A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole as Adjunctive Therapy in the Maintenance Treatment of Adults With Major Depressive Disorder
Overview
- Phase
- Phase 3
- Intervention
- Brexpiprazole
- Conditions
- Major Depressive Disorder
- Sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- Enrollment
- 1149
- Locations
- 1
- Primary Endpoint
- Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
Major depressive disorder (MDD) is a serious medical illness associated with significant suicidal risk and marked disability. Despite the availability of numerous treatments, achievement of consistent and favorable long-term outcomes remains challenging.
This study will assess the safety, efficacy and tolerability of brexpiprazole as adjunctive therapy to protocol-specific open-label antidepressant therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants with both a diagnosis of recurrent major depressive disorder, and in a current major depressive episode of ≥ 8 weeks in duration, as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and confirmed by both the Mini International Neuropsychiatric Interview (MINI) and an adequate clinical psychiatric evaluation.
- •Participants must have reported a history for the current major depressive episode of an inadequate response to 1 or 2 adequate antidepressant treatments, and participants must currently be taking a protocol-mandated antidepressant treatment at an adequate dose and duration, and most not have reported ≥ 50% improvement. For participants who are currently on an adequate dose of protocol-mandated antidepressant therapy (ADT), but for an inadequate duration, can use the screening period to achieve adequate duration. At Phase A baseline visit, all participants must have either 2 or 3 documented inadequate responses to antidepressant treatment in total for the current episode as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ).
- •Participants with a Hamilton Rating Scale for Depression (HAM-D17) total score ≥ 18 at the screening visit, and Phase A baseline visits.
- •Participants willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period.
Exclusion Criteria
- •Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving investigational medicinal product (IMP).
- •Sexually active males or females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP.
- •Participants who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of 3 weeks during the current major depressive episode.
- •Participants who report allergies or an intolerability (lifetime treatment history) to trial-provided ADTs that have not been prescribed to the participant during the current major depressive episode.
- •Participants who have received electroconvulsive therapy (ECT) for the current major depressive episode.
- •Participants 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 at any time for the management of treatment-resistant depression. Participants who have had transcranial magnetic stimulation during the current major depressive episode.
- •Participants with a current need for involuntary commitment or who have been hospitalized within 4 weeks of screening for the current major depressive episode.
- •Participants with a primary DSM-5 diagnosis of:
- •Schizophrenia Spectrum and Other Psychotic Disorders
- •Bipolar and Related Disorders
Arms & Interventions
Phase A: Brexpiprazole + ADT
Participants received brexpiprazole 2 or 3 milligrams per day (mg/day) along with protocol-specified antidepressant therapy (ADT), orally, for 6 to 8 weeks during Phase A. Participants were initially titrated to a target dose of brexpiprazole 2 mg over a 2 to 4-week period. Thereafter, participants who had not met response criteria as defined in the blinded addendum, did not have potentially dose-related adverse events (AEs), and had not achieved the maximum dose of medication had their dose increased up to 3 mg.
Intervention: Brexpiprazole
Phase A: Brexpiprazole + ADT
Participants received brexpiprazole 2 or 3 milligrams per day (mg/day) along with protocol-specified antidepressant therapy (ADT), orally, for 6 to 8 weeks during Phase A. Participants were initially titrated to a target dose of brexpiprazole 2 mg over a 2 to 4-week period. Thereafter, participants who had not met response criteria as defined in the blinded addendum, did not have potentially dose-related adverse events (AEs), and had not achieved the maximum dose of medication had their dose increased up to 3 mg.
Intervention: Antidepressant therapy
Phase B: Brexpiprazole + ADT
Eligible participants completing Phase A were enrolled in Phase B to receive brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 12 weeks.
Intervention: Brexpiprazole
Phase B: Brexpiprazole + ADT
Eligible participants completing Phase A were enrolled in Phase B to receive brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 12 weeks.
Intervention: Antidepressant therapy
Phase C: Brexpiprazole + ADT
Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Intervention: Brexpiprazole
Phase C: Brexpiprazole + ADT
Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Intervention: Antidepressant therapy
Phase C: Placebo + ADT
Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Intervention: Antidepressant therapy
Outcomes
Primary Outcomes
Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum
Time Frame: Up to 14 days post last dose in Phase C (up to 28 weeks)
Relapse criteria included:At same visit, increase in Montgomery Asberg Depression Rating Scale\[MADRS\] total score(10 items, 0=no symptoms to 6=severe symptoms,total score=0 to 60)of 50% from randomization and Clinical Global Impression-Severity of Illness \[CGI-\](8-point scale of 0=not assessed to 7=most extremely ill)score ≥4,hospitalization for depression, discontinuation for lack of efficacy/worsening of depression, active suicidality(score of ≥4 on MADRS item10 of suicidality)or yes answered on question 4 or 5 of Columbia-Suicide Severity Rating Scale\[C-SSRS\](Suicidal Ideation \[SI\] has 5 questions: wish to be dead,non-specific active suicidal thoughts,active SI with any methods \[not plan\]without intent to act,active SI with some intent to act without specific plan,active SI with specific plan,intent)or yes answered to any question in suicidal behavior section (5 questions:preparatory acts/behavior,aborted attempt,interrupted attempt,actual attempt\[non-fatal\],completed suicide).
Secondary Outcomes
- Phase C: Change From Baseline for Randomization Phase in MADRS Total Score at Week 46(Baseline and Week 46)
- Phase C: Change From Baseline for Randomization Phase in CGI-S Score at Week 46(Baseline and Week 46)
- Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46(Baseline and Week 46)
- Phase C: Percentage of Participants Meeting Any Relapse Criteria(Up to 26 weeks in Phase C)
- Phase C: Percentage of Participants Maintaining Remission(Weeks 21, 23, 25, 29, 33, 37, 41, 45, and 46)
- Phase C: Change From Baseline for Randomization Phase in Sheehan Disability Scale (SDS) Mean Total Score at Week 46(Baseline and Week 46)
- Phase C: Time-to-functional Relapse Based on SDS Criteria(Up to 14 days post last dose in Phase C (up to 28 weeks))