A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Safety and Efficacy of Brexpiprazole as Adjunctive Therapy in the Treatment of Major Depressive Disorder
Overview
- Phase
- Phase 3
- Intervention
- Brexpiprazole
- Conditions
- Major Depressive Disorder
- Sponsor
- Otsuka Beijing Research Institute
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit) in the MADRS Total Score
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
This study is a multicenter, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of brexpiprazole as adjunctive therapy in the treatment of Major Depressive Disorder. A total of approximately 1100 subjects will be enrolled into the single-blind treatment for 6 weeks, and 480 incomplete responders will be randomized to brexpiprazole (2~3 mg) or placebo in a 1:1 ratio (approximately 240 subjects in each group), for treatment of 6 weeks.
Detailed Description
Screening phase: It can last up to 28 days and will begin when informed consent is signed. The screening phase will serve the following purposes: 1) To review the inclusion and exclusion criteria; 2) To allow for appropriate washout of prohibited medications; 3) To establish a pretreatment baseline of critical outcome measures. Single-blind Prospective Treatment Phase (Phase A): It lasts 8 weeks; the purpose of the Phase A is to select the MDD subjects with incomplete response to ADT. Randomized Double-blind Treatment Phase (Phase B): It lasts 6 weeks; the purpose of Phase B is to compare the efficacy and safety of Brexpiprazole as adjunctive therapy in the treatment of MDD patients with incomplete response to ADT. Continued Treatment Phase after Phase A (Phase A+): It lasts 6 weeks; the purpose of Phase A+ is to continue treatment for subjects with complete response to ADT and not satisfying the criteria for Phase B. Follow-up Phase: It lasts 4 weeks and only applies to the subjects from Phase B; the purpose of Follow-up Phase is to collect the safety information after the last dose of IMP.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subject who are able to provide signed written informed consent.
- •Male and female outpatients 18 to 65 years of age, inclusive, at the time of signing the informed consent.
- •Subjects with both a diagnosis of MDD, and in a current Major Depressive Episode, according to the diagnostic criteria in DSM-IV-TR and confirmed by the Mini International Neuropsychiatric Interview (MINI). The current Major Depressive Episode must be ≥ 8 weeks in duration.
- •Subjects must have reported a history for the current Major Depressive Episode of an inadequate response to at least one and no more than three standard antidepressant treatments (including any antidepressants being received during Screening period, if the antidepressants treatment meets criteria of standard treatment). For the most recent antidepressant treatment, the subject must not report ≥ 50% improvement.
- •Standard treatment is defined as: an antidepressant treatment for at least 6 weeks in duration (at least 3 weeks if combined treatment) at a minimum effective dose (or higher) according to prescription drug labels. At least once of 1 to 3 standard treatments is monotherapy for more than 6 weeks.
- •An inadequate response is defined as: \< 50% reduction in depressive symptom severity, as measured by the subject's self-report score on Visual Analogue Scale (VAS).
- •Subjects with a HAM-D17 Total Score ≥ 18 at the Screening and Baseline visits.
- •Phase B (Double-blind Randomization Phase)
- •At the end of Phase A (Week 8 visit), the subjects entering Phase B should also meet all of the following inclusion criteria (criteria for incomplete response):
- •HAM-D17 total score ≥14 at the end of phase A.
Exclusion Criteria
- •Females of childbearing potential and male subjects who are not willing to or cannot practice contraceptive methods during the trial and for 30 days after the last dose.
- •Females who are breast-feeding or lactating and who have a positive pregnancy test result (Urine or serum test) prior to screening or randomization (within 72 hours).
- •Subjects who report treatment with adjunctive antipsychotic medication with an antidepressant during the current Major Depressive Episode.
- •Subjects who report allergies or an intolerability to all protocol-specified ADTs or subjects with contraindication for protocol-specified ADTs described in their prescription drug labels.
- •Subjects who have had an ECT treatment history at any time in the past or at present, or who have had a vagus nerve stimulation or deep brain stimulation device implanted for management of treatment-resistant depression.
- •Subjects with a current need for hospitalization or who have been hospitalized within four weeks prior to screening for the current Major Depressive Episode.
- •Subjects with a current Axis I (DSM-IV-TR) diagnosis of:
- •Delirium, dementia, amnestic or other cognitive disorder
- •Schizophrenia, schizoaffective disorder, or other psychotic disorder
- •Bipolar I or II disorder
Arms & Interventions
Brexpiprazole
2-3 mg/day, once daily for 6 weeks, oral administration
Intervention: Brexpiprazole
Placebo
2-3 mg/day, once daily for 6 weeks, oral administration
Intervention: Placebo
Outcomes
Primary Outcomes
Change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit) in the MADRS Total Score
Time Frame: Week 8 and Week 14
The objective of the primary analysis is to compare the efficacy of brexpiprazole (2\~3 mg/day) to placebo as adjunctive therapy to an assigned open-label ADT in adult subjects with MDD who demonstrate an incomplete response after 8 weeks of treatment with the same assigned open-label antidepressant therapy (ADT). The efficacy is assessed by the change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit) in the MADRS Total Score
Secondary Outcomes
- Change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit) in 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) Score(Week 8 and Week 14)
- Change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit) in SDS Mean Score(Week 8 and Week 14)
- Change from the end of Phase A (Week 8 visit) in MADRS Total Score for every trial week visit in Phase B other than Week 14 visit(Week 8 and Week 14)
- CGI-I Response rate at every trial week visit in Phase B(Week 8 and Week 14)
- QIDS-SR16 Response Rate at every trial week visit in Phase B(Week 8 and Week 14)
- QIDS-SR16 Complete Remission Rate (recovery) at every trial week visit in Phase B(Week 8 and Week 14)
- Change from the end of Phase A (Week 8 visit) for every trial week visit in Phase B in CGI - Severity of Illness scale (CGI-S) score(Week 8 and Week 14)
- Change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit) in HAM-D17 Score(Week 8 and Week 14)
- MADRS Response Rate at every trial week visit in Phase B(Week 8 and Week 14)
- CGI - Improvement scale (CGI-I) score for every trial week visit in Phase B(Week 8 and Week 14)