A phase I study to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H 2 O, a novel dual-acting serotonergic antidepressant, in healthy subjects

Purpose HEC113995PA·H 2 O is a novel, potent and selective serotonin (5-HT) reuptake inhibitor and a 5-HT1A receptor partial agonist, and thus is categorized as a serotonin partial agonist-reuptake inhibitor. The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of HEC113995PA·H 2 O in healthy subjects after single and multiple dosing, as well as the food effect on pharmacokinetics and safety of HEC113995PA·H 2 O. Methods The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 121 healthy subjects were enrolled in the study. HEC113995PA·H 2 O tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events. Results In Part I, AUC and C max were found to by and large linear within the 2.5–80 mg dose range. t 1/2 of HEC113995PA·H 2 O was 27.17∼38.58 h. In Part II, we revealed that HEC113995PA·H 2 O administration post meal could increase C max and AUC 0-t . In Part III, multiple administration led to accumulated body exposure and the PK of healthy subjects reached a steady state after 7 days of continuous administration in each dose group. Conclusion HEC113995PA·H 2 O was safe and generally well-tolerated in healthy subjects. Based on the pharmacokinetic and safety data mentioned above, we expect that postprandial administration will favorably increase drug concentrations in the body and reduce gastrointestinal adverse events.