2015
Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use
Telen M, Wun T, McCavit T, De Castro L, Krishnamurti L, Lanzkron S, Hsu L, Smith W, Rhee S, Magnani J, Thackray H. Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use. Blood 2015, 125: 2656-2664. PMID: 25733584, PMCID: PMC4408290, DOI: 10.1182/blood-2014-06-583351.Peer-Reviewed Original ResearchConceptsVaso-occlusive crisisSickle cell diseaseComposite primary end pointPrimary end pointPhase 2 studyEnd pointRandomized phase 2 studySCD vaso-occlusive crisisOpioid analgesic useSecondary end pointsActive treatment groupPhase 3 studyVaso-occlusive eventsAnalgesic usePlacebo groupProspective multicenterStudy drugAdverse eventsOpioid useSymptom reliefMedian timeSCD patientsCell diseaseTreatment groupsAnimal models
2013
GMI 1070: Reduction In Time To Resolution Of Vaso-Occlusive Crisis and Decreased Opioid Use In a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase 2 Study In Sickle Cell Disease
Telen M, Wun T, McCavit T, De Castro L, Krishnamurti L, Lanzkron S, Hsu L, Smith W, Rhee S, Magnani J, Thackray H. GMI 1070: Reduction In Time To Resolution Of Vaso-Occlusive Crisis and Decreased Opioid Use In a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase 2 Study In Sickle Cell Disease. Blood 2013, 122: 776. DOI: 10.1182/blood.v122.21.776.776.Peer-Reviewed Original ResearchVaso-occlusive crisisSickle cell diseaseOpioid useMedian timeTreatment groupsPlacebo groupCell diseaseSustained reductionVisual analog scale pain scoreTotal adverse event rateCumulative opioid useOral pain medicationPatients ages 12Opioid analgesic usePrimary efficacy endpointScale pain scoresPhase 2 studyPhase 3 studyPrimary efficacy analysisAdverse event ratesDaily opioid useStatistical significanceOral analgesiaSerious AEsVAS reductionAn Analysis Of The Pediatric Sub-Group From The Phase 2 Study Of GMI 1070 – A Novel Agent For The Vaso-Occlusive Crisis Of Sickle Cell Anemia
McCavit T, Krishnamurti L, Hsu L, Quinn C, Odame I, Alvarez O, Driscoll C, Smith-Whitley K, Rhee S, Wun T, Telen M, Thackray H. An Analysis Of The Pediatric Sub-Group From The Phase 2 Study Of GMI 1070 – A Novel Agent For The Vaso-Occlusive Crisis Of Sickle Cell Anemia. Blood 2013, 122: 2206. DOI: 10.1182/blood.v122.21.2206.2206.Peer-Reviewed Original ResearchVaso-occlusive crisisSerious adverse eventsSickle cell anemiaAcute chest syndromeStudy drugPediatric subjectsAdult subjectsMaintenance dosesOpioid useSecondary outcomesMedian timePlacebo-controlled phase 2 trialCell anemiaRed blood cell transfusionPhase 3 clinical trialsStrong efficacy signalBlood cell transfusionPhase 2 studyPhase 2 trialKaplan-Meier methodVisual analog scaleInitial medical evaluationPan-selectin inhibitorAdvisory CommitteeMinimal safety concernsA double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease
Wun T, Soulieres D, Frelinger A, Krishnamurti L, Novelli E, Kutlar A, Ataga K, Knupp C, McMahon L, Strouse J, Zhou C, Heath L, Nwachuku C, Jakubowski J, Riesmeyer J, Winters K. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease. Journal Of Hematology & Oncology 2013, 6: 17. PMID: 23414938, PMCID: PMC3585853, DOI: 10.1186/1756-8722-6-17.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnemia, Sickle CellBiomarkers, TumorCell Adhesion MoleculesDouble-Blind MethodFemaleFollow-Up StudiesHumansMaleMicrofilament ProteinsMiddle AgedPainPhosphoproteinsPiperazinesPlatelet ActivationPlatelet Aggregation InhibitorsPrasugrel HydrochloridePrognosisPurinergic P2Y Receptor AntagonistsThiophenesYoung AdultConceptsSickle cell diseaseHemorrhagic eventsAdult patientsAntiplatelet agentsSCD patientsCell diseaseP-selectinMedical interventionsMulticenter phase 2 studyPlatelet surface P-selectinMethodsThe primary endpointPlatelet activation biomarkersSafety of prasugrelSerious hemorrhagic eventsPlacebo-controlled studyPhase 2 studyVivo platelet activationSoluble P-selectinSurface P-selectinThienopyridine antiplatelet agentPain ratePrasugrel armPrimary endpointActivation biomarkersStudy arms
2011
A Randomized, Double-Blind, Adaptive Phase 2 Multi-Center Study of Prasugrel Compared to Placebo in Adults with Sickle Cell Disease
Wun T, Soulieres D, Krishnamurti L, Kutlar A, Ataga K, Zhou C, Heath L, Nwachuku C, Jakubowski J, Winters K, Riesmeyer J. A Randomized, Double-Blind, Adaptive Phase 2 Multi-Center Study of Prasugrel Compared to Placebo in Adults with Sickle Cell Disease. Blood 2011, 118: 847. DOI: 10.1182/blood.v118.21.847.847.Peer-Reviewed Original ResearchSickle cell diseasePrasugrel armHemorrhagic eventsCell diseaseMedical attentionPain rateAdult patientsPlacebo armPlatelet inhibitionAntiplatelet agentsPharmacodynamic effectsEli LillyP2Y12 ADP receptor antagonistsHemorrhagic adverse eventsInsufficient platelet inhibitionP2Y12 reactivity unitsPrasugrel-treated patientsSerious hemorrhagic eventsADP receptor antagonistsPlatelet reactivity indexAcute coronary syndromeBaseline pain intensityPhase 2 studyPhase 3 studySeverity of pain