SPL026 With or Without SSRIs in Participants With MDD

An Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics & Exploratory Efficacy of Intravenous SPL026 Drug Product (DMT Fumarate) Alone or in Combination With SSRIs in Patients With Major Depressive Disorder

The main aim of the study is to test the safety and tolerability of single doses of SPL026 (N,N-dimethyltryptamine [DMT] fumarate, a psychedelic tryptamine) in patients currently taking a selective serotonin reuptake inhibitor (SSRI) for their depression, but for whom the SSRI is not fully relieving their depression.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9NQ
      • MAC Clinical Research
  • Prescot
    • Liverpool, Prescot, United Kingdom, L34 1BH
      • MAC Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• MDD diagnosis
• Previously tried at least one approved method of treatment for their depression
• No monoamine oxidase-inhibitor class antidepressants for at least 3 months
• Deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, laboratory tests of blood and urine
• No psychedelic drug use in the 6 months before dosing until the end of the study
• Willing to follow the contraception requirements of the trial
• Willing to be contacted by email and video call, and have online access
• Able to give fully informed written consent
• Test Cohort only: currently on a stable dose of an unspecified single SSRI alone and not in combination with any other psychiatric medications, for at least 6 weeks prior to Screening with no intention of making any changes
• Control Cohort only: no antidepressant medication for 6 months before dosing

Exclusion Criteria:

• Substance use disorder
• Current or clinically relevant history of a psychotic disorder, or first-degree relatives with a clinically relevant history of a psychotic disorder
• Significant history of mania
• Significant risk of suicide
• Clinically relevant abnormal findings at the screening assessment
• Blood pressure, heart rate, or QTcF outside the acceptable ranges
• Acute or chronic illness (other than MDD) or infection
• Clinically relevant abnormal medical history or concurrent medical condition (other than MDD)
• Use of any serotonergic psychedelics within 6 months prior to dosing
• Patients of child-bearing potential who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception
• History of a severe adverse reaction to any drug or sensitivity to serotonergic psychedelic drugs
• Use of over-the-counter or prescribed medication (excluding oral contraceptives, hormone replacement therapy and SSRIs [Test Cohort only]) within previous 28 day before dose of trial medication; or paracetamol or ibuprofen within 4 hours prior to dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Cohort; Patients who are currently taking an SSRI that is not effective in fully relieving their depression (prescribed outside of study). Patients will be administered a single dose of SPL026 by intravenous infusion.	Drug: SPL026; Intravenous; Other Names: N,N-dimethyltryptamine; DMT
Experimental: Control Cohort; Patients who are not currently taking any pharmacological treatment for their depression. Patients will be administered a single dose of SPL026 by intravenous infusion.	Drug: SPL026; Intravenous; Other Names: N,N-dimethyltryptamine; DMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety & tolerability: Adverse Events	Adverse events (AEs)	Screening to End-of-Study Follow-up (Day 29)
Safety & tolerability: Lab biochemistry	Values of potential clinical importance	Screening, Day -1 and Day 1
Safety & tolerability: Vital signs - Heart Rate	Heart rate	Screening to Day 2
Safety & tolerability: Vital signs - Blood pressure	Blood pressure	Screening to Day 2
Safety & tolerability: Vital signs - Temperature	Temperature	Screening to Day 2
Safety & tolerability: Electrocardiogram	QTcX intervals	Screening to Day 2
Safety & tolerability: Suicidal Ideation	Columbia-Suicide Severity Rating Scale	Screening to End-of-Study Follow-up (Day 29)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of plasma levels of DMT	Pharmacokinetic parameter calculation in the Test Cohort compared to the Control Cohort	2, 5, 7, 10, 11, 13, 15, 30, 60, 120, 240 minutes post-dose
Mystical Experience Questionnaire (MEQ)	MEQ in the Test Cohort compared to the Control Cohort	Day 1 (dosing day)
Challenging Experience Questionnaire (CEQ)	CEQ in the Test Cohort compared to the Control Cohort	Day 1 (dosing day)
Ruminative Responses Scale (RRS)	RRS in the Test Cohort compared to the Control Cohort	Day -1 and Day 29
Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)	WEMWBS in the Test Cohort compared to the Control Cohort	Day -1, Day 15 and Day 29

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory efficacy: Montgomery-Åsberg Depression Rating Scale (MADRS)	MADRS in the Test Cohort compared to the Control Cohort	Day -1, Day 8, Day 15 and Day 29

Collaborators and Investigators

• Sponsor: Small Pharma Ltd
• Investigators: Principal Investigator: Fabian Devlin, MD, MAC Clinical Research; Principal Investigator: Neel Bhatt, MD, MAC Clinical Research

Publications and helpful links

Helpful Links

• Redacted Clinical Study Report Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Actual): August 3, 2023
• Study Completion (Actual): August 3, 2023

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 21, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: June 13, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Depression; MDD; Major Depressive Disorder; SSRI; N,N-dimethyltryptamine; DMT
• 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_004; 2022-001767-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No