SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients

• ClinicalTrials.gov Identifier: NCT04673383
• Recruitment Status: Completed
• First Posted: December 17, 2020
• Last Update Posted: March 27, 2024
• Sponsor: Small Pharma Ltd
• Information provided by (Responsible Party): Small Pharma Ltd

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: SPL026; Drug: Placebo	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: RCT
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: February 4, 2021
• Actual Primary Completion Date: October 1, 2022
• Actual Study Completion Date: December 22, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability in healthy volunteers [ Time Frame: Up to three months after a single dose ]
   Safety and tolerability measured by lab biochemistry, adverse events and intensity rating scale to measure tolerability of the psychedelic experience
2. Efficacy of SPL026 in MDD patients with moderate to severe depression [ Time Frame: 2 weeks after a single dose ]
   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)

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United Kingdom

MAC Clinical Research

Liverpool, United Kingdom, L34 1BH

Hammersmith Medicines Research

London, United Kingdom

Sponsors and Collaborators

Small Pharma Ltd

Investigators

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

More Information

Additional Information:

Clinical Trial Report Synopsis Available Here 

Publications of Results:

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.

• Responsible Party: Small Pharma Ltd
• ClinicalTrials.gov Identifier: NCT04673383
• Other Study ID Numbers: CT026_001
• First Posted: December 17, 2020
• Last Update Posted: March 27, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No plan for this yet.

• 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

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; N,N-Dimethyltryptamine; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Receptor Agonists