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.

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