The OptiMARK clinical development program: Summary of safety data

Abstract

Purpose: To describe and summarize the safety data from the OptiMARK clinical development program. Materials and Methods:In the 18 clinical studies comprising the clinical program, doses ranging from 0.1 to 0.7 mmol/kg were administered to healthy adult volunteers, patients with hepatic or renal impairment, and patients with confirmed or highly suspected central nervous system (CNS), liver, breast, vascular, bone, or soft tissue pathologies. A total of 2038 injections of OptiMARK, Magnevist, or placebo were administered to 1684 subjects. Safety assessments were performed at appropriate intervals during all Phase 1, 2, and 3 studies. Results:Of the 1684 subjects exposed to a study drug or placebo in the clinical development program, 646 subjects experienced 1293 adverse events. Thirty-one percent of the OptiMARK injections were associated with an adverse event. In comparison, 35% of Magnevist injections and 48% of placebo injections were associated with at least one adverse event.Conclusions: OptiMARK was safe and well-tolerated with a safety profile similar to that of Magnevist.

Safety of gadoversetamide in patients with acute and chronic myocardial infarction

“…Third, no difference was detected in the QTc interval between different dose groups. This finding is consistent with those of previous studies in which the QTc interval did not differ between subjects administered either saline or gadoversetamide (7)(8)(9)(10)(11)(12).…”

“…Of the 164 AEs reported in the combined population, only 8 (4.9%) were classified as likely to be related to gadoversetamide. This rate is slightly lower than that reported in past studies (7). Furthermore, only two of the eight that were likely related to gadoversetamide were considered to have any clinical significance and merit discussion.…”

“…Serum levels of calcium in the AMI and CMI studies were both higher and lower than baseline levels, and no systematic trend for hypercalcemia was seen. Other investigators have also reported no correlation between gadoversetamide administration and hypercalcemia (7)(8)(9)11,12). Furthermore, Baker et al (10) recently reported a minimal decrease in calcium concentration after gadoversetamide administration in pediatric patients.…”

“…Mallinckrodt, St. Louis, MO) is a nonionic Gd-chelate approved by the FDA for use in imaging of the liver and central nervous system (CNS) (7)(8)(9)(10)(11)(12)(13). Swan et al and others have described in detail the pharmacokinetics and safety of gadoversetamide for use in imaging of the liver and CNS (12,13).…”

MR contrast agents: Physical and pharmacologic basics

“…Numerous studies have been performed comparing ProHance, Omniscan, and OptiMARK to Magnevist, and no significant differences have been found in the incidence of adverse reactions (10,13,(15)(16)(17)(18)(19). For example, the incidence of hives has been reported as ranging from 0.2% to Ͻ2%, these figures being statistically indistinguishable.…”