To analyze the dissociative effects, antidepressant efficacy, pharmacokinetic parameters, and safety of KET01, a prolonged-release oral formulation of racemic ketamine, in patients with treatment-resistant depression (TRD).
Approach:
KET01-03 Phase 1 Trial: A randomized, head-to-head, double-blind, double-dummy, single-center, crossover trial comparing oral KET01 (240 mg) to intranasal esketamine (84 mg) in healthy male volunteers.
KET01-02 Phase 2 Trial: A randomized, placebo-controlled, double-blind trial in adult outpatients with TRD, comparing two doses of KET01 (120 mg/d and 240 mg/d) to a placebo over three weeks.
Key Findings:
KET01 demonstrated limited dissociative properties compared to intranasal esketamine.
Both trials adhered to ethical guidelines and were double-blinded to minimize bias.
The primary endpoints included changes in dissociative symptoms and depression severity as measured by CADSS and MADRS scores, respectively.
Interpretation:
The findings suggest that KET01 may offer a safer alternative to existing ketamine formulations for managing TRD, with reduced dissociative effects.
Limitations:
The KET01-03 trial was conducted only in healthy male volunteers, limiting generalizability.
The KET01-02 trial's results may be influenced by ongoing standard antidepressant therapy.
Conclusion:
KET01 shows promise as a treatment for TRD with a favorable safety profile, warranting further investigation.
by Martin Walter, Christine zu Eulenburg, Ani Damyanova, Karin Schmid, Isabel Schwienbacher, Evangelos Papanastasiou, Katarina Maiboe, Lars Arvastson, Caren Strote, Daniel Gehrlach, Hans Eriksson
The partner in the next room, the hormone in the blister pack, the cat on the couch, the minute-long chair stand. Several new studies suggest the factor shaping outcomes may be the one clinicians aren’t routinely measuring.
