Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study

Table 3 MADRS Total Score: Change From Baseline to Day 28 MMRM; DB Induction Phase

Category	Esk28 (*N =* 41)	Esk56 (*N =* 40)	Esk84 (*N =* 41)	Placebo (*N =* 80)
Baseline
N	41	40	41	80
Mean (SD)	38.4 (6.07)	37.9 (5.41)	35.9 (5.28)	37.7 (5.65)
Median (Range)	36.0 (28; 58)	37.5 (29; 49)	35.0 (28; 47)	37.0 (29; 51)
Day 28
N	39	34	39	72
Mean (SD)	22.9 (12.46)	23.6 (11.01)	21.0 (11.24)	22.4 (11.43)
Median (Range)	24.0 (0; 55)	22.0 (2; 47)	19.0 (1; 43)	21.5 (1; 46)
Change from baseline to Day 28 (DB)
N	39	34	39	72
Mean (SD)	- 15.2 (13.07)	- 14.5 (10.53)	- 15.1 (12.21)	- 15.3 (11.68)
Median (Range)	- 13.0 (− 52; 7)	- 15.0 (− 40; 5)	- 15.0 (− 44; 5)	- 13.0 (− 50; 4)
MMRM analysis^a
Diff. of LS means (SE) (Esk minus Placebo)	- 1.0 (2.25)	0.6 (2.33)	- 0.9 (2.26)
90% confidence interval on diff^b	- 5.77; 3.70	- 4.32; 5.47	- 5.66; 3.83
1-sided p-value (Esk minus Placebo)^b	0.475	0.504	0.482

MADRS total score ranges from 0 to 60; a higher score indicates a more severe condition
Negative change in score indicates improvement.
Results based on sensitivity analyses (ANCOVA LOCF model and MMRM analyses based on follow-up data were consistent with the primary MMRM analysis).
^aTest for no difference between treatments based on MMRM with change from baseline as the response variable and the fixed effect model terms for treatment (Esk28, Esk56, Esk84, Placebo), day and treatment-by-day, and baseline value as a covariate. A negative difference favors esketamine
^bConfidence interval and p-value are based on the Dunnett adjustment
Abbreviations: ANCOVA analysis of covariance, DB double-blind, diff difference, Esk esketamine, LOCF last observation carried forward, LS least-square, MADRS Montgomery-Asberg depression rating scale, MMRM mixed-model for repeated measures, N number of patients, SD standard deviation, SE standard error

ISSN: 1471-244X