Confirmation of longer FIX activity half-life with prolonged sample collection after single doses of nonacog alfa in patients with haemophilia B.
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 t½estimate 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.
Baolai
B
Hua
Runhui
R
Wu
FeiFei
F
Sun
Binyu
B
Luo
Christine
C
Alvey
Robert
R
Labadie
Peng Roger
PR
Qu
Joan M. Korth-Bradley, Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426, USA, Tel.: +1 484 865 2914, Fax: +1 484 865 6457, E-mail: joan.korth-bradley@pfizer.com.
Joan M
JM
Korth-Bradley
Pablo
P
Rendo
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002648:Child; D002681:China; D005164:Factor IX / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D002836:Hemophilia B / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D013048:Specimen Handling; D013997:Time Factors; D055815:Young Adult
D011994:Recombinant Proteins; D005164:Factor IX
BeneFIX; Chinese; paediatrics; pharmacokinetics; recombinant factor IX