Human Immunodeficiency Virus-1 (HIV-1) Infection
Conditions
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.
Interventions
DRUGHRS5685；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
Sponsors
RetroLead (Shanghai) BioPharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This is a randomized, double-blinded, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability: Incidence and severity of adverse events | Up to Day 63 after the last dose |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Area under the concentration-time curve during a dosing interval (AUCtau), | 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 |
| Apparent volume of distribution (Vz/F) | Pre-dose up to Day 63 after the last dose |
Contacts
Primary ContactLiping Ma
Backup ContactShujin Cheng
Outcome results
None listed