A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics ，Pharmacodynamics of Oral SHR2150 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The study is a randomized, Double-Blind, Placebo-Controlled study to evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of SHR2150. will consist of 50 healthy subjects, 5 groups. The purpose of this part is to explore the safety, tolerability ,pharmacokinetics and pharmacodynamics of single doses of SHR2150 capsule in healthy subjects.

Official Title
-----------------
A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics, Pharmacodynamics of Oral SHR2150 in Healthy Subjects With Single Dose of SHR2150 in Healthy Subjects

Conditions
-----------------
HIV-1 Infection

Intervention / Treatment
-----------------
* Drug: SHR2150；Placebo
* Drug: SHR2150；Placebo
* Drug: SHR2150；Placebo
* Drug: SHR2150；Placebo
* Drug: SHR2150；Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent. Aged 18 45. Body weight ≥ 50 kg for male; ≥ 45 kg for female, body mass index (BMI) between 18 to 28 kg/m2 ( Including boundary value) . Vital signs, physical examination, laboratory results are within normal range or considered not clinically significant. Female subjects (including partner) of childbearing potential must be using a medically acceptable form of birth control. Exclusion Criteria: Currently suffering from cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases. Have severe infection, severe trauma or major surgical operations within 3 months. Plan to receive surgery during the trial and within two weeks after the end of the trial.. 12-ECG test have clinical significant abnormality or the QT interval (QTc) > 450 ms(male)/QTc)> 460 ms(male) or<300ms(female). Screening for infectious diseases is positive (Including HBsAg, Anti-HCV, TPPA, Anti-HIV) Suspected allergy to any ingredient in the study drug. Have any drug that inhibits or induces liver metabolism within 1 month. Any condition or disease that affects the absorption, metabolism, and/or excretion of the study drug judged by the investigator; Treatment with immunosuppressant or interferon-containing drugs within 6 months of study drug administration; Participated in clinical trials of any drug or medical device within 3 months before screening, or within 5 half-lives before screening; Treatment with live(attenuated) vaccine within 2 months before taking the study drug or during the study or within 1 months after administration; Had donated blood or blood transfusion≥ 200 mL within 1 months before taking the study drug or had donated blood or blood transfusion≥ 400 mL within 3 months prior to screening; The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol); Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet; History of drug abuse , drug dependence or drug screening test is positive; Pregnant or lactating women; Other conditions that the investigator believes the subject is not suitable.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br> | Drug: SHR2150；Placebo<br>* Single dose；SHR2150-dose 1 or Placebo-dose 1<br>|
| Experimental: Treatment group B<br> | Drug: SHR2150；Placebo<br>* Single dose；SHR2150-dose 2 or Placebo-dose 2<br>|
| Experimental: Treatment group C<br> | Drug: SHR2150；Placebo<br>* Single dose；SHR2150-dose 3 or Placebo-dose 3<br>|
| Experimental: Treatment group D<br> | Drug: SHR2150；Placebo<br>* Single dose；SHR2150-dose 4 or Placebo-dose 4<br>|
| Experimental: Treatment group E<br> | Drug: SHR2150；Placebo<br>* Single dose；SHR2150-dose 5 or Placebo-dose 5<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of treatment-related adverse events as assessed by CTCAE v5.0. |  | 9 DAYS for Group A.B.C.D.E | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma ：[AUC0-last] | The area under the concentration-time curve from time zero (pre-dose) to last time. | Up to 96hours | 
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma ： [AUC0-∞] | The area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. | Up to 96hours | 
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma ：[t1/2] | Terminal Half-life | Up to 96hours | 
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma： [Tmax] | Time to Maximum Observed Concentration | Up to 96hours | 
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma ： [Cmax] | Maximum Observed Plasma Concentration | Up to 96hours | 
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma ： [CL/F] | Apparent clearance | Up to 96hours | 
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma ： [Vz/F] | Apparent volume of distribution | Up to 96hours | 
| Pharmacokinetic parameters of SHR2150, , main metabolite and identified major metabolites in plasma ： [MRT] | Mean retention time | Up to 96hours | 
| Pharmacodynamics: Changes in Cytokines in Serum: interferon γ-inducible protein-10 |  | Up to 48hhours | 
| Pharmacodynamics: Changes in Cytokines in Serum: Interferon-α |  | Up to 48hours |