Table 2.
Single-Blind Stabilization Phase (Stabilization Phase Efficacy Sample; n=449) | Double-Blind Maintenance Phase (Maintenance Phase efficacy sample; n=200) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline Mean (SD) | Mean (SD) Change at Last (Post-Baseline) Visit | Baseline Mean (SD) | MMRM analysis | LOCF, ANCOVA | ||||||||
LS Mean Change (SE) at Week 52 | Treatment Difference (95% CI) | P Value | LS Mean Change (SE) at Week 52 | Treatment Difference (95% CI) | P Value | |||||||
Brex | Brex | Brex | Placebo | Brex | Placebo | Brex | Placebo | |||||
PANSS total score | 84.26 (12.33) | -15.13 (15.99) | 56.66 (8.51) | 58.07 (8.13) | 0.61 (3.34) | 6.92 (4.53) | -6.31 (-18.1, 5.46) | .2800 | 3.25 (1.94) | 11.20 (1.77) | -7.95 (-12.5, -3.41) | .0007 |
[n=449] | [n=447] | [n=96] | [n=104] | [n=15] | [n=9] | [n=96] | [n=104] | |||||
PANSS positive subscale score | 21.35 (4.75) | -4.99 (5.45) | 12.48 (3.66) | 12.63 (3.13) | -1.21 (0.73) | 1.50 (0.99) | -2.71 (-5.20, -0.22) | .0339 | 0.99 (0.64) | 4.17 (0.59) | -3.18 (-4.70, -1.66) | <.0001 |
[n=449] | [n=447] | [n=96] | [n=104] | [n=15] | [n=9] | [n=96] | [n=104] | |||||
PANSS negative subscale score | 22.14 (4.64) | -3.16 (4.61) | 16.30 (3.46) | 17.00 (3.64) | 1.30 (1.37) | 0.87 (1.71) | 0.43 (-4.14, 5.00) | .8470 | 0.39 (0.54) | 1.63 (0.49) | -1.24 (-2.50, 0.01) | .0516 |
[n=449] | [n=447] | [n=96] | [n=104] | [n=15] | [n=9] | [n=96] | [n=104] | |||||
CGI-S score | 4.31 (0.78) | -0.73 (0.96) | 3.00 (0.60) | 3.08 (0.60) | -0.23 (0.17) | 0.28 (0.22) | -0.51 (-1.09, 0.06) | .0780 | 0.02 (0.11) | 0.55 (0.11) | -0.53 (-0.79, -0.26) | .0002 |
[n=449] | [n=449] | [n=96] | [n=104] | [n=15] | [n=9] | [n=96] | [n=104] | |||||
CGI-I score | NA | 2.84 (1.24) a | NA | NA | - | - | - | - | 3.77 (1.26)b | 4.40 (1.32) b | -0.61 (-0.96, -0.25) | .0009 |
[n=454] | [n=96] | [n=104] | ||||||||||
PSP score | - | - | 49.82 (12.20) | 48.22 (11.64) | 18.63 (2.76) | 12.55 (3.48) | 6.08 (-2.71, 14.87) | .1677 | 15.06 (1.43) | 10.31 (1.34) | 4.75 (1.31, 8.18) | .0071 |
[n=94] | [n=100] | [n=15] | [n=9] | [n=94] | [n=100] | |||||||
GAF score | 45.82 (10.34) | 11.42 (12.30) | 64.22 (9.00) | 63.00 (8.31) | 5.72 (1.87) | -0.16 (2.37) | 5.88 (-0.06, 11.82) | .0522 | 0.55 (1.38) | -6.01 (1.28) | 6.55 (3.28, 9.83) | .0001 |
[n=449] | [n=426] | [n=95] | [n=102] | [n=15] | [n=9] | [n=95] | [n=102] | |||||
PANSS excited component score | 11.03 (3.44) | -1.89 (3.97) | 6.98 (1.92) | 7.37 (2.50) | -0.04 (0.46) | 1.00 (0.59) | -1.03 (-2.58, 0.51) | .1803 | 0.82 (0.41) | 2.35 (0.38) | -1.54 (-2.52, -0.56) | .0023 |
[n=449] | [n=447] | [n=96] | [n=104] | [n=15] | [n=9] | [n=96] | [n=104] | |||||
PANSS Marder factor scores | ||||||||||||
Positive symptoms | 25.46 (5.13) | -5.48 (5.66) | 15.89 (3.99) | 15.80 (3.21) | -1.62 (0.83) | 1.78 (1.05) | -3.40 (-6.05, -0.75) | .0136 | 0.58 (0.66) | 4.02 (0.60) | -3.44 (-4.99, -1.89) | <.0001 |
Negative symptoms | 21.05 (4.92) | -3.23 (4.81) | 15.07 (3.53) | 16.06 (3.68) | 1.37 (1.39) | 1.06 (1.77) | 0.31 (-4.40, 5.02) | .8927 | 0.34 (0.56) | 1.57 (0.50) | -1.23 (-2.52, 0.07) | .0630 |
Disorganized thought | 19.98 (3.86) | -3.42 (3.95) | 14.54 (2.89) | 14.31 (3.06) | -0.37 (0.99) | -0.30 (1.24) | -0.07 (-3.32, 3.17) | .9632 | 0.29 (0.48) | 1.97 (0.45) | -1.69 (-2.81, -0.56) | .0035 |
Uncontrolled hostility/ excitement | 8.58 (3.14) | -1.42 (3.35) | 5.56 (1.76) | 5.72 (2.17) | -0.20 (0.40) | 0.94 (0.50) | -1.14 (-2.46, 0.18) | .0875 | 0.49 (0.37) | 1.75 (0.34) | -1.26 (-2.12, -0.39) | .0046 |
Anxiety/depression | 9.18 (3.21) | -1.57 (3.42) | 5.59 (1.76) | 6.18 (2.47) | 0.04 (0.43) | 0.28 (0.56) | -0.23 (-1.68, 1.21) | .7437 | 1.17 (0.31) | 1.88 (0.29) | -0.72 (-1.47, 0.03) | .0608 |
[n=449] | [n=447] | [n=96] | [n=104] | [n=15] | [n=9] | [n=96] | [n=104] | |||||
Cogstate cognitive test battery | Last (post-baseline) visit, ANCOVA | |||||||||||
Composite change score c | 0.09 (0.88) | -0.12 (0.70) | 0.10 (0.89) | 0.11 (0.88) | - | - | - | - | 0.06 (0.07) | -0.13 (0.07) | 0.19 (0.01, 0.37) | .0419 |
[n=441] | [n=161] | [n=82] | [n=82] | [n=82] | [n=82] | |||||||
Detection task (log10 msec) d | 2.66 (0.17) | 0.02 (0.13) | 2.68 (0.17) | 2.67 (0.17) | - | - | - | - | 0.01 (0.01) | 0.01 (0.01) | -0.01 (-0.04, 0.03) | .7724 |
[n=444] | [n=164] | [n=82] | [n=82] | [n=82] | [n=82] | |||||||
Identification task (log10 msec)d | 2.79 (0.12) | 0.01 (0.10) | 2.80 (0.12) | 2.80 (0.12) | - | - | - | - | -0.01 (0.01) | 0.02 (0.01) | -0.03 (-0.06, 0.00) | .0312 |
[n=444] | [n=164] | [n=84] | [n=83] | [n=84] | [n=83] | |||||||
One-card learning task c | 0.92 (0.17) | -0.01 (0.16) | 0.95 (0.18) | 0.94 (0.16) | - | - | - | - | 0.02 (0.02) | -0.04 (0.02) | 0.06 (0.01, 0.11) | .0321 |
[n=447] | [n=167] | [n=84] | [n=85] | [n=84] | [n=85] | |||||||
Groton maze learning task d | 72.5 (46.9) | 0.4 (68.3) | 68.24 (36.15) | 63.21 (27.34) | - | - | - | - | 0.22 (3.26) | 2.43 (3.34) | -2.21 (-11.4, 7.02) | .6371 |
[n=432] | [n=163] | [n=84] | [n=80] | [n=84] | [n=80] |
Abbreviations: Brex, brexpiprazole 1–4mg; CGI-I, Clinical Global Impressions – Improvement; CGI-S, Clinical Global Impressions – Severity of illness; GAF, Global Assessment of Functioning; LOCF, last observation carried forward; LS, least squares; MMRM, mixed-effect model repeated measures; NA, not applicable; PANSS, Positive and Negative Syndrome Scale; PSP, Personal and Social Performance; –, not assessed/analysis not performed.
aMean (SD) score at patients’ last (post-baseline) visit.
bMean (SD) score at week 52.
cAn increase in score indicates improvement.
dA decrease in score indicates improvement.
In the maintenance phase, MMRM analyses using observed data (treatment, trial center, visit, treatment–visit interaction, and baseline value as fixed effects; baseline–visit interaction as covariate) were performed, along with LOCF sensitivity analyses using an ANCOVA model (treatment and trial center as factors; baseline value as covariate). In the maintenance phase, CGI-I score was analyzed using the Cochran–Mantel–Haenszel method with LOCF data. For Cogstate analyses in the maintenance phase, an ANCOVA model (treatment as factor; baseline value as covariate) was used.