Results of a proof-of-concept, dose-finding, double-blind, placebo-controlled study of RX-10100 (Serdaxin®) in subjects with major depressive disorder.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Atlanta Center for Medical Research, Atlanta, GA, USA.
Robert
R
Riesenberg
Joshua
J
Rosenthal
Leslie
L
Moldauer
Christine
C
Peterson
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome; D047090:beta-Lactams / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000928:Antidepressive Agents; C575195:RX-10100; D047090:beta-Lactams