Clinical TrialHealthy VolunteersDMTDMTPlaceboCompleted

Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and effects of intravenous (IV) and intramuscular (IM) dosing of SPL028 (deuterated DMT fumarate [a serotonergic psychedelic]) in healthy volunteers and participants with major depressive disorder (MDD)

Randomised, double-blind, placebo-controlled Phase I trial (n=38) assessing safety, tolerability, PK and PD of IV and IM SPL028 (deuterated DMT fumarate) in healthy participants; optional Part B (MDD) did not take place.

Target Enrollment
38 participants
Study Type
Phase I interventional
Design
Randomized, double Blind

Detailed Description

Phase I, double-blind study in healthy participants testing SPL028 (deuterated DMT fumarate) administered by IV infusion or IM injection across up to five cohorts; randomisation in Part A was 6 active:2 placebo per cohort and cohorts 1–2 included two treatment periods spaced 3–6 weeks apart.

Outcomes included safety/tolerability (AEs, vitals, ECG, labs), suicidal ideation/behaviour (BSS), PK (frequent sampling: IV up to 2 h, IM up to 4 h), PD measures (WEMWBS, STAI-T, MEQ, EDI, EBI, CEQ, PTCS) and blinding integrity; Part B (open-label MDD cohort) did not take place.

Study Protocol

Preparation

sessions

Dosing

2 sessions
300 min each

Integration

1 sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

SPL028

experimental

Deuterated DMT fumarate (SPL028) administered IV or IM; randomisation 6:2 active:placebo per cohort; cohorts 1–2 may have two treatment periods.

Interventions

  • DMT
    via IV• single dose

    Deuterated DMT fumarate (SPL028); IV infusion; some participants in cohorts 1–2 had two treatment periods 3–6 weeks apart.

  • DMT
    via IM• single dose

    Deuterated DMT fumarate (SPL028); IM injection; some participants in cohorts 1–2 had two treatment periods 3–6 weeks apart.

Placebo

inactive

Matched placebo (IV or IM) pooled across routes.

Interventions

  • Placebo
    via IV• single dose

    Matched placebo; participants randomized to placebo for respective route and cohort.

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • 1. Participant has a body mass index (BMI) of 18 to 33.9 kg/m², inclusive.
  • 2. Participant has not been administered any Monoamine Oxidase (MAO) inhibitor class antidepressants for at least 3 months prior to Screening.
  • 3. Registered with a GP in the UK.
  • 4. Sufficient intelligence to understand the nature of the trial and any hazards of participation in it. Ability to communicate satisfactorily with the Investigator and therapist team to participate in, and comply with the requirements of, the entire trial.
  • 5. Healthy as determined by a responsible physician, based on no clinically significant findings from medical evaluation including medical history, a physical examination, concomitant medication, vital signs, 12-lead ECG and clinical laboratory evaluations (including haematology, coagulation, biochemistry and urinalysis) at the Screening visit and admission.
  • 6. Agree to follow the contraception requirements of the trial.
  • 7. Willing to be contacted by email and telephone and video call.
  • 8. Proficient in reading and writing English sufficient to complete questionnaires.
  • 9. Willing to give written consent to have data entered into The Over-volunteering Prevention System.
  • 10. Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form, after having the opportunity to discuss the trial with the Investigator or their delegate.
  • Part A – Cohorts 1 and 2 Only
  • 1. Healthy participants aged 25 to 65 years, inclusive.
  • 2. Healthy psychedelic-experienced participants (defined in protocol).
  • 3. No psychedelic drug use 6 weeks prior to dosing (excluding the study drug) until the end of the study.
  • Part A – Cohorts 3, 4 and 5 Only
  • 1. Healthy participants aged 25 to 65 years, inclusive.
  • 2. Healthy participants with little to no psychedelic experience (defined in protocol).
  • 3. No psychedelic drug use 6 months prior to dosing (excluding the study drug) until the end of the study.

Exclusion Criteria

  • Psychiatric Exclusion Criteria:
  • 1. DSM-5 substance use disorder as assessed by MINI or positive urine drugs of abuse (excluding cannabis within 24 hours).
  • 2. Current or clinically relevant history of a psychotic disorder (including schizophrenia, psychosis, bipolar disorder, schizoaffective disorder, borderline personality disorder, etc.).
  • 3. First-degree relatives with a clinically relevant history of a psychotic disorder.
  • 4. Significant history of mania.
  • 5. Psychiatric condition incompatible with rapport with the therapy team and/or safe exposure to DMT.
  • 6. Significant suicide risk (see details).
  • General Medical Exclusion Criteria:
  • 1. Clinically relevant abnormal physical or mental health interfering with the study.
  • 2. Clinically relevant abnormal laboratory results, ECG or vital signs at Screening or Day -1.
  • 3. Any acute condition or infection or chronic illness posing unacceptable risk.
  • 4. Significant cardiovascular history or family history of long QT or sudden death.
  • 5. AST, ALT, GGT or total bilirubin >1×ULN (with specified exceptions).
  • 6. Neurological conditions associated with seizures.
  • 7. Blood pressure or heart rate outside specified ranges at Screening.
  • 8. QTcF ≥450 msec (males) or ≥470 msec (females) at Screening or predose on Day 1.
  • 9. Clinically significant ECG abnormalities.
  • 10. Positive test for HBsAg, anti-HCV or anti-HIV I/II at Screening.
  • 11. Intake of >21 units alcohol weekly or inability to refrain from alcohol.
  • 12. Receipt of an investigational product in another trial within 3 months prior to Day -1.
  • 13. Use of prescription or OTC medications (except hormonal contraception/HRT) within 28 days unless assessed case-by-case.
  • 14. Current use of long-term prescription medicine deemed to pose interaction risk.
  • 15. History of severe adverse reaction to any drug or sensitivity to serotonergic psychedelics.
  • 16. POCBP who are pregnant, lactating or planning to conceive or not using reliable contraception; required negative pregnancy tests.
  • 17. Blood/plasma donation >400 mL within 3 months prior to dosing.
  • 18. Phobia of needles or blood.
  • 19. Unsuitable veins for venepuncture and/or cannulation.
  • 20. Unlikely to cooperate with study requirements.
  • 21. Objection by GP to participant entering the trial.
  • Part A – additional cohort-specific exclusions on recent psychedelic use and smoking abstinence as detailed in protocol.

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Randomizeddouble Blind
  • Target Enrollment38 participants
  • Timeline
    Start: 2022-06-01
    End: 2023-12-15
  • Compounds
    DMTDMTPlacebo
  • Topic
    Healthy Volunteers

Locations

MAC Clinical Research Manchester — Manchester, United Kingdom

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