An Evaluation of Psilocybin's Effect on Cardiac Repolarization and the Effect of Food on Psilocybin's Pharmacokinetics

Study Overview
=================
Brief Summary
-----------------
This study is comprised of two parts. The purpose of the first part of this study is to evaluate the effects of a supratherapeutic dose of psilocybin on cardiac repolarization. The purpose of the second part of the study is to evaluate the effects of food on the pharmacokinetics of psilocybin.

Detailed Description
-----------------
Part one of this study will be a double-blind, single-dose, randomized, placebo-controlled, 4-treatment, 4-period, 12-sequence crossover design in 36 healthy volunteers (adult male and/or female subjects). Subjects will be randomly assigned to 1 of 12 different treatment administration sequences, whereby each sequence will include 3 double-blind treatments (therapeutic dose of psilocybin, supratherapeutic dose of psilocybin, and placebo) and 1 open-label positive control treatment (moxifloxacin). Part two of this study will be an open-label, randomized, 2-period, 2-sequence crossover design in 24 healthy volunteers (adult male and/or female subjects). Each assigned treatment will be administered under fasting or fed conditions as a single dose on Day 1 of the respective study period.

Official Title
-----------------
A Phase 1, Two-Part Study in Healthy Volunteers to Evaluate The Effect of Psilocybin on Cardiac Repolarization and The Effect of Food on Psilocybin Pharmacokinetics

Conditions
-----------------
QTc Interval, Pharmacokinetics

Intervention / Treatment
-----------------
* Drug: Psilocybin
* Drug: Moxifloxacin
* Drug: Micro-Crystalline Cellulose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated informed consent form (ICF) Stated willingness to comply with all study procedures and availability for the duration of the study Healthy adult male or female Aged at least 18 years but not older than 65 years, inclusive Body mass index (BMI) within 18.0 kg/m2 to 32.0 kg/m2 (for Part 1) or to 33.0 kg/m2 (for Part 2), inclusively Exclusion Criteria: History of significant hypersensitivity to psilocybin or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease Showing suicidal ideation or behavior as per the Columbia Suicide Severity Rating Scale (C-SSRS) administered at screening Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS < 60 msec, QRS >110 msec and QTcF > 450 msec for males and > 470 for females) on the ECG at screening or other clinically significant ECG abnormalities, unless deemed non-significant by an Investigator History of risk factors for Torsades de Pointes (TdP), including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesaemia Family history of long QT syndrome or Brugada syndrome Any clinically significant illness in the 28 days prior to the first study drug administration Intake of psilocybin or any other psychedelic (including 3,4-methylenedioxymethamphetamine [MDMA] and ketamine) in the 28 days prior to the first study drug administration Not suitable for participation in the study at the discretion of the Principal Investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Treatment A (IP at Therapeutic Dose)<br>A single therapeutic dose of psilocybin. | Drug: Psilocybin<br>* The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains psilocybin (API only in a capsule).<br>* Other names: Indocybin;|
| Experimental: Part 1: Treatment B (IP at Supratherapeutic Dose)<br>A single supratherapeutic dose of psilocybin. | Drug: Psilocybin<br>* The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains psilocybin (API only in a capsule).<br>* Other names: Indocybin;|
| Placebo Comparator: Part 1: Treatment C (Placebo - Negative Control)<br>A single dose of placebo-to-match psilocybin MCC capsules. | Drug: Micro-Crystalline Cellulose<br>* The placebo used in this study is encapsulated using a HPMC capsule and contains micro-crystalline cellulose.<br>|
| Active Comparator: Part 1: Treatment D (Placebo - Positive Control)<br>A single 400 mg dose of moxifloxacin. | Drug: Moxifloxacin<br>* The positive comparator used in this study is a 400 mg moxifloxacin tablet.<br>* Other names: Moxeza;|
| Experimental: Part 2: IP at Therapeutic Dose (Fasted Conditions)<br>A single therapeutic dose of psilocybin administered under fasted conditions. | Drug: Psilocybin<br>* The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains psilocybin (API only in a capsule).<br>* Other names: Indocybin;|
| Experimental: Part 2: IP at Therapeutic Dose (Fed Conditions)<br>A single therapeutic dose of psilocybin under fed conditions. | Drug: Psilocybin<br>* The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains psilocybin (API only in a capsule).<br>* Other names: Indocybin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change from baseline (Day -1) QTcF (ΔΔQTcF) following up to 24 hours post administration of a supratherapeutic dose of psilocybin. | Replicate electrocardiograms (ECGs) (10 ECG replicates) for the determination of ΔQTc interval will be extracted from the continuous digital 12-lead ECG recording at the -0.75, -0.50, and -0.25 hours prior to dosing and then at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose. | Up to 24 hours post-dose | 
| Part 2: Change from baseline (T=0 hours) of AUC of psilocybin and its metabolite psilocin following up to 24 hours post administration of a therapeutic dose of psilocybin under fed and fasted conditions. | Pharmacokinetic endpoints for psilocybin and psilocin (AUC) will be evaluated at 0.00, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose. | Up to 24 hours post-dose | 
| Part 2: Change from baseline (T=0 hours) of Cmax of psilocybin and its metabolite psilocin following up to 24 hours post administration of a therapeutic dose of psilocybin under fed and fasted conditions. | Pharmacokinetic endpoints for psilocybin and psilocin (CMax) will be evaluated at 0.00, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose. | Up to 24 hours post-dose | 
| Part 2: Change from baseline (T=0 hours) of Tmax of psilocybin and its metabolite psilocin following up to 24 hours post administration of a therapeutic dose of psilocybin under fed and fasted conditions. | Pharmacokinetic endpoints for psilocybin and psilocin (TMax) will be evaluated at 0.00, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose. | Up to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of participants with Treatment-Related Adverse Events as assessed by CTCAE v4.0. | Number of participants with TEAEs following administration of psilocybin and moxifloxacin. | Up to 30 Days Post Dose | 
| Part 2: Number of participants with Treatment-Related Adverse Events as assessed by CTCAE v4.0 | Number of participants with TEAE following administration of psilocybin. | Up to 15 Days Post Dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Psilocybin, Psychedelics