Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, MDD, Depression, SSRI, N,N-dimethyltryptamine, DMT
Brief summary
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.
Interventions
DRUGSPL026
Intravenous
Sponsors
Small Pharma Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety & tolerability: Suicidal Ideation | Screening to End-of-Study Follow-up (Day 29) | Columbia-Suicide Severity Rating Scale |
| Safety & tolerability: Adverse Events | Screening to End-of-Study Follow-up (Day 29) | Adverse events (AEs) |
| Safety & tolerability: Lab biochemistry | Screening, Day -1 and Day 1 | Values of potential clinical importance |
| Safety & tolerability: Vital signs - Heart Rate | Screening to Day 2 | Heart rate |
| Safety & tolerability: Vital signs - Blood pressure | Screening to Day 2 | Blood pressure |
| Safety & tolerability: Vital signs - Temperature | Screening to Day 2 | Temperature |
| Safety & tolerability: Electrocardiogram | Screening to Day 2 | QTcX intervals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of plasma levels of DMT | 2, 5, 7, 10, 11, 13, 15, 30, 60, 120, 240 minutes post-dose | Pharmacokinetic parameter calculation in the Test Cohort compared to the Control Cohort |
| Mystical Experience Questionnaire (MEQ) | Day 1 (dosing day) | MEQ in the Test Cohort compared to the Control Cohort |
| Challenging Experience Questionnaire (CEQ) | Day 1 (dosing day) | CEQ in the Test Cohort compared to the Control Cohort |
| Ruminative Responses Scale (RRS) | Day -1 and Day 29 | RRS in the Test Cohort compared to the Control Cohort |
| Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) | Day -1, Day 15 and Day 29 | WEMWBS in the Test Cohort compared to the Control Cohort |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory efficacy: Montgomery-Åsberg Depression Rating Scale (MADRS) | Day -1, Day 8, Day 15 and Day 29 | MADRS in the Test Cohort compared to the Control Cohort |
Countries
United Kingdom
Outcome results
None listed