The Safety, Tolerability, and Pharmacokinetics Study of HEC113995 PA•H2O Tablets in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The Safety, Tolerability and Pharmacokinetics Study of HEC113995 PA•H2O Tablets in Healthy Male and Female Subjects

Official Title
-----------------
A Phase I, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Clinical Study to Assess the Safety, Tolerability and Pharmacokinetics of HEC113995 PA•H2O Tablets in Healthy Subjects

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: HEC113995 PA•H2O tablets
* Drug: Placebo tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Subjects who are willing and are able to provide a written informed consent to participate in the study. 2. Without Plan for pregnancy or pregnant within 3 months after enrollment throughout the trial. 3. Subjects aged between 18 and 45 (both inclusive) years old. 4. Healthy volunteers has a body weight ≥50 kg (for male) or ≥ 45kg (for female) and body mass index ≥18 and ≤28 kg/m2 at screening. 5. 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: 1.Subjects with serum creatinine, ALT and AST levels ≥1.5 times of the upper limit of normal value at screening. 2.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. 3. 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 epilepsy, bipolar disorder/mania, high intraocular pressure, or acute angular-closure glaucoma. 4. Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s)# anaphylaxis physique. 5. Use of any prescription or non-prescription medications within 14 days prior to initial dosing#Use of any medications known to inhibit or induce cytochrome P enzyme drug metabolism within 28 days prior to initial dosing. 6. Consume foods or beverages containing caffeine, xanthine, alcohol, and grapefruit within 48 hours prior to initial dosing. 7. Positive results from urine drug screen test. 8. 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. 9.Regular smoking of more than 10 cigarettes per day within 3 months before administration of study drug, or inability to refrain from smoking during the course of the study. 10. Donate blood or lose blood 400 mL or more within 1 month prior to initial dosing. 11. Subjects who plan to receive or have had organ transplants. 12. Subjects who participated in another clinical trial within 3 months prior to initial dosing. 13. Any other condition with in the opinion of the investigator would render the patient unsuitable for inclusion in the study.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEC113995 PA•H2O 2.5mg<br>Healthy subjects are given HEC113995 PA•H2O 2.5 mg in a single dose. | Drug: HEC113995 PA•H2O tablets<br>* Each dose of HEC113995 PA•H2O tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|
| Active Comparator: HEC113995 PA•H2O 5mg<br>Healthy subjects are given HEC113995 PA•H2O 5 mg in a single dose. | Drug: HEC113995 PA•H2O tablets<br>* Each dose of HEC113995 PA•H2O tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|
| Active Comparator: HEC113995 PA•H2O 10mg<br>Healthy subjects are given HEC113995 PA•H2O 10 mg in a single dose. | Drug: HEC113995 PA•H2O tablets<br>* Each dose of HEC113995 PA•H2O tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|
| Active Comparator: HEC113995 PA•H2O 20mg<br>Healthy subjects are given HEC113995 PA•H2O 20 mg in a single dose. | Drug: HEC113995 PA•H2O tablets<br>* Each dose of HEC113995 PA•H2O tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|
| Active Comparator: HEC113995 PA•H2O 40mg<br>Healthy subjects are given HEC113995 PA•H2O 40 mg in a single dose. | Drug: HEC113995 PA•H2O tablets<br>* Each dose of HEC113995 PA•H2O tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|
| Active Comparator: HEC113995 PA•H2O 60mg<br>Healthy subjects are given HEC113995 PA•H2O 60 mg in a single dose. | Drug: HEC113995 PA•H2O tablets<br>* Each dose of HEC113995 PA•H2O tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|
| Active Comparator: HEC113995 PA•H2O 80mg<br>Healthy subjects are given HEC113995 PA•H2O 80 mg in a single dose. | Drug: HEC113995 PA•H2O tablets<br>* Each dose of HEC113995 PA•H2O tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|
| Placebo Comparator: placebo<br>Healthy subjects are given placebo in a single dose. | Drug: Placebo tablets<br>* Placebo tablets will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of HEC113995 PA•H2O by Assessment of the Number of Adverse Events (AEs) Following Administration in Single Ascending Dose | To investigate the safety and tolerability of HEC113995 PA•H2O by assessment of AEs (non-serious and serious) following administration in SAD | up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters - AUC0-∞ | area under the concentration versus time curve (AUC) from time zero to infinity | up to 144 hours | 
| PK parameters - Cmax | Geometric Mean of Maximum Observed Plasma Concentration of HEC113995 PA•H2O | up to 144 hours | 
| PK parameters -tmax | time to peak | up to 144 hours | 
| PK parameters -t½ | apparent terminal elimination half-life | up to 144 hours | 
| PK parameters -Vz/F | apparent volume of distribution | up to 144 hours | 
| PK parameters - MRT | the Mean Residence Time | up to 144 hours | 
| PK parameters -CL/F | the Apparent Clearance | up to 144 hours |