Oral Slow-Release Ketamine for Hard-to-Treat Depression: Two Clinical Trials

KET01, a novel oral ketamine formulation, demonstrated minimal dissociation with a maximum plasma concentration of 39.1 ng/mL.

• In a phase 1 trial, intranasal esketamine caused significant dissociation, with a mean change in dissociative scores of 29.6 points compared to 0.7 points for KET01 (P < .001).
• KET01 showed a higher exposure to its metabolites compared to esketamine, suggesting different metabolic pathways.
• Blood pressure and pulse rates remained stable in the KET01 group, unlike the increases observed following esketamine administration.
• The primary efficacy endpoint was not achieved in the phase 2 trial, with KET01 showing a LS mean difference in depression scores of -1.82 points at day 21 (P = .41).
• A significant reduction in depression scores was noted at day 4 (-3.66 points; nominal P = .02) and day 7 (-3.95 points; nominal P = .04) after the first dose of KET01.

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