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Trial registered on ANZCTR


Registration number
ACTRN12623000860662
Ethics application status
Approved
Date submitted
20/07/2023
Date registered
10/08/2023
Date last updated
11/08/2024
Date data sharing statement initially provided
10/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Food Effect of GT-02287 in Healthy Participants
Scientific title
A First-in-Human, Randomized, Double-blind, Dose Escalation, Single and Multiple Ascending Dose (SAD/MAD) Study to Assess the Safety, Tolerability, Pharmacokinetics, and Food Effect of GT-02287 in Healthy Participants
Secondary ID [1] 310026 0
GANX-001-V101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's Disease 330560 0
Condition category
Condition code
Neurological 327401 327401 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single centre, randomized, double-blind, placebo-controlled study of single and multiple ascending doses of GT-02287 in healthy volunteers.

This study will consist of 2 parts: single and multiple ascending doses of GT-02287. Participants will provide informed consent and undergo screening for the study no more than 28 days prior to Day 1. Eligible participants will check in to the clinical research unit (CRU) on Day -1, the day prior to dosing. All participants in both parts will attend a Follow-up Visit scheduled 7-10 days after their last dose of IP, or after early termination.

- Part 1 (single ascending doses; SAD):
Study participants will be randomly assigned to receive a single dose of GT-02287 or placebo administered as an oral solution on day 1. There will be 5 ascending dose cohorts in this part with 8 participants per cohort. Sentinel dosing will occur within each cohort. The first 2 participants assigned to each cohort will be randomized 1:1 to GT02287 or placebo. The remaining 6 participants in each cohort will be randomized 5:1 to GT02287 or placebo, for an overall 3:1 randomization ratio for each cohort, including cohort 4.
- Cohort 1: 2.4 mg/kg
- Cohort 2: 4.8 mg/kg
- Cohort 3: 7.7 mg/kg
- Cohort 4: 10 mg/kg, then another 10 mg/kg after at a 1-to-2-week washout (FE)
- Cohort 5: 12 mg/kg

Participants in Part 1 will be confined to the CRU from Day -1 to Day 4, with a single dose of IP administered on Day 1. Participants in Cohort 4 only (the FE cohort) will be recalled, following investigator review of safety data, after a 1-to-2-week washout of their Day 1 dose of IP to assess impact of FE on safety and PK of single dose GT02287. Participants in the FE cohort will be re-admitted to the CRU on FE Day -1 and confined until FE Day 4, with a second single dose of the same allocated treatment on FE Day 1 in a fed state.

The enrollment of the next dose cohort will begin only after review of the safety and tolerability data (through Day 4) and available plasma PK data (through the 60-hour post dose sample) for at least 6 out of 8 participants of the previous dose cohort.

Part 2 (multiple ascending doses; MAD):
This part can begin once safety, tolerability, and PK data are available from the first 3 dose levels from Part 1. Progression to MAD will be confirmed by a blinded Safety Review Committee (SRC). Study participants will be randomly assigned to receive multiple doses of GT 02287 or placebo administered as an oral solution once a day for 14 days. Participants will be confined from Day -1 to Day 17, with once-a-day dosing from Day 1 to Day 14. There will be 4 ascending dose cohorts in this part with 8 healthy adult participants per cohort. The sentinel dosing will not be used, and all participants will be directly randomized in a 3:1 ratio (6 participants will receive GT-02287 and 2 will receive placebo).
- Cohort 1: 2.4 mg/kg/day
- Cohort 2: 4.8 mg/kg/day
- Cohort 3: 7.7 mg/kg/day
- Cohort 4: 10 mg/kg/day

For all cohorts in both parts, all doses of IP will be administered in a fasted state (other than the second dose for the FE cohort). In Part 1, participants will fast overnight for at least 10 hours before their dose in the morning, followed by an additional 4-hour postdose fast. In Part 2, participants will fast for at least 8 hours overnight predose, followed by an additional 4-hour postdose fast. Water will be allowed as often as desired except for the intervals from 1 hour before dosing to 1 hour after dosing.

The second dose of the FE cohort in part 1 will be used to evaluate single-dose PK under fed conditions. Before their dose in the morning, participants will fast for at least 10 hours overnight, then eat a high-fat (=50 percent of total caloric content of the meal), high-calorie (approximately 800 to 1000 calories) meal 30 minutes prior to dose administration. The high-fat meal should be consumed within 30 minutes or less and IP should be administered 30 minutes after the start of the meal. Participants will then fast for at least 4 hours postdose. Water will be allowed as often as desired except the intervals from 10 minutes before dosing to 1 hour after dosing.

Individual doses will be provided for participants by Clinical Reasearch Unit staff on the day of administration in 60 mL amber glass bottles with a polypropylene top seal and screw cap. All participants will receive the IP at the study site under the surveillance of appropriate study personnel.
Intervention code [1] 326451 0
Treatment: Drugs
Comparator / control treatment
Placebo (magnesium aluminometasilicate) will be provided as a powder for oral suspension in vehicle (VIT-E TPGS 2.5% w/w in water). Study participants randomized to receive placebo will have the placebo administered as an oral solution by the study staff in an identical manner to GT-02287.
Control group
Placebo

Outcomes
Primary outcome [1] 335277 0
To evaluate the safety and tolerability of single and multiple ascending oral doses of GT-02287 in healthy adult participants. Safety will be assessed by evaluation of the Incidence, nature, and severity of all adverse events (AEs) from Screening to Follow-up visit, including time of onset/offset from administration of GT 02287.
Timepoint [1] 335277 0
Part 1:
AEs: Day-1, Day1, Day2, Day 3, Day 4, early termination and follow-up.

Part 2:
AEs: Day-1, Day1, Day2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, early termination and follow-up.
Primary outcome [2] 335279 0
To evaluate the safety and tolerability of single and multiple ascending oral doses of GT-02287 in healthy adult participants. Safety will be assessed by evaluation of the Incidence of clinically significant findings for:
- Clinical laboratory evaluations (hematology, coagulation, biochemistry, and urinalysis)
- Physical and neurological examinations
- Vital signs measurements (tympanic temperature, resting pulse, and resting pressure [BP])
- 12-lead electrocardiograms (ECGs)
Timepoint [2] 335279 0
Part 1:
- Clinical laboratory evaluations: Screening, Day-1, Day 1 (2 hours postdose), Day2 (24 hours postdose), Day 4, early termination and Follow-up.

- Physical and neurological examinations: Screening, early termination and follow-up

- Vital signs measurements: Screening, Day-1, Day 1 (within 1 hour predose), Day2, Day 3, Day 4, early termination and Follow-up

- ECGs: to be performed after the participant has been supine for at least 5 minutes in triplicate at screening, Day -1, Day 1 at 2 hours postdose, Day 4, early termination and follow-up.

Part 2:
- Clinical laboratory evaluations: Screening, Day-1, Day 3 (within 1 hour predose), Day 6 (within 1 hour predose), Day 10 (within 1 hour predose), Day 13 (within 1 hour predose and at 2 hours postdose), Day 17, early termination and Follow-up.

- Physical and neurological examinations: Screening, early termination and follow-up

- Vital signs measurements: Screening, Day-1, Day 1 (within 1 hour predose), Day2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (within 1 hour predose), Day 15, Day 16, Day 17, early termination and follow-up.

- ECGs: to be performed after the participant has been supine for at least 5 minutes in triplicate at screening, Day -1, Day 1 (2 hours postdose), Day 14 (2 hours postdose), Day 17, early termination and follow-up.
Primary outcome [3] 335280 0
To evaluate the safety and tolerability of single and multiple ascending oral doses of GT-02287 in healthy adult participants. Safety will be assessed by evaluation of Questionnaires: Bond and Lader Visual Analogue Scale (BL-VAS), Profile of Mood States Short Form (POMS-SF) and Columbia Suicide Severity Rating Scale (C SSRS).
Timepoint [3] 335280 0
Part 1:
- C-SSRS: screening, Day-1, Day1, Day2, Day 3 and Day 4 and early termination
- BL-VAS: screening, Day 1 (within 1 hour predose and 6 hours postdose), Day 2 and Day 3
- POMS-SF: screening, Day 1 (within 1 hour predose and 6 hours postdose), Day 2 and Day 3

Part 2:
- C-SSRS: screening, Day-1, Day 1, Day 2, Day 3, Day 8, Day 14, Day 17 and early termination
- BL-VAS: screening, Day 1 (within 1 hour predose and 6 hours postdose), Day 2, Day 3, Day 8 and Day 14
- POMS-SF: screening, Day 1 (within 1 hour predose and 6 hours postdose), Day 2, Day 3, Day 8 and Day 14
Secondary outcome [1] 423717 0
To evaluate the PK of single and multiple ascending oral doses of GT 02287 in healthy adult participants. PK parameters of GT 02287, other parameters, as appropriate, including dose-adjusted parameters, following a single dose and/or multiple doses of GT 02287.
Timepoint [1] 423717 0
Part 1:
Blood sampling for PK of GT 02287 to take place on:
- Day 1 predose, and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 12 hours postdose;
- Day 2 at 24 hours postdose; and
- Day 3 at 48 and 60 hours postdose.
Every effort should be made to collect PK samples at their scheduled time, with predose samples collected within 30 minutes of dosing.

Part 2:
Planned blood sampling for PK of GT-02287 at:
- Day 1: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 and 18 hours postdose;
- Day 2: 24 hours post Day 1 dose just before the Day 2 administration;
- Day 7: predose,
- Day 11: predose,
- Day 12: predose,
- Day 13: predose,
- Day 14: predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 and 18 hours postdose
- Day 15: 24, 30 and 36 hours post Day 14 dose;
- Day 16: 48 and 60 hours post Day 14 dose.
PK sampling in MAD might be adjusted based on the results of SAD.
Secondary outcome [2] 423718 0
Part 1 Cohort 4 only: To evaluate Food Effect on the safety, tolerability, and PK of a single oral dose of GT-02287 in healthy adult participants. Safety and PK parameters as described in primary endpoints above following a single dose of GT 02287 under fed conditions.
Timepoint [2] 423718 0
- AE(s): Day-1, Day 1, Day 2, Day 3, Day 4, - (1- to 2-week washout) - FE Day -1, FE Day 1, FE Day 2, FE Day 3, FE Day 4, early termination and follow-up.

- Clinical laboratory evaluations: Screening, Day -1, Day 1 (2 hours postdose), Day 2 (24 hours postdose), Day 4 - (1- to 2-week washout) - FE Day -1, FE Day 1 (2 hours postdose under non-fasted conditions), FE Day 2 (24 hours postdose), FE Day 4, early termination and follow-up

- Vital signs measurements: Screening, Day-1, Day 1 (within 1 hour predose), Day 2, Day 3, Day 4, - (1- to 2-week washout) - FE Day -1, FE Day 1 (within 1 hour predose), FE Day 2, FE Day 3, FE Day 4, early termination and Follow-up

- ECGs: to be performed after the participant has been supine for at least 5 minutes in triplicate at screening, Day -1, Day 1 (2 hours postdose), Day 4, - (1- to 2-week washout) - FE Day -1, FE Day 1 (2 hours postdose), FE Day 4, early termination and follow-up.

- C-SSRS: screening, Day-1, Day 1, Day 2, Day 3, Day 4, - (1- to 2-week washout) - FE Day -1, Day 2, FE Day 3, FE Day 4 and early termination

- BL-VAS: screening, Day 1 (within 1 hour predose and 6 hours postdose), Day 2, Day 3, (1- to 2-week washout) - FE Day 1 (within 1 hour predose and 6 hours postdose), FE Day 2 and FE Day 3

- POMS-SF: screening, Day 1 (within 1 hour predose and 6 hours postdose), Day 2, Day 3, (1- to 2-week washout) - FE Day 1 (within 1 hour predose and 6 hours postdose), FE Day 2 and FE Day 3

- PK sample: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 12 hours postdose); Day 2 (24 hours postdose); Day 3 (48 and 60 hours postdose), - (1- to 2-week washout) - FE Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 12 hours postdose); FE Day 2 (24 hours postdose); FE Day 3 (48 and 60 hours postdose).
Secondary outcome [3] 425031 0
Exploratory outcome in Part 2 only: To investigate the pharmacodynamic response to GT-02287 in blood in healthy adult participants. Pharmacodynamic parameters to be analyzed will be GCase protein levels and GCase enzyme activity of GT-02287.
Timepoint [3] 425031 0
Participants in Part 2 only will provide samples for pharmacodynamics at Day 1: predose and 2, 6, and 12 hours postdose, Day 11: predose and 12 hours postdose, Day 14: predose and 2, 6, and 12 hours postdose.

Participants will also be asked to optionally provide 1 additional blood sample at each timepoint planned for pharmacodynamic blood sampling. These samples will be
collected for research purposes as de-identified healthy controls to be used in connection with clinical studies that may be done in the future with GT-02287 in patients with PD or other conditions.

Eligibility
Key inclusion criteria
1. Participant must be able and willing to provide written informed consent and be willing to comply with the requirements and restrictions of the study.
2. Participant is of any sex, >/=18 and < /=65 years of age.
3. Participant has a body mass index >/=18 and < /=32 kg/m2 at Screening.
4. Participant is not pregnant and not lactating.
5. If participant is either of childbearing potential or produces potentially viable sperm, participant must agree to use 2 forms of contraception (barrier method and a second highly effective form of birth control/contraception, as per definitions below) if engaging in potentially reproductive intercourse (with a partner who produces potentially viable sperm or is of childbearing potential, respectively) from Screening until at least 30 or 90 days respectively following final study dose administration:
- Barrier method: condom, diaphragm or cap
AND
- Second highly effective form of birth control/contraception: established use of oral, injected, intravaginal, or implanted hormonal contraception (combined or progestogen-only, associated with inhibition of ovulation), intrauterine device, or intrauterine hormone-releasing system
Note: A participant is considered to be of childbearing potential if they are postmenarchal and premenopausal, unless surgically sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or physiologically incapable of becoming pregnant. A postmenopausal state is defined as no menses for at least 1 year without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration >/= 40 IU/L.
6. Participant must agree to not donate ova or sperm from Screening until at least 30 or 90 days respectively following final study dose administration.
7. Participant must agree to not participate in another investigational study while taking part in this study.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Participant has a suspected hypersensitivity to GT-02287 or excipients.
2. Participant has AST, ALT, alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT] or TBIL >1.5 × ULN at Screening. If a participant is initially excluded due to this criterion, the assessment may be repeated once at the investigator’s discretion prior to Day -1.
3. Participant has any clinically significant history of allergies (including drug allergies, allergic eczema, or anaphylactic reactions, but excluding untreated allergic rhinitis or rhinoconjunctivitis caused by seasonal or house dust mite allergy).
4. Participant has a history of suicidal behavior or suicide attempts (an answer of “yes” to any lifetime suicidal behaviors on the C-SSRS), has had any active suicidal ideation within the last 3 months before Screening (an answer of “yes” to categories 4 or 5 of the C SSRS), or who is at significant risk to commit suicide, as judged by the investigator using the C-SSRS at Screening.
5. Participant has or had an active febrile illness or a symptomatic viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 2 weeks before Day -1.
6. Participant has any clinically significant abnormality following the Investigator’s review of the physical examinations, ECG, and clinical laboratory tests at Screening or on Day -1. If a participant is initially excluded due to this criterion, the assessment may be repeated once at the investigator’s discretion prior to Day -1.
7. Participant has the below mean pulse rate, systolic blood pressure (SBP), or diastolic blood pressure (DBP) when measured at rest in triplicate at Screening or Day -1:
- Mean pulse rate <45 or >100 beats per minute.
- Mean SBP >160 mmHg.
- Mean DBP >95 mmHg.
If the mean pulse, mean SBP, or mean DBP is out of the range specified above, 1 additional triplicate measurement may be taken at Screening or on Day -1. If this triplicate also gives an abnormal result, the participant should be excluded.
8. Participant has a mean QT interval corrected using Fridericia’s Formula (QTcF) of >450 msec (for males) and >470 msec (for females) at Screening or Day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken. If this triplicate also gives an abnormal result, the participant should be excluded.
9. Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease, or a family history of long QT syndrome.
10. Participant has a history of seizures, head trauma, or loss of consciousness.
11. Participant uses any prescribed or nonprescribed drugs (including vitamins, dietary supplements, hormone replacement therapy, natural and herbal remedies, e.g., St. John’s Wort) within 2 weeks or 5 half-lives (whichever is longer) before Day -1. Paracetamol at doses up to 2 g/day and hormonal birth control/contraception is allowed.
12. Participant has used cigarettes (or equivalent nicotine-containing product) within 4 weeks prior to Screening or has urine cotinine >200 ng/mL level at Screening or on Day -1. If a participant is initially excluded due to this criterion, the assessment may be repeated once at the investigator’s discretion prior to Day -1.
13. Participant has a history of consuming more than 14 units of alcoholic beverages per week (note: 1 unit equal to 250 mL of beer, 100 mL of wine, or 30 mL of spirits/hard liquor) within 6 months prior to Screening, has a history of alcoholism within 2 years prior to Screening, or has a positive alcohol breath test at Screening or Day -1. If a participant has a positive alcohol breath test at Screening, the assessment may be repeated once at the investigator’s discretion prior to Day -1. A positive test on Day 1 is exclusionary.
14. Participant has excessive caffeine consumption (defined as greater than 4 cups per day of caffeinated coffee, tea, soda, energy drinks and/or other beverages containing caffeine, or equivalent in chocolate, supplements, or other sources of caffeine) within 2 weeks prior to Day -1.
15. Participant is unable to refrain from consumption of grapefruit, grapefruit juice, Seville oranges, star fruit, or pomelo fruit within 7 days prior to Day 1 and for the duration of the study.
16. Participant has used amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates (drugs of abuse) within 3 months before Day -1 or has a positive urine drug screen at Screening or Day -1. If a participant has a positive urine drug screen at Screening, the assessment may be repeated once at the investigator’s discretion prior to Day -1.
17. Participant has used medications known to interfere with the CYP3A4 and/or P-glycoprotein metabolic pathways in the 3 months prior to Day -1.
18. Participant has used dietary supplements or herbal remedies known to interfere with the CYP3A4 and/or P-glycoprotein metabolic pathways in the 4 weeks prior to Day -1.
19. Participant has had any significant blood loss (equal to 450 mL), donated 1 unit (equal to 450 mL) of blood, or received a transfusion of any blood or blood products within 60 days before Day -1, or has donated plasma within 7 days before Day -1.
20. Participant has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus immunoglobulin M antibodies (anti-HAV IgM), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus 1 and 2 antibodies (anti-HIV-1, anti-HIV-2).
21. Participant has a history of malabsorption, inflammatory bowel disease, pancreatitis, irritable bowel disease, cholecystectomy, Gilbert’s Syndrome, or any other clinically relevant disorder which may impact the absorption of GT 02287.
22. Participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the investigator or designee. A history of childhood asthma that is resolved (in the opinion of the investigator) is not exclusionary.
23. Participant has current or recent history (within the past 6 months) of recurrent headache (e.g., tension-type, cluster, or migraine with a frequency of >/=2 episodes per month and requiring treatment), which, in the opinion of the investigator, precludes participation in the study.
24. Participant has a history of severe depression, or mild/moderate depression lasting >/=3 months, requiring hospitalization and/or pharmacological therapy, or recent history (within the past 6 months) of any other psychiatric condition which, in the opinion of the investigator, precludes participation in the study.
25. Participant’s estimated glomerular filtration rate (calculated based on Cockcroft-Gault formula) is <60 mL/min/1.73 m2.
26. Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 3 months or 5 half-lives, whichever is longer, before Screening.
27. Participant is an employee of the Gain Therapeutics group, or any vendor involved in the study.
Food effect cohort exclusion criterion:
28. Participant has any allergies, intolerances, or dietary preferences that prevents them from consuming the high-fat breakfast.

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)
Computer generated randomization schema that will be sent to the unblinded pharmacist.
The allocation is concealed and involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization schedule will be computer generated using a permuted block algorithm and will randomly allocate IP to randomization numbers. The randomization numbers will be assigned to participants sequentially as they are entered into the study.
Cohort 1 of Part 2 may begin enrollment following completion of Cohort 3 in Part 1, following approval by the SRC. Participants who meet study entry criteria will be randomized to GT 02287 or placebo upon admission to the CRU.

Part 1 (single ascending doses; SAD) consists of up to 5 cohorts of 8 healthy adult participants, each receiving a single oral dose of investigational product (IP; GT-02287 or placebo) in a 3:1 ratio.

Part 2 (multiple ascending doses; MAD) consists of up to 4 cohorts of 8 healthy adult participants, each receiving oral GT 02287 or placebo in a 3:1 ratio once a day (QD) for 14 days.
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Single ascending dose and multiple ascending dose cohorts.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Analysis Populations:
- The Safety Analysis Set (SAS) will be the primary analysis set for all safety assessments and will consist of all participants who received at least 1 dose of IP.
- The PK Analysis Set (PKAS) will be the primary analysis set for all PK analyses and will consist of all participants from the SAS with sufficient plasma concentration data available to facilitate the calculation of at least one PK parameter.
- The PD Analysis Set (PDAS) will consist of all participants from the SAS who received at least 1 dose in Part 2 with sufficient plasma data available to facilitate the calculation of at least one PD parameter.
Protocol deviations affecting PK or PD variables will be determined during a pre-analysis review of the data prior to database lock. Participants with confirmed important protocol deviations will be excluded from the PKAS/PDAS, respectively.

Participant Characteristics and Disposition:
Participant characteristics will be summarized overall and by cohort using descriptive statistics for all participants enrolled in the study. Continuous variables will be summarized using descriptive statistics (number of observations, mean, standard deviation [SD], minimum, median, maximum, geometric mean, and coefficient of variation [CV%]). Categorical variables will be described using absolute and relative frequency.
The disposition of all participants enrolled will be summarized overall and by cohort, including the number of participants randomized, the number assigned to each analysis population, the number completing the study, and the number discontinued from the study (along with discontinuation reason).

Safety Analyses:
Safety will be assessed by evaluation of AEs, clinical laboratory values, vital signs, ECG readings, physical and neurological examination results, and the C-SSRS, BL VAS, and POMS-SF assessment scales.
All AEs (from Screening through Follow-up Visit) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA®) Version 26.0 or higher, by preferred term and system organ class.
Clinically significant safety variables will be summarized by cohort.

The C-SSRS, BL-VAS, and POMS-SF assessment scales will be summarized using descriptive statistics by cohort. Mean and absolute value change from baseline at each post-baseline measurement will be provided.

Pharmacokinetic Analyses:
Descriptive statistics for GT 02287 concentrations and calculated PK parameters will be provided, and will include sample size, mean, SD, median, minimum, maximum, geometric mean, and CV%.
Dose-proportionality analysis will be performed as an exploratory analysis.

Pharmacodynamic Analyses:
Descriptive statistics for calculated pharmacodynamic parameters will be provided, and will include sample size, mean, SD, median, minimum, maximum, geometric mean, and CV%.

Sample size:
The sample size for this study is designed to evaluate preliminary safety and PK data, but not to show statistically significant differences between groups. The sample size of 8 participants per cohort (6 active + 2 placebo) in both parts of the study, with the possibility to expand each cohort to a maximum of 12 total participants (9 active + 3 placebo), is considered sufficient to evaluate the SAD and MAD safety profile and provide sufficient PK information.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/09/2023
Actual
28/09/2023
Date of last participant enrolment
Anticipated
3/05/2024
Actual
20/06/2024
Date of last data collection
Anticipated
15/07/2024
Actual
25/07/2024
Sample size
Target
72
Accrual to date
Final
73
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 25075 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 40740 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 314205 0
Commercial sector/Industry
Name [1] 314205 0
Gain Therapeutics, Inc.
Country [1] 314205 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Gain Therapeutics, Australia Pty Ltd
Address
Gain Therapeutics, Australia Pty Ltd
c/- Prime Accounting & Business Advisory Pty Ltd
Level 17 HWT Tower, 40 City Road
Southbank VIC 3006, Australia
Country
Australia
Secondary sponsor category [1] 316140 0
None
Name [1] 316140 0
Address [1] 316140 0
Country [1] 316140 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313331 0
Bellberry Limited HREC
Ethics committee address [1] 313331 0
Ethics committee country [1] 313331 0
Australia
Date submitted for ethics approval [1] 313331 0
20/07/2023
Approval date [1] 313331 0
04/09/2023
Ethics approval number [1] 313331 0

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

Contacts
Principal investigator
Name 127762 0
Dr Michele de Sciscio
Address 127762 0
CMAX Clinical Research
Ground Floor, 21-24 North Terrace
Adelaide, SA 5000
Country 127762 0
Australia
Phone 127762 0
+61 422 447 902
Fax 127762 0
Email 127762 0
michele.desciscio@sa.gov.au
Contact person for public queries
Name 127763 0
Michele de Sciscio
Address 127763 0
CMAX Clinical Research
Ground Floor, 21-24 North Terrace
Adelaide, SA 5000
Country 127763 0
Australia
Phone 127763 0
+61 422 447 902
Fax 127763 0
Email 127763 0
michele.desciscio@sa.gov.au
Contact person for scientific queries
Name 127764 0
Michele de Sciscio
Address 127764 0
CMAX Clinical Research
Ground Floor, 21-24 North Terrace
Adelaide, SA 5000
Country 127764 0
Australia
Phone 127764 0
+61 422 447 902
Fax 127764 0
Email 127764 0
michele.desciscio@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.