Phase 1 Study to Assess the Safety/Tolerability of Brexpiprazole as Adjunctive Therapy in Elderly Subjects With Major Depressive Disorder

A Phase 1, Multicenter, Randomized, Double-blind, Sequential Cohort, Placebo-controlled Trial to Assess the Safety and Tolerability of Ascending Multiple Oral Doses of Brexpiprazole as Adjunctive Therapy in the Treatment of Elderly Subjects With Major Depressive Disorder

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.

This is a phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial in 3 sequential cohorts of elderly subjects (age 70 to 85 years old) with MDD. Brexpiprazole will be administered as an adjunct treatment to the current antidepressant therapy that the subject is receiving. Total individual subject duration is expected to be no more than 119 days (a 30-day screening period, a 14-day washout period, up to 45-day in-clinic treatment period, and a 30-day follow-up after the last dose of trial medication).

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.