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

Phase 1

Completed

• Conditions: Major Depressive Disorder
• Interventions: Drug: CYB003; Behavioral: Psychotherapy; Behavioral: Psychological Support; Drug: Placebo

• Registration Number: NCT05385783
• Lead Sponsor: Cybin IRL Limited

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-10
• Study First Submitted QC: 2022-05-18
• Study First Posted: 2022-05-23
• Study Start: 2022-08-02
• Primary Completion: 2023-10-16
• Study Completion: 2024-01-18
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-22
• Last Update Posted: 2024-03-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: MDD Participants - CYB003 in 2 of 2 Medicine Sessions	CYB003	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.
A: MDD Participants - CYB003 in 2 of 2 Medicine Sessions	Psychotherapy	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.
B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2	CYB003	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.
B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2	Psychotherapy	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.
B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2	Placebo	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.
C: Healthy Volunteers - CYB003 in 2 of 2 Medicine Sessions	CYB003	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.
C: Healthy Volunteers - CYB003 in 2 of 2 Medicine Sessions	Psychological Support	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.
E: Healthy Volunteers - CYB003 in 3 of 3 Medicine Sessions	Psychological Support	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.
D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2	CYB003	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.
D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2	Placebo	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.
D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2	Psychological Support	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.
E: Healthy Volunteers - CYB003 in 3 of 3 Medicine Sessions	CYB003	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.

Primary Outcome Measures

Name	Time	Method
Resting 12 Lead ECG QRS duration (Arms A & B)	Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23	QRS duration (milliseconds)
Resting 12 Lead ECG QRS duration (Arms E)	Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16	QRS duration (milliseconds)
Adverse Events (All Arms)	Day 1 thru End of Study Visit (which is: Day 56 Arms A & B; Day 28 Arms C & D; Day 35 Arms E)	Any untoward medical occurrence in a clinical investigation participant administered a drug and does not necessarily have a causal relationship with the treatment
Resting 12 Lead ECG ventricular rate (Arms A & B)	Screening, Day -1, Day 1, Day 2, Day 21, Day 22, & Day 23	ventricular rate (beats per minute)
Resting 12 Lead ECG ventricular rate (Arms C & D)	Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9	ventricular rate (beats per minute)
Resting 12 Lead ECG PR interval (Arms C & D)	Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9	PR interval (milliseconds)
Resting 12 Lead ECG QTcF (Arms E)	Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16	Corrected QT interval by Fredericia (milliseconds)
Columbia Suicide Severity Rating Scale (CSSRS) Lifetime version (All Arms)	Screening	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).
Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arm E)	Day -1, Day 2, Day 7, Day 9, Day 14, Day 16, Day 21, Day 28, Day 35	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).
Resting 12 Lead ECG ventricular rate (Arms E)	Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16	ventricular rate (beats per minute)
Resting 12 Lead ECG PR interval (Arms E)	Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16	PR interval (milliseconds)
Resting 12 Lead ECG PR interval (Arms A & B)	Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23	PR interval (milliseconds)
Resting 12 Lead ECG QT interval (Arms A & B)	Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23	QT interval (milliseconds)
Resting 12 Lead ECG QT interval (Arms C & D)	Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9	QT interval (milliseconds)
Resting 12 Lead ECG QT interval (Arms E)	Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16	QT interval (milliseconds)
Resting 12 Lead ECG QTcF (Arms A & B)	Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23	Corrected QT interval by Fredericia (milliseconds)
Resting 12 Lead ECG QTcF (Arms C & D)	Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9	Corrected QT interval by Fredericia (milliseconds)
Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arms A & B)	Day -1, Day 2, Day 10, Day 17, Day 21, Day 23, Day 31, Day 38, Day 42, and Day 56	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).
Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arms C & D)	Day -1, Day 2, Day 7, Day 9, Day 15, Day 21, Day 28	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).
Resting 12 Lead ECG QRS duration (Arms C & D)	Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9	QRS duration (milliseconds)
Holter monitoring (Arms A & B)	Day -1, Day 1, Day 22	Record of the electrical activity of the heart (Hz)
Holter monitoring (Arms C & D)	Day -1, Day 1, Day 8	Record of the electrical activity of the heart (Hz)
Holter monitoring (Arm E)	Day -1, Day 1, Day 8, Day 15	Record of the electrical activity of the heart (Hz)

Secondary Outcome Measures

Name	Time	Method
Mystical Experience Questionnaire (MEQ30) (Arms C & D)	Day 1, Day 8, & Day 15	The revised MEQ30 consists of 30 questions looking back on the entirety of a medicine session, participants are asked to answer each question according to one's feelings, thoughts, and experiences at the time of the session. each item rated on a Likert scale (0-None/not at all to 5-Extreme, more than any other time in my life). The minimum score is 0 and the maximum score is 150 with higher scores indicating a greater degree of mystical experience. The MEQ total score is computed by taking the average response to all items.
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arm E)	Day 1, Day 8, & Day 15	The 5D-ASC consists of a set of 94 items that participants are asked to rate to what extent the statements apply to one's particular experience, compared to normal waking consciousness. This has 11 subscales and higher scores are indicative of good outcomes.
Hallucinogen Rating Scale (HRS) (Arms A & B)	Day 1 & Day 22	The HRS is a questionnaire with up to 100 items and is designed to assess the subjective effects of hallucinogenic substances. Responses to the majority of questions are on a 5 point intensity scale: 0=not at all; 1=slightly; 2=moderately; 3=quite a bit; and 4=extremely. Some questions have a slightly modified scale, and one question asks to rate the amount of time between when the drug was administered and feeling an effect from: no effect, 0 5 minutes, 5-15 minutes, 15-30 minutes, 30 60 minutes, or more than one hour. The minimum score is zero and maximum score is 400 with higher scores indicating greater hallucinogenic effect.
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms C & D)	Day 1 & Day 8	The 5D-ASC consists of a set of 94 items that participants are asked to rate to what extent the statements apply to one's particular experience, compared to normal waking consciousness. This has 11 subscales and higher scores are indicative of good outcomes.
Hallucinogen Rating Scale (HRS) (Arms C & D)	Day 1 & Day 8	The HRS is a questionnaire with up to 100 items and is designed to assess the subjective effects of hallucinogenic substances. Responses to the majority of questions are on a 5 point intensity scale: 0=not at all; 1=slightly; 2=moderately; 3=quite a bit; and 4=extremely. Some questions have a slightly modified scale, and one question asks to rate the amount of time between when the drug was administered and feeling an effect from: no effect, 0 5 minutes, 5-15 minutes, 15-30 minutes, 30 60 minutes, or more than one hour. The minimum score is zero and maximum score is 400 with higher scores indicating greater hallucinogenic effect.
Hallucinogen Rating Scale (HRS) (Arm E)	Day 1, Day 8, & Day 15	The HRS is a questionnaire with up to 100 items and is designed to assess the subjective effects of hallucinogenic substances. Responses to the majority of questions are on a 5 point intensity scale: 0=not at all; 1=slightly; 2=moderately; 3=quite a bit; and 4=extremely. Some questions have a slightly modified scale, and one question asks to rate the amount of time between when the drug was administered and feeling an effect from: no effect, 0 5 minutes, 5-15 minutes, 15-30 minutes, 30 60 minutes, or more than one hour. The minimum score is zero and maximum score is 400 with higher scores indicating greater hallucinogenic effect.
Mystical Experience Questionnaire (MEQ30) (Arms A & B)	Day 1 & Day 22	The revised MEQ30 consists of 30 questions looking back on the entirety of a medicine session, participants are asked to answer each question according to one's feelings, thoughts, and experiences at the time of the session. Each item is rated on a Likert scale (0-None/not at all to 5-Extreme, more than any other time in my life). The minimum score is 0 and the maximum score is 150 with higher scores indicating a greater degree of mystical experience. The MEQ total score is computed by taking the average response to all items.
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms A & B)	Day 1 & Day 22	The 5D-ASC consists of a set of 94 items that participants are asked to rate to what extent the statements apply to one's particular experience, compared to normal waking consciousness. This has 11 subscales and higher scores are indicative of good outcomes.
Persisting Effects Questionnaire (PEQ) (Arms A & B)	Day 1 & Day 22	The PEQ is a 5-item questionnaire that assesses the meaningfulness, spiritual significance, psychological insightfulness, and how psychologically challenging a participant experience was during the medicine session. Scores are assessed on a scale from 0 (not at all) to 5 (extremely). Higher scores (under consideration of reverse-scored items) indicate stronger persisting treatment effects.
Persisting Effects Questionnaire (PEQ) (Arms C & D)	Day 1 & Day 8	The PEQ is a 5-item questionnaire that assesses the meaningfulness, spiritual significance, psychological insightfulness, and how psychologically challenging a participant experience was during the medicine session. Scores are assessed on a scale from 0 (not at all) to 5 (extremely). Higher scores (under consideration of reverse-scored items) indicate stronger persisting treatment effects.
Persisting Effects Questionnaire (PEQ) (Arm E)	Day 1, Day 8, & Day 15	The PEQ is a 5-item questionnaire that assesses the meaningfulness, spiritual significance, psychological insightfulness, and how psychologically challenging a participant experience was during the medicine session. Scores are assessed on a scale from 0 (not at all) to 5 (extremely). Higher scores (under consideration of reverse-scored items) indicate stronger persisting treatment effects.
VAS Ratings of "Any Drug Effect" (Arms A & B)	Day 1 & Day 22	The visual analog scale (VAS) for "Any Drug Effect" consists of a 100mm bipolar line with the far-left side of the line marked "not at all" and the far-right side of the line marked "extremely" to assess if participants feel any drug effect.
VAS Ratings of "Any Drug Effect" (Arms C & D)	Day 1 & Day 8	The visual analog scale (VAS) for "Any Drug Effect" consists of a 100mm bipolar line with the far-left side of the line marked "not at all" and the far-right side of the line marked "extremely" to assess if participants feel any drug effect.
VAS Ratings of "Any Drug Effect" (Arm E)	Day 1, Day 8, & Day 15	The visual analog scale (VAS) for "Any Drug Effect" consists of a 100mm bipolar line with the far-left side of the line marked "not at all" and the far-right side of the line marked "extremely" to assess if participants feel any drug effect.
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from screening (Arms A & B)	Screening, Day -1, Day 1, Day 10, Day 17, Day 31, & Day 38	The minimum and maximum values are 0 and 60 with a higher score indicating a worse outcome.
Pharmacokinetic parameter of psilocin (Cmax) (Arms A & B)	Day 1, Day 2, Day 22, & Day 23	Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data.
Pharmacokinetic parameter of psilocin (Cmax) (Arms C & D)	Day 1, Day 2, Day 8, & Day 9	Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data.
Pharmacokinetic parameter of psilocin (Cmax) (Arm E)	Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16	Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data.
Pharmacokinetic parameter of psilocin (AUC) (Arms A & B)	Day 1, Day 2, Day 22, & Day 23	AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.
Pharmacokinetic parameter of psilocin (AUC) (Arms C & D)	Day 1, Day 2, Day 8, & Day 9	AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.
Pharmacokinetic parameter of psilocin (AUC) (Arm E)	Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16	AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.

Trial Locations

Locations (3)

CenExel ACMR; 🇺🇸 Atlanta, Georgia, United States

Clinilabs Drug Development Corporation; 🇺🇸 Eatontown, New Jersey, United States

iResearch Atlanta; 🇺🇸 Decatur, Georgia, United States