Clinical trial NCT05553691: SPL026 With or Without SSRIs in Participants With MDD
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
MDD
Depression
SSRI
N,N-dimethyltryptamine
DMT
Lead sponsor: Small Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2022-09-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety & tolerability: Adverse Events
timeFrame: Screening to End-of-Study Follow-up (Day 29)
measure: Safety & tolerability: Lab biochemistry
timeFrame: Screening, Day -1 and Day 1
measure: Safety & tolerability: Vital signs - Heart Rate
timeFrame: Screening to Day 2
measure: Safety & tolerability: Vital signs - Blood pressure
timeFrame: Screening to Day 2
measure: Safety & tolerability: Vital signs - Temperature
timeFrame: Screening to Day 2
measure: Safety & tolerability: Electrocardiogram
timeFrame: Screening to Day 2
measure: Safety & tolerability: Suicidal Ideation
timeFrame: Screening to End-of-Study Follow-up (Day 29)
Secondary outcomes:
measure: Evaluation of plasma levels of DMT
timeFrame: 2, 5, 7, 10, 11, 13, 15, 30, 60, 120, 240 minutes post-dose
measure: Mystical Experience Questionnaire (MEQ)
timeFrame: Day 1 (dosing day)
measure: Challenging Experience Questionnaire (CEQ)
timeFrame: Day 1 (dosing day)
measure: Ruminative Responses Scale (RRS)
timeFrame: Day -1 and Day 29
measure: Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)
timeFrame: Day -1, Day 15 and Day 29
Other outcomes:
measure: Exploratory efficacy: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Day -1, Day 8, Day 15 and Day 29
Locations:
city: Manchester
country: United Kingdom
facility: Mac Clinical Research
state: Greater Manchester
city: Liverpool
country: United Kingdom
facility: MAC Clinical Research
state: Prescot
Study officials:
affiliation: MAC Clinical Research
name: Fabian Devlin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MAC Clinical Research
name: Neel Bhatt, MD
role: PRINCIPAL_INVESTIGATOR
References: