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

• ClinicalTrials.gov Identifier: NCT01563471
• Recruitment Status: Completed
• First Posted: March 27, 2012
• Last Update Posted: January 13, 2017
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Congenital Bleeding Disorder; Haemophilia A With Inhibitors; Haemophilia B With Inhibitors; Healthy	Drug: activated recombinant human factor VII; Drug: placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2001
• Actual Primary Completion Date: July 2002
• Actual Study Completion Date: July 2002

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment sequence 1	Drug: activated recombinant human factor VII; 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; Drug: placebo; 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
Experimental: Treatment sequence 2	Drug: activated recombinant human factor VII; 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; Drug: placebo; 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
Experimental: Treatment sequence 3	Drug: activated recombinant human factor VII; 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; Drug: placebo; 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
Placebo Comparator: Treatment sequence 4	Drug: activated recombinant human factor VII; 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; Drug: placebo; 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

Outcome Measures

Primary Outcome Measures :

1. Area under the Curve (AUC) of FVII:C (Factor VII clotting activity) from 0-24 hours

Secondary Outcome Measures :

1. Mean residence time (MRT)
2. Maximum plasma concentration (Cmax)
3. Time to reach maximum plasma concentration (tmax)
4. Area under the Curve (AUC) from 0-24 hours of the PT (Prothrombin Time)
5. Adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

France

Novo Nordisk Investigational Site

Paris, France, 75015

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452); Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

Publications of Results:

Fridberg MJ, Hedner U, Roberts HR, Erhardtsen E. A study of the pharmacokinetics and safety of recombinant activated factor VII in healthy Caucasian and Japanese subjects. Blood Coagul Fibrinolysis. 2005 Jun;16(4):259-66.

Levy JH, Fingerhut A, Brott T, Langbakke IH, Erhardtsen E, Porte RJ. Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile. Transfusion. 2006 Jun;46(6):919-33.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01563471
• Other Study ID Numbers: F7LIVER-1465
• First Posted: March 27, 2012
• Last Update Posted: January 13, 2017
• Last Verified: January 2017

Additional relevant MeSH terms:

Hemostatic Disorders; Hemophilia A; Hemophilia B; Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Vascular Diseases; Cardiovascular Diseases