NCT07146945

A Study Testing the Safety and Effects of Single Doses of S1-221 in Healthy Volunteers

A Phase 1 Double-blind, Randomised, Placebo Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of S1-221 Following Oral Administration

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 84 (estimated)
• Sponsor: Delphian Therapeutics Australia Pty, Ltd · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The purpose of this Phase 1 study is to evaluate the safety, tolerability, and pharmacokinetics (PK) profile of single ascending doses of S1-221 administered orally to healthy adult participants. S1-221 is a liquid containing cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Acute subjective effects will be evaluated as a pharmacodynamic (PD) assessment and changes in plasma endocannabinoid levels will be assessed as an exploratory objective. Data from this study will be used to select doses to be evaluated in subsequent studies to investigate the efficacy and safety of S1-221 in migraine patients.

Detailed description

This is a first-in-human, Phase 1, randomised, double-blind study to evaluate safety, tolerability, PK, and PD following the oral administration of single ascending doses (SAD) of S1-221 to fasted and fed healthy participants. Due to known sex differences in CBD metabolism, every effort will be made to enrol an equal number of biological females and males in each cohort (ideally no fewer than 30% females in each cohort). Individuals will only be permitted to participate in 1 study part. Up to 10 cohorts of 8-10 participants each will be enrolled into this study. The study will consist of 3 parts. Part A will be a SAD evaluation in up to 8 cohorts. Eligible participants will be randomised in a ratio of 3:1 to receive a single oral dose of S1-221 or placebo on Day 1. Within each cohort, a sentinel group of 2 participants, randomised 1:1 to S1-221 or placebo, will be dosed at least 24 hours prior to the remaining participants in the cohort. The minimum 24-hour safety data for these sentinels will be reviewed by the Investigator, and if the dosing is deemed to be safe and well tolerated, the remaining participants in the cohort will be dosed. Study drug will be administered in a fasted state. The study duration for each fasted cohort participant will be approximately 35 days. Parts B and C will proceed at the discretion of the Sponsor, and after review of 4 or more cohorts from Part A. Doses evaluated in Part B and C will not exceed those evaluated in Part A. Part B will be a crossover evaluation, with and without food. Participants in Part B will be administered S1 221 or placebo once on Day 1 under fasted conditions and once on Day 15 under fed conditions. The 2 periods will be separated by a washout period of at least 14 days. A sentinel group of 2 participants, randomised 1:1 to S1-221 or placebo, will be dosed at least 24 hours prior to the remaining participants in the cohort. The minimum 24-hour safety data for these sentinels will be reviewed by the Investigator, and if the dosing is deemed to be safe and well tolerated, the remaining participants in the cohort will be dosed. Participants in the Food Effect Cohort will be screened and administered a single oral dose of S1-221 or placebo under fasted conditions on Day 1. Participants will be discharged on Day 3 and return for an outpatient follow-up visit on Day 4 and Day 7 (+/- 2 days). Following a washout period of at least 14 days after administration of the first dose, participants will be re-admitted 1 day prior to the second (fed) administration of study drug. On Day 15, participants will receive the same dose as in Period 1, this time following consumption of a standardised, FDA-compliant high-fat, high-calorie meal. The study duration for each Food Effect Cohort participant will be approximately 49 days. Part C will be a crossover evaluation of S1-221 compared to THC alone. Participants in the Part C cohort will be randomised 1:1 to treatment sequence (S1-221/THC or THC/S1-221) and administered the first treatment assignment on Day 1 and the alternative assigned drug on Day 15. The 2 periods will be separated by a washout period of at least 14 days. Both doses will be administered in a fasted state and no sentinel dosing will be performed in Part C. The study duration for each Active Comparator Cohort participant will be approximately 49 days.

Conditions

• Healthy Participants

Interventions

Type	Name	Description
DRUG	S1-221	S1-221 will be administered orally to participants.
DRUG	Placebo	Matching placebo will be administered orally to participants.
DRUG	THC	A single dose of THC will be administered to participants orally.

Timeline

• Start date: 2025-08-30
• Primary completion: 2026-02-22
• Completion: 2026-02-28
• First posted: 2025-08-28
• Last updated: 2025-08-28

Locations

1 site across 1 country: Australia