September 19 , 2018 Page | 76 economic inadequacy, caregiver respite, family circumstances, administrative reason). Potential Drug Induced Liver Injury (DILI) Wherever possible, timel y confirmation of initial liver-related laboratory abnormalities should occu r prior to the reporting of a potential DILI event. All occurrences of potential DILIs, meeting the defined criteria, must be repo rted as SAEs Potential drug induced liver injury is defined as: 1) ALT or AST elevation > 3 times upper limit of normal (ULN) AND 2) Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline phosphatase) AND 3) No other immediate ly apparent possible causes of AST/ALT elevation and hyperbilirubinemia, including, but not limite d to, viral hepatitis , pre-existin g chroni c or acute liver disease , or the administration of other drug(s) known to be hepatotoxic. ADVERSE EVENTS An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. The causal relationship to study drug is determined by a physician and should be used to assess all adverse events (AE). The casual relationship can be one of the following: Related: There is a reasonable causal relationship between study drug administration and the AE. Not related: There is not a reasonable causal relationship between study drug administration and the AE. The term "reasonable causal relationship" means there is evidence to suggest a causal relationship. Adverse events can be spontaneously reported or elicited during open- ended questioning, examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be questioned regarding the specific occurrence of one or more AEs.) NONSERIOUS ADVERSE EVENT Protocol Version 8.0. September 19 , 2018 Page | 77 • Nonserious Adverse Events are to be provided to BMS in aggregate via interim or final study reports as specified in the agreement or, if a regulatory requirement [e.g. IND US trial] as part of an annual reporting requirement. • Nonserious AE information should also be collected from the start of a place bo lead - in period or other observational period intended to establish a baseline status for the subjects. A nonserious adverse event is an AE not classified as serious. Nonserious Adverse Event Collection and Reporting The collection of nonserious AE information should begin at initiation of study drug. All nonserious adverse events (not only those deemed to be treatment -related) should be collected continuously during the treatment period and for a minimum of 100 days following the last dose of study tre atment. Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they become serious. Follow -up is also required for nonserious AEs that cause interruption or discontinuation of study drug and for those present at the end of study treatment as appropriate. Laboratory Test Abnormalities All laboratory test results captured as part of the study should be recorded following institutional procedures. Test results that constitute SAEs should be documented and reported as such. The following laboratory abnormalities should be documented and reported appropriately: • any laboratory test result that is clinically significant or meets the definition of an SAE • any laboratory abnormality that required the subject to have study drug disc ontinued or interrupted • any laboratory abnormality that required the subject to receive specific corrective therapy. Pregnancy If, following initiation of the investigational product, it is subsequently discovered that a study subject is pregnant or may have been pregnant at the time of investigational product exposure, including during at least 6 half lives after product administration, the investigational product will be permanently discontinued in an appropriate manner (eg, dose tapering if necessary for subject safety). Protocol Version 8.0. September 19 , 2018 Page | 78 The investigator must immediately notify Worldwide Safety @BMS of this event via the Pregnancy Surveillance Form in accordance with SAE reporting procedures. Follow- up information regarding the course of the pregnancy, including perinatal and neonatal outcome and, where applicable, offspring information must be reported on the Pregnancy Surveillance Form [provided upon request from BMS] Any pregnancy that occurs in a female partner of a male study participant should be reported to BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form. Overdose An overdose is defined as the accidental or intentional administration of any dose of a product that is considered both excessive and medically important. All occ urrences of overdose must be reported as an SAE. Other Safety Considerations Any significant worsening noted during interim or final physical examinations, electrocardiograms, x -rays, and any other potential safety assessments, whether or not these procedures are required by the protocol, should also be recorded as a nonserious or serious AE, as appropriate, and reported accordingly. NOTE: In cases of an anexpected or unforeseen discrepancy regarding procedures for the reporting of adverse events between the content of the protocol (section 7.2) and the BMS guidelines outlined in section 11.7, it is the latter guidelines/instructions that should prevail for the purposes of patient management on protocol. Protocol Version 8.0.