Results of a proof-of-concept, dose-finding, double-blind, placebo-controlled study of RX-10100 (Serdaxin®) in subjects with major depressive disorder
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RX-10100 (Serdaxin®), a nonantibiotic small molecule beta-lactam compound, has shown potent antidepressant and anxiolytic activities in preclinical models. RX-10100 does not bind to the serotonin transporter or other receptors associated with monoamine activity. In microdialysis studies with rats, RX-10100 increased the release of dopamine and serotonin metabolites. A clinical proof-of-concept study was conducted to determine the clinical effectiveness of RX-10100 in treating depression.
This was a multicenter, randomized, double-blind, placebo-controlled, parallel group study of people with depression (n = 77; HAM-D-17 baseline score ≥ 20). Eligible subjects were randomly assigned to receive RX-10100 (5, 10, or 15 mg twice daily) or placebo for 8 weeks. Change from baseline in the MADRS total score was the primary endpoint.
Mean changes in MADRS scores were −46.0%, −37.9%, and −41.4%, for 5, 10, and 15 mg RX-10100, respectively, as compared with 43.1% for placebo. In subjects with severe depression (baseline MADRS ≥ 29; n = 28) scores improved 55.6% with 5 mg RX-10100 but only 34% with placebo (p = 0.041). In an analysis of responders (i.e., subjects with 50% change from baseline score), 64.3% of subjects treated with 5 mg RX-10100 responded. All doses of RX-10100 were well-tolerated.
In this proof-of-concept study, RX-10100 treatment (5 mg twice daily) improved MADRS scores in subjects with severe depression. RX-10100 does not appear to have many of the typical side effects of other antidepressants. These results indicate a need for larger studies further evaluating RX-10100 at 5 mg and lower doses.
KeywordsDepression Antidepressant Hippocampus Serotonin Serotonergic Dopamine Dopaminergic Anxiety Microdialysis
Conflicts of interests
This study was registered at www.clinicaltrials.gov trial identifier: NCT00839176. This study was financially supported by Rexahn Pharmaceuticals, Inc. who designed, conducted, analyzed the study results and wrote the reports. All authors contributed to and approved the final manuscript. Drs. Riesenberg, Rosenthal and Moldauer have no conflicts of interest to declare. Dr. Peterson is employed by Rexahn Pharmaceuticals, Inc.
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