Details

Autor(en) / Beteiligte

• 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

Titel

Prasugrel in children with sickle cell disease: pharmacokinetic and pharmacodynamic data from an open-label, adaptive-design, dose-ranging study

Ist Teil von

• Journal of pediatric hematology/oncology, 2015-01, Vol.37 (1), p.1-9

Ort / Verlag

United States

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 VerifyNow®P2Y12 (VN) platelet inhibition and decreases in VNP2Y12 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. No hemorrhagic events occurred in Part A; 3 occurred in Part B, all mild and self-limited. Most children with sickle cell disease may achieve clinically relevant platelet inhibition with titration of daily-dose prasugrel.