Indication: Major Depressive Disorder

# of Subjects: 32 Randomized (2 cohorts of 16)

Inpatient Period: 18 days

Objectives

Primary

To determine the safety and tolerability of XXXXX when administered as adjunctive therapy to other antidepressant ther-apy (ADT) to MDD patients following multiple ascending oral doses.

Secondary

To determine the steady-state pharmacokinetics (PK) of XXXXX and its metabolitesin MDD patients following multipleoral doses of XXXXX.

Ratings

Mini International Neuropsychiatric Interview (M.I.N.I.), Simpson Angus Scale (SAS), Abnormal Involuntary MovementScale (AIMS), Barnes Akathisia Rating Scale (BARS), Columbia-Suicide Severity Rating Scale (C-SSRS)

Lab Assessments — 24 per subject:

Screening

Day -1 Days 1: pre-dose

Days 16: pre-dose

Days 17: pre-dose

Day 18: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 , 48, 72 ,96, 120, 144, 168, 192, and 216 hours post-dose

ECGs—42 per subject: Screening

Day -1

Day 1: pre-dose, 2, 4, and 6 hours post-dose

Days 2 to 4: pre-dose

Days 5: pre-dose, 2, 4, 6, 8 and 12 hours post-dose

Days 6 to 17: pre-dose only

Days 18: pre-dose, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, and 216 hours post-dose

Resting 12-lead ECG performed after the subjecthas been supine at rest for 10 minutes

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Vitals — 42 per subject in triplicate = 126

Screening Day -1

Day 1: pre-dose, 2, 4, and 6 hours post-dose

Days 2 to 4: pre-dose

Day 5: pre-dose, 2, 4, 6, 8 and 12 hours post-dose

Days 6 to 17 at pre-dose

Day 18: pre-dose, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144,168, 192, and 216 hours post-dose

Blood pressure and heart rate taken in the supine, sitting, and standing positions after remaining for3 minutes in each position.

Respiratory rate and oral body temperature taken with the subject in the supine position.