Dose-Response in PD and Safety of Cofact Under VKA Anticoagulation

A Phase 1/2 Study of the Dose-Response in Pharmacodynamics and Safety of Prothrombin Complex Concentrate Cofact in Healthy Subjects Under Vitamin K Antagonist Anticoagulation.

This is a randomized, open label, placebo-controlled, parallel design, single center, prospective study. Subjects will receive treatment with VKA. Subjects who reach the targeted INR, will receive single dose of Cofact. Multiple coagulation laboratory tests will be evaluated over a period of 15 days

Inclusion Criteria:

• Male or female of nonchildbearing potential.
• Healthy subjects.

Exclusion Criteria:

• Evidence of coagulation disturbances, or disposition for thrombo-embolic events
• Liver function tests more than 1.2 times the upper normal limits
• Participants with thyroid disorders as evidenced by assessment of TSH levels outside the normal reference range at screening.
• Prior history of thromboembolic complications including those in first degree relatives.
• Glomerular filtration rate (GFR) is lower than estimated GFR 62 mL/min/1.73 m2 using the Modification of Diet in Renal Disease Study equation.
• Anaphylactic or systemic reactions to human plasma, plasma products, or blood products.
• History of hypersensitivity to active or inactive excipients of VKA
• Gastrointestinal disease that may impair VKA absorption..
• Participation in another clinical study <30 days prior to study entry.
• Any clinically significant history of or current clinically significant disease or disorder as judged by the Investigator.
• Positive nasopharyngeal PCR test for SARS-CoV-2 on Day -11 or Day -1.
• Positive pregnancy test at screening, Day -11, or Day -1.