BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) 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 m2, 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.
- Klíčová slova
- angiotensin II, endothelin, focal segmental glomerulosclerosis, proteinuria, sparsentan,
- MeSH
- antagonisté endotelinového receptoru A aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- blokátory receptoru 1 pro angiotenzin II aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- dítě MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- fokálně segmentální glomeruloskleróza farmakoterapie moč MeSH
- irbesartan aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kreatinin moč MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- proteinurie farmakoterapie moč MeSH
- senioři MeSH
- spirosloučeniny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- sulfonamidy aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- antagonisté endotelinového receptoru A MeSH
- blokátory receptoru 1 pro angiotenzin II MeSH
- irbesartan MeSH
- kreatinin MeSH
- sparsentan MeSH Prohlížeč
- spirosloučeniny MeSH
- sulfonamidy MeSH
