Clinical trial NCT05385783: A Study of a Psilocybin Analog (CYB003) in Healthy Participants With and Without Major Depressive Disorder
Official title: A Phase I/IIa, Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Relative Bioavailability and Food Effect Cohort to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of CYB003 in Healthy Participants With and Without Major Depressive Disorder (MDD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
MDD
Psilocybin
Psychedelic
Psilocin
CYB003
CYB003-001
Depression
Healthy
Lead sponsor: Cybin IRL Limited
Sponsor class: INDUSTRY
Collaborators: name: Clinilabs Drug Development Corporation
name: Drug Safety Navigator
First posted: 2022-05-23
Enrollment: 57
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and tolerability of ascending oral doses of CYB003 in healthy participants with and without major depressive disorder (MDD).


Eligibility 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 - 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).

Primary outcomes:
measure: Adverse Events (All Arms)
timeFrame: Day 1 thru End of Study Visit (which is: Day 56 Arms A & B; Day 28 Arms C & D; Day 35 Arms E)
measure: Resting 12 Lead ECG ventricular rate (Arms A & B)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 21, Day 22, & Day 23
measure: Resting 12 Lead ECG ventricular rate (Arms C & D)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
measure: Resting 12 Lead ECG ventricular rate (Arms E)
timeFrame: Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16
measure: Resting 12 Lead ECG PR interval (Arms A & B)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23
measure: Resting 12 Lead ECG PR interval (Arms C & D)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
measure: Resting 12 Lead ECG PR interval (Arms E)
timeFrame: Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16
measure: Resting 12 Lead ECG QRS duration (Arms A & B)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23
measure: Resting 12 Lead ECG QRS duration (Arms C & D)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
measure: Resting 12 Lead ECG QRS duration (Arms E)
timeFrame: Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16
measure: Resting 12 Lead ECG QT interval (Arms A & B)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23
measure: Resting 12 Lead ECG QT interval (Arms C & D)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
measure: Resting 12 Lead ECG QT interval (Arms E)
timeFrame: Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16
measure: Resting 12 Lead ECG QTcF (Arms A & B)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23
measure: Resting 12 Lead ECG QTcF (Arms C & D)
timeFrame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
measure: Resting 12 Lead ECG QTcF (Arms E)
timeFrame: Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16
measure: Holter monitoring (Arms A & B)
timeFrame: Day -1, Day 1, Day 22
measure: Holter monitoring (Arms C & D)
timeFrame: Day -1, Day 1, Day 8
measure: Holter monitoring (Arm E)
timeFrame: Day -1, Day 1, Day 8, Day 15
measure: Columbia Suicide Severity Rating Scale (CSSRS) Lifetime version (All Arms)
timeFrame: Screening
measure: Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arms A & B)
timeFrame: Day -1, Day 2, Day 10, Day 17, Day 21, Day 23, Day 31, Day 38, Day 42, and Day 56
measure: Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arms C & D)
timeFrame: Day -1, Day 2, Day 7, Day 9, Day 15, Day 21, Day 28
measure: Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arm E)
timeFrame: Day -1, Day 2, Day 7, Day 9, Day 14, Day 16, Day 21, Day 28, Day 35
Secondary outcomes:
measure: Mystical Experience Questionnaire (MEQ30) (Arms A & B)
timeFrame: Day 1 & Day 22
measure: Mystical Experience Questionnaire (MEQ30) (Arms C & D)
timeFrame: Day 1 & Day 8
measure: Mystical Experience Questionnaire (MEQ30) (Arms C & D)
timeFrame: Day 1, Day 8, & Day 15
measure: 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms A & B)
timeFrame: Day 1 & Day 22
measure: 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms C & D)
timeFrame: Day 1 & Day 8
measure: 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arm E)
timeFrame: Day 1, Day 8, & Day 15
measure: Hallucinogen Rating Scale (HRS) (Arms A & B)
timeFrame: Day 1 & Day 22
measure: Hallucinogen Rating Scale (HRS) (Arms C & D)
timeFrame: Day 1 & Day 8
measure: Hallucinogen Rating Scale (HRS) (Arm E)
timeFrame: Day 1, Day 8, & Day 15
measure: Persisting Effects Questionnaire (PEQ) (Arms A & B)
timeFrame: Day 1 & Day 22
measure: Persisting Effects Questionnaire (PEQ) (Arms C & D)
timeFrame: Day 1 & Day 8
measure: Persisting Effects Questionnaire (PEQ) (Arm E)
timeFrame: Day 1, Day 8, & Day 15
measure: VAS Ratings of "Any Drug Effect" (Arms A & B)
timeFrame: Day 1 & Day 22
measure: VAS Ratings of "Any Drug Effect" (Arms C & D)
timeFrame: Day 1 & Day 8
measure: VAS Ratings of "Any Drug Effect" (Arm E)
timeFrame: Day 1, Day 8, & Day 15
measure: Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from screening (Arms A & B)
timeFrame: Screening, Day -1, Day 1, Day 10, Day 17, Day 31, & Day 38
measure: Pharmacokinetic parameter of psilocin (Cmax) (Arms A & B)
timeFrame: Day 1, Day 2, Day 22, & Day 23
measure: Pharmacokinetic parameter of psilocin (Cmax) (Arms C & D)
timeFrame: Day 1, Day 2, Day 8, & Day 9
measure: Pharmacokinetic parameter of psilocin (Cmax) (Arm E)
timeFrame: Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16
measure: Pharmacokinetic parameter of psilocin (AUC) (Arms A & B)
timeFrame: Day 1, Day 2, Day 22, & Day 23
measure: Pharmacokinetic parameter of psilocin (AUC) (Arms C & D)
timeFrame: Day 1, Day 2, Day 8, & Day 9
measure: Pharmacokinetic parameter of psilocin (AUC) (Arm E)
timeFrame: Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: CenExel ACMR
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Eatontown
country: United States
facility: Clinilabs Drug Development Corporation
state: New Jersey
Study officials:
affiliation: Cybin IRL Limited
name: Amir Inamdar, MBBS,DNB,MFPM
role: STUDY_DIRECTOR
References: