Clinical trial NCT05480592: A Study of HS-10380 in Chinese Participants
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of HS-10380 in Chinese Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Schizophrenia
HS-10380
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-07-29
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the safety and tolerability of single and multiple oral administered doses of HS-10380 in Chinese healthy subjects.

Detailed description: This is a phase I, randomized, double-blinded, placebo-controlled, both single ascending doses (SAD) study and multiple ascending dose (MAD) clinical trial to assess the safety, tolerability, and pharmacokinetics of HS-10380 in Chinese healthy subjects.

There will be four phases in SAD and MAD study: a 2-week screening phase, a 1-day baseline phase, a double-blind treatment phase, and a 1-week post-treatment (follow-up) phase.

Eligibility criteria: Inclusion Criteria:

1. Healthy subject aged from 18 to 45 years;
2. Subject has a Body Mass Index (BMI) between 18.5 and 26.0 kg/m2 at screening and the weight of male subjects is not less than 50 kg, and the weight of female subjects is not less than 45 kg;
3. Voluntary subject who signs the informed consent form after understanding the purpose, content, process and possible risks of the trial;
4. Subject is able to communicate well with the investigator and comply with the lifestyle constraints specified in the protocol, and cooperate to complete the trial procedures.

Exclusion Criteria:

1. Subject has history or presence of disease or dysfunction affecting the clinical trial, including but not limited to neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, musculoskeletal system, metabolic endocrine system, skin disease, blood system disease, immune system and tumor, etc.;
2. Subject has any surgical condition or condition that may significantly affect the absorption, distribution, metabolism, and excretion of the drug, or any surgical condition or condition that may pose a hazard to the subjects participating in the trial, such as gastrointestinal surgery (gastrectomy, Gastrointestinal anastomosis, intestinal resection, etc.), urinary tract obstruction or dysuria, gastroenteritis, peptic ulcer, history of gastrointestinal bleeding, etc.;
3. Subject has a history of significant drug allergies or known allergies to the components of the test drug;
4. Subject has history or presence of psychiatric disorders and cerebral dysfunction, or subjects at risk of suicide according to the Columbia Suicide Severity Rating Scale (C-SSRS) or at risk of suicide according to the investigator's clinical judgment, or has a history of self-harm;
5. Subject has a history of drug abuse within 1 year prior to screening, or has a positive urine drug result screen at screening;
6. Subject has history of alcohol abuse or a single consumption of more than 14 units of alcohol (1 unit = 285 mL of beer, 25 mL of spirits, 150 mL of wine) in the nearly one year prior to screening or a positive breath test for alcohol at screening;
7. Subject has smoked ≥5 cigarettes per day or consumed an average of ≥5 (200mL/cup) cups of coffee or tea per day in the 3 months before screening, or could not stop users during the study;
8. Subject has special requirements for food or is unwilling to accept a uniform diet or has difficulty swallowing;
9. Pregnant or breastfeeding women, or those who refuse to use effective contraception (eg, abstinence, IUD) throughout the study period and 6 months after the end of the study, or those who have a sperm or egg donation plan;
10. Subject has clinically significant abnormal comprehensive physical examination, vital signs, laboratory tests, and 12-lead electrocardiograms, which are judged by the investigator (eg: QTcF\>450ms for men and \>470ms for women, Friericia correction);
11. Subject with resting pulse rate \<55 bpm or \>100 bpm; systolic blood pressure \<90mmHg or \>140mmHg; diastolic blood pressure \<60mmHg or \>90mmHg at screening;
12. Subject has detectable hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), or human immunodeficiency virus (HIV) antibody at screening;
13. Subject with alanine aminotransferase (ALT), creatinine (Cr), blood urea nitrogen (BUN) exceeding the upper limit of normal or serum prolactin greater than 2 times the upper limit of normal at the time of screening;
14. Subject has donated blood or lost blood ≥ 400ml within 3 months before screening, or donated blood or lost blood ≥ 200ml within one month, or has a history of using blood products;
15. Subject with a history of surgery within 3 months prior to screening, or who have not recovered from surgery, or who have anticipated surgery plans during the trial;
16. Subject has taken any medication within 2 weeks (or 5 half-lives, whichever is longer) prior to screening or takes any medication throughout study, including prescription and over-the-counter medications, Chinese herbal medicines, and any drugs that inhibit or induce liver drug metabolizing enzymes (such as inducers and/or inhibitors of CYP3A4, CYP2D6 and CYP3A5);
17. Subject has participated in any clinical trial or took any clinical trial drugs within 3 months before screening;
18. Subject has dieted or received dietary therapy, or had significant changes in dietary habits within 30 days prior to screening;
19. Subject has a history of vaccination within 30 days prior to screening, or has a vaccination schedule throughout the study;
20. Subject with poor compliance or other problems which the investigator considers unsuitable for subject to participate.

Primary outcomes:
measure: Number of Subjects Experiencing Adverse Events (AEs)
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Changes from baseline in laboratory tests
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Changes from baseline in vital signs
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Change from baseline in Electrocardiogram (ECG)
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Change from baseline in weight (kg)
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Change from baseline in physical examination
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Change from baseline in Simpson-Angus Scale (SAS) score
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
measure: Change from baseline in Barnes Akathisia Rating Scale (BARS) score
timeFrame: Baseline to end of follow-up (a maximum of 20 days)
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Time of the Maximum Concentration (Tmax) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Terminal rate constant (λz) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Elimination half-life (t1/2) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC0-∞) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Apparent clearance (CL/F) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Apparent volume of distribution (Vd/F) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Mean retention time (MRT) of single-dose HS-10380 administration
timeFrame: Up to 120 hours post-dose
measure: Maximum plasma concentration (Cmax) of first HS-10380 administration
timeFrame: Up to 12 days
measure: Time of the Maximum Concentration (Tmax) of first HS-10380 administration
timeFrame: Up to 12 days
measure: Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24) first HS-10380 administration
timeFrame: Up to 24 hours
measure: Maximum concentration at steady state (Css, max) of multiple-dose HS-10380 administration
timeFrame: Up to 12 days
measure: Time of the maximum concentration at steady state (Tss, max) of multiple-dose HS-10380 administration
timeFrame: Up to 12 days
measure: Minimum concentration at steady state (Css, min) of multiple-dose HS-10380 administration
timeFrame: Up to 12 days
measure: Area under the concentration-time curve at steady state (AUCss) of multiple-dose HS-10380 administration
timeFrame: Up to 12 days
measure: Accumulation ratio (RAC) after multiple doses
timeFrame: Up to 12 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
References: