Adaptive Phase IIa/IIb study (n=70) with open-label dose-finding (30/50/70 mg oral MSP-1014.OX) followed by a double-blind, randomised, placebo-controlled proof-of-concept single-dose study with preparatory and integration psychotherapy in MDD patients with partial/no SSRI response.
Part 1 is an open-label, multiple-ascending-dose, dose-finding study (30, 50, 70 mg oral MSP-1014.OX, three doses four weeks apart) to assess safety, cardiovascular effects, pharmacokinetics and pharmacodynamics in ~10 patients.
Part 2 is a double-blind, randomised (1:1) placebo-controlled proof-of-concept study of the selected dose with single dosing; all participants receive preparatory psychotherapy (3 sessions) and integration therapy (three sessions for Part 2).
Primary outcomes: Part 1 safety signals and cardiovascular parameters (HR, BP, QTc); Part 2 efficacy on MADRS at 4 weeks. Secondary outcomes include pharmacokinetics (psilocin plasma), subjective intensity, cognitive and biomarker measures (BDNF), and quality-of-life metrics.
Part 1 open-label: oral MSP-1014.OX 30, 50 and 70 mg; multiple-ascending-dose, three doses four weeks apart
Open-label dose escalation; planned n=10 for Part 1
Part 2 double-blind, randomised, placebo-controlled: selected MSP-1014.OX dose (from Part 1) administered as single dosing with psychotherapy
Selected dose (30/50/70 mg determined in Part 1); Part 2 randomised 1:1; approx. 60 participants (may increase to 82 after interim)
Matched oral placebo for Part 2
Placebo comparator, 1:1 allocation in Part 2