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Trial registered on ANZCTR


Registration number
ACTRN12624001294549
Ethics application status
Approved
Date submitted
9/10/2024
Date registered
24/10/2024
Date last updated
15/12/2024
Date data sharing statement initially provided
24/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A 2-part Phase I study to evaluate the safety, tolerability, pharmacokinetics and food effects of AXN-027
Scientific title
A 2-part Phase I study to evaluate the safety, tolerability, pharmacokinetics including food effect and relative bioavailability of capsules vs tablets, and pharmacodynamic effects of AXN-027 in healthy adult volunteers
Secondary ID [1] 312970 0
AXN-027-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 335142 0
Condition category
Condition code
Neurological 331641 331641 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be confined at the site during the dosing period where dosing will be done via direct supervision and they can only participate in one of the following cohorts:
- Part 1 cohorts 1, 2, 4, 5 (oral capsule): Screening/ baseline period of up to 28 days with total duration up to 42 days. Single ascending doses of AXN-027 Salt between 100 mg and 1200 mg or placebo (Day 1) administered under fasting conditions. Increases will be based on safety and tolerability at each dose level.
-Part 1 cohort 3: (oral capsule and tablets): Screening/baseline period of up to 28 days with total duration up to 56 days. Three single doses of AXN-027 Salt between 100 mg and 1200 mg or placebo (one capsule and two tablets) administered either fasted or with a high fat, high calorie meal with a 7-day washout between each dose. According to FDA guidance, 'high fat' is an 800-1000 calorie meal with 60% of the calories from fat. An example of a high fat meal is two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes and eight ounces of whole milk - with the whole meal containing approximately 60% fat.
Part 1 cohort 6 (oral capsule): Screening/ baseline period of up to 28 days with total duration up to 42 days. Single doses of AXN-027 Salt between 100 mg and 1200 mg (Day 1) administered under fasting conditions .
- Part 2 (oral tablet): screening/ baseline period of up to 28 days with total duration up to 51 days. Twice daily doses of up to 600 mg AXN-027 Salt or placebo (Day 1-7 or Day 1-10) administered under fasting conditions
Exact dose of AXN-027 Salt for Part 1 cohorts 2-6 and Part 2 will be based on safety, tolerability and PK data from initial cohorts of Part 1. After all participants in a cohort are discharged from the site, a safety review committee (SRC) will determine if the next dose level cohort will be initiated. Each consecutive cohort will start approximately 2 weeks after the previous cohort are discharged from the site. Adherence to dosing will be assessed by direct observation of dosing at the site and site direct provision of dose for each timepoint.
Intervention code [1] 329500 0
Treatment: Drugs
Comparator / control treatment
Placebo capsules and placebo tablets that are the same in appearance as AXN-027 Salt capsules and tablets without the active ingredient
Control group
Placebo

Outcomes
Primary outcome [1] 339373 0
Part 1 and Part 2: Safety and tolerability of AXN-027 Salt will be assessed as a composite endpoint through an integrated analysis of the following assessments.
Timepoint [1] 339373 0
Part 1: D1, D2, D4, D11 post initial dose
Part 1: Food Effect Cohort: D1, D2, D3, D4, D8, D9, D10, D11, D15, D16, D17, D18, D25 post initial dose
Part 2: D1, D2, D3, D4, D5, D6, D7, D8, D9, D10, D17, D20 post initial dose
Secondary outcome [1] 439725 0
Part 1 Cohorts 1-2, 4-6: To evaluate the plasma pharmacokinetics (PK) of a single oral dose of AXN-027 Salt
Part 1 Cohort 3: To evaluate the plasma PK of a single oral dose of AXN-027 Salt administered as capsules and tablets, as well as to evaluate and and compare the plasma PK of a single oral dose of AXN-027 Salt tablets administered under fasted and fed states.
Part 2: To evaluate the plasma PK of multiple oral doses of AXN-027 Salt
Timepoint [1] 439725 0
Part 1 Cohorts 1-5:: predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose
Part 1 Cohort 6: predose and 1, 2, and 4 hours postdose
Part 2: predose and 0.25, 0.5, 1,1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose
Secondary outcome [2] 439726 0
Part 1 Cohorts 3-5: To evaluate the urine PK of a single oral dose of AXN-027 Salt
Part 2: To evaluate the urine PK of multiple oral doses of AXN-027 Salt
Timepoint [2] 439726 0
Part 1 Cohorts 3-5: Predose and 0-4, 4-8, 8-12, 12-24, 24-48 and 48-72 hours postdose
Part 2: Predose and 0-12 hours postdose
Secondary outcome [3] 439727 0
Part 1 Cohort 6: To evaluate the cerebrospinal fluid (CSF) levels of a single oral dose of AXN-027 Salt
Timepoint [3] 439727 0
Part 1 Cohort 6: 2 hours postdose

Eligibility
Key inclusion criteria
- Female or male and between the ages of 18 and 55 years, inclusive.
- Weight of at least 50 kg for men and at least 45 kg for women, with body mass index (BMI) between 18.5 and 32 kg/m2 (inclusive).
- Medically healthy (without significant medical issues, e.g. high blood pressure)
-Must 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
- Ongoing or history of any psychiatric, medical or surgical condition that might jeopardize the participant’s safety or interfere with the absorption, distribution, metabolism or excretion of the study drug.
- Any abnormal ECG findings, laboratory value or physical examination findings
- Positive ethanol, drug screen or cotinine test
- Use of systemic prescription medications or over-the-counter (OTC) medication, including multivitamins, and dietary and herbal supplement within 7 days
- Use of any experimental or investigational drug or device within 30 days
- Donation or loss of 480 mL or more of blood within 30 weeks and/or donation of plasma within 30 days

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)
All study participants who sign consent will receive a unique sequential number (i.e., a screening number).
Participants who meet the study eligibility criteria will be assigned a randomization number at check-in or predose on Day 1, which corresponds to a study treatment (AXN-027 Salt or placebo).
A sealed envelope containing the study drug assignment for each participant will be provided to the Investigator and kept in a secure location.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/12/2024
Actual
4/12/2024
Date of last participant enrolment
Anticipated
10/03/2025
Actual
Date of last data collection
Anticipated
30/04/2025
Actual
Sample size
Target
69
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 317402 0
Commercial sector/Industry
Name [1] 317402 0
Axonis Australia Pty Ltd
Country [1] 317402 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Axonis Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 319900 0
None
Name [1] 319900 0
Address [1] 319900 0
Country [1] 319900 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316127 0
Bellberry Human Research Ethics Committee D
Ethics committee address [1] 316127 0
Ethics committee country [1] 316127 0
Australia
Date submitted for ethics approval [1] 316127 0
25/09/2024
Approval date [1] 316127 0
24/10/2024
Ethics approval number [1] 316127 0

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

Contacts
Principal investigator
Name 136882 0
Dr Thomas Polasek
Address 136882 0
CMAX Clinical Research, Ground Floor, 21/24 North Terrace, Adelaide SA 5000
Country 136882 0
Australia
Phone 136882 0
+61 458 162 715
Fax 136882 0
Email 136882 0
Thomas.Polasek@cmax.com.au
Contact person for public queries
Name 136883 0
Jennifer Burg
Address 136883 0
Axonis Therapeutics, 75 Kneeland St, 14th Floor, Boston, MA
Country 136883 0
United States of America
Phone 136883 0
+1 617 674 3143
Fax 136883 0
Email 136883 0
clinicaltrials@axonis.us
Contact person for scientific queries
Name 136884 0
Donald Manning
Address 136884 0
Axonis Therapeutics, 75 Kneeland St, 14th Floor, Boston, MA
Country 136884 0
United States of America
Phone 136884 0
+1 617 674 3143
Fax 136884 0
Email 136884 0
clinicaltrials@axonis.us

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.