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Trial registered on ANZCTR


Registration number
ACTRN12622000713796
Ethics application status
Approved
Date submitted
14/03/2022
Date registered
18/05/2022
Date last updated
17/04/2023
Date data sharing statement initially provided
18/05/2022
Date results information initially provided
27/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Double-Blind, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single, Ascending, Subcutaneous Doses of FT-104 HCl In Healthy Volunteers
Safety, Tolerability, and Pharmacokinetics of Subcutaneous FT-104 HCl (SAIL-101)
Scientific title
A Double-Blind, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single, Ascending, Subcutaneous Doses of FT-104 HCl In Healthy Volunteers
Safety, Tolerability, and Pharmacokinetics of Subcutaneous FT-104 HCl (SAIL-101)
Secondary ID [1] 306500 0
FT-104-101
Universal Trial Number (UTN)
Trial acronym
SAIL-101
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post Partum Depression
 325364 0
Treatment Resistant Depression 326318 0
Condition category
Condition code
Mental Health 322749 322749 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a study of safety, tolerability and pharmacokinetics of a single ascending dose of FT-104 HCl in healthy volunteers. It is cohort designed with up to 6 cohorts of eight participants, where 6 will receive FT-104 HCl and two will receive placebo as a sub-cutaneous injection in the upper arm in the Clinical Research Unit. The dose escalation decisions between cohorts will be managed by a Safety Review Committee.
Eligibility will be assessed during a screening period of up to 28 days prior to dosing. For the treatment period, subjects will be admitted to the clinical research unit (CRU) one day prior to the dosing (Day -1). Randomisation will occur on the morning of dosing (Day 1).
On Day 1, all subjects will receive the assigned subcutaneous dose of FT-104 HCl or placebo. Participants will be discharged from the clinic on Day 2 (~24 hours post-dose) after all required study procedures are completed and if deemed medically fit. Subjects will return to the clinic on Day 10 (± 2 days) for a follow up visit.
Up to 6 cohorts may be enrolled in the study. Four (4) single doses are planned to be tested in 4 cohorts (Cohort 1 to Cohort 4) of up to 8 healthy volunteers (up to 6 active and 2 placebo). Two (2) additional ascending dose levels (Cohort 5 and Cohort 6), each consisting of up to 8 subjects (up to 6 active and 2 placebo), may be added based on emerging safety, tolerability, and PK data.
The following dose levels are planned for the study:
• Cohort 1: 5.5 mg FT-104 HCl or placebo
• Cohort 2: 11 mg FT-104 HCl or placebo
• Cohort 3: 22 mg FT-104 HCl or placebo
• Cohort 4: 33 mg FT-104 HCl or placebo
• Cohort 5: 44 mg FT-104 HCl or placebo
Cohort 6: 38mg FT-104 HCl or placebo
The highest dose that may be evaluated is 52.7 mg FT-104 HCl.
Sentinels will be used in all cohorts. Within each cohort, 2 subjects will be treated first: 1 subject will receive FT-104 HCl and 1 subject will receive placebo. Provided no clinically significant safety issues, are noted at least in the 24 hours following the sentinels’ dosing, as judged by the Principal Investigator (PI), the remaining 6 subjects of the cohort can be dosed (5 active, 1 placebo).
Intervention code [1] 322927 0
Treatment: Drugs
Comparator / control treatment
This study is placebo controlled.
Each dose cohort will have a total of eight (8) participants. Of these, two will receive placebo. The placebo is Normal Saline (0.9% sodium chloride) for injection.
Control group
Placebo

Outcomes
Primary outcome [1] 330552 0
Adverse event data will be collected from the time of consent until the last study visit (Day 10). Examples of expected adverse events include mild headache and mild lethargy immediately after administration. Some transient changes in mood and /or mental state such as anxiety, panic, paranoid/delusional thinking could occur, Adverse event data collection will occur at each interaction with the subject from the time of informed consent. Subjects will also be instructed to inform the investigator or clinic staff of any AEs or inter-current illnesses experienced during the study. Adverse events may also be recorded from observations from laboratory tests, ECG measurements, physical examination. The Investigator will decide the severity of the event (mild, moderate or severe) based on guidance contained in the study protocol.
Safety Laboratory Tests from blood (biochemistry, haematology) and from urine (urinalysis)
Vital sign data: blood pressure - measured by sphygmomanometer; pulse rate measured manually; body temperature measured by tympanic or oral thermometer. Assessment of vital signs may occur at additional time points, at the investigator’s discretion.
ECG measurements (measured using a 12 Lead ECG Machine). Injection site observations will be performed by qualified medical personnel to assess local tolerability. Systematic assessment of suicidal ideation and behavior will be assessed by using Columbia-Suicide Severity Rating Scale.
All AEs will be assessed for severity (mild, moderate, severe) by the Investigator, causality to study drug and study procedures (related, unrelated), outcome (recovered/resolved recovering/resolving, recovered/resolved with sequelae, not recovered/not resolved, fatal, based on guidance contained in the study protocol. Adverse events (AEs) and SAEs’s will be coded using the most current MedDRA available at the time of study commencement (Version 24.1 or greater).
Timepoint [1] 330552 0
Adverse event data will be collected from the time of consent until the last study visit (Day 10)
Safety Laboratory Tests (biochemistry, haematology, urinalysis) are collected at Screening, Day -1, Day 2 and Day 10
Vital signs assessments will be conducted at screening, on Day -1, on Day 1 (at 30 min ± 15 min predose and at 1 h ± 15 min, 4h ± 15 min, 8h ± 30 min, 12h ± 30 min post-dose), on Day 2 (24 h ± 30 min post-dose), and on Day 10 or early termination visit.
ECG Data will be collected at screening, on Day -1, on Day 1 (at 30 minutes [min] ± 15 min pre-dose and at 1 hour [h] ± 15 min, 4h ± 15 min, 8h ± 30 min, 12h ± 30 min post-dose), on Day 2 (24 h ± 30 min post-dose), and on Day 10 or early termination visit.
Secondary outcome [1] 406648 0
To investigate the pharmacokinetics (PK) properties of single escalating doses of FT-104 HCl administered subcutaneously.
The measured individual plasma concentrations of FT-104 and isoprocin will be used to directly obtain Cmax and Tmax.
AUC0-t will be calculated according to the linear up/log down trapezoidal method using the measured concentration-time values above the lower limit of quantification (LLOQ). AUC0-inf will be calculated by combining AUC0-t and Extrapolated portion of the AUC (AUCextrap). AUCextrap represents an extrapolated value obtained by Ct/(lambda)Z, where Ct is the last plasma concentration measured above the LLOQ and (lambda)Z represents the terminal elimination rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase. The half-life of FT-104 and isoprocin will be calculated as follows: t1/2 = ln 2/(lambda)Z.
The PK parameters will be calculated using actual blood sampling times [hours, h] (relative to the corresponding administration time), and negative pre-dose times will be set to zero. PK parameters will be listed and summarized with descriptive statistics (number of available observations, mean, median, standard deviation, min, max, coefficient of variation as a percent [%CV], geometric mean and geometric %CV).
The PK population will be used for the PK parameter summaries.
Dose proportionality following single dose administration will be assessed using the power model. Plasma PK parameters Cmax and AUCs, will be assessed by fitting the following power model and determining the 90% confidence interval for ß:
Parameter = a x Doseß
Where a 90% confidence interval for ß that includes 1 indicates dose proportionality.
Timepoint [1] 406648 0
Blood for the assessment of PK will be collected at the following time points: Pre-dose, 3 ± 1 min, 7 ± 1 min, 15 ± 2 min, 30 ± 2 min, 45 ± 2 min, 60 ± 5 min, 75 ± 5 min, 90 ± 5 min, 2 h ± 10 min, 3h ± 10 min, 4h ± 20 min, 5h ± 20min, 6h ± 30 min, 8h ± 30 min, 12h ± 30 min, 16h ± 30 min and 24h (Day 2) ± 30 min post-dose.

Eligibility
Key inclusion criteria
1. Signed informed consent in a language understandable to the subject prior to any study-related procedure.
2. The subject has at least one prior recreational experience with hallucinogenic or psychedelic compounds
3. The subject weighs at least 60kg and has a BMI between 18 - 30 kg/m2
4. Women of childbearing potential (WOCBP) must be non-lactating and have a negative pregnancy test. Females who are not WOCBP must be either surgically sterile or post-menopausal.
5. In the opinion of the investigator, the subject is capable of understanding and is willing and able to comply with all conditions and requirements of the study.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subject has current or a history of any clinically significant illness which may affect safety, or potentially confound the study results.
2. Subject has current or a history of clinically significant mental disorders as assessed by questionnaire and interview by a qualified medical personnel professional at screening.
3. Subject has a risk of suicide per the Columbia-Suicide Severity Rating Scale (C-SSRS) or has a history of suicidal ideation or suicidal behavior.
4. Immediate (1st degree) blood-related family members, or personal currently or previously diagnosed with psychotic or bipolar disorder.
5. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks prior to screening.
6. Subject has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to screening.
7. Previous major adverse response to a hallucinogenic or psychedelic drug, as determined by the qualified/trained investigator.
8. Use of ayahuasca, kambó, yopo, ibogaine, psilocybin, dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), Syrian Rue, or other psychedelic agents or mixtures in their synthetic or naturally-occurring form, and use of amphetamines, opioids, or 3,4-Methylenedioxymethamphetamine (MDMA), in the 90 days before screening and through to EOS/ET.
9. Use of synthetic or naturally-occurring cannabinoids from 28 days prior to study drug administration and agree not to use through to EOS/ET.
10. Subject has a positive cotinine at screening or on Day -1.
11. Positive alcohol breath test or urine screen for drugs of abuse at screening or on Day -1.
12. Subject has a history of drug abuse
13. Excessive alcohol consumption
14. Consumption of products containing caffeine, xanthine or poppy seeds from 48 hours prior to study drug administration until last PK sample had been collected.
15. Participation in another clinical study involving study treatment within 30 days or 5 half-lives, whichever is longer, prior to screening.
16. Administration of any vaccine within 28 days prior to study drug administration and through to through to EOS/ET.
17. Use of any psychoactive medication (e.g., a selective serotonin reuptake inhibitor such as paroxetine or citalopram) haloperidol or a medication with monoamine oxidase (MAO) activity (such as isocarboxazid, phenelzine, selegiline or tranylcypromine, linezolid, and methylene blue) within 28 days prior to study drug administration and through to EOS/ET.
18. Any positive results for serum hepatitis B surface antigen (HbsAg), hepatitis C antibody and human immunodeficiency virus (HIV) at screening.
19. Resting (for at least 5 minutes) systolic blood pressure > 140 or < 90 mmHg or resting diastolic blood pressure > 90 or < 40 mmHg; Resting (for at least 5 minutes) pulse rate outside the range of < 40 or > 100 beats/min at screening or at any time point prior to study drug administration.
20. Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting electrocardiogram (ECG),

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation to FT-104 HCl or placebo will be made by the study pharmacist referring to a randomization list held by the pharmacist. The physicians and nurses conducting the study will be unaware of the allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The study sample size is not based on any statistical testing or formal statistical power calculation. The sample sizes selected are appropriate for this FIH study with FT-104 HCl and should be sufficient to fulfill the objectives of this study. This study does not include formal hypothesis testing, and all statistics will be descriptive.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
29/06/2022
Actual
20/07/2022
Date of last participant enrolment
Anticipated
23/03/2023
Actual
23/03/2023
Date of last data collection
Anticipated
3/04/2023
Actual
3/04/2023
Sample size
Target
48
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 21798 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 36856 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 310844 0
Commercial sector/Industry
Name [1] 310844 0
Field Trip Psychedelics Inc
Country [1] 310844 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Field Trip Psychedelics Inc
Address
30 DUNCAN STREET,
SUITE 400,
TORONTO, ON, CANADA
M5V 2C3
Country
Canada
Secondary sponsor category [1] 312099 0
Commercial sector/Industry
Name [1] 312099 0
Beyond Drug Development Pty Ltd
Address [1] 312099 0
17 Brereton St
South Brisbane QLD 4101
Country [1] 312099 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310409 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 310409 0
Level 3, Roma Mitchell House
136 North Terrace
Adelaide, South Australia, 5000
Ethics committee country [1] 310409 0
Australia
Date submitted for ethics approval [1] 310409 0
25/02/2022
Approval date [1] 310409 0
20/06/2022
Ethics approval number [1] 310409 0

Summary
Brief summary
This is a first in human study designed to investigate the safety, tolerability and pharmacokinetics of a single dose of FT-104 HCL in healthy volunteers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117562 0
Prof Guy Ludbrook
Address 117562 0
Level 4G.1 East, Royal Adelaide Hospital,
Port Road, Adelaide,
South Australia, Australia 5000.
Country 117562 0
Australia
Phone 117562 0
+61 8 7074 1544
Fax 117562 0
Email 117562 0
Guy.Ludbrook@sa.gov.au
Contact person for public queries
Name 117563 0
Prof Guy Ludbrook
Address 117563 0
Level 4G.1 East, Royal Adelaide Hospital,
Port Road, Adelaide,
South Australia, Australia 5000.
Country 117563 0
Australia
Phone 117563 0
+61 8 7074 1544
Fax 117563 0
Email 117563 0
Guy.Ludbrook@sa.gov.au
Contact person for scientific queries
Name 117564 0
Prof Guy Ludbrook
Address 117564 0
Level 4G.1 East, Royal Adelaide Hospital,
Port Road, Adelaide,
South Australia, Australia 5000.
Country 117564 0
Australia
Phone 117564 0
+61 8 7074 1544
Fax 117564 0
Email 117564 0
Guy.Ludbrook@sa.gov.au

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.