SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients

Major Depressive Disorder Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04673383
• Other study ID #: CT026_001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 4, 2021
• Est. completion date: December 22, 2022

Study information

• Verified date: March 2024
• Source: Small Pharma Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: December 22, 2022
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• SPL026
Intravenous solution
• Placebo
SPL026-matched placebo

Locations

Country	Name	City	State
United Kingdom	MAC Clinical Research	Liverpool
United Kingdom	Hammersmith Medicines Research	London

Sponsors (1)

Lead Sponsor	Collaborator
Small Pharma Ltd

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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/s13318-0 — View Citation

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 fu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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

External Links

•   Clinical Trial Report Synopsis Available Here