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

Phase 1
Completed
Conditions
QTc Interval
Pharmacokinetics
Interventions
Registration Number
NCT05478278
Lead Sponsor
Usona Institute
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Part 1: Treatment B (IP at Supratherapeutic Dose)PsilocybinA single supratherapeutic dose of psilocybin.
Part 1: Treatment C (Placebo - Negative Control)Micro-Crystalline CelluloseA single dose of placebo-to-match psilocybin MCC capsules.
Part 1: Treatment D (Placebo - Positive Control)MoxifloxacinA single 400 mg dose of moxifloxacin.
Part 2: IP at Therapeutic Dose (Fasted Conditions)PsilocybinA single therapeutic dose of psilocybin administered under fasted conditions.
Part 2: IP at Therapeutic Dose (Fed Conditions)PsilocybinA single therapeutic dose of psilocybin under fed conditions.
Part 1: Treatment A (IP at Therapeutic Dose)PsilocybinA single therapeutic dose of psilocybin.
Primary Outcome Measures
NameTimeMethod
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.Up to 24 hours post-dose

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.

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.Up to 24 hours post-dose

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.

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.Up to 24 hours post-dose

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.

Part 1: Change from baseline (Day -1) QTcF (ΔΔQTcF) following up to 24 hours post administration of a supratherapeutic dose of psilocybin.Up to 24 hours post-dose

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.

Secondary Outcome Measures
NameTimeMethod
Part 1: Number of participants with Treatment-Related Adverse Events as assessed by CTCAE v4.0.Up to 30 Days Post Dose

Number of participants with TEAEs following administration of psilocybin and moxifloxacin.

Part 2: Number of participants with Treatment-Related Adverse Events as assessed by CTCAE v4.0Up to 15 Days Post Dose

Number of participants with TEAE following administration of psilocybin.

Trial Locations

Locations (1)

Altasciences Clinical Kansas, Inc

🇺🇸

Overland Park, Kansas, United States

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