To Evaluate the Tolerability, Pharmacodynamics and Pharmacokinetics of GST-HG141 Tablets in Multiple-center, Randomized, Double-blind, Placebo-controlled Multiple-dose, Multiple-administration Study in Patients With Chronic Hepatitis B (CHB)
This study includes 3 cohorts of 25 mg BID, 50 mg BID and 100 mg BID. 30 patients with chronic hepatitis B will be enrolled in this study and each cohort will enroll 10 patients (GST-HG141 tablets : PBO=8:2). All enrolled patients will be given research drugs twice a day for 28 days (D28 was administered only once in the morning). And each cohort requires at least 4 subjects with elevated ALT. Tolerability, pharmacodynamics and pharmacokinetics will be evaluated according to the protocol.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
Administrate GST-HG141 tablets orally in fed state twice daily at 25 mg or 50mg or 100 mg doses
Administrate the placebos for GST-HG141 tablets orally in fed state twice daily at 25 mg or 50mg or 100 mg doses
The first hospital of Jilin University
Changchun, Jilin, China
Number of patients with chronic HBV infection with treatment-related adverse events and laboratory abnormalities.
Symptoms and physical examination, clinical laboratory examination, vital signs,12 lead ECG and adrenal ultrasounds were collected and assessed by CTCAE v5.0.
Time frame: Up to 33 days
Cmax of GST-HG141
Plasma samples were collected at different points for pharmacokinetic analysis
Time frame: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
AUC of GST-HG141
Plasma samples were collected at different points for pharmacokinetic analysis
Time frame: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
t1/2 of GST-HG141
Plasma samples were collected at different points for pharmacokinetic analysis
Time frame: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
Cl/F of GST-HG141
Plasma samples were collected at different points for pharmacokinetic analysis
Time frame: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
The value of serum HBV DNA decreased from baseline
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Plasma samples were collected at different points for pharmacodynamics analysis
Time frame: Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33
The value of serum HBV pgRNA decreased from baseline
Plasma samples were collected at different points for pharmacodynamics analysis
Time frame: Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33
The value of serum HBsAg decreased from baseline
Plasma samples were collected at different points for pharmacodynamics analysis
Time frame: Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33
The value of serum HBeAg decreased from baseline
Plasma samples were collected at different points for pharmacodynamics analysis
Time frame: Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33