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Safety and dose‐dependency of eptacog beta (activated) in a dose escalation study of non‐bleeding congenital haemophilia A or B patients, with or without inhibitors
Author(s) -
Ducore J.,
Lawrence J. B.,
Simpson M.,
Boggio L.,
Bellon A.,
Burggraaf J.,
Stevens J.,
Moerland M.,
Frieling J.,
Reijers J.,
Wang M.
Publication year - 2017
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.13357
Subject(s) - medicine , haemophilia , haemophilia a , haemophilia b , pharmacokinetics , cmax , pharmacodynamics , therapeutic index , gastroenterology , pharmacology , surgery , drug
Varying initial doses of activated eptacog beta (recombinant human FVII a, rh FVII a) may provide therapeutic options when treating bleeding in patients with congenital haemophilia who have developed inhibitory antibodies to factor VIII ( FVIII ) or factor IX ( FIX ). This study evaluated escalated doses of a new rh FVII a product as a prelude to selecting the doses for clinical efficacy evaluation in haemophilia patients. Aim To assess the safety, pharmacokinetics, and laboratory pharmacodynamics of 3 doses of rh FVII a in non‐bleeding patients with congenital haemophilia A or B with or without inhibitors. Methods Adult male patients (18‐75 years old) with congenital haemophilia A or B (with or without inhibitors) received infusions of rh FVII a at doses of 25, 75 or 225 μg/kg body weight. Ten patients were treated at each dose level, and each patient received 2 different dose levels. Descriptive methods were used to analyse the data. Results Administration of rh FVII a at all doses was well tolerated. Pharmacokinetic analyses showed that peak FVII a plasma levels ( C max ) were approximately proportional to dose and correlated well with peak thrombin generation. Total AUC 0‐inf also was approximately dose proportional. Clot formation and duration correlated with FVII a activity. Repeat doses did not produce an immunological response. Conclusion In the first dose‐escalation study of rh FVII a to support product registration, eptacog beta at doses of 25, 75, and 225 μg/kg was pharmacodynamically active and well tolerated in non‐bleeding patients with congenital haemophilia A or B.