Sparsentan for the Treatment of VEGF Signaling Pathway Inhibitor-Associated Proteinuria

Exclusion Criteria

• •1. Estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73m2
• •2. Baseline high grade proteinuria ≥ 2+ proteinuria on dipstick or a calculated urinary protein-to creatinine ratio or microalbumin-to-creatinine ≥ 1.0 g/g prior to VSPI initiation
• •3. Acute kidney injury defined as serum creatinine at least 1.5 times above the most proximal serum creatinine prior to VSPIs initiation
• •4. History of allergic reactions or angioedema to any angiotensin receptor blocker (ARB) or ERA, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications.
• •5. Any potassium value \>5 mEq/L in the 14 days preceding high-grade proteinuria
• •6. History of organ transplantation, with the exception of corneal transplants.
• •7. History of congestive heart failure (New York Heart Association Class II-IV)
• •8. History of clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction or unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularization procedure) within 6 months prior to screening.
• •9. Jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or alanine aminotransferase and/or aspartate aminotransferase \>2 times the upper limit of the normal at screening.
• •10. Body weight \<50 kg at screening
• •11. Unable to hold renin-angiotensin-aldosterone system (RAAS) inhibitors such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), spironolactone, eplerenone, aliskiren, aldosterone blockers during run-in period
• •12. Concomitant use of the following medications:
• •1. Inhibitors of endothelin system such as ambrisentan, bosentan, macitentan
• •2. Potassium-sparing diuretics such as amiloride, triamterene
• •3. Antiarrhythmic medications such as amiodarone, digoxin
• •4. Weight loss medications such as orlistat or amphetamine derivative agents
• •5. St. John's wort or other hypericum-derived products
• •6. Strong CYP3A inhibitors such as ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, ritonavir- or cobicistat-boosted regimens, boceprevir, telaprevir, conivaptan, mibefradil
• •13. Pregnant or breastfeeding
• •14. Concurrent participation in a study with an alternative experimental therapy that may interact with sparsentan
• •15. Any condition that, in the view of the principal investigator, might place the patient at increased risk or compromise the integrity of the study
• •16. Conflict with other study