A Study of ALKS 5461 for Treatment Refractory Major Depressive Disorder (MDD)

Inclusion Criteria:

- Have a Major Depressive Disorder (MDD) primary diagnosis

- Have a body mass index (BMI) of 18.0 to
- Be willing and able to follow the study procedures and visits as outlined in the
protocol (including agreeing not to enroll in any other clinical trials)

- Have inadequate responses to antidepressant therapy (ADT) in the current Major
Depressive Episode (MDE)

- Additional criteria may apply

Exclusion Criteria:

- Has any finding that would compromise the safety of the subject or affect their
ability to adhere to the protocol visit schedule or fulfill visit requirements

- Has any other significant medical condition (eg, neurological, psychiatric, or
metabolic) or clinical symptom that could unduly risk the subject or affect the
interpretation of study data

- Has any current primary diagnosis other than MDD, where primary diagnosis is defined
as the primary source of current distress and functional impairment

- Has experienced hallucinations, delusions, or any psychotic symptoms in the current
MDE

- Has been hospitalized for MDD within 3 months before screening

- Has used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid
antagonists (eg, naloxone, naltrexone) within 14 days prior to screening

- Has received electroconvulsive therapy treatment within the last 2 years or within the
current MDE or failed a course of electroconvulsive treatment at any time

- Has a significant risk for suicide

- Has a positive breath alcohol test at screening

- Has a positive test for drugs of abuse at screening or visit 2

- Is pregnant, planning to become pregnant, or is breastfeeding during the study

- Additional criteria may apply