Abstract
ObjectiveDue to the high prevalence of diabetes in patients with hypertension, co-administration of metformin with anti-hypertensive drugs is likely. The aldosterone synthase inhibitor baxdrostat (CIN 107) was developed to treat hypertension. Baxdrostat inhibits the multidrug and toxin extrusion (MATE)-1 and MATE2-K renal transporters in vitro. Metformin is a MATE substrate, so this study assessed the potential for Baxdrostat to affect the pharmacokinetics of metformin, and to determine whether co-administration requires dose adjustment. MethodsTwenty-seven healthy subjects received 1000 mg metformin alone and 1000-mg metformin in the presence of 10 mg baxdrostat in a randomized sequence. Each treatment was separated by 10 days or more. Blood and urine samples were collected over a 3-day period after each treatment for measurement of plasma concentrations and cumulative urinary excretion of metformin. Safety was assessed by adverse events (AEs), physical examinations, electrocardiograms, vital signs, and clinical laboratory evaluations. ResultsTwenty-six subjects completed the study; 1 withdrew consent and discontinued. In the presence or absence of baxdrostat, plasma and urine concentrations of metformin were similar at all time points (Figure 1). There were no deaths, serious AEs, discontinuations due to treatment-emergent AEs (TEAEs), or noteworthy increases in AEs with either treatment. All TEAEs were mild. No meaningful changes were observed for all other safety evaluations. ConclusionsThese findings suggest that metformin and baxdrostat were safe and well-tolerated when co-administered. Baxdrostat did not significantly affect plasma concentrations or renal clearance of metformin. Therefore, diabetic patients with hypertension prescribed metformin and baxdrostat are unlikely to require dose adjustment.
Published Version
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