open-label study (ClinicalTrials.gov registry: NCT02466386) enrolled aged 4–5 meeting Diagnostic Statistical Manual Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for a primary ADHD diagnosis having baseline Rating Scale-IV Preschool...

<h3>Background</h3> Current guidelines recommend initiating urate-lowering therapy (ULT) in people with gout who have experienced ≥2 acute flares within the past year. However, no clinical trials investigating early stages of and potential benefits ULT had been available. <h3>Objectives</h3> The aim this study was to assess effect treatment febuxostat over a two year period on joint damage by imaging assessments hyperuricemic subjects compared placebo. <h3>Methods</h3> In phase 2,...