Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPlaceboPsilocybinPsilocybinPlaceboPsilocybinPsilocybinCompleted

A Study of a Psilocybin Analog (CYB003) in Healthy Participants With and Without Major Depressive Disorder

This Phase I/II randomised, double-blind, placebo-controlled trial (n=57) studied the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending oral doses of CYB003, a synthetic psilocybin analogue, in healthy participants and those with major depressive disorder (MDD).

Target Enrollment
57 participants
Study Type
Phase I/II interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomised, quadruple-blind, parallel Phase I/II study (n=57) evaluating ascending oral doses of CYB003 in healthy volunteers and participants with MDD; key outcomes include safety, tolerability, PK and PD.

MDD participants received EMBARK manualised psychotherapy throughout; healthy volunteers received manualised psychological support. Medicine sessions occurred 1–3 weeks apart depending on cohort, with some cohorts receiving three sessions to assess bioavailability and food effects.

Safety assessments included vital signs, labs, ECG, and psychiatric evaluation; exclusion criteria include clinically significant suicidality, MAOI use, pregnancy, relevant medical conditions, and recent investigational drug exposure.

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

MDD CYB003 2x

experimental

MDD participants receive CYB003 in both medicine sessions (~3 weeks apart) with EMBARK psychotherapy throughout.

Interventions

  • Psilocybin
    via Oral• two sessions

    Ascending oral doses per cohort; dose depends on cohort/time of enrollment.

  • Compound
    • throughout study

    EMBARK psychotherapy (manualised) provided throughout study.

MDD Placebo→CYB003

inactive

MDD participants receive placebo in session 1 and CYB003 in session 2 (~3 weeks apart) with EMBARK psychotherapy.

Interventions

  • Placebo
    via Oral• single dose

    Placebo in medicine session 1

  • Psilocybin
    via Oral• single dose

    CYB003 in medicine session 2

  • Compound
    • throughout study

    EMBARK psychotherapy (manualised) provided throughout study

HV CYB003 2x

experimental

Healthy volunteers receive CYB003 in both medicine sessions (~1–2 weeks apart) with psychological support.

Interventions

  • Psilocybin
    via Oral• two sessions

    Dose per cohort/time of enrollment.

  • Compound
    • throughout study

    Manualised psychological support provided throughout study

HV Placebo→CYB003

inactive

Healthy volunteers receive placebo in session 1 and CYB003 in session 2 (~1–2 weeks apart) with psychological support.

Interventions

  • Placebo
    via Oral• single dose

    Placebo in medicine session 1

  • Psilocybin
    via Oral• single dose

    CYB003 in medicine session 2

  • Compound
    • throughout study

    Manualised psychological support provided throughout study

HV CYB003 3x

experimental

Healthy volunteers receive CYB003 in three medicine sessions (~1 week apart) to assess bioavailability and food effect; psychological support provided.

Interventions

  • Psilocybin
    via Oral• three sessions

    Dose selected by safety review committee; bioavailability and food-effect cohort assessments

  • Compound
    • throughout study

    Manualised psychological support provided throughout study

Participants

Ages
21 – 55
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria - MDD & Healthy Volunteer Participants:
  • Aged between 21 to 65 years, inclusive, at Screening.
  • Has a BMI of 18 to 30 kg/m2, inclusive, at Screening.
  • Is ≥60 kg.
  • Is negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test at Screening and at Day -1.
  • Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Additional Inclusion Criteria - MDD Participants Only:
  • Has a diagnosis of MDD (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-V] of moderate to severe degree), established through a full psychiatric work up, who are otherwise healthy.
  • Has been on a stable dose of antidepressant medication (no more than 50% change) in the last month prior to Screening and has had an inadequate response, as judged by the Investigator.

Exclusion Criteria

  • Exclusion Criteria - MDD & Healthy Volunteer Participants:
  • Clinically significant risk of suicidality, as determined through a comprehensive psychiatric interview.
  • Clinically relevant history of abnormal physical health interfering with the study as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including [but not limited to], neurological, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder).
  • Diagnosis of hypertension or an arrhythmia.
  • History of hypothyroidism and/or current abnormal thyroid function tests.
  • Clinically relevant abnormal laboratory results.
  • History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
  • Any other concomitant disease or condition that could interfere with, or for which the treatment might interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study.
  • Not fluent in the English language.
  • Has a presence or relevant history of any of the following medical conditions: organic brain disorders (e.g., epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmal disease, brain tumor or other medical conditions associated with seizures or convulsions).
  • Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (anti- HCV) or human immunodeficiency virus I and II (anti-HIV I/II) at Screening.
  • Has participated in a clinical study and has received a medication or a new chemical entity within 3 months prior to dosing of current study medication.
  • Is taking or has taken any drugs known to inhibit monoamine oxidase within 28 days prior to receiving the study drug.
  • Is taking or has taken over the counter (OTC) doses of 5-hydroxytrptophan or St John's Wort within 28 days prior to receiving the study drug.
  • Donation of blood or plasma of >400 mL within 1 month prior to first dosing until 4 weeks after final dosing.
  • Is pregnant, breastfeeding or planning to conceive.
  • Known difficulty with obtaining intravenous access.
  • Other eligibility considerations (i.e., participant personal circumstances, behavior, and/or any current problem that might interfere with participation or that is incompatible with establishment of rapport or safe exposure to the study drug), as judged by the Investigator.
  • Additional Exclusion Criteria - Healthy Volunteers Only:
  • Current or previously diagnosed with a mental health disorder as defined by DSM-V criteria.
  • Use of any prescription medicine (except for hormonal contraceptives, if applicable), certain herbal supplements (to be reviewed by the Investigator), or OTC medicine during the 28 days before dosing.
  • Additional Exclusion Criteria - MDD Participants Only:
  • Current or previous diagnosis of treatment-resistant MDD, defined as failure to respond to 2 or more antidepressant treatments given at an adequate dose for an adequate duration.
  • Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder or brief psychotic disorder; current or previous history of bipolar disorder, or current personality disorder.
  • Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressant, mirtazapine, an antipsychotic or a mood stabilizer.
  • Use of a prescription medicine (except participants may take a stable chronic dose of antidepressant medication(s) and/or sedatives/hypnotics, and may take hormonal contraceptives, if applicable), certain herbal supplements (to be reviewed by the Investigator), or OTC medicine during the 28 days before dosing (some exceptions apply).

Study Details

Locations

CenExel ACMR — Atlanta, Georgia, United States
iResearch Atlanta — Decatur, Georgia, United States
Clinilabs Drug Development Corporation — Eatontown, New Jersey, United States

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