A phase 2 uncontrolled,open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression

Abstract

Aims:

To evaluate the safety and effect on clinical outcomes of depression of Beckley Psytech Ltd (BPL)-003, an intranasal formulation of 5-methoxy-N,N-dimethyltryptamine, in patients with moderate-to-severe major depressive disorder (MDD) with treatment-resistant depression (TRD).

Methods:

Twelve participants with TRD were enrolled in a 12-week, open-label, phase 2a trial. Safety of a single intranasal dose of 10 mg BPL-003 was assessed through clinical evaluations, treatment-emergent adverse events (TEAEs) and Readiness for Discharge Questionnaire (RDQ). Key depression-related assessments were Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline, percentage of responders, and participants in remission on Days 2, 8, 29, 57 and 85 post-dose.

Results:

All participants completed the trial; 2 females, 10 males, aged 31–55 years. Nine (75.0%) participants had 18 treatment-related TEAEs; 8 mild, 9 moderate and 1 severe (increased blood pressure, which returned to baseline within the observation period), with nausea and nasal discomfort the most frequently reported. Ten participants were ready after their first RDQ (nominal time 90 minutes post-dose). Median time from dosing to discharge readiness was 98 minutes (range 95–167). There was a mean decrease in MADRS total score from baseline of 12.2–13.0 points across all timepoints between Days 2 and 85; most participants (10/11) were responders, and 7 were in remission at ⩾1 post-dose timepoint.

Conclusion:

Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, suggesting BPL-003 could be beneficial in TRD, warranting investigation in larger controlled trials.