CC BY-NC-ND 4.0 · Thromb Haemost 2017; 117(02): 238-245
DOI: 10.1160/TH16-03-0224
Coagulation and Fibrinolysis
Schattauer GmbH

Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban

Jack E. Ansell
1   New York, New York, USA
,
Sasha H. Bakhru
2   Perosphere Inc., Danbury, Conneticut, USA
,
Bryan E. Laulicht
2   Perosphere Inc., Danbury, Conneticut, USA
,
Solomon S. Steiner
2   Perosphere Inc., Danbury, Conneticut, USA
,
Michael A. Grosso
3   Daiichi Sankyo Pharma Development, Edison, New Jersey, USA
,
Karen Brown
3   Daiichi Sankyo Pharma Development, Edison, New Jersey, USA
,
Victor Dishy
3   Daiichi Sankyo Pharma Development, Edison, New Jersey, USA
,
Hans J. Lanz
3   Daiichi Sankyo Pharma Development, Edison, New Jersey, USA
,
Michele F. Mercuri
3   Daiichi Sankyo Pharma Development, Edison, New Jersey, USA
,
Robert J. Noveck
4   Duke University Medical Center, Durham, North Carolina, USA
,
James C. Costin
2   Perosphere Inc., Danbury, Conneticut, USA
› Author Affiliations
Financial support: This study was funded by Peropshere, Inc. Danbury CT; Clinicaltrials.gov number NCT01826266.
Further Information

Publication History

Publication Date:
01 December 2017 (online)

Summary

Of the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.

Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA