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Trial registered on ANZCTR


Registration number
ACTRN12621000160831
Ethics application status
Approved
Date submitted
20/01/2021
Date registered
16/02/2021
Date last updated
27/06/2022
Date data sharing statement initially provided
16/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GRX-917 in Healthy Subjects
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of GRX-917 in Healthy Adult Subjects
Secondary ID [1] 302919 0
Protocol GRX-917-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anxiety 320777 0
Condition category
Condition code
Mental Health 317875 317875 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 76 healthy men or women will be enrolled in this study. There will be two parts to the study.

In the first part of the study approximately 40 healthy men and women will be enrolled in up to 5 single ascending dose cohorts comprising 8 subjects each. Subjects within each cohort will be randomised to receive a single dose of either oral GRX-917 (6 subjects) or oral placebo (2 subjects). All cohorts will be started with sentinel dosing. All doses will be administered under direct observation in the Phase 1 unit. The doses for each cohort are shown below
Cohort 1: 25mg
Cohort 2: 50mg
Cohort 3: 100mg
Cohort 4: 250mg
Cohort 5: 500mg

In the second part of the study approximately 36 healthy men and women will be enrolled into up to 3 multiple ascending dose cohorts comprising 12 subjects each. Subjects within each cohort will be randomised to receive multiple doses of either oral GRX-917 (9 subjects) or oral placebo (3 subjects). Each dose regimen will be administered for 7 days (13 total doses); dosing every 12 hours on Day 1 through Day 6 with a single last dose given on Day 7. All doses will be administered under direct observation in the Phase 1 unit. The doses for each cohort are shown below
Cohort 1: 100mg every 12 hours
Cohort 2: 200mg every 12 hours
Cohort 3: 300mg every 12 hours
Intervention code [1] 319206 0
Treatment: Drugs
Comparator / control treatment
Placebo control group. Placebo is a capsule filled with microcrystalline cellulose matched to the GRX-917 capsule
Control group
Placebo

Outcomes
Primary outcome [1] 325893 0
To evaluate the safety of single doses of GRX-917 when compared with placebo in healthy volunteers through the assessment of: treatment-emergent adverse events assessed through regular solicitation of volunteers and review of physical examination data, vital sign data including blood pressure measured using a digital blood pressure monitor, heart rate measured as beats per minute, temperature assessed using a digital thermometer and respiratory rate measured using a manual counting of breaths per minute, sedation scored on the Ramsay sedation scale, ECG data including continuous telemetry, and clinical laboratory assessments of blood and urine: hematology (standard panel), chemistry (standard panel) and urinalysis (standard panel)
Timepoint [1] 325893 0
Treatment-emergent adverse events will be collected from the time of signing the informed consent form through the final follow-up visit which is on Day 11 for Cohorts 1, 2, 4, and 5, and on Day 25 for Cohort 3,
Physical examinations in Cohort 1, 2, 4 and 5 will be conducted at screening, on Day -1, Day 3, and Day 11. Physical examinations in Cohort 3 will be conducted at screening, on Day -1, Day 3, Day 14, Day 17 and Day 25.
Clinical laboratory assessments of blood and urine in Cohort 1, 2, 4 and 5 will be collected at screening, on Day -1, Day 2, and Day 11. Clinical laboratory assessments of blood and urine in Cohort 3 will be collected at screening, on Day -1, Day 2, Day 14, Day 16 and Day 25.
ECGs in Cohort 1, 2, 4 and 5 will be collected at screening, pre-dose on Day 1, and at 4, and 24 hours post dose, and on Day 11. ECGs in Cohort 3 will be collected at screening, on Day 1 pre-dose and at 4, and 24 hours post dose, on Day 15 pre-dose and at 4, and 24 hours post dose, and on Day 25.
Continuous telemetry in Cohorts 1, 2, 4 and 5 will be collected for at least 16 hours prior to dosing and for 24 hours after dosing on Day 1 pre-dose. Continuous telemetry in Cohort 3 will be collected for at least 16 hours prior to dosing and for 24 hours after dosing on Day 1 and on Day 15.
Vital signs in Cohorts 1, 2, 4 and 5 will be collected at screening, on Day -1, on Day 1 pre-dose and 1, 2, 4, 8, 12, 24 and 48 hours post dose, and on Day 11. Vital signs in Cohort 3 will be collected at screening, on Day -1, on Day 1 pre-dose and 1, 2, 4, 8, 12, 24 and 48 hours post dose, on Day 14, on Day 15 pre-dose and 1, 2, 4, 8, 12, 24 and 48 hours post dose and on Day 25.
In Cohort 1, 2, 4, and 5 sedation will be scored on Day 1 pre-dose and at 1, 2, 4, 8, 12, 24 and 48 hours post dose and on Day 11. In Cohort 3, sedation will be scored on Day 1 pre-dose and at 1, 2, 4, 8, 12, 24 and 48 hours post dose, on Day 15 pre-dose and at 1, 2, 4, 8, 12, 24 and 48 hours post dose and on Day 25.
Primary outcome [2] 325964 0
To evaluate the safety of multiple doses of GRX-917 when compared with placebo in healthy volunteers through the assessment of: treatment-emergent adverse events assessed through regular solicitation of volunteers and review of physical examination data, vital sign data including blood pressure measured using a digital blood pressure monitor, heart rate measured as beats per minute, temperature and respiratory rate measured as breaths per minute, ECG data and clinical laboratory assessments of blood and urine: hematology (standard panel), chemistry (standard panel) and urinalysis (standard panel)
Timepoint [2] 325964 0
Treatment-emergent adverse events will be collected from the time of signing the informed consent form through the final follow-up visit which is on Day 17,
Physical examinations will be conducted at screening, on Day -1, Day 3, Day 5, Day 9 and Day 17..
Clinical laboratory assessments of blood and urine will be collected at screening, on Day -1, Day 2, Day 3, Day 5, Day 7, Day 8 and Day 17.
ECGs will be collected at screening, and pre-dose and 4 hours post dose on Day 1, Day 3 , Day 5, and Day 7, prior to discharge on Day 9 and on Day 17
Continuous telemetry will be collected for at least 16 hours prior to dosing and until 24 hours after the last dosing on Day 7.
Vital signs will be collected at screening, on Day -1, within 2 hours prior to and 2, 4, 8 and 12 hours after the first dose of study drug on Days 1 to 7, on Day 8 at 24 hours post-dose, and Day 9 prior to discharge and on Day 17.
Sedation will be scored on Day 1 pre-dose and at 2, 4, 8, and 12, hours post first dose on Days 1 to 7, on Day 8, on Day 9 and on Day 17.
Secondary outcome [1] 389707 0
This outcome is a composite outcome of the plasma concentrations of GRX-917 and its key metabolite after a single oral dose of GRX-917
Timepoint [1] 389707 0
In Cohorts, 1, 2, 4 and 5, samples will be collected on Day 1 pre-dose and then at 30 and 60 minutes, and 2, 4, 6, 8 and 12 hours after dosing. A 24-hour post dosing sample will be collected on Day 2 and a 48-hour post dosing sample will be collected on Day 3 prior to discharge. Additional samples will be collected on Day 5, Day 7, Day 9 and on Day 11.

In Cohort 3, samples will be collected on Day 1 pre-dose and then at 30 and 60 minutes, and 2, 4, 6, 8 and 12 hours after dosing. A 24-hour post dosing sample will be collected on Day 2 and a 48-hour post dosing sample will be collected on Day 3 prior to discharge. Additional samples will be collected on Day 5, Day 7, Day 9. On Day 15 a sample will be collected pre-dose and then at 30 and 60 minutes, and 2, 4, 6, 8 and 12 hours after dosing. A 24-hour post dosing sample will be collected on Day 16 and a 48-hour post dosing sample will be collected on Day 17 prior to discharge. Additional samples will be collected on Day 19, Day 21, Day 23 and Day 25.
Secondary outcome [2] 389708 0
This outcome is a composite outcome of the plasma concentrations of GRX-917 and its key metabolite after multiple oral doses of GRX-917
Timepoint [2] 389708 0
On Day 1, samples will be collected pre-dose and then at 30 and 60 minutes, and 2, 4, 6, 8, 10 and 12 hours after dosing. A 24-hour post dosing sample will be collected prior to the first study drug dose on Day 2. On Day 4, Day 5, and Day 6, samples will be collected immediately prior to the first dose of study drug for that day. On Day 7, samples will be collected pre-dose and then at 30 and 60 minutes, and 2, 4, 6, 8, 10 and 12 hours after dosing. A 24-hour post dosing sample will be collected on Day 8 and a 48-hour sample will be collected on Day 9 prior to discharge. Additional samples will be collected on Day 11, Day 13, Day 15 and on Day 17.
Secondary outcome [3] 389709 0
This outcome is a composite outcome of the urine concentrations of GRX-917 and its key metabolite after a single oral dose of GRX-917
Timepoint [3] 389709 0
On Day 1, urine will be collected predose and then pooled urine will be collected at 0-4, 4-8, 8-12, 12-24 and 24-48 hours after dosing.
Secondary outcome [4] 389710 0
This outcome is a composite outcome of the urine concentrations of GRX-917 and its key metabolite after multiple oral doses of GRX-917
Timepoint [4] 389710 0
On Day 1, urine will be collected predose and then pooled urine will be collected at 0-4, 4-8, and 8-12 hours after dosing. On Day 7, pooled urine will be collected at 0-4, 4-8, and 8-12 hours after the final dose of study drug.
Secondary outcome [5] 389711 0
Quantitative electroencephalogram changes measured through power spectral analysis after a single oral dose of GRX-917
Timepoint [5] 389711 0
Recordings collected pre-dose and then at 30 and 60 minutes, and 2, 4, 6, 8 and 12 hours after the first dose of GRX-917.

Eligibility
Key inclusion criteria
1. Aged between 18 and 55 years of age at time of consent
2. Male or female and meet the following conditions:
a. Female participants must be of non-childbearing potential, or,
b. If of childbearing potential, be non-pregnant or lactating and agree to use highly effective contraception from screening through 30 days post- dose. Hormonal forms of contraception are contraindicated in this study.
c. Male participants, if engaging in sexual intercourse with a female partner of childbearing potential, must be willing to use highly effective contraception from screening through 90 days post-dose and agree not to donate sperm during this period.
3. Is judged to be in good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests performed at the screening visit and/or before the first dose of study drug.
4. Weigh at least 50 kg at the time of screening
5. Have a body mass index (BMI) between 18.0 and 32.0 kg/m2 at the time of screening
6. Negative SARS-CoV2 test on Day -2 per site standards
7. Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the schedule of assessments
8. Willing to refrain from will refrain from any systemic or topical medication, including herbal supplements taken within 6 times the elimination half-life of the medication or within 14 days of the first dose administration, whichever is longer.
9. Willing and able to refrain from consuming any strong inhibitors or inducers of CYP3A4 and CYP2B6 within 30 days prior to dosing
10. Willing to refrain from alcohol and caffeine from 48 hours before first dose through the last dose of study drug
11. Subjects who smoke no more than 2 cigarettes or equivalent per week can be included in the study but must be willing to abstain from smoking during the confinement period.
12. Willing and able to provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of seizures, convulsions or increased intra-cranial pressure with the exception of pediatric febrile seizures
2. History of moderate or severe psychiatric illness
3. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years prior to screening
4. History of cardiovascular, cerebrovascular, or peripheral vascular disease, including, but not limited to, unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, hypertension, hypotension, bradycardia, or tachycardia.
5. Has a clinically significant history or presence of electrocardiogram (ECG) findings as judged by the PI or designee at screening
6. Has clinically significant laboratory abnormalities
7. History of moderate or severe substance abuse within 5 years prior to screening
8. History of alcohol abuse within 5 years prior to screening
9. Positive alcohol breath test or urine test for drugs of abuse
10. Positive test results for hepatitis B surface antigen, hepatitis B core antibodies, hepatitis C virus antigen, and anti-human immunodeficiency virus (HIV) type 1 antibody
11. Has received treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer) prior to dosing; prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable.
12. Has taken a Serotonin-Norepinephrine Reuptake Inhibitors or Selective Serotonin Reuptake Inhibitor or benzodiazepine within 30 days prior to dosing.
13. Prior use of a 5-alpha reductase inhibitor within 3 months prior to dosing.
14. Has donated blood or plasma within 30 days prior to screening, or had a loss of whole blood of more than 500 mL within the 30 days prior to screening, or receipt of a blood transfusion within one year prior to screening
15. Has experienced symptoms of acute illness or chronic disease within 14 days prior to screening, or any disease or condition that, by the determination of the PI, might compromise interpretation of safety or PK data, or would place the subject at risk as a result of participation in the study.

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated simple randomisation sequence
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
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This is an exploratory study and therefore it is not powered for inferential statistical analyses. It is anticipated that approximately 76 healthy male or female adult subjects will be enrolled. This sample size is commonly used in studies of this design to obtain sufficient information on the safety, tolerability and PK.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/06/2021
Actual
3/06/2021
Date of last participant enrolment
Anticipated
1/11/2021
Actual
26/05/2022
Date of last data collection
Anticipated
17/11/2021
Actual
11/06/2022
Sample size
Target
76
Accrual to date
Final
102
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18174 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 32175 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 307340 0
Commercial sector/Industry
Name [1] 307340 0
Gaba Therapeutics Australia Pty Ltd a subsidiary of Gaba Therapeutics, Inc
Country [1] 307340 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Gaba Therapeutics Australia Pty Ltd a subsidiary of Gaba Therapeutics, Inc
Address
58 Gipps Street
Collingwood, VIC 3066
Country
Australia
Secondary sponsor category [1] 307980 0
None
Name [1] 307980 0
Address [1] 307980 0
Country [1] 307980 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307427 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 307427 0
Ethics committee country [1] 307427 0
Australia
Date submitted for ethics approval [1] 307427 0
22/02/2021
Approval date [1] 307427 0
29/03/2021
Ethics approval number [1] 307427 0

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

Contacts
Principal investigator
Name 107206 0
Dr Ben Snyder
Address 107206 0
Nucleus Network,
Level 5, Burnet Building, AMREP Precinct
89 Commercial Rd,
Melbourne, VIC 3004
Country 107206 0
Australia
Phone 107206 0
+61 3 3593 9817
Fax 107206 0
Email 107206 0
[email protected]
Contact person for public queries
Name 107207 0
Georgina Kilfoil
Address 107207 0
Gaba Therapeutics
58 Gipps Street
Collingwood, VIC 3066
Country 107207 0
Australia
Phone 107207 0
+61 432388772
Fax 107207 0
Email 107207 0
[email protected]
Contact person for scientific queries
Name 107208 0
Georgina Kilfoil
Address 107208 0
Gaba Therapeutics
58 Gipps Street
Collingwood, VIC 3066
Country 107208 0
Australia
Phone 107208 0
+61 432388772
Fax 107208 0
Email 107208 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be made available for this study. All subject data obtained will be de-identified and captured in a final study report that will not identify individual participants.


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.