A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral HRS5685 in Healthy Subjects

Study Overview
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Brief Summary
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This is a randomized, double-blinded, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of single ascending dose (Part A) and multiple ascending dose (Part B) of HRS5685 tablet in healthy subjects.

Official Title
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A Phase I Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral HRS5685 in Healthy Subjects

Conditions
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Human Immunodeficiency Virus-1 (HIV-1) Infection

Intervention / Treatment
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* Drug: HRS5685；Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide written informed consent and to comply with the study protocol; Must be 18 to 45 years of age (inclusive); Body weight of at least 50 kg for male, and 45 kg for female; and Body Mass Index (BMI) within the range of 18 to 28 kg/m2 (inclusive); Physical examination, vital signs, laboratory tests, 12-lead ECG, eGFR (CKD-EPI formula), abdominal ultrasound and chest radiograph are normal or are judged not clinically significant by the investigator; Subjects (including partners) of childbearing potential are willing to useprotocol specified effective methods of contraception from screening to at least 8 months (for female) or 6 months (for male) after the final dose of study drug; Exclusion Criteria: History or presence of any clinically significant cardiovascular, endocrine, neurological, gastrointestinal, respiratory, hematological, immunological, psychiatric, metabolic disorders or any diseases that may interfere with the study results; Subjects with severe infections, severe trauma or major surgical operation within 3 months before drug administration; or subjects plan to undergo surgery during the trial and within two weeks after the end of trial; Abnormal ECG that is clinically significant, or QTcF< 300 msec or >450 msec for men and >460 msec for women; Positive test result of any of the following at screening: hepatitis B surface antigen (HBsAg), hepatitis C antibody, syphilis, or human immunodeficiency virus (HIV) antibody; Suspected allergy to any ingredient in the study drug; Use of any drug that inhibits or induces hepatic metabolism within 1 month prior to the first dose of study drug; Any condition or disease that affects the absorption, metabolism, and/or excretion of the study drug as judged by the investigator; Use of any prescription or over-the-counter medication, including herbal medications within 1 month prior to the first dose of study drug; Participation in clinical trials of any drug or medical device (except for screening failures) within 3 months before screening, or within 5 half-lives of the drug at screening (whichever is longer); Receiving vaccine(s) within 1 month prior to the first dose of study drug; Donation or loss of blood of ≥ 200 mL within 1 month or of ≥ 400 mL within 3 months prior to the first dose of study drug; or receiving blood transfusion within 8 weeks prior to the first dose of study drug; or have difficulty in venous blood collection, or whose physical condition cannot withstand intensive blood sampling; An average daily smoking of ≥ 5 cigarettes or an average daily alcohol intake of 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol liquor) within 3 months before screening; Subjects who cannot refrain from smoking and alcohol intake from 2 days before the start of study treatment until the last follow-up; Subjects who consume alcoholic beverages, Seville oranges, grapefruit or juices, or products containing caffeine or xanthine (such as coffee, tea, cola drinks and chocolate) from 2 days before the start of study treatment, and those who have special dietary requirements and cannot comply with the unified diet; Subjects with a history of drug abuse, drug dependence, or a positive drugs of abuse test, or a positive alcohol breath test before study drug administration; Pregnant or lactating females; Other conditions judged by the investigator to be not suitable to participate in the trial;

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, double-blinded, placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A（Part A）<br>Drug1: HRS5685, dose 1; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|
| Experimental: Treatment group B（Part A）<br>Drug1: HRS5685, dose 2; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|
| Experimental: Treatment group C（Part A）<br>Drug1: HRS5685, dose 3; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|
| Experimental: Treatment group D（Part A）<br>Drug1: HRS5685, dose 4; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|
| Experimental: Treatment group E（Part A）<br>Drug1: HRS5685, dose 5; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|
| Experimental: Treatment group F（Part A）<br>Drug1: HRS5685, dose 6; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|
| Experimental: Treatment group G（Part B）<br>Drug1: HRS5685, dose 3; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|
| Experimental: Treatment group H（Part B）<br>Drug1: HRS5685, dose 4; Drug2: Placebo | Drug: HRS5685；Placebo<br>* Drug1: HRS5685 Single dose in group A-F and multiple doses in group G-H Drug2: Placebo Single dose in group A-F and multiple doses in group G-H<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Incidence and severity of adverse events |  | Up to Day 63 after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve during a dosing interval (AUCtau), |  | Pre-dose up to Day 63 after the last dose | 
| Area under the concentration-time curve from time zero to the last quantifiable time point t (AUC0-t) |  | Pre-dose up to Day 63 after the last dose | 
| Area under the concentration-time curve extrapolated to infinity (AUC0-inf ) |  | Pre-dose up to Day 63 after the last dose | 
| Maximum observed concentration (Cmax) |  | Pre-dose up to Day 63 after the last dose | 
| Time to Maximum observed concentration (Tmax) |  | Pre-dose up to Day 63 after the last dose | 
| Half-life (t1/2), |  | Pre-dose up to Day 63 after the last dose | 
| Apparent clearance (CL/F) |  | Pre-dose up to Day 63 after the last dose | 
| Apparent volume of distribution (Vz/F) |  | Pre-dose up to Day 63 after the last dose | 
| Trough concentration (Ctrough) |  | Pre-dose up to Day 63 after the last dose | 
| Accumulation ratio (Rac), |  | Pre-dose up to Day 63 after the last dose | 
| Renal clearance (CLr) |  | Pre-dose up to 72 hours post-dose | 
| Cumulative amount of drug excreted (Ae) |  | Pre-dose up to 72 hours post-dose | 
| Cumulative percentage of dose recovered (fe) |  | Pre-dose up to 72 hours post-dose |