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

NCT07146945 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: DLP-S-0-1.01
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Participants

Keywords

Healthy Participants

Outcome Measures

Primary Outcomes (46)

• Percentage of participants with treatment-emergent Adverse Events (AE). An AE will be considered treatment-emergent if the onset date and time is at the time of or after first study drug administration.

  Incidence, severity and relationship of AEs.

  Through to study completion, up to approximately 49 days.

• Percentage of participants with treatment-emergent abuse-related Adverse Events (AE). An AE will be considered treatment-emergent if the onset date and time is at the time of or after first study drug administration.

  Incidence, severity and relationship of abuse-related AEs.

  Through to study completion, up to approximately 49 days.

• Percentage of participants with out-of-range red blood cell count (cells/µL).

  Changes from baseline in red blood cell count (cells/µL).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with out-of-range haematocrit (L/L).

  Changes from baseline in haematocrit (L/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with out-of-range haemoglobin (g/L).

  Changes from baseline in haemoglobin (g/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with out-of-range white blood cell count including differential count (neutrophils, eosinophils, basophils, monocytes, and lymphocytes) (cells/µL).

  Changes from baseline in white blood cell count including differential count (neutrophils, eosinophils, basophils, monocytes, and lymphocytes) (cells/µL).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with out-of-range platelets (cells/µL).

  Changes from baseline in platelets (cells/µL).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Sodium (mmol/L).

  Changes from baseline in Sodium (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Potassium (mmol/L).

  Changes from baseline in Potassium (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Chloride (mmol/L).

  Changes from baseline in Chloride (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Calcium (mmol/L).

  Changes from baseline in Calcium (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Bicarbonate (mmol/L).

  Changes from baseline in Bicarbonate (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Magnesium (mmol/L).

  Changes from baseline in Magnesium (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Aspartate transaminase (U/L).

  Changes from baseline in Aspartate transaminase (U/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Alanine Transaminase (U/L).

  Changes from baseline in Alanine Transaminase (U/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Alkaline Phosphatase (U/L).

  Changes from baseline in Alkaline Phosphatase (U/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Gamma-Glutamyl Transferase (U/L).

  Changes from baseline in Gamma-Glutamyl Transferase (U/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Lactate dehydrogenase(U/L).

  Changes from baseline in Lactate dehydrogenase(U/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Bilirubin (µmol/L).

  Changes from baseline in Bilirubin (µmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in urea (mmol/L).

  Changes from baseline in urea (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Creatinine (µmol/L).

  Changes from baseline in Creatinine (µmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Phosphorus (mmol/L).

  Changes from baseline in Phosphorus (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Uric acid (mmol/L).

  Changes from baseline in Uric acid (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in glucose (mmol/L).

  Changes from baseline in glucose (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in HbA1c (%).

  Changes from baseline in HbA1c (%).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Albumin (g/L).

  Changes from baseline in Albumin (g/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Total protein (g/L).

  Changes from baseline in Total protein (g/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Globulin (g/L).

  Changes from baseline in Globulin (g/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Cholesterol (mmol/L).

  Changes from baseline in Cholesterol (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Triglycerides (mmol/L).

  Changes from baseline in Triglycerides (mmol/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Creatine Kinase (U/L).

  Changes from baseline in Creatine Kinase (U/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in C-reactive protein (mg/L).

  Changes from baseline in C-reactive protein (mg/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Estimated Glomerular Filtration Rate (mL/min/1.73m2).

  Changes from baseline in Estimated Glomerular Filtration Rate (mL/min/1.73m2).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Thyroid Stimulating Hormone (mIU/L).

  Changes from baseline in Thyroid Stimulating Hormone (mIU/L).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Activated Partial Thromboplastin Time (sec).

  Changes from baseline in Activated Partial Thromboplastin Time (sec).

  Through to study completion, up to approximately 49 days.

• Percentage of participants with changes from baseline in Prothrombin Time (sec).

  Changes from baseline in Prothrombin Time (sec).

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline in International Normalised Ratio (ratio).

  Changes from baseline in International Normalised Ratio (ratio).

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline in urinalysis laboratory parameters. Assessment from the patient through dipstick testing on a freshly voided urine sample to measure the presence or absence of protein glucose, blood (erythrocytes),

  Changes from baseline in urinalysis laboratory parameters. Assessment from the patient through dipstick testing on a freshly voided urine sample to measure the presence or absence of protein glucose, blood (erythrocytes), leucocytes, ketone bodies, nitrite, bilirubin, urobilinogen (present/absent).

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline in urine pH.

  Changes from baseline in urine pH.

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline of systolic and diastolic blood pressure, measured in mmHg.

  Changes from baseline of systolic and diastolic blood pressure, measured in mmHg.

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline heart rate, measured in beats per minute (bpm).

  Changes from baseline heart rate, measured in beats per minute (bpm).

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline respiratory rate, measured in breaths per minute.

  Changes from baseline respiratory rate, measured in breaths per minute.

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline body temperature, measured in degrees Celsius.

  Changes from baseline body temperature, measured in degrees Celsius.

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline of 12-lead ECG parameters. The following parameters are included: heart rate, RR interval, PR interval, QRS duration, QT interval, and QTcF interval (all measured in mV/s).

  Changes from baseline of 12-lead ECG parameters. The following parameters are included: heart rate, RR interval, PR interval, QRS duration, QT interval, and QTcF interval (all measured in mV/s).

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline in physical examination measured by presence or absence of investigator-assessed abnormalities.

  Changes from baseline in physical examination measured by presence or absence of investigator-assessed abnormalities. The following parameters are included: general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin/soft tissues, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.

  Through to study completion, up to approximately 49days.

• Percentage of participants with changes from baseline in suicidal ideation and behaviour as assessed by Columbia-Suicide Severity Rating Scale with scoring is based on the most severe response reported for suicidal ideation and behaviours.

  Changes from baseline in suicidal ideation and behavior as assessed by Columbia-Suicide Severity Rating Scale with scoring is based on the most severe response reported for suicidal ideation and behaviours. Suicidal ideation will be reported with scores of 0-25, with 0 being no suicidal ideation and 25 being the most severe ideation. Behaviour will be reported in terms of presence or absence, frequency, and their severity (actual attempt, interrupted/aborted attempt, or mere preparation).

  Through to study completion, up to approximately 49 days.

Secondary Outcomes (12)

• Pharmacokinetics parameter - maximum observed concentration (Cmax)

  Through to study completion, up to approximately 49 days.

• Pharmacokinetics parameter - Time for maximum observed Concentration (Tmax).

  Through to study completion, up to approximately 49 days.

• Pharmacokinetics parameter - Area under the curve (AUC)

  Through to study completion, up to approximately 49 days.

• Pharmacokinetics parameter - Elimination rate constant

  Through to study completion, up to approximately 49 days.

• Pharmacokinetics parameter - Apparent total plasma clearance

  Through to study completion, up to approximately 49 days.

Study Arms (6)

S1-221 Single Ascending Dose

EXPERIMENTAL

Participants will be enrolled in 1 of 8 single ascending dose cohorts. Six participants in each cohort will receive one dose of oral S1-221. Doses to be administered are not pre-specified, but will be proposed, reviewed and approved by the Safety Review Committee.

Drug: S1-221

Single Ascending Dose Placebo

PLACEBO COMPARATOR

Two participants in each ascending dose cohort will receive one dose of oral matching placebo.

Drug: Placebo

S1-221 Food Effect

EXPERIMENTAL

Eight participants will receive one dose of oral S1-221 under fasting conditions in Period 1 and will receive one dose of oral S1-221 under non-fasting conditions in Period 2. Food effect participants will be enrolled in 1 cohort. Doses to be administered are not pre-specified, but will be proposed, reviewed and approved by the Safety Review Committee.

Drug: S1-221

Placebo Food Effect

PLACEBO COMPARATOR

Two participants will receive one dose of oral matching placebo under fasting conditions in Period 1 and will receive one dose of oral matching placebo under non-fasting conditions in Period 2. Food effect participants will be enrolled in 1 cohort.

Drug: Placebo

THC - active comparator crossover

ACTIVE COMPARATOR

Five participants will receive one dose of oral THC in Period 1 and will receive one dose of oral S1-221 in Period 2. Participants will be enrolled in 1 cohort. The dose will be based on review of single ascending doses by the Safety Review Committee.

Drug: S1-221; Drug: THC

S1-221 crossover

EXPERIMENTAL

Five participants will receive one dose of oral S1-221 in Period 1 and will receive one dose of oral THC in Period 2. Participants will be enrolled in 1 cohort. The dose will be based on review of single ascending doses by the Safety Review Committee.

Drug: S1-221; Drug: THC

Interventions

S1-221 DRUG

S1-221 will be administered orally to participants.

S1-221 Food Effect; S1-221 Single Ascending Dose; S1-221 crossover; THC - active comparator crossover

Placebo DRUG

Matching placebo will be administered orally to participants.

Placebo Food Effect; Single Ascending Dose Placebo

THC DRUG

A single dose of THC will be administered to participants orally.

S1-221 crossover; THC - active comparator crossover

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated participant informed consent form (PICF) and willing and able to follow all study procedures and requirements for the duration of the study.
• Healthy adult males and females aged 18 to 65 years, inclusive, at Screening.
• Body mass index (BMI) of 18 to 32.0 kg/m2, inclusive, and body weight ≥50.0 kg, at Screening.
• Considered healthy, as determined by no clinically significant findings from medical history or physical examination at Screening and Day -1, in the opinion of the Investigator.
• Vital signs after 5 minutes resting in supine position within the following ranges (assessment may be repeated once per schedule time point, at the discretion of the Investigator, to obtain a clinically reliable result):
• Systolic blood pressure: 90 to 140 mmHg inclusive;
• Diastolic blood pressure: 40 to 90 mmHg inclusive;
• Heart rate: 40 to 100 bpm inclusive.
• Standard 12-lead ECG with parameters (average of triplicate readings) after 10 minutes in supine position within the following ranges (assessment may be repeated once per schedule time point, at the discretion of the Investigator, to obtain a clinically reliable result):
• QRS \<120 msec;
• QT \<500 msec;
• QTc ≤450 msec (both genders);
• PR interval ≥120 to ≤220 msec.
• Screening and Day -1 (and Day 14 for Parts B and C) safety laboratory test values within normal ranges. Out of normal range values may be accepted by the Investigator if not considered clinically significant, with the exception of the following:
• ALT or AST \>1.5 x upper limit of normal (ULN);

You may not qualify if:

• Female participant who is pregnant or breastfeeding, or planning to become pregnant or breastfeed during study participation.
• Evidence of clinically significant abnormalities or disease, including, but not limited to, the following:
• Any pulmonary, cardiovascular, neurologic, gastrointestinal, hepatic, renal, endocrine or other disease, at the discretion of the Investigator including, but not limited to, history of epilepsy.
• Any history of gastrointestinal condition, including surgeries, or use of any medications (including glucagon-like peptide-1 \[GLP-1\] agonists) which may affect absorption or gastric motility after oral administration.
• Has a lifetime history or current diagnosis of a significant psychiatric disorder including, but not limited to, schizophrenia spectrum or other psychotic disorders, major depressive disorder, or generalized anxiety disorder per Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5), and/or has first-degree relative with a history of psychosis or schizophrenia.
• Meets DSM-5 criteria for lifetime or current substance use disorder for any psychoactive substances other than nicotine or caffeine.
• Has a history of, or active, suicidal ideation as identified by positive response to questions 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening, or has any prior history of suicidal behaviour, as evidenced by medical history of suicide attempt or a "Yes" response to the following suicidal behaviour questions on the C-SSRS: actual attempt, interrupted attempt, or aborted attempt.
• History or ECG evidence of myocardial ischemia or infarct, 2nd or 3rd degree AV block, bundle branch block, with the exception of incomplete right bundle branch block in the absence of clinical heart disease, or multiple or multifocal premature ventricular contractions.
• History of fainting or syncope that, in the Investigator's opinion, would interfere with study conduct or compliance.
• Any other laboratory, vital sign, ECG abnormality, or clinical history or finding that, in the Investigator's opinion, is likely to unfavourably alter the risk-benefit of study participation, confound study results, or interfere with study conduct or compliance.
• Positive urine drug test or alcohol breath test at Screening or Day -1 (and Day 14 for the Parts B and C), unless there is an explanation deemed acceptable by the Investigator and/or the participant tests negative upon re-test. Note: one re-test for drug screen is permitted per scheduled time point. No retest is permitted for alcohol breath test.
• History of clinically significant allergy, hypersensitivity, or adverse reaction to cannabis or any cannabinoid, including dysphoria, or to any excipient in the investigational product (e.g., sesame allergy) at the discretion of the Investigator.
• Donation or loss of greater than 1 unit (450 mL) of blood within the 4 weeks prior to Screening.
• Has received any prescription medication within 14 days or 5 half-lives (whichever is longer) of Day -1 and throughout the study (exceptions: contraceptives are permitted). Prescriptions of known inhibitors or inducers of hepatic drug metabolism (e.g., rifampin, carbamazepine, phenytoin, barbiturates \[e.g., phenobarbital and butalbital\], dexamethasone, antidepressants \[e.g., fluoxetine, paroxetine\], proton pump inhibitors, ketoconazole itraconazole and clarithromycin) will be prohibited.
• Has received any non-prescription medication within 5 days of Day -1 and throughout the study (exception: occasional \[PRN\] paracetamol \[up to 2 g/day\] or ibuprofen \[up to 1.2 g/day\] use may be permitted, at Investigator discretion).

Sponsors & Collaborators

• Delphian Therapeutics Australia Pty, Ltd: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Interventions

Dronabinol

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Ryan Lanier

  DelphianTherapeutics

  STUDY CHAIR

Central Study Contacts

Sarah Thayer

CONTACT

+1 (650) 223-4015; s.thayer@s1therapeutics.com

George Pappas

CONTACT

+1 (630) 533-1989; g.pappas@s1therapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A will involve sequential ascending doses in up to 8 cohorts. Part B is a single intervention, two period, fed vs fasting comparison. Part C is an active comparator, two period crossover design. Parts B and C will only proceed after Part A has been reviewed by the Safety Review Committee (SRC) and the SRC has selected the doses for Parts B and C.

Study Record Dates

• First Submitted: August 2, 2025
• First Posted: August 28, 2025
• Study Start: August 30, 2025
• Primary Completion: February 22, 2026
• Study Completion: February 28, 2026
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)