Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects.

BACKGROUND: NN1731 is a recombinant activated factor VII (rFVIIa) analog with enhanced activity.
OBJECTIVES: This clinical trial aimed to assess the safety and pharmacokinetics of single doses of NN1731 in healthy male subjects.
METHODS: This was a randomized, placebo-controlled dose-escalation trial with four dose tiers (NN1731 5-30 microg kg(-1)). Eight subjects were randomized to either NN1731 (n = 6) or placebo (n = 2) in each tier.
RESULTS: No thromboembolic or serious adverse events were reported and no antibody formation towards NN1731 was detected. NN1731 was demonstrated to be pharmacologically active based on coagulation-related parameters (prothrombin fragment 1+2, activated partial thromboplastin time and prothrombin time). There were five mild/moderate adverse events in three subjects. The FVIIa activity of NN1731 after ascending single-dose administration of NN1731 fits well with a two-compartment model, indicating a bi-exponential decline with a rapid initial distribution of approximately 73% FVIIa activity (half-life = 20 min), followed by a less rapid terminal elimination phase eliminating the remaining 27% (half-life = 3 h). Dose proportionality in healthy male subjects at the dose levels investigated (5-30 microg kg(-1)) was supported by the FVIIa activity data.
CONCLUSIONS: Based on the results of this trial, NN1731 appears safe and well tolerated in healthy subjects at doses up to 30 microg kg(-1). No immunogenic or thromboembolic events were reported. The pharmacokinetic profile of NN1731 as measured by FVIIa activity appears to follow two-compartment pharmacokinetics characterized by an initial rapid distribution phase followed by a less rapid elimination phase.

RCT Entities:   Population Interventions Outcomes