The primary objectives of this study are to evaluate the safety and tolerance of single and multiple oral administration of PA3670 tablets in Chinese adult healthy subjects and the effect of food on pharmacokinetics of PA3670 tablets in Chinese adult healthy subjects.
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 PA3670 tablets in Chinese healthy subjects. There are three dose groups of PA3670(5 mg、15 mg、30 mg) proposed to be tested sequentially in this study. A total of 30 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 PA3670 tablets or placebo. All subjects will be dosed in a single dose, and the dose-related safety, tolerability and PK of PA3670 will be evaluated. Stage Ⅱ: Multiple dose This is a randomized, double-blind, placebo-controlled, multiple dose clinical trial. A total of 10 subjects are planned to be enrolled in this study and will be randomly assigned in a ratio of 4:1 to receive 15mg PA3670 tablets or placebo. All subjects will be dosed for 9 consecutive days, and safety, tolerability and PK of PA3670 will be evaluated. Stage Ⅲ: Study on the effect of food on Pharmacokinetics This is a randomized, open, two group crossover 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 15 mg PA3670 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
60
Placebo as control
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
Body temperature
Vital sign-body 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
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
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ECG parameter-QTc interval
A 12-lead electrocardiogram (ECG) will be recorded using an ECG machine that automatically measures QTc interval
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 interval.
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: 7 days or 15 days
Pharmacokinetics of PA3670-Cmax
Blood samples will be collected serially, and the concentrations of PA3670 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: 4 days or 12 days
Pharmacokinetics of PA3670-Tmax
Blood samples will be collected serially, and the concentrations of PA3670 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: 4 days or 12 days
Pharmacokinetics of single dose of PA3670-AUC
Blood samples will be collected serially, and the concentrations of PA3670 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: 4 days or 12 days