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Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers

Primary Purpose

Congenital Bleeding Disorder, Healthy

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

vatreptacog alfa (activated)

placebo

About this trial

This is an interventional treatment trial for Congenital Bleeding Disorder

Eligibility Criteria

20 Years - 45 Years (Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

vatreptacog alfa, 5 mcg/kg

vatreptacog alfa, 10 mcg/kg

vatreptacog alfa, 20 mcg/kg

vatreptacog alfa, 30 mcg/kg

Arm Description

Outcomes

Primary Outcome Measures

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

Subjects With Anti-Vatreptacog Alfa Antibody

Post-dosing samples from subjects were evaluated for the presence of Anti-Vatreptacog alfa antibody

Secondary Outcome Measures

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.

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.

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 / λz), Where Ct is the last quantifiable activity and t the time of Ct.

Vatreptacog Alfa Clot Activity: Maximum FVIIa Activity (Cmax)

Vatreptacog Alfa Clot Activity: FVIIa Activity Measured 5 Min After Administration of NN1731 (C5min)

Vatreptacog Alfa Clot Activity: Back Extrapolated Estimate of the Initial FVIIa Activity (C0)

Vatreptacog Alfa Clot Activity- Terminal Slope (λz)

Vatreptacog Alfa Clot Activity: Terminal Half-life (t1/2)

Vatreptacog Alfa Clot Activity- Total Clearance (CL)

Vatreptacog Alfa Clot Activity- Apparent Volume of Distribution at Steady State (Vss)

Vatreptacog Alfa Clot Activity- Initial Volume of Distribution (VD)

Vatreptacog Alfa Clot Activity- Mean Residence Time (MRT)

Mean residence time of the unchanged drug in the systemic circulation

Full Information

NCT ID

NCT00822185

First Posted

January 13, 2009

Last Updated

December 12, 2014

Sponsor

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT00822185

Brief Title

Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Completed

Study Start Date

January 2009 (undefined)

Primary Completion Date

July 2009 (Actual)

Study Completion Date

July 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novo Nordisk A/S

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congenital Bleeding Disorder, Healthy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

vatreptacog alfa, 5 mcg/kg

Arm Type

Experimental

Arm Title

vatreptacog alfa, 10 mcg/kg

Arm Type

Experimental

Arm Title

vatreptacog alfa, 20 mcg/kg

Arm Type

Experimental

Arm Title

vatreptacog alfa, 30 mcg/kg

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

vatreptacog alfa (activated)

Intervention Description

One single dose is injected i.v. over 2 minutes to 6 subjects, 5 mcg/kg

Intervention Type

Drug

Intervention Name(s)

vatreptacog alfa (activated)

Intervention Description

One single dose is injected i.v. over 2 minutes to 6 subjects, 10 mcg/kg

Intervention Type

Drug

Intervention Name(s)

vatreptacog alfa (activated)

Intervention Description

One single dose is injected i.v. over 2 minutes to 6 subjects, 20 mcg/kg

Intervention Type

Drug

Intervention Name(s)

vatreptacog alfa (activated)

Intervention Description

One single dose is injected i.v. over 2 minutes to 6 subjects, 30 mcg/kg

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 5 mcg/kg

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 10 mcg/kg

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 20 mcg/kg

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Single dose is injected i.v. over 2 minutes to 2 subjects per dose level: 30 mcg/kg

Primary Outcome Measure Information:

Title

Safety (Physical Examination, Vital Signs, ECG, Haematology, Biochemistry, Urinalysis, Coagulation Factors, Coagulation-related Parameters, Injection Site Tolerability and Adverse Events (AE))

Description

Any safety issue was reported as AE

Time Frame

between dosing and 2-3 weeks after dosing

Title

Subjects With Anti-Vatreptacog Alfa Antibody

Description

Post-dosing samples from subjects were evaluated for the presence of Anti-Vatreptacog alfa antibody

Time Frame

between dosing, 2-3 weeks after dosing, and 11-13 weeks after dosing

Secondary Outcome Measure Information:

Title

Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 and up Until the Last Quantifiable Activity (AUC0-t)

Description

AUC0-t was computed using the linear trapezoid rule. Plasma FVIIa clot activity at time 0 was calculated by log linear interpolation.

Time Frame