Prasugrel in Children With Sickle Cell Disease. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Styles, Lori; Heiselman, Darell; Heath, Lori E.; Moser, Brian A.; Small, David S.; Jakubowski, Joseph A.; Zhou, Chunmei; Redding-Lallinger, Rupa; Heeney, Matthew M.; Quinn, Charles T.; Rana, Sohail R.; Kanter, Julie; Winters, Kenneth J.
• Is Part Of: Journal of pediatric hematology/oncology. Volume 37:Issue 1(2015)
• Publication Date: 2015-01
• Subjects: Pediatric hematology -- Periodicals; Tumors in children -- Periodicals; 618.9215
• DOI: 10.1097/MPH.0000000000000291
• Languages: English
• ISSNs: 1077-4114

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Introduction:</title> <p>This phase 2 study was designed to characterize the relationship among prasugrel dose, prasugrel's active metabolite (Pras-AM), and platelet inhibition while evaluating safety in children with sickle cell disease. It was open-label, multicenter, adaptive design, dose ranging, and conducted in 2 parts. Part A: Patients received escalating single doses leading to corresponding increases in Pras-AM exposure and Verify<italic>Now</italic>®P2Y12 (VN) platelet inhibition and decreases in VNP2Y<sub>12</sub> reaction units and vasodilator-stimulated phosphoprotein platelet reactivity index. Part B: Patients were assigned daily doses (0.06, 0.08, and 0.12 mg/kg) based on VN pharmacodynamic measurements at the start of 2 dosing periods, each 14±4 days. Platelet inhibition was significantly higher at 0.12 mg/kg (56.3%±7.4%; least squares mean±SE) compared with 0.06 mg/kg (33.8%±7.4%) or 0.08 mg/kg (37.9%±5.6%). Patients receiving 0.12 mg/kg achieved ≥30% platelet inhibition; only 1 patient receiving 0.06 mg/kg exceeded 60% platelet inhibition. High interpatient variability in response to prasugrel and the small range of exposures precluded rigorous characterization of the relationship among dose, Pras-AM, and platelet inhibition.</p> </sec> <sec> <title>Safety:</title> <p>No hemorrhagic events occurred in Part A; 3 occurred in Part B, all mild and self-limited.</p> </sec> <sec> <title>Conclusions:</title> <p>Most children with sickle cell disease may achieve clinically relevant platelet inhibition with titration of daily-dose prasugrel.</p> </sec> </abstract>