Pharmacokinetics of recombinant factor XIII in young children with congenital FXIII deficiency and comparison with older patients. (9th July 2013)

• Record Type: Journal Article
• Authors: Williams, M.; Will, A.; Stenmo, C.; Rosholm, A.; Tehranchi, R.
• Is Part Of: Haemophilia. Volume 20:Number 1(2014:Jan.)
• Page Start: 99
• Page End: 105
• Publication Date: 2013-07-09
• Subjects: Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.12224
• Languages: English
• ISSNs: 1351-8216

Abstract

<abstract abstract-type="main" id="hae12224-abs-0001"> <title>Summary</title> <p>Congenital factor XIII (FXIII) deficiency is a rare bleeding disorder, which in its severe form is associated with a significant bleeding phenotype, requiring regular prophylactic therapy. A recently developed recombinant FXIII (rFXIII) has demonstrated safety and efficacy in children aged ≥6 years and adults (mentor™1 trial). This article describes the mentor™4 trial, which has assessed the pharmacokinetics (PK) and safety of rFXIII in younger children (1 to <6 years) with congenital FXIII deficiency, and compares extrapolated PK parameters with the mentor™1 trial. Six children with congenital FXIII A‐subunit deficiency received a single, 35 IU kg<sup>−1</sup> rFXIII dose. PK properties were similar in all the children, with a mean area under the concentration vs. 30‐day time curve of 248.6 IU h<sup>−1</sup> mL<sup>−1</sup>, maximal FXIII activity (30 min) of 0.67 IU mL<sup>−1</sup>, and mean 30‐day trough of 0.21 IU mL<sup>−1</sup>. All patients maintained FXIII activity above the lower target level (0.1 IU mL<sup>−1</sup>). rFXIII half‐life was 15.1 days (range, 10–25). No safety findings of clinical concern were observed. PK properties of rFXIII were similar in patients from both trials. The study demonstrated that a single dose of 35 IU kg<sup>−1</sup> rFXIII maintained plasma FXIII levels above 0.1 IU mL<sup>−1</sup> over a 30‐day period in young children with congenital FXIII deficiency, and is, therefore, likely to provide adequate prophylaxis in this age group. The study extends the previous findings of the mentor™1 trial and confirms that no dose adjustment is required for different age groups with congenital FXIII deficiency.</p> </abstract>