JAMA network open

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

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Abstract

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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Competing interests

Conflict of Interest Disclosures: Prof Walter reported having an institutional advisory role with HMNC, receiving personal fees from Janssen, receiving speaker compensation from Heel, receiving advisor compensation from Boehringer Ingelheim, and participating in an institutional study with Perception Neuroscience during the conduct of the study. Dr zu Eulenburg reported holding shares in and receiving consulting fees from HMNC Holding GmbH (one of the owners of the study sponsor, Ketabon GmbH) outside the submitted work. Ms Damyanova reported receiving personal fees from HMNC Holding GmbH during the study and outside the submitted work. Dr Papanastasiou reported receiving personal fees from HMNC Holding GmbH during the study and outside the submitted work. Ms Strote reported receiving personal fees from HMNC Holding GmbH during the study and outside the submitted work. Dr Gehrlach reported receiving personal fees from HMNC Holding GmbH during the study and outside the submitted work. Dr Eriksson reported receiving personal fees from and having stock options in HMNC Holding GmbH during the conduct of the study and outside the submitted work and having a pending patent application for an induction regimen for the administration of 2-(2-chlorphenyl)-2-(methylamino)cyclohexan-1-one. No other disclosures were reported.
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