Results from a Phase 1 Study Assessing the Pharmacokinetics of the Aldosterone Synthase Inhibitor Baxdrostat in Participants with Varying Degrees of Renal Function.

Autor: Freeman MW; Center for Computational and Integrative Biology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; CinCor Pharma, Inc., Waltham, MA, USA., Halvorsen YD; CinCor Pharma, Inc., Waltham, MA, USA., Bond M; CinRx Pharma, LLC, Cincinnati, OH, USA., Murphy B; CinRx Pharma, LLC, Cincinnati, OH, USA., Isaacsohn J; CinRx Pharma, LLC, Cincinnati, OH, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2024 Apr; Vol. 13 (4), pp. 410-418. Date of Electronic Publication: 2024 Feb 04.
DOI: 10.1002/cpdd.1371
Abstrakt: Baxdrostat is a selective small-molecule aldosterone synthase inhibitor in development for treatment of hypertension and chronic kidney disease. This phase 1, open-label, parallel-group study assessed the safety and pharmacokinetics (PK) of baxdrostat in participants with varying degrees of renal function. Participants were enrolled into control (estimated glomerular filtration rate [eGFR] ≥60 mL/min), moderate to severe renal impairment (eGFR 15-59 mL/min), or kidney failure (eGFR <15 mL/min) groups and received a single 10-mg baxdrostat dose followed by 7 days of inpatient PK blood and urine sampling. Safety was assessed by adverse events, clinical laboratory evaluations, vital signs, physical examinations, and electrocardiograms (ECGs). Thirty-2 participants completed the study. There were no deaths and only 1 mild drug-related adverse event (diarrhea). No clinically meaningful changes in laboratory values, vital signs, physical examinations, or ECGs occurred. Plasma concentration-time curves of baxdrostat were similar among all groups. Urine PK parameters were similar (approximately 12% excreted) in the moderate to severe renal impairment and control groups. Inadequate urine production in the kidney failure group resulted in minimal urinary baxdrostat excretion. Renal impairment had no significant impact on systemic exposure or clearance of baxdrostat, suggesting that dose adjustment due to PK differences in patients with kidney disease is unnecessary.
(© 2024 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
Databáze: MEDLINE
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