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).