Journal of Psychiatric Practice Vol. 21, No. 2 140 March 2015 Background. Approximately 45% of patients with major depressive disorder (MDD) do not remit when treated with biogenic amine antidepressants. Consequently, there is a significant need for antide- pressant agents with different mechanisms of action. Early proof of concept (POC) studies with such novel agents play a significant role in helping drug developers identify agents and mechanisms of action that merit more intensive research. Studies have demonstrated that high affinity N-methyl-D- aspartate (NMDA) receptor blockers (eg, ketamine) can produce rapid antidepressant effects in patients who have not responded to currently available agents, but treatment with these agents is accompa- nied by psychotomimetic effects that make their use problematic. This column describes a POC study involving GLYX-13, an N-methyl-D-aspartate recep- tor glycine site functional partial agonist. Method. In this double-blind, randomized, placebo-con- trolled study, a single intravenous (IV) dose of GLYX-13 (1, 5, 10, or 30 mg/kg) or placebo was admin- istered to 116 subjects with MDD who had not bene- fitted from a trial of at least one biogenic amine antidepressant during the current episode. The pri- mary outcome measure was score on the Hamilton Depression Rating Scale-17 (Ham-D 17 ), which was used to rate overall depressive symptoms at base- line and at 24 hours and days 3, 7, 14, and, in some arms, days 21 and 28 after administration. Results. GLYX-13, 5 or 10 mg/kg IV, reduced depressive symp- toms as assessed by the Ham-D 17 at days 1 through 7. Onset of action as assessed using the Bech-6 occurred within 2 hours. GLYX-13 did not elicit psy- chotomimetic or other significant side effects. wide LLC, St Louis, MO; and Gary Zammit, PhD, Clinilabs, New York, NY. Funding for this study was provided in its entirety by Naurex, Inc, 1801 Maple Avenue, Suite 4300, Evanston IL 60201, which owns patents, patent applications, and commercialization rights to GLYX-13. Dr. Burch is an employee of Naurex and has received financial compensation and stock. Drs. Macaluso, Mehra, Presko- rn, and Zammit were paid clinical investigators for Naurex. Dur- ing the past 12 months, Dr. Preskorn has been a consultant for AssureX, Delphor, Eisai, Johnson & Johnson, Merck, Naurex, Sunovion, and Tashio. Dr. Moskal is the founder of Naurex, Inc. He has founders' shares of stock in the company and receives financial compensation as a consultant. Clinical trial registration. Single IV Dose of GLYX-13 in Patients With Treatment-Resistant Depression, http://www.clinicaltrials .gov/ct2/show/NCT01234558?term=Naurex&rank=2, NCT01234558; Single Ascending Dose Safety, Tolerability and Pharmacokinetics Study of GLYX-13 in Normal Volunteers, http://www.clinicaltrials.gov/ct2/show/NCT01014650?term=Nau- rex&rank=3, NCT01014650. Note: Portions of this column are adapted with permission from Moskal et al. 2014. 9 DOI: 10.1097/01.pra.0000462606.17725.93 PRESKORN and MACALUSO: University of Kansas School of Medicine, Wichita, KS; MEHRA: Artemis Institute for Clinical Research, San Diego, CA; ZAMMIT: CliniLabs, New York, NY; MOSKAL: Dept Biomedical Engineering, Falk Center for Molecular Therapeutics, McCormick School of Engineering and Applied Sciences, Northwestern University, and Naurex Inc, Evanston, IL; BURCH: Naurex Inc, Evanston, IL. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Please send correspondence to: Ronald M Burch, MD, PhD, Naurex, Inc, 1801 Maple Avenue, Suite 4300, Evanston IL, 60201 ronburch@naurex.com Acknowledgements. The GLYX-13 Clinical Study Group Principal Investigators were Misha Backonja, MD, Lifetree Clinical Research, Salt Lake City, UT; Daniel Greuner, MD, Lifetree Clini- cal Research, Philadelphia, PA; Paul Gross, MD, Lehigh Center for Clinical Research, Allentown, PA; David Krefetz, DO, Lifetree Clin- ical Research, Willingboro, NJ; Benji Kurian, MD, University of Texas Southwestern Medical Center, Dallas, TX; Michael Lesem, MD, Claghorn-Lesem Clinical Research Ltd, Houston, TX; Matthew Macaluso, DO, and Sheldon Preskorn, MD, University of Kansas School of Medicine, Wichita, KS; Raymond Manning, MD, CNRI-LA, Pico Rivera, CA; Vishaal Mehra, MD, Artemis Institute for Clinical Research, San Diego, CA; Rick Mofsen, MD, CRI World- Randomized Proof of Concept Trial of GLYX-13, an N-Methyl-D-Aspartate Receptor Glycine Site Partial Agonist, in Major Depressive Disorder Nonresponsive to a Previous Antidepressant Agent Psychopharmacology SHELDON PRESKORN, MD MATTHEW MACALUSO, DO VISHAAL MEHRA, MD GARY ZAMMIT, MD JOSEPH R. MOSKAL PhD RONALD M BURCH, MD, PhD and the GLYX-13 Clinical Study Group Copyright © Wolters฀Kluwer฀Health,฀Inc.฀ Unauthorized reproduction of this article is prohibited.