SPL026 With or Without SSRIs in Participants With MDD

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: SPL026


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Test Cohort of patients already taking an SSRI for their depression, compared to the Control Cohort who are not already taking an SSRI. All patients will receive SPL026
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Cohort<br>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<br>* Intravenous<br>* Other names: DMT;|
| Experimental: Control Cohort<br>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<br>* Intravenous<br>* Other names: DMT;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, MDD, Depression, SSRI, N,N-dimethyltryptamine, DMT