Healthy Participants
Conditions
Brief summary
This is a single-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK characteristics, and food effect of single ascending oral doses of SYH2056 tablets in healthy participants. The study is planned to have two Parts: Part 1 \[the single ascending dose (SAD) study\] and Part 2 (the food effect study).
Interventions
DRUGSYH2056 tablets
SYH2056 tablets, 2mg/tablet or 8mg/tablet, \[WQQ1.1\]taken according to the dosage of arm1 to arm7 on day1 SYH2056 tablets, 8mg/tablet, taken according to the dosage of arm8 and arm9 on day1 or say5
DRUGSYH2056 placebo
Placebo Comparator, taken matching the dosage of arm1 to arm7 on day1
Sponsors
InnovStone Therapeutics Limited
Shanghai Mental Health Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1: single ascending dose (SAD) Study randomized, double-blind, placebo-controlled, single ascending dose study Part 2: Food Effect (FE) Study randomized, single-dose, two-period, crossover design
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Participants must meet all of the following criteria to be enrolled in this study: 1. Age from 18 to 55 years (inclusive). 2. Male or female, with the proportion of either sex being no less than 1/3. 3. Weight ≥45.0 kg (females) or ≥50.0 kg (males), and body mass index (BMI) within the range of 18.0 to 26.0 kg/m2 (inclusive). 4. Results of vital signs, physical examination, 12-lead ECG, laboratory tests, chest X-ray, B-mode ultrasound (liver, gallbladder, spleen, pancreas, kidneys), thyroid function test, etc., are normal or abnormal but not clinically significant as judged by the investigator. 5. The participate and their partner agree to use effective non-hormonal contraceptive methods (e.g., condom, inert intrauterine device, female barrier methods \[cervical cap or diaphragm with spermicide\], vaginal ring, etc.) from signing the ICF until 3 months after the last dose, or have undergone permanent sterilization (e.g., bilateral tubal ligation, vasectomy, etc.). The participate has no plans to donate sperm or eggs from signing the ICF until 3 months after the end of the study. 6. Participates must able to read and understand the written informed consent containing study-related information, fully understand the study content, procedures, and possible adverse reactions, voluntarily participate in the clinical study, sign the written ICF, and comply with the study procedures.
Exclusion criteria
A participate will not be eligible for inclusion in this study if any of the following criteria apply: 1. Participates with history of clinically significant neurological, psychiatric, pulmonary, endocrine, hematological, musculoskeletal, gastrointestinal, cardiovascular, hepatic or renal diseases, or other diseases that might affect the study results or participants' safety as deemed by the investigator or designee. 2. Participates with history of neuropsychiatric disorders, including current or past history of mental illness, current or recent use of psychotropic drugs, or other mental or psychological conditions deemed unsuitable for enrollment by the investigator or designee. 3. Participates with abnormal blood pressure, such as systolic blood pressure ≥140 mmHg or \<90 mmHg; diastolic blood pressure ≥90 mmHg or \<60 mmHg. 4. Participates with abnormal renal function, such as serum creatinine (Scr) \> upper limit of normal (ULN), or estimated glomerular filtration rate (eGFR) \<90 mL/min/1.73m2 or ≥130 mL/min/1.73m2. 5. Participates with history of severe drug or food allergies, or judged by the investigator to be potentially allergic to the investigational drug. 6. Participates who have taken any prescription drugs, over-the-counter drugs, herbal medicines, vitamin/dietary supplements, or health products within 4 weeks before signing the ICF. Or those who are using long-acting oral contraceptives, long-acting contraceptive implants, or hormone-releasing intrauterine devices. 7. Participates with history of diseases which could affect drug absorption, distribution, metabolism, or excretion (e.g., acute or chronic diarrhea or gastritis, gastrectomy, enterectomy, or cholecystectomy, etc., with the exception of appendectomy). 8. Participates who have undergone any surgery within 6 months before signing the ICF, or those who plan to undergo surgery (including cosmetic surgery, dental operation, and oral surgery) during the study. 9. Participates with QTcF interval \>450 ms (males) or \>470 ms (females), or those who have a history of QT interval prolongation. 10. Participates who have experienced blood loss or blood donation exceeding 400 mL within 3 months before signing the ICF, or those who have received a blood transfusion or have used blood products. 11. Regular alcohol consumption, defined as an average weekly alcohol intake \>14 units of alcohol within the 3 months prior to signing the ICF (1 unit = 285 mL of beer, 25 mL of spirits or 150 mL of wine), or positive breath alcohol test, or unable to abstain from alcohol during the study. 12. Participates who smoked ≥ 5 cigarettes per day within 6 months before signing the ICF, or who are unable to abstain from any tobacco products during the study. 13. Participates with habitual excessive consumption of foods, fruits, or beverages containing purines, caffeine, or grapefruit and grapefruit juice, or other foods that may affect drug absorption, distribution, metabolism, or excretion, within 2 weeks before dosing, such as coffee (\>1,100 mL/day), tea (\>2,200 mL/day), cola (\>2,200 mL/day), energy drinks (\>1,100 mL/day) and chocolate (\>510 g/day). 14. Participates who have enrolled in any clinical studies of drug or medical device within 3 months before signing the ICF. 15. Participates with history of drug abuse within 1 year before signing the ICF, or who have a positive drug test as screening. 16. Female participates with a positive pregnancy test at screening or who is lactating. 17. Participates who have positive results in one or more of the following examinations: hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, anti-human immunodeficiency virus (HIV) antibody, or anti-Treponema pallidum-specific antibody. 18. Participates with history of needle or blood phobia, or those who have difficulty with venous blood collection or can't tolerate venipuncture for other reasons. 19. Participates with special dietary requirements and cannot accept the standardized diet and schedule. 20. Any other factors that the investigator deems unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events assessments | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Incidence, severity, seriousness, and relationship of treatment-emergent adverse events (TEAEs) will be assessed by CTCAE V5.0 |
| Changes in Systolic and Diastolic Blood Pressure Blood Pressure | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Changes in systolic and diastolic blood pressure will be assessed during the study（Unit: mmHg） |
| Changes in Pulse Rate | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Changes in pulse rate will be assessed during the study（Unit: beats/min） |
| Changes in Body Temperature | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Changes in body temperature will be assessed during the study（Unit: °C） |
| Incidence of Clinically Significant Abnormal Findings in Physical Examination | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Clinically significant abnormalities identified by physical examination, including general condition, skin and mucous membranes, superficial lymph nodes, head, neck, thyroid, chest (including thorax, lungs, and heart), abdomen, spine/limbs, and nervous system examinations, will be assessed during the study. The results will be presented as the percentage of participants (%) with clinically significant abnormalities |
| Clinically Significant Abnormal Findings in Hematology Tests | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Clinically significant abnormalities identified by hematology tests, including complete blood count parameters, will be assessed during the study. The results will be presented as the percentage of participants(%) with clinically significant abnormalitiesClinically significant abnormalities identified by hematology tests, including complete blood count parameters, will be assessed during the study. The results will be presented as the percentage of participants(%) with clinically significant abnormalities |
| Clinically Significant Abnormal Findings in Blood Biochemistry Tests | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Clinically significant abnormalities identified by blood biochemistry tests, including liver function, renal function, and metabolic parameters, will be assessed during the study. The results will be presented as the percentage of participants(%) with clinically significant abnormalities |
| Clinically Significant Abnormal Findings in Coagulation Tests | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Clinically significant abnormalities identified by coagulation tests, including coagulation parameters, will be assessed during the study. The results will be presented as the percentage of participants(%) with clinically significant abnormalities |
| Clinically Significant Abnormal Findings in Urinalysis | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Clinically significant abnormalities identified by urinalysis, including urine parameters, will be assessed during the study. The results will be presented as the percentage of participants(%) with clinically significant abnormalities |
| 12-lead electrocardiograms (ECGs) | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Changes in 12-lead electrocardiogram parameters, including heart rate, PR interval, QRS interval, QT interval, and QTc interval, will be assessed |
| Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Potential effects of SYH2056 on neuropsychiatric status will be assessed by the MOAA/S Score. The MOAA/S score ranges from 0 to 5, with higher scores indicating a higher level of alertness (less sedation) and lower scores indicating a deeper level of sedation. |
| Columbia Suicide Severity Rating Scale (C-SSRS) Assessed | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Potential effects of SYH2056 on neuropsychiatric status will be assessed by the C-SSRS. Suicidal ideation severity is rated from 0 to 5, with higher scores indicating greater severity of suicidal ideation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Administered Dissociative States Scale (CADSS) | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Hallucinogenic properties of SYH2065 will be assessed by the CADSS. The CADSS total score ranges from 0 to 92, with higher scores indicating greater severity of dissociative symptoms. |
| Brief Psychiatric Rating Scale (BPRS) | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Hallucinogenic properties of SYH2065 will be assessed by the BPRS. The BPRS total score ranges from 18 to 126, with higher scores indicating greater severity of psychiatric symptoms. |
| the Physician Withdrawal Checklist 20 (PWC-20) | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Subject's subjective liking of SYH2065 will be assessed by the PWC-20 |
| The Drug Liking Visual Analogue Scale (VAS) | Up to Day11 for Part1 SAD study, up to Day15 for Part2 FE study | Subject's subjective liking of SYH2065 will be assessed by the VAS. The score ranges from 0 to 100, with higher scores indicating greater subjective liking of the drug. |
| t1/2 | Day1 to Day4 for Part1 SAD study, Day1 to Day8 for Part2 FE study | Elimination Half-Life of SYH2056 |
| Tmax | Day1 to Day4 for Part1 SAD study, Day1 to Day8 for Part2 FE study | Time to Peak Concentration of SYH2056 |
| Cmax | Day1 to Day4 for Part1 SAD study, Day1 to Day8 for Part2 FE study | Maximum Plasma Concentration of SYH2056 |
| AUC0-t | Day1 to Day4 for Part1 SAD study, Day1 to Day8 for Part2 FE study | Area under the Drug Concentration-Time Curve from Time 0 to the Last Measurable Time Point of SYH2056 |
| AUC0-inf | Day1 to Day4 for Part1 SAD study, Day1 to Day8 for Part2 FE study | Area under the Drug Concentration-Time Curve from Time 0 to Infinity of SYH2056 |
| CL/F | Day1 to Day4 for Part1 SAD study, Day1 to Day8 for Part2 FE study | Apparent Volume of Distribution of SYH2056 |
| Vz/F | Day1 to Day4 for Part1 SAD study, Day1 to Day8 for Part2 FE study | Apparent Volume of Distribution of SYH2056 |
| SYH2056 Metabolites | Up to Day11 for Part1 SAD study | Identification of SYH2056 metabolites in plasma and urine, and to characterize its metabolic pathways |
Contacts
CONTACTClinical Trials Information Group officer
Outcome results
None listed