ALK33BUP-201: Safety and Tolerability Study of ALKS 33-BUP (ALKS 5461) Administration in Subjects With MDD

• ALKS 5461 (Drug): Sublingual administration once daily for 7 consecutive days.
• Placebo (Drug): Sublingual administration once daily for 7 consecutive days.

Primary outcomes

• The number and percent of subjects with treatment-emergent adverse events following sublingual administration of ALKS 33 and buprenorphine co-formulation (ALKS 5461) [7 days]: Measured over a range of dose levels in subjects with inadequate/partial response to antidepressant therapy during the current episode of MDD.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Male and female subjects between 18 and 65 years of age, inclusive.
* Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for MDD.
* Current episode lasting ≥8 weeks prior to screening with an inadequate/partial response to an adequate trial (defined as at least 8 weeks) of a stable dose of an SSRI or SNRI. Inadequate/partial response is defined as:

  1. A Hamilton Depression Rating Scale total score (HAM-D17) ≥14, and
  2. Less than 50% reduction in depressive symptom severity on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ), and
  3. Clinical Global Impression - Severity (CGI-S) score of ≥3.

Exclusion Criteria:

* Axis I diagnosis of delirium, dementia, amnestic or other cognitive disorder, schizophrenia or other psychotic disorder, bipolar I or II disorder, eating disorder, obsessive-compulsive disorder, panic disorder, or posttraumatic stress disorder.
* A clinically significant current Axis II diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder.
* Experiencing hallucinations, delusions, or any psychotic symptomatology in the current episode.
* The use of inducers or inhibitors of cytochrome P450 (CYP) 3A4 (prescription medications, over-the-counter \[OTC\] medications, or dietary supplements) within 30 days before dosing.
* Have received electroconvulsive therapy during the current MDD episode.
* Pose current suicide risk as confirmed by the Columbia Suicide Severity Rating Scale (C SSRS).
* History of intolerance or hypersensitivity to buprenorphine.
* History of allergy or hypersensitivity to opioid antagonists (eg, naltrexone, naloxone) or quinine.

• Richard Leigh-Pemberton, M.D., Study director, Medical Director