Clinical TrialHealthy VolunteersPsilocybinPlaceboCompleted

A study carried out on healthy volunteers to understand how COMP360 can be taken in a safe and well-tolerated way

Phase I, randomised double‑blind placebo‑controlled single‑dose PK study (n=44) with an integrated open‑label food‑effect crossover (25 mg) assessing safety, tolerability, PK and QTcF of COMP360 (psilocybin) in healthy volunteers.

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

Detailed Description

This interventional Phase I trial enrolled 44 healthy volunteers to characterise the pharmacokinetics and safety of oral COMP360 (psilocybin), using single‑dose PK cohorts (1, 10, 25, 50 mg; 6 active:2 placebo per cohort) and a separate food‑effect crossover (25 mg fasted vs fed).

Primary endpoints include adverse events, 12‑lead ECG/QTcF monitoring, vital signs and clinical laboratories; secondary endpoints include plasma concentrations of psilocybin, psilocin and metabolites and PK parameters.

Dosing was observed in a clinical research unit with overnight stay for 24‑hour monitoring; suicidality assessments (C‑SSRS) and post‑dose safety checks were performed prior to discharge.

Study Protocol

Preparation

sessions

Dosing

2 sessions
1440 min each

Integration

sessions

Study Arms & Interventions

COMP360

experimental

Oral COMP360 (psilocybin) single-dose PK cohorts (1, 10, 25, 50 mg) and food-effect crossover (25 mg).

Interventions

  • Psilocybin25 - 50 mg
    via Oral• single dose

    Single-dose PK cohorts: 1, 10, 25, 50 mg (6 active:2 placebo per cohort). FE component: 25 mg given fasted and fed in crossover; participants stay overnight.

Placebo

inactive

Matching placebo capsule used in single-dose PK cohorts (2 per cohort).

Interventions

  • Placebo
    via Oral• single dose

    Placebo used in PK component (2 of 8 per cohort).

Participants

Ages
18 – 55
Sexes
Male & Female

Inclusion Criteria

  • 1. Signed ICF.
  • 2. Participant is male or female from any ethnic origin.
  • 3. Participant is aged between 18 to 55 years, inclusive, at Screening visit 1 (V1).
  • 4. Participant has a body mass index of 18.5 to 30 kg/m2, inclusive, at Screening (V1) and day 1 (V3).
  • 5. Participant is a non-smoker (including e-cigarettes) for at least 12 months prior to Screening (V1) and day 1 (V3).
  • 6. Negative RT-PCR test for SARS-CoV-2 at Screening (V1) and day -1 (V2).
  • 7. Willing to comply with fasting and food intake requirements.
  • 8. Healthy as determined by a responsible physician, based on medical evaluation including medical history, physical examinations, prior and concomitant medications, vital signs, 12-lead ECG and clinical laboratory evaluations.
  • 9. Male participants must use a condom during the study and for 3 months after their final dose of study medication if their partner is a woman of childbearing potential. In addition, their female partner of childbearing potential must use an additional method of highly protective contraception from first dosing until 3 months following the final dosing.
  • 10. Female participants: 10.1. Of childbearing potential must be established on a highly effective method of contraception prior to dosing until 3 months after the last dose in combination with male partner’s use of a condom during the trial and for 3 months after the last dose of trial medication. Participants must have a negative pregnancy test at Screening (V1) and day 1 (V3). 10.2. Of non-childbearing potential i.e., postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Postmenopausal is defined as women ≥60 years and having had >12 months of natural (spontaneous) amenorrhea, and a serum follicle-stimulating hormone level in the menopausal range, unless the subject is taking hormone replacement therapy or is using hormonal contraception.
  • 11. In the FE component, the participant is willing to eat a high-fat breakfast, including bacon, in line with Food and Drug Administration guidance.
  • 12. Able to complete all protocol-required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.

Exclusion Criteria

  • Psychiatric Exclusion Criteria:
  • 1. Current (within the last year) or history of alcohol or substance abuse (including nicotine) as informed by DSM-5 at Screening (V1), as determined by self-report or a positive urine drugs of abuse test, alcohol breath test and urine cotinine screen at Screening (V1) or day 1 (V3).
  • 2. Use of pharmacological compounds for psychiatric or neurological conditions acting on the central nervous system within 30 days or 5 half-lives (whichever is longer) prior to Screening (V1).
  • 3. Current or clinically relevant history of schizophrenia, psychotic, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, major depression, panic disorder, generalised anxiety disorder, obsessive-compulsive disorder, eating disorder or body-dysmorphic disorder, as assessed by MINI.
  • 4. In first-degree relatives, a history of schizophrenia, psychotic, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, major depression, panic disorder, generalised anxiety disorder, obsessive-compulsive disorder, eating disorder or body-dysmorphic disorder.
  • 5. Significant suicide risk as defined by: 5.1. Suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within 1 year prior to Screening (V1), or on day 1 (V3), or 5.2. Suicidal behaviours within 1 year prior to Screening (V1), or 5.3. Clinical assessment of significant suicidal risk during Participant interview.
  • 6. Other personal circumstances and behaviour that is incompatible with establishment of rapport or safe exposure to psilocybin, as judged by the Investigator.
  • 7. Exposure to psilocybin, or any other psychedelics, such as ayahuasca, mescaline, LSD, or peyote within 1 year prior to Screening (V1).
  • General Medical Exclusion Criteria:
  • 8. Women of childbearing potential who are pregnant, breastfeeding, or planning to conceive.
  • 9. Clinically relevant history of abnormal physical or mental health interfering with the study.
  • 10. Clinically relevant abnormal laboratory results ...
  • 11. Current or previous medical history of any cardiovascular conditions. Participants with a blood pressure ≥140/90 mmHg at Screening (V1) or day 1 (V3), following triplicate readings, will not be eligible.
  • 12. Recent substance use within the last month (excluding alcohol) or a positive urine drugs screen.
  • 13. Current enrolment in any investigational drug or device study within 30 days or 5 half-lives.
  • 14. Current or previous medical history of epilepsy or conditions associated with seizures.
  • 15. Any other concomitant disease or condition that could interfere with the conduct of the study.
  • 16. Participants with AST, ALT, GGT or total bilirubin ≥1.5 x ULN at Screening or day -1.
  • 17. QTcF >450 msec at Screening (V1) or pre-dose on day 1 (V3), following triplicate ECG readings.
  • 18. Positive test for HBsAg, anti-HCV or anti-HIV I/II at Screening (V1).
  • 19. Intake of >21 units of alcohol weekly, or alcohol within 48 hours of Screening or dosing until end of study.
  • 20. Habitual and heavy consumption of caffeinated beverages (>8 cups/day) at Screening; and/or inability to refrain from (methyl) xanthine from 48 hours prior to visits until end of study.
  • 21. Use of any prescription or non-prescription medications within 30 days of first dosing and throughout the study (exceptions apply).
  • 22. Strenuous exercise within 48 hours prior to each blood collection for clinical lab tests.
  • 23. Donation of blood or plasma >400 ml within 4 weeks prior to first dosing until 4 weeks after final dosing.
  • 24. Male participant who will not abstain from sperm donation between first dosing and 3 months after final dosing.

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Randomizeddouble Blind
  • Target Enrollment44 participants
  • Timeline
    Start: 2020-11-01
    End: 2022-10-20
  • Compounds
    PsilocybinPlacebo
  • Topic
    Healthy Volunteers

Locations

MAC Clinical Research Liverpool — Liverpool, United Kingdom

Your Library