A Phase I Study to Evaluate the Safety, Tolerability and PK, PD of Oral HRS9950 in Healthy Subjects With Single or Multiple Dose and Chronic Hepatitis B Patients With Multiple Dose, and Food Effects of HRS9950 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- HRS9950
- Conditions
- Chronic Hepatitis b
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 146
- Locations
- 1
- Primary Endpoint
- The incidence and severity of treatment-related adverse events as assessed by CTCAE v5.0
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The study is a randomized, Double-Blind, Placebo-Controlled study to evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics and food effect of HRS9950. The study will be conducted in three parts sequentially:
Part 1, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of single doses and multiple dose of HRS9950 tablet in healthy subjects. Part 1 will consist of 84 healthy subjects, 8 groups.There will be 14 subjects in 0.75mg dose group,10 subjects in each other dose group .
Part 2, evaluate food effect of HRS9950 in healthy subjects. Part 2 will consist of 14 healthy subjects, 1 group (one of groups in Part 1).
Part 3, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of multiple doses of HRS9950 tablet in naive and treatment-experienced chronic hepatitis B (CHB) patients. Part 3 will consist of 60 CHB patients, 1 group for naive patients and 5 groups for treatment-experienced patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy subjects
- •Signed informed consent.
- •Body weight ≥ 50 kg for male; ≥ 45 kg for female, body mass index (BMI) between 18 to 28 kg/m
- •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.
- •CHB subjects
- •Signed informed consent.
- •CHB subjects should meet the following two criteria:
- •IgM HBcAb negative and HBsAg positive.
- •Two recorded HBsAg positive, and the time interval between the two tests was at least 6 months, one of which was the result of this screening
Exclusion Criteria
- •Healthy subjects
- •Currently suffering from cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases.
- •Medical history of malignant tumor.
- •Have a digestive system disease or a medical history of severe digestive system disease.
- •Have severe infection, severe trauma or major surgical operations within 3 months.
- •12-ECG test have clinical significant abnormality or the QT interval (QTc) \> 450 ms.
- •Clinical laboratory examinations or chest radiographs have clinical significant abnormality.
- •Have a medical history of immune-mediated diseases.
- •Screening for infectious diseases is positive (Including HBsAg, Anti-HCV, TPPA, Anti-HIV).
- •Suspected allergy to any ingredient in the study drug.
Arms & Interventions
Treatment group I
multiple doses
Intervention: HRS9950
Treatment group I
multiple doses
Intervention: Placebo
Treatment group J
multiple doses
Intervention: HRS9950
Treatment group J
multiple doses
Intervention: Placebo
Treatment group K
single dose
Intervention: HRS9950
Treatment group K
single dose
Intervention: Placebo
Treatment group L
single dose
Intervention: HRS9950
Treatment group L
single dose
Intervention: Placebo
Treatment group M
single dose
Intervention: HRS9950
Treatment group M
single dose
Intervention: Placebo
Treatment group N
multiple doses
Intervention: HRS9950
Treatment group N
multiple doses
Intervention: Placebo
Treatment group O
multiple doses
Intervention: HRS9950
Treatment group O
multiple doses
Intervention: Placebo
Treatment group H
multiple doses
Intervention: HRS9950
Treatment group H
multiple doses
Intervention: Placebo
Treatment group A
single dose
Intervention: HRS9950
Treatment group A
single dose
Intervention: Placebo
Treatment group B
single dose
Intervention: HRS9950
Treatment group B
single dose
Intervention: Placebo
Treatment group C
single dose; food effect
Intervention: HRS9950
Treatment group C
single dose; food effect
Intervention: Placebo
Treatment group D
single dose
Intervention: HRS9950
Treatment group D
single dose
Intervention: Placebo
Treatment group E
single dose
Intervention: HRS9950
Treatment group E
single dose
Intervention: Placebo
Treatment group F
multiple doses
Intervention: HRS9950
Treatment group F
multiple doses
Intervention: Placebo
Treatment group G
multiple doses
Intervention: HRS9950
Treatment group G
multiple doses
Intervention: Placebo
Outcomes
Primary Outcomes
The incidence and severity of treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 8 DAYS for Group A-M; 29 DAYS for Group F; 50 DAYS for Group G-O
Maximum Plasma Concentration [Cmax]
Time Frame: 0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 1 and Day 22
Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
Area under the concentration time curve [AUC]
Time Frame: 0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 1 and Day 22
Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
Time to maximum plasma concentration [Tmax]
Time Frame: 0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 1 and Day 22
Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
Apparent clearance [CL/F]
Time Frame: 0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22
Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
Half-time [t1/2]
Time Frame: 0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22
Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
Apparent volume of distribution [Vz/F（Vd）]
Time Frame: 0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22
Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
Mean residence time [MRT]
Time Frame: 0-48 hours after each dose for Group A-E、K-M；Group F- J、N、O at Day 22
Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
The concentration of IL-12p40 in the serum
Time Frame: 0-48 hours after each dose for Group A-E、G-O
After single or multiple administration of HRS9950