The Phase I trial was designed to evaluate the safety and tolerability of M118 in combination with aspirin (ASA) and clopidogrel, the impact of multiple doses of ASA and clopidogrel on the pharmacokinetics (PK) and pharmacodynamics (PD) of an IV injection of M118 and the impact of a single IV injection of M118 on the PK and PD of ASA and clopidogrel.
This randomized, double-blind, placebo-controlled, crossover study was conducted in 15 healthy subjects receiving IV M118 (75 IU/kg) alone, ASA (325mg) and clopidogrel (300mg loading-dose + 75mg) administered together, and the combination of all three drugs. Each subject received all three treatments.
Blood samples were collected for the determination of anti-Factor Xa and anti-Factor IIa activities, ASA, Salicylic Acid (SA) and clopidogrel levels. PD and safety monitoring included activated clotting time (ACT), bleeding time (BT) and platelet aggregation (PA).
These results indicate that there was no significant drug interaction between the agents. With respect to PD effects, the administration of M118 had no effect on the inhibition of platelet aggregation or the increase in bleeding time caused by the combination of ASA plus clopidogrel.
In addition, M118 administration increased ACT and the administration of the combination of ASA plus clopidogrel had no effect on this increase. No severe or serious adverse events occurred in the study.