Safety assessment
The test and reference drug of lisinopril/amlodipinebesylate FDC product showed good tolerance in all subjects. During the study, the vital signs of subjects were stable except that some subjects had signs of blood pressure reduction due to the expected effect of the study drug, and there was no clinically significant change in the follow-up laboratory examination after the administration compared with the baseline value.In the study of fasting condition, a total of 33 treatment emergent adverse events (TEAEs) were recorded in 20 subjects (50% of 40 subjects) after T treatment, and 25 TEAEs were recorded in 16 subjects (40% of 40 subjects) after R treatment. In the fed study, 13 TEAEs were recorded in 10 subjects (22.7% of 44 subjects) after T treatment, and 12 TEAEs were recorded in 9 subjects (20.5% of 44 subjects) after R treatment.All AEs were light and spontaneously recovered without specific intervention except for one instance of tonsillitis, which may be irrelevant to the study drugs, and a case ofatopic dermatitis.No subjects withdrew from the study due to AEs except for one case of tonsillitis and no severe adverse events (SAE) occurred. There was no significant difference in the incidence of AEs between the two treatments. All TEAEs were summarized according to system organ classification (SOC) and preferred term (PT), and were presented in Table5.Hypotension was the most common AE, and Figure 3 illustrates the changes in mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to 24 hours.The results showed that the blood pressure decreased maximally from pre-dose values by 6 h after one dose of lisinopril/amlodipinebesylate FDC product and the suppression lasted up to 12 h. There was no significant difference in mean SBP between the fasting and fed groups, except at 8 h after administration of test product (P=0.038). However, the DBP decreasedmore than SBP in healthy Chinese subjects, and compared to fed study, the DBPdecreased obviously more at 4 h, 6 h, 8 h following the dosing with both regimens in the fasting state (P<0.05).