Long-term Safety and Tolerability Study of Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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To evaluate the long-term safety and tolerability of brexpiprazole as adjunctive treatment in patients with Major Depressive Disorder (MDD)

Detailed Description
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This extension safety study was terminated early because one of the lead-in studies (14571A) in elderly was terminated and because the Sponsor considered that sufficient long-term safety data has already been collected in the development programme in the population aged 18-65 yrs.

Official Title
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Interventional, Open-label, Long-term Extension Study to Evaluate the Safety and Tolerability of Brexpiprazole as Adjunctive Treatment 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: The patient is judged to benefit from adjunctive treatment with brexpiprazole according to the clinical opinion of the investigator. The patient had MDD at entry in lead-in brexpiprazole studies, NCT01838681 / 14570A or NCT01837797 / 14571A, diagnosed according to DSM-IV-TR™. The patient agrees to protocol-defined use of effective contraception. Exclusion Criteria: The patient has a disease or takes medication that could, in the investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with the conduct or interpretation of the study. The patient has been diagnosed with a psychiatric disorder other than MDD during the lead-in studies NCT01838681 / 14570A or NCT01837797 / 14571A. The patient, in the opinion of the investigator or according to C-SSRS, is at significant risk of suicide. The patient has any relevant medical history or current presence of systemic disease. The patient has, at the Baseline Visit an abnormal ECG that is, in the investigator's opinion, clinically significant. The patient has a moderate or severe ongoing adverse event related to study medication from the lead-in studies considered of potential safety risk by the investigator. 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: 18 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>Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant (ADT) | Drug: Brexpiprazole<br>* 1, 2, or 3 mg/day, once daily dose, tablets, orally. Uptitration in weekly steps from 0.5 mg/day (patients ≥65) or 1 mg/day (patients 18-64 years)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events | Number of participants with Treatment-Emergent Adverse Events | From baseline to Week 52 | 
| Number of Withdrawals | Number of withdrawals | From baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. The electronic C-SSRS (eC-SSRS) is a patient-rated electronic version using interactive voice response technology. A structured CSSRS script of standardised questions, follow-up prompts, error-handling and scoring conventions is used for administration. | From baseline to Week 52 | 
| Change in Depressive Symptoms | The Montgomery and Aasberg Depression Rating Scale (MADRS) total score | From baseline to Week 52 | 
| Proportion of Patients in Remission | Based on a pre-specified MADRS total score | From baseline to Week 52 | 
| Change in Clinical Global Impression | Clinical Global Impression - Severity of illness (CGI-S) score | From baseline to Week 52 | 
| Change in Health-related Quality of Life | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-(SF)) total score | From baseline to Week 52 | 
| Change in Health-related Quality of Life | The EuroQoL 5 Dimensions 5L version (EQ-5D-5L) Visual Analogue Scale (VAS) is a patient-reported assessment designed to measure the patient's wellbeing. It consists of 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a visual analogue scale (VAS) of the overall health state. Each descriptive item is rated on a 5-point index ranging from 1 (no problems) to 5 (extreme problems) and a single summary index (from 0 to 1) can be calculated. The VAS ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline and Week 52 |