Use of Activated Recombinant Human Factor VII to Reduce Bleeding Caused by Warfarin Treatment

Study Overview
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Brief Summary
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This trial is conducted in the United States of America (USA). The aim of this trial is to evaluate the efficacy of activated recombinant human factor VII to mitigate experimentally-induced bleeding in healthy volunteers treated with warfarin to reach a targeted INR (International Normalization Ratio).

Official Title
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Use of Recombinant FVIIa to Mitigate Warfarin Anticoagulation Therapy-Mediated Bleeding in a Single Centre, Randomized, Placebo-controlled, Double-blind Clinical Trial

Conditions
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Haemostasis, Healthy

Intervention / Treatment
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* Drug: warfarin
* Drug: eptacog alfa (activated)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: INR below or equal to 1.2 Exclusion Criteria: The receipt of any investigational drug within 1 month prior to this trial Use of anticoagulation therapy-defined as vitamin K antagonists, platelet antagonists, heparin (or low molecular weight heparin), aspirin or NSAIDs (Non-Steroidal Anti-Inflammatory Drug) within 14 days prior to trial African-American race Weight above 160 kg Supplemental Vitamin K use

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-warfarin treatment (trial part A)<br> | Drug: warfarin<br>* After a baseline punch biopsy (B0), warfarin is administered over a period of approximately 7-14 days. Dose is adjusted individually to achieve INR target. Once a stable INR is achieved, a second biopsy (B1) will be performed<br>|
| Experimental: Post-warfarin treatment (trial part B)<br> | Drug: eptacog alfa (activated)<br>* If the subject is eligible to continue in trial part B, trial drug will be administered i.v. as a slow bolus injection over 2 to 5 minutes in five different doses followed by two biopsies (B2) and (B3) 15 minutes and 5 hours and 15 minutes, respectively, after trial drug administration<br>* Other names: activated recombinant human factor VII;Drug: placebo<br>* If the subject is eligible to continue in trial part B, trial drug will be administered i.v. as a slow bolus injection over 2 to 5 minutes in five different doses followed by two biopsies (B2) and (B3) 15 minutes and 5 hours and 15 minutes, respectively, after trial drug administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding duration measured in minutes after biopsies in trial part A |  | From onset of bleeding till the end of the bleeding | 
| Bleeding duration measured in minutes after biopsy B1 in trial part B |  | From onset of bleeding till the end of the bleeding | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood volume reported in millilitres after biopsies in trial part A |  | From onset of bleeding till the end of the bleeding | 
| Blood volume reported in millilitres after biopsy B1 in trial part B |  | From onset of bleeding till the end of the bleeding | 
| Adverse events, including thrombotic events |  | From day 0 to days 14-28 | 
| Change in coagulation-related parameters after biopsy B1 |  | From baseline to 3 hours after B1 | 
| Change in coagulation-related parameters after biopsy B2 |  | From baseline to 3 hours after B2 | 
| Change in coagulation-related parameters after biopsy B3 |  | From baseline to 3 hours after B3 | 
| Clot dynamics: R in minutes (trial part B) |  | Time to onset of clot formation | 
| Clot dynamics: K in minutes (trial part B) |  | Time to achieve 20mm clot strength |