Pharmacokinetic (PK) Profile
- An open-label, prospective, randomized, controlled, two-arm, cross-over study was conducted in 22 subjects with congenital fibrinogen deficiency (afibrinogenemia), ranging in age from 12 to 53 years (6 adolescents, 16 adults)1
- Each subject received a single intravenous 70 mg/kg dose of fibryga and a comparator product. Blood samples were drawn to determine fibrinogen activity at baseline and up to 14 days after the infusion1
- Incremental in vivo recovery (IVR) was determined from levels obtained up to 4 hours post-infusion. Median incremental IVR was a 1.8 mg/dL (range 1.1 – 2.6 mg/dL) increase per mg/kg. Median in vivo recovery indicates that a dose of 70 mg/kg will increase patients’ fibrinogen plasma concentration by approximately 125 mg/dL.
Fibryga demonstrated a similar PK profile for fibrinogen concentration compared to an active control, achieving levels well within the recommended target range of 1 to 1.5 g/L (see Table and Figure)1,2
- No difference in fibrinogen activity was observed between males and females1
- No difference in pharmacokinetics was observed between adults and adolescents.
|PK Parameters (N=21) for Fibrinogen Activity1|
|Parameters||Mean ± SD (range)|
|Half-life (hr)||75.9± 23.8
|Cmax (mg/dL)||139.0 ± 36.9
|AUC (mg*hr/mL)||124.8 ± 34.6
|AUCnorm for dose of 70 mg/kg (mg*hr/mL)||113.7± 31.5
|Clearance (mL/hr/kg)||0.7 ± 0.2
|Mean residence time (hr)||106.3 ± 30.9
|Volume of distribution at steady state (mL/kg)||70.2 ± 29.9
AUC = area under the curve; AUCnorm = area under the curve to normalized to the dose administered; Cmax = maximum plasma concentration; PK = pharmacokinetic; SD = standard deviation.
As shown in the figure, mean fibrinogen concentration peaked within 2 hours after administration and decreased to pre-infusion levels by 216 hours (9 days). Across the first 144 hours (6 days), mean plasma fibrinogen activity showed higher values for fibryga than for the active control.2
|Mean (±SD) fibrinogen activity (g/L) during PK assessment after fibryga and active control administration (N=21)2|
Fibrinogen activity plotted against time for fibryga and active control following normalization to the dose administered and standardization to 70 mg kg-1.
Per protocol patient analysis set.
LOQ=limit of quantification.
Source: Ross C, Rangarajan S, Karimi M, et al. Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency. J Thromb Haemost. 2018;16:253-261.
- Fibryga full Prescribing Information. Hoboken, NJ: Octapharma USA, Inc.; rev 2017.
- Ross C, Rangarajan S, Karimi M, et al. Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency. J Thromb Haemost. 2018;16:253-261.