Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers

Healthy Clinical Trial

Official title:

A Single-centre, Randomised, Placebo-controlled, Double-blind, Single-dose, Dose-escalation Trial to Assess the Safety, Tolerability and Pharmacokinetics of Ascending Intravenous Doses of an Activated Recombinant FVII Analogue (NN1731) in Healthy Japanese Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00822185
• Other study ID #: NN1731-3604
• Secondary ID: JapicCTI-090681
• Status: Completed
• Phase: Phase 1
• First received: January 13, 2009
• Last updated: December 12, 2014
• Start date: January 2009
• Est. completion date: July 2009

Study information

• Verified date: December 2014
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Japan. The aim of this trial is to assess the safety and tolerability of activated recombinant human coagulation factor VII analogue (NN1731, vatreptacog alfa (activated)) in healthy Japanese male subjects. In addition, the pharmacokinetics of NN1731 will be examined

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• Japanese male subjects, who are considered to be generally healthy based on assessment of medical history, physical examination and clinical laboratory data at screening, as judged by the Investigator or Sub-investigator

• Body Mass Index (BMI) between 18.0 and 27.0 kg/m^2 (inclusive)

Exclusion Criteria:

• Any clinical laboratory values deviated from the reference range at the laboratory (except for cases within physiological change) or any abnormal electrocardiogram (ECG) findings at the screening, as judged by the Investigator or Sub-investigator

• Presence or history of cancer or any clinically significant cardiac, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, dermatological, venereal, haematological, neurological, or psychiatric diseases or disorders

• Evidence of clinically relevant pathology or a potential thromboembolic risk as judged by the Investigator or Sub-investigator

• Presence or history of atherosclerosis, arteriosclerosis or thromboembolic events

• Any past history of migraine

• Overt bleeding, including from the gastrointestinal tract

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Congenital Bleeding Disorder
• Healthy
• Hemostatic Disorders

Intervention

Drug:
• vatreptacog alfa (activated)
One single dose is injected i.v. over 2 minutes to 6 subjects, 5 mcg/kg
• vatreptacog alfa (activated)
One single dose is injected i.v. over 2 minutes to 6 subjects, 10 mcg/kg
• vatreptacog alfa (activated)
One single dose is injected i.v. over 2 minutes to 6 subjects, 20 mcg/kg
• vatreptacog alfa (activated)
One single dose is injected i.v. over 2 minutes to 6 subjects, 30 mcg/kg
• placebo
Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 5 mcg/kg
• placebo
Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 10 mcg/kg
• placebo
Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 20 mcg/kg
• placebo
Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 30 mcg/kg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (Physical Examination, Vital Signs, ECG, Haematology, Biochemistry, Urinalysis, Coagulation Factors, Coagulation-related Parameters, Injection Site Tolerability and Adverse Events (AE))	Any safety issue was reported as AE	between dosing and 2-3 weeks after dosing	No
Primary	Subjects With Anti-Vatreptacog Alfa Antibody	Post-dosing samples from subjects were evaluated for the presence of Anti-Vatreptacog alfa antibody	between dosing, 2-3 weeks after dosing, and 11-13 weeks after dosing	No
Secondary	Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 and up Until the Last Quantifiable Activity (AUC0-t)	AUC0-t was computed using the linear trapezoid rule. Plasma FVIIa clot activity at time 0 was calculated by log linear interpolation.	during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 to 24 h (AUC0-24)	Blood samples were collected at following time points: -30 min, -20 min, -10 min, 5 min, 10 min, 20 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 8h, 12h and 24h to calculate area under the curve.	during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 h to Infinity (AUC 0-inf)	AUC0-inf = AUC0-t + (Ct / ?z), Where Ct is the last quantifiable activity and t the time of Ct.	during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity: Maximum FVIIa Activity (Cmax)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity: FVIIa Activity Measured 5 Min After Administration of NN1731 (C5min)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity: Back Extrapolated Estimate of the Initial FVIIa Activity (C0)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity- Terminal Slope (?z)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity: Terminal Half-life (t1/2)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity- Total Clearance (CL)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity- Apparent Volume of Distribution at Steady State (Vss)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity- Initial Volume of Distribution (VD)		during 1-2 days after drug administration	No
Secondary	Vatreptacog Alfa Clot Activity- Mean Residence Time (MRT)	Mean residence time of the unchanged drug in the systemic circulation	during 1-2 days after drug administration	No

External Links

•   Clinical Trials at Novo Nordisk