Trial Outcomes & Findings for Human Fibrinogen - Pharmacokinetics (NCT NCT00496262)

NCT ID: NCT00496262

Last Updated: 2016-09-15

Results Overview

MCF is a functional parameter that depends on the activation of coagulation, the fibrinogen content of the sample (in plasma), and the polymerization and crosslinking of the fibrin network. MCF was determined by rotational thromboelastometry (ROTEM) testing.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Pre-infusion and 1 hour post-infusion

Results posted on

2016-09-15

Participant Flow

Subjects were enrolled at study sites in the USA and Italy.

Participant milestones

Participant milestones
Measure	Human Fibrinogen Concentrate All enrolled subjects received a single IV infusion of 70 mg/kg body weight of human fibrinogen concentrate.
Overall Study STARTED	15
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Human Fibrinogen - Pharmacokinetics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Human Fibrinogen Concentrate n=15 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.
Age, Continuous	29.5 years STANDARD_DEVIATION 15.9 • n=5 Participants
Age, Customized <16 years	4 participants n=5 Participants
Age, Customized ≥16 to < 65 years	11 participants n=5 Participants
Age, Customized >=65 years	0 participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-infusion and 1 hour post-infusion

Population: All subjects in the intention to treat (ITT) population. The ITT population included all subjects who received any portion of any infusion of human fibrinogen concentrate. (Note: 2 subjects in the ITT population had missing MCF data; the change from baseline MCF was entered as 0.0 for these subjects.)

MCF is a functional parameter that depends on the activation of coagulation, the fibrinogen content of the sample (in plasma), and the polymerization and crosslinking of the fibrin network. MCF was determined by rotational thromboelastometry (ROTEM) testing.

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=15 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion n=15 Participants 1 hour after end of infusion
Maximum Clot Firmness (MCF)	0 millimeters Standard Deviation 0	8.9 millimeters Standard Deviation 4.4

SECONDARY outcome

Timeframe: 0.5 hours to 13 days post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

t1/2 for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Terminal Elimination Half-life (t1/2)	78.7 hours Standard Deviation 18.1	—

SECONDARY outcome

Timeframe: Pre-infusion to 13 days post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

Cmax for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Maximum Concentration (Cmax)	1.4 g/L Standard Deviation 0.27	—

SECONDARY outcome

Timeframe: Pre-infusion to 13 days post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

AUC for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Area Under the Concentration-time Curve (AUC) Standardized for 70 mg/kg Body Weight Dose	124.3 hour*mg/mL Standard Deviation 24.16	—

SECONDARY outcome

Timeframe: Pre-infusion to 13 days post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

Cl for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Clearance (Cl)	0.59 mL/hour/kg Standard Deviation 0.13	—

SECONDARY outcome

Timeframe: Pre-infusion to 13 days post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

MRT for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Mean Residence Time (MRT)	92.8 hours Standard Deviation 20.1	—

SECONDARY outcome

Timeframe: Pre-infusion to 13 days post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

Vss for fibrinogen activity was determined from samples taken at 11 timepoints during the specified time frame.

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Volume of Distribution at Steady State (Vss)	52.7 mL/kg Standard Deviation 7.48	—

SECONDARY outcome

Timeframe: Pre-infusion to 4 hours post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

Maximum fibrinogen activity increase in plasma per mg/kg dosed

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Incremental In Vivo Recovery (IVR)	1.7 mg/dL increase per mg/kg body weight Interval 1.3 to 2.7	—

SECONDARY outcome

Timeframe: Pre-infusion to 4 hours post-infusion

Population: The pharmacokinetic analysis population (PK PP) included all subjects who received \>90% of the infusion and who also had sufficient data for a reliable PK analysis (n=14).

Maximum fibrinogen activity increase in plasma times plasma volume per mg/kg dose

Outcome measures

Outcome measures
Measure	Human Fibrinogen Concentrate n=14 Participants Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	1 Hour Post-infusion 1 hour after end of infusion
Classical In Vivo Recovery (IVR)	61.8 % of expected increase in fibrinogen Interval 52.5 to 97.4	—

Adverse Events

Human Fibrinogen Concentrate

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Human Fibrinogen Concentrate n=15 participants at risk Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.7% 1/15 • Number of events 1
General disorders Pain	6.7% 1/15 • Number of events 1
Nervous system disorders Headache	6.7% 1/15 • Number of events 1
Respiratory, thoracic and mediastinal disorders Epistaxis	6.7% 1/15 • Number of events 1

Additional Information

Program Director, Clinical R&D

CSL Behring

Phone: Use email contact.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator must provide a copy of any results communication to the sponsor for review at least 30 days prior to public release. The sponsor may request any changes necessary to prevent forfeiture of patent rights to data not in the public domain. For a multi-center study, the investigator must wait (i) at least 1 year after the study is completed at all sites or (ii) until notified by the sponsor that no multi-center publication is planned before seeking publication review.
Publication restrictions are in place

Restriction type: OTHER