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Trial registered on ANZCTR


Registration number
ACTRN12624000547549
Ethics application status
Approved
Date submitted
2/01/2024
Date registered
1/05/2024
Date last updated
1/05/2024
Date data sharing statement initially provided
1/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Open-label, Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of a Single Intravenous Infusion of TRP-8803 (Psilocin) in Healthy Adult Participants
Scientific title
A Phase 1, Open-label, Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of a Single Intravenous Infusion of TRP-8803 (Psilocin) in Healthy Adult Participants
Secondary ID [1] 309940 0
TRYP-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mental Health 330423 0
Condition category
Condition code
Mental Health 327258 327258 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase 1, open-label, 3-cohort study. Participants will be prescreened for interest and eligibility and, after completion of the informed consent form, will complete screening assessments. Psilocin will be administered in the Clinical Research Unit (CRU), and participants will be kept overnight for safety observation and PK sampling. Each of the 3 cohorts will comprise 3 participants who will receive a single TRP-8803 IV infusion in an open-label fashion. At least a 1-day interval will be scheduled for psilocin administration between sequential subjects within a cohort. Participants will remain on site during the single dose IV infusion

Cohort 1: 7.5 mg total psilocin (1.5 mg/20 min + 6 mg/120 min [0.05 mg/min])

Cohort 2: 14 mg total psilocin (3.0 mg/20 min + 11 mg/120 min [0.10 mg/min])

Cohort 3: 20.5 mg total psilocin (4.5 mg/20 min + 16 mg/120 min [0.15 mg/min])

In Cohort 1, participants will receive a total of 7.5 mg psilocin; Cohort 2 will receive a total of 14mg psilocin, and Cohort 3 will receive a total of 20.5mg of psilocin. The initial 20minute loading dose infusion will provide a therapeutic dose of psilocin that will be maintained by infusing either 0.05 mg/minute (min), 0.10 mg/min, or 0.15 mg/min psilocin by IV over 120 minutes.

After each dose in the ascending dose study, the Safety Review Committee (SRC) will perform a PK and safety data review before advancing to the next dose. Dose escalation will stop in the unlikely event that any participant in that dose cohort exhibits an increased risk of harm to self or others, or any other sign that continuing in the study would present undue risks or has an adverse event (AE) related to the intervention such as psychosis or hypertension during the infusion.

Safety will be assessed by measuring incidence of AEs and SAEs and physical examination, vital signs, ECG, clinical laboratory, suicidality findings, and Persistent Effects Questionnaire. PK will be measured at designated times predose to 24 hours postdose.
Intervention code [1] 326363 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335139 0
To assess the safety of a single 140-minute IV infusion of TRP 8803 in healthy participants administered as a 20-minute initial loading dose followed by 120 minute infusion for a total of 11, 14, or 20.5 mg psilocin
Timepoint [1] 335139 0
Safety is measured as a composite outcomes by the incidence of AE and SAE; physical examination, vital signs, ECG, clinical laboratory, and suicidality findings from the time of dosing to EOT visit ( 4 weeks post dose)
Secondary outcome [1] 423234 0
To determine the plasma concentrations and PK profile of TRP-8803 after IV administration as a composite outcome
Timepoint [1] 423234 0
PK descriptions of TRP-8803 exposure including Cmax, Tmax, t1/2, AUC0-8, AUC0-24, and AUC0-t after an IV dose of TRP-8803 of plasma samples collected at 0 (pre-dose), 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours after the start of the infusion.
Secondary outcome [2] 423235 0
Grading of the psychedelic experience post dose using the MEQ30
Timepoint [2] 423235 0
Grading of the psychedelic experience at 6 and 24 hours post dose, and then 14 days post dose.
Secondary outcome [3] 432220 0
Qualitative description of the psychedelic experience postdose using AWES, CEQ, EBI, and PEQ
Timepoint [3] 432220 0
Grading of the psychedelic experience at 6 and 24 hours post dose, and then 14 days post dose

Eligibility
Key inclusion criteria


1. Overtly healthy and medically stable in the judgment of the Principal Investigator, as determined by screening medical history, physical examination, ECG, and no clinically significant laboratory abnormality detected on routine blood tests and urinalysis.

2. Male and female participants, age 18 to 55 years, inclusive, at the time of signing the ICF.

3. Weight between 50kg and 120kg, inclusive; and body mass index (BMI) between 20 and 30, inclusive.

4. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

5. Has adequate venous access for IV administration and for PK blood sampling.

6. Contraceptive use by women and men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

a. 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.

b. 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.

7. WOCBP must have a negative serum pregnancy test at Screening, and negative urine pregnancy test at Baseline and on psilocin administration day (confirmed before psilocin administration). A WOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

a. has not undergone a hysterectomy or bilateral oophorectomy, or

b. has not been naturally postmenopausal for at least 12 consecutive months (ie, has had menses at any time in the preceding 12 consecutive months)

8. Agrees to refrain from using any legal psychoactive substance (except for caffeine, described below), for the following defined time periods:

a. Must be non- or ex-smokers (tobacco) and not use other nicotine-containing products from 90 days prior to study drug administration until participant study termination; or use less than 5 tobacco or nicotine-containing products a week by self-report and have a negative cotinine test at Screening and Dose Day (prior to dosing).

b. Alcohol for 72 hours prior to the psilocin administration visit by self-report

9. 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.

10. 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 study investigators. Exceptions will include acetaminophen, non-steroidal anti-inflammatory drugs, common doses of vitamins and minerals, and contraceptives.

11. 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 Principal Investigator. No pro re nata (PRN) medications are allowed on the morning of study intervention administration.

12. If the participant routinely consumes caffeinated beverages, he/she must agree to stop consuming all caffeine-containing products at least 48 hours prior to the psilocin administration day and for the period of confinement in the clinical unit.

Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria

1. Currently meets diagnostic criteria for any Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) psychiatric condition as assessed by the MINI.

2. Prior history of primary psychotic disorder (unless substance-induced or due to a medical condition), bipolar disorder Type I or Type II, or schizophrenia, as determined by the MINI.

3. Concurrent or recent (within 5 years) history of major depressive disorder, obsessive compulsive disorder, generalized anxiety disorder, panic disorder, anorexia nervosa or bulimia nervosa, overeating disorder, post traumatic stress disorder, or substance use disorder as determined by the MINI and psychiatric history.

4. First degree family history of primary psychotic disorder, bipolar disorder Type I or Type II, or schizophrenia, as determined via the Family History Screen form conducted by trained staff.

5. 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.

NOTE: If a participant cannot complete the assessment, the site must document this.

6. Participant has a history of alcohol abuse disorder within 1 year prior to screening or regular abuse of alcohol within 3months prior to the screening visit (defined as consistently consuming more than 10 units of alcohol per week [1 unit=150mL of wine, 360mL of beer, or 45mL of 40% alcohol]).

7. Meets DSM-5 criteria for substance use disorder (other than alcohol) within the past 12 months.

8. Vital signs of systolic BP >160mm Hg, diastolic BP >95mm Hg, and HR >100 bpm on 2 or more consecutive readings within 15 minutes.

9. Have any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, prior myocardial infarction, tachycardia, artificial heart valve, QTc interval >470msec (women) or >450msec (men), PR >220msec, or QRS >120msec at the Screening visit, any other clinically significant screening ECG abnormality, or any other significant cardiovascular condition at the Principal Investigator’s discretion.

10. Currently under treatment for epilepsy.

11. Blood chemistry test prior to study intervention administration as follows:

a. Any liver function test with results greater than 1.5 times the ULN

b. Estimated glomerular filtration rate (by Cockcroft & Gault) less than 60mL/min

12. 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). If urine drug test at Screening is positive, a repeat test may be conducted up until Day 1 (the end of the Screening period) at the discretion of the Principal Investigator or delegate.

13. Prior adverse effects from psilocybin or other psychedelics based on self-report.

14. Currently taking (within 5 half-lives of Visit 5, Dose Day) prohibited medications, including antihypertensive medications, UDP Glucuronosyltransferase Family 1 Member A9 (UGT1A9) or intestinal UDPglucuronosyltransferases 1A10 inhibitors (eg, regorafenib, rifampicin, phenytoin, eltrombopag, mefenamic acid, diflunisal, niflumic acid, sorafenib, isavuconazole, deferasiroxor, ginseng), and aldehyde or alcohol dehydrogenase inhibitors (eg, disulfiram).

15. Currently (for at least 2 weeks; or at least 4 weeks for fluoxetine) taking an antidepressant.

16. Participation in another concurrent clinical study or use of investigational drugs, or biologics within 5 half-lives or 30 days (whichever is longer), or investigational devices within 30 days prior to the Baseline visit (Day 1/Visit 2).

17. Not suitable for study participation due to other reasons at the discretion of the study investigators.

18. Women who are pregnant, lactating, or planning on becoming pregnant during the study

19. Unwilling to withhold prohibited concomitant medications.



Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
24/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
9
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 314119 0
Commercial sector/Industry
Name [1] 314119 0
Tryp Therapeutics, Inc.
Country [1] 314119 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Tryp Therapeutics, Inc.
Address
301 - 1632 Ellis Street Kelowna, BC V1Y 2B#
Country
Canada
Secondary sponsor category [1] 316034 0
None
Name [1] 316034 0
None
Address [1] 316034 0
None
Country [1] 316034 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313256 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 313256 0
Ethics committee country [1] 313256 0
Australia
Date submitted for ethics approval [1] 313256 0
18/10/2023
Approval date [1] 313256 0
11/01/2024
Ethics approval number [1] 313256 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127498 0
Dr sepehr shakib
Address 127498 0
Cmax Clinical Research, 21-24 North Terrace, Adelaide SA 5000
Country 127498 0
Australia
Phone 127498 0
+61 08 7088 7900
Fax 127498 0
Email 127498 0
Sepehr.shakib@cmax.com.au
Contact person for public queries
Name 127499 0
Daniel Engeler
Address 127499 0
iNGENu CRO, Unit 11, 456 St Kilda Road, Melbourne, 3004
Country 127499 0
Australia
Phone 127499 0
+61 0422156206
Fax 127499 0
Email 127499 0
daniel.engeler@ingenucro.com
Contact person for scientific queries
Name 127500 0
James Gilligan
Address 127500 0
Try Therapeutics, 301 - 1632 Ellis Street Kelowna, BC V1Y 2B3
Country 127500 0
Canada
Phone 127500 0
+1 908 727 3312
Fax 127500 0
Email 127500 0
jgilligan@tryptherapeutics.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.