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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Human Immunodeficiency Virus-1 (HIV-1) Infection
• Intervention / Treatment: Drug: HRS5685；Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Liping Ma; Phone Number: 0518-82342973; Email: liping.ma@hengrui.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: RetroLead (Shanghai) BioPharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 15, 2022
• Primary Completion (Anticipated): March 10, 2023
• Study Completion (Anticipated): March 10, 2023

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 6, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: HRS5685-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No