SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients

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)

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

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SPL026; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L34 1BH
    • MAC Clinical Research
  • London, United Kingdom
    • Hammersmith Medicines Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy volunteers (active); SPL026 to be administered by IV injection	Drug: SPL026; Intravenous solution; Other Names: DMT; dimethyltryptamine; n,n-dimethytryptaimine
Experimental: Healthy volunteers (placebo); SPL026-matched placebo to be administered by IV injection	Drug: Placebo; SPL026-matched placebo; Other Names: Dummy; SPL026-matched placebo
Experimental: Patients (active); SPL026 to be administered by IV injection	Drug: SPL026; Intravenous solution; Other Names: DMT; dimethyltryptamine; n,n-dimethytryptaimine
Experimental: Patients (placebo); SPL026-matched placebo to be administered by IV injection	Drug: Placebo; SPL026-matched placebo; Other Names: Dummy; 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

Collaborators and Investigators

• Sponsor: Small Pharma Ltd
• Investigators: Principal Investigator: Fabian Devlin, MD, MAC Clinical Research; Principal Investigator: David Erritzoe, MD, Imperial College London; Principal Investigator: Malcolm Boyce, MD, Hammersmith Medicines Research

Publications and helpful links

General Publications

• Good M, Joel Z, Benway T, Routledge C, Timmermann C, Erritzoe D, Weaver R, Allen G, Hughes C, Topping H, Bowman A, James E. Pharmacokinetics of N,N-dimethyltryptamine in Humans. Eur J Drug Metab Pharmacokinet. 2023 May;48(3):311-327. doi: 10.1007/s13318-023-00822-y. Epub 2023 Apr 22.
• James E, Erritzoe D, Benway T, Joel Z, Timmermann C, Good M, Agnorelli C, Weiss BM, Barba T, Campbell G, Baker Jones M, Hughes C, Topping H, Boyce M, Routledge C. Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial. Front Psychiatry. 2024 Jan 11;14:1305796. doi: 10.3389/fpsyt.2023.1305796. eCollection 2023.

Helpful Links

• Clinical Trial Report Synopsis Available Here

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; N,N-Dimethyltryptamine
• Other Study ID Numbers: CT026_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan for this yet.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No