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Safety and pharmacokinetics of olokizumab, an anti‐IL‐6 monoclonal antibody, administered to healthy male volunteers: A randomized phase I study
Author(s) -
Kretsos Kosmas,
Golor Georg,
Jullion Astrid,
Hickling Matthew,
McCabe Suzanne,
Shaw Stevan,
Jose Joby,
Oliver Ruth
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.121
Subject(s) - medicine , pharmacokinetics , tolerability , adverse effect , pharmacology , pharmacodynamics , placebo , immunogenicity , bioavailability , monoclonal antibody , gastroenterology , antibody , immunology , pathology , alternative medicine
Interleukin‐6 (IL‐6) is implicated in the pathophysiology of several inflammatory conditions. Olokizumab, a humanized anti‐IL‐6 monoclonal antibody, selectively blocks the final assembly of the IL‐6 signaling complex. A randomized, double‐blind, placebo‐controlled, phase I dose‐escalation study assessed the safety and tolerability of escalating single doses of olokizumab administered intravenously (iv) or subcutaneously (sc) to 67 healthy male volunteers. The pharmacokinetics, pharmacodynamics and immunogenicity of olokizumab were also assessed. Olokizumab was tolerated at doses up to 3.0 mg/kg sc and 10.0 mg/kg iv; the maximum tolerated dose was not reached. No serious adverse events or withdrawals as a result of treatment‐emergent adverse events were reported. Pharmacokinetic analysis showed that both maximum serum concentration and area under the concentration–time curve increased linearly with increasing dose. Mean terminal half‐life was 31.5 days (standard deviation 12.4 days). The bioavailability of the sc doses ranged from 84.2% to 92.5%. Rapid decreases in C‐reactive protein concentrations were observed, with no dose dependency.