Confirmation of longer FIX activity half-life with prolonged sample collection after single doses of nonacog alfa in patients with haemophilia B

Thromb Haemost. 2017 Jun 2;117(6):1052-1057. doi: 10.1160/TH16-10-0765. Epub 2017 Mar 23.

Abstract

A multicentre, single-dose study enrolled 12 previously treated patients with moderately severe to severe (factor IX [FIX] levels ≤2 IU/dl) haemophilia B to assess FIX pharmacokinetics after nonacog alfa administration and to evaluate the impact of length of sampling time on half-life (t½). After refraining from FIX replacement for four days, patients received 50 IU/kg as an intravenous (IV) infusion over 10 minutes. Blood samples were collected predose and 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72, and 96 h post dose. Tolerability and safety were assessed by monitoring adverse events and were subsequently summary tabulated. FIX activity was measured by a one-stage clotting assay with a lower limit of quantification of 0.010 IU/ml, and inhibitors to FIX were measured using the Bethesda assay. Pharmacokinetic parameters were calculated by noncompartmental analysis and were descriptively summarised. Half-life estimates were calculated first using all available data, then excluding 96-h observations (truncated at 72 h) and, finally, excluding both 72- and 96-h observations (truncated at 50 h). No patient was positive for FIX inhibitors. No treatment-emergent adverse events were reported. Prolonging the duration of the sample collection to 96 h resulted in a terminal t½ estimate of 39.6 ±7.4 h in the eight patients aged 18 years and older, which was longer than the estimates obtained using shorter periods of observation: 29.6 ± 5.5 h (truncated at 72 h) and 27.2 ± 7.0 h (truncated at 50 h). To accurately assess an adult patient's t½, sampling should be continued for at least 96 h.

Keywords: BeneFIX; Chinese; paediatrics; pharmacokinetics; recombinant factor IX.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Coagulation
  • Blood Coagulation Tests
  • Child
  • China
  • Factor IX / pharmacokinetics
  • Factor IX / therapeutic use*
  • Half-Life
  • Hemophilia B / diagnosis
  • Hemophilia B / drug therapy*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Specimen Handling
  • Time Factors
  • Young Adult

Substances

  • Recombinant Proteins
  • Factor IX