A Long-Term Study of Brexpiprazole in Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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This trial is a 52-week study to assess the safety of long-term use of brexpiprazole as adjunctive therapy in combination with an antidepressant.

Official Title
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A Multi-center, Open-label Trial to Assess the Long-term Safety and Efficacy of Brexpiprazole as Adjunctive Therapy in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Brexpiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rollover subjects Outpatients Subjects who have completed the double-blind period of the double-blind trial and can commence the treatment period of this trial within 28 days from the completionof the double-blind period of the double-blind trial Subjects who have a level of comprehension sufficient to allow them to give written informed consent to all of the observation/examination/evaluation items specified in the protocol, and who can understand the contents of the trial Subjects with a DSM-5 classification-based diagnosis of major depressive disorder, single episode or major depressive disorder, recurrent episode New subjects Outpatients Male and female patients ≥ 65 years of age (at the time of informed consent) Subjects who have a level of comprehension sufficient to allow them to give written informed consent to all of the observation/examination/evaluation items specified in the protocol, and who can understand the contents of the trial Patients with a DSM-5 classification-based diagnosis of major depressive disorder, single episode or major depressive disorder, recurrent episode whose current episode has persisted for at least 8 weeks Exclusion Criteria: Rollover subjects Female subjects who are pregnant or breastfeeding or who have positive pregnancy test (urine) results at baseline Sexually active male subjects or sexually active female subjects of childbearing potential, who will not agree to practice 2 different methods of birth control or to remain abstinent during the trial and for 30 days after the final IMP administration. For birth control, 2 of the following methods must be used: vasectomy, tubal ligation, vaginal diaphragm, intra-uterine contraceptive device (IUD), oral contraceptives, or condom with spermicide. Subjects who experience a change to the manic state in the antidepressant treatment period of the double-blind trial Subjects who are discovered to not meet the inclusion criteria or to fall under any of the exclusion criteria in the doubleblind trial Subjects who showed marked noncompliance with the IMP treatment in the double-blind trial (subjects whose IMP compliance rates are < 65% between prescribed visits) New subjects Sexually active male subjects who will not agree to practice 2different methods of birth control or to remain abstinent during the trial and for 30 days after the final IMP administration. For birth control, 2 of the following methods must be used: vasectomy, tubal ligation, vaginal diaphragm, intra-uterine contraceptive device (IUD), oral contraceptives, or condom with spermicide. Patients with a treatment history showing that all antidepressants (also including those not used for the current major depressive episode) cannot be tolerated Patients with a history of electroconvulsive therapy Patients with a diagnosis of any of the following diseases according to DSM-5 Neurocognitive disorders Schizophrenia spectrum and other psychotic disorders Bipolar and related disorders Feeding and eating disorders Obsessive-compulsive disorder Panic disorder Posttraumatic stress disorder

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brexpiprazole<br>2 mg/day (starting dose 1mg/day) of Brexpiprazole will be orally administered once daily | Drug: Brexpiprazole<br>* 2 mg/day (starting dose 1mg/day) of Brexpiprazole will be orally administered once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency of Adverse Events | The incidence of the following events will be summarized: •Adverse events occurring after initiation of Interventional Medicinal Product administration | From baseline to week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean changes from baseline in Montgomery Åsberg Depression Rating Scale（MADRS) at Week 52. | The proportion of subjects who decrease MADRS total scores more than 50%. Reaction Rate and Remission Rate.The MADRS consists of 10 items assessing apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thought. Each item is scored from 0 to 6, with higher scores indicating worse condition. | Baseline and Week 52 | 
| The proportion of subjects who score 1 or 2 on the Clinical Global Impression-Improvement(CGI-I) scale at Week 52 | The CGI-I Scale is a clinician-rated scale which assesses the total improvement of the patient's condition compared to that at baseline. Scores range from 0 to 7: 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. Higher scores indicate worse condition. | Baseline and Week 52 | 
| Mean changes from baseline in Clinical Global Impression-Severity of illness(CGI-S) at Week 52 | The CGI-S Scale is a clinician-rated scale which assesses how mentally ill the patient is at the time. Scores range from 0 to 7: 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 patients. Higher scores indicate worse condition. | Baseline and Week 52 | 
| Mean changes from baseline in Hamiliton Depression Rating Scale(HAM-D) item total scores at Week 52 | The HAM-D is a clinician-rated scale which evaluates the level of depression. The HAM-D consists of 17 items such as depression mood, feeling of guilt, suicide, insomnia, work and activities, retardation, and so on. Each item is scored from 0 to 2, 3 or 4, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 53 , with higher score indicating worse condition. | Baseline and Week 52 | 
| Mean changes from baseline in Sheehan Disability Scale (SDS) scores at Week 52 | SDS Scale is a patient-rated scale which assesses the degree of impairment for each of 3 items (work/school, social life, and family life/home responsibilities) on a 11-point scale ranging from 0 to 10 and the number of days lost and days unproductive caused by in the past week. | Baseline and Week 52 |