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DIVISIONOFMICROBIOLOGYANDINFECTIOUSDISEASES(DMID)ADULTTOXICITYTABLENOVEMBER2007DRAFTNote:ThefollowingtoxicitytableisaDRAFTanddesignedtoprovidegeneralguidanceonparametersformonitoringsafetyinclinicaltrials.Thistoxicitytableisnotcomprehensiveandshouldnotbeapplieddirectlytoalltrials.Whenselectingatoxicitytable,thefollowingaresomeoftheitemsthatmustbetakenintoconsideration:ThepopulationbeingstudiedoDoestheclinicaltrialevaluatehealthysubjects,subjectswithaparticulardiseaseorcondition?ThestageoftestarticledevelopmentoIstheclinicaltrialaPhaseI,II,IIIorIV?ThetypeoftestarticleoDoestheclinicaltrialevaluateadrug,device,vaccineorotherbiologicagent?ThepriorhumanandpreclinicalexperiencewiththetestarticleoArethereanyspecificfindingsthatrequireadjustmentofthetoxicitytable?Singlesiteclinicaltrialsevaluatinghealthysubjectsshouldconformtothelaboratorynormalvaluesatthesinglesite.Multi-centerclinicaltrialsshouldreconcileamongtheirlaboratorynormalvalueswhenevaluatingahealthyvolunteerpopulation.PleaseconferwiththeDMIDprotocolteamandDMID'sOfficeofClinicalResearchAffairswhenselectingordevelopingatoxicitytableforaDMID-sponsoredtrial.DIVISIONOFMICROBIOLOGYANDINFECTIOUSDISEASES(DMID)ADULTTOXICITYTABLENOVEMBER2007DRAFTABBREVIATIONS:AbbreviationsutilizedintheTable:ULN=UpperLimitofNormalLLN=LowerLimitofNormalRx=TherapyReq=RequiredMod=ModerateIV=IntravenousADL=ActivitiesofDailyLivingDec=DecreasedESTIMATINGSEVERITYGRADEForabnormalitiesNOTfoundelsewhereintheToxicityTablesusethescalebelowtoestimategradeofseverity:GRADE1MildTransientormilddiscomfort(48hours);nomedicalintervention/therapyrequiredGRADE2ModerateMildtomoderatelimitationinactivity-someassistancemaybeneeded;noorminimalmedicalintervention/therapyrequiredGRADE3SevereMarkedlimitationinactivity,someassistanceusuallyrequired;medicalintervention/therapyrequired,hospitalizationspossibleGRADE4Life-threateningExtremelimitationinactivity,significantassistancerequired;significantmedicalintervention/therapyrequired,hospitalizationorhospicecareprobableSERIOUSORLIFE-THREATENINGAEsANYclinicaleventdeemedbythecliniciantobeseriousorlife-threateningshouldbeconsideredagrade4event.Clinicaleventsconsideredtobeseriousorlife-threateninginclude,butarenotlimitedto:seizures,coma,tetany,diabeticketoacidosis,disseminatedintravascularcoagulation,diffusepetechiae,paralysis,acutepsychosis,severedepression.COMMENTSREGARDINGTHEUSEOFTHESETABLES•Standardizedandcommonlyusedtoxicitytables(DivisionofAIDS,NCI’sCommonToxicityCriteria(CTC),andWorldHealthOrganization(WHO))havebeenadaptedforusebytheDivisionofMicrobiologyandInfectiousDiseases(DMID)andmodifiedtobettermeettheneedsofparticipantsinDMIDtrials.•ForparametersnotincludedinthefollowingToxicityTables,sitesshouldrefertothe“GuideForEstimatingSeverityGrade”locatedabove.•Criteriaaregenerallygroupedbybodysystem.•Someprotocolsmayhaveadditionalprotocolspecificgradingcriteria,whichwillsupercedetheuseofthesetablesforspecifiedcriteria.DIVISIONOFMICROBIOLOGYANDINFECTIOUSDISEASES(DMID)ADULTTOXICITYTABLENOVEMBER2007DRAFTHEMATOLOGYGrade1Grade2Grade3Grade4Hemoglobin9.5-10.5gm/dL8.0-9.4gm/dL6.5-7.9gm/dL6.5gm/dLAbsoluteNeutrophilCount1000-1500/mm3750-999/mm3500-749/mm3500/mm3Platelets75,000-99,999/mm350,000-74,999/mm320,000-49,999/mm320,000/mm3WBCs11,000-13,000/mm313,000-15,000/mm315,000-30,000/mm330,000or1,000/mm3%PolymorphonuclearLeucocytes+BandCells80%90–95%95%----------AbnormalFibrinogenLow:100-200mg/dLHigh:400-600mg/dLLow:100mg/dLHigh:600mg/dLLow:50mg/dL----------FibrinogenassociatedwithgrossbleedingorwithdisseminatedcoagulationFibrinSplitProduct20-40mcg/ml41-50mcg/ml51-60mcg/ml60mcg/mlProthrombinTime(PT)1.01-1.25xULN1.26-1.5xULN1.51-3.0xULN3xULNActivatedPartialThromboplastin(APPT)1.01-1.66xULN1.67-2.33xULN2.34-3xULN3xULNMethemoglobin5.0-9.9%10.0-14.9%15.0-19.9%20.0%DIVISIONOFMICROBIOLOGYANDINFECTIOUSDISEASES(DMID)ADULTTOXICITYTABLENOVEMBER2007DRAFTCHEMISTRIESGrade1Grade2Grade3Grade4Hyponatremia130-135mEq/L123-129mEq/L116-122mEq/L116mEq/LorabnormalsodiumwithmentalstatuschangesorseizuresHypernatremia146-150mEq/L151-157mEq/L158-165mEq/L165mEq/LorabnormalsodiumwithmentalstatuschangesorseizuresHypokalemia3.0-3.4mEq/L2.5-2.9mEq/L2.0-2.4mEq/Lorintensivereplacementtherapyorhospitalizationrequired2.0mEq/Lorabnormalpotassiumwithparesis,ileusorlife-threateningarrhythmiaHyperkalemia5.6-6.0mEq/L6.1-6.5mEq/L6.6-7.0mEq/l7.0mEq/Lorabnormalpotassiumwithlife-threateningarrhythmiaHypoglycemia55-64mg/dL40-54mg/dL30-39mg/dL30mg/dLorabnormalglucosewithmentalstatuschangesorcomaHyperglycemia(nonfastingandnopriordiabetes)116-160mg/dL161-250mg/dL251-500mg/dL500mg/dLorabnormalglucosewithketoacidosisorseizuresHypocalcemia(correctedforalbumin)8.4-7.8mg/dL7.7-7.0mg/dL6.9-6.1mg/dL6.1mg/dLorabnormalcalciumwithlifethreateningarrhythmiaortetanyDIVISIONOFMICROBIOLOGYANDINFECTIOUSDISEASES(DMID)ADULTTOXICITYTABLENOVEMBER2007DRAFTCHEMISTRIES(continued)Grade1Grade2Grade3Grade4Hypercalcemia(correctforalbumin)10.6-11.5mg/dL11.6-12.5mg/dL12.6-13.5mg/dL13.5mg/dLorabnormalcalciumwithlifethreatenin