Figure 1. Efficacy Endpoints.

Differences between crinecerfont and placebo are shown for the following: percent reduction in glucocorticoid (GC) dose while maintaining androstenedione (adrenal androgen) control (Panel A) and percentage of participants achieving reduction to a physiological GC range (≤11 mg/m²/day in hydrocortisone equivalents) while maintaining androstenedione control (Panel B); changes from baseline to week 4 in serum androstenedione (Panel C) and 17-hydroxyprogesterone (17OHP) (Panel D). Change in GC dose was set to zero in participants who had a reduction in GC dose but did not achieve androgen control. Androstenedione and 17OHP values for the two 4-week end points (Panels C and D) are based on samples collected before participants received their morning GC doses. Androstenedione control was defined as equal to or less than either 120% of baseline or the upper limit of normal, based on samples collected after participants received their morning GC doses. Error bars represent 95% confidence intervals (CI) for mean changes. The widths of these CIs have not been adjusted for multiplicity, and the intervals may not be used in place of hypothesis testing. Least-squares mean differences (LSMDs) with 95% CIs and P-values are presented for the primary end point (Panel A) and first key secondary end point (Panel C); P-value for the second key secondary end point is also presented (Panel B, LSMD not applicable). Analyses for the primary and key secondary end points included all randomized participants, as missing values were imputed (Methods).