Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00822185
First received: January 13, 2009
Last updated: December 12, 2014
Last verified: December 2014

January 13, 2009
December 12, 2014
January 2009
July 2009   (final data collection date for primary outcome measure)
  • Safety (Physical Examination, Vital Signs, ECG, Haematology, Biochemistry, Urinalysis, Coagulation Factors, Coagulation-related Parameters, Injection Site Tolerability and Adverse Events (AE)) [ Time Frame: between dosing and 2-3 weeks after dosing ] [ Designated as safety issue: No ]
    Any safety issue was reported as AE
  • Subjects With Anti-Vatreptacog Alfa Antibody [ Time Frame: between dosing, 2-3 weeks after dosing, and 11-13 weeks after dosing ] [ Designated as safety issue: No ]
    Post-dosing samples from subjects were evaluated for the presence of Anti-Vatreptacog alfa antibody
  • Safety (physical examination, vital signs, ECG, haematology, biochemistry, urinalysis, coagulation factors, coagulation-related parameters, injection site tolerability and AE) [ Time Frame: between dosing and 2-3 weeks after dosing ] [ Designated as safety issue: Yes ]
  • Anti-NN1731 antibody [ Time Frame: between dosing, 2-3 weeks after dosing, and 11-13 weeks after dosing ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00822185 on ClinicalTrials.gov Archive Site
  • Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 and up Until the Last Quantifiable Activity (AUC0-t) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
    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) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
    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) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
    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) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity: FVIIa Activity Measured 5 Min After Administration of NN1731 (C5min) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity: Back Extrapolated Estimate of the Initial FVIIa Activity (C0) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity- Terminal Slope (λz) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity: Terminal Half-life (t1/2) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity- Total Clearance (CL) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity- Apparent Volume of Distribution at Steady State (Vss) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity- Initial Volume of Distribution (VD) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
  • Vatreptacog Alfa Clot Activity- Mean Residence Time (MRT) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: No ]
    Mean residence time of the unchanged drug in the systemic circulation
NN1731 clot activity (AUC0-t, AUC0-24, AUC0-inf, Cmax, C5min, C0, terminal slope, t1/2, CL, Vss, Vc and MRT) [ Time Frame: during 1-2 days after drug administration ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers
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

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

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Congenital Bleeding Disorder
  • Healthy
  • Drug: vatreptacog alfa (activated)
    One single dose is injected i.v. over 2 minutes to 6 subjects, 5 mcg/kg
  • Drug: vatreptacog alfa (activated)
    One single dose is injected i.v. over 2 minutes to 6 subjects, 10 mcg/kg
  • Drug: vatreptacog alfa (activated)
    One single dose is injected i.v. over 2 minutes to 6 subjects, 20 mcg/kg
  • Drug: vatreptacog alfa (activated)
    One single dose is injected i.v. over 2 minutes to 6 subjects, 30 mcg/kg
  • Drug: placebo
    Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 5 mcg/kg
  • Drug: placebo
    Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 10 mcg/kg
  • Drug: placebo
    Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 20 mcg/kg
  • Drug: placebo
    Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 30 mcg/kg
  • Experimental: vatreptacog alfa, 5 mcg/kg
    Interventions:
    • Drug: vatreptacog alfa (activated)
    • Drug: placebo
  • Experimental: vatreptacog alfa, 10 mcg/kg
    Interventions:
    • Drug: vatreptacog alfa (activated)
    • Drug: placebo
  • Experimental: vatreptacog alfa, 20 mcg/kg
    Interventions:
    • Drug: vatreptacog alfa (activated)
    • Drug: placebo
  • Experimental: vatreptacog alfa, 30 mcg/kg
    Interventions:
    • Drug: vatreptacog alfa (activated)
    • Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
July 2009
July 2009   (final data collection date for primary outcome measure)

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
Male
20 Years to 45 Years
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00822185
NN1731-3604, JapicCTI-090681
No
Novo Nordisk A/S
Novo Nordisk A/S
Not Provided
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
Novo Nordisk A/S
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP