Efficacy and Safety of Brexpiprazole as Adjunctive Treatment in Elderly Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of brexpiprazole as adjunctive treatment in elderly patients with Major Depressive Disorder (MDD)

Official Title
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Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose Study to Evaluate the Efficacy and Safety of Brexpiprazole (1 and 3 mg/Day) as Adjunctive Treatment in Elderly Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Brexpiprazole 1 mg
* Drug: Brexpiprazole 3 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is an outpatient consulting a psychiatrist. The patient has a recurrent Major Depressive Disorder diagnosed according to DSM-IV-TR™. The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI). The patient had at least one previous MDE before the age of 60 years. The patient has a moderate to severe depression and an insufficient response to at least one and no more than three adequate antidepressants treatments. The patient, if a woman, must have had her last natural menstruation ≥24 months prior to the Screening Visit. The patient, if a man, agrees to protocol-defined use of effective contraception if his female partner is of childbearing potential. Exclusion Criteria: The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the primary diagnosis, other than MDD. The patient has a current Axis II (DSM-IV-TR™) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypical or histrionic personality disorder. The patient has experienced/experiences hallucinations, delusions or any psychotic symptomatology in the current MDE. The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria). The patient, in the opinion of the investigator, or according to Columbia Suicide Severity Rating Scale (C-SSRS), is at significant risk of suicide. The patient has had neuroleptic malignant syndrome. The patient has any relevant medical history or current presence of systemic disease. The patient has a neurodegenerative disorder. The patient has, at the Screening Visit an abnormal ECG that is, in the investigator's opinion, clinically significant. 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. The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo adjunct to open-label treatment with a commercially available antidepressant (ADT) | Drug: Placebo<br>* Once daily, tablets, orally<br>|
| Experimental: Brexpiprazole 1 mg<br>Brexpiprazole adjunct to open-label treatment with a commercially available ADT. Brexpiprazole dosing was 0.5 mg/day in the first 1 week followed by 1 mg/day. | Drug: Brexpiprazole 1 mg<br>* once daily dose, tablets, orally<br>|
| Experimental: Brexpiprazole 3 mg<br>Brexpiprazole adjunct to open-label treatment with a commercially available ADT. Brexpiprazole dosing was 0.5 mg/day in the first 1 week, 1 mg/day in the second week, followed by 3 mg/day. | Drug: Brexpiprazole 3 mg<br>* once daily dose, tablets, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Randomisation in Depressive Symptoms During the Randomised Treatment | Montgomery and Aasberg Depression Rating Scale (MADRS) total score | From randomisation to end of treatment (week 20) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | 15 patients were enrolled to Period 2; only 3 patients completed due to study termination | From randomisation to follow-up (week 24) | 
| Change From Randomisation in Clinical Global Impression During the Randomised Treatment | Clinical Global Impression - Severity of illness (CGI-S) score | From randomisation to end of treatment (week 20) | 
| Change From Randomisation in Functionality Assessed by SDS During the Randomised Treatment | Sheehan Disability Scale (SDS) total score | From randomisation to end of treatment (week 20) | 
| Change From Randomisation in Social Adaptation During the Randomised Treatment | Social Adaptation Self-evaluation Scale (SASS) total score | From randomisation to end of treatment (week 20) | 
| Response During the Randomised Treatment | Based on a pre-specified decrease in MADRS total score | From randomisation to end of treatment (week 20) | 
| Sustained Response During the Randomised Treatment | Based on a pre-specified decrease in MADRS total score | From randomisation to end of treatment (week 20) | 
| Remission During the Randomised Treatment | Based on a pre-specified MADRS total score | From randomisation to end of treatment (week 20) | 
| Sustained Remission During the Randomised Treatment | Based on a pre-specified MADRS total score | From randomisation to end of treatment (week 20) | 
| Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | The Columbia Suicide Severity Rating Scale (eC-SSRS) is a semi-structured interview developed to systematically assess suicidal ideation and behaviour of patients participating in a clinical study. The C-SSRS has 5 questions addressing suicidal ideation, 5 sub-questions assessing the intensity of ideation, and 4 questions addressing suicidal behaviour. | From randomisation to end of treatment (week 20) |