Comparative Pharmacokinetic Study of Ramelteon Modified-Release Tablets and Ramelteon Tablets in Healthy Subjects

The trial was divided into screening period, period I, period II and safety follow-up period. The washout period is 2 days during the period.

Screening period: All subjects must sign an informed consent prior to participating in the trial. Screening tests were performed from Day -14 to Day 1 of administration.

Period I: 12 qualified subjects were screened and admitted to the Phase I ward of the Clinical Research Center on Day-1. After being reviewed and confirmed by the investigators, they were randomly divided into 2 groups, T-R group and R-T group, with 6 participants in each group. The normal diet was set at 8:00, 12:00 and 18:00 on the day of administration, and the uniform diet was required during the trial. After dinner at 18:00, all subjects were given 120mL whole milk starting at 21:57, one test product (Ramelteon Modified-Release Tablets (strength: 8 mg/tablet) or one reference product (Ramelteon Tablets (trade name: Rozerem®, strength: 8 mg/tablet) , and 120mL of warm water, the subject can lie down half after taking the drug, had no water within 1 hour after taking the drug, and fasted until breakfast the next day. PK blood samples were collected according to the time required by the scheme.

Period II : With a washout period of 2 days, the subjects underwent the period II of administration and blood collection on the night of Day 3, and the trial method in period II is the same as that in period I.

Vital signs (including body temperature, respiration, pulse, and blood pressure) were measured 1 hour before administration, at 2.0±0.5h, 5.0±0.5h, and 24.0±1.0h after each period of administration. Subjects were hospitalized throughout the trial period and underwent physical examination, vital signs measurement, electrocardiogram, and laboratory-related tests on Day 3 after the period II of dosing (female subjects were required to undergo blood pregnancy tests). Subject Lelt the stage I ward after completing PK sampling and the above examination.

Safety Follow-up: During the Day 8-Day 11 period, subjects will be contacted by telephone to collect information on drug combinations and adverse events after discharge from the study center.

Blood sample collection and processing: Cubital venous blood will be collected at 29 time points: before administration (0 h) (within 1.0h before administration) and 20min, 40min, 1h, 1h20min, 1h40min, 2h, 2h20min, 2h40min, 3h, 3h20min, 3h40min, 4h, 4h20min, 4h40min, 5h, 5h20min, 5h40min, 6h, 6h20min, 6h40min, 7h, 7h20min, 7h40min, 8h, 9h, 10h, 12h and 24h after administration of each period, and 4.0mL of blood was drawn and placed in the labeled EDTA-2K anticoagulant vacuum blood collection tube. Immediately after blood collection, the sampling vessels were gently and completely reversed three times and mixed with anticoagulant and temporarily placed at room temperature until centrifugation, centrifuged at 4℃ (set at 2-8 ℃) at 1700g for 10min. After centrifugation, the samples were removed from the centrifuge, and the plasma was collected and divided into two tubes (detection tube and backup tube) with corresponding labels. The test tube is about 0.8mL, and the remaining plasma is loaded into the backup tube. Blood samples were collected from the beginning, centrifugation was completed within 60 minutes, and plasma was frozen at -20 ° C (-30 ° C \~-10 ° C) or -80 ° C (-90 ° C \~-60 ° C) within 120 minutes. Samples stored in the -20 ° C refrigerator were transferred to the -80 ° C refrigerator for storage after 24 hours of blood collection. After the collection of blood samples of all subjects, the plasma samples of the detection tube will be transferred to the analysis and testing center for blood concentration determination, and the plasma samples of the backup tube will be stored in the clinical research unit or a third party designated by the sponsor.