Improved Pharmacokinetics with BAY 81-8973 Versus Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method: A Randomized Pharmacokinetic Study in Patients with Severe Hemophilia A.

Autor: Shah A; Bayer, 100 Bayer Blvd, Whippany, NJ, 07981, USA. anita.shah@bayer.com., Solms A; Bayer AG, Berlin, Germany., Garmann D; Bayer AG, Wuppertal, Germany., Katterle Y; Bayer AG, Berlin, Germany., Avramova V; Specialized Hospital for Active Treatment of Hematologic Diseases, Sofia, Bulgaria., Simeonov S; Specialized Hospital for Active Treatment of Hematologic Diseases, Sofia, Bulgaria., Lissitchkov T; Specialized Hospital for Active Treatment of Hematologic Diseases, Sofia, Bulgaria.
Jazyk: angličtina
Zdroj: Clinical pharmacokinetics [Clin Pharmacokinet] 2017 Sep; Vol. 56 (9), pp. 1045-1055.
DOI: 10.1007/s40262-016-0492-2
Abstrakt: Background: BAY 81-8973 is a full-length, unmodified, recombinant human factor VIII (FVIII) for the treatment of hemophilia A.
Objective: 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 (AUC last ; primary outcome) and half-life (t ½ ) were calculated. A population PK model was developed to simulate various treatment scenarios.
Results: Eighteen patients were randomized and analyzed. Using both assays, geometric mean (coefficient of variation [%CV]) AUC last was significantly higher, and t ½ was significantly longer, for BAY 81-8973 versus rAHF-PFM (one-stage, AUC last : 1660 IU·h/dL [29.4] vs. 1310 IU·h/dL [29.0], p < 0.0001; one-stage, t ½ : 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.
Conclusions: 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.
Databáze: MEDLINE
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