Safety, Tolerability, Pharmacokinetics(PK), Pharmacodynamics(PD) and Food Effect of HRS9950 in Healthy and CHB Subjects
- Registration Number
- NCT04464733
- Lead Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 146
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Healthy subjects
- Signed informed consent.
- Aged 18~55.
- Body weight ≥ 50 kg for male; ≥ 45 kg for female, body mass index (BMI) between 18 to 28 kg/m2.
- 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.
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CHB subjects
- Signed informed consent.
- Aged 18~65.
- 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 4. Treatment-experienced CHB subjects should also meet the following criteria:
- Have received nucleoside analogue treatment for at least 6 months
- HBeAg positive or negative, and the HBV DNA concentration should be less than 20 IU/mL for at least 6 months before enrollment
- Confirm ALT <1.5 ULN (upper limit of normal value) by two measurements within 6 months before enrollment 5. Treatment-naïve CHB subjects should also meet the following criteria:
- Have not received antiviral therapy (nucleosides or interferons) at screening
- HBeAg positive or negative, and the HBV DNA concentration should be greater than 2000 IU/mL for at least 6 months before enrollment
- Confirm ALT> 1 ULN by two measurements within 6 months before enrollment 6. Female subjects (including partner) of childbearing potential must be using a medically acceptable form of birth control.
-
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.
- Have any drug that inhibits or induces liver metabolism within 1 month.
- Take any prescription drugs, over-the-counter drugs and Chinese herbal medicines within 14 days before taking the study drug, or took any drugs within 5 half-lives at the time of screening; plan to take other drugs during the test period.
- Participated in clinical trials of any drug or medical device within 3 months before screening, or within 5 half-lives before screening.
- Had donated blood or blood transfusion in 8 weeks or ≥ 400 mL within 3 months prior to screening or ≥ 200 mL within 1 months.
- The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);
- Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet;
- Pregnant or lactating women;
- Drug screening or alcohol breath test is positive.
- Other conditions that the investigator believes the subject is not suitable.
-
CHB subjects
-
Currently suffering from serious cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases other than hepatitis B.
-
People have acute or chronic liver disease by non-HBV infection.
-
Liver stiffness (LSM)> 12.4 kPa by noninvasive transient liver elastography (eg Fibroscan®) or recorded liver biopsy suggesting cirrhosis or extensive fibrosis
-
Primary liver cancer, high-risk groups of primary liver cancer or AFP> 50g/L;
-
Have clinically demonstrated or history of liver function decompensation, including but not limited to: hepatic encephalopathy, hepatorenal syndrome, splenomegaly, ascites, etc.;
-
Laboratory inspection:
- Platelet count <90×109/L;
- White blood cell count <3.0×109/L;
- Absolute value of neutrophils <1.5×109/L;
- Serum total bilirubin>2×ULN;
- Albumin <30 g/L;
- Creatinine clearance rate ≤60ml/min;
- INR>1.5;
- ALT exceeds 5 times the upper limit of normal value on screening/baseline visit
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HIV and/or syphilis antibody positive
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Subjects who have previously received organ/bone marrow transplantation;
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Have used immunosuppressants, immunomodulators or cytotoxic drugs within 6 months before the study medication;
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Suspected allergy to any ingredient in the study drug.
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The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);
-
Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet;
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Pregnant or lactating women;
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Drug screening or alcohol breath test is positive.
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Other conditions that the investigator believes the subject is not suitable.
-
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment group J HRS9950 multiple doses Treatment group M HRS9950 single dose Treatment group N HRS9950 multiple doses Treatment group O HRS9950 multiple doses Treatment group G HRS9950 multiple doses Treatment group G Placebo multiple doses Treatment group H HRS9950 multiple doses Treatment group H Placebo multiple doses Treatment group I HRS9950 multiple doses Treatment group I Placebo multiple doses Treatment group J Placebo multiple doses Treatment group K HRS9950 single dose Treatment group K Placebo single dose Treatment group L HRS9950 single dose Treatment group L Placebo single dose Treatment group M Placebo single dose Treatment group N Placebo multiple doses Treatment group O Placebo multiple doses Treatment group A HRS9950 single dose Treatment group A Placebo single dose Treatment group B HRS9950 single dose Treatment group B Placebo single dose Treatment group C HRS9950 single dose; food effect Treatment group C Placebo single dose; food effect Treatment group D HRS9950 single dose Treatment group D Placebo single dose Treatment group E HRS9950 single dose Treatment group E Placebo single dose Treatment group F HRS9950 multiple doses Treatment group F Placebo multiple doses
- Primary Outcome Measures
Name Time Method The incidence and severity of treatment-related adverse events as assessed by CTCAE v5.0 8 DAYS for Group A-M; 29 DAYS for Group F; 50 DAYS for Group G-O Maximum Plasma Concentration [Cmax] 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] 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] 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] 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] 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）] 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] 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 0-48 hours after each dose for Group A-E、G-O After single or multiple administration of HRS9950
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Beijing Youan Hospital,Capital Medical University
🇨🇳Beijing, Beijing, China