The primary objective of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of multiple ascending dose (MAD) of PA1010 tablets in Chinese adults with Chronic Hepatitis B.
This is a multicenter, randomized, open-label, controlled, dose-escalation clinical trial, the objective is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of PA1010 tablets in Chinese patients with Chronic Hepatitis B (CHB). There are three dose groups of PA1010 ( 5 mg, 10 mg, and 20 mg) proposed to be tested sequentially in this study. A total of 36 patients with CHB, either hepatitis B e antigen (HBeAg)-positive (+) or HBeAg-negative (-), are planned to be enrolled in this study and will be stratified by HBeAg status by the ratio of 2: 1, that is, 24 of HBeAg + and 12 of HBeAg- patients. Twelve subjects in each dose group were randomly assigned in a 3: 1 ratio to receive either PA1010 tablets or or tenofovir disoproxil fumarate (TDF) tablets. All patients will be dosed for 28 consecutive days, and the dose-related safety, PK, and antiviral efficacy of PA1010 will be evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
TDF as control
Beijing Tsinghua Changgung Hospital affiliated to Tsinghua
Beijing, Beijing Municipality, China
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
Southern Hospital of Southern Medical University
Guangzhou, Guangdong, China
The First Affiliated Hospital of Medical College of Zhejiang University
Hangzhou, Zhejiang, China
Evaluation the change from baseline in Serum HBV DNA in patients
The primary efficacy endpoint is the change from baseline in Serum HBV DNA in patients on day 28 in all patients. The safety and tolerance are also observed in all treatment groups.
Time frame: 28 days
Evaluation the rate of change from Baseline in Serum HBV DNA
Rate of change from Baseline in Serum HBV DNA
Time frame: 28 days
Evaluation the change from Baseline in Serum HBsAg
Change from Baseline in Serum HBsAg
Time frame: 28 days
Evaluation the change from Baseline in Serum ALT
Change from Baseline in Serum ALT
Time frame: 28 days
Number of subjects experiencing adverse events (AEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical study subject administered a medicinal product which does not necessarily have a causal relationship with this treatment.
Time frame: 28 days
Pharmacokinetics of single dose of PA1010-Cmax
Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Maximum Observed Plasma Concentration (Cmax)
Time frame: 28 days
Pharmacokinetics of single dose of PA1010-Tmax
Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Time to Reach Maximum Observed Plasma Concentration (Tmax)
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Time frame: 28 days
Pharmacokinetics of single dose of PA1010-AUC
Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Area Under the Plasma Concentration-Time Curve (AUC)
Time frame: 28 days
ECG parameter-QTc interval、PR interval、QRS duration
A 12 lead electrocardiogram (ECG) will be recorded using an ECG machine that automatically measures QTc interval、PR interval、QRS duration
Time frame: 28 days
Number of new abnormal signs with clinical significance
Physical examination records include: skin, lymph nodes, head and neck (including thyroid), nervous system examination (including but not limited to speech, cranial nerves, motor ability, tendon reflex, sensation, ataxia), chest (heart, lung), abdomen (liver, gallbladder, spleen, kidney), etc.
Time frame: 28 days
Body temperature, blood pressure, pulse, respiratory rate
Vital signs body temperature, blood pressure, pulse, respiratory rate
Time frame: 28 days
Pharmacokinetics of single dose of PA1010-T1/2
Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Elimination Half-Life Period (T1/2)
Time frame: 28 days
Pharmacokinetics of single dose of PA1010-Vz/F
Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Apparent Volume of Distribution(Vz/F)
Time frame: 28 days
Pharmacokinetics of single dose of PA1010-CL/F
Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Apparent Clearance(CL/F)
Time frame: 28 days
Pharmacokinetics of single dose of PA1010-λz
Blood samples will be collected serially, and the concentrations of PA1010 in plasma samples are determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS), followed by the calculation of pharmacokinetic parameter Elimination Rate Constant(λz)
Time frame: 28 days