Study of Safety, Tolerability and Pharmacokinetics of NRX-1074 in Normal Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of multiple oral (PO) ascending doses of NRX-1074 in normal healthy volunteers.

Detailed Description
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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 the safety and tolerability of multiple oral (PO) ascending doses of NRX-1074 as evidenced by the incidence and severity of adverse events (AEs), changes in serum chemistry, hematology, and urinalysis, changes in physical examination findings, psychotomimetic findings and subject-reported symptoms.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Multiple Oral Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of NRX-1074 in Normal Healthy Volunteers

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: NRX-1074 375 mg
* Drug: NRX-1074 500 mg
* Drug: NRX-1074 750 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects Aged 18 to 55 years For female subjects, surgically sterile or at least 2 years menopausal, or using an acceptable method of birth control. If of childbearing potential, have a documented negative blood or urine pregnancy test within 24 hours prior to dosing. Clinical laboratory values <2 times upper limit of normal (ULN) or deemed not clinically significant by the investigator 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 Exclusion Criteria: Human immunodeficiency virus (HIV) infection, or hepatitis or other ongoing infectious disease. Current evidence of alcohol abuse (greater than 4 units of alcohol on most days; 1 unit = 1/2 pint of beer, 1 glass of wine or 1 oz. of spirits), or in the option of the investigator that subject may be alcoholic. Current abuse of illicit substances, using the Diagnostic and Statistical Manual (DSM) IV definition of drug abuse. Current smoker or use of other tobacco products. Currently pregnant, planning to become pregnant during the course of the study, or nursing mother. Type I or Type II diabetes. Malignancy in the last 5 years, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix. Currently taking prescription or over-the-counter medications including herbal therapies, within 14 days of enrollment into the study. History of allergy, sensitivity, or intolerance to NMDAR ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone or concomitant use of such agents. Received another investigational drug or device within 30 days of enrollment in this study. Previously participated in this study. Psychiatric disease including major depression, bipolar disorder, anxiety, or schizophrenia, or other medical condition that, in the opinion of the investigator, would interfere with the evaluation of the study drug safety. 13) In the option of the Investigator or the Sponsor's Study Monitor, has a history of severe renal or hepatic impairment, severe active hepatic disease, or other clinically significant medical condition that may preclude safe study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Drug: Placebo<br>Single oral administration on Day 1 | Drug: Placebo<br>* Single oral administration of placebo consumption on Day 1<br>|
| Experimental: Drug: NRX-1074 375 mg<br>Single oral administration on Day 1 | Drug: NRX-1074 375 mg<br>* Single oral administration of 375 mg consumption on Day 1<br>* Other names: NRX-1074 single oral dose;|
| Experimental: Drug: NRX-1074 500 mg<br>Single oral administration on Day 1 | Drug: NRX-1074 500 mg<br>* Single oral administration of 500 mg consumption on Day 1<br>* Other names: NRX-1074 single oral dose;|
| Experimental: Drug: NRX-1074 750 mg<br>Single oral administration on Day 1 | Drug: NRX-1074 750 mg<br>* Single oral administration of 750 mg consumption on Day 1<br>* Other names: NRX-1074 single oral dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability | Observed side effects and changes in laboratory values | 28 days following study drug dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetics Cmax | Cmax after administration | For 24 hours after drug dose on Day 1 | 
| Plasma pharmacokinetics - Tmax | Tmax after administration | For 24 hours after drug dose on Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NRX-1074, NMDA Receptor Modulator, Major Depressive Disorder, Glycine Site Modulator