Safety and Tolerability of Intravenous Doses of Activated Recombinant Human Factor VII in Healthy Volunteers

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to investigate the pharmacokinetics of three different single doses activated recombinant human factor VII in Caucasian and Japanese healthy subjects.

Official Title
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Single-centre, Randomised, Placebo-controlled, Double-blind, Dose Escalation Trial Investigating Pharmacokinetics, Pharmacodynamics and Tolerability of Three Different Single Intravenous Doses of Activated Recombinant Factor VIIa (rFVIIa/NovoSeven®) in Healthy Caucasian and Japanese Subjects

Conditions
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Congenital Bleeding Disorder, Haemophilia A With Inhibitors, Haemophilia B With Inhibitors, Healthy

Intervention / Treatment
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* Drug: activated recombinant human factor VII
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian or Japanese Healthy as defined by medical history, physical and biological examinations Exclusion Criteria: History of allergy or hypersensitivity reaction to any medication History or presence of any organic disorder likely to modify absorption, distribution or elimination of the medication Alcohol or substance abuse disorder Subject in his exclusion period in the Healthy Volunteers National Register of the French Ministry of Health

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1<br> | Drug: activated recombinant human factor VII<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>Drug: placebo<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>|
| Experimental: Treatment sequence 2<br> | Drug: activated recombinant human factor VII<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>Drug: placebo<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>|
| Experimental: Treatment sequence 3<br> | Drug: activated recombinant human factor VII<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>Drug: placebo<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>|
| Placebo Comparator: Treatment sequence 4<br> | Drug: activated recombinant human factor VII<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>Drug: placebo<br>* Subjects will be randomised to one of four treatment sequences. Subjects will receive single bolus i.v. injection of 40, 80 or 160 mcg/kg body weight of trial drug or placebo on each day of the three separate visits<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Curve (AUC) of FVII:C (Factor VII clotting activity) from 0-24 hours |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean residence time (MRT) |  |  | 
| Maximum plasma concentration (Cmax) |  |  | 
| Time to reach maximum plasma concentration (tmax) |  |  | 
| Area under the Curve (AUC) from 0-24 hours of the PT (Prothrombin Time) |  |  | 
| Adverse events |  |  |