A Shah1, H Delesen2, S Garger3, S Lalezari4. 1. Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. 2. Bayer Pharma AG, Wuppertal, Germany. 3. Bayer HealthCare, Berkeley, CA, USA. 4. Israel National Hemophilia Center and Thrombosis Unit, Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
Abstract
INTRODUCTION: BAY 81-8973 is a full-length recombinant factor VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated recombinant FVIII (rFVIII-FS) but is produced with advanced manufacturing technologies. AIM: To analyse the pharmacokinetics (PK) of BAY 81-8973 after single and multiple dosing across different age and ethnic groups in the LEOPOLD clinical trial programme. METHODS: The LEOPOLD trials enrolled patients with severe haemophiliaA aged 12-65 years (LEOPOLD I and II) or ≤12 years (LEOPOLD Kids) with ≥150 (LEOPOLD I and II) or ≥50 (LEOPOLD Kids) exposure days to any FVIII product and no history of FVIII inhibitors. PK were assessed using chromogenic and one-stage assays (only chromogenic assay for LEOPOLD Kids) after a single 50-IU kg(-1) dose of BAY 81-8973 and, in a subset of patients in LEOPOLD I, after repeated dosing. Pharmacokinetic analyses were also performed based on age (18 to 65, 12 to <18, 6 to <12 and <6 years) and ethnicity (Asian and non-Asian). RESULTS: Pharmacokinetic assessments in the LEOPOLD I trial showed non-inferiority of BAY 81-8973 vs. rFVIII-FS. The PK of BAY 81-8973 were comparable after single and multiple dosing. Age-based analysis in the three trials showed that plasma concentrations were slightly lower for children, but similar for adolescents compared with adults. Pharmacokinetic results were similar in the different ethnic groups. CONCLUSIONS: Results of the LEOPOLD trials show that the BAY 81-8973 pharmacokinetic profile is non-inferior to rFVIII-FS. Similar BAY 81-8973 pharmacokinetic values were observed following single and repeated dosing and across ethnic groups.
RCT Entities:
INTRODUCTION:BAY 81-8973 is a full-length recombinant factor VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated recombinant FVIII (rFVIII-FS) but is produced with advanced manufacturing technologies. AIM: To analyse the pharmacokinetics (PK) of BAY 81-8973 after single and multiple dosing across different age and ethnic groups in the LEOPOLD clinical trial programme. METHODS: The LEOPOLD trials enrolled patients with severe haemophilia A aged 12-65 years (LEOPOLD I and II) or ≤12 years (LEOPOLD Kids) with ≥150 (LEOPOLD I and II) or ≥50 (LEOPOLD Kids) exposure days to any FVIII product and no history of FVIII inhibitors. PK were assessed using chromogenic and one-stage assays (only chromogenic assay for LEOPOLD Kids) after a single 50-IU kg(-1) dose of BAY 81-8973 and, in a subset of patients in LEOPOLD I, after repeated dosing. Pharmacokinetic analyses were also performed based on age (18 to 65, 12 to <18, 6 to <12 and <6 years) and ethnicity (Asian and non-Asian). RESULTS: Pharmacokinetic assessments in the LEOPOLD I trial showed non-inferiority of BAY 81-8973 vs. rFVIII-FS. The PK of BAY 81-8973 were comparable after single and multiple dosing. Age-based analysis in the three trials showed that plasma concentrations were slightly lower for children, but similar for adolescents compared with adults. Pharmacokinetic results were similar in the different ethnic groups. CONCLUSIONS: Results of the LEOPOLD trials show that the BAY 81-8973 pharmacokinetic profile is non-inferior to rFVIII-FS. Similar BAY 81-8973 pharmacokinetic values were observed following single and repeated dosing and across ethnic groups.