A cross-over pharmacokinetic study of a double viral inactivated factor IX concentrate (15 nm filtration and SD) compared to a SD factor IX concentrate.
A double blind randomized cross-over multi-center study has been conducted to compare the pharmacokinetic and coagulation activation markers of high-purity factor IX concentrate subjected to both solvent/ detergent (SD) treatment and 15 nm-filtration (FIX-SD-15) with the licensed product subjected only to solvent-detergent (FIX-SD). This filtration process allows the elimination of small particles, such as non-enveloped viruses (i.e., hepatitis A and parvovirus B19). Eleven severe hemophilia B patients (FIX coagulant activity <2 IU/dl) received one infusion of 60 IU/kg of FIX-SD and one infusion of 60 IU/kg of FIX-SD-15 at least at 10 days interval. Blood samples were obtained before and at various time up to 72 h after infusion. The decay curves of factor IX (FIX:C and FIX:Ag) were evaluated by a model independent method. Bioequivalence was found between the two concentrates using the Schuirmann test. The mean FIX:C and FIX:Ag recovery of FIX-SD-15 was 1.08 and 0.89 IU/dl/IU/kg respectively with a mean half-life of 33.3 h for FIX:C and 25.6 h for FIX:Ag. Six months after initial enrollment, pharmacokinetic parameters were similar in the 7 patients tested. There was no significant variation of prothrombin fragment 1+2 and thrombin-antithrombin complexes measured up to 6 h after infusion, indicating that there was no activation process after administration of FIX. In conclusion, these data demonstrate that the introduction of a 15 nm filtration does not alter the pharmacokinetic profile of a well characterized SD FIX concentrate while providing additional viral safety.
Goudemand
J
J
Department of Hematology B, Claude Huriez Hospital, Lille, France.
Peynet
J
J
Chambost
H
H
Négrier
C
C
Briquel
M E
ME
Claeyssens
S
S
Derlon-Borel
A
A
Guérois
C
C
Caron
C
C
Scherrmann
J M
JM
Debray
M
M
Bridey
F
F
D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D019540:Area Under Curve; D015415:Biomarkers; D002648:Child; D018592:Cross-Over Studies; D003902:Detergents; D004311:Double-Blind Method; D005164:Factor IX / Q000302:isolation & purification / Q000493:pharmacokinetics*; D005374:Filtration; D006207:Half-Life; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D012449:Safety; D012997:Solvents; D016896:Treatment Outcome; D014777:Virus Diseases / Q000517:prevention & control
D015415:Biomarkers; D003902:Detergents; D010446:Peptide Fragments; D012997:Solvents; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D005164:Factor IX; D010447:Peptide Hydrolases