the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of HEC83518 Tablets

Study Overview
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Brief Summary
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Multiple Dose Safety, Tolerability, PK ，PD and Food Effect Study of HEC83518 in Healthy Subjects

Official Title
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A Phase I,Double-Blind, Placebo-Controlled, Multiple Oral Dose, Safety, Tolerability, Pharmacokinetics and Food Effect Study of HEC83518 Tablets in Healthy Chinese Subjects

Conditions
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Insomnia

Intervention / Treatment
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* Other: Food
* Drug: HEC83518
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are willing and are able to provide a written informed consent to participate in the study. Without Plan for pregnancy or pregnant within 3 months after enrollment throughout the trial. Subjects aged between 18 and 45 (both inclusive) years old. Healthy volunteers have a body weight ≥50 kg (for male) or ≥ 45kg (for female) and body mass index ≥18 and ≤28 kg/m2 at screening. Subjects, who are healthy, as having no clinically significant abnormalities in vital signs, physical examination, clinical laboratory test results, Chest X-ray and 12-lead electrocardiogram (ECG). Exclusion Criteria: Subjects with a heart rate ≥100 beats per minute or ≤ 60 beats per minute at screening or baseline. Subjects with a positive serology for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies and/or TP antibodies at screening. Subjects with history of digestive system,urinary system, liver,central nervous system, blood system, endocrine system,respiratory system,immune system,cardiovascular system,and/or malignant tumor or others medical conditions (such as history of mental illness, etc.) that are not suitable for clinical trial participation;Subjects with history of stroke, epilepsy, bipolar disorder/mania, high intraocular pressure, or acute angular-closure glaucoma. Subjects with history of sleep-related illness. Subjects with history of severe involuntary hypoglycemia Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s) ,or anaphylaxis physique. Use of any prescription or non-prescription medications within 14 days prior to initial dosing,or Use of any medications known to inhibit or induce cytochrome P enzyme drug metabolism within 28 days prior to initial dosing. Consume foods or beverages containing caffeine, xanthine, alcohol, and grapefruit within 48 hours prior to initial dosing. Positive results from urine drug screen test. History of alcoholism or drink regularly within 3 months prior to the study(defined as Alcohol consumption of > 21 units/week), or positive results from alcohol breath test. Regular smoking of more than 10 cigarettes per day within 3 months before administration of study drug. Donate blood or lose blood 400 mL or more within 1 month prior to initial dosing. Subjects who plan to receive or have had organ transplants. Females who are lactating/breastfeeding, or positive result from pregnancy test for women of child-bearing potential. 15 Subjects who participated in another clinical trial within 3 months prior to initial dosing. 16.Any other condition with in the opinion of the investigator would render the patient unsuitable for inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Food effect<br>HEC83518 40mg will be administered fasted, or with high-fat meal for once. | Other: Food<br>* HEC83518 40mg will be taken orally fasted or with food<br>|
| Experimental: Multiple Ascending Doses-HEC83518 20mg<br>HEC83518 20mg will be administered before sleep for 15 days . | Drug: HEC83518<br>* HEC83518 will be taken orally before sleep for 15 days<br>|
| Experimental: Multiple Ascending Doses-HEC83518 40mg<br>HEC83518 40mg will be administered before sleep for 15 days . | Drug: HEC83518<br>* HEC83518 will be taken orally before sleep for 15 days<br>|
| Experimental: Multiple Ascending Doses-HEC83518 80mg<br>HEC83518 80mg will be administered before sleep for 15 days . | Drug: HEC83518<br>* HEC83518 will be taken orally before sleep for 15 days<br>|
| Placebo Comparator: Multiple Ascending Doses-placebo<br>Placebo will be administered before sleep for 15 days . | Drug: placebo<br>* The placebo will be administered before sleep for 15 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event | To assess the safety and tolerability of therapy | up to 34 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration versus time curve (AUC) from time zero to infinity(AUC0-∞ ) |  | up to 72 hours | 
| Maximum Plasma Concentration ( Cmax) |  | up to 72 hours | 
| Time to peak(tmax) |  | up to 72 hours | 
| Apparent terminal elimination half-life(t½) |  | up to 72 hours | 
| Apparent volume of distribution(Vz/F) |  | up to 72 hours | 
| The Mean Residence Time#(MRT) |  | up to 72 hours | 
| The Apparent Clearance (CL/F) |  | up to 72 hours | 
| The Accumulation Ratio(R) |  | up to 60 hours | 
| Food Effect on the Cmax |  | up to 72 hours | 
| Food Effect on the AUC |  | up to 72 hours |