SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients

Study Overview
=================
Brief Summary
-----------------
SPL026 (N,N-dimethyltryptamine [DMT] fumarate) is a psychedelic tryptamine being developed as a therapy for patients with major depressive disorder (MDD).

Detailed Description
-----------------
2-part study. Part A in psychedelic-naïve healthy volunteers. Part B in patients with MDD who score moderate-severe on Ham-D. Healthy volunteers will receive a single dose of SPL026 in a dose-escalation parallel group study. Patients will receive up to 2 single doses of SPL026, 2 weeks apart. Dose 1 will be randomised double-blind with placebo. Dose 2 will be open label, active SPL026. SPL026 will be administered by IV injection. Safety and tolerability, PK, PD and efficacy will be measured.

Official Title
-----------------
A Double-blind, Randomised, Placebo-controlled Study of Intravenous Doses of SPL026 (DMT Fumarate), a Serotonergic Psychedelic, in Healthy Subjects (Part A) and Patients With Major Depressive Disorder (Part B)

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: SPL026
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Normotensive male or female, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, laboratory tests of blood and urine, Mini-International Neuropsychiatric Interview (MINI) and Beck Scale for Suicidal Ideation (BSS); willing to follow the contraception requirements of the trial; willing to refrain from psychedelic drug use (excluding the study drug) during the trial and ≥ 3 months afterwards; willing to be contacted by email and video call, and have online access; able to give fully informed written consent. Part A only: psychedelic-naïve, ie have never taken a serotonergic psychedelic drug, in any form. Must be 25 years or older. Part B only: MDD diagnosis (as per DSM-V); not on antidepressant medication or willing to discontinue antidepressant medication (eg selective serotonin reuptake inhibitor [SSRI] treatment) for a sufficient time before and during the study; no psychedelic drug use in the 6 months before dosing. Exclusion Criteria: Pre-menopausal females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception; clinically relevant abnormal findings at the screening assessment; acute or chronic illness (other than MDD [Part B only]) or infection; clinically relevant abnormal medical history or concurrent medical condition (other than MDD [Part B only]); positive tests for hepatitis B & C, or HIV; severe adverse reaction to any drug; use of over-the-counter or prescribed medication (excluding oral contraceptives) within previous 28 days (paracetamol [acetaminophen] permitted up to 7 days, and antidepressant medication must have ceased for at least 14 days; 28 days for MOAIs) before first dose of trial medication; drug or alcohol abuse; use of cannabis in the 24 h before each study visit; heavy smokers (> 10 [Part A] or > 20 cigarettes [Part B] daily); supine blood pressure, heart rate, or QTcF outside the acceptable ranges; participation in other clinical trials of unlicensed medicines, or loss of more than 400 mL blood, within the previous 3 months; phobia of needles or blood; possibility that volunteer will not cooperate with the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy volunteers (active)<br>SPL026 to be administered by IV injection | Drug: SPL026<br>* Intravenous solution<br>* Other names: n,n-dimethytryptaimine;|
| Experimental: Healthy volunteers (placebo)<br>SPL026-matched placebo to be administered by IV injection | Drug: Placebo<br>* SPL026-matched placebo<br>* Other names: SPL026-matched placebo;|
| Experimental: Patients (active)<br>SPL026 to be administered by IV injection | Drug: SPL026<br>* Intravenous solution<br>* Other names: n,n-dimethytryptaimine;|
| Experimental: Patients (placebo)<br>SPL026-matched placebo to be administered by IV injection | Drug: Placebo<br>* SPL026-matched placebo<br>* Other names: SPL026-matched placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability in healthy volunteers | Safety and tolerability measured by lab biochemistry, adverse events and intensity rating scale to measure tolerability of the psychedelic experience | Up to three months after a single dose | 
| Efficacy of SPL026 in MDD patients with moderate to severe depression | Montgomery-Åsberg Depression Rating Scale (MADRS) score (where 7 - 19 is mild depression, 20 - 34 is moderate depression, and >34 is severe depression) change from baseline at 2 weeks after the first dose (± 2 days) | 2 weeks after a single dose |