A Summary of safety of gadofosveset (MS-325) at 0.03 mmol/kg body weight dose: Phase II and Phase III clinical trials data.

摘要

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.