Study methods

This study examined all phase I clinical trial projects conducted at our institution and developed the following inclusion and exclusion criteria: (I) Phase I clinical trials that enrolled only healthy subjects were included, and phase I clinical trials that enrolled patients or phase II, III, or IV clinical trials were excluded; (II) clinical trials with no special restrictions on sex were included; otherwise, the trials were excluded; (III) clinical trials with no special restrictions regarding the sex ratio of the successfully enrolled group were included; otherwise, the trials were excluded; (IV) clinical trials with no special restrictions on age were included, and trials with special restrictions (such as middle-aged and older people) were excluded; and (V) clinical trials with no special restrictions on study drugs were included, and trials with special restrictions (such as radiopharmaceuticals) were excluded.

The inclusion criteria were as follows: (I) male or female subjects aged 18 years or older; (II) a body mass index [(BMI) = body weight (kg)/height² (m²)] within the range of 19–26 kg/m², with male and female subjects weighing no less than 50 and 45 kg, respectively; (III) normal physical examination, vital signs, or abnormal results without clinical significance; (IV) subjects (including male subjects) who reported no plans to become pregnant in the next 6 months and were voluntarily using effective non-pharmacological contraception; and (V) subjects who voluntarily participated and signed an informed consent form (ICF), with the informed consent process conducted in compliance with the Good Clinical Practice (GCP) guidelines.

The exclusion criteria were as follows: (I) people with an allergic constitution (such as those allergic to two or more drugs and food) and people with allergic symptoms such as bronchial asthma, rash, and urticaria; (II) people with severe renal dysfunction; (III) people with dysphagia or with a history of gastrointestinal disease that could affect drug absorption; (IV) people who had taken any prescription drugs, non-prescription drugs, vitamin products, or herbal medicines within 28 days before the test, especially any drugs that changed liver enzyme activity; (V) people who had a special diet and/or exercise factors that could affect drug absorption, distribution, metabolism, and excretion during the test, including but not limited to eating special foods (including dragon fruit, mango, grapefruit, chocolate, and/or a diet containing caffeine or xanthine) within 48 hours before the test that could affect drug metabolism; (VI) people with positive hepatitis B surface antigen (HBSAG), hepatitis C virus antibody (HVC-Ab), human immunodeficiency virus (HIV) antibody, or treponema pallidum antibody (TPAB) test results; (VII) people with positive pregnancy test results; (VIII) people with abnormal physical examinations, vital signs, complete blood count (CBC), routine urine test, blood biochemistry, coagulation function test, and ECG examination results; (IX) people who had a history of drug abuse within the past 5 years, had used drugs within 3 months before the test, or had a positive urine drug screening result; (X) pregnant or breastfeeding women; (XI) people who had participated in other clinical trials within the past 3 months or had lost more than 400 mL of blood within the last 3 months (such as blood donation but excluding menstrual blood loss); (XII) special lifestyles: people who smoked regularly (≥5 cigarettes/day) and those who could not abstain from smoking during the trial; a history of alcohol abuse (drinking 14 units of alcohol per week: 1 unit =25 mL of spirits with more than 40% alcohol, 85 mL of wine, or 285 mL of beer); previous long-term consumption of any food or beverage containing caffeine or xanthine (e.g., coffee, tea, cocoa-based beverages, caffeine-containing soda, and chocolate, alone or as an ingredient; more than 8 cups per day, 1 cup =250 mL); (XIII) people who could not comply with the study protocol; (XIV) people who could not tolerate venipuncture or had difficulty during blood collection; and (XV) other factors, such as people considered unsuitable by the investigators.

The screening process for day 1 (D1) was as follows: (I) each subject’s identification (ID) information was verified, followed by the subject’s registration; (II) information was publicly provided to groups of potential subjects—the involved physician explained the entire trial process so that subjects could fully understand the requirements and consider whether to participate in the trial; (III) the subjects and study physicians signed ICFs individually; (IV) the external network (subject-screening database) was consulted to determine whether the subject had been involved in another clinical trial within the past 3 months; (V) demographic data were collected; (VI) height, weight, and vital sign measurements, consultations, and the physical examination screening were performed; and (VII) subjects who failed the screening were informed of relevant precautions and were signed out.

The screening process for day 2 (D2) was as follows: (I) qualified subjects who passed the screening on D1 checked in and underwent laboratory tests and ECG examinations; (II) imaging examinations were completed, and subjects signed out after completing the relevant examinations; (III) after the physician evaluated the relevant examination results, subjects were assessed for qualification; (IV) concomitant medications were documented; (V) the list of qualified subjects was confirmed; and (VI) qualified subjects were informed by telephone follow-up.