ANZCTR - Registration

Registration number

ACTRN12625000403437p

Ethics application status

Submitted, not yet approved

Date submitted

16/04/2025

Date registered

5/05/2025

Date last updated

5/05/2025

Date data sharing statement initially provided

5/05/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

Evaluation of the safety of the intravenously (IV) administered psychedelic, psilocin in healthy adults.

Scientific title

A Phase 1, Open-label, Single Cohort Study to Evaluate the Safety and Pharmacokinetics (PK) of a Single Intravenous (IV) Infusion of TRP-8803 [Psilocin Besylate formulation] in Healthy Adult Participants

Secondary ID [1]

TRYP-006

Universal Trial Number (UTN)

Trial acronym

HC-IV

Linked study record

The current study is a follow-up to ACTRN12624000547549

Health condition

Health condition(s) or problem(s) studied:

Binge Eating Disorder

Condition category

Condition code

Mental Health

Eating disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

INTERVENTIONAL: This is a phase 1 open label uncontrolled trial of TRP-8803 (Psilocin Besylate) administered intravenously in conjunction with psychedelic-assisted psychotherapy.

PSYCHEDELIC-ASSISTED PSYCHOTHERAPY:
The study is a combined pharmacological and psychological treatment, and as such, each individual participant will receive psychotherapy before, during, and after each dosing session. All participants will be seen by the same two therapists from baseline through to the completion of the study. The trial therapists are qualified and experienced mental health professionals (i.e., psychiatrists, psychologists) with specialty training in empirically based therapeutic modalities and psychedelic-assisted psychotherapy. The therapist dyad will typically consist of one male and one female therapist. In every dyad, at least one therapist will be a medically qualified healthcare practitioner. This ensures appropriately qualified staff are able to administer trial medication, both the study drug and any medical interventions if required (i.e., anti-anxiety medication due to persistent psychological distress), and manage any medical events that emerge.

The psychotherapy focuses on three distinct phases of this approach: (1) Preparation: emphasising therapeutic alliance, non-avoidance training, psychological and practical preparation for dosing sessions, nature of and relationship to distress, anxiety management strategies, the importance of set and setting, and intention formation; (2) Dosing session: establishing suitable set and setting, and providing non-directive support when necessary; (3) Integration: focus on sustaining the change, emotion and body-focused therapy, meaning-centred integration into wider context, mindfulness training, ongoing peer- and professional support, and facilitating contextual changes to support outcomes. Therapy guides will ensure trial fidelity.

The intervention scheduled for all participants will commence with two hours of preparatory psychotherapy session (week 1). In week 2, the investigational medical product (IMP) will be administered, followed by two, 1 hour sessions of integration psychotherapy; the first within 24 hours after the dosing session (week 2) and the second 2 weeks later (week 4). Treatment will be delivered to individual participants separately. Adherence to trial protocol (i.e., session attendance) will be documented.

TRP-8803 (Psilocin Besylate) ADMINISTRATION:
TRP-8803 will be administered via an intravenous (IV) infusion once (1) to each participant in week 2. During the single dosing session, participants will receive an initial 5 mg loading dose infused over the first 20 minutes to provide a therapeutic/psychoactive dose of psilocin that will be maintained by infusing the maintenance dose of 5 mg over the following 120 minutes. Participant dosing will be staggered with at least a 48-hour interval scheduled between the start of psilocin administration for the first and remaining participants, with no more than one participant being dosed on a single day. The nature and severity of any adverse events related to the dosing of the first participant will be reviewed by the investigators and the Data Safety Monitoring Board (DSMB) to determine whether to proceed with the remaining dosing, modify the study, pause the study, or stop the study in accordance with pre-defined discontinuation rules.

Adherence to the study intervention will be monitored by the therapist dyad facilitating the dosing session, essential documentation (i.e., IMP accountability records), and audiovisual recording of dosing session.

Intervention code [1]

Treatment: Other

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Assess the safety of a single IV infusion of TRP-8803 [Psilocin Besylate] in healthy adult participants

Timepoint [1]

i) During TRP-8803 dosing sessions via continuous therapists monitoring of participant physical and mental wellbeing for emergent AEs commencing prior to IMP administration until discharge. Blood pressure, HR, and ECG will be measured during IMP administration using an automated device and recorded in the source documentation at the following intervals: • Ninety minutes before dosing • Within 15 minutes, 30 minutes, and 45 minutes (± 10 minutes) after the start of the infusion • Within 1 hour (± 20 minutes) after the start of the infusion • Within 1.5 hours (± 20 minutes) after the start of the infusion • Within 2 hours (± 30 minutes) after the start of the infusion and every hour afterwards until the end of the session. ii) Through to 2 weeks post dosing (week 2) via a) scheduled post-dose psychotherapy, b) physical examinations completed b) within 24 hours of dosing, b) 2 weeks post dosing (week 4), c) week 3 wellbeing check; 2 week post dose follow up assessment (week 4); d) participant initiated contact with trial team.

Secondary outcome [1]

Determine the plasma concentrations and pharmacokinetic (PK) profile of TRP-8803 [Psilocin Besylate] during IV administration.

Timepoint [1]

i) Predose (90-minute window before dosing); the following timepoints after the start of the infusion (±10 minutes): ii) 15 minutes; iii) 30 minutes; iv) 40 minutes; v) 50 minutes; vi) 60 minutes; vii) 90 minutes; viii) 120 minutes; ix) 130 minutes; x) 150 minutes; xi) 3 hours; xii) 4 hours; xiii) 6 hours; xiv) 8 hours; and xv) 24 hours.

Secondary outcome [2]

Determine the plasma concentrations and pharmacokinetic (PK) profile of TRP-8803 [Psilocin Besylate] during IV administration.

Timepoint [2]

i) Predose (90-minute window before dosing); the following timepoints after the start of the infusion (±10 minutes): ii) 15 minutes; iii) 30 minutes; iv) 40 minutes; v) 50 minutes; vi) 60 minutes; vii) 90 minutes; viii) 120 minutes; ix) 130 minutes; x) 150 minutes; xi) 3 hours; xii) 4 hours; xiii) 6 hours; xiv) 8 hours; and xv) 24 hours.

Secondary outcome [3]

Examine the effect of TRP-8803 on participant tendency to feel positive emotions

Timepoint [3]

2 weeks post dose (week 4)

Secondary outcome [4]

Determine the effect of TRP-8803 [Psilocin Besylate] on challenging experiences encountered during dosing in healthy adult participants.

Timepoint [4]

i) 24 hours post dosing; ii) 2 weeks post dosing

Secondary outcome [5]

Determine the time course and intensity of the acute psychedelic effect of TRP-8803 [Psilocin Besylate] in healthy adult participants

Timepoint [5]

the following timepoints after the start of the infusion (±10 minutes): i) 10 minutes; ii) 20 minutes; iii) 30 minutes; iv) every 15 minutes from that until 6 hours after the start of the infusion.

Secondary outcome [6]

Determine the plasma concentrations and pharmacokinetic (PK) profile of TRP-8803 [Psilocin Besylate] during IV administration

Timepoint [6]

i) Predose (90-minute window before dosing); the following timepoints after the start of the infusion (±10 minutes): ii) 15 minutes; iii) 30 minutes; iv) 40 minutes; v) 50 minutes; vi) 60 minutes; vii) 90 minutes; viii) 120 minutes; ix) 130 minutes; x) 150 minutes; xi) 3 hours; xii) 4 hours; xiii) 6 hours; xiv) 8 hours; and xv) 24 hours.

Secondary outcome [7]

Examine the effect of TRP-8803 on participant mental wellbeing

Timepoint [7]

2 weeks post dose (week 4)

Secondary outcome [8]

Determine the persisting psychological, emotional, and spiritual effects of TRP-8803 [Psilocin Besylate] in healthy adult participants.

Timepoint [8]

i) 24 hours post dosing; ii) 2 weeks post dosing

Secondary outcome [9]

Determine the plasma concentrations and pharmacokinetic (PK) profile of TRP-8803 [Psilocin Besylate] during IV administration.

Timepoint [9]

i) Predose (90-minute window before dosing); the following timepoints after the start of the infusion (±10 minutes): ii) 15 minutes; iii) 30 minutes; iv) 40 minutes; v) 50 minutes; vi) 60 minutes; vii) 90 minutes; viii) 120 minutes; ix) 130 minutes; x) 150 minutes; xi) 3 hours; xii) 4 hours; xiii) 6 hours; xiv) 8 hours; and xv) 24 hours.

Secondary outcome [10]

Determine the effect of TRP-8803 [Psilocin Besylate] on emotional breakthroughs encountered during dosing in healthy adult participants.

Timepoint [10]

i) 24 hours post dosing; ii) 2 weeks post dosing

Secondary outcome [11]

Determine the plasma concentrations and pharmacokinetic (PK) profile of TRP-8803 [Psilocin Besylate] during IV administration.

Timepoint [11]

i) Predose (90-minute window before dosing); the following timepoints after the start of the infusion (±10 minutes): ii) 15 minutes; iii) 30 minutes; iv) 40 minutes; v) 50 minutes; vi) 60 minutes; vii) 90 minutes; viii) 120 minutes; ix) 130 minutes; x) 150 minutes; xi) 3 hours; xii) 4 hours; xiii) 6 hours; xiv) 8 hours; and xv) 24 hours.

Secondary outcome [12]

Examine the subjective experience of participants

Timepoint [12]

2 weeks post dose (week 4)

Secondary outcome [13]

Determine how the brains electrical activity changes with the course and intensity of psychedelic effects of TRP-8803 [Besylate] in healthy adult participants

Timepoint [13]

Continuous monitoring commencing prior to administration of study drug until discharge from the TRP-8803 dosing session.

Secondary outcome [14]

Determine the effect of TRP-8803 [Psilocin Besylate] on mystical experiences encountered during dosing in healthy adult participants.

Timepoint [14]

i) 24 hours post dosing; ii) 2 weeks post dosing

Eligibility

Key inclusion criteria

• Voluntary consent to participate in the study (including follow-up visits) and to undergo the procedures described.
• Ability to take medication intravenously (i.e., has adequate venous access for IV administration) and be willing to adhere to the study regimen.
• Medically stable in the judgement of the Medical Officer and Lead Psychiatrist, as determined by screening medical, physical examination, ECG, and routine laboratory tests including blood and urinalysis.
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that they consumes on a usual morning, before arriving at the research unit on the mornings of drug session day. If the participant does not routinely consume caffeinated beverages, they must agree not to do so on a session day.
• Agree to follow the directions of the Medical Officer regarding the consumption of non-prescription and prescription medications and supplements:
• Agree that for 7 days before the psilocin administration day, including the morning of the dose, participant will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the Medical Officer. Exceptions will include acetaminophen, non-steroidal anti-inflammatory drugs, common doses of vitamins and minerals, and contraceptives.
• Agree that for 14 days before the study intervention administration session, participants must refrain from taking any prescription medication (except for hormonal contraceptives or hormone replacement therapy) except when approved by the Medical Officer. No pro re nata (PRN) medications are allowed on the morning of study intervention administration.
• Agree that a support person will assist them personally with transport after each dosing session.
• If required, successful withdraw of nominated medications prior to baseline.
• Able to provide the contact detail of a medically qualified doctor or medical practice that they are a patient of and give consent for them to be contacted by a trial staff member.
• Non- or ex-smokers and not use other nicotine-containing products from 90 days prior to Stage 1 Screening until participant study termination.
• Weight between 50kg and 120 kg, inclusive; and body mass index (BMI) between 20 and 30 inclusive.
• Has had no psychedelic drug use in the 3 months prior to psilocin administration visit and agrees to refrain from psychedelic drug use other than study drug during the course of the study by self-report. Psychedelic drugs include but are not limited to psilocybin, LSD, methylenedioxymethamphetamine (MDMA), and ayahuasca. If another suspected psychedelic agent is used, Sponsor must be contacted for approval.
• Women of childbearing potential (WOCBP) in sexual relationships with men must use 2 acceptable methods of contraception from 30 days prior to study screening until 30 days after completing the dose of study intervention. Ova donation is not permitted for 30 days after completing the dose of study intervention.
• Men must agree to avoid impregnation of women and sperm donation during and for 90 days after completing the dose of study intervention through use of an acceptable method of contraception.
NOTE: acceptable methods of contraception include, but are not limited to, intrauterine device; injected/implanted/intravaginal/transdermal hormonal method; oral hormones plus a barrier contraception; abstinence; vasectomized sole partner; or double barrier contraception (eg, barrier method). The 2 methods of contraception cannot both be hormonal.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

• Meets DSM-5 criteria for any psychiatric conditions (including personality disorders), ongoing experience or history of trauma, or other personal or situational factors (e.g., lacking social support, lacking a stable living situation, domestic violence, high autistic trait) judged by the investigating team as part of the eligibility review process to be incompatible with establishment of rapport or the safe exposure to treatment.
• Recent (within 5 years) history of major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, anorexia nervosa or bulimia nervosa, overeating disorder, posttraumatic stress disorder, or substance use disorder.
• At the time of screening, experiencing mild levels of depression or greater.
• Participant has a recent history of suicide attempt (defined as an active, interrupted, or aborted attempt with the past 5 years) or reports suicidal ideation in the past 6 months as indicated by a positive response (“Yes”) to either Question 4 or Question 5 of the C-SSRS performed at the Screening Visit
• History of psychosis: past or present diagnosis DSM-5 of bipolar disorder, schizophrenia, or schizoaffective disorder.
• Family history of psychosis: past or present DSM-5 diagnosis of bipolar disorder in first-degree relative, or schizophrenia, or schizoaffective disorder in first or second-degree relative.
• Participant has a history of alcohol abuse disorder within 1 year prior to screening or regular abuse of alcohol (AUDIT > 8 at screening).
• Meets DSM-5 criteria for substance use disorder (other than alcohol) within the past 12 months or regular abuse of substances (DAST-10 > 3 at screening).
• Currently taking (or where applicable, testing positive on urine drug test), drugs of abuse such as amphetamines, buprenorphine, benzodiazepines, cocaine, methamphetamines, MDMA/Ecstasy, morphine, methadone, oxycodone, marijuana, ethyl glucuronide, fentanyl, tramadol, and synthetic cannabinoids (K2).
• Prior adverse effects from psilocybin or other psychedelics (such as severe headache and/or severe hypertension requiring treatment) based on self-report.
• History of HPPD.
• Serious medical condition that, in the judgment of the medical officer and/or lead psychiatrist, will interfere with the ability so safety participate in the treatment e.g., Cardiovascular, Metabolic, Neurological, Respiratory, Oncological, haematological disorder, epilepsy or seizures.
• Currently under treatment for epilepsy.
• Cardiovascular conditions: uncontrolled hypertension (Systolic >140 and diastolic >90), angina, a clinically significant ECG abnormality (e.g., atrial fibrillation), TIA in the last 6 months, stroke, or cerebrovascular disease, peripheral or pulmonary vascular disease (no active claudication). This could include patients presenting with abnormal QT interval prolongation at screening or with a history of this (QTc at screening above 450 ms for men and above 470 ms for women), PR >220 msec, or QRS >120 msec
• Known conditions putting participant at risk for hypercalcaemia, Cushing's syndrome, hypoglycaemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid syndrome
• Serious abnormal haematology or electrolyte, renal or liver test result (indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to 2 or total bilirubin greater than or equal to 1.5 x upper limit of normal (ULN), which remains above these limits if provided by their GP or assessed during the screening phase, unless there is specific medical clearance.
• Insulin-dependent diabetes; if taking oral hypoglycaemic agents only excluded if they also have a history of hypoglycaemia.
• Currently taking (within 5 half-lives dosing days) prohibited medications, including antihypertensive medications, UDP Glucuronosyltransferase Family 1 Member A9 (UGT1A9) or intestinal UDP-glucuronosyltransferases 1A10 inhibitors (eg, regorafenib, rifampicin, phenytoin, eltrombopag, mefenamic acid, diflunisal, niflumic acid, sorafenib, isavuconazole, deferasiroxor, ginseng), and aldehyde or alcohol dehydrogenase inhibitors (eg, disulfiram).
• Currently (for at least 2 weeks; or at least 4 weeks for fluoxetine) taking an antidepressant.
• Serious infection requiring hospitalisation within the last 28 days.
• Women of childbearing potential who are pregnant, nursing, or trying to become pregnant.
• Participation in another clinical study involving investigational study treatment within 30 days or 5 half-lives, whichever is longer, prior to screening.
• Any laboratory test results deemed clinically significant by the medical officer or lead psychiatrist or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening.
• Not suitable for study participation due to other reasons at the discretion of the study investigators
• Return a positive saliva drug test on the day of dosing, prior to session commencement.
• Blood alcohol reading above zero on the day of dosing, prior to session commencement.
• Donation of blood or blood product(s) >500mL within 30 days before screening.

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/09/2025

Actual

Date of last participant enrolment

Anticipated

30/09/2025

Actual

Date of last data collection

Anticipated

4/11/2025

Actual

Sample size

Target

4

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Tryptamine Theraputics

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Tryptamine Theraputics

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

Swinburne University of Technology Human Research Ethics Committee

Ethics committee address [1]

https://www.swinburne.edu.au/research/ethics/human-research/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

24/04/2025

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Orally administered psilocybin has shown promise as an effective treatment for a range of mental health disorders. Psilocybin is a prodrug that is rapidly converted in the body to its active form, psilocin. As such, the therapeutic effects observed in psilocybin studies are attributable to psilocin. TRP-8803 is a novel, intravenously administered formulation of synthesised psilocin. Previous studies conducted by the study Sponsor demonstrated that a hydrochloride (HCl) formulation of TRP-8803 was safe and well tolerated in healthy adult humans, with an acceptable pharmacokinetic profile. However, a new besylate formulation has been developed to enhance physicochemical stability and reduce hygroscopicity. These properties will support more reliable manufacturing, storage, and intravenous administration, without altering the identity of the primary psychoactive compound or safety profile of TRP-8803. This Phase 1 study will evaluate the safety and pharmacokinetics of TRP-8803 [Psilocin Besylate] in healthy adult participants to inform its further clinical development.

Trial website

Public notes

Contacts

Principal investigator

Name

Prof Susan Rossell

Address

Centre for Mental Health and Brain Sciences, Swinburne University of Technology, John Street, Hawthorn, VIC, 3122

Country

Australia

Phone

+61 3 92148173

Email

[email protected]

Contact person for public queries

Name

Dr Sean Carruthers

Address

Centre for Mental Health and Brain Sciences, Swinburne University of Technology, John Street, Hawthorn, VIC, 3122

Country

Australia

Phone

+61 3 92148173

Email

[email protected]

Contact person for scientific queries

Name

Dr Sean Carruthers

Address

Centre for Mental Health and Brain Sciences, Swinburne University of Technology, John Street, Hawthorn, VIC, 3122

Country

Australia

Phone

+61 3 92148173

Email

[email protected]

Trial Review

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Documents added automatically