Completed Clinical Trials
Phase 2b study of BPL-003 in patients with treatment resistant depression
Study Overview
The eight-week, quadruple-masked, dose-finding, core stage of the Phase 2b clinical trial evaluated the efficacy and safety of a single dose of BPL-003 in 193 patients with moderate-to-severe treatment-resistant depression (TRD, defined as non-response to two or more prior treatments in the current depressive episode). Patients were randomized to receive a single 12 mg (n=73), 8 mg (n=46), or 0.3 mg comparator (n=74) dose of BPL-003 and were followed for eight weeks with efficacy assessments conducted by centralized, blinded raters using the Montgomery-Åsberg Depression Rating Scale (MADRS) at Day 2, Day 8, Day 29 and Day 57.
Key findings
- A single 12 mg dose of BPL-003 led to a mean reduction in MADRS score from baseline of 11.1 points compared with 5.8 points in the 0.3 mg comparator arm (p=0.0038) at Day 29, with the 8 mg dose arm showing a mean MADRS reduction from baseline of 12.1 points versus the 0.3mg comparator arm (p=0.0025) at that same timepoint.
- The 8 mg and 12 mg doses of BPL-003 demonstrated equivalent efficacy suggesting the 8 mg dose may be sufficient to achieve therapeutic benefit from a single dose.
- The difference in MADRS scores between the 8 mg and 12 mg doses versus the 0.3 mg dose were statistically significant in both active arms from as early as Day 2, with mean MADRS reductions from baseline of 8.8 points in the 8 mg group and 8.9 points in the 12 mg group observed at that timepoint, compared to a reduction from baseline of 3.9 points in the 0.3 mg group. These mean reductions from baseline increased to 11.1 points in the 8 mg group and 10.8 points in the 12 mg group at Day 8.
- A durable effect was also observed for both higher doses, with the 8 mg group showing a mean reduction of 10.8 points from baseline at Day 57 and the 12 mg group showing a mean reduction of 10.2 points from baseline compared with the 0.3 mg group (5.2-point reduction). These findings highlight the potential of BPL-003 to be a durable treatment for patients with TRD.
- BPL-003 was generally well-tolerated at all doses. More than 99% of treatment-emergent adverse events (TEAEs) were mild or moderate.
- Dose related increases in administration site discomfort, nausea, headache, blood pressure and anxiety suggest the 8mg dose was better tolerated than the 12mg dose.
- The average time to meet readiness for discharge criteria across all arms was within two hours of dosing, with the majority of patients deemed ready for discharge at the 90-minutes post-dose assessment.
Phase 2a study of BPL-003 in patients with treatment resistant depression currently taking SSRIs
Study overview
The open-label Phase 2a study investigated the safety, efficacy and pharmacokinetics of a single dose of BPL-003 in 12 patients with moderate-to-severe depression who had failed to respond to at least two or more prior treatments of depression and were taking defined SSRIs. Patients were followed for 12 weeks post-dosing, with assessments conducted at multiple points throughout the study.
Key findings
- A single dose of BPL-003 induced rapid antidepressant effect, with a mean MADRS reduction of 18 points from baseline observed the day after dosing.
- This antidepressant effect was long-lasting, with a mean MADRS reduction of 19 points from baseline observed one month after dosing and a mean MADRS reduction of 18 points from baseline observed three months after dosing.
- BPL-003 was shown to be well-tolerated. All adverse events (AEs) were mild or moderate in severity and there were no serious adverse events (SAEs) reported.
- Acute effects resolved on the day of dosing, with patients deemed dischargeable within an average time of less than two hours.
Phase 2a study of BPL-003 in patients with treatment resistant depression
Study overview
The open-label Phase 2a study investigated the safety, efficacy and pharmacokinetics of 10 mg of BPL-003 in patients with TRD who were not taking concomitant antidepressants. TRD was defined as a failure to respond to two or more pharmacological treatments within the current depressive episode.
Key findings
- A single administration of BPL-003 demonstrated a rapid antidepressant effect, with 55% of patients having a 50% or greater improvement in depression symptoms the day after dosing (day 2).
- A robust and lasting antidepressant effect was shown, with 55% of patients meeting the criteria for remission from symptoms of depression at day 29 and 45% in remission at day 85.
- BPL-003 required a short time in clinic, with patients deemed dischargeable within an average time of less than two hours. This underlines the potential to deliver a scalable treatment model that, if approved, could fit within the existing interventional psychiatry treatment paradigm.
Phase 2a study of 2-dose induction of BPL-003 in patients with Treatment-Resistant Depression
Study overview
The open-label Phase 2a study investigated the safety, tolerability and efficacy of a two-dose induction of BPL-003, where patients were given an 8 mg dose of BPL-003 followed by a 12 mg dose two weeks later, in patients with Treatment-Resistant Depression who were not on concurrent antidepressants. 13 patients were enrolled and 12 met the criteria for per-protocol analysis. Assessments were conducted at various timepoints for 12 weeks following the initial dose using multiple validated depression rating scales including the MADRS (Montgomery-Asberg Depression Rating Scale).
Key findings
- Following the first (8 mg) dose, patients experienced a mean MADRS reduction of 13.3 points from baseline at Day 2 and a mean MADRS reduction of 12.9 at Day 8. One week after the second dose (12 mg), there was a further decrease in MADRS score to a total of a 19.0-point reduction from baseline, with sustained antidepressant effects observed through Week 12 (13.7 points from baseline).
- The second dose of BPL-003 increased the proportion of patients meeting response and remission criteria for depression. Remitter rates one week after the initial 8mg dose were 25%, with rates doubling to 50% at Week 8 (6 weeks after the second dose administration) and 42% at Week 12.
- BPL-003 was shown to be generally well-tolerated, with all adverse events classified as mild to moderate, and there were no severe or serious drug-related adverse events reported.
- Patients met discharge readiness criteria within two hours after dosing for both doses.
Phase 2a study of BPL-003 in patients with alcohol use disorder
Study overview
The open-label Phase 2a study investigated the safety, tolerability, pharmacodynamic effects and impact on alcohol use of a single dose of BPL-003—when given in combination with relapse prevention cognitive behavioural therapy—in 12 patients diagnosed with moderate-to-severe Alcohol Use Disorder.
Key findings
- The mean number of alcohol units per day decreased from 9.3 in the 12 weeks prior to dosing to 2.2 at the end of the study (12 weeks post-dosing).
- The mean percentage of Heavy Drinking Days dropped from 56% in the pre-dose period to 13% at the end of the study.
- The mean number of abstinent days increased from 33% in the pre-dose period to 81% at the end of the study.
- 50% of participants remained completely abstinent during the 12-week follow-up period following a single dose.
- BPL-003 was shown to be well-tolerated with AEs being reported as mild or moderate and there were no serious or severe adverse events reported.
- Most patients were also assessed as ready for discharge within approximately two hours.
Phase 1 study of BPL-003 in healthy volunteers
Study overview
The double-blind, placebo-controlled, single ascending dose study explored the safety, tolerability, pharmacokinetics and pharmacodynamics of BPL-003 treatment in 44 healthy volunteers. In the study, participants across seven cohorts were given either a single dose of BPL-003 between 1 mg to 12 mg or a placebo.
Key findings
- The study found that BPL-003 was safe and well-tolerated with no serious or severe adverse events reported.
- BPL-003 was rapidly absorbed and eliminated, with 5‑MeO-DMT systemic exposure increasing approximately dose‑proportionally.
- There was a reliable onset of subjective effects within minutes and these effects were resolved in less than two hours.
- 87% of participants who received BPL-003 said they would accept the same or higher dose again, with 100% of participants who received the highest (12 mg) dose stating they would accept the same or higher dose again.