Statistical analysis
SAD
The sample size for SAD and MAD studies adhered to the “Guidelines for clinical pharmacokinetic studies of chemical drugs” by the China National Medical Products Administration, which recommends 8–12 healthy subjects in each dose group for both studies. However, in order to reduce drug exposure in high-dose groups for safety and tolerability reasons, the 60 mg and 80 mg groups for the SAD study were limited to 6 subjects per group. The sample size for the FE study was determined according to the “Food-Effect Bioavailability and Fed Bioequivalence Studies” by United States Food and Drug Administration, which recommends enrolling at least 12 subjects in the FE group. No formal statistical calculation was used to predefine the sample size. The study administrator used SAS version 9.4 of the PLAN program to allocate study subjects randomly. Randomized tables for each dose group in SAD and MAD studies were generated with the ratio of AD16/placebo. The FE arm was randomly divided into two groups in a 1:1 ratio using a stratified block randomization method. Further details about study randomization are provided in Additional file Full analysis set (FAS) consisted of all subjects who underwent randomization and received at least one dose. All randomized subjects with at least one dose and post-dose safety information were included in the safety analysis set (SS). All subjects who underwent randomization and had at least one measurable concentration without a protocol deviation that could have impacted the PK data are included in the PK analysis set (PKS).PK parameters in PKS were computed using the WinNonlin version 6.4 non-AV model. The relationship between drug dose and drug plasma exposure was assessed by plotting the scatterplots of log-transformed PK parameters (The impact of taking food on AD16 tablets was assessed by calculating the geometric mean ratio (GMR) of fasting and post-prandial AUCStatistical analysis was performed using the statistical software SAS 9.4. AD16 plasma, urine, and fecal concentrations were tabulated, and descriptive statistical analyses were conducted by dose group, subject, and visit/sampling time point. The research results were reported in the form of summary tables and lists.