None listed
Conditions
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
Interventions
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
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.
Sponsors
Xylo Bio
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
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.
Outcome results
None listed