Clinical TrialHealthy VolunteersMDMAPlaceboCompleted

A Phase 1 Randomized, First-in-Human, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of EMP-01 in Healthy Adult Volunteers

This randomised, double-blind, placebo-controlled Phase I trial (n=32) assesses safety, tolerability, PK and PD of single-ascending oral doses of EMP-01 (ar-MDMA) in healthy adults across four cohorts (75–225 mg).

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

Detailed Description

Randomised, double-blind, placebo-controlled, single-ascending dose study in healthy volunteers across four cohorts (8 per cohort). Doses: 75 mg, 125 mg, 175 mg and 225 mg; cohort 2 includes two treatment periods (fasted and fed) with the same investigational product.

Safety assessments include AEs/SAEs, vitals (BP, HR, RR, temperature), ECG and clinical labs. Intensive PK sampling scheduled up to 30 hours postdose (multiple timepoints on Day 1 and Day 2; additional sampling for Cohort 2 Day 9/10). SMG sentinel review after initial two participants per cohort, with progression decisions after safety review.

Study Arms & Interventions

EMP-01

experimental

Single-ascending oral doses of EMP-01 (ar-MDMA) across four sentinel-sequenced cohorts (75,125,175,225 mg); cohort 2 includes fed and fasted periods.

Interventions

  • MDMA75 - 225 mg
    via Oral• single dose

    Cohorts receive 75, 125, 175 or 225 mg. Cohort 2 receives two periods (fasted then fed) with same IP; sentinel dosing (1 active,1 placebo) then remaining 6 randomized 5:1 (overall 6:2 active:placebo per cohort).

Placebo

inactive

Matching oral capsules (microcrystalline cellulose) administered under same conditions as EMP-01.

Interventions

  • Placebo
    via Oral• single dose

    Matching capsule; administered under same fasting/feeding restrictions.

Participants

Ages
18 – 55
Sexes
Male & Female

Inclusion Criteria

  • Each participant must meet all the following criteria to be enrolled in this study:
  • 1. Male or female aged between 18 and 55 years of age, inclusive, at time of consent.
  • 2. Female participants must have a negative serum pregnancy test result at Screening (all cohorts) and Day 8 (Cohort 2 only), and a negative urine pregnancy test at admission to the CRU on Day -1 (all cohorts), are not currently breast-feeding, and meet one of the following criteria: a) undergone a sterilization procedure ≥6 months before first dosing; b) be postmenopausal with amenorrhea ≥1 year and FSH consistent with postmenopausal status; c) WOCBP must use at least one protocol-specified effective/ highly effective method of birth control AND agree to use barrier contraception (male condom) during heterosexual intercourse from Screening until at least 90 days after EMP-01 administration. Complete abstinence is acceptable but pregnancy testing continues per protocol.
  • 3. Male participants must agree to use double barrier contraception or sexual abstinence and not donate sperm from consent until 120 days after EMP-01 administration (contraceptive requirements not applicable to participants exclusively in same-sex relationships unless they become heterosexual).
  • 4. Judged to be in good health based on medical history, physical exam, vitals and safety labs at screening and prior to first dose.
  • 5. Participant weight ≥45 kg and ≤100 kg and BMI between 18.0 and 32.0 kg/m2 inclusive at Screening.
  • 6. Agrees to be available for all study visits and cooperate with protocol requirements.
  • 7. Participants who smoke ≤2 cigarettes/pipes/cigars/e-cigarettes or equivalent per week from 3 months prior to Screening may be included and must abstain from smoking/nicotine for 24 hours prior to IP administration and during CRU confinement.
  • 8. Capable of using common smartphone applications.
  • 9. Willing to have psychiatric screening, dosing session, and integration session audio recorded.
  • 10. Willing and able to provide written informed consent.

Exclusion Criteria

  • Participants who meet any of the following criteria will be excluded:
  • 1. Known allergy or hypersensitivity to MDMA or any excipients.
  • 2. History of cardiovascular, cerebrovascular, or peripheral vascular disease (eg unstable angina, MI, CHF, arrhythmia, hypertension/hypotension, bradycardia, tachycardia).
  • 3. Clinically significant vital signs at Screening (SBP <80 or >140 mmHg; DBP <40 or >90 mmHg; RR <10 or >22), with confirmation repeats allowed per PI.
  • 4. Past or current significant mental, behavioural, or neurodevelopmental disorder per DSM-5 as assessed by MINI, including schizophrenia, schizotypal, delusional disorders, current mood (affective) disorders, neurotic/stress-related/somatoform disorders, or personality disorders.
  • 5. Family (first degree) history of psychotic disorders such as bipolar disorder, schizophrenia, or depression with psychotic features.
  • 6. Current suicidal ideation as assessed by the C-SSRS up to 1 month prior to Screening; lifetime history may be excluded at PI discretion.
  • 7. History of >25 lifetime administrations of psychedelic drugs or MDMA, or last use of a psychedelic or MDMA within 6 months prior to Screening.
  • 8. History of seizures or convulsions (except pediatric febrile seizures) or raised intracranial pressure.
  • 9. Active malignancy or history of malignancy within 2 years (excluding basal/squamous cell carcinoma).
  • 10. Clinically significant ECG findings at Screening as judged by PI (eg HR <40 or >100 bpm; QTcF >450 ms males or >470 ms females; QRS >120 ms; PR >220 ms), with repeats allowed for confirmation.
  • 11. Clinically significant lab abnormalities at Screening (eg Hb <=130 g/L males or <=115 g/L females; ALT/AST >1.5×ULN or bilirubin >2×ULN; estimated creatinine clearance <80 mL/min). Abnormal labs may be retested once to confirm.
  • 12. History of alcohol use disorder defined as average weekly intake >21 drinks (males) or >14 drinks (females) within 5 years prior to Screening.
  • 13. History of substance use disorder or dependency within 5 years, recreational IV drug use within 5 years, or positive tox screen (including MDMA/THC/amphetamines/opiates/etc) or positive alcohol breath test at Screening or prior to dosing.
  • 14. Positive serology (HBsAg or confirmed HCV) and/or positive HIV antibody/p24 antigen screen.
  • 15. Unwilling to refrain from systemic or topical medications (including herbal supplements) taken within 5× elimination half-life of the IP or within 14 days of IP administration, whichever is longer; or medications that chronically alter drug absorption/elimination within 30 days; or slow-release formulations within 14 days unless judged non-interfering by PI/Sponsor.
  • 16. Unwilling to refrain from alcohol and caffeine from 48 hours before IP administration through discharge from CRU.
  • 17. Received another investigational drug/device/approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer); prior participation in non-drug methodology trials acceptable.
  • 18. Donated blood/plasma within 30 days prior to Screening, lost >500 mL whole blood within 30 days, or received blood transfusion within 1 year prior to Screening.
  • 19. Acute illness or chronic disease symptoms within 14 days prior to Screening or any condition that may compromise safety or interpretation of safety/PK data.
  • 20. Is from a vulnerable population as defined by ICH GCP E6(R2).
  • 21. Unable to cooperate with protocol requirements or likely to be non-compliant.
  • 22. Other reasons judged by PI or Sponsor to make participant unsuitable.

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Randomizeddouble Blind
  • Target Enrollment32 participants
  • Timeline
    Start: 2023-05-16
    End: 2023-08-04
  • Compounds
    MDMAPlacebo
  • Topic
    Healthy Volunteers

Locations

Unknown facility — Australia

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