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

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy; Haemostasis
• Intervention / Treatment: Drug: warfarin; Drug: eptacog alfa (activated); Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-warfarin treatment (trial part A)	Drug: warfarin; 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
Experimental: Post-warfarin treatment (trial part B)	Drug: eptacog alfa (activated); 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; Other Names: activated recombinant human factor VII; Drug: placebo; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 21, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 23, 2012

Study Record Updates

• Last Update Posted (Estimate): November 25, 2016
• Last Update Submitted That Met QC Criteria: November 23, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Anticoagulants; Warfarin
• Other Study ID Numbers: F7HAEM-1825