Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to assess the long-term safety, tolerability and efficacy of oral OPC-34712 as adjunctive therapy in the treatment of adult patients with Major Depressive Disorder (MDD).
Interventions
DRUGADT
Once daily dosing during the duration of the study.
DRUGOPC-34712
OPC-34712, Oral Tablets, 0.25 - 3 mg
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 a diagnosis of a single or recurrent, non-psychotic episode of major depressive disorder, as defined by DSM-IV-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) which is equal to or greater than 8 weeks in duration. * Subjects must currently be taking allowable antidepressant therapy at an adequate dose for a minimum of six weeks by the end of the screening period (ie at the time of the Baseline visit). * Subjects must report a history for the current depressive episode of an inadequate response to at least one and no more than four 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, eating disorder (including anorexia nervosa or bulimia), obsessive compulsive disorder, panic disorder, post-traumatic stress 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 |
|---|---|---|
| Participants With Adverse Events (AEs). | After the Informed Consent Form (ICF) was signed, through Follow up 30 (+2) days after last visit | An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the physician. The severity was assessed as mild, moderate, or severe. A treament-emergent AE (TEAE) was defined as any AE that started after start of open-label brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (last-observation-carried-forward [LOCF]) | The CGI-S is a 7-point scale from 1 through 7. The items on CGI-S scale are: 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, 7 = among the most extremely ill participants. The score 0 (= not assessed) was set to missing. |
| Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (LOCF) | The items on CGI-I scale are 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) was set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI improvement was compared to the participants condition at Baseline. |
Countries
United States
Participant flow
Recruitment details
1036 participants entered trial, including 792 who had rolled over from previous studies and 244 de novo participants. Of the 792 rollovers, 337 were 6-week enrollers and the 52-week enrollers consisted of 699 enrolled participants (455 rollover and 244 de novo). This was a single arm study and all participants received the same treatment.
Pre-assignment details
Eligible participants received daily treatment with open-label brexpiprazole (0.25 up to 3.0 milligrams (mg)/day) and commercially marketed ADT.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole+ADT All participants received brexpiprazole 0.25 to 3.0 mg/day plus ADT. | 1,036 |
| Total | 1,036 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 127 |
| Overall Study | Lack of Efficacy | 68 |
| Overall Study | Lost to Follow-up | 52 |
| Overall Study | Participant met withdrawal criteria | 40 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Protocol deviation | 83 |
| Overall Study | Withdrawal by Subject | 100 |
Baseline characteristics
| Characteristic | Brexpiprazole+ADT |
|---|---|
| Age, Continuous | 44.0 Years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 702 Participants |
| Sex: Female, Male Male | 334 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 684 / 1,034 |
| serious Total, serious adverse events | 29 / 697 |
Outcome results
Primary
Participants With Adverse Events (AEs).
An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the physician. The severity was assessed as mild, moderate, or severe. A treament-emergent AE (TEAE) was defined as any AE that started after start of open-label brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study drug.
Time frame: After the Informed Consent Form (ICF) was signed, through Follow up 30 (+2) days after last visit
Population: The primary safety dataset included all participants exposed to at least 1 dose of brexpiprazole.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole+ADT | Participants With Adverse Events (AEs). | Participants with TEAEs | 851 Participants |
| Brexpiprazole+ADT | Participants With Adverse Events (AEs). | Participants with serious TEAEs | 30 Participants |
Secondary
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score.
The CGI-S is a 7-point scale from 1 through 7. The items on CGI-S scale are: 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, 7 = among the most extremely ill participants. The score 0 (= not assessed) was set to missing.
Time frame: Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (last-observation-carried-forward [LOCF])
Population: Efficacy dataset had participants who received at least 1 dose of brexpiprazole and had a baseline and at least 1 postbaseline efficacy evaluation for CGI-S. LOCF dataset included data recorded at a given visit in treatment phase or, if no observation was recorded at that visit, data carried forward from the previous visit in the Treatment Phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 1 | -0.09 Units on a scale | Standard Deviation 0.6 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 2 | -0.35 Units on a scale | Standard Deviation 0.82 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 4 | -0.63 Units on a scale | Standard Deviation 0.96 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 6 | -0.79 Units on a scale | Standard Deviation 1.03 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 8 | -0.92 Units on a scale | Standard Deviation 1.12 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 14 | -0.93 Units on a scale | Standard Deviation 1.14 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 20 | -1.08 Units on a scale | Standard Deviation 1.17 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 26 | -1.13 Units on a scale | Standard Deviation 1.24 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 32 | -1.24 Units on a scale | Standard Deviation 1.24 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 38 | -1.37 Units on a scale | Standard Deviation 1.28 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 44 | -1.46 Units on a scale | Standard Deviation 1.27 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 52 | -1.52 Units on a scale | Standard Deviation 1.34 |
| Brexpiprazole+ADT | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score. | Week 52-LOCF | -0.81 Units on a scale | Standard Deviation 1.24 |
Secondary
Mean Clinical Global Impression - Improvement (CGI-I) Scale Score.
The items on CGI-I scale are 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) was set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI improvement was compared to the participants condition at Baseline.
Time frame: Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and 52 (LOCF)
Population: Efficacy dataset had participants who received at least 1 dose of brexpiprazole and had a baseline and atleast 1 postbaseline efficacy evaluation for CGI-S. LOCF dataset included data recorded at a given visit in treatment phase or, if no observation was recorded at that visit, data carried forward from the previous visit in the Treatment Phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 1 | 3.38 Units on a scale | Standard Deviation 0.94 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 2 | 3.04 Units on a scale | Standard Deviation 1.06 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 4 | 2.67 Units on a scale | Standard Deviation 1.09 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 6 | 2.46 Units on a scale | Standard Deviation 1.1 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 8 | 2.36 Units on a scale | Standard Deviation 1.1 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 14 | 2.36 Units on a scale | Standard Deviation 1.23 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 20 | 2.22 Units on a scale | Standard Deviation 1.17 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 26 | 2.16 Units on a scale | Standard Deviation 1.12 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 32 | 2.08 Units on a scale | Standard Deviation 1.13 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 38 | 1.97 Units on a scale | Standard Deviation 1.11 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 44 | 1.91 Units on a scale | Standard Deviation 1.14 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 52 | 1.92 Units on a scale | Standard Deviation 1.15 |
| Brexpiprazole+ADT | Mean Clinical Global Impression - Improvement (CGI-I) Scale Score. | Week 52-LOCF | 2.57 Units on a scale | Standard Deviation 1.31 |