Browsing by Author "Austin, S.K."

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Efficacy, Safety and Pharmacokinetics of a New High-Purity Factor X Concentrate in Subjects With Hereditary Factor X Deficiency
(Blackwell Publishing Ltd, 2016) Austin, S.K.; Kavakli, K.; Norton, M.; Peyvandi, F.; Shapiro, A.; Álvarez Román, M.-T.; Timur, C.
Introduction: Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available. Aim: The aim of this study was to assess safety and efficacy of a new, high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary FX deficiency. Methods: Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL-1) received 25 IU kg-1 pdFX as on-demand treatment or short-term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end-of-study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters. Results: Sixteen enrolled subjects (six aged 12-17 years; 10 aged 18-58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half-life were 2.00 (2.12; 1.79-2.37) IU dL-1 per IU kg-1 and 29.4 (28.6; 25.8-33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters. Conclusion: These results demonstrate that a dose of 25 IU kg-1 pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency. © 2016 John Wiley & Sons Ltd.
Pharmacokinetics of a High-Purity Plasma-Derived Factor X Concentrate in Subjects With Moderate or Severe Hereditary Factor X Deficiency
(Blackwell Publishing Ltd, 2016) Austin, S.K.; Brindley, C.; Kavakli, K.; Norton, M.; Shapiro, A.; Álvarez Román, M.-T.; Timur, C.
Introduction: Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 of individuals. There are few published data on the pharmacokinetics (PK) of FX for existing treatments for FX deficiency, and no specific replacement factor concentrate exists. A high-purity plasma-derived FX concentrate (pdFX) has been developed for use as replacement therapy in subjects with hereditary FX deficiency. Aim: This analysis assessed pdFX PK after a single 25 IU kg-1 bolus dose in subjects with hereditary moderate or severe FX deficiency (plasma FX activity [FX:C] <5 IU dL-1). Methods: For a baseline PK assessment, blood samples were taken predose and at intervals up to 144 h (7 days) post dose. After ≥6 months of on-demand pdFX treatment and treatment of ≥1 bleed with pdFX, subjects underwent repeat PK assessment. Samples were assayed for plasma FX:C (measured using the clotting and chromogenic assays) and FX antigen. Results: FX:C peaked at 0.4-0.5 h and subsequently declined over the course of 144 h with a biphasic decay curve. PK parameters observed at the baseline (n = 16) and repeat (n = 15) assessments were equivalent, therefore summary PK values were obtained by combining data from both visits (n = 31). The mean terminal half-life and incremental recovery of pdFX was 29.4 h and 2.00 IU dL-1 per IU kg-1 respectively. Conclusion: This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pdFX and provide the PK data required for the treatment of hereditary FX deficiency using pdFX replacement therapy. © 2016 John Wiley & Sons Ltd.