E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
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E.1.1.1 | Medical condition in easily understood language |
Major Depressive Disorder |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025461 |
E.1.2 | Term | Major depressive disorder, recurrent episode, severe degree, without mention of psychotic behavior |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025463 |
E.1.2 | Term | Major depressive disorder, single episode |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025469 |
E.1.2 | Term | Major depressive disorder, single episode, severe degree, without mention of psychotic behavior |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025462 |
E.1.2 | Term | Major depressive disorder, recurrent episode, unspecified degree |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025467 |
E.1.2 | Term | Major depressive disorder, single episode, moderate degree |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025458 |
E.1.2 | Term | Major depressive disorder, recurrent episode, moderate degree |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025470 |
E.1.2 | Term | Major depressive disorder, single episode, unspecified degree |
E.1.2 | System Organ Class | 100000004873 |
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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 |
Efficacy on depressive symptoms during long-term treatment with brexpiprazole versus placebo as adjunctive treatment to antidepressants in patients with an inadequate response to antidepressant treatment |
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E.2.2 | Secondary objectives of the trial |
- Efficacy of brexpiprazole versus placebo during long-term adjunctive treatment on functionality
- Efficacy of brexpiprazole versus placebo during long-term adjunctive treatment on clinical global impression
- Efficacy of brexpiprazole versus placebo during long-term adjunctive treatment on health-related quality of life
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•The patient is an outpatient consulting a psychiatrist.
•The patient has an MDD diagnosed according to DSM-IV-TR™. The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
•The patient has a moderate to severe depression and an insufficient response to at least one and no more than three adequate antidepressant treatments.
•The patient agrees to protocol-defined use of effective contraception.
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E.4 | Principal exclusion criteria |
1.The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the primary diagnosis, other than MDD.
2.The patient has a current Axis II (DSM-IV-TR™) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypical or histrionic personality disorder.
3.The patient has experienced/experiences hallucinations, delusions or any psychotic symptomatology in the current MDE.
4.The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
5.The patient, in the opinion of the investigator or according to Columbia- Suicide Severity Rating Scale (C-SSRS), is at significant risk of suicide.
6.The patient has had neuroleptic malignant syndrome.
7.The patient has any relevant medical history or current presence of systemic disease.
8.The patient has, at the Screening Visit an abnormal ECG that is, in the investigator's opinion, clinically significant.
9.The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for >5 years prior to the first dose of IMP.
10.The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Full remission during the randomised treatment period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Full functional remission during the randomised treatment
2.Full global score remission in global clinical impression during the randomised treatment
3.Change from randomisation in depressive symptoms during the randomised treatment
4.Response during the randomised treatment
5.Remission during the randomised treatment
6.Total time in remission during the randomised treatment
7.Time to full remission during the randomised treatment
8.Change from randomisation in clinical global impression during the randomised treatment
9.Change from randomisation in functionality
10.Change from randomisation in health-related quality of life
11.Safety and tolerability
12.Risk of suicidality
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.Randomisation to week 32
2. Randomisation to week 32
3. Randomisation to week 32
4. Randomisation to week 32
5. Randomisation to week 32
6. Randomisation to week 32
7. Randomisation to week 32
8. Randomisation to week 32
9. Randomisation to week 32
10. Randomisation to week 32
11.Up to 32 weeks and a 4-week safety follow up
12.Up to 32 weeks
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 71 |
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 |
Bulgaria |
Canada |
Estonia |
Finland |
Germany |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Poland |
Romania |
Russian Federation |
Sweden |
Ukraine |
United Kingdom |
United States |
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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
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End of trial for an individual patient is the last protocol-specified contact with that patient. The overall end of trial is the last protocol-specified contact with the last patient ongoing in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 17 |