Brexpiprazole as Adjunctive Therapy With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy

Inclusion criteria

• Clinical diagnosis of MDD
• In current major depressive episode of ≥ 8 weeks in duration and includes an inadequate response to at least 1 adjunctive treatment.
• Positive history of at least 1 additional failure to an adequate monotherapy antidepressant treatment.
• HAM-D17 total score≥ 18
• Currently receiving SSRI of SNRI with adjunctive treatment for at least 6 weeks before screening.
• Willing to discontinue use of all prohibited psychotropic medications
• Historical positive serological results for HIV, hepatitis B/C
• Able to provide written informed consent prior to the initiation of any protocol-required procedures
• Subjects who could potentially benefit from adjunctive treatment with Brexpiprazole

Exclusion criteria

• Sexually active women of childbearing potential
• Male subjects not practicing 2 different methods of birth control
• Females who are breastfeeding and/or who have a positive pregnancy test result
• Subjects who have received ECT for the current major depressive episode.
• Subjects who have had an inadequate response to ECT
• Current need for involuntary commitment or who have been hospitalized within 4 weeks of screening
• Current Axis I (DSM-IV-TR)
• Current Axis II (DSM-IV-TR)
• Subjects experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode.
• Subjects receiving new onset psychotherapy.
• Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4, Item 5, or on any of the 5 C-SSRS Suicidal Behavior Items
• Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days
• Hypothyroidism or hyperthyroidism
• Clinically significant neurological, hepatic, renal, metabolic, haematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders
• Currently treated with insulin for diabetes
• Uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension
• Known ischemic heart disease or history of myocardial infarction, congestive heart failure, angioplasty, stenting, or coronary artery bypass surgery
• Epilepsy or history of seizures
• Positive drug screen
• The following laboratory test and ECG results are exclusionary:

• Platelets ≤ 75,000/mm3
• Hemoglobin ≤ 9 g/dL
• Neutrophils, absolute ≤ 1000/mm3
• AST > 2 × ULN
• ALT > 2 × ULN
• CPK > 3 × ULN, unless discussed with and approved by the medical monitor
• Creatinine ≥ 2 mg/dL
• HbA1c ≥ 7.0%
• Abnormal free T4 (Note: Free T4 is measured only if result for TSH is abnormal.)
• QTcF ≥ 470 msec for females and ≥ 450 msec for males
• Treatment with an MAOI or EMSAM within 14 days of the Baseline visit.
• Use of benzodiazepines and/or hypnotics within 7 days prior to the first dose of IMP
• Use of oral neuroleptics within 7 days prior or long-acting approved atypical antipsychotics ≤ 1 full cycle plus ½ cycle prior to the first dose of IMP
• Subjects who would be likely to require prohibited concomitant therapy during the trial.
• Subjects who previously participated in any prior brexpiprazole trial
• History of neuroleptic malignant syndrome or serotonin syndrome
• History of true allergic response to more than one class of medications
• Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
• Subjects who participated in a clinical trial within the last 180 days or who participated in more than 2 clinical trials within the past year.
• Any subject who, in the opinion of the investigator or medical monitor, should not participate.