Shamsi Kohkan, Yucel E Kent, Chamberlin Paul
Medical Development Diagnostic Imaging and Radiopharmaceuticals, Berlex Laboratories Inc., Montville, New Jersey 07045, USA.
Invest Radiol. 2006 Nov;41(11):822-30. doi: 10.1097/01.rli.0000242836.25299.8f.
We sought to summarize the Phase II and Phase III clinical trials safety data for gadofosveset (Vasovist, MS-325), a new magnetic resonance angiography contrast agent.
Subjects with known or suspected vascular disease were administered 0.03 mmol/kg gadofosveset (767 subjects) or placebo (49 subjects) in phase II and phase III studies. Overall safety data were pooled from 8 studies and included adverse event monitoring, clinical laboratory assays, vital signs, oxygen saturation, physical examination, and electrocardiography. The safety was monitored for 72 to 96 hours postinjection (PI), and safety comparison with x-ray angiography using iodinated contrast media also was performed in 318 subjects. In the phase II trial, 5 doses of gadofosveset and placebo were evaluated. In this study, 38 patients were administered placebo and 39 patients received 0.03 mmol/kg gadofosveset.
In pooled data, treatment related adverse events were reported by 176 (22.9%) patients receiving gadofosveset and by 16 (32.7%) patients receiving placebo. In phase II trial, treatment-related adverse events were reported by 13 of the 39 (33.3%) patients receiving gadofosveset and 9 of the 38 (23.7%) patients receiving placebo. No severe or serious adverse events were reported in either gadofosveset or placebo groups in this phase II trial. Pooled data revealed no clinically significant trends in adverse events, laboratory assays, vital signs, or oxygen saturation. A QTc prolongation of 2.8 milliseconds was observed at 45 minutes after MS-325 injection; however, this trend was similar to that of the placebo group at the same time point (3.2 milliseconds).
Gadofosveset has exhibited a good safety profile and can be safely administered as an intravenous bolus injection. The overall rate and experience of adverse events was similar to that of placebo. The safety profile of gadofosveset is comparable with that of other gadolinium contrast agents as reported in the literature.
我们试图总结新型磁共振血管造影剂gadofosveset（Vasovist，MS - 325）的II期和III期临床试验安全性数据。
在II期和III期研究中，给已知或疑似血管疾病的受试者静脉注射0.03 mmol/kg的gadofosveset（767例受试者）或安慰剂（49例受试者）。汇总了8项研究的总体安全性数据，包括不良事件监测、临床实验室检测、生命体征、血氧饱和度、体格检查和心电图检查。在注射后（PI）72至96小时监测安全性，还对318例受试者进行了与使用碘化造影剂的X线血管造影的安全性比较。在II期试验中，评估了5种剂量的gadofosveset和安慰剂。在本研究中，38例患者接受安慰剂，39例患者接受0.03 mmol/kg的gadofosveset。
汇总数据显示，接受gadofosveset的176例（22.9%）患者和接受安慰剂的16例（32.7%）患者报告了与治疗相关的不良事件。在II期试验中，接受gadofosveset的39例患者中有13例（33.3%）报告了与治疗相关的不良事件，接受安慰剂的38例患者中有9例（23.7%）报告了此类事件。在该II期试验中，gadofosveset组和安慰剂组均未报告严重或重大不良事件。汇总数据显示，不良事件、实验室检测、生命体征或血氧饱和度方面均无临床显著趋势。注射MS - 325后45分钟观察到QTc延长2.8毫秒；然而，该趋势与同一时间点安慰剂组的趋势相似（3.2毫秒）。
gadofosveset已显示出良好的安全性，可作为静脉推注安全给药。不良事件的总体发生率和情况与安慰剂相似。gadofosveset的安全性与文献报道的其他钆造影剂相当。
