Clinical trial NCT02067793: Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder
Official title: Phase 2, Randomized, Double-Blind, Multiple-Dose Level, Placebo Controlled, Single Intravenous Dose, Parallel Efficacy and Safety Study of NRX-1074 in Subjects With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: NRX-1074
NMDA Receptor Modulator
Major Depressive Disorder
Glycine site modulator
Lead sponsor: Naurex, Inc, an affiliate of Allergan plc
Sponsor class: INDUSTRY
First posted: 2014-02-20
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of NRX-1074 following a single intravenous dose in subjects with major depressive disorder.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the mean change from baseline in Hamilton Depression Rating Scale 17 (HDRS-17) score for each NRX-1074 dose group versus the placebo group's mean change
timeFrame: Day 1, Day 3, Day 7, Day 14
Secondary outcomes:
measure: Change in Brief Psychiatric Rating Scale positive symptoms (BPRS+) scale
timeFrame: Day 1
measure: Change in Clinician Administered Dissociative States Scale (CADSS)
timeFrame: Day 1
measure: Change in Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Day 1
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Pacific Research Partners
state: California
city: Skokie
country: United States
facility: Psychiatric Medicine Associates
state: Illinois
city: Wichita
country: United States
facility: University of Kansas School of Medicine Clinical Trial Unit
state: Kansas
city: Roslindale
country: United States
facility: Boston Clinical Trials, Inc.
state: Massachusetts
city: O'Fallon
country: United States
facility: Psychiatric Care and Research Center
state: Missouri
city: Elmsford
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: Mason
country: United States
facility: Lindner Center of HOPE
state: Ohio
city: Memphis
country: United States
facility: Research Strategies Memphis
state: Tennessee
city: Dallas
country: United States
facility: Research Across America
state: Texas
city: Salt Lake City
country: United States
facility: Lifetree Clinical Research
state: Utah
city: Charlottesville
country: United States
facility: Psychiatric Alliance of the Blue Ridge
state: Virginia
Study officials:
affiliation: Naurex, Inc, an affiliate of Allergan plc
name: Medical Director
role: STUDY_DIRECTOR
References: