"Sparsentan"

Sparsentan (Filspari) - reduce proteinuria in adults with primary immunoglobulin A nephropathy Skip to main contentSkip to FDA SearchSkip to footer links An official website of the United States government Here's how you know U.S. Food and Drug Administration  Search   MenuSearch FDASubmit search Home Drugs Drug Approvals and Databases Drugs@FDADrug Approval Package

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin-angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint

Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. An unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin-angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown. In this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of ≤1.5

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment

Sparsentan ameliorates glomerular hypercellularity and inflammatory-gene networks induced by IgA1-IgG immune complexes in a mouse model of IgA nephropathy. IgA nephropathy (IgAN), is characterized by glomerular deposition of immune complexes (IC) consisting of IgA1 with -glycans deficient in galactose (Gd-IgA1) and Gd-IgA1-specific IgG autoantibodies. These ICs induce kidney injury . In this model, we assessed the protective effects of sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA) vs. vehicle on EIC-induced glomerular proliferation and dysregulation of gene expression in kidney. Oral administration of sparsentan (60 or 120 mg/kg daily) to mice intravenously injected with EIC attenuated the EIC-induced glomerular hypercellularity. Furthermore

Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study. The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel -group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics

Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety. Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years. Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years. Patients with FSGS, excluding secondary FSGS. Sparsentan (200, 400, and 800 mg/d). Urinary protein-creatinine ratio, FSGS partial

Sparsentan improves glomerular hemodynamics, cell functions and tissue repair in a mouse model of FSGS. Dual endothelin-1 (ET-1) and angiotensin II (AngII) receptor antagonism with sparsentan has strong antiproteinuric actions via multiple potential mechanisms that are more pronounced, or additive compared to current standard of care using angiotensin receptor blockers (ARB). Considering the many actions of ET-1 and AngII on multiple cell types, this study aimed to determine glomeruloprotective mechanisms of sparsentan compared to the ARB losartan by direct visualization of its effects in the intact kidney in focal segmental glomerulosclerosis (FSGS) using intravital multiphoton microscopy. In both healthy and FSGS models, sparsentan treatment increased afferent/efferent arteriole diameters

Implications of Complete Proteinuria Remission at any Time in Focal Segmental Glomerulosclerosis: Sparsentan DUET Trial. Focal segmental glomerulosclerosis (FSGS) is a rare glomerular disease with high unmet clinical need. Interest in proteinuria as a surrogate end point for regulatory approval of novel treatments has increased. We assessed the relationship between achieving complete remission (CR) of proteinuria at least once during follow-up and long-term kidney outcomes. This analysis included all patients enrolled in the DUET trial of sparsentan in FSGS and the open-label extension (OLE). Evaluations occurred every 12 weeks, including blood pressure (BP), edema, proteinuria, and kidney function. CR was defined as a urine protein/creatinine ratio ≤0.3g/g in a first morning urine

Effect of Multiple Doses of Sparsentan on the Single-Dose Pharmacokinetics of Dapagliflozin: An Open-Label Drug-Drug Interaction Study in Healthy Adults. Sparsentan is a single-molecule dual antagonist of the endothelin type A receptor and angiotensin II type 1 receptor under investigation for the treatment of focal segmental glomerulosclerosis and immunoglobulin A nephropathy. Dapagliflozin , a sodium-glucose cotransporter 2 inhibitor, has recently been indicated in chronic kidney disease. Sparsentan may be considered for concomitant use with dapagliflozin. The purpose of this open-label, 1-sequence crossover study was to determine whether drug-drug interactions between sparsentan and dapagliflozin affect dapagliflozin pharmacokinetics (PK). In addition, exposure to the inactive metabolite

IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study. Sparsentan is a novel single-molecule dual endothelin angiotensin receptor antagonist with hemodynamic and anti-inflammatory properties and is not an immunosuppressant. The ongoing phase 3 PROTECT trial examines sparsentan in adults with IgA nephropathy (IgAN). The PROTECT trial (NCT03762850) is a multicenter , international, randomized, double-blind, parallel-group, active-controlled study. The efficacy and safety of sparsentan versus the active control irbesartan is being evaluated in adults with biopsy-proven IgAN and proteinuria ≥1.0 g/d despite maximized treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) for at least 12 weeks. Blinded and aggregated

Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS), a histologic lesion in the kidney caused by varied pathophysiological processes, leads to end-stage kidney disease in a large proportion of patients. Sparsentan is a first-in-class orally active compound combining endothelin type A (ET) receptor blockade with angiotensin II type 1 (AT) receptor antagonism in a single molecule. A Randomized, Multicenter, Double-Blind, Parallel, Active-Control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS (DUPLEX) study evaluates the long-term antiproteinuric efficacy, nephroprotective potential

DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS We evaluated and compared the effects of sparsentan, a dual endothelin type A (ET) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 mg/d

Efficacy and Safety of Sparsentan for the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis PROSPERO International prospective register of systematic reviews Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms

Efficacy and Safety of Sparsentan Compared With Irbesartan in Patients With Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (DUET) Primary focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and end-stage renal disease. There are no US Food and Drug Administration-approved therapies for FSGS, and treatment often fails to reduce proteinuria. Endothelin is an important factor in the pathophysiology of podocyte disorders, including FSGS. Sparsentan is a first-in-class, orally active, dual-acting angiotensin receptor blocker (ARB) and highly selective endothelin Type A receptor antagonist. This study is designed to evaluate whether sparsentan lowers proteinuria compared with an ARB alone and has a favorable safety profile in patients

Efficacy and safety of sparsentan in IgA Nephropathy and Focal Segmental Glomerulosclerosis: A Meta-Analysis and Systematic Review PROSPEROInternational prospective register of systematic reviews Print | PDFEfficacy and safety of sparsentan in IgA Nephropathy and Focal Segmental Glomerulosclerosis: A Meta-Analysis and Systematic ReviewLimei Xiong, Yuhong TaoTo enable PROSPERO to focus on COVID . Efficacy and safety of sparsentan in IgA Nephropathy and Focal Segmental Glomerulosclerosis: A Meta-Analysis and Systematic Review. PROSPERO 2024 CRD42024508388 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024508388Review questionIgA nephropathy is the most common primary glomerular disease worldwide and often causes kidney failure for a substantial proportion

Effectiveness and safety of Sparsentan versus irbesartan in focal segmental glomerulosclerosis and IgA nephropathy : A systematic review and meta analysis PROSPEROInternational prospective register of systematic reviews Print | PDFPROSPEROThis information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO

Sparsentan VS Irbesartan in patients with Primary Focal Segmental Glomerulosclerosis a systematic review with meta-analysis. PROSPERO International prospective register of systematic reviews Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms

Efficacy and Safety of Sparsentan in Glomerular Disease: a Systematic Review and Meta-analysis. PROSPERO International prospective register of systematic reviews Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms that the information supplied

Efficacy and safety of sparsentan in IgA Nephropathy: A Meta-Analysis and Systematic Review PROSPEROInternational prospective register of systematic reviews Print | PDFEfficacy and safety of sparsentan in IgA Nephropathy: A Meta-Analysis and Systematic ReviewUmm E Salma Banatwala, Muhammad Sohaib KhanTo enable PROSPERO to focus on COVID-19 submissions, this registration record has undergone basic automated checks for eligibility and is published exactly as submitted. PROSPERO has never provided peer review, and usual checking by the PROSPERO team does not endorse content. Therefore, automatically published records should be treated as any other PROSPERO registration. Further detail is provided here.CitationUmm E Salma Banatwala, Muhammad Sohaib Khan. Efficacy and safety of sparsentan