Randomised, double‑blind, placebo‑controlled Phase I/II two‑part study (n=66 actual) of IV SPL026 (DMT fumarate): single‑dose, dose‑escalation in healthy volunteers; patients with MDD receive dose 1 randomised vs placebo and an open‑label second dose 2 weeks later.
Two‑part study: Part A tests single IV SPL026 in psychedelic‑naïve healthy volunteers in a parallel dose‑escalation design; Part B treats patients with moderate‑severe MDD with up to two single IV doses (dose 1 randomised double‑blind vs placebo; dose 2 open‑label active 2 weeks later).
Outcomes include safety and tolerability, pharmacokinetics and pharmacodynamics, and clinical efficacy measures (eg HAM‑D) with acute and follow‑up assessments.
Healthy volunteers — single IV SPL026, dose-escalation, parallel-group.
Single IV dose; dose-escalation in parallel groups (no mg specified).
Healthy volunteers — SPL026-matched placebo IV.
Placebo (SPL026-matched) single IV dose.
Patients with MDD — up to two single IV doses; dose 1 randomised vs placebo, dose 2 open-label active.
Dose 1 randomised double-blind vs placebo; dose 2 open-label SPL026.
Patients with MDD — placebo for dose 1 only.
Placebo given for dose 1; dose 2 is open-label active.
In a randomized, placebo‑controlled Phase 1 trial in psychedelic‑naïve healthy volunteers, single escalating IV doses of SPL026 (DMT fumarate) were well tolerated with an acceptable safety profile and showed dose‑related increases in acute psychometric intensity that correlated with plasma concentrations; based on safety, PK and pharmacodynamic data a 21.5 mg two‑phase 10‑minute infusion was selected for the subsequent Phase 2a study.