Evaluation of 2R,6R-Hydroxynorketamine Infusions Compared to Placebo for Adults with Treatment-Resistant Major Depressive Disorder

What this Trial Is About

Researchers are evaluating the antidepressant effects of 2R,6R-hydroxynorketamine HNK in adults with treatment-resistant major depressive disorder MDD. This phase 2 randomized, double-blind, placebo-controlled, crossover study aims to determine if HNK can improve overall depressive symptoms faster than current treatments. The study focuses on adults aged 18 to 70 years with MDD who have undergone a prior screening assessment and experienced inadequate responses to antidepressant therapies. Participants will taper off their current antidepressant medications over 2 to 5 weeks and then remain off these drugs for up to 2 weeks before starting study treatments. They will receive HNK or placebo infusions intravenously through a vein, with four infusions over two weeks during each of two test sessions. One test session involves HNK, and the other involves placebo, with a crossover design where participants receive both treatments in different orders. Doses range from 0.25 mgkg up to 2.0 mgkg, adjusted based on response and tolerability. Participants stay overnight at the clinical center after each infusion or for the study duration. Throughout the trial, participants undergo physical exams, blood tests, heart function assessments, mood and cognitive evaluations, and complete symptom questionnaires. Optional brain imaging and brain activity scans may be performed. Researchers measure changes in depression severity using the Montgomery-Asberg Depression Rating Scale MADRS and other mood and anxiety scales. Safety is monitored through adverse event reports, vital signs, laboratory tests, and electrocardiograms. The total participation spans the infusion sessions and follow-up assessments up to day 12 after each test session.

Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression