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

Phase 1

• Conditions: Human Immunodeficiency Virus-1 (HIV-1) Infection
• Interventions: Drug: HRS5685；Placebo

• Registration Number: NCT05328583
• Lead Sponsor: RetroLead (Shanghai) BioPharma Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-03
• Study First Submitted: 2022-03-29
• Study First Submitted QC: 2022-04-06
• Last Update Submitted: 2022-04-06
• Study First Posted: 2022-04-14
• Last Update Posted: 2022-04-14
• Study Start: 2022-04-15
• Primary Completion: 2023-03-10
• Study Completion: 2023-03-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Able and willing to provide written informed consent and to comply with the study protocol;
2. Must be 18 to 45 years of age (inclusive);
3. 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);
4. 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;
5. 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

1. 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;
2. 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;
3. Abnormal ECG that is clinically significant, or QTcF< 300 msec or >450 msec for men and >460 msec for women;
4. 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;
5. Suspected allergy to any ingredient in the study drug;
6. Use of any drug that inhibits or induces hepatic metabolism within 1 month prior to the first dose of study drug;
7. Any condition or disease that affects the absorption, metabolism, and/or excretion of the study drug as judged by the investigator;
8. Use of any prescription or over-the-counter medication, including herbal medications within 1 month prior to the first dose of study drug;
9. 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);
10. Receiving vaccine(s) within 1 month prior to the first dose of study drug;
11. 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;
12. 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;
13. Subjects who cannot refrain from smoking and alcohol intake from 2 days before the start of study treatment until the last follow-up;
14. 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;
15. 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;
16. Pregnant or lactating females;
17. Other conditions judged by the investigator to be not suitable to participate in the trial;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment group A（Part A）	HRS5685；Placebo	Drug1: HRS5685, dose 1; Drug2: Placebo
Treatment group D（Part A）	HRS5685；Placebo	Drug1: HRS5685, dose 4; Drug2: Placebo
Treatment group H（Part B）	HRS5685；Placebo	Drug1: HRS5685, dose 4; Drug2: Placebo
Treatment group B（Part A）	HRS5685；Placebo	Drug1: HRS5685, dose 2; Drug2: Placebo
Treatment group C（Part A）	HRS5685；Placebo	Drug1: HRS5685, dose 3; Drug2: Placebo
Treatment group E（Part A）	HRS5685；Placebo	Drug1: HRS5685, dose 5; Drug2: Placebo
Treatment group F（Part A）	HRS5685；Placebo	Drug1: HRS5685, dose 6; Drug2: Placebo
Treatment group G（Part B）	HRS5685；Placebo	Drug1: HRS5685, dose 3; Drug2: Placebo

Primary Outcome Measures

Name	Time	Method
Safety and tolerability: Incidence and severity of adverse events	Up to Day 63 after the last dose

Secondary Outcome Measures

Name	Time	Method
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
Apparent clearance (CL/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
Cumulative percentage of dose recovered (fe)	Pre-dose up to 72 hours post-dose
Area under the concentration-time curve during a dosing interval (AUCtau),	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
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
Half-life (t1/2),	Pre-dose up to Day 63 after the last dose