Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the recombinant factor VIIa variant BAY 86-6150 in hemophilia
dc.contributor.author | Mahlangu, J. N. | |
dc.contributor.author | Coetzee, M. J. | |
dc.contributor.author | Laffan, M. | |
dc.contributor.author | Windyga, J. | |
dc.contributor.author | Yee, T. T. | |
dc.contributor.author | Schroeder, J. | |
dc.contributor.author | Haaning, J. | |
dc.contributor.author | Siegel, J. E. | |
dc.contributor.author | Lemm, G. | |
dc.date.accessioned | 2016-03-24 | |
dc.date.accessioned | 2016-04-06T07:35:14Z | |
dc.date.available | 2012 | |
dc.date.available | 2016-04-06T07:35:14Z | |
dc.date.issued | 2012 | |
dc.description.abstract | Background: BAY 86-6150 is a new human recombinant factor VIIa variant developed for high procoagulant activity and longer action in people with hemophilia with inhibitors. Objectives: To investigate the safety, tolerability, pharmacodynamics, pharmacokinetics and immunogenicity of BAY 86-6150 in non-bleeding hemophilia subjects. Methods: The study included non-bleeding men (18–65 years of age)withmoderate or severe hemophilia AorBwith or without inhibitors. Sixteen subjects were randomized 3 : 1 to four cohorts of escalating doses of BAY 86-6150 (6.5, 20, 50 or 90 lg kg)1 [n = 3 per cohort]) or placebo (n = 1 per cohort); an independent data-monitoring committee reviewed previous cohort data before the next dose escalation. Blood samplingwas performed predose and postdose; subjects were monitored for 50 days postdose. Results: At the tested doses, BAY 86-6150 was not associated with clinically significant adverse events or dose-limiting toxicities. BAY 86-6150 pharmacokinetics exhibited a linear dose response, with a half-life of 5–7 h. Subjects demonstrated consistent, dose-dependent thrombin generation ex vivo in platelet-poor plasma (PPP) (mean peak effect, 26– 237 nMthrombin from 6.5 to 90 lg kg)1). Peak thrombin levels over time paralleled BAY 86-6150, with thrombin kinetics appearing to be slightly shorter; thus, circulating BAY 86-6150 retained activity. There were corresponding decreases in activated partial thromboplastin and prothrombin times. No subject developed de novo anti-BAY 86-6150 neutralizing antibodies during the 50-day follow-up. Conclusions: In this first-in-human, multicenter, randomized, double-blind, placebo- controlled, single-dose escalation study, BAY 86-6150 was tolerated at the highest dose (90 lg kg)1), with no safety concerns. Safety and efficacy will be further evaluated in phase II/III studies. | en_ZA |
dc.description.version | Publisher's version | en_ZA |
dc.identifier.citation | Mahlangu, J. N., Coetzee, M. J., Laffan, M., Windyga, J., Yee, T. T., Schroeder, J., ... & Lemm, G. (2012). Phase I, randomized, double‐blind, placebo‐controlled, single‐dose escalation study of the recombinant factor VIIa variant BAY 86‐6150 in hemophilia. Journal of Thrombosis and Haemostasis, 10(5), 773-780. | en_ZA |
dc.identifier.issn | 1538-7836 | |
dc.identifier.uri | http://hdl.handle.net/11660/2379 | |
dc.language.iso | en | en_ZA |
dc.publisher | International Society on Thrombosis and Haemostasis | en_ZA |
dc.rights.holder | International Society on Thrombosis and Haemostasis | en_ZA |
dc.subject | Hemophilia | en_ZA |
dc.subject | Recombinant factor VIIa variant | en_ZA |
dc.subject | Pharmacokinetics | en_ZA |
dc.title | Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the recombinant factor VIIa variant BAY 86-6150 in hemophilia | en_ZA |
dc.type | Article | en_ZA |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- MAHLANGU_et_al-2012-Journal_of_Thrombosis_and_Haemostasis.pdf
- Size:
- 267.6 KB
- Format:
- Adobe Portable Document Format
- Description:
License bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- license.txt
- Size:
- 1.71 KB
- Format:
- Item-specific license agreed upon to submission
- Description: