Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, MDD, Psilocybin, Psychedelic, Psilocin, CYB003, CYB003-001, Depression, Healthy
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).
Interventions
DRUGCYB003
CYB003 is a synthetic psilocybin analog.
BEHAVIORALPsychotherapy
Manualized psychotherapy (called EMBARK) performed by facilitators
DRUGPlacebo
Placebo
BEHAVIORALPsychological Support
Manualized psychological support performed by facilitators
Sponsors
Clinilabs Drug Development Corporation
Drug Safety Navigator
Cybin IRL Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 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 A & B) | 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) | Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9 | PR interval (milliseconds) |
| 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 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 C & D) | Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9 | 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) |
| 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 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) |
| 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) |
| 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) (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 QTcF (Arms C & D) | Screening, Day -1, Day 1, Day 2, Day 7, Day 8, & Day 9 | Corrected QT interval by Fredericia (milliseconds) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mystical Experience Questionnaire (MEQ30) (Arms C & D) | Day 1 & Day 8 | 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) (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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Outcome results
None listed