Pharmacokinetics and safety of plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency.

Abstract

UNLABELLED:

Congenital factor XIII (FXIII) deficiency is a rare condition with substantial risk for life-threatening bleeding. Replacement of deficient FXIII with plasma-derived FXIII concentrate is a treatment option. The current 12-week study evaluated the steady-state pharmacokinetic (PK) and safety profile of prophylactic infusions of FXIII concentrate (human) in patients with congenital FXIII deficiency. Patients received FXIII concentrate (human) 40 IU kg(-1) on Days 0, 28, and 56. FXIII levels were assessed before and after each infusion; steady-state PK parameters were assessed up to 28 days after the infusion on Day 56. Treatment effectiveness in maintaining trough FXIII activity levels ≥ 5% over 28 days and safety parameters were also assessed. Fourteen patients received FXIII concentrate (human) and 13 completed the study. Post-infusion, FXIII activity levels increased to within the range found in patients without congenital FXIII deficiency without reaching supra-therapeutic levels. Non-baseline-adjusted trough FXIII activity levels were maintained at or above 10% at all post-baseline visits in all patients. Steady-state PK parameters were baseline-adjusted; maximum FXIII activity was 87.7% at 1.72 h post-infusion, subsequently declining to a minimum of 5.0%. The half-life was 6.6 days. FXIII concentrate (human) was generally well tolerated. Two patients had possibly treatment-related adverse events. There were no reports of thromboembolism, viral transmission, bleeding events or treatment-related hypersensitivity. These findings support use of FXIII concentrate (human) 40 IU kg(-1) every 28 days as an appropriate regimen for routine, long-term prophylaxis in children and adults with congenital FXIII deficiency.

CLINICAL TRIAL REGISTRATION:

www.clinicaltrials.gov/ct2/show/NCT00883090.

• Authors: D J Nugent, C Ashley, J García-Talavera, L C Lo, A S Mehdi, A Mangione
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 21 Issue 1 Pg. 95-101 (Jan 2015) ISSN: 1365-2516 [Electronic] England
• PMID: 25458735 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Biomarkers, Pharmacological
• Factor XIII

Topics

• Adolescent
• Adult
• Biomarkers, Pharmacological
• Child
• Child, Preschool
• Factor XIII (pharmacokinetics, therapeutic use)
• Factor XIII Deficiency (congenital, drug therapy)
• Female
• Humans
• Male
• Young Adult