Safety, Tolerability, Pharmacokinetics and Efficacy Study... | NCT05964790

Label	Type	Description	Intervention Names
HS-10380	Experimental	Participants received HS-10380 tablet orally once daily for 28 days.	Drug: HS-10380
Placebo	Placebo Comparator	Participants received placebo tablet matching HS-10380 1.5mg tablet orally once daily for 28 days.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
HS-10380	Drug	Participants in arm HS-10380 will receiving multiple ascending doses of HS-10380 (1.5 mg initial dose) orally once daily for 28 days	HS-10380

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Dose escalation cohorts: Incidence and severity of adverse events(AE) ，serious AEs and AE leading to withdrawal from treatment.	An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect.	Baseline to Day 43
Dose escalation cohorts: Changes from baseline in complete blood count (CBC).	Hematology parameters to be reported: white blood cells, red blood cells and platelets.	Baseline to Day 36
Dose escalation cohorts: Changes from baseline in urinalysis.	Parameters to be reported: protein, glucose, ketones, red blood cells, and white blood cells.	Baseline to Day 36
Dose escalation cohorts: Changes from baseline in blood biochemistry test.	Parameters to be reported: glucose, urea, serum creatinine, alanine aminotransferase, aspartate transaminase, albumin, total protein, bilirubin, and blood lipid index.	Baseline to Day 36
Dose escalation cohorts: Changes from baseline in coagulation function test.	prothrombin time, activated partial thromboplastin time and international normalized ratio.	Baseline to Day 36
Dose escalation cohorts: Changes from baseline in thyroid function test.

Secondary Outcomes

Measure	Description	Time Frame
Dose escalation cohorts: Maximum plasma concentration (Cmax) of first HS-10380 administration	Pharmacokinetics describes the action of a drug in the body over a period of time. Blood samples are collected to measure plasma concentrations of the study drug at different times after dosing.	Baseline to Day 36

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Dose escalation cohorts:
1. Patients are 18 to 55 years of age, inclusive.
2. Body mass index (BMI) between 18.5 and 30.0 kg/m2 ,inclusive. Weight ≥ 50 kg for male subjects and ≥ 45 kg for female subjects.
3. Patient meets DSM-5 criteria for schizophrenia.
4. Currently not taking antipsychotics. Or on a stable dose of single second-generation antipsychotics (SGA) for at least 2 weeks, limited to either risperidone, olanzapine, quetiapine, aripiprazole, or paliperidone.
5. PANSS total score ≤ 90. Rating ≤ 4 on hostility and uncooperativeness,
6. Negative urine pregnancy test (women of childbearing potential only).
7. Male and female patients must agree to use a highly effective method of birth control during the course of the entire study and for 3 months after the last dose of investigational product.
8. Written informed consent has been obtained.

Expansion cohorts:

Patients are 18 to 65 years of age, inclusive.
Patient meets DSM-5 criteria for schizophrenia.
No current use of antipsychotics. Or withdrawing from antipsychotics other than clozapine for more than 5 half-lives prior to randomization.
PANSS total score ≥70 and ≤120. Rating of at least 4 (moderate) on at least 2 of the following 4 PANSS positive symptoms; P1: delusions; P2: conceptual disorganization; P3: hallucinatory behavior; P6: suspiciousness/persecution.
Negative urine pregnancy test (women of childbearing potential only).
Male and female patients must agree to use a highly effective method of birth control during the course of the entire study and for 3 months after the last dose of investigational product.
Written informed consent has been obtained.

Exclusion Criteria:

Dose escalation cohorts:
1. Patients meet DSM-5 criteria for a mental illness other than schizophrenia, and might interfere with the conduct of the study as determined by the investigator.
2. Current risk of self-harm or violence, including: having any suicidal ideation or suicidal behavior within the last 6 months, as assessed using Columbia-Suicidal Severity Rating Scale (C-SSRS).
3. Patients who have a clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorder, etc. Medical conditions that are minor or well-controlled may be considered acceptable if the condition does not interfere with the conduct of the study.
4. Patients who received electroconvulsive therapy (ECT) within 3 months prior to screening.
5. Received a long-acting antipsychotic within 6 months prior to screening or within the duration of 5 half-lives of the drug.
6. History of seizure disorder (with the exception of febrile seizure).
7. History of malignant syndrome.
8. Any condition that would be expected to affect drug absorption, distribution, metabolism and excretion, including gastrointestinal surgery, urinary tract obstruction or difficulty in urination, etc.
9. History of severe allergies.
10. Female patients who are pregnant, puerperal or breastfeeding.
11. History of drug addiction within 1 year prior to screening.
12. Patients who has a history of alcohol abuse (defined as more than 14 standard units of alcohol consumption per week, 1 standard unit = 360 mL of beer, 45 mL of distilled spirits or 150 mL of wine) within 6 months prior to screening, or are unable to abstain from alcohol use during the study period.
13. Patients who smoke ≥10 cigarettes per day within 3 months prior to screening, or are unable to quit smoking during the study period.
14. Abnormal physical examination results that may interfere with the study.
15. Abnormal vital signs that may interfere with the study, including: resting heart rate <60 or >100 beats per minute, systolic blood pressure <90mmHg or ≥140mmHg, diastolic blood pressure <60mmHg or ≥90mmHg.
16. Abnormal electrocardiogram (ECG) results may interfere with the study, including: QTcF>450ms for male subjects and >470ms for female subjects based on Fridericia correction.
17. Abnormal clinical laboratory test results may interfere with the study, including: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) results >1.5 × the upper limit of normal (ULN); serum prolactin levels >5 × ULN or significant clinical symptoms like amenorrhea, gynecomastia, and lactation.
18. Patients whose results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or syphilis serological reaction (TRUST) is not negative.
19. Blood donation or blood loss ≥ 200ml within 1 month prior to screening.
20. Patients requiring concomitant treatment with a moderate or strong cytochrome P450 (CYP) 3A4 inhibitors or CYP3A4 inducers, or a moderate or strong cytochrome CYP2D6 inhibitors or CYP3A4 inducers.
21. Prior participation in any Interventional clinical trials within 3 months.
22. Unsuitable for any other reason, as judged by the investigator.

Expansion cohorts:

Patients meet DSM-5 criteria for a mental illness other than schizophrenia, and might interfere with the conduct of the study as determined by the investigator.
Current risk of self-harm or violence, including: having any suicidal ideation or suicidal behavior within the last 6 months, as assessed using Columbia-Suicidal Severity Rating Scale (C-SSRS).
Patients who have a clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorder, etc. Medical conditions that are minor or well-controlled may be considered acceptable if the condition does not interfere with the conduct of the study.
Patients who received electroconvulsive therapy (ECT) within 3 months prior to screening.
Received a long-acting antipsychotic within 6 months prior to screening or within the duration of 5 half-lives of the drug.
History of seizure disorder (with the exception of febrile seizure).
History of malignant syndrome.
Any condition that would be expected to affect drug absorption, distribution, metabolism and excretion, including gastrointestinal surgery, urinary tract obstruction or difficulty in urination, etc.
History of severe allergies.
Female patients who are pregnant, puerperal or breastfeeding.
History of drug addiction within 1 year prior to screening.
Patients who has a history of alcohol abuse (defined as more than 14 standard units of alcohol consumption per week, 1 standard unit = 360 mL of beer, 45 mL of distilled spirits or 150 mL of wine) within 6 months prior to screening, or are unable to abstain from alcohol use during the study period.
Abnormal physical examination results that may interfere with the study.
Abnormal vital signs that may interfere with the study, including: resting heart rate <60 or >100 beats per minute, systolic blood pressure <90mmHg or ≥140mmHg, diastolic blood pressure <60mmHg or ≥90mmHg.
Abnormal electrocardiogram (ECG) results may interfere with the study, including: QTcF>450ms for male subjects and >470ms for female subjects based on Fridericia correction.
Abnormal clinical laboratory test results may interfere with the study, including: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) results > 2 × the upper limit of normal (ULN).
Patients whose results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or syphilis serological reaction (TRUST) is not negative.
Patients requiring concomitant treatment with a moderate or strong cytochrome P450 (CYP) 3A4 inhibitors or CYP3A4 inducers, or a moderate or strong cytochrome CYP2D6 inhibitors or CYP3A4 inducers.
Blood donation or blood loss ≥ 200ml within 1 month prior to screening.
Prior participation in any Interventional clinical trials within 3 months.
Unsuitable for any other reason, as judged by the investigator.

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders