The study will be a single center, double-blind, randomized, placebo-controlled, multiple-ascending-dose study to evaluate the safety, tolerability, PK and PD of AP303 following 2-week oral administration to healthy Chinese participants.
Eligible study participants will be enrolled and randomized into one of the two dose cohorts, each cohort will include 9 participants randomized to AP303 and placebo at 2:1 ratio (6 on AP303 and 3 on placebo).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
18
AP303 Tablet 150 μg QD
Placebo Tablet 150 μg QD
AP303 Tablet 300 μg QD
Peking University Third Hospital
Beijing, China
Cmax
Maximum observed plasma concentration
Time frame: Day 1, Day 3-14
Tmax
Time to maximum observed plasma concentration
Time frame: Day 1, Day 3-14
AUC0-24h
Area under the plasma concentration versus time curve up to 24 hours
Time frame: Day 1
AUC0-last
Area under the plasma concentration versus time curve up to the last measurable concentration
Time frame: Day 1
AUC0-inf
Area under the plasma concentration versus time curve extrapolated to infinity
Time frame: Day 1
AUC0-t
Area under the plasma concentration-time curve for a dosing interval
Time frame: Day 3-14
t1/2
Apparent terminal half-life, computed as ln(2)/λz
Time frame: Day 1, Day 3-14
CL/F
Apparent oral clearance calculated from Dose/ AUC0-inf
Time frame: Day 1
V/F
Apparent volume of distribution of oral drug
Time frame: Day 1, Day 3-14
Cav
average plasma concentration
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Placebo Tablet 300 μg QD
Time frame: Day 3-14
Ctrough
Trough plasma concentration
Time frame: Day 3-14
Rac
Ratio of accumulation
Time frame: Day 3-14
Incidence and severity of adverse events
Incidence and severity of adverse events
Time frame: Day 1-28
Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results
Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results
Time frame: Day 1-28
Effect of AP303 on ECG parameters
Heart rate in beats/min
Time frame: Day 1-28
Effect of AP303 on ECG parameters
QT in ms
Time frame: Day 1-28
Effect of AP303 on ECG parameters
PR in ms
Time frame: Day 1-28
Effect of AP303 on ECG parameters
QRS in ms
Time frame: Day 1-28
Effect of AP303 on ECG parameters
QTcF in ms
Time frame: Day 1-28
Effect of AP303 on ECG parameters
QTcB in ms
Time frame: Day 1-28
Vital signs
Effect of AP303 on vital signs, e.g. blood pressure
Time frame: Day 1-28
Effect of AP303 on physical examination result
nature, frequency, and severity of abnormality of physical examination result
Time frame: Day 1-28
body weight
Effect of AP303 on body weight, e.g. change of body weight after administration of AP303
Time frame: Day 1-28
Fasting glucose
Fasting glucose
Time frame: Baseline, Days 5, 10, 14 and 28
Fasting lipid profile
Triglyceride, HDL-C, LDL-C, Total cholesterol
Time frame: Baseline, Days 5, 10, 14 and 28
Serum creatinine
Serum creatinine
Time frame: Baseline, Days 5, 10, 14 and 28
eGFR
Estimated glomerular filtration rate
Time frame: Baseline, Days 5, 10, 14 and 28