Major Depressive Disorder
Conditions
Keywords
OPC-34712, Major Depressive Disorder, Adjunctive Treatment
Brief summary
This is a Double-blind study wherein patients with Major Depressive Disorder (MDD) will receive either from 1 to 3 mg a day of study medication (OPC-34712)or placebo (an inactive substance) in addition to an FDA approved antidepressant in order to determine if the study medication is effective as an add on treatment of MDD.
Interventions
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects between 18 and 65 years of age, with diagnosis of major depressive disorder, as defined by DSM-IV-TR criteria * The current depressive episode must be equal to or greater than 8 weeks in duration * Subjects must report a history for the current depressive episode of an inadequate response to at least one and no more than three adequate antidepressant treatments.
Exclusion criteria
* Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug. * Subjects who report an inadequate response to more than three adequate trials of antidepressant treatments during current depressive episode at a therapeutic dose for an adequate duration. * Subjects with a current Axis I (DSM-IV-TR) diagnosis of: Delirium, dementia,amnestic or other cognitive disorder Schizophrenia, schizoaffective disorder, or other psychotic disorder Bipolar I or II disorder * Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score. | Baseline (end of week 8) to Week 14 | The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Baseline (end of week 8) to Week 14 | The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. |
| Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Baseline (end of week 8) to Week 14 | The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the investigator had to answer the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. |
| Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Baseline (end of week 8) to Week 14 | The IDS-SR was a 30-item self-report measure, that was used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorder (MDD). For individual items, the scores range from 0 to 3. The IDS-SR are scored by summing responses to 28 of the 30 items to obtain a total score ranging from 0 to 84, higher values indicate greater disruption in the depressive symptoms. |
| Change From End of Phase A (Week 8) to End of Phase B (Week 14) in the Hamilton Depression Rating Scale 17-item Version (HAM-D17) Total Score. | Baseline (end of week 8) to Week 14 | The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the best rating and the highest score (2 or 4) was the worst rating. The possible total scores were from 0 to 52. |
| Change From End of Phase A (Week 8) to Phase B in Sheehan Disability Scale (SDS) Score. | Baseline (end of week 8) to Week 14 | The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all, to 10= extremely. Scores of 5 and above are associated with significant functional impairment. The SDS total score ranges from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable. |
| Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Baseline (end of week 8) to Week 14 | A MADRS response was defined as \>=50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. |
| Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Baseline (end of week 8) to Week 14 | A MADRS remission was defined as MADRS Total Score =\< 10 and \>= 50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. |
| Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Baseline (end of week 8) to Week 14 | CGI-I Response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved). |
| Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Baseline (end of week 8) to Week 14 | The efficacy of study medication was rated for each participant using the CGI-I. The study physician would rate the participants total improvement whether or not it is due entirely to drug treatment. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. |
Countries
United States
Participant flow
Recruitment details
This trial was conducted in the United States in 773 participants at 44 centers. A total of 1226 participants were screened, 773 participants were enrolled in Phase A, and 769 were treated in Phase A. Of the 623 participants who completed Phase A, 372 participants were randomized in to Phase B.
Pre-assignment details
A 7 to 28-day Screening period, 8-Week single-blind placebo-ADT (antidepressant therapy) prospective Phase, 6-Week double-blind randomization Phase (Phase B), and 30-day follow-up after last dose of medication. Any participant randomized/completed all visits through Week 14 were allowed into an open-label rollover trial (NCT01052077).
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT. | 185 |
| Placebo Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT. | 187 |
| Total | 372 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Phase A | Adverse Event | 32 | 0 | 0 | 0 |
| Phase A | Lost to Follow-up | 22 | 0 | 0 | 0 |
| Phase A | Met Withdrawal Criteria | 26 | 0 | 0 | 0 |
| Phase A | Physician Decision | 10 | 0 | 0 | 0 |
| Phase A | Protocol Deviation | 27 | 0 | 0 | 0 |
| Phase A | Withdrawal by Subject | 29 | 0 | 0 | 0 |
| Phase A+ | Adverse Event | 0 | 0 | 0 | 4 |
| Phase A+ | Lost to Follow-up | 0 | 0 | 0 | 8 |
| Phase A+ | Met Withdrawal Criteria | 0 | 0 | 0 | 2 |
| Phase A+ | Withdrawal by Subject | 0 | 0 | 0 | 7 |
| Phase B | Adverse Event | 0 | 9 | 2 | 0 |
| Phase B | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Phase B | Lost to Follow-up | 0 | 2 | 3 | 0 |
| Phase B | Met Withdrawal Criteria | 0 | 2 | 1 | 0 |
| Phase B | Physician Decision | 0 | 1 | 1 | 0 |
| Phase B | Protocol Deviation | 0 | 3 | 4 | 0 |
| Phase B | Withdrawal by Subject | 0 | 0 | 5 | 0 |
Baseline characteristics
| Characteristic | Brexpiprazole | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.7 Years STANDARD_DEVIATION 11.7 | 42.4 Years STANDARD_DEVIATION 11.7 | 43.5 Years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 123 Participants | 130 Participants | 253 Participants |
| Sex: Female, Male Male | 62 Participants | 57 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 90 / 185 | 63 / 187 |
| serious Total, serious adverse events | 0 / 185 | 3 / 187 |
Outcome results
Primary
Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score.
The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the Full Analysis Set (FAS) comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole | Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score. | -8.20 Units on a scale | Standard Error 0.62 |
| Placebo | Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score. | -7.02 Units on a scale | Standard Error 0.62 |
Comparison: Week 14p-value: 0.141695% CI: [-2.75, 0.39]ANCOVA
Secondary
Change From End of Phase A (Week 8) to End of Phase B (Week 14) in the Hamilton Depression Rating Scale 17-item Version (HAM-D17) Total Score.
The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the best rating and the highest score (2 or 4) was the worst rating. The possible total scores were from 0 to 52.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole | Change From End of Phase A (Week 8) to End of Phase B (Week 14) in the Hamilton Depression Rating Scale 17-item Version (HAM-D17) Total Score. | -5.98 Units on a scale | Standard Error 0.45 |
| Placebo | Change From End of Phase A (Week 8) to End of Phase B (Week 14) in the Hamilton Depression Rating Scale 17-item Version (HAM-D17) Total Score. | -5.40 Units on a scale | Standard Error 0.45 |
Comparison: Week 14p-value: 0.324795% CI: [-1.71, 0.57]ANCOVA
Secondary
Change From End of Phase A (Week 8) to Phase B in Sheehan Disability Scale (SDS) Score.
The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all, to 10= extremely. Scores of 5 and above are associated with significant functional impairment. The SDS total score ranges from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole | Change From End of Phase A (Week 8) to Phase B in Sheehan Disability Scale (SDS) Score. | -0.91 Units on a scale | Standard Error 0.19 |
| Placebo | Change From End of Phase A (Week 8) to Phase B in Sheehan Disability Scale (SDS) Score. | -0.69 Units on a scale | Standard Error 0.19 |
Comparison: Week 14p-value: 0.377895% CI: [-0.69, 0.26]ANCOVA
Secondary
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 9 (N= 181, 180) | -3.30 Units on a scale | Standard Error 0.42 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 10 (N= 184, 181) | -5.92 Units on a scale | Standard Error 0.5 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 11 (N= 184, 181) | -7.23 Units on a scale | Standard Error 0.57 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 12 (N= 184, 181) | -8.42 Units on a scale | Standard Error 0.59 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 13 (N= 184, 181) | -9.00 Units on a scale | Standard Error 0.59 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 14 (N= 184, 181) | -8.20 Units on a scale | Standard Error 0.62 |
| Placebo | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 13 (N= 184, 181) | -7.18 Units on a scale | Standard Error 0.59 |
| Placebo | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 9 (N= 181, 180) | -1.99 Units on a scale | Standard Error 0.42 |
| Placebo | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 12 (N= 184, 181) | -6.21 Units on a scale | Standard Error 0.59 |
| Placebo | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 10 (N= 184, 181) | -4.01 Units on a scale | Standard Error 0.5 |
| Placebo | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 14 (N= 184, 181) | -7.02 Units on a scale | Standard Error 0.62 |
| Placebo | Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B. | Week 11 (N= 184, 181) | -5.22 Units on a scale | Standard Error 0.57 |
Comparison: Week 9p-value: 0.016295% CI: [-2.38, -0.24]ANCOVA
Comparison: Week 10p-value: 0.003195% CI: [-3.15, -0.65]ANCOVA
Comparison: Week 11p-value: 0.006195% CI: [-3.44, -0.58]ANCOVA
Comparison: Week 12p-value: 0.003895% CI: [-3.69, -0.72]ANCOVA
Comparison: Week 13p-value: 0.017495% CI: [-3.32, -0.32]ANCOVA
Comparison: Week 14p-value: 0.141695% CI: [-2.75, 0.39]ANCOVA
Secondary
Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score.
The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the investigator had to answer the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 9 (N= 181, 180) | -0.29 Units on a scale | Standard Error 0.05 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 10 (N= 184, 181) | -0.58 Units on a scale | Standard Error 0.06 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 11 (N= 184, 181) | -0.76 Units on a scale | Standard Error 0.07 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 12 (N= 184, 181) | -0.94 Units on a scale | Standard Error 0.07 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 13 (N= 184, 181) | -1.00 Units on a scale | Standard Error 0.08 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 14 (N= 184, 181) | -0.95 Units on a scale | Standard Error 0.08 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 13 (N= 184, 181) | -0.81 Units on a scale | Standard Error 0.08 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 9 (N= 181, 180) | -0.20 Units on a scale | Standard Error 0.05 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 12 (N= 184, 181) | -0.68 Units on a scale | Standard Error 0.07 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 10 (N= 184, 181) | -0.44 Units on a scale | Standard Error 0.06 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 14 (N= 184, 181) | -0.85 Units on a scale | Standard Error 0.08 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score. | Week 11 (N= 184, 181) | -0.59 Units on a scale | Standard Error 0.07 |
Comparison: Week 9p-value: 0.148195% CI: [-0.21, 0.03]ANCOVA
Comparison: Week 10p-value: 0.069195% CI: [-0.28, 0.01]ANCOVA
Comparison: Week 11p-value: 0.045795% CI: [-0.35, 0]ANCOVA
Comparison: Week 12p-value: 0.006195% CI: [-0.45, -0.08]ANCOVA
Comparison: Week 13p-value: 0.057295% CI: [-0.38, 0.01]ANCOVA
Comparison: Week 14p-value: 0.331895% CI: [-0.29, 0.1]ANCOVA
Secondary
Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score.
The IDS-SR was a 30-item self-report measure, that was used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorder (MDD). For individual items, the scores range from 0 to 3. The IDS-SR are scored by summing responses to 28 of the 30 items to obtain a total score ranging from 0 to 84, higher values indicate greater disruption in the depressive symptoms.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 9 (N= 181, 179) | -1.65 Units on a scale | Standard Error 0.54 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 10 (N= 184, 181) | -2.91 Units on a scale | Standard Error 0.6 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 11 (N= 184, 181) | -3.92 Units on a scale | Standard Error 0.68 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 12 (N= 184, 181) | -4.82 Units on a scale | Standard Error 0.74 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 13 (N= 184, 181) | -5.60 Units on a scale | Standard Error 0.75 |
| Brexpiprazole | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 14 (N= 184, 181) | -5.70 Units on a scale | Standard Error 0.8 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 13 (N= 184, 181) | -5.59 Units on a scale | Standard Error 0.75 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 9 (N= 181, 179) | -1.99 Units on a scale | Standard Error 0.53 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 12 (N= 184, 181) | -4.76 Units on a scale | Standard Error 0.74 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 10 (N= 184, 181) | -2.93 Units on a scale | Standard Error 0.6 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 14 (N= 184, 181) | -5.84 Units on a scale | Standard Error 0.8 |
| Placebo | Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. | Week 11 (N= 184, 181) | -3.64 Units on a scale | Standard Error 0.68 |
Comparison: Week 9p-value: 0.627295% CI: [-1.02, 1.69]ANCOVA
Comparison: Week 10p-value: 0.969795% CI: [-1.48, 1.54]ANCOVA
Comparison: Week 11p-value: 0.74995% CI: [-2, 1.44]ANCOVA
Comparison: Week 12p-value: 0.945995% CI: [-1.94, 1.81]ANCOVA
Comparison: Week 13p-value: 0.989395% CI: [-1.91, 1.88]ANCOVA
Comparison: Week 14p-value: 0.891895% CI: [-1.89, 2.17]ANCOVA
Secondary
Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
The efficacy of study medication was rated for each participant using the CGI-I. The study physician would rate the participants total improvement whether or not it is due entirely to drug treatment. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 9 (N= 181, 179) | 3.33 Units on a scale | Standard Deviation 0.82 |
| Brexpiprazole | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 10 (N= 184, 180) | 3.03 Units on a scale | Standard Deviation 0.97 |
| Brexpiprazole | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 11 (N= 184, 180) | 3.00 Units on a scale | Standard Deviation 1.08 |
| Brexpiprazole | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 12 (N= 184, 180) | 2.63 Units on a scale | Standard Deviation 1.12 |
| Brexpiprazole | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 13 (N= 184, 180) | 2.60 Units on a scale | Standard Deviation 1.14 |
| Brexpiprazole | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 14 (N= 184, 181) | 2.68 Units on a scale | Standard Deviation 1.18 |
| Placebo | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 13 (N= 184, 180) | 2.80 Units on a scale | Standard Deviation 1.02 |
| Placebo | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 9 (N= 181, 179) | 3.37 Units on a scale | Standard Deviation 0.74 |
| Placebo | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 12 (N= 184, 180) | 2.91 Units on a scale | Standard Deviation 1.02 |
| Placebo | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 10 (N= 184, 180) | 3.15 Units on a scale | Standard Deviation 0.84 |
| Placebo | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 14 (N= 184, 181) | 2.78 Units on a scale | Standard Deviation 1.07 |
| Placebo | Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A. | Week 11 (N= 184, 180) | 3.02 Units on a scale | Standard Deviation 0.99 |
Comparison: Week 9p-value: 0.5616Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.19Cochran-Mantel-Haenszel
Comparison: Week 11p-value: 0.0501Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.0137Cochran-Mantel-Haenszel
Comparison: Week 13p-value: 0.0711Cochran-Mantel-Haenszel
Comparison: Week 14p-value: 0.3438Cochran-Mantel-Haenszel
Secondary
Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
CGI-I Response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 10 (N= 184, 180) | 47 participants |
| Brexpiprazole | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 11 (N= 184, 180) | 73 participants |
| Brexpiprazole | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 12 (N= 184, 181) | 88 participants |
| Brexpiprazole | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 13 (N= 184, 181) | 90 participants |
| Brexpiprazole | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 14 (N= 184, 181) | 84 participants |
| Brexpiprazole | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 9 (N= 181, 179) | 23 participants |
| Placebo | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 14 (N= 184, 181) | 72 participants |
| Placebo | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 10 (N= 184, 180) | 39 participants |
| Placebo | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 13 (N= 184, 181) | 70 participants |
| Placebo | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 11 (N= 184, 180) | 51 participants |
| Placebo | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 9 (N= 181, 179) | 19 participants |
| Placebo | Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8). | Week 12 (N= 184, 181) | 63 participants |
Comparison: Week 9p-value: 0.460595% CI: [0.7, 2.18]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.326795% CI: [0.83, 1.72]Cochran-Mantel-Haenszel
Comparison: Week 11p-value: 0.02395% CI: [1.05, 1.8]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.010595% CI: [1.08, 1.71]Cochran-Mantel-Haenszel
Comparison: Week 13p-value: 0.041795% CI: [1.01, 1.58]Cochran-Mantel-Haenszel
Comparison: Week 14p-value: 0.234595% CI: [0.91, 1.44]Cochran-Mantel-Haenszel
Secondary
Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
A MADRS remission was defined as MADRS Total Score =\< 10 and \>= 50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 9 (N= 181, 180) | 7 participants |
| Brexpiprazole | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 10 (N= 184, 181) | 15 participants |
| Brexpiprazole | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 11 (N= 184, 181) | 31 participants |
| Brexpiprazole | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 12 (N= 184, 181) | 42 participants |
| Brexpiprazole | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 13 (N= 184, 181) | 46 participants |
| Brexpiprazole | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 14 (N= 184, 181) | 48 participants |
| Placebo | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 13 (N= 184, 181) | 25 participants |
| Placebo | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 9 (N= 181, 180) | 3 participants |
| Placebo | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 12 (N= 184, 181) | 19 participants |
| Placebo | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 10 (N= 184, 181) | 7 participants |
| Placebo | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 14 (N= 184, 181) | 27 participants |
| Placebo | Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 11 (N= 184, 181) | 18 participants |
Comparison: Week 9p-value: 0.240495% CI: [0.55, 9.3]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.098395% CI: [0.83, 4.98]Cochran-Mantel-Haenszel
Comparison: Week 11p-value: 0.049695% CI: [0.99, 2.82]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.001995% CI: [1.31, 3.46]Cochran-Mantel-Haenszel
Comparison: Week 13p-value: 0.006895% CI: [1.17, 2.67]Cochran-Mantel-Haenszel
Comparison: Week 14p-value: 0.008995% CI: [1.14, 2.57]Cochran-Mantel-Haenszel
Secondary
Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
A MADRS response was defined as \>=50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time frame: Baseline (end of week 8) to Week 14
Population: The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 9 (N= 181, 180) | 11 participants |
| Brexpiprazole | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 10 (N= 184, 181) | 29 participants |
| Brexpiprazole | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 11 (N= 184, 181) | 41 participants |
| Brexpiprazole | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 12 (N= 184, 181) | 56 participants |
| Brexpiprazole | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 13 (N= 184, 181) | 55 participants |
| Brexpiprazole | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 14 (N= 184, 181) | 55 participants |
| Placebo | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 13 (N= 184, 181) | 33 participants |
| Placebo | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 9 (N= 181, 180) | 4 participants |
| Placebo | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 12 (N= 184, 181) | 28 participants |
| Placebo | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 10 (N= 184, 181) | 16 participants |
| Placebo | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 14 (N= 184, 181) | 36 participants |
| Placebo | Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit. | Week 11 (N= 184, 181) | 26 participants |
Comparison: Week 9p-value: 0.067995% CI: [0.88, 8.81]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.03695% CI: [1.01, 3.14]Cochran-Mantel-Haenszel
Comparison: Week 11p-value: 0.052195% CI: [0.99, 2.35]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.000895% CI: [1.31, 2.86]Cochran-Mantel-Haenszel
Comparison: Week 13p-value: 0.007495% CI: [1.14, 2.38]Cochran-Mantel-Haenszel
Comparison: Week 14p-value: 0.033995% CI: [1.03, 2.08]Cochran-Mantel-Haenszel