Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects

BACKGROUND: Due to the high comorbidity of diabetes and hypertension, co-administration of metformin with anti-hypertensive drugs is likely. Baxdrostat is an aldosterone synthase inhibitor in development for the potential treatment of hypertension. In vitro data indicated that baxdrostat inhibits the multidrug and toxin extrusion 1 (MATE1) and MATE2-K renal transporters. Metformin is a MATE substrate, so this study assessed potential effects of baxdrostat on the pharmacokinetics of metformin. METHODS: Twenty-seven healthy volunteers received 1000 mg metformin alone and 1000 mg metformin in the presence of 10 mg baxdrostat in a randomized, crossover manner. Each treatment was separated by 10 or more days. Blood and urine samples were collected over a 3-day period after each treatment to measure plasma and urine concentrations of metformin. Safety was assessed by adverse events (AEs), physical examinations, electrocardiograms, vital signs, and clinical laboratory evaluations. RESULTS: There were no deaths, serious AEs, discontinuations due to treatment-emergent AEs, or noteworthy increases in AEs with either treatment, indicating that metformin and baxdrostat were well-tolerated when co-administered. Baxdrostat did not significantly affect plasma concentrations or renal clearance of metformin. CONCLUSION: The results of this study suggest that diabetic patients with hypertension receiving both metformin and baxdrostat are unlikely to require dose adjustment. REGISTRATION: ClinicalTrials.gov identifier no. NCT05526690. GRAPHICAL ABSTRACT: [Image: see text]