Oliver Kornmann1, Henrik Watz2, Rainard Fuhr3, Norbert Krug4, Veit J Erpenbeck5, Guenther Kaiser6. 1. Pulmonary Department, Internal Medicine, University Hospital Mainz, Langenbeckstraße 1, 55131 Mainz, Germany. Electronic address: kornmann@ikf-pneumologie.de. 2. Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany. Electronic address: H.Watz@pulmoresearch.de. 3. PAREXEL International GmbH, Klinikum Westend, Haus 17, D-14050 Berlin, Germany. Electronic address: Rainard.Fuhr@parexel.com. 4. Fraunhofer Institut für Toxikologie und Experimentelle Medizin, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany. Electronic address: norbert.krug@item.fraunhofer.de. 5. Novartis Pharma AG, Basel, Switzerland. Electronic address: veit.erpenbeck@novartis.com. 6. Novartis Pharma AG, Basel, Switzerland. Electronic address: guenther.kaiser@novartis.com.
Abstract
BACKGROUND: When first approved in the European Union (EU), the omalizumab dosing table had upper bodyweight and IgE limits of 150 kg and 700 IU/mL, respectively. In this study, we assessed the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of omalizumab in patients with IgE/bodyweight combinations above those in the original dosing table. METHODS: A multicentre, open-label, parallel-group study assessed the safety, PK and PD of omalizumab in 32 patients with mild-to-moderate allergic (IgE-mediated) asthma. Patients received two subcutaneous injections of omalizumab at one of three dosage levels (450, 525, or 600 mg), chosen according to baseline IgE (300-2000 IU/mL) and bodyweight (40-150 kg), with a 14-day interval between injections. RESULTS: Overall, 69 adverse events (AEs), none of them serious, were reported by 26 (81.3%) patients. Analysis of laboratory measurements, vital signs and ECG data revealed no adverse findings of clinical relevance. The PK profile was consistent with previous data for lower doses. Mean maximum decrease of free IgE from screening was ≥99% for all three doses, and mean free IgE concentrations remained <25 ng/mL for at least 2 weeks after the second dose. The reductions in free IgE were consistent with levels previously associated with clinical improvements. CONCLUSIONS: The safety and PK/PD findings from this study are consistent with previous data, and supported the extension of the omalizumab dosing table to include those patients with higher IgE/bodyweight combinations. Clinical trial registry and registration number: clinicaltrials.gov (NCT00546143).
RCT Entities:
BACKGROUND: When first approved in the European Union (EU), the omalizumab dosing table had upper bodyweight and IgE limits of 150 kg and 700 IU/mL, respectively. In this study, we assessed the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of omalizumab in patients with IgE/bodyweight combinations above those in the original dosing table. METHODS: A multicentre, open-label, parallel-group study assessed the safety, PK and PD of omalizumab in 32 patients with mild-to-moderate allergic (IgE-mediated) asthma. Patients received two subcutaneous injections of omalizumab at one of three dosage levels (450, 525, or 600 mg), chosen according to baseline IgE (300-2000 IU/mL) and bodyweight (40-150 kg), with a 14-day interval between injections. RESULTS: Overall, 69 adverse events (AEs), none of them serious, were reported by 26 (81.3%) patients. Analysis of laboratory measurements, vital signs and ECG data revealed no adverse findings of clinical relevance. The PK profile was consistent with previous data for lower doses. Mean maximum decrease of free IgE from screening was ≥99% for all three doses, and mean free IgE concentrations remained <25 ng/mL for at least 2 weeks after the second dose. The reductions in free IgE were consistent with levels previously associated with clinical improvements. CONCLUSIONS: The safety and PK/PD findings from this study are consistent with previous data, and supported the extension of the omalizumab dosing table to include those patients with higher IgE/bodyweight combinations. Clinical trial registry and registration number: clinicaltrials.gov (NCT00546143).