Table 3.
Key Secondary Efficacy Endpoints Assessed in the Double-Blind Treatment Phase
| Esketamine Plus AD | AD Plus Placebo | |
|---|---|---|
| Change in MADRS total scorea from baseline to Day 2 (24 hours) | ||
| Baseline | ||
| N | 124 | 126 |
| Mean (SD) | 36.5 (5.21) | 35.9 (4.50) |
| Median (range) | 36.0 (25, 50) | 36.0 (27, 48) |
| Day 2 (24 hours) | ||
| N | 123 | 125 |
| Mean (SD) | 28.5 (9.39) | 31.5 (8.30) |
| Median (range) | 30.0 (0, 47) | 33.0 (1, 49) |
| Change from baseline to Day 2 (24 hours) | ||
| N | 123 | 125 |
| Mean (SD) | −8.0 (9.01) | −4.4 (7.66) |
| Median (range) | −6.0 (−38, 13) | −3.0 (−31, 12) |
| MMRM analysisb | ||
| Difference of LS means (SE) | −3.3 (1.02) | |
| 95% CI on difference | −5.33, −1.33 | |
| Change in SDS total scorec from baseline to Day 28 | ||
| Baseline | ||
| N | 119 | 122 |
| Mean (SD) | 22.9 (5.18) | 22.5 (5.20) |
| Median (range) | 24.0 (6, 30) | 23.5 (8, 30) |
| Day 28 | ||
| N | 100 | 99 |
| Mean (SD) | 16.6 (8.34) | 17.1 (8.31) |
| Median (range) | 17.0 (0, 30) | 18.0 (0, 30) |
| Change from baseline to Day 28 | ||
| N | 99 | 98 |
| Mean (SD) | −6.3 (7.54) | −5.3 (7.03) |
| Median (range) | −4.0 (−30, 6) | −4.0 (−22, 10) |
| MMRM analysisb | ||
| Difference of LS means (SE) | −1.0 (1.00) | |
| 95% CI on difference | −2.96, 0.97 | |
Notes: aMADRS total score ranges from 0 to 60; a higher score indicates a more severe condition. Negative change in score indicates improvement. bTest for treatment effect is based on MMRM analysis with change from baseline as the response variable and the fixed effect model terms for treatment (esketamine plus AD, AD plus placebo), day, country, class of oral AD (SNRI or SSRI), and treatment-by-day, and baseline value as a covariate. A negative difference favors esketamine. cSDS total score ranges from 0 to 30; a higher score indicates greater impairment. Negative change in score indicates improvement.
Abbreviations: AD, antidepressant; CI, confidence interval; LS, least squares; MADRS, Montgomery-Åsberg Depression Rating Scale; MMRM, mixed model for repeated measures; SD, standard deviation; SDS, Sheehan Disability Scale; SE, standard error; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.