Clinical TrialMajor Depressive Disorder (MDD)DMTDMTCompleted

Safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of intravenous dosing of SPL026 drug product (N, N-dimethyltryptamine fumarate; DMT Fumarate [A Serotonergic Psychedelic]) alone or in combination with selective serotonin reuptake inhibitors in patients with major depressive disorder

Open-label Phase I study (n=24 planned; 18 enrolled) single 27.5 mg IV SPL026 (DMT fumarate) 10-minute infusion in adults with major depressive disorder, comparing patients on stable SSRI versus those not on pharmacotherapy; primary outcomes: safety, PK/PD and exploratory efficacy.

Target Enrollment
24 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

Phase Ib open-label study of a single 27.5 mg IV SPL026 (DMT fumarate) infusion administered as a 10-minute continuous infusion in adults with major depressive disorder; two cohorts enrolled: patients on a stable SSRI and patients not receiving pharmacological treatment who receive concurrent therapy.

Primary assessments include adverse events, vital signs, ECG and laboratory safety to Day 29 and C-SSRS for suicidal ideation/behaviour; secondary measures cover PK sampling and multiple PD/psychometric scales (DAS, RRS, SCS-R, WEMWBS, PIS, PTCS, MEQ, EDI, EBI, CEQ, VAS).

Sentinel dosing of two patients in the Test Cohort occurred with a minimum 48-hour safety review before continuation of dosing in the remaining cohort participants.

Study Protocol

Preparation

sessions

Dosing

1 sessions
10 min each

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Test cohort (SSRI)

experimental

Patients on a stable SSRI; single IV SPL026 infusion with sentinel dosing and safety review.

Interventions

  • DMT27.5 mg
    via IV• single dose• 1 doses total

    Given as 10-minute continuous IV infusion. Test cohort: patients remain on stable SSRI; two sentinel patients dosed first with ≥48 h safety review.

Control cohort (no SSRI + therapy)

active comparator

Patients not on pharmacological treatment; single IV SPL026 infusion plus therapy.

Interventions

  • DMT27.5 mg
    via IV• single dose• 1 doses total

    Given as 10-minute continuous IV infusion. Control cohort receive concurrent therapy and are not on SSRI.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • 1. Patients with MDD, as defined in DSM-5, of a mild to severe degree (scoring ≥14 on the 17-item HAM-D).
  • 2. Patient is aged ≥18 years.
  • 3. Patient has a body mass index (BMI) of 18 to 33.9 kg/m2, inclusive.
  • 4. Test Cohort Only: Patient is 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.
  • 5. Patient has tried at least one approved method of treatment for their depression.
  • 6. Patient has not been administered any MAO-inhibitor class antidepressants for at least 3 months prior to Screening.
  • 7. No psychedelic drug use 6 months prior to dosing (excluding the study drug) until the end of the study.
  • 8. Registered with a GP in the UK.
  • 9. Under the care of a healthcare professional who can confirm the diagnosis and previous treatment received.
  • 10. Sufficient intelligence to understand the nature of the trial and communicate satisfactorily.
  • 11. Healthy as determined by physician based on medical evaluation including ECG and labs at Screening.
  • 12. Agree to follow contraception requirements.
  • 13. Willing to be contacted by email/telephone/video call.
  • 14. Proficient in reading and writing English sufficient to complete questionnaires.
  • 15. Willing to give written consent to have data entered into The Over-volunteering Prevention System.
  • 16. Provision of written informed consent.

Exclusion Criteria

  • 1. Meets DSM-5 criteria for substance abuse disorder or positive urine drug screen at Screening or Day -1 (excluding cannabis up to 24 h).
  • 2. Current or clinically relevant history of a psychotic disorder, including schizophrenia, psychosis, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, emotionally unstable personality disorder or panic disorder.
  • 3. In first-degree relatives, a clinically relevant history of a psychotic disorder (see full protocol).
  • 4. Significant history of mania.
  • 5. Psychiatric condition judged incompatible with rapport/safe exposure to DMT.
  • 6. Significant suicide risk, defined by C-SSRS items 4 or 5 within 1 year, suicidal behaviours within 1 year, history of serious suicide attempts requiring hospitalisation, or clinical assessment of significant suicide risk.
  • 7. Control Cohort Only: received any pharmacological treatment for MDD within 6 months of dosing (except MAO-inhibitors exception noted above).
  • 8. Test Cohort Only: ongoing use of antidepressant augmentation or combination therapies other than a single SSRI.
  • 9. Clinically relevant abnormal physical/mental health interfering with study.
  • 10. Clinically relevant abnormal labs, ECG or vital signs at Screening/Day -1 as judged by Investigator.
  • 11. Any acute condition or infection or chronic illness posing unacceptable risk.
  • 12. Current or previous significant cardiovascular conditions or family history of long QT/sudden death.
  • 13. AST/ALT/GGT/total bilirubin ≥1.5×ULN at Screening or Day -1 (with Gilbert's allowance per protocol).
  • 14. Psychological or neurological conditions associated with seizures or convulsions.
  • 15. BP or HR outside specified ranges at Screening.
  • 16. QTcF ≥450 ms (males) or ≥470 ms (females) at Screening or predose on Day 1.
  • 17. Presence of clinically significant ECG abnormalities at Screening.
  • 18. Positive HBsAg, anti-HCV or anti-HIV I/II at Screening.
  • 19. Use of serotonergic psychedelics within 6 months prior to dosing.
  • 20. Intake of >21 units alcohol weekly or inability to refrain from alcohol from 24 h prior to visits.
  • 21. Unable to refrain from smoking from 4 h prior to dosing until 4 h after dosing (low-dose nicotine patch permitted).
  • 22. Receipt of an investigational product in another trial within 3 months prior to Day -1 or during Follow-up.
  • 23. Current use of long-term prescription/acute medicine (except Test Cohort SSRI or HRT) posing interaction risk.
  • 24. Use of new medications/supplements within 28 days of dosing (paracetamol/ibuprofen exceptions noted).
  • 25. History of severe adverse reaction or sensitivity to serotonergic psychedelics.
  • 26. Persons of childbearing potential who are pregnant, lactating or planning to conceive and not using reliable contraception.
  • 27. Donation of blood/plasma (>400 mL) within 3 months prior to dosing.
  • 28. Phobia of needles or blood; unsuitable veins for venepuncture/cannulation.
  • 29. Unlikely to cooperate with study requirements.
  • 30. Objection by GP to patient entering the trial.

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment24 participants
  • Timeline
    Start: 2022-12-13
    End: 2023-08-03
  • Compounds
    DMTDMT
  • Topic
    Major Depressive Disorder (MDD)

Locations

MAC Clinical Research Neuroscience Centre of Excellence — Manchester, United Kingdom
MAC Clinical Research Neuroscience Centre of Excellence — Prescot, United Kingdom

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