| 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) |
|
| 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 | 16.0 |
| 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 compare the efficacy of brexpiprazole (flexible
dose) with placebo as adjunctive therapy to an assigned openlabel
antidepressant therapy (ADT) in the proposed subject
population with MDD.
|
|
| E.2.2 | Secondary objectives of the trial |
Secondary: To evaluate the safety and tolerability of
brexpiprazole (flexible dose) as adjunctive therapy to ADT in
the proposed subject population with MDD. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent.
4. Subjects with both a diagnosis of MDD, and in a current major depressive episode, as defined by DSM-IV-TR criteria and confirmed by both the M.I.N.I. and an adequate clinical psychiatric
evaluation. The current major depressive episode must be >= 8 weeks in duration. In addition, subjects must have reported a history for the current major depressive episode of an inadequate
response to at least one and no more than 3 adequate antidepressant treatments. An inadequate response is defined as < 50% reduction in depressive symptom severity, as assessed by the ATRQ. Adequate treatment is defined as an antidepressant treatment for at least 6 weeks in duration at a
minimum dose (or higher) as specified in the ATRQ. If the subject showed >= 50% improvement on any antidepressant treatment in the current episode, then the subject must have had an inadequate response to a subsequent adequate antidepressant treatment (as defined above by the ATRQ) of another antidepressant drug prior to entry into the trial. For the most recent antidepressant treatment, the subject must not report
>= 50% improvement (as defined above by the ATRQ).
5. Subjects with MADRS Total Score >= 26 at the Screening and Baseline visits.
6. Subjects willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period. |
|
| E.4 | Principal exclusion criteria |
For full details on exclusion criteria, please refer to Section 3.4.3 of teh trial protocol.
- Subjects who report an inadequate response (less than 50% reduction in depressive symptom severity) to more than 3 antidepressant treatments during the current major depressive episode at a therapeutic dose (as defined by the ATRQ) and for an adequate duration (minimum duration of 6 weeks), including any antidepressant that the subject may be taking at screening if it meets the criteria for adequate treatment.
- Subjects who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of 3 weeks during the current major depressive episode.
- Subjects who have received ECT for the current major depressive episode.
- 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 treatmentresistant depression.
-Subjects with a current need for involuntary commitment or who have been hospitalized within 4 weeks of screening for the current major depressive episode.
- 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 disorder, bipolar II disorder, or bipolar disorder NOS
-- Eating disorder (including anorexia nervosa or bulimia)
-- Obsessive-compulsive disorder
-- Panic disorder
-- Posttraumatic stress disorder
-Subjects with a current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder, or mental retardation.
- Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current major depressive episode.
-Subjects who answer “Yes” on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR
Subjects who answer “Yes” on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this C-SSRS Item 5 occurred within the last 6 months OR
Subjects who answer “Yes” on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR
Subjects who, in the opinion of the investigator, present a serious risk of suicide.
- Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days; including alcohol and benzodiazepines, but excluding nicotine dependence. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary outcome endpoint for determination of efficacy is
the change from randomization to endpoint in the MADRS
Total Score. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoint will be evaluated at the end of treatment visit according to the blinded study design. The actual week when each individual subject will have their end of treatment visit is determined by the randomization system (IWRS) in a blinded manner. |
|
| E.5.2 | Secondary end point(s) |
| The key secondary efficacy endpoint is the change from randomization to endpoint in SDS Score (the mean of 3 individual item scores). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The secondary endpoint will be evaluated at the end of treatment visit according to the blinded study design. The actual week when each individual subject will have their end of treatment visit is determined by the randomization system (IWRS) in a blinded manner. |
|
| 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 | No |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 |
| France |
| Germany |
| Poland |
| Russian Federation |
| Serbia |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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