A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in patients with treatment-resistant depression
This 12‑week, open‑label Phase IIa trial of a single 10 mg intranasal dose of 5‑MeO-DMT (BPL‑003) in patients (n=12) with treatment‑resistant major depressive disorder, found that the drug was generally well tolerated with mostly mild–moderate adverse events and rapid discharge readiness (median ~98 minutes). A rapid and sustained mean MADRS reduction of 12–13 points was observed from Day 2 through Day 85, with most participants meeting response criteria and several achieving remission, supporting further evaluation in larger controlled trials.
Authors
- Mathieu Seynaeve
- Fiona Dunbar
- Anna Ermakova
Published
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.
Research Summary of 'A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in patients with treatment-resistant depression'
Blossom's Take
This is one of the first clinical trials of 5-MeO-DMT in a psychiatric patient population, and the first to test an intranasal formulation in treatment-resistant depression. The intranasal route and short session duration (median discharge readiness under 100 minutes) distinguish it from most psychedelic therapy models, which typically require longer clinical supervision. The sustained symptom improvement over 12 weeks after a single dose is notable if confirmed in controlled trials, as current approved options for treatment-resistant depression (such as repeated esketamine dosing) generally require ongoing administration. However, the open-label design, very small sample size (n=12) and lack of a placebo arm mean that the clinical signal cannot yet be separated from expectancy, natural fluctuation or regression to the mean.
Introduction
Major depressive disorder (MDD) is a highly prevalent and often debilitating illness, and up to 30% of patients fail to respond adequately to conventional antidepressant treatments, a condition termed treatment-resistant depression (TRD). Pharmacological options for TRD are limited and can carry substantial side-effect burdens; currently approved medications specifically indicated for TRD include olanzapine–fluoxetine combination therapy and esketamine (with evolving approvals). Interest in psychedelic compounds as potential rapid-acting treatments for TRD has increased. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a short-acting tryptamine with potent serotonergic activity (notably high affinity for 5-HT1A receptors) that produces rapid, profound subjective effects. Intranasal delivery of 5-MeO-DMT may offer more consistent dosing and greater acceptability than vapour inhalation or injection, and a Phase I placebo-controlled single-ascending-dose study of intranasal BPL-003 (5-MeO-DMT benzoate) showed good safety and tolerability in healthy volunteers at doses up to 12 mg. Roberts and colleagues designed a Phase 2a, open-label, single-cohort study to evaluate the safety, tolerability, pharmacokinetics (PK) and effects on depression-related clinical outcomes of a single 10 mg intranasal dose of BPL-003, delivered with standardised psychological support, in adults with moderate-to-severe MDD meeting criteria for TRD. The trial aimed to generate preliminary safety and efficacy signals to inform larger, controlled trials.
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References (16)
Papers cited by this study that are also in Blossom
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