Pharmacokinetics of recombinant factor XIII at steady state in patients with congenital factor XIII A‐subunit deficiency. (25th October 2014)

• Record Type: Journal Article
• Authors: Kerlin, B.; Brand, B.; Inbal, A.; Halimeh, S.; Nugent, D.; Lundblad, M.; Tehranchi, R.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 12:Number 12(2014:Dec.)
• Page Start: 2038
• Page End: 2043
• Publication Date: 2014-10-25
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12739
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12739-abs-0001"> <title>Summary</title> <sec id="jth12739-sec-0001" sec-type="section"> <title>Background</title> <p>The use of monthly recombinant factor XIII (rFXIII) recently demonstrated favorable safety and efficacy for congenital FXIII A‐subunit deficiency patients aged ≥ 6 years (mentor<sup>™</sup>1 trial), although the pharmacokinetics (PK) were not fully evaluated.</p> </sec> <sec id="jth12739-sec-0002" sec-type="section"> <title>Objectives</title> <p>To comprehensively evaluate the steady‐state PK of rFXIII in patients aged ≥ 6 years with congenital FXIII A‐subunit deficiency.</p> </sec> <sec id="jth12739-sec-0003" sec-type="section"> <title>Patients/methods</title> <p>mentor<sup>™</sup>2 is an ongoing, multinational safety and efficacy trial in which patients are receiving monthly rFXIII (35 IU kg<sup>−1</sup>) for ≥ 52 weeks. For this 28‐day PK analysis, blood samples were collected immediately predosing, and 1 h, 2 h, 3, 7, 14, 21, and 28 days postdosing. FXIII activity was measured and PK parameters were calculated using non‐compartmental analysis, without prior baseline adjustment. Information regarding adverse events and bleeding was collected at each visit. Antibody assessments were performed predosing and at day 28.</p> </sec> <sec id="jth12739-sec-0004" sec-type="section"> <title>Results</title> <p>PK analysis in 23 patients revealed first‐order elimination of rFXIII with a geometric mean half‐life of 13.6 days. Mean FXIII activity was > 0.1 IU mL<sup>−1</sup> throughout the 28‐day period, with a geometric mean peak activity of 0.87 IU mL<sup>−1</sup> and trough of 0.16 IU mL<sup>−1</sup>. The geometric mean clearance was 0.15 mL h<sup>−1</sup> kg<sup>−1</sup>. No bleeding episodes occurred during the PK session, and no anti‐rFXIII antibodies were detected. Peak and trough FXIII activities were constant over time, compared with previous activities (≥ 10 rFXIII doses) in the same patients.</p> </sec> <sec id="jth12739-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Clearance of rFXIII is unaffected over time, and monthly prophylaxis with 35 IU kg<sup>−1</sup> rFXIII provides FXIII activity > 0.1 IU mL<sup>−1</sup> throughout the dosing interval in patients with congenital FXIII A‐subunit deficiency.</p> </sec> </abstract>