Safety and pharmacokinetics of a recombinant factor VIII with pegylated liposomes in severe hemophilia A

Jerry S Powell, D. J. Nugent, J. A. Harrison, A. Soni, A. Luk, H. Stass, E. Gorina

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background: BAY 79-4980 is a sucrose-formulated recombinant factor VIII (rFVIII-FS) combined with pegylated liposomes to prolong activity. Objectives: To investigate the safety, tolerability, bioavailability, pharmacokinetics and pharmacodynamics of a single administration of BAY 79-4980 compared with standard rFVIII-FS in patients with severe hemophilia A. Methods: This randomized, double-blind study consisted of two crossover substudies comparing two doses of liposomal rFVIII-FS with standard rFVIII-FS. Males (12-60years) with severe hemophilia A received a single infusion of standard rFVIII-FS (35IUkg -1) followed by a single infusion of BAY 79-4980 (13 or 22mgkg -1 pegylated liposomes) or vice versa, with 12 observation days and a 2-day washout period between treatments. Results: Twenty-six subjects were enrolled at two centers. No serious adverse events were reported. Transient increases in complement C3a, but not CH50, were seen in subjects receiving both the low- and high-liposome-dose BAY 79-4980. Mild transient elevations of total and low-density lipoprotein cholesterol were observed. There were no clinically significant differences in clotting or laboratory parameters or in pharmacokinetic behavior between BAY 79-4980 and standard rFVIII-FS. The number of subjects with spontaneous bleeds on days 1-14 postinfusion was low, and group comparisons were inconclusive. Conclusions: Single-dose administration of BAY 79-4980 is well tolerated in patients with severe hemophilia A. Plasma pharmacokinetics of FVIII cannot explain the extended protection from bleeding observed previously with BAY 79-4980. Further studies of efficacy and long-term safety of chronic administration are planned.

Original languageEnglish (US)
Pages (from-to)277-283
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

Factor VIII
Hemophilia A
Liposomes
Pharmacokinetics
Safety
Complement C3a
Double-Blind Method
LDL Cholesterol
Biological Availability
Sucrose
sugar formulated recombinant FVIII
Observation
Hemorrhage

Keywords

  • Hemophilia
  • Liposome
  • Longer-acting factor VIII
  • Pegylation
  • Pharmacokinetics
  • Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Safety and pharmacokinetics of a recombinant factor VIII with pegylated liposomes in severe hemophilia A. / Powell, Jerry S; Nugent, D. J.; Harrison, J. A.; Soni, A.; Luk, A.; Stass, H.; Gorina, E.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 2, 02.2008, p. 277-283.

Research output: Contribution to journalArticle

Powell, Jerry S ; Nugent, D. J. ; Harrison, J. A. ; Soni, A. ; Luk, A. ; Stass, H. ; Gorina, E. / Safety and pharmacokinetics of a recombinant factor VIII with pegylated liposomes in severe hemophilia A. In: Journal of Thrombosis and Haemostasis. 2008 ; Vol. 6, No. 2. pp. 277-283.
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abstract = "Background: BAY 79-4980 is a sucrose-formulated recombinant factor VIII (rFVIII-FS) combined with pegylated liposomes to prolong activity. Objectives: To investigate the safety, tolerability, bioavailability, pharmacokinetics and pharmacodynamics of a single administration of BAY 79-4980 compared with standard rFVIII-FS in patients with severe hemophilia A. Methods: This randomized, double-blind study consisted of two crossover substudies comparing two doses of liposomal rFVIII-FS with standard rFVIII-FS. Males (12-60years) with severe hemophilia A received a single infusion of standard rFVIII-FS (35IUkg -1) followed by a single infusion of BAY 79-4980 (13 or 22mgkg -1 pegylated liposomes) or vice versa, with 12 observation days and a 2-day washout period between treatments. Results: Twenty-six subjects were enrolled at two centers. No serious adverse events were reported. Transient increases in complement C3a, but not CH50, were seen in subjects receiving both the low- and high-liposome-dose BAY 79-4980. Mild transient elevations of total and low-density lipoprotein cholesterol were observed. There were no clinically significant differences in clotting or laboratory parameters or in pharmacokinetic behavior between BAY 79-4980 and standard rFVIII-FS. The number of subjects with spontaneous bleeds on days 1-14 postinfusion was low, and group comparisons were inconclusive. Conclusions: Single-dose administration of BAY 79-4980 is well tolerated in patients with severe hemophilia A. Plasma pharmacokinetics of FVIII cannot explain the extended protection from bleeding observed previously with BAY 79-4980. Further studies of efficacy and long-term safety of chronic administration are planned.",
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T1 - Safety and pharmacokinetics of a recombinant factor VIII with pegylated liposomes in severe hemophilia A

AU - Powell, Jerry S

AU - Nugent, D. J.

AU - Harrison, J. A.

AU - Soni, A.

AU - Luk, A.

AU - Stass, H.

AU - Gorina, E.

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N2 - Background: BAY 79-4980 is a sucrose-formulated recombinant factor VIII (rFVIII-FS) combined with pegylated liposomes to prolong activity. Objectives: To investigate the safety, tolerability, bioavailability, pharmacokinetics and pharmacodynamics of a single administration of BAY 79-4980 compared with standard rFVIII-FS in patients with severe hemophilia A. Methods: This randomized, double-blind study consisted of two crossover substudies comparing two doses of liposomal rFVIII-FS with standard rFVIII-FS. Males (12-60years) with severe hemophilia A received a single infusion of standard rFVIII-FS (35IUkg -1) followed by a single infusion of BAY 79-4980 (13 or 22mgkg -1 pegylated liposomes) or vice versa, with 12 observation days and a 2-day washout period between treatments. Results: Twenty-six subjects were enrolled at two centers. No serious adverse events were reported. Transient increases in complement C3a, but not CH50, were seen in subjects receiving both the low- and high-liposome-dose BAY 79-4980. Mild transient elevations of total and low-density lipoprotein cholesterol were observed. There were no clinically significant differences in clotting or laboratory parameters or in pharmacokinetic behavior between BAY 79-4980 and standard rFVIII-FS. The number of subjects with spontaneous bleeds on days 1-14 postinfusion was low, and group comparisons were inconclusive. Conclusions: Single-dose administration of BAY 79-4980 is well tolerated in patients with severe hemophilia A. Plasma pharmacokinetics of FVIII cannot explain the extended protection from bleeding observed previously with BAY 79-4980. Further studies of efficacy and long-term safety of chronic administration are planned.

AB - Background: BAY 79-4980 is a sucrose-formulated recombinant factor VIII (rFVIII-FS) combined with pegylated liposomes to prolong activity. Objectives: To investigate the safety, tolerability, bioavailability, pharmacokinetics and pharmacodynamics of a single administration of BAY 79-4980 compared with standard rFVIII-FS in patients with severe hemophilia A. Methods: This randomized, double-blind study consisted of two crossover substudies comparing two doses of liposomal rFVIII-FS with standard rFVIII-FS. Males (12-60years) with severe hemophilia A received a single infusion of standard rFVIII-FS (35IUkg -1) followed by a single infusion of BAY 79-4980 (13 or 22mgkg -1 pegylated liposomes) or vice versa, with 12 observation days and a 2-day washout period between treatments. Results: Twenty-six subjects were enrolled at two centers. No serious adverse events were reported. Transient increases in complement C3a, but not CH50, were seen in subjects receiving both the low- and high-liposome-dose BAY 79-4980. Mild transient elevations of total and low-density lipoprotein cholesterol were observed. There were no clinically significant differences in clotting or laboratory parameters or in pharmacokinetic behavior between BAY 79-4980 and standard rFVIII-FS. The number of subjects with spontaneous bleeds on days 1-14 postinfusion was low, and group comparisons were inconclusive. Conclusions: Single-dose administration of BAY 79-4980 is well tolerated in patients with severe hemophilia A. Plasma pharmacokinetics of FVIII cannot explain the extended protection from bleeding observed previously with BAY 79-4980. Further studies of efficacy and long-term safety of chronic administration are planned.

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KW - Pharmacokinetics

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