Table 2.
Efficacy Endpoints*
| Crinecerfont | Placebo | Difference | |||||
|---|---|---|---|---|---|---|---|
| Primary end point† | N | LSM CFB | N | LSM CFB | LSMD (95% CI) | P-value | 2-sided Significance Level |
| Percent change in glucocorticoid dose while androstenedione was controlled (week 24) | 122 | −27.3±2.4 | 60 | −10.3±3.2 | −17.0 (−23.8, −10.2) | <0.001 | 0.05 |
| Key secondary end points† | N | LSM CFB | N | LSM CFB | LSMD (95% CI) | P-value | 2-sided Significance Level |
| Serum androstenedione (week 4) – ng/dL‡ | 122 | −299±37.7 | 60 | 45.5±51.0 | −345 (−457, −232) | <0.001 | 0.02 |
| Achieved physiological glucocorticoid dose while androstenedione was controlled (week 24) – no. (%)§ | 122 | 74 (62.7) | 60 | 10 (17.5) | Not applicable | <0.001 | 0.03 |
| Homeostatic model assessment for insulin resistance (week 24) | 122 | −0.65±0.21 | 60 | −0.36±0.28 | −0.29 (−0.89, 0.32) | ¶ | |
| Percent change in body weight (week 24) | 122 | −1.45±0.53 | 60 | −0.07±0.72 | −1.38 (−2.96, 0.20) | ¶ | |
| Percent total fat mass (week 24) ║ | 122 | −0.11±0.66 | 60 | −1.04±0.98 | 0.93 (−1.04, 2.90) | ¶ | |
Unless noted otherwise, all end points are presented as least-squares mean (LSM) change from baseline (CFB) at week 24 with standard error of the mean (SEM), along with the least-squares mean difference (LSMD) between treatment arms and 95% confidence interval (CI) for the LSMD.
For the primary and key secondary end points, participants with missing data were multiply imputed for statistical testing. Therefore, analyses are based on the full analysis set, which includes all randomized participants. The number of participants with complete data for each end point are as follows: primary (118 crinecerfont, 57 placebo); key secondary, androstenedione (117 crinecerfont, 56 placebo), key secondary, achievement of physiological glucocorticoid dose while androstenedione was controlled (118 crinecerfont, 57 placebo); key secondary, homeostatic model for insulin resistance (112 crinecerfont, 54 placebo); key secondary, weight (118 crinecerfont, 57 placebo); key secondary, total fat mass (93 crinecerfont, 43 placebo).
Based on pre-morning glucocorticoid dose samples. Normal ranges and conversion factors for conventional units to standard international units are in Appendix Table S2.
Percentages are based on observed data (118 crinecerfont, 57 placebo). However, participants with missing data were multiply imputed for statistical testing (procedure for key secondary end point).
These three key secondary end points were tested using a Holm procedure, and none achieved statistical significance.
Least-squares mean change from baseline (±standard error of the mean) in total fat mass were follows: crinecerfont, 0.1±1.0 kg; placebo, −1.4±1.4 kg. The least-squares mean difference (95% confidence interval) was +1.5 kg (−1.5, 4.5).
Abbreviations: CFB, change from baseline; CI, confidence interval; LSM, least-squares mean; LSMD, least-squares mean difference.