Table 4.
Primary and secondary antidepressant efficacy outcomes at end of study (56 days post randomization)
| MODIFIED ITT POPULATION | PP POPULATION | |||
|---|---|---|---|---|
| TCOAD | PLACEBO | TCOAD | PLACEBO | |
| PRIMARY END POINT | ||||
| Change in HAMD-17 total score from baseline | ||||
| N (modified ITT/ LOCF; PP/OC) | 202 | 204 | 135 | 162 |
| Mean (SD) | -11.4 (8.2) | -9.3 (7.9) | -13.0 (8.0) | -10.4 (7.8) |
| 95% CI | -12.3, -10.1 | -10.3, -8.2 | -14.1, -11.5 | -11.7, -9.4 |
| P value† | 0.012 | 0.009 | ||
| MMRM analysis | ||||
| N (OC) | 141 | 163 | N/A | N/A |
| MMRM estimate | -11.1 | -8.9 | N/A | N/A |
| 95% CI | -14.2, -8.1 | -11.8, -5.9 | N/A | N/A |
| P value | 0.006 | N/A | ||
| SECONDARY END POINTS | ||||
| Changes from baseline to last study visit | ||||
| Change in HAMD-17 depressed mood item | ||||
| N (modified ITT/ LOCF; PP/OC) | 202 | 204 | 135 | 162 |
| Mean (SD) | -1.6 (1.3) | -1.3 (1.2) | -1.9 (1.3) | -1.5 (1.2) |
| P value† | 0.030 | 0.009 | ||
| Change in MADRS total score | ||||
| N (OC) | 178 | 182 | 134 | 160 |
| Mean (SD) | -16.6 (11.3) | -14.1 (11.9) | -18.7 (10.8) | -15.5 (11.6) |
| P value† | 0.036 | 0.010 | ||
| Change in CGI-S from baseline | ||||
| N (modified ITT/ LOCF; PP/OC) | 202 | 204 | 135 | 162 |
| Mean (SD) | -1.7 (1.4) | -1.4 (1.4) | -2.0 (1.3) | -1.6 (1.4) |
| P value† | 0.036 | 0.017 | ||
| Responders and remitters at last study visit | ||||
| HAMD-17 responders | ||||
| N (modified ITT/ LOCF; PP/OC) | 202 | 204 | 136 | 162 |
| Responders, n | 109 (54.0%) | 84 (41.2%) | 84 (62.2%) | 77 (47.5%) |
| P value† | 0.003 | 0.006 | ||
| HAMD-17 remitters | ||||
| N (modified ITT/ LOCF; PP/OC) | 202 | 204 | 136 | 162 |
| Remitters, n | 72 (35.6%) | 65 (31.9%) | 59 (43.7%) | 62 (38.3%) |
| P value† | 0.22 | 0.26 | ||
| CGI-I responders | ||||
| Last study visit, N | 180 | 183 | 133 | 160 |
| Responders, n | 96 (53.3%) | 89 (48.6%) | 84 (62.7%) | 87 (54.4%) |
| P value‡ | 0.22 | 0.066 | ||
| PGI-I responders | ||||
| Last study visit, N | 176 | 183 | 133 | 160 |
| Responders, n | 90 (51.1%) | 80 (43.7%) | 76 (57.1%) | 77 (48.1%) |
| P value‡ | 0.15 | 0.15 | ||
| Improvement of illness | ||||
| CGI-I (n) | ||||
| Last study visit, N | 178 | 182 | 134 | 160 |
| Very much improved | 52 (29.2%) | 57 (31.3%) | 46 (34.3%) | 56 (35.0%) |
| Much improved | 44 (24.7%) | 32 (17.6%) | 38 (28.4%) | 31 (19.4%) |
| Minimally improved | 43 (24.2%) | 42 (23.1%) | 33 (24.6%) | 37 (23.1%) |
| No change | 33 (18.5%) | 45 (24.7%) | 16 (11.9%) | 34 (21.3%) |
| Minimally worse | 4 (2.2%) | 2 (1.1%) | — | — |
| Much worse | 1 (0.6%) | 3 (1.6%) | 1 (0.7%) | 2 (1.3%) |
| Very much worse | 1 (0.6%) | 1 (0.5%) | — | — |
| P value‡ | 0.22 | 0.066 | ||
| PGI-I (n) | ||||
| Last study visit, N | 176 | 183 | 133 | 160 |
| Very much improved | 35 (19.9%) | 34 (18.6%) | 32 (24.1%) | 34 (21.3%) |
| Much improved | 55 (31.3%) | 46 (25.1%) | 44 (33.1%) | 43 (26.9%) |
| Minimally improved | 48 (27.3%) | 48 (26.2%) | 38 (28.6%) | 43 (26.9%) |
| No change | 31 (17.6%) | 39 (21.3%) | 17 (12.8%) | 33 (20.6%) |
| Minimally worse | 3 (1.7%) | 10 (5.5%) | 1 (0.8%) | 5 (3.1%) |
| Much worse | 3 (1.7%) | 3 (1.6%) | 1 (0.8%) | 1 (0.6%) |
| Very much worse | 1 (0.6%) | 3 (1.6%) | — | 1 (0.6%) |
| P value‡ | 0.084 | 0.033 | ||
| Discontinuations due to lack of efficacy | ||||
| Safety population, N | 202 | 204 | N/A | N/A |
| Discontinuations due to lack of efficacy, n | 8 (4.0%) | 9 (4.4%) | N/A | N/A |
| P value$ | > 0.99 | — | ||
LOCF, last observation carried forward; OC, observed cases; MMRM, mixed-model repeated-measures
†
ANCOVA
‡
Cochran-Mantel-Haenszel test
$
Fisher's exact test
N/A: Not applicable
TCOAD=Trazodone Contramid OAD