Thromb Haemost 2017; 117(06): 1052-1057
DOI: 10.1160/TH16-10-0765
Coagulation and Fibrinolysis
Schattauer GmbH

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

Baolai Hua
1  Peking Union Medical College Hospital (PUMCH), Department of Haematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Runhui Wu
2  Beijing Children’s Hospital, Haematology Department, Capital Medical University, Beijing, China
,
FeiFei Sun
3  Pfizer Inc, Beijing, China
,
Binyu Luo
4  Pfizer Inc, Shanghai, China
,
Christine Alvey
5  Pfizer Inc, Groton, Conneticut, USA
,
Robert R. LaBadie
5  Pfizer Inc, Groton, Conneticut, USA
,
Peng Roger Qu
4  Pfizer Inc, Shanghai, China
,
Joan M. Korth-Bradley
6  Pfizer Inc, Collegeville, Pennsylvania, USA
,
Pablo Rendo
6  Pfizer Inc, Collegeville, Pennsylvania, USA
› Author Affiliations
Financial support: This study was sponsored by Pfizer Inc. Editorial support was provided by Teri O’Neill of Peloton Advantage and was funded by Pfizer Inc. No author received an honorarium related to the development of this manuscript.
Further Information

Publication History

Received: 07 October 2016

Accepted after major revision: 01 March 2017

Publication Date:
07 November 2017 (online)

Summary

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.