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

Cybin IRL

Status and phase: Completed; Phase 2; Phase 1

Conditions: Major Depressive Disorder

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

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT05385783

CYB003-001

Details and patient eligibility

About

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).

Enrollment: 57 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria - MDD & Healthy Volunteer Participants:

• Aged between 21 to 65 years, inclusive, at Screening.
• Has a BMI of 18 to 30 kg/m2, inclusive, at Screening.
• Is ≥60 kg.
• Is negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test at Screening and at Day -1.
• Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Additional Inclusion Criteria - MDD Participants Only:

• Has a diagnosis of MDD (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-V] of moderate to severe degree), established through a full psychiatric work up, who are otherwise healthy.
• Has been on a stable dose of antidepressant medication (no more than 50% change) in the last month prior to Screening and has had an inadequate response, as judged by the Investigator.

Exclusion Criteria - MDD & Healthy Volunteer Participants:

• Clinically significant risk of suicidality, as determined through a comprehensive psychiatric interview.
• Clinically relevant history of abnormal physical health interfering with the study as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including [but not limited to], neurological, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder).
• Diagnosis of hypertension or an arrhythmia.
• History of hypothyroidism and/or current abnormal thyroid function tests.
• Clinically relevant abnormal laboratory results.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
• Any other concomitant disease or condition that could interfere with, or for which the treatment might interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study.
• Not fluent in the English language.
• Has a presence or relevant history of any of the following medical conditions: organic brain disorders (e.g., epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmal disease, brain tumor or other medical conditions associated with seizures or convulsions).
• Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (anti- HCV) or human immunodeficiency virus I and II (anti-HIV I/II) at Screening.
• Has participated in a clinical study and has received a medication or a new chemical entity within 3 months prior to dosing of current study medication.
• Is taking or has taken any drugs known to inhibit monoamine oxidase within 28 days prior to receiving the study drug.
• Is taking or has taken over the counter (OTC) doses of 5-hydroxytrptophan or St John's Wort within 28 days prior to receiving the study drug.
• Donation of blood or plasma of >400 mL within 1 month prior to first dosing until 4 weeks after final dosing.
• Is pregnant, breastfeeding or planning to conceive.
• Known difficulty with obtaining intravenous access.
• Other eligibility considerations (i.e., participant personal circumstances, behavior, and/or any current problem that might interfere with participation or that is incompatible with establishment of rapport or safe exposure to the study drug), as judged by the Investigator.

Additional Exclusion Criteria - Healthy Volunteers Only:

• Current or previously diagnosed with a mental health disorder as defined by DSM-V criteria.
• Use of any prescription medicine (except for hormonal contraceptives, if applicable), certain herbal supplements (to be reviewed by the Investigator), or OTC medicine during the 28 days before dosing.

Additional Exclusion Criteria - MDD Participants Only:

• Current or previous diagnosis of treatment-resistant MDD, defined as failure to respond to 2 or more antidepressant treatments given at an adequate dose for an adequate duration.
• Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder or brief psychotic disorder; current or previous history of bipolar disorder, or current personality disorder.
• Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressant, mirtazapine, an antipsychotic or a mood stabilizer.
• Use of a prescription medicine (except participants may take a stable chronic dose of antidepressant medication(s) and/or sedatives/hypnotics, and may take hormonal contraceptives, if applicable), certain herbal supplements (to be reviewed by the Investigator), or OTC medicine during the 28 days before dosing (some exceptions apply).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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57 participants in 5 patient groups, including a placebo group

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

Experimental group

Description:

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.

Treatment:

Behavioral: Psychotherapy

Drug: CYB003

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

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Behavioral: Psychotherapy

Drug: CYB003

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

Experimental group

Description:

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.

Treatment:

Behavioral: Psychological Support

Drug: CYB003

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

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Behavioral: Psychological Support

Drug: CYB003

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

Experimental group

Description:

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.

Treatment:

Behavioral: Psychological Support

Drug: CYB003