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Trial registered on ANZCTR


Registration number
ACTRN12619001485123
Ethics application status
Approved
Date submitted
17/10/2019
Date registered
28/10/2019
Date last updated
7/04/2020
Date data sharing statement initially provided
28/10/2019
Date results information initially provided
7/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Study of the Pharmacokinetics, Pharmacodynamics, and Safety of Oral Etifoxine in Normal Healthy Volunteers
Scientific title
A Phase 1, Two Stage, Double-Blind, Placebo-Controlled Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Oral Etifoxine in Normal Healthy Volunteers
Secondary ID [1] 299546 0
Gaba Therapeutics Protocol GRx-ETI-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anxiety 314807 0
Condition category
Condition code
Mental Health 313146 313146 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Stage 1: Etifoxine 100mg single oral dose (2 x 50mg capsules). This is an active to placebo crossover design. Subjects will receive the single oral dose of either etifoxine or placebo on Day 1 and then receive a single oral dose of the alternate treatment on Day 7. Subjects will receive all medication in the clinic

Stage 2: Etifoxine 100mg oral dose (2 x 50mg capsules) every 12 hours for 7 days. Participants will use a subject diary to ensure compliance with the medication regimen.

Participants in Stage 2 are different to those in Stage 1. The decision to proceed to Stage 2 will be based on the safety in Stage 1
Intervention code [1] 315799 0
Treatment: Drugs
Comparator / control treatment
Placebo control group. Placebo is a microcellulose capsule matched to the etifoxine capsule

Placebo is used in both Stage 1 and Stage 2 of the study
Control group
Placebo

Outcomes
Primary outcome [1] 321675 0
The primary outcome is a composite outcome of the serum concentrations of etifoxine and its key metabolite after a single oral dose of etifoxine
Timepoint [1] 321675 0
15, 30, 45, 60 and 90 minutes and 2, 3, 4, 5, 6, 8, 12 and 24 hours post dose
Primary outcome [2] 321676 0
The primary outcome is a composite outcome of the serum concentrations of etifoxine and its key metabolites after oral etofoxine dosed every 12 hours for 7 days
Timepoint [2] 321676 0
15, 30, 45, 60 and 90 minutes and 2, 3, 4, 5, 6, 8, 12 and 24 hours post dose on Day 1 and Day 7
Secondary outcome [1] 375850 0
This secondary outcome is a composite outcome of the serum concentrations of the circulating steroids allopregnanolone and pregnenolone after a single oral dose of etifoxine
Timepoint [1] 375850 0
15, 30, 45, 60 and 90 minutes and 2, 3, 4, 5, 6, 8, 12 and 24 hours post dose
Secondary outcome [2] 375851 0
This secondary outcome is a composite outcome of the serum concentrations of the circulating steroids allopregnanolone and pregnenolone after oral etifoxine dosed every 12 hours for 7 days
Timepoint [2] 375851 0
15, 30, 45, 60 and 90 minutes and 2, 3, 4, 5, 6, 8, 12 and 24 hours post dose on Day 1 and Day 7
Secondary outcome [3] 375852 0
Quantitative electroencephalogram changes measured through power spectral analysis after a single oral dose of etifoxine
Timepoint [3] 375852 0
15, 30, 45, 60 and 90 minutes and 2, 3, 4, 5, 6, 8, and 12 hours post dose
Secondary outcome [4] 375853 0
Quantitative electroencephalogram changes measured through power spectral analysis after oral etifoxine dosed every 12 hours for 7 days
Timepoint [4] 375853 0
15, 30, 45, 60 and 90 minutes and 2, 3, 4, 5, 6, 8, and 12 hours post dose on Day 1 and Day 7

Eligibility
Key inclusion criteria
1. Males aged between 18 and 65 years of age at time of consent
2. Agrees to and comply with using single barrier method of birth control or sexual abstinence, and not donate sperm, for the duration of the study and for 90 days after last dose of study drug.
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. Has a body mass index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2
5. Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the schedule of assessments
6. Willing to refrain from over-the-counter or prescription medications or herbal, nutritional or dietary supplements from 7 days before first dose through the EOS assessments, except for acetyl-para-aminophenol or in the case of necessary treatment of adverse events
7. Willing to refrain from alcohol from 48 hours before first dose through the last dose of study drug
8. 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.
9. Willing and able to provide written informed consent
Minimum age
18 Years
Maximum age
65 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known allergy or hypersensitivity to etifoxine or any of the excipients of etifoxine.
2. Has congenital galactosemia, glucose and galactose malabsorption syndrome or is lactose intolerant
3. History of seizures, convulsions or increased intra-cranial pressure with the exception of pediatric febrile seizures
4. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years prior to screening
5. 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. Clinically significant screening values measured after 5 minutes of rest in a supine position include:
a. Abnormal systolic blood pressure (<90 or > 140 mmHg)
b. Abnormal diastolic blood pressure (<40 or > 90 mmHg)
c. Abnormal respiratory rate (<10 or > 22 bpm)
6. Has a clinically significant history or presence of electrocardiogram (ECG) findings as judged by the PI or designee at screening, including:
a. Abnormal sinus rhythm (heart rate <50bpm or > 100 bpm);
b. Average QT interval corrected using Fridericia’s formula (QTcF) interval duration > 450 msec;
c. Average QRS interval > 120 msec after being confirmed by manual over-read
d. Average PR interval > 220 msec
7. Has clinically significant laboratory abnormalities including:
a. Impaired renal function (serum creatinine levels >106 µmol/L) at screening.
b. ALT or AST laboratory values >1.2X upper normal limits.
c. Subject has an estimated creatinine clearance of <80 mL/min as determined by the Cockcroft-Gault equation
8. History of moderate or severe substance abuse defined by the DSM-V criteria within 5 years prior to screening
9. History of alcohol abuse defined as an average daily intake >3 units, or an average weekly intake >21 units, where 1 unit is equivalent to 1 can or bottle (355mL) of beer, or 1 measure (25mL) of spirits, or 1 glass (175 mL) of wine within 5 years prior to screening
10. Positive alcohol breath test or urine test for drugs of abuse
11. Positive test results for hepatitis B surface antigen, hepatitis B core antibodies, hepatitis C virus antibody, and anti-human immunodeficiency virus (HIV) type 1 antibody
12. 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.
13. Has taken a Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) or Selective Serotonin Reuptake Inhibitor (SSRI) within 30 days prior to dosing.
14. Prior use of a 5-alpha reductase inhibitor (e.g., finasteride or dutasteride).
15. Has donated blood or plasma within 30 days prior to screening, or had a loss of whole blood of more than 50 mL within the 30 days prior to screening, or receipt of a blood transfusion within one year prior to screening
16. Has experienced symptoms of acute illness or chronic disease within 15 days prior to screening, or any disease or condition (medical or surgical) 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
17. Is from a vulnerable population as defined by ICH Guideline for GCP E6 (R2), including but not limited to, employees or family member of the research staff conducting the study, or of the Sponsor, or of the CRO, or the HREC
18. Is unable to cooperate fully with the requirements of the study protocol, including the schedule of assessments, or likely to be non-compliant with any study requirements
19. Other unspecified reasons that, in the opinion of the PI or Sponsor, make the subject unsuitable for enrollment.

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

Intervention assignment
Other
Other design features
Stage 1 is a crossover assignment to active or placebo
Stage 2 is a parallel assignment to active or placebo
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
All summary statistics will be descriptive unless noted otherwise. Descriptive summaries will include mean, standard deviation, median, and range for continuous variables and counts, and percentages for categorical variables. Two-sided 95% confidence intervals will be provided for the means and percentages as needed.

This is an exploratory study and therefore it is not powered for inferential statistical analyses. It is anticipated that approximately 30 normal healthy male volunteers will be enrolled. This sample size is commonly used in studies of this design to obtain sufficient information on the safety and PK.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14958 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 28244 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304034 0
Commercial sector/Industry
Name [1] 304034 0
Gaba Therapeutics Australia Pty Ltd a subsidiary of Gaba Therapeutics, Inc
Address [1] 304034 0
58 Gipps Street
Collingwood, VIC 3066
Country [1] 304034 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] 304226 0
None
Name [1] 304226 0
Address [1] 304226 0
Country [1] 304226 0
Other collaborator category [1] 280990 0
Commercial sector/Industry
Name [1] 280990 0
Avance Clinical Pty Ltd
Address [1] 280990 0
Level 1, 2 Ann Nelson Drive
Thebarton, SA 5031
Country [1] 280990 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304525 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 304525 0
55 Commercial road, Melbourne , Vic - 3004
Ethics committee country [1] 304525 0
Australia
Date submitted for ethics approval [1] 304525 0
30/10/2019
Approval date [1] 304525 0
25/11/2019
Ethics approval number [1] 304525 0

Summary
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of both single and multiple oral doses of an already approved drug called etifoxine.

This study will run in 2 stages and involve approximately 30 participants in total.

Stage 1 will evaluate the pharmacokinetics, pharmacodynamics and safety of single doses of etifoxine. This stage will enrol approximately 12 participants into a crossover design study where they will receive either etifoxine as a single dose or a placebo at the first visit and then they will receive the opposite intervention at the next visit 7 days later.

Stage 2 will evaluate the pharmacokinetics, pharmacodynamics and safety of multiple doses of etifoxine. This stage will enrol approximately 18 participants who will be randomised to receive either etifoxine or a placebo given every 12 hours for 7 days.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97262 0
Dr Ben Snyder
Address 97262 0
Nucleus Network Pty Ltd.
Address: Level 5, Burnet Tower, AMREP Precinct, 89 Commercial Road
Melbourne, VIC 3004
Country 97262 0
Australia
Phone 97262 0
+61 3 8593 9838
Fax 97262 0
Email 97262 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 97263 0
Ms Georgina Kilfoil
Address 97263 0
Gaba Therapeutics
58 Gipps Street
Collingwood, VIC 3066
Country 97263 0
Australia
Phone 97263 0
+61 0432 388 772
Fax 97263 0
Email 97263 0
gkilfoil@gabarx.com
Contact person for scientific queries
Name 97264 0
Ms Georgina Kilfoil
Address 97264 0
Gaba Therapeutics
58 Gipps Street
Collingwood, VIC 3066
Country 97264 0
Australia
Phone 97264 0
+61 0432 388 772
Fax 97264 0
Email 97264 0
gkilfoil@gabarx.com

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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary