A Phase 1 Randomized Study: Garadacimab Pharmacokinetics, Safety, and Tolerability After Administration via Autoinjector/Pre-Filled Pen Versus Pre-Filled Syringe in Healthy Participants.

IF 2.3 4区 医学
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.

一项1期随机研究:健康人通过自动注射器/预填充笔与预填充注射器给药后加达西单抗的药代动力学、安全性和耐受性
Garadacimab是一种新型的全人源性抗活化因子XII单克隆抗体,被批准用于遗传性血管性水肿患者的长期预防。这项开放标签、平行组、1期、单中心、桥接研究在健康成人(18-55岁)中进行,研究了通过自动注射器/预充笔(AI/PFP)单次皮下注射加达西单抗的药代动力学和安全性,并与之前研究中使用的预充注射器(PFS)进行了比较。该研究的目的是在PFS和AI/PFP给药模式之间架起理解加达西单抗PK和安全性的桥梁。参与者(N = 132)按体重分层,按器械(AI/PFP或PFS)和注射部位(腹部、大腿或上臂)平均随机分为六组。主要终点包括器械之间的药代动力学参数比较。安全性/耐受性是次要终点。PFS和AI/PFP给药Cmax和AUC0-inf的几何平均比(GMR)接近1,90%的置信区间在0.8 ~ 1.25范围内,符合生物等效性标准;Cmax的GMR(90%)为0.92 (0.81,1.05),AUC0-inf的GMR为0.96(0.87,1.07)。在这项研究中,没有参与者有抗garadacimab的抗药物抗体。PFS组9/66(13.6%)和AI/PFP组11/66(16.7%)的参与者报告了与治疗相关的紧急不良事件。Garadacimab 200mg通过AI/PFP单次皮下给药与通过PFS给药具有一致的安全性和耐受性。这些发现支持通过AI/PFP给药garadacimab,为患者和医生在家提供便利。
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来源期刊
Journal of Clinical Pharmacology
Journal of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
自引率
3.40%
发文量
0
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.
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