The pharmacokinetic diversity of two von willebrand factor (VWF)/ factor VIII (FVIII) concentrates in subjects with congenital von willebrand disease: Results from a prospective, randomised crossover study

Craig M. Kessler, Ken Friedman, Bruce A. Schwartz, Joan C. Gill, Jerry S Powell

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII (FVIII) concentrates are important for treatment efficacy and safety of von Willebrand disease (VWD) patients. This prospective, head-to-head, randomised crossover study compared the PK profile of a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate®, with the PK profile of an intermediate purity (pd)VWF/FVIII concentrate, Humate-P®, in VWD patients. Subjects with inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF ristocetin cofactor activity [VWF:RCo]) of Wilate® or Humate-P® in Period 1, and switched to the other study drug in Period 2. Each period was preceded by a washout time of ≥7 days. Coagulation factor parameters were analysed at multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles, which indicated comparability for VWF antigen and VWF:RCo between Wilate® and Humate-P®. The reported VWF:Rco average and terminal t1/2 of 10.4 and 15.8 hours (h), respectively, for Wilate® and 9.3 h and 12.8 h for Humate-P®, were not statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate® 1.89, Humate-P® 1.99 IU/dl per IU/kg) were similar between the two replacement therapies. Wilate® showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P® displayed a plateau between 0 and 12-24 h. This study demonstrated bioequivalent PK properties for VWF between Wilate® and Humate-P®. The PK profile of Wilate®, combined with the 1:1 VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in individuals with VWD.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalThrombosis and Haemostasis
Volume106
Issue number2
DOIs
StatePublished - 2011

Fingerprint

von Willebrand Diseases
von Willebrand Factor
Cross-Over Studies
Pharmacokinetics
Blood Coagulation Factors
factor VIII, von Willebrand factor drug combination
Factor VIII
human F8 protein
Hemorrhage
Safety

Keywords

  • Factor VIII/von willebrand factor concentrate
  • Humate-p®
  • Pharmacokinetics
  • Ristocetin co-factor
  • Wilate®

ASJC Scopus subject areas

  • Hematology

Cite this

@article{ba77ea524d4b446dac3ad3826bdf6a65,
title = "The pharmacokinetic diversity of two von willebrand factor (VWF)/ factor VIII (FVIII) concentrates in subjects with congenital von willebrand disease: Results from a prospective, randomised crossover study",
abstract = "The pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII (FVIII) concentrates are important for treatment efficacy and safety of von Willebrand disease (VWD) patients. This prospective, head-to-head, randomised crossover study compared the PK profile of a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate{\circledR}, with the PK profile of an intermediate purity (pd)VWF/FVIII concentrate, Humate-P{\circledR}, in VWD patients. Subjects with inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF ristocetin cofactor activity [VWF:RCo]) of Wilate{\circledR} or Humate-P{\circledR} in Period 1, and switched to the other study drug in Period 2. Each period was preceded by a washout time of ≥7 days. Coagulation factor parameters were analysed at multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles, which indicated comparability for VWF antigen and VWF:RCo between Wilate{\circledR} and Humate-P{\circledR}. The reported VWF:Rco average and terminal t1/2 of 10.4 and 15.8 hours (h), respectively, for Wilate{\circledR} and 9.3 h and 12.8 h for Humate-P{\circledR}, were not statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate{\circledR} 1.89, Humate-P{\circledR} 1.99 IU/dl per IU/kg) were similar between the two replacement therapies. Wilate{\circledR} showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P{\circledR} displayed a plateau between 0 and 12-24 h. This study demonstrated bioequivalent PK properties for VWF between Wilate{\circledR} and Humate-P{\circledR}. The PK profile of Wilate{\circledR}, combined with the 1:1 VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in individuals with VWD.",
keywords = "Factor VIII/von willebrand factor concentrate, Humate-p{\circledR}, Pharmacokinetics, Ristocetin co-factor, Wilate{\circledR}",
author = "Kessler, {Craig M.} and Ken Friedman and Schwartz, {Bruce A.} and Gill, {Joan C.} and Powell, {Jerry S}",
year = "2011",
doi = "10.1160/TH11-02-0057",
language = "English (US)",
volume = "106",
pages = "279--288",
journal = "Thrombosis and Haemostasis",
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TY - JOUR

T1 - The pharmacokinetic diversity of two von willebrand factor (VWF)/ factor VIII (FVIII) concentrates in subjects with congenital von willebrand disease

T2 - Results from a prospective, randomised crossover study

AU - Kessler, Craig M.

AU - Friedman, Ken

AU - Schwartz, Bruce A.

AU - Gill, Joan C.

AU - Powell, Jerry S

PY - 2011

Y1 - 2011

N2 - The pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII (FVIII) concentrates are important for treatment efficacy and safety of von Willebrand disease (VWD) patients. This prospective, head-to-head, randomised crossover study compared the PK profile of a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate®, with the PK profile of an intermediate purity (pd)VWF/FVIII concentrate, Humate-P®, in VWD patients. Subjects with inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF ristocetin cofactor activity [VWF:RCo]) of Wilate® or Humate-P® in Period 1, and switched to the other study drug in Period 2. Each period was preceded by a washout time of ≥7 days. Coagulation factor parameters were analysed at multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles, which indicated comparability for VWF antigen and VWF:RCo between Wilate® and Humate-P®. The reported VWF:Rco average and terminal t1/2 of 10.4 and 15.8 hours (h), respectively, for Wilate® and 9.3 h and 12.8 h for Humate-P®, were not statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate® 1.89, Humate-P® 1.99 IU/dl per IU/kg) were similar between the two replacement therapies. Wilate® showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P® displayed a plateau between 0 and 12-24 h. This study demonstrated bioequivalent PK properties for VWF between Wilate® and Humate-P®. The PK profile of Wilate®, combined with the 1:1 VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in individuals with VWD.

AB - The pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII (FVIII) concentrates are important for treatment efficacy and safety of von Willebrand disease (VWD) patients. This prospective, head-to-head, randomised crossover study compared the PK profile of a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate®, with the PK profile of an intermediate purity (pd)VWF/FVIII concentrate, Humate-P®, in VWD patients. Subjects with inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF ristocetin cofactor activity [VWF:RCo]) of Wilate® or Humate-P® in Period 1, and switched to the other study drug in Period 2. Each period was preceded by a washout time of ≥7 days. Coagulation factor parameters were analysed at multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles, which indicated comparability for VWF antigen and VWF:RCo between Wilate® and Humate-P®. The reported VWF:Rco average and terminal t1/2 of 10.4 and 15.8 hours (h), respectively, for Wilate® and 9.3 h and 12.8 h for Humate-P®, were not statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate® 1.89, Humate-P® 1.99 IU/dl per IU/kg) were similar between the two replacement therapies. Wilate® showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P® displayed a plateau between 0 and 12-24 h. This study demonstrated bioequivalent PK properties for VWF between Wilate® and Humate-P®. The PK profile of Wilate®, combined with the 1:1 VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in individuals with VWD.

KW - Factor VIII/von willebrand factor concentrate

KW - Humate-p®

KW - Pharmacokinetics

KW - Ristocetin co-factor

KW - Wilate®

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U2 - 10.1160/TH11-02-0057

DO - 10.1160/TH11-02-0057

M3 - Article

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AN - SCOPUS:79961073761

VL - 106

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JO - Thrombosis and Haemostasis

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