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. [GRAPHICS]