Human Fibrinogen - Pharmacokinetics

Pharmacokinetics of Haemocomplettan® P in Subjects With Congenital Fibrinogen Deficiency

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00496262

Enrollment

Registered

2007-07-04

Start date

2007-07-31

Completion date

2008-05-31

Last updated

2016-09-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fibrinogen Deficiency

Keywords

Congenital fibrinogen deficiency, Fibrinogen concentrate, Pharmacokinetics, Thrombelastography

Brief summary

This study evaluated the single-dose pharmacokinetics of human fibrinogen concentrate and clot strength (maximum clot firmness \[MCF\]) in subjects with congenital fibrinogen deficiency. MCF was measured to demonstrate the functional activity of replacement fibrinogen when a fixed dose of human fibrinogen concentrate was administered.

Interventions

BIOLOGICALHuman Fibrinogen Concentrate

Single intravenous infusion of 70 mg/kg body weight

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to No maximum

Healthy volunteers

Inclusion criteria

* Aged ≥ 6 years * Documented congenital fibrinogen deficiency: fibrinogen deficiency manifested as afibrinogenemia with plasma fibrinogen activity and antigen at screening undetectable (i.e. \< 20 mg/dL) * Informed consent signed by subject or legal guardian

Exclusion criteria

* Presence or history of hypersensitivity to Human Fibrinogen Concentrate or human plasma proteins, * Presence or history of deep vein thrombosis, pulmonary embolism, or arterial thrombosis * Acute bleeding * History of esophageal varicose bleeding * End stage liver disease (i.e. Child-Pugh score B or C) * Planned major surgery with a need for blood transfusion during the PK blood sampling period * Polytrauma within 1 year prior to enrollment

Design outcomes

Primary

Measure	Time frame	Description
Maximum Clot Firmness (MCF)	Pre-infusion and 1 hour post-infusion	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.

Secondary

Measure	Time frame	Description
Maximum Concentration (Cmax)	Pre-infusion to 13 days post-infusion	Cmax for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.
Area Under the Concentration-time Curve (AUC) Standardized for 70 mg/kg Body Weight Dose	Pre-infusion to 13 days post-infusion	AUC for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.
Clearance (Cl)	Pre-infusion to 13 days post-infusion	Cl for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.
Terminal Elimination Half-life (t1/2)	0.5 hours to 13 days post-infusion	t1/2 for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.
Volume of Distribution at Steady State (Vss)	Pre-infusion to 13 days post-infusion	Vss for fibrinogen activity was determined from samples taken at 11 timepoints during the specified time frame.
Incremental In Vivo Recovery (IVR)	Pre-infusion to 4 hours post-infusion	Maximum fibrinogen activity increase in plasma per mg/kg dosed
Classical In Vivo Recovery (IVR)	Pre-infusion to 4 hours post-infusion	Maximum fibrinogen activity increase in plasma times plasma volume per mg/kg dose
Mean Residence Time (MRT)	Pre-infusion to 13 days post-infusion	MRT for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame.

Countries

Italy, United States

Participant flow

Recruitment details

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

Participants by arm

Arm	Count
Human Fibrinogen Concentrate Includes all subjects who received any portion of the infusion of human fibrinogen concentrate.	15
Total	15

Baseline characteristics

Characteristic	Human Fibrinogen Concentrate
Age, Continuous	29.5 years STANDARD_DEVIATION 15.9
Age, Customized ≥16 to < 65 years	11 participants
Age, Customized <16 years	4 participants
Age, Customized >=65 years	0 participants
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	10 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	2 / 15
serious Total, serious adverse events	0 / 15

Outcome results

Primary

Maximum Clot Firmness (MCF)

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.

Time frame: 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.)

Arm	Measure	Value (MEAN)	Dispersion
Pre-infusion	Maximum Clot Firmness (MCF)	0 millimeters	Standard Deviation 0
1 Hour Post-infusion	Maximum Clot Firmness (MCF)	8.9 millimeters	Standard Deviation 4.4

Comparison: This is an open-label study with statistical comparison between MCF pre-infusion and 1 hour post-infusion.p-value: <0.00012-sided, 1-sample t-test

Secondary

Area Under the Concentration-time Curve (AUC) Standardized for 70 mg/kg Body Weight Dose

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

Time frame: Pre-infusion to 13 days post-infusion