Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers (NCT NCT00822185)
NCT ID: NCT00822185
Last Updated: 2015-01-05
Results Overview
Any safety issue was reported as AE
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
between dosing and 2-3 weeks after dosing
Results posted on
2015-01-05
Participant Flow
This trial was conducted at a single site in Japan.
Participant milestones
| Measure |
Vatreptacog Alfa 5 mcg/kg
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
8
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
6
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability and Pharmacokinetics of NN1731 in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
n=8 Participants
A single dose of placebo was administered intravenously
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
28.8 years
STANDARD_DEVIATION 6.5 • n=39 Participants
|
23.3 years
STANDARD_DEVIATION 3.4 • n=41 Participants
|
26.5 years
STANDARD_DEVIATION 3.5 • n=35 Participants
|
26.3 years
STANDARD_DEVIATION 5.1 • n=31 Participants
|
26.5 years
STANDARD_DEVIATION 7.7 • n=146 Participants
|
26.3 years
STANDARD_DEVIATION 5.6 • n=19 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=146 Participants
|
0 Participants
n=19 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
6 Participants
n=31 Participants
|
8 Participants
n=146 Participants
|
32 Participants
n=19 Participants
|
PRIMARY outcome
Timeframe: between dosing and 2-3 weeks after dosingPopulation: Safety analysis set included all the randomised subjects who received at least one dose of the trial product.
Any safety issue was reported as AE
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
n=8 Participants
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Safety (Physical Examination, Vital Signs, ECG, Haematology, Biochemistry, Urinalysis, Coagulation Factors, Coagulation-related Parameters, Injection Site Tolerability and Adverse Events (AE))
|
0 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
PRIMARY outcome
Timeframe: between dosing, 2-3 weeks after dosing, and 11-13 weeks after dosingPopulation: Safety analysis set included all the randomised subjects who received at least one dose of the trial product.
Post-dosing samples from subjects were evaluated for the presence of Anti-Vatreptacog alfa antibody
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
n=8 Participants
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Subjects With Anti-Vatreptacog Alfa Antibody
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation.
AUC0-t was computed using the linear trapezoid rule. Plasma FVIIa clot activity at time 0 was calculated by log linear interpolation.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 and up Until the Last Quantifiable Activity (AUC0-t)
|
7.875 (IU*h)/mL
Geometric Coefficient of Variation 10.7
|
13.845 (IU*h)/mL
Geometric Coefficient of Variation 15.0
|
30.268 (IU*h)/mL
Geometric Coefficient of Variation 7.5
|
46.986 (IU*h)/mL
Geometric Coefficient of Variation 6.4
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation. One (1) subject did not contribute to PK evaluation.
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.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 to 24 h (AUC0-24)
|
7.970 (IU*h)/mL
Geometric Coefficient of Variation 11.8
|
13.143 (IU*h)/mL
Geometric Coefficient of Variation 8.1
|
30.310 (IU*h)/mL
Geometric Coefficient of Variation 7.5
|
47.021 (IU*h)/mL
Geometric Coefficient of Variation 6.3
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation. One (1) subject did not contribute to PK evaluation.
AUC0-inf = AUC0-t + (Ct / λz), Where Ct is the last quantifiable activity and t the time of Ct.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity: Area Under the FVIIa Activity-time Curve From Time 0 h to Infinity (AUC 0-inf)
|
8.128 (IU*h)/mL
Geometric Coefficient of Variation 14.7
|
13.195 (IU*h)/mL
Geometric Coefficient of Variation 8.1
|
30.351 (IU*h)/mL
Geometric Coefficient of Variation 7.7
|
47.060 (IU*h)/mL
Geometric Coefficient of Variation 6.4
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity: Maximum FVIIa Activity (Cmax)
|
15.767 IU/mL
Geometric Coefficient of Variation 10.4
|
27.569 IU/mL
Geometric Coefficient of Variation 13.9
|
55.732 IU/mL
Geometric Coefficient of Variation 5.9
|
86.974 IU/mL
Geometric Coefficient of Variation 4.4
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity: FVIIa Activity Measured 5 Min After Administration of NN1731 (C5min)
|
15.767 IU/mL
Geometric Coefficient of Variation 10.4
|
27.569 IU/mL
Geometric Coefficient of Variation 13.9
|
55.732 IU/mL
Geometric Coefficient of Variation 5.9
|
86.974 IU/mL
Geometric Coefficient of Variation 4.4
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity: Back Extrapolated Estimate of the Initial FVIIa Activity (C0)
|
19.802 IU/mL
Geometric Coefficient of Variation 8.4
|
34.497 IU/mL
Geometric Coefficient of Variation 14.2
|
69.474 IU/mL
Geometric Coefficient of Variation 7.3
|
106.916 IU/mL
Geometric Coefficient of Variation 5.5
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation. One (1) subject did not contribute to PK evaluation.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity- Terminal Slope (λz)
|
0.09 1/h
Geometric Coefficient of Variation 59.0
|
0.14 1/h
Geometric Coefficient of Variation 32.1
|
0.22 1/h
Geometric Coefficient of Variation 49.9
|
0.23 1/h
Geometric Coefficient of Variation 53.5
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation. One (1) subject did not contribute to data.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity: Terminal Half-life (t1/2)
|
7.51 hours
Geometric Coefficient of Variation 59.0
|
4.90 hours
Geometric Coefficient of Variation 32.1
|
3.14 hours
Geometric Coefficient of Variation 49.9
|
3.07 hours
Geometric Coefficient of Variation 53.5
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation. Two (2) subjects did not contribute to data.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity- Total Clearance (CL)
|
105.14 mL/h/kg
Geometric Coefficient of Variation 16.5
|
129.56 mL/h/kg
Geometric Coefficient of Variation 6.3
|
110.82 mL/h/kg
Geometric Coefficient of Variation 6.6
|
108.30 mL/h/kg
Geometric Coefficient of Variation 6.2
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation. Two (2) subject did not contribute to PK evaluation.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity- Apparent Volume of Distribution at Steady State (Vss)
|
164.23 mL/kg
Geometric Coefficient of Variation 55.0
|
131.72 mL/kg
Geometric Coefficient of Variation 15.4
|
83.23 mL/kg
Geometric Coefficient of Variation 18.5
|
79.67 mL/kg
Geometric Coefficient of Variation 9.8
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation.
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity- Initial Volume of Distribution (VD)
|
43.15 mL/kg
Geometric Coefficient of Variation 10.5
|
49.31 mL/kg
Geometric Coefficient of Variation 15.2
|
48.41 mL/kg
Geometric Coefficient of Variation 5.8
|
47.67 mL/kg
Geometric Coefficient of Variation 4.9
|
—
|
SECONDARY outcome
Timeframe: during 1-2 days after drug administrationPopulation: PK analysis set included all the subjects not violating the protocol in a manner that was judged to affect PK endpoint evaluation. One (1) subject did not contribute to PK evaluation.
Mean residence time of the unchanged drug in the systemic circulation
Outcome measures
| Measure |
Vatreptacog Alfa 5 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 5 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 10 mcg/kg
n=5 Participants
A single dose of Vatreptacog alfa 10 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 20 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 20 mcg/kg bodyweight was administered intravenously
|
Vatreptacog Alfa 30 mcg/kg
n=6 Participants
A single dose of Vatreptacog alfa 30 mcg/kg bodyweight was administered intravenously
|
Placebo
A single dose of placebo was administered intravenously
|
|---|---|---|---|---|---|
|
Vatreptacog Alfa Clot Activity- Mean Residence Time (MRT)
|
1.56 hours
Geometric Coefficient of Variation 73.0
|
1.02 hours
Geometric Coefficient of Variation 14.5
|
0.75 hours
Geometric Coefficient of Variation 20.5
|
0.74 hours
Geometric Coefficient of Variation 13.0
|
—
|
Adverse Events
Vatreptacog Alfa 5 mcg/kg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Vatreptacog Alfa 10 mcg/kg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Vatreptacog Alfa 20 mcg/kg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Vatreptacog Alfa 30 mcg/kg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Novo Nordisk reserves the right to defer data release until specified milestones, e.g. availability of a clinical trial report. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property. Novo Nordisk reserves the right to prior review of site-specific publications and to ask for deferment of publication of individual site results until after the primary manuscript is accepted for publication.
- Publication restrictions are in place
Restriction type: OTHER