A Phase I, Double-blind, Placebo-controlled, Single Oral Dose, Safety, Tolerability, and Pharmacokinetic Study, Incorporating an Evaluation of the Effect of Food on the Pharmacokinetics of HEC68498 in Healthy Male and Female Subjects
Single-dose, sequential-group design incorporating a food-effect evaluation. Each subject will participate in 1 treatment period, except for Group 5, where each subject will participate in 2 treatment periods. In each group, 6 subjects will receive HEC68498 and 2 subjects will receive placebo. Subjects in Group 5 will receive the same dose level of HEC68498 (or placebo) in both treatment periods. All doses will be administered either after an overnight fast of at least 8 hours or, for subjects in the food-effect evaluation, approximately 30 minutes after starting a standard high-fat breakfast. The first 2 subjects in each group will be dosed (1 subject receiving HEC68498 and 1 subject receiving placebo) 48 hours prior to the remainder of the subjects. There will be a minimum of 7 days between dose escalations. The washout period for subjects in Group 5 will be determined following review of available PK data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
55
HEC68498 is a potent,highly selective inhibitor of class 1 isozymes of phosphoinositide 3-kinase/mammalian(PI3K) and of the mammalian target of rapamycin (mTOR). It has shown good activity against fibrosis and inflammation in vitro and in vivo, with a lower effective dose and better efficacy than pirfenidone and nintedanib.
Placebo
Covance Clinical Research Unit, Inc.
Daytona Beach, Florida, United States
Adverse event
To assess the safety and tolerability of single dose administered
Time frame: up to 4 weeks
AUC0-∞
area under the concentration versus time curve (AUC) from time zero to infinity
Time frame: up to one week
AUC0-t
AUC from time zero to the time of the last quantifiable concentration time zero to the time of the last quantifiable concentration
Time frame: up to one week
Cmax
maximum observed plasma concentration
Time frame: up to one week
tmax
time of the maximum observed plasma concentration
Time frame: up to one week
t½
apparent terminal elimination half-life
Time frame: up to one week
Vz/F
apparent volume of distribution
Time frame: up to one week
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