Efficacy, Safety, and Tolerability Study of AVP-786 as an Adjunctive Therapy in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment

It is estimated that up to approximately 200 patients will participate in the study at
approximately 30 enrolling centers in the US.

Eligible patients for this study must have MDD as defined by the Diagnostic and Statistical
Manual of Mental Disorders (DSM-IV-TR) criteria, and have shown an inadequate response to
standard antidepressant treatment.

This is a multicenter, randomized, double-blind, placebo-controlled, study of 10 weeks
duration.

Following screening procedures for assessment of inclusion and exclusion criteria, eligible
patients will be randomized into the study. Study medication will be administered orally BID
(1 capsule in the morning and 1 capsule in the evening, approximately 12 hours apart)
throughout the treatment period.

Inclusion Criteria:

- Clinical diagnosis of major depressive episode ≤ 24 months in duration

- HAM-D17 score ≥ 20.

- Documented to not have a significant (25% or greater) change in QIDS-SR16 score
between Screening and Baseline visits.

- Patients have been deemed to have an inadequate response (less than 50% symptom
reduction) to at least 1 but no more than 3 adequate antidepressant trials during the
current depressive episode.

- Patients must be receiving ongoing treatment with an adequate dose of
antidepressants.

- Body Mass Index (BMI) of 18-35 kg/m².

Exclusion Criteria:

- History of myasthenia gravis.

- Have cardiovascular concerns such as:

- History of complete heart block, QT interval corrected for heart rate (QTc)
prolongation, or torsades de pointes.

- QTc using the Fridericia's formula (QTcF) at screening > 450 msec for males and
> 470 msec for females based on central review at the screening visit, unless
due to ventricular pacing.

- Any family history of congenital QT interval prolongation syndrome.

- Known hypersensitivity/intolerance to DM, Q, opiate drugs (codeine, etc.), or any
other ingredient of the study medication.

- Pose a current suicide risk, as evidenced by any of the following:

- It is the judgment of the investigator that the subject may be at risk for
suicide.

- The subject is rated a "yes" to question 4 or question 5 on the Baseline C-SSRS,
if the most recent episode occurred within the past 12 months.

- The subject has attempted suicide within the past 6 months

- Presence of any other current DSM-IV-TR Axis I disorders with the exception of:
generalized anxiety disorder (GAD: 300.02), social anxiety disorder (300.23),
dysthymic disorder (300.4), or specific phobia (300.29). Patients with co-morbid GAD,
social anxiety disorder, or specific phobia are ineligible if the co-morbid condition
is clinically unstable, or has been the primary focus of treatment within the 6 month
period prior to screening

- Axis I diagnosis of:

- Delirium, dementia, amnestic, or other cognitive disorder;

- Schizophrenia or other psychotic disorder, based on the M.I.N.I.;

- Bipolar I or II disorder, based on the M.I.N.I.

- Clinically significant Axis II (DSM-IV-TR) diagnosis of borderline, antisocial,
paranoid, schizoid, schizotypal or histrionic personality disorder.