ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12626000686303

Ethics application status

Approved

Date submitted

4/05/2026

Date registered

10/06/2026

Date last updated

10/06/2026

Date data sharing statement initially provided

10/06/2026

Type of registration

Prospectively registered

Titles & IDs

Public title

Single and multiple dose study of XYL-2499 in healthy adults

Scientific title

Phase 1, Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose, Multiple Ascending Dose to Evaluate the Safety, Tolerability, and Pharmacokinetics of XYL-2499 in Healthy Adult Participants

Additional trial identifiers [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Related trial records

Health condition

Health condition(s) studied:

Depression

Condition category

Condition code

Mental Health

Depression

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

Part A (Single Ascending Dose)
Part A will comprise a total of 6 sequential cohorts with up to 42 participants.
Cohort A1 will include 2 participants, of whom 1 will be randomised to receive XYL-2499 and 1 to placebo.
Cohorts A2 to A6 will each include 8 participants, with 6 participants randomized to receive XYL-2499 and 2 to receive placebo (3:1 ratio). Dosing will be performed in a double-blinded manner.
The escalation in dosing will be done in sequential cohorts. The starting dose will be 1 mg and subsequent dose levels will be decided by the Dose Level Review Committee (DLRC), but escalation steps will not exceed 3-fold increases.
Enrolment into the next cohort will commence after the DLRC has reviewed the data from the cohort and has made the decision that it is safe to dose escalate. The maximum dose is capped at a pre-specified exposure and the specific doses for each cohort will be determined from safety and pharmacokinetic data.

Total of up to 42 participants:
Cohort A1 (1 mg): n = 1 XYL-2499, n = 1 placebo
Cohort A2 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo
Cohort A3 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo
Cohort A4 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo
Cohort A5 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo
Cohort A6 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo

Part B (Multiple Ascending Dose)
Part B will comprise 3 cohorts of 8 participants each to receive a daily dose of the allocated treatment for a period of 1 week. The planned dose level must have already been assessed in the SAD part of the study and determined to be safe.
The 1-week treatment cycle will consist of a dose of allocated treatment administered daily (QD) for a period of 1 week. All dosing will be performed in a double-blind manner. At minimum, the first (Day 1) and last (Day 7) doses should be performed after an overnight fast of at least 8 hours. For standardization purposes, doses on other study days should also be performed after an overnight fast.

Escalation in dosing will be done in sequential cohorts. XYL-2499 doses will be determined by the Dose Level Review Committee (DLRC). Enrolment into the next cohort will commence after the DLRC has reviewed the data and has made the decision that it is safe to dose escalate.

Total of 24 participants:
Cohort B1 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo
Cohort B2 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo
Cohort B3 (Dose Level TBD): n = 6 XYL-2499, n = 2 placebo

For Part A (SAD) and Part B (MAD):
Adherence to monitoring the intervention will be ensured through site-based supervised dosing by study staff. Drug accountability will be maintained, including reconciliation of administered doses. As dosing is conducted in a controlled clinical setting, no additional participant-led adherence measures (e.g., tablet return) are applicable.

Intervention code [1]

Treatment: Drugs

Description of the comparator or control

The comparator used in this study is a commercially available oral solution that does not contain the active investigational product, XYL-2499. The placebo formulation consists of Ora-Sweet® SF, a sugar-free oral suspending and sweetening vehicle commonly used in clinical research and pharmaceutical compounding. The placebo will be administered orally in a volume matched to that of the active XYL-2499 formulation to ensure comparability between treatments. Components are purified water, glycerin, sorbitol, sodium saccharin, xanthan gum and flavouring, buffered with sodium citrate and preserved with methyl paraben, potassium sobate and propyl paraben.

Control group

Placebo

Outcomes

Primary outcome [1]

Composite assessment of safety and tolerability following single and multiple ascending dose administration of XYL-2499, evaluated by the incidence of adverse events (AEs), changes in vital signs, electroencephalograms (EEGs), electrocardiograms (ECGs), clinical laboratory parameters, and findings from neurological, physical, and suicide risk assessments.

Assessment method [1]

AEs: Adverse events (AEs) will be assessed by monitoring the incidence, severity, seriousness, timing, duration, and relationship to XYL-2499, with all treatment-emergent AEs recorded from dosing through end of follow-up in accordance with the protocol. Examples of known or possible AEs, as identified in the Investigator’s Brochure, include headache, nausea, anxiety, dizziness, elevated blood pressure, and increased heart rate. Vital Signs: Pulse rate will be measured using a calibrated digital monitor or cardiac monitor; blood pressure will be measured using an automated sphygmomanometer; oxygen saturation will be assessed using pulse oximetry; respiratory rate will be measured by direct observation (breaths per minute); and body temperature will be measured using a digital thermometer. Measurements will be taken in a seated or supine position, as appropriate, after adequate rest. Electroencephalograms (EEGs): EEGs will be performed for both safety monitoring, and pharmacodynamic assessment. Screening and Day 1 Predose EEGs will have 60 minutes recording. All Post Dose EEGs will have 30 minutes recording. Electrocardiograms (ECGs): Pulse rate, PR interval, QRS duration, QT interval, QTcF interval ECG will be performed in a supine position, and in triplicate. Triplicate ECG readings will be taken and are to be within 2 to 5 minutes of each other Mean (average of the 3). Laboratory parameters: Clinical Chemistry, Hematology, Coagulation, Urinalysis. Neurological Examination: Neurological examination is to be completed to assess: 1. Cranial Nerves: testing of the cranial nerves, focusing on pupillary response, extraocular movements, facial symmetry, hearing, and tongue movement. 2. Motor Function: Evaluation of muscle strength in upper and lower extremities, testing major muscle groups bilaterally and noting asymmetries. 3. Coordination and Gait: Finger-to-nose testing, rapid alternating movements, heel-toshin testing, and observation of gait, finger rolling and forearm rolling. 4. Reflexes: Deep tendon reflexes including biceps (C5 to C6), triceps (C7), patellar (L2 to L4), and ankle (S1), graded on a 0 to 5 scale. 5. Sensation: Testing of light touch, pain, temperature, vibration, and proprioception using simple tools like cotton swabs or tuning forks. Physical Examination: Physical and neurological exams will be performed by a qualified study clinician at protocol specified time points. Complete physical examinations will include general appearance, head, ears, eyes, nose, throat, mouth / dental (if required), neck (incl. thyroid & nodes), cardiovascular, respiratory, gastrointestinal, renal, neurological, musculoskeletal, skin, other. Suicide risk assessment: Columbia-Suicide Severity Rating Scale (C-SSRS)- Suicidal Ideation will be assessed using the C-SSRS, a suicidal ideation and behavior rating scale to evaluate suicide risk. The tool is to be administered by a qualified rater via interview with the participants throughout the study.

Timepoint [1]

AEs: From Day 1 (Screening) up to Day 12 (End of study) Vital Signs: From Day 1 (Screening) up to Day 12 (End of study) Electroencephalograms (EEGs): Days 1, 7 and 10. Electrocardiograms (ECGs): Days 1,2,3,5,6,7, 8,10 and 12. Laboratory parameters: Days 1,2,3,4,5,6,7,8,9 and 12 Neurological Examination: Day 1,2,3,4,5,6,7,8,9 and 12. Physical Examination: Day 1, 2,3,4,5,6,7,8,9 and 10 Suicide risk assessment: Columbia-Suicide Severity Rating Scale (C-SSRS): Day 1, 4, 5 and 10

Secondary outcome [1]

Pharmacokinetics (PK) of XYL-2499 following single and multiple ascending oral doses.

Timepoint [1]

For Single Ascending Dose (SAD): From Day 1 (dose administration) through Day 4 post-dose. For Multiple Ascending Dose (MAD): From Day 1 (first dose) through Day 10 (3 days post final dose)

Secondary outcome [2]

Renal excretion of XYL-2499 following multiple ascending doses.

Timepoint [2]

Day 7 (Day of final dose of the multiple ascending dose phase), during which a 24-hour urine collection (0–24 hours post-dose) will be performed.

Secondary outcome [3]

Presence, and intensity of any psychedelic, dissociative, or psychoactive effects induced by XYL-2499 and will be assessed as a composite outcome

Timepoint [3]

Xylo Visual Analogue Scale (VAS-X15Q): Assessed on Day 1 (pre-dose and post-dose) and daily from Day 2 to Day 10 following dose administration. Xylo Visual Analogue Scale (VAS-X5Q): Assessed on Day 1 (pre-dose and post-dose) and daily from Day 2 to Day 10 following dose administration. Mystical Experiences Questionnaire (MEQ30): Assessed on Day 1 (post-dose) and Days 2, 3, 4, 5, 6, 7, and 10 following dose administration. Clinician-Assessed Dissociative States Scale (CADSS): Assessed on Day 1 (pre-dose and post-dose) and Days 2, 3, 4, 5, 6, 7, and 10 post-dose. Brief Psychiatric Rating Scale (BPRS): Assessed on Day 1 (pre-dose) and follow-up visits on Days 2 and 8.

Eligibility

Key inclusion criteria

1. Adult males and females age 18 to 65 years (inclusive) at time of Screening.
2. Participant is judged to be in good health by the Investigator based upon the results of
medical history, physical examination, vital signs, ECG, and clinical laboratory safety tests.
3. Laboratory test results must be within the normal range. If any results are outside the normal range the study doctor must decide that they are not medically important.
4.Body weight must be appropriate for height with a body mass index between 18 and 32 kilograms per square meter at the time of screening.
5. Willing and able to provide written informed consent
6. Females must meet the following criteria:
a) Confirmed as being non-childbearing potential; or
b) Must have a negative serum pregnancy test at Screening and negative urine pregnancy test prior to dosing.
c) Must not be lactating;
d) Must refrain from egg collection or donation from 30 days prior to first dose of study
medication, and for 90 days following after the last study drug administration
e) They must agree to use a highly effective medical method of birth control starting thirty days before the first study dose during the study and continuing until ninety days after the last dose
7. Males must meet the following criteria:
a) They must either have no sperm due to vasectomy or a medical condition
b) Must agree to use a male condom plus partner use of an additional contraceptive method from the start of confinement (Day -1) up to 90 days after the last study drug administration when having penile-vaginal intercourse with a woman of childbearing potential.
c) Must refrain from sperm donation from the start of confinement (Day -1) up to 90 days
after the last study drug administration.
d) Men with a pregnant or breastfeeding partner must either avoid vaginal sex or always use a condom
8. Participants must agree to follow all study requirements including
a) Fasting, medication dosing, therapy, and study procedures.
b) Not doing strenuous exercise and not consuming alcohol nicotine or caffeine from 48 hours before dosing until the end of each study stay
c) Being available and contactable for the entire study duration
d) Informing the study doctor within 48 hours of any new medical condition or medical procedure
e) Not taking part in any other interventional clinical study during this study
f) Agreeing that their data will be kept confidential and that anonymised data may be used for scientific publications

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Healthy volunteers

Yes

Key exclusion criteria

1. Abnormal laboratory test results considered clinically important
2. Positive test results for HIV hepatitis C or active hepatitis B infection at screening. Participants immune to hepatitis B may be allowed.
3. Positive test for drugs of abuse or alcohol at screening or Day minus 1.
4. History of alcohol abuse heavy alcohol use or drug or chemical abuse within 1 year before Day 1.
5. History of any significant medical condition affecting major organs or body systems unless considered not clinically important by the study doctor.
6. History of significant heart or blood vessel disease or rhythm disorders.
7. History of cancer within the last 5 years except certain treated skin cancers or low-grade prostate cancer.
8. Major surgery within 3 months before Day minus 1 or planned surgery during the study period.
9. Use of any medications other than oral contraceptives unless approved by the study doctor for treatment of side effects.
10. Use of any investigational drug within 30 days or participation in another clinical study.
11. Vaccination within 14 days before dosing.
12. Use of psychedelic or hallucinogenic substances within the past 1 year or more than 2 lifetime uses.
13. History of hospitalization for depression or current diagnosis of major depressive disorder at screening.
14. Any medical condition that causes problems with thinking memory or understanding.
15. Current or relevant past history of major psychiatric illness such as schizophrenia bipolar disorder or panic disorder.
16. Unwilling or unable to avoid strenuous physical activity from 7 days before Day minus 1 until the end of the study period.
17. Not able to read or speak the main language used at the study site.
18. Any other reason that the study doctor believes may be unsafe affect study results or is not in the participant’s best interest.

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)

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?

The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

29/06/2026

Actual

Date of last participant enrolment

Anticipated

26/10/2026

Actual

Date of last data collection

Anticipated

8/11/2026

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Xylo Bio

Address [1]

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Xylo Bio

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee A

Ethics committee address [1]

https://bellberry.com.au/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/04/2026

Approval date [1]

18/05/2026

Ethics approval number [1]

Summary

Brief summary

1. This study is an early-stage clinical trial in healthy adults to understand how safe XYL-2499 is and how the body handles it.
2. XYL-2499 is an investigational medicine that affects certain brain pathways and is being developed for possible use in mental health conditions.
3. Participants will receive either a single dose or multiple doses of the study drug or a placebo, with careful monitoring throughout the study.
4. Doctors will closely monitor participants for side effects, changes in mood or perception, and effects on thinking or behavior using standard tests.
5. The study uses small groups, step-by-step dosing, and close medical supervision to help ensure participant safety

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Sepehr Shakib

Address

CMAX Clinical Research- Gound Floor 21 – 24 North Terrace | Adelaide SA 5000

Country

Australia

Phone

+61 0411 100 278

Fax

[email protected]

Contact person for public queries

Name

Prof. Sepehr Shakib

Address

CMAX Clinical Research- Gound Floor 21 – 24 North Terrace | Adelaide SA 5000

Country

Australia

Phone

+61 0411 100 278

Fax

[email protected]

Contact person for scientific queries

Name

Prof. Sepehr Shakib

Address

CMAX Clinical Research- Gound Floor 21 – 24 North Terrace | Adelaide SA 5000

Country

Australia

Phone

+61 0411 100 278

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

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.

Trial Review

Documents added manually

Documents added automatically