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document
Safety and pharmacokinetics of a glycoPEGylated recombinant activated factor VII derivative : a randomized first human dose trial in healthy subjects . BACKGROUND Extensive research is currently ongoing to prolong the half-life of coagulation factors . One of these techniques is glycoPEGylation , which has also been applied to recombinant activated factor VII ( rFVIIa ) , resulting in a rFVIIa derivative ( N7-GP ) with a prolonged terminal half-life ( t ( 1/2 ) ) . The main clinical purpose of N7-GP is to provide safe and effective prophylaxis to patients with hemophilia and inhibitors . The prolonged t ( 1/2 ) of N7-GP can potentially reduce the dosing frequency and thereby facilitate convenience and compliance , which are two significant barriers to effective prophylaxis . OBJECTIVES To determine the safety and pharmacokinetics of single doses of N7-GP in healthy men . METHODS A randomized , placebo-controlled , dose-escalation trial with five cohorts ( N7-GP dose of 12.5-100 μg kg ( -1 ) ) was performed . In each cohort , eight subjects were randomized to receive N7-GP ( n = 6 ) or placebo ( n = 2 ) . RESULTS The mean FVIIa activity was measurable for up to at least 72 h after dosing , and the overall mean t ( 1/2 ) for FVIIa activity was 15 h. The pharmacokinetics of N7-GP appeared to be dose-proportional in the dose range investigated . No serious adverse events ( including thromboembolic events ) were reported . The frequency of adverse events was similar in both the placebo and N7-GP groups . No neutralizing antibodies against N7-GP were detected . A pharmacologic effect was apparent from a dose-dependent statistically significant decrease in the mean prothrombin time in all N7-GP groups as compared with placebo . CONCLUSIONS N7-GP had a plasma half-life of 15 h and a profile that makes it a potential candidate for prophylaxis in patients with hemophilia and inhibitors .
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Intervention_Physical
N7-GP
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Outcome_Other
Safety
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Outcome_Physical
pharmacokinetics