The primary objectives of this study are to evaluate the safety, tolerability and pharmacokinetics characteristics of single ascending dose (SAD) of PA1010 tablets in Chinese healthy adults and the impact of food and gender on the pharmacokinetics
Stage I: Single dose, Single Ascending Dose (SAD) This is a randomized, double-blind, placebo-controlled, dose-escalation clinical trial. The objective is to evaluate the safety, tolerability and pharmacokinetics characteristics of PA1010 tablets in Chinese healthy subjects. There are six dose groups of PA1010 ( 5 mg、10 mg、20 mg、30 mg、45 mg and 60 mg) proposed to be tested sequentially in this study. A total of 60 healthy subjects are planned to be enrolled in this study and will be randomly assigned to the corresponding dose group in equal proportion, stratified by gender (male vs female). 10 subjects in each dose group are randomly assigned in a ratio of 4:1 to receive PA1010 tablets or placebo. All subjects will be dosed in a single dose, and the dose-related safety, tolerability and PK of PA1010 will be evaluated. Stage II: Study on the effect of food on Pharmacokinetics This is a single center, randomized, open, two group crossover, self-control clinical trial. A total of 20 subjects are planned to be enrolled in this study, and will be randomly assigned to a dosing order (i.e. fasting administration followed by high-fat meal administration, or high-fat meal administration followed by fasting administration) in a ratio of 1:1. Subjects will be dosed 10 mg PA1010 tablets in a single dose, and the food-related PK of PA1010 will be evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
Placebo as control
Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, China
Number of subjects having abnormal hematology laboratory parameters
Absolute and relative number of subjects with values below, within or above the normal range will be assessed.
Time frame: Up to 72 hours after last dose
Number of subjects with abnormal clinical chemistry parameters
Absolute and relative number of subjects with values below, within or above the normal range will be assessed.
Time frame: Up to 72 hours after last dose
Number of subjects with abnormal values for urinalysis
Absolute and relative number of subjects with values below, within or above the normal range will be assessed.
Time frame: Up to 72 hours after last dose
Number of subjects with abnormal with blood coagulation function
Absolute and relative number of subjects with values below, within or above the normal range will be assessed.
Time frame: Up to 72 hours after last dose
Ear temperature
Vital sign-ear temperature
Time frame: Up to 72 hours after last dose
Systolic and diastolic blood pressure
Vital sign-Systolic and diastolic blood pressure
Time frame: Up to 72 hours after last dose
Pulse rate
Vital sign-Pulse rate
Time frame: Up to 72 hours after last dose
Breathing rate
Vital sign-Breathing rate
Time frame: Up to 72 hours after last dose
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ECG parameter-QTc interval
A 12 lead electrocardiogram (ECG) will be recorded using an ECG machine that automatically calculates the QTc intervals
Time frame: Up to 72 hours after last dose
ECG parameter-PR interval
A 12 lead electrocardiogram (ECG) will be recorded using an ECG machine that automatically measures PR intervals
Time frame: Up to 72 hours after last dose
ECG parameter-QRS duration
A 12 lead electrocardiogram (ECG) will be recorded using an ECG machine that automatically measures QRS duration
Time frame: Up to 72 hours after last dose
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: Up to 4days after the last dose
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: Up to 72 hours after last dose
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)
Time frame: Up to 72 hours after last dose
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: Up to 72 hours after last dose
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: Up to 72 hours after last dose
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: Up to 72 hours after last dose
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: Up to 72 hours after last dose
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: Up to 72 hours after last dose