Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder

NRX-1074 is a N-methyl-D-aspartate (NMDA) receptor functional partial agonist with efficacy
in animal models of affective disorders including major depressive disorder. The purpose of
this study is to evaluate efficacy and safety of NRX-1074 at dose levels that are predicted
by comparison of human and animal pharmacokinetics to be efficacious.

Inclusion Criteria:

- Male and female subjects

- Aged 18 to 65 years

- Meets Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR)
criteria for major depressive disorder (MDD)

- Current episode has lasted ≥ 8 weeks before Screening

- HDRS-17 score ≥ 21 before beginning the washout of all current antidepressant agents
and/or adjuvant agents

- HDRS-17 score ≥ 21 at Baseline (after 14 days of washout of current antidepressant
agents)

- Female subjects of childbearing potential with a negative serum pregnancy test prior
to entry into the study and who are practicing an adequate method of birth control
(eg oral or parenteral contraceptives, intrauterine device, barrier, abstinence) and
who do not plan to become pregnant during the course of the study. Female subjects
may be included without a negative serum pregnancy test if they are surgically
sterile or at least 2 years post-menopausal

- Male subjects and their female sexual partner should use an acceptable method of
birth control during the study

- Clinical laboratory values < 2 times the upper limit of normal (ULN) or deemed not
clinically significant per the investigator and Naurex medical monitor

- Ability to understand the requirements of the study, provide written informed
consent, abide by the study restrictions, and agree to return for the required
assessments

- Based on both the investigator and Naurex medical monitor's clinical judgment,
subjects with eating disorders, obsessive compulsive disorder (OCD), panic disorder,
post-traumatic stress disorder (PTSD), and generalized anxiety disorders secondary to
major depressive episodes are permitted

Exclusion Criteria:

- Axis I diagnosis of delirium, dementia, dysthymia, amnestic or other cognitive
disorder, schizophrenia or other psychotic disorder, bipolar I or II disorder, eating
disorder (anorexia or bulimia nervosa), obsessive-compulsive disorder, panic
disorder, agoraphobia, social phobia, attention-deficit hyperactivity disorder
(ADHD), or PTSD

- 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; lifetime history of psychosis

- Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or a history of seizures
or strokes

- Currently hospitalized or residing in an in-patient facility during the study
participation

- Substance abuse within the last 12 months, including greater than or equal to 5 units
of alcohol per day where 1 unit = 1/2 pint of beer, 1 glass of wine, or 1 oz. of
spirits consumed most weeks or in the opinion of the investigator

- Allergy or intolerance to current antidepressant or other current medications

- Participation in any clinical trial of an investigational product or device within 30
days of enrollment in this trial

- Positive screen for drugs of abuse: cocaine, marijuana, PCP, ketamine, opioid or
other agent that in the opinion of the investigator is being abused

- Have received electroconvulsive therapy, transcranial magnetic stimulation (TMS), or
vagal nerve stimulation (VNS) for the current depressive episode

- Post current (past 6 months) suicide risk based on administration of the C-SSRS and
the investigator's clinical judgment

- Human immunodeficiency virus (HIV) infection (based on the HIV-1 & HIV-2 antibody
screen) or other ongoing infectious disease

- Females or female partners of male subjects who are currently pregnant or planning to
become pregnant during the course of the study. Women who are breastfeeding

- Currently taking prescription (psychiatric treatments, antidepressant treatments) or
over-the-counter medications including herbal therapies to treat their MDD or
conditions secondary to their period following study drug dosing. Dextromethorphan or
tramadol since these are serotonin uptake inhibitors.