Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers

Phase 1

Completed

• Conditions: Congenital Bleeding Disorder; Healthy
• Interventions: Drug: vatreptacog alfa (activated); Drug: placebo

• Registration Number: NCT00822185
• Lead Sponsor: Novo Nordisk A/S

Brief 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

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-01-13
• Study First Submitted QC: 2009-01-13
• Study First Posted: 2009-01-14
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Results First Submitted: 2013-09-27
• Results First Submitted QC: 2014-09-22
• Results First Posted: 2014-09-23
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-12
• Last Update Posted: 2015-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 32

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
vatreptacog alfa, 5 mcg/kg	placebo	-
vatreptacog alfa, 20 mcg/kg	placebo	-
vatreptacog alfa, 10 mcg/kg	vatreptacog alfa (activated)	-
vatreptacog alfa, 5 mcg/kg	vatreptacog alfa (activated)	-
vatreptacog alfa, 10 mcg/kg	placebo	-
vatreptacog alfa, 20 mcg/kg	vatreptacog alfa (activated)	-
vatreptacog alfa, 30 mcg/kg	placebo	-
vatreptacog alfa, 30 mcg/kg	vatreptacog alfa (activated)	-

Primary Outcome Measures

Name	Time	Method
Safety (Physical Examination, Vital Signs, ECG, Haematology, Biochemistry, Urinalysis, Coagulation Factors, Coagulation-related Parameters, Injection Site Tolerability and Adverse Events (AE))	between dosing and 2-3 weeks after dosing	Any safety issue was reported as AE
Subjects With Anti-Vatreptacog Alfa Antibody	between dosing, 2-3 weeks after dosing, and 11-13 weeks after dosing	Post-dosing samples from subjects were evaluated for the presence of Anti-Vatreptacog alfa antibody

Secondary Outcome Measures

Name	Time	Method
Vatreptacog Alfa Clot Activity- Total Clearance (CL)	during 1-2 days after drug administration
Vatreptacog Alfa Clot Activity- Apparent Volume of Distribution at Steady State (Vss)	during 1-2 days after drug administration
Vatreptacog Alfa Clot Activity- Initial Volume of Distribution (VD)	during 1-2 days after drug administration
Vatreptacog Alfa Clot Activity- Mean Residence Time (MRT)	during 1-2 days after drug administration	Mean residence time of the unchanged drug in the systemic circulation
Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 and up Until the Last Quantifiable Activity (AUC0-t)	during 1-2 days after drug administration	AUC0-t was computed using the linear trapezoid rule. Plasma FVIIa clot activity at time 0 was calculated by log linear interpolation.
Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 to 24 h (AUC0-24)	during 1-2 days after drug administration	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.
Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 h to Infinity (AUC 0-inf)	during 1-2 days after drug administration	AUC0-inf = AUC0-t + (Ct / λz), Where Ct is the last quantifiable activity and t the time of Ct.
Vatreptacog Alfa Clot Activity: Maximum FVIIa Activity (Cmax)	during 1-2 days after drug administration
Vatreptacog Alfa Clot Activity: FVIIa Activity Measured 5 Min After Administration of NN1731 (C5min)	during 1-2 days after drug administration
Vatreptacog Alfa Clot Activity: Back Extrapolated Estimate of the Initial FVIIa Activity (C0)	during 1-2 days after drug administration
Vatreptacog Alfa Clot Activity- Terminal Slope (λz)	during 1-2 days after drug administration
Vatreptacog Alfa Clot Activity: Terminal Half-life (t1/2)	during 1-2 days after drug administration