Nonacog alfa

The annualized bleed rate (ABR) or the annualized number of bleeding episodes per year, will be derived for each participant for each treatment period by using the following formula: ABR = number of bleeds / (Days on treatment period / 365.25) The number of bleeds for the ABR calculation includes all bleeds requiring treatment with factor IX product during the time on treatment.

Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hrs after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens.

Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hrs after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens.

Incidence of FIX inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory with Nijmegen assay result \>=0.6 Bethesda Unit (BU). Incidence was stratified by participant exposure history - Minimally Treated Patients (MTPs): those who had received at least one prior FIX infusion, and \<= 100 documented Exposure Days (EDs); while Previously Treated Patients (PTPs): those who had received \>100 documented prior EDs. When number of prior EDs for an individual was not known to be at least 100, participants were included in the MTP population.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state.

Linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.

AUMCinf/AUCinf, where AUMCinf is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Incremental recovery: Increase in circulating increase in FIX activity for every IU of BeneFIX administered per kg of body weight.