沙格列汀在肾功能不全2型糖尿病的有效性ppt课件

Saxagliptin StudytoEvaluatetheTreatmentEffectofSaxagliptinComparedWithPlaceboinAdultPatientsWithType2DiabetesandRenalImpairment Objectives EfficacyToevaluateefficacyofsaxagliptin2 5mgcomparedwithplacebobyassessmentofabsolutechangefrombaselineinHbA1candFPGToassessthechangefrombaselineinbackgroundantihyperglycemictherapy includingdailydoseofexistingtherapyortheadditionofnewtherapy OADtherapyorinsulin FPG fastingplasmaglucose HbA1c glycatedhemoglobin LT long term OAD oralantidiabetic ST short term Objectives SafetyToevaluatethesafetyandtolerabilityofsaxagliptin2 5mgcomparedwithplacebobyassessmentof AEsLabvalues includingestimatedCrCl Cockcroft Gault estimatedGFR andurinaryalbumin creatineratioECG vitalsigns bodyweight physicalexaminationDoublingofserumcreatineorprogressiontoend stagerenalimpairment AE adverseevent CrCl creatinineclearance ECG electrocardiogram GFR glomerularfiltrationrate StudyDesign Stratifiedenrollmentbasedondegreeofrenalimpairment69Sitesin12EuropeancountriesandtheUnitedStates PlaceboLead in STTreatmentPeriod Placebo 2 5mgSaxagliptinoncedaily 1 1 12Weeks 2Weeks LTTreatmentPeriod 40Weeks ContinueallowedstableOADand orinsulintherapy AdjustmentofbackgroundOADand orinsulinasneeded Reference CSRFigure1 SelectedInclusionandExclusionCriteria InclusionCriteriaPatientswithT2DMandrenalimpairment documentedhistoryofCrCl1 5xULNBilirubin 1 5xULNCK 3xULN Reference CSR5 1 CSR5 3 1 CSP3 3 2 CSP3 3 3 CSPAmendmentNumber1 ALT alaninetransaminase AST aspartateaminotransferase CK creatinekinase T2DM type2diabetesmellitus ULN upperlimitofnormal SubjectDisposition Randomizedandtreated N 170 Saxagliptin5mg n 85 CompletedSTperiodandcontinuedtoLTperiod n 61 DiscontinuedSTandLT n 43 AE n 5 Death n 3 Incorrectenrollment n 2 Nolongermeetsstudycriteria n 16 Withdrewconsent n 17 CompletedLT n 42 Moderate n 29 Severe n 7 End stage n 6 Placebo n 85 CompletedSTperiodandcontinuedtoLTperiod n 68 DiscontinuedSTandLT n 35 AE n 2 Death n 4 Incorrectenrollment n 1 Nolongermeetsstudycriteria n 13 Other n 1 Poor non compliance n 4 Withdrewconsent n 10 CompletedLT n 50 Moderate n 27 Severe n 14 End stage n 9 aBeforerandomization totalnumberenrolled 572andtotalnumberexcluded 402 Reference CSRFigure2 DemographicandBaselineCharacteristics RandomizedAnalysisSet Reference CSRTable11 N numberofsubjectsineachcategory PBO placebo SAXA saxagliptin SD standarddeviation BaselineDiabetesCharacteristics RandomizedAnalysisSet Reference CSRTable12 HbA1cChangeFromBaselinetoWeek52 LOCF FullAnalysisSet 2of2 Reference Figure7 1LT Table7 2 2aLT p 0 001vsPBO ST LTPeriod Reference Table7 2 2bLT Figure7 2LT HbA1cChangeFromBaselinetoWeek52byRenalImpairmentCategory LOCF FullAnalysisSet 3of3 ST LTPeriod MeanChangeFromBaselineHbA1c LOCF FullAnalysisSet Reference Table7 2 2dLT Figure7 20LT ST LTPeriod FPGChangeFromBaselinetoWeek52byRenalImpairmentCategory LOCF FullAnalysisSet 3of3 Reference Table7 2 1aLT Figure7 10LT AllSAXAvsPBOcomparisonswithineachrenalimpairmentcategorywerenotsignificant ST LTPeriod SummaryofEfficacyResults HbA1cMeandecreaseinHbA1cafter52weeksoftreatmentwithsaxagliptin2 5mgoncedailywasgreaterthanaftertreatmentwithplacebo p 0 001 MeandecreasesinHbA1cafter52weeksoftreatmentwithsaxagliptinwerenumericallygreatercomparedwithplaceboinsubjectswithmoderateorsevererenalimpairment meandecreasesinsubjectswithESRDwascomparablebetweenthetreatmentgroupsFPGTherewasanumericallylargerreductioninmeanfastingglucosevalueafter52weeksoftreatmentwithsaxagliptin2 5mgoncedailycomparedwithplaceboinsubjectswithmoderateorsevererenalimpairmentAreductioninFPGwasnotconsistentlydemonstratedinsubjectswithESRD ChangeinAntihyperglycemicMedications ST LTPeriod 39 164 24 ofsubjectsinthefullanalysissethadchangesinbaselineinsulinand orOADmedicationduringthe52 weektreatmentperiodSaxagliptin 20 81 25 subjectsPlacebo 19 83 23 subjects Reference CSR7 1 4 OverallSummaryofAdverseEvents SafetyAnalysisSet Reference Table8 1aLT aEventsofhypoglycemiaareincludedinallcategories AE adverseevent SAE seriousadverseevent ST LTPeriod MostCommonAdverseEvents 2 bySOC Reference Table8 1kLT aExcludingalleventsofhypoglycemia SOC systemorganclass ST LTPeriod SummaryofDeaths SafetyAnalysisSet Reference Table8 2aLT ST LTPeriod SAEs 2 bySOCandPreferredTerm SafetyAnalysisSet Reference Table8 3aLT ST LTPeriod SummaryofHypoglycemicEvents Atotalof12subjectsexperienced25confirmedhypoglycemiceventsSAXA2 5mg 8subjects 9 4 reported16eventsPBO 4subjects 4 7 reported9events Reference Table8 6 1mLT Table8 6 1aLT ST LTPeriod SummaryofAdverseEventsofInterestDuringST LTPeriod SafetyAnalysisSet Proportionofsubjectswithpredefinedcardiovasculareventswassimilarinthetwogroups 5 9 insaxagliptinand7 1 inplaceboProportionofsubjectswithpredefinedskindisorderswas2 4 ineachtreatmentgroupProportionofsubjectswith 1AEininfections infestationssystemorganclass 23 5 saxagliptinsubjects 25 9 placebosubjectsTheonlyopportunisticinfectionwasoralfungalinfectioninoneplacebosubjectLymphocytopenia 2subjects thrombocytopenia 1subject hypersensitivity 1subject pancreatitis 1subject andfracture 2subjects wereonlyreportedintheplacebogroup bypredefinedterms Nolocalizededemabypredefinedlowerleveltermsreported Reference CSR8 3 4 CSR8 3 5 Appendix8 1LT