| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder (MDD) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Major Depressive Disorder (MDD) is a mental disorder characterised by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities. |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025454 |
| E.1.2 | Term | Major depressive disorder, recurrent episode |
| E.1.2 | System Organ Class | 100000004873 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the long-term safety and tolerability of oral OPC-34712 as adjunctive therapy in the treatment of adults with MDD. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the long-term efficacy of oral OPC-34712 as adjunctive therapy in the treatment of adults with MDD. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects are required to meet the following inclusion criteria:
1. Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by IRB/IEC) prior to the initiation of any protocol-required procedures.
2. Ability, in the opinion of the principal investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet/capsule ingestion, and discontinuation of prohibited concomitant medication; to read and understand the written word in order to complete subject-reported outcomes measures; and to be reliably rated on assessment scales.
3. 331-10-227 and 331-10-228 Subjects Only - Subjects who, in the opinion of the investigator, could potentially benefit from administration of OPC-34712 as adjunctive therapy to their antidepressant therapy and who meet one of the following criteria:
a) Subjects who completed participation in the Double-blind Randomization Phase (ie, Week 14 visit of Phase B) in Trial 331-10-227 or Trial 331-10-228 or
b) Subjects who continued into Phase A+ at the end of prospective treatment (ie, Week 8 visit of Phase A) in Trial 331-10-227 or Trial 331-10-228, BUT DID NOT meet criteria for remission (defined as a MADRS Total Score of ≤ 10) at the Week 14 visit of Phase A+ in Trial 331-10- 227 or Trial 331-10-228.
4. Eligible Subjects From Other Double-Blind Phase 3 Brexpiprazole MDD Trials: Subjects who completed the last scheduled visit of the prior double-blind phase 3 trial, and who in the opinion of the investigator, could potentially benefit from administration of brexpiprazole as adjunctive therapy to their antidepressant therapy.
5. Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent for Trial 331-10-238.
6. Subjects willing to discontinue all prohibited psychotropic medications starting from the time of signing the ICF and during the trial period.
|
|
| E.4 | Principal exclusion criteria |
For full details on exclusion criteria please refer to Section 3.4.3 of the trial protocol.
Subjects will be excluded if they meet any of the following selected exclusion criteria:
1. Sexually active females of childbearing potential and male subjects who are not practicing two different methods of birth control with their partner during the trial and for 30 days after the last dose of trial medication or who will not remain abstinent during the trial and for 30 days after the last dose.
2. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving open-label OPC-34712 in Trial 331-10-238.
3. Subjects with a major protocol violation during the course of their participation in the prior double-blind phase 3 trial.
4. Subjects who have received ECT for the current depressive episode.
5. Subjects who have had an inadequate response to ECT at any time in the past or who have had a vagus nerve stimulation or deep brain stimulation device implanted for management of treatment resistant depression.
6. Subjects with a current need for involuntary commitment or who have been hospitalized during the prior double-blind phase 3 trial for the current major depressive episode.
7. 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
8. Subjects with a current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
9. Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode.
10. Subjects receiving new onset psychotherapy (individual, group, marriage, or family therapy) during the prior double-blind phase 3 trial.
11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness must not be enrolled into this trial.
12. Any subject who, in the opinion of the investigator, should not participate in the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary outcome variable is the safety and tolerability of OPC-34712 which will be assessed by examining the frequency and severity of adverse events (AEs). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoint will be evaluated using data collected throughout by trial week and at the last visit (week 52/early termination). The final evaluation of the data will be completed following the last visit of the last patient enrolled on the study. |
|
| E.5.2 | Secondary end point(s) |
Efficacy variables will be as follows:
• Change from baseline in Clinical Global Impression - Severity of Illness scale (CGI-S) score;
• Mean Clinical Global Impression - Improvement scale (CGI-I) score;
• Change from baseline in Sheehan Disability Scale (SDS) score.
• Change from baseline in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score
Safety variables to be examined in this trial will include physical examinations, vital signs, body weight, waist circumference, clinical laboratory tests (hematology, serum chemistry, urinalysis, and pregnancy tests), ECGs, the Simpson Angus Scale (SAS), the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Rating Scale (BARS), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the Massachusetts General Hospital Sexual Functioning Questionnaire (MSFQ). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The secondary endpoints will be evaluated using data collected throughout by trial week and at the last visit (week 52/early termination). The final evaluation of the data will be completed following the last visit of the last patient enrolled on the study. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Poland |
| Romania |
| Russian Federation |
| Slovakia |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of trial date is defined as the last date of contact or the date of final contact attempt from the post-treatment follow-up eCRF page for the last subject completing or withdrawing from the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 63 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 63 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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