Phase 1 Study to Assess the Safety/Tolerability of Brexpiprazole as Adjunctive Therapy in Elderly Subjects With Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Brexpiprazole; Placebo
Intervention description: up to 3mg oral dose once daily
Intervention MeSH terms: Brexpiprazole
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 18.0
Sex: All
Minimum age: 70 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Major Depressive Disorder (MDD)

Summary:

      The purpose of this study is to assess the safety and tolerability of ascending multiple oral
      doses of brexpiprazole as adjunctive therapy in the treatment of elderly subjects with MDD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who are able to provide written informed consent

          -  Ability to understand the nature of the trial and follow protocol requirements

          -  Male and female patients 70 to 85 years of age

          -  Subjects with normal or clinically stable findings on physical examination, medical
             history, clinical laboratory determinations, ECGs in relation to age

          -  BMI of 18 to 35 kg/m2.

          -  Stable subjects with a principal psychiatric diagnosis of MDD

          -  Subjects willing to discontinue all prohibited psychotropic and other prohibited
             medication

        Exclusion Criteria:

          -  Sexually active males who are not practicing 2 different methods of birth control
             during the trial and for 30 days after the last dose of trial medication or who will
             not remain abstinent during the trial and for 30 days after the last dose

          -  Subjects who have had a vagus nerve stimulation device implanted or who have received
             ECT within 6 months of Screening

          -  Subjects with a current Axis I (DSM-IV-TR) diagnosis of:

               -  Delirium, dementia, amnestic, or other cognitive disorder

               -  Eating disorder (including anorexia nervosa or bulimia)

               -  Obsessive-compulsive disorder

               -  Panic disorder

               -  Posttraumatic stress disorder or current or prior Axis I (DSM-IV-TR) diagnosis of
                  Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I
                  or II disorder or bipolar disorder not otherwise specified

          -  Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of
             borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality
             disorder

          -  Subjects experiencing hallucinations, delusions, or any psychotic symptomatology

          -  Subjects who have Active Suicidal Ideation with Some Intent to Act and whose most
             recent episode occurred within the last 6 months

          -  Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the
             past 180 days

          -  Subjects with hypothyroidism or hyperthyroidism and/or an abnormal result for free T4
             at Screening

          -  Subjects who currently have clinically significant neurological, hepatic, renal,
             metabolic, hematological, immunological, cardiovascular, pulmonary, or
             gastrointestinal disorders

          -  Subjects with IDDM

          -  Subjects with uncontrolled hypertension (DBP > 95 mmHg) or symptomatic hypotension

          -  Subjects with epilepsy, a history of epilepsy, or a history of seizure

          -  Subjects with a positive drug screen for cocaine or other drugs of abuse

          -  The following laboratory test and ECG results are exclusionary:

               1. Platelets ≤ 75,000/mm3

               2. Hemoglobin ≤ 9 g/dL

               3. Neutrophils, absolute ≤ 1000/mm3

               4. AST > 3 × upper limit of normal

               5. ALT > 3 × upper limit of normal

               6. Creatinine ≥ 2 mg/dL

               7. HbA1c ≥ 7%

               8. QTcF ≥ 450 msec

          -  Treatment with a MAOI within the 2 weeks prior to the first dose of trial medication

          -  Use of benzodiazepines and/or hypnotics within 1 week prior the first dose of trial
             medication

          -  Use of oral neuroleptics within 30 days prior to or long-acting approved neuroleptics
             ≤ 1 full cycle plus 14 days prior to the first dose of trial medication on Day 1

          -  Prohibited concomitant medications used prior to randomization or anticipated need for
             such medications during the trial

          -  Subjects who would be likely to require prohibited concomitant therapy during the
             trial

          -  Subjects who received brexpiprazole in any prior clinical trial

          -  Subjects with a history of neuroleptic malignant syndrome

          -  Subjects with a history of true allergic response to more than 1 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.