Study design
PD
Subjects were randomized in a 3:1 ratio to baxdrostat or placebo once daily for 10 days as follows:Cohort 1: 2.5 mg baxdrostat or matching placebo on a low-salt diet, 9 subjects receiving baxdrostat and 3 subjects receiving placeboCohort 2: 5.0 mg baxdrostat or matching placebo on a low-salt diet, 9 subjects receiving baxdrostat and 3 subjects receiving placeboCohort 3: 1.5 mg baxdrostat or matching placebo on a normal-salt diet, 9 subjects receiving baxdrostat and 3 subjects receiving placeboCohort 4: 2.5 mg baxdrostat or matching placebo on a normal-salt diet, 6 subjects receiving baxdrostat and 2 subjects receiving placeboCohort 5: 0.5 mg baxdrostat or matching placebo on a normal-salt diet, 9 subjects receiving baxdrostat and 3 subjects receiving placebo.Cohorts 1 and 2 were dosed concurrently with a minimum 5-day lag between the first dose for cohort 2 and the first dose for cohort 1. A data review committee met between cohorts 2 and 3 and determined that cohorts 3 through 5 could be dosed concurrently. Each patient had a screening period of up to 28 days, followed by a 5-day run-in period in which the subjects adhered to a controlled, standardized diet and underwent baseline PD assessments (Supplementary Fig. The study drug was a 2 mg/mL baxdrostat oral solution and matching oral placebo solution. Subjects received a single dose of oral solution of baxdrostat or placebo on the mornings of days 1 through 10 at 8:00 a.m. (± 2 h). On days 1 and 10, the dose was given following an overnight fast (of at least 8 h), and subjects remained fasted for at least 4 h after dosing on these days. On all other days, subjects fasted for a minimum of 2 h before and 2 h after dosing.For cohort 1, the controlled, standardized low-salt diet consisted of 50 to 60 mEq NaCohorts 1 and 2 also underwent an ACTH (Cortrosyn