FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3048364296> ?p ?o ?g. }

• W3048364296 endingPage "2251" @default.
• W3048364296 startingPage "2251" @default.
• W3048364296 abstract "Abstract INTRODUCTION Activated platelets promote the adhesion of sickle cells to endothelial cells and the formation of platelet-leukocyte aggregates, contributing to vaso-occlusion (VOC). It has been suggested that inhibition of platelet reactivity may reduce the rate of VOCs in sickle cell disease (SCD). A study with ticlopidine reported a reduced rate of VOCs versus placebo. A recent, placebo-controlled, pediatric study with prasugrel showed a non-significant reduction in VOCs events, which was likely due to the low level of platelet inhibition. Ticagrelor is a reversible P2Y12 receptor antagonist shown to inhibit ADP-induced platelet aggregation and is approved for use in adults with coronary artery disease (CAD). A phase 2 study was conducted to characterize the pharmacokinetic (PK), pharmacodynamic (PD) and safety profiles of ticagrelor in children aged 2-17 years with SCD (HbSS or HbS/β0; NCT02214121). METHODS This study was conducted in 2 parts: Part A was an open-label, randomized, dose-ranging study in which patients received two single doses of ticagrelor 1 week apart, followed by twice daily (bid) ticagrelor for 1 week. Initially, single doses of 0.125-0.563 mg/kg were given, followed by repeated dosing with 0.125 mg/kg bid. Individual platelet response was used to inform further dosing. After an interim analysis including the first 14 patients in Part A, single doses were increased to a maximum of 2.25 mg/kg and repeated dosing up to 0.75 mg/kg bid. Part B (optional) immediately followed the repeated dosing in Part A: patients were randomized 2:1 to continue ticagrelor with the same dose used during Part A or matching placebo as a double-blind treatment for 4 weeks. Safety was assessed during both parts, pain and analgesic use were recorded daily in an eDiary, and painful crises were reported at each visit. Exposure to ticagrelor and the active metabolite (AR-C124910XX), as well as the subsequent platelet inhibition, were determined after single and repeated doses in Parts A and B. RESULTS A total of 45 children with SCD, mean age 11.2 years (range: 3-17) received study drug in Part A and 23 (15 ticagrelor, 8 placebo) children, mean age 10.0 years (range: 3-17) in Part B. Most patients were of African descent (35/45 in Part A and 22/23 in Part B). Ticagrelor exposure increased approximately dose-linearly, with maximum plasma concentration values ranging from 15.2 to 566.6 ng/mL (with 0.125 mg/kg to 2.25 mg/kg) for ticagrelor and 3.1-156.0 ng/mL for AR-C124910XX. The parent:metabolite ratio in children with SCD was similar to that previously observed in adults. Mean P2Y12 reaction units (PRU) after single doses of ticagrelor decreased from pre-dose to 2 hours post-dose (change from baseline: -23.4 to -207.8 PRU for 0.125 mg/kg to 2.25 mg/kg), and returned towards baseline up to the last timepoint (6 or 8 hours' post-dose). In Part B, no difference was seen between the placebo and ticagrelor groups in pain ratings and analgesic use, although the study was not statistically powered to detect differences in these outcomes. Ticagrelor was well tolerated, with no bleeding during treatment and no patient discontinued treatment due to an adverse event. CONCLUSIONS The PK/PD profile of ticagrelor in children with SCD was suitably characterized and the exposure-response relationship appeared similar to that previously observed in adults with CAD. Ticagrelor was well tolerated and no safety concerns were raised. The potential to impact SCD-related pain crises needs further evaluation, as the number of patients, low doses for some patients and short study duration limit the efficacy conclusions from this study. Disclosures Hsu: AstraZeneca: Other: steering committee for HESTIA trial; Emmi: Other: consultant for Emmi. Sarnaik: AstraZeneca: Other: Advisory Board. Amilon: AstraZeneca: Employment. Rensfeldt: AstraZeneca: Employment. Berggren: AstraZeneca: Employment." @default.
• W3048364296 created "2020-08-13" @default.
• W3048364296 creator A5014431886 @default.
• W3048364296 creator A5016997827 @default.
• W3048364296 creator A5023851992 @default.
• W3048364296 creator A5029639633 @default.
• W3048364296 creator A5035252702 @default.
• W3048364296 creator A5050797953 @default.
• W3048364296 date "2017-12-07" @default.
• W3048364296 modified "2023-09-28" @default.
• W3048364296 title "Pharmacokinetics, Pharmacodynamics and Safety of Ticagrelor in Children with Sickle Cell Disease: Results of a Two-Part Phase 2 Study" @default.
• W3048364296 doi "https://doi.org/10.1182/blood.v130.suppl_1.2251.2251" @default.
• W3048364296 hasPublicationYear "2017" @default.
• W3048364296 type Work @default.
• W3048364296 sameAs 3048364296 @default.
• W3048364296 citedByCount "0" @default.
• W3048364296 crossrefType "journal-article" @default.
• W3048364296 hasAuthorship W3048364296A5014431886 @default.
• W3048364296 hasAuthorship W3048364296A5016997827 @default.
• W3048364296 hasAuthorship W3048364296A5023851992 @default.
• W3048364296 hasAuthorship W3048364296A5029639633 @default.
• W3048364296 hasAuthorship W3048364296A5035252702 @default.
• W3048364296 hasAuthorship W3048364296A5050797953 @default.
• W3048364296 hasConcept C111113717 @default.
• W3048364296 hasConcept C112705442 @default.
• W3048364296 hasConcept C126322002 @default.
• W3048364296 hasConcept C142724271 @default.
• W3048364296 hasConcept C204787440 @default.
• W3048364296 hasConcept C22979827 @default.
• W3048364296 hasConcept C27081682 @default.
• W3048364296 hasConcept C2777028646 @default.
• W3048364296 hasConcept C2777288759 @default.
• W3048364296 hasConcept C2777628954 @default.
• W3048364296 hasConcept C2777849778 @default.
• W3048364296 hasConcept C2778335254 @default.
• W3048364296 hasConcept C2778905298 @default.
• W3048364296 hasConcept C2780890252 @default.
• W3048364296 hasConcept C2993802102 @default.
• W3048364296 hasConcept C42219234 @default.
• W3048364296 hasConcept C49059817 @default.
• W3048364296 hasConcept C71924100 @default.
• W3048364296 hasConcept C89560881 @default.
• W3048364296 hasConcept C98274493 @default.
• W3048364296 hasConceptScore W3048364296C111113717 @default.
• W3048364296 hasConceptScore W3048364296C112705442 @default.
• W3048364296 hasConceptScore W3048364296C126322002 @default.
• W3048364296 hasConceptScore W3048364296C142724271 @default.
• W3048364296 hasConceptScore W3048364296C204787440 @default.
• W3048364296 hasConceptScore W3048364296C22979827 @default.
• W3048364296 hasConceptScore W3048364296C27081682 @default.
• W3048364296 hasConceptScore W3048364296C2777028646 @default.
• W3048364296 hasConceptScore W3048364296C2777288759 @default.
• W3048364296 hasConceptScore W3048364296C2777628954 @default.
• W3048364296 hasConceptScore W3048364296C2777849778 @default.
• W3048364296 hasConceptScore W3048364296C2778335254 @default.
• W3048364296 hasConceptScore W3048364296C2778905298 @default.
• W3048364296 hasConceptScore W3048364296C2780890252 @default.
• W3048364296 hasConceptScore W3048364296C2993802102 @default.
• W3048364296 hasConceptScore W3048364296C42219234 @default.
• W3048364296 hasConceptScore W3048364296C49059817 @default.
• W3048364296 hasConceptScore W3048364296C71924100 @default.
• W3048364296 hasConceptScore W3048364296C89560881 @default.
• W3048364296 hasConceptScore W3048364296C98274493 @default.
• W3048364296 hasLocation W30483642961 @default.
• W3048364296 hasOpenAccess W3048364296 @default.
• W3048364296 hasPrimaryLocation W30483642961 @default.
• W3048364296 hasRelatedWork W109410924 @default.
• W3048364296 hasRelatedWork W175926515 @default.
• W3048364296 hasRelatedWork W1807736252 @default.
• W3048364296 hasRelatedWork W1977178370 @default.
• W3048364296 hasRelatedWork W2037164262 @default.
• W3048364296 hasRelatedWork W2086366797 @default.
• W3048364296 hasRelatedWork W2146104782 @default.
• W3048364296 hasRelatedWork W2284874790 @default.
• W3048364296 hasRelatedWork W2292310851 @default.
• W3048364296 hasRelatedWork W2418485858 @default.
• W3048364296 hasRelatedWork W2560219091 @default.
• W3048364296 hasRelatedWork W2584710856 @default.
• W3048364296 hasRelatedWork W2595767897 @default.
• W3048364296 hasRelatedWork W2609813387 @default.
• W3048364296 hasRelatedWork W2755345907 @default.
• W3048364296 hasRelatedWork W2912721619 @default.
• W3048364296 hasRelatedWork W2988325953 @default.
• W3048364296 hasRelatedWork W3042915720 @default.
• W3048364296 hasRelatedWork W3176979830 @default.
• W3048364296 hasRelatedWork W794693135 @default.
• W3048364296 hasVolume "130" @default.
• W3048364296 isParatext "false" @default.
• W3048364296 isRetracted "false" @default.
• W3048364296 magId "3048364296" @default.
• W3048364296 workType "article" @default.