A Phase 1 Randomized Study: Garadacimab Pharmacokinetics, Safety, and Tolerability After Administration via Autoinjector/Pre-Filled Pen Versus Pre-Filled Syringe in Healthy Participants.
Fiona Glassman, John-Philip Lawo, Mihai Alexandru Bica, Anthony Roberts, David Kormann, Ligia Chialda, Soeren Miethke, Iwona Dziadowiec, Stephen Caltabiano, Thomas Puchalski
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引用次数: 0
Abstract
Garadacimab is a novel, fully human, anti-activated factor XII monoclonal antibody approved for long-term prophylaxis of patients with hereditary angioedema. This open-label, parallel-group, Phase 1, single-center, bridging study in healthy adults (18-55 years of age) characterized the pharmacokinetics and safety of a single 200 mg subcutaneous injection of garadacimab administered via autoinjector/pre-filled pen (AI/PFP) compared with the pre-filled syringe (PFS) used in previous studies. The aim of the study was to bridge the understanding of the PK and safety of garadacimab between PFS and AI/PFP modes of administration. Participants (N = 132) were stratified by body weight, randomized evenly in six groups by device (AI/PFP or PFS) and injection site (abdomen, thigh, or upper arm). The primary endpoint comprised pharmacokinetic parameter comparison between devices. Safety/tolerability were secondary endpoints. The geometric mean ratio (GMR) for Cmax and AUC0-inf comparing administration by PFS and AI/PFP was close to 1 with 90% confidence intervals within a range of 0.8-1.25, meeting bioequivalence criteria; GMR (90%) was 0.92 (0.81, 1.05) for Cmax and 0.96 (0.87, 1.07) for AUC0-inf. No participants in this study had anti-drug antibodies against garadacimab. Treatment-related emergent adverse events were reported in 9/66 (13.6%) participants in the PFS group and 11/66 (16.7%) participants in the AI/PFP group. Garadacimab 200 mg administered as a single subcutaneous dose via AI/PFP had a consistent safety and tolerability profile to that administered via PFS. These findings support administration of garadacimab via AI/PFP, providing at-home convenience for patients and physicians.
期刊介绍:
The Journal of Clinical Pharmacology (JCP) is a Human Pharmacology journal designed to provide physicians, pharmacists, research scientists, regulatory scientists, drug developers and academic colleagues a forum to present research in all aspects of Clinical Pharmacology. This includes original research in pharmacokinetics, pharmacogenetics/pharmacogenomics, pharmacometrics, physiologic based pharmacokinetic modeling, drug interactions, therapeutic drug monitoring, regulatory sciences (including unique methods of data analysis), special population studies, drug development, pharmacovigilance, womens’ health, pediatric pharmacology, and pharmacodynamics. Additionally, JCP publishes review articles, commentaries and educational manuscripts. The Journal also serves as an instrument to disseminate Public Policy statements from the American College of Clinical Pharmacology.