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DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS
H. Trachtman, P. Nelson, S. Adler, KN. Campbell, A. Chaudhuri, VK. Derebail, G. Gambaro, L. Gesualdo, DS. Gipson, J. Hogan, K. Lieberman, B. Marder, KE. Meyers, E. Mustafa, J. Radhakrishnan, T. Srivastava, M. Stepanians, V. Tesar, O. Zhdanova, R....
Language English Country United States
Document type Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Grant support
UL1 TR001445
NCATS NIH HHS - United States
NLK
Free Medical Journals
from 1990 to 1 year ago
PubMed Central
from 2008 to 1 year ago
Europe PubMed Central
from 2008 to 1 year ago
Open Access Digital Library
from 1990-07-01
- MeSH
- Endothelin A Receptor Antagonists administration & dosage adverse effects therapeutic use MeSH
- Angiotensin II Type 1 Receptor Blockers administration & dosage adverse effects therapeutic use MeSH
- Child MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Glomerulosclerosis, Focal Segmental drug therapy urine MeSH
- Irbesartan administration & dosage adverse effects therapeutic use MeSH
- Creatinine urine MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Proteinuria drug therapy urine MeSH
- Aged MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
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.
Department of Research and Development Retrophin Inc San Diego California
Division of Nephrology and Kidney Research Institute University of Washington Seattle Washington
Division of Nephrology Columbia University New York New York
Division of Nephrology Icahn School of Medicine at Mount Sinai New York New York
Division of Nephrology New York University School of Medicine New York New York
Division of Pediatric Nephrology Stanford University Palo Alto California
Division of Pediatric Nephrology University of Michigan Ann Arbor Michigan
Division of Transplant Research Colorado Kidney Care Denver Colorado
References provided by Crossref.org
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- $a Trachtman, Howard $u Division of Pediatric Nephrology, Department of Pediatrics, New York University School of Medicine, Langone Medical Center, New York, New York; howard.trachtman@nyumc.org radko.komers@retrophin.com.
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- $a 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.
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