title: Improved Pharmacokinetics with BAY 81-8973 Versus Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method: A Randomized Pharmacokinetic Study in Patients with Severe Hemophilia A.
abstract: BAY 81-8973 is a full-length, unmodified, recombinant human factor VIII (FVIII) for the treatment of hemophilia A.
  
  
  
  The aim of this study was to compare the pharmacokinetic (PK) profile of BAY 81-8973 with antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM) PATIENTS/METHODS: In this phase I, open-label, crossover study, men aged 18-65 years with severe hemophilia A and ≥150 exposure days to FVIII were randomized to receive a single intravenous infusion of 50 IU/kg BAY 81-8973 or rAHF-PFM, followed by crossover to a single infusion of the other treatment. FVIII levels were measured in plasma over 48 h using one-stage and chromogenic assays. PK parameters, including area under the curve from time zero to the last data point (AUClast; primary outcome) and half-life (t½) were calculated. A population PK model was developed to simulate various treatment scenarios.
  
  
  
  Eighteen patients were randomized and analyzed. Using both assays, geometric mean (coefficient of variation [%CV]) AUClastwas significantly higher, and t½was significantly longer, for BAY 81-8973 versus rAHF-PFM (one-stage, AUClast: 1660 IU·h/dL [29.4] vs. 1310 IU·h/dL [29.0], p < 0.0001; one-stage, t½: 14.5 [25.7] vs. 11.7 h [27.3], p < 0.0001). Simulations showed that median time to 1 IU/dL was approximately 27% longer for BAY 81-8973 versus rAHF-PFM over doses of 25-50 IU/kg; plasma levels >1 IU/dL could be maintained with 14.4 IU/kg BAY 81-8973 or 39.1 IU/kg rAHF-PFM 3×/week.
  
  
  
  BAY 81-8973 showed a superior PK profile versus rAHF-PFM. The same FVIII trough threshold level could be achieved with lower doses of BAY 81-8973 versus rAHF-PFM. ClinicalTrials.gov: NCT02483208.
authors.affiliation: Bayer, 100 Bayer Blvd, Whippany, NJ, 07981, USA. anita.shah@bayer.com.
authors.forename: Anita
authors.identifier: 0000-0002-7846-3115
authors.initials: A
authors.lastname: Shah
authors.affiliation: Bayer AG, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Solms
authors.affiliation: Bayer AG, Wuppertal, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Garmann
authors.affiliation: Bayer AG, Berlin, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Katterle
authors.affiliation: Specialized Hospital for Active Treatment of Hematologic Diseases, Sofia, Bulgaria.
authors.forename: Verzhiniya
authors.initials: V
authors.lastname: Avramova
authors.affiliation: Specialized Hospital for Active Treatment of Hematologic Diseases, Sofia, Bulgaria.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Simeonov
authors.affiliation: Specialized Hospital for Active Treatment of Hematologic Diseases, Sofia, Bulgaria.
authors.forename: Toshko
authors.initials: T
authors.lastname: Lissitchkov
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D012709:Serum Albumin; C078147:F8 protein, human; D005169:Factor VIII
keywords: Chromogenic Assay; FVIII Activity; Mean Residence Time; Severe Hemophilia; Trough Level