This study will evaluate the safety, tolerability and pharmacokinetics (PK) of escalating single- and multiple-oral doses of IMM-H014 on fasted condition, and characterize PK of IMM-H014 on an empty stomach (fasted condition) and following a high fat, high calorie meal (fed condition) in a 2-period, 2-sequence manner. The study will be conducted in 3 parts (Ascending single dose, multiple dose and food effect). Participants will receive either IMM-H014 or placebo.
The study is a randomized, double-blind phase 1 trial including 3 parts: single ascending dose (SAD) part, multiple ascending dose (MAD) part and food effect (FE) part. SAD and MAD parts adopt "sentinel method "which2 healthy subjects first will receive IMM-H014, and if are evaluated to be tolerable, the remaining 8 subjects will be randomly assigned to receive IMM-H014 and placebo in a ratio of 3:1(10 in per experimental Cohort). Subjects in SAD will receive 12.5,37.5,75, 125, 225, 275, 325mg (Cohort 1-4 and Cohort 6-8) once daily respectively. Subjects in MAD will receive 37.5, 75, 125, 175, 225mg (Cohort 9 - Cohort 13) once daily for 7days respectively. FE part is divided into two groups: 8 subjects will receive IMM-H014 and 2 subjects will receive placebo In group A .All 8 subjects will receive IMM-H014 in group B. Group A adopts "sentinel method ".The treatment in food effect consists of 2 periods, and subjects will receive175mg(SAD Cohort 5) on fasting and postprandial states respectively. There will be a 7-day wash out period between treatment periods. To monitor AEs, record abnormalities (12-lead ECG, Vital signs, Physical examination, Clinical Laboratory), and detect the pharmacokinetics of IMM-H014.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
138
SAD and MAD adopt "sentinel method "which 2 healthy subjects first will receive IMM-H014, and if are evaluated to be tolerable, the remaining 8 subjects will be randomly assigned to receive IMM-H014 and placebo in a ratio of 3:1(10 in per experimental Cohort).
SAD and MAD adopt "sentinel method "which 2 healthy subjects first will receive IMM-H014, and if are evaluated to be tolerable, the remaining 8 subjects will be randomly assigned to receive IMM-H014 and placebo in a ratio of 3:1(10 in per experimental Cohort).
FE part is divided into two groups: 8 subjects will receive IMM-H014 and 2 subjects will receive placebo In group A .All 8 subjects will receive IMM-H014 in group B. Group A adopts "sentinel method ".The treatment in food effect consists of 2 periods.
FE part is divided into two groups: 8 subjects will receive IMM-H014 and 2 subjects will receive placebo In group A .All 8 subjects will receive IMM-H014 in group B. Group A adopts "sentinel method ".The treatment in food effect consists of 2 periods.
The first Bethune hospital of Jilin University
Changchun, Jilin, China
RECRUITINGAdverse Events following oral doses (single, multiple and food effect)of IMM-H014 and placebo
the adverse events are recorded according to the actual occurrence
Time frame: through study completion, up to 11, 17, 18 days for SAD, MAD, FE part
Number of participants with abnormal laboratory tests results and abnormal physical exam findings
The data of the clinical research center is collected and analyzed according to the time point of the test flow chart
Time frame: through study completion, up to 4, 10, 11 days for SAD, MAD, FE part
PK parameters: AUClast(AUC0-t)
AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
Time frame: Up to 4, 10, 11 days for SAD, MAD, FE part
PK parameters: AUCinf(AUC0-∞)
AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).
Time frame: Up to 4, 10, 11 days for SAD, MAD, FE part
PK parameters: Cmax
Cmax is defined as the maximum observed concentration of drug in plasma.
Time frame: Up to 4, 10, 11 days for SAD, MAD, FE part
PK parameters: Tmax
Tmax is defined as the time to maximum concentration.
Time frame: Up to 4, 10, 11 days for SAD, MAD, FE part
PK parameters: t1/2
t1/2z is defined as the time to decline half of the drug concentration in plasma.
Time frame: Up to 4, 10, 11 days for SAD, MAD, FE part
PK parameters: CL/F
λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound.
Time frame: Up to 4, 10, 11 days for SAD, MAD, FE part
PK parameters: λz
λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound.
Time frame: Up to 4, 10, 11 days for SAD, MAD, FE part
Multiple-dose plasma PK parameter: Rac
Rac (Accumulation Index) is defined as the ratio between AUC0-XX in Day XX and AUC0-XX in Day1
Time frame: Up to 10 days
Multiple-dose plasma PK parameter: DF
DF is defined as the percentage of fluctuation in steady state is 100 \* (Cmax, ss - Cmin, ss)/Cavg, ss
Time frame: Up to 10 days
Multiple-dose plasma PK parameter: Cmin
Cmin is defined as the minimum observed concentration of drug in plasma at steady state.
Time frame: Up to 10 days
Multiple-dose plasma PK parameter: Cmax
Cmax is defined as the maximum observed concentration of drug in plasma at steady state.
Time frame: Up to 10 days
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