DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS
| Autor: | Kenneth Lieberman, Brad Marder, Abanti Chaudhuri, Kirk N. Campbell, Giovanni Gambaro, Peter T. Nelson, Esmat Mustafa, Kevin E.C. Meyers, Tarak Srivastava, Loreto Gesualdo, Sharon G. Adler, Radko Komers, Debbie S. Gipson, Howard Trachtman, Vladimir Tesar, Jai Radhakrishnan, Olga Zhdanova, Vimal K. Derebail, Miganush Stepanians, Jonathan J. Hogan |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Angiotensin receptor 030232 urology & nephrology Phases of clinical research angiotensin II 030204 cardiovascular system & hematology urologic and male genital diseases Glomerulosclerosis 0302 clinical medicine Focal segmental glomerulosclerosis Child Sulfonamides Proteinuria Glomerulosclerosis Focal Segmental General Medicine Middle Aged female genital diseases and pregnancy complications Nephrology Creatinine Female Drug medicine.symptom endothelin Endothelin receptor medicine.drug Adult medicine.medical_specialty Adolescent Endothelin A Receptor Antagonists Urinary system Urology Dose-Response Relationship Focal Segmental 03 medical and health sciences Young Adult Irbesartan Double-Blind Method Clinical Research medicine Humans Spiro Compounds sparsentan Aged focal segmental glomerulosclerosis Dose-Response Relationship Drug business.industry urogenital system medicine.disease Angiotensin II business Angiotensin II Type 1 Receptor Blockers |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 29(11) |
| ISSN: | 1533-3450 |
| Popis: | Background We evaluated and compared the effects of sparsentan, a dual endothelin type A (ET A ) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. Methods 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 2 , and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300 mg/d) for 8 weeks, followed by open-label sparsentan only. End points at week 8 were reduction from baseline in UP/C (primary) and proportion of patients achieving FSGS partial remission end point (FPRE) (UP/C: ≤1.5 g/g and >40% reduction [secondary]). Results Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients did when all doses (45% versus 19%; P =0.006) or the 400 and 800 mg doses (47% versus 19%; P =0.01) were pooled for analysis. The FSGS partial remission end point was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients ( P =0.04). After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments. Overall, the incidence of adverse events was similar between groups. Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals. Conclusions Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated. |
| Databáze: | OpenAIRE |
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