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

NCT05385783 | Completed Phase 1 FDA Drug

• 1 other identifier: CYB003-001
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 3

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).

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; MDD; Psilocybin; Psychedelic; Psilocin; CYB003; CYB003-001; Depression; Healthy

Outcome Measures

Primary Outcomes (23)

• Adverse Events (All Arms)

  Any untoward medical occurrence in a clinical investigation participant administered a drug and does not necessarily have a causal relationship with the treatment

  Day 1 thru End of Study Visit (which is: Day 56 Arms A & B; Day 28 Arms C & D; Day 35 Arms E)

• Resting 12 Lead ECG ventricular rate (Arms A & B)

  ventricular rate (beats per minute)

  Screening, Day -1, Day 1, Day 2, Day 21, Day 22, & Day 23

• Resting 12 Lead ECG ventricular rate (Arms C & D)

  ventricular rate (beats per minute)

  Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9

• Resting 12 Lead ECG ventricular rate (Arms E)

  ventricular rate (beats per minute)

  Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16

• Resting 12 Lead ECG PR interval (Arms A & B)

  PR interval (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23

• Resting 12 Lead ECG PR interval (Arms C & D)

  PR interval (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9

• Resting 12 Lead ECG PR interval (Arms E)

  PR interval (milliseconds)

  Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16

• Resting 12 Lead ECG QRS duration (Arms A & B)

  QRS duration (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23

• Resting 12 Lead ECG QRS duration (Arms C & D)

  QRS duration (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9

• Resting 12 Lead ECG QRS duration (Arms E)

  QRS duration (milliseconds)

  Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16

• Resting 12 Lead ECG QT interval (Arms A & B)

  QT interval (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23

• Resting 12 Lead ECG QT interval (Arms C & D)

  QT interval (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9

• Resting 12 Lead ECG QT interval (Arms E)

  QT interval (milliseconds)

  Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16

• Resting 12 Lead ECG QTcF (Arms A & B)

  Corrected QT interval by Fredericia (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23

• Resting 12 Lead ECG QTcF (Arms C & D)

  Corrected QT interval by Fredericia (milliseconds)

  Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9

• Resting 12 Lead ECG QTcF (Arms E)

  Corrected QT interval by Fredericia (milliseconds)

  Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16

• Holter monitoring (Arms A & B)

  Record of the electrical activity of the heart (Hz)

  Day -1, Day 1, Day 22

• Holter monitoring (Arms C & D)

  Record of the electrical activity of the heart (Hz)

  Day -1, Day 1, Day 8

• Holter monitoring (Arm E)

  Record of the electrical activity of the heart (Hz)

  Day -1, Day 1, Day 8, Day 15

• Columbia Suicide Severity Rating Scale (CSSRS) Lifetime version (All Arms)

  Evaluation tool that evaluates a lifetime history of suicidal ideation and/or behavior. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of actual attempts are rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care).

  Screening

• Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arms A & B)

  Evaluation tool that evaluates risk for suicide since the last study visit. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of actual attempts are rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care).

  Day -1, Day 2, Day 10, Day 17, Day 21, Day 23, Day 31, Day 38, Day 42, and Day 56

• Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arms C & D)

  Evaluation tool that evaluates risk for suicide since the last study visit. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of actual attempts are rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care).

  Day -1, Day 2, Day 7, Day 9, Day 15, Day 21, Day 28

• Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arm E)

  Evaluation tool that evaluates risk for suicide since the last study visit. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of actual attempts are rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care).

  Day -1, Day 2, Day 7, Day 9, Day 14, Day 16, Day 21, Day 28, Day 35

Secondary Outcomes (22)

• Mystical Experience Questionnaire (MEQ30) (Arms A & B)

  Day 1 & Day 22

• Mystical Experience Questionnaire (MEQ30) (Arms C & D)

  Day 1 & Day 8

• Mystical Experience Questionnaire (MEQ30) (Arms C & D)

  Day 1, Day 8, & Day 15

• 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms A & B)

  Day 1 & Day 22

• 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms C & D)

  Day 1 & Day 8

Study Arms (5)

A: MDD Participants - CYB003 in 2 of 2 Medicine Sessions

EXPERIMENTAL

Arm A MDD participants will receive CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. The CYB003 dose received will depend on the cohort/time of enrollment. All MDD participants will receive supportive EMBARK psychotherapy throughout the study.

Drug: CYB003; Behavioral: Psychotherapy

B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2

PLACEBO COMPARATOR

Arm B MDD participants will receive placebo in Medicine Session 1, and approximately three weeks later will receive CYB003 in Medicine Session 2. The CYB003 dose received will depend on the cohort/time of enrollment. All MDD participants will receive supportive EMBARK psychotherapy throughout the study.

Drug: CYB003; Behavioral: Psychotherapy; Drug: Placebo

C: Healthy Volunteers - CYB003 in 2 of 2 Medicine Sessions

EXPERIMENTAL

Arm C healthy volunteers will receive CYB003 in 2 of 2 medicine sessions, approximately one to two weeks apart. The CYB003 dose received will depend on the cohort/time of enrollment. All healthy volunteers will receive psychological support throughout the study.

Drug: CYB003; Behavioral: Psychological Support

D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2

PLACEBO COMPARATOR

Arm D healthy volunteers will receive placebo in Medicine Session 1, and approximately one to two weeks later will receive CYB003 in Medicine Session 2. The CYB003 dose received will depend on the cohort/time of enrollment. All healthy volunteers will receive psychological support throughout the study.

Drug: CYB003; Drug: Placebo; Behavioral: Psychological Support

E: Healthy Volunteers - CYB003 in 3 of 3 Medicine Sessions

EXPERIMENTAL

Arm E healthy volunteers will receive CYB003 in 3 of 3 medicine sessions, approximately one week apart from each other, to assess bioavailability and food effect. The CYB003 dose received will depend on the safety review committee selection/time of enrollment. All healthy volunteers will receive psychological support throughout the study.

Drug: CYB003; Behavioral: Psychological Support

Interventions

CYB003 DRUG

CYB003 is a synthetic psilocybin analog.

A: MDD Participants - CYB003 in 2 of 2 Medicine Sessions; B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2; C: Healthy Volunteers - CYB003 in 2 of 2 Medicine Sessions; D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2; E: Healthy Volunteers - CYB003 in 3 of 3 Medicine Sessions

Psychotherapy BEHAVIORAL

Manualized psychotherapy (called EMBARK) performed by facilitators

A: MDD Participants - CYB003 in 2 of 2 Medicine Sessions; B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2

Placebo DRUG

Placebo

B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2; D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2

Psychological Support BEHAVIORAL

Manualized psychological support performed by facilitators

C: Healthy Volunteers - CYB003 in 2 of 2 Medicine Sessions; D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2; E: Healthy Volunteers - CYB003 in 3 of 3 Medicine Sessions

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cybin IRL Limited: lead
• Clinilabs Drug Development Corporation: collaborator
• Drug Safety Navigator: collaborator

Study Sites (3)

CenExel ACMR

Atlanta, Georgia, 30331, United States

Location

iResearch Atlanta

Decatur, Georgia, 30030, United States

Location

Clinilabs Drug Development Corporation

Eatontown, New Jersey, 07724, United States

Location

Related Links

• New Jersey Site Recruitment Website. Please click on link to apply

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Psychotherapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Amir Inamdar, MBBS,DNB,MFPM

  Cybin IRL Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2022
• First Posted: May 23, 2022
• Study Start: August 2, 2022
• Primary Completion: October 16, 2023
• Study Completion: January 18, 2024
• Last Updated: March 25, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)