Major Depressive DisorderPhase 1/2NCT05385783
A Study of a Psilocybin Analog (CYB003) in Healthy Participants With and Without Major Depressive Disorder
A Phase 1/2 study testing CYB003, Psychotherapy and Psychological Support in people with Major Depressive Disorder, run by Cybin IRL Limited at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- CYB003, Psychotherapy and Psychological Support
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 3 sitesUnited States
- Study dates
- 2 Aug 2022to 18 Jan 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
CenExel ACMR
Atlanta, Georgia, 30331
iResearch Atlanta
Decatur, Georgia, 30030
Clinilabs Drug Development Corporation
Eatontown, New Jersey, 07724
About this study
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)
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
- Being tested
- CYB003, Psychotherapy, Placebo, Psychological Support
- Keywords
- Major Depressive Disorder, MDD, Psilocybin, Psychedelic, Psilocin, CYB003, CYB003-001, Depression, Healthy
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYB003Drug
CYB003 is a synthetic psilocybin analog.
PsychotherapyBehavioural
Manualized psychotherapy (called EMBARK) performed by facilitators
PlaceboDrug
Placebo
Psychological SupportBehavioural
Manualized psychological support performed by facilitators
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: CYB003; Behavioral: Psychological Support |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
Resting 12 Lead ECG PR interval (Arms E)
PR interval (milliseconds)
Measured: 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)
Measured: 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)
Measured: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
Resting 12 Lead ECG QRS duration (Arms E)
QRS duration (milliseconds)
Measured: 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)
Measured: 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)
Measured: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
Resting 12 Lead ECG QT interval (Arms E)
QT interval (milliseconds)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Day -1, Day 1, Day 22
Holter monitoring (Arms C & D)
Record of the electrical activity of the heart (Hz)
Measured: Day -1, Day 1, Day 8
Holter monitoring (Arm E)
Record of the electrical activity of the heart (Hz)
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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)
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.
Measured: Day 1 & Day 22
Mystical Experience Questionnaire (MEQ30) (Arms C & D)
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.
Measured: Day 1 & Day 8
Mystical Experience Questionnaire (MEQ30) (Arms C & D)
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.
Measured: Day 1, Day 8, & Day 15
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms A & B)
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.
Measured: Day 1 & Day 22
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms C & D)
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.
Measured: Day 1 & Day 8
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arm E)
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.
Measured: Day 1, Day 8, & Day 15
Hallucinogen Rating Scale (HRS) (Arms A & B)
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.
Measured: Day 1 & Day 22
Hallucinogen Rating Scale (HRS) (Arms C & D)
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.
Measured: Day 1 & Day 8
Hallucinogen Rating Scale (HRS) (Arm E)
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.
Measured: Day 1, Day 8, & Day 15
Persisting Effects Questionnaire (PEQ) (Arms A & B)
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.
Measured: Day 1 & Day 22
Persisting Effects Questionnaire (PEQ) (Arms C & D)
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.
Measured: Day 1 & Day 8
Persisting Effects Questionnaire (PEQ) (Arm E)
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.
Measured: Day 1, Day 8, & Day 15
VAS Ratings of "Any Drug Effect" (Arms A & B)
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.
Measured: Day 1 & Day 22
VAS Ratings of "Any Drug Effect" (Arms C & D)
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.
Measured: Day 1 & Day 8
VAS Ratings of "Any Drug Effect" (Arm E)
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.
Measured: Day 1, Day 8, & Day 15
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from screening (Arms A & B)
The minimum and maximum values are 0 and 60 with a higher score indicating a worse outcome.
Measured: Screening, Day -1, Day 1, Day 10, Day 17, Day 31, & Day 38
Pharmacokinetic parameter of psilocin (Cmax) (Arms A & B)
Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data.
Measured: Day 1, Day 2, Day 22, & Day 23
Pharmacokinetic parameter of psilocin (Cmax) (Arms C & D)
Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data.
Measured: Day 1, Day 2, Day 8, & Day 9
Pharmacokinetic parameter of psilocin (Cmax) (Arm E)
Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data.
Measured: Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16
Pharmacokinetic parameter of psilocin (AUC) (Arms A & B)
AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.
Measured: Day 1, Day 2, Day 22, & Day 23
Pharmacokinetic parameter of psilocin (AUC) (Arms C & D)
AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.
Measured: Day 1, Day 2, Day 8, & Day 9
Pharmacokinetic parameter of psilocin (AUC) (Arm E)
AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.
Measured: Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2022
- Study start2 Aug 2022
- Primary completion16 Oct 2023
- Study completion18 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cybin IRL Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinilabs Drug Development Corporation, Drug Safety Navigator
- Responsible party
- Sponsor
- Investigators
- Amir Inamdar, MBBS,DNB,MFPM, Study director, Cybin IRL Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05385783
- Sponsor's protocol ID
- CYB003-001
- Status last verified
- Mar 2024
- First submitted
- 10 May 2022
- Last updated
- 25 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05385783
- Acronym / sponsor ID
- CYB003-001
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, MDD, Psilocybin, Psychedelic, Psilocin, CYB003, CYB003-001, Depression
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Cybin IRL LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Clinilabs Drug Development Corporation, Drug Safety Navigator
- Study start
- 2 Aug 2022 (actual)
- Primary completion
- 16 Oct 2023 (actual)
- Study completion
- 18 Jan 2024 (actual)
- First posted
- 23 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| A: MDD Participants - CYB003 in 2 of 2 Medicine Sessions | Experimental | Drug: CYB003, Behavioral: PsychotherapyArm 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 | Placebo comparator | Drug: CYB003, Behavioral: Psychotherapy, Drug: PlaceboArm 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 | Experimental | Drug: CYB003, Behavioral: Psychological SupportArm 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. |
| D: Healthy Volunteers - Placebo in Medicine Session 1, CYB003 in Medicine Session 2 | Placebo comparator | Drug: CYB003, Drug: Placebo, Behavioral: Psychological SupportArm 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 | Experimental | Drug: CYB003, Behavioral: Psychological SupportArm 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. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYB003CYB003 is a synthetic psilocybin analog. | Drug | 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 |
| PsychotherapyManualized psychotherapy (called EMBARK) performed by facilitators | Behavioural | A: MDD Participants - CYB003 in 2 of 2 Medicine Sessions, B: MDD Participants - Placebo in Medicine Session 1, CYB003 in Medicine Session 2 |
| PlaceboPlacebo | Drug | 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 SupportManualized psychological support performed by facilitators | Behavioural | 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 |
Primary outcome
Adverse Events (All Arms)
Time frame: 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)
Time frame: 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)
Time frame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
ventricular rate (beats per minute)
Resting 12 Lead ECG ventricular rate (Arms E)
Time frame: 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 A & B)
Time frame: Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23
PR interval (milliseconds)
Resting 12 Lead ECG PR interval (Arms C & D)
Time frame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
PR interval (milliseconds)
Resting 12 Lead ECG PR interval (Arms E)
Time frame: 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 QRS duration (Arms A & B)
Time frame: Screening, Day -1, Day 1, Day 2, Day 21, Day 22, Day 23
QRS duration (milliseconds)
Resting 12 Lead ECG QRS duration (Arms C & D)
Time frame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
QRS duration (milliseconds)
Resting 12 Lead ECG QRS duration (Arms E)
Time frame: Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16
QRS duration (milliseconds)
Resting 12 Lead ECG QT interval (Arms A & B)
Time frame: 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)
Time frame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
QT interval (milliseconds)
Resting 12 Lead ECG QT interval (Arms E)
Time frame: 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)
Time frame: 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)
Time frame: Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9
Corrected QT interval by Fredericia (milliseconds)
Resting 12 Lead ECG QTcF (Arms E)
Time frame: Screening, Day -1, Day1, Day 2, Day 7, Day 8, Day 9, Day 14, Day 15, Day 16
Corrected QT interval by Fredericia (milliseconds)
Holter monitoring (Arms A & B)
Time frame: Day -1, Day 1, Day 22
Record of the electrical activity of the heart (Hz)
Holter monitoring (Arms C & D)
Time frame: Day -1, Day 1, Day 8
Record of the electrical activity of the heart (Hz)
Holter monitoring (Arm E)
Time frame: Day -1, Day 1, Day 8, Day 15
Record of the electrical activity of the heart (Hz)
Columbia Suicide Severity Rating Scale (CSSRS) Lifetime version (All Arms)
Time frame: 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) (Arms A & B)
Time frame: 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)
Time frame: 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).
Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit (SLV) (Arm E)
Time frame: 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).
22 secondary outcomes
Mystical Experience Questionnaire (MEQ30) (Arms A & B)
Time frame: Day 1 & Day 22
Mystical Experience Questionnaire (MEQ30) (Arms C & D)
Time frame: Day 1 & Day 8
Mystical Experience Questionnaire (MEQ30) (Arms C & D)
Time frame: Day 1, Day 8, & Day 15
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms A & B)
Time frame: Day 1 & Day 22
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arms C & D)
Time frame: Day 1 & Day 8
5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Arm E)
Time frame: Day 1, Day 8, & Day 15
Hallucinogen Rating Scale (HRS) (Arms A & B)
Time frame: Day 1 & Day 22
Hallucinogen Rating Scale (HRS) (Arms C & D)
Time frame: Day 1 & Day 8
Hallucinogen Rating Scale (HRS) (Arm E)
Time frame: Day 1, Day 8, & Day 15
Persisting Effects Questionnaire (PEQ) (Arms A & B)
Time frame: Day 1 & Day 22
Persisting Effects Questionnaire (PEQ) (Arms C & D)
Time frame: Day 1 & Day 8
Persisting Effects Questionnaire (PEQ) (Arm E)
Time frame: Day 1, Day 8, & Day 15
VAS Ratings of "Any Drug Effect" (Arms A & B)
Time frame: Day 1 & Day 22
VAS Ratings of "Any Drug Effect" (Arms C & D)
Time frame: Day 1 & Day 8
VAS Ratings of "Any Drug Effect" (Arm E)
Time frame: Day 1, Day 8, & Day 15
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from screening (Arms A & B)
Time frame: Screening, Day -1, Day 1, Day 10, Day 17, Day 31, & Day 38
Pharmacokinetic parameter of psilocin (Cmax) (Arms A & B)
Time frame: Day 1, Day 2, Day 22, & Day 23
Pharmacokinetic parameter of psilocin (Cmax) (Arms C & D)
Time frame: Day 1, Day 2, Day 8, & Day 9
Pharmacokinetic parameter of psilocin (Cmax) (Arm E)
Time frame: Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16
Pharmacokinetic parameter of psilocin (AUC) (Arms A & B)
Time frame: Day 1, Day 2, Day 22, & Day 23
Pharmacokinetic parameter of psilocin (AUC) (Arms C & D)
Time frame: Day 1, Day 2, Day 8, & Day 9
Pharmacokinetic parameter of psilocin (AUC) (Arm E)
Time frame: Day 1, Day 2, Day 8, Day 9, Day 15, & Day 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2024.
- New Jersey Site Recruitment Website. Please click on link to applyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amir Inamdar, MBBS,DNB,MFPM study director
Cybin IRL Limited
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CYB003, Psychotherapy and Psychological Support in people with Major Depressive Disorder, run by Cybin IRL Limited at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (All Arms) (time frame: Day 1 thru End of Study Visit (which is: Day 56 Arms A & B; Day 28 Arms C & D; Day 35 Arms E)). The study lists 23 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2024.