Table 2

Investigational product dose modification and stopping criteria

Parameter	Dose modification criterion	Action to be taken
Cannabidiol
INR	Grade 2 changes ie, >1.5 for patients not on anticoagulants	CBD held for one week then laboratory tests repeated: If abnormality resolves, recommence dosing at previous dose (300 mg) If abnormality does not resolve and there is no other cause for the AE identified, (ie, the AE is probably or definitely attributed to the study medication) study medication to be ceased and participant to be withdrawn If there is uncertainty about the cause of the AE or the test values fluctuating, the investigator has discretion to continue to hold the medication and repeat testing
Total bilirubin	Grade 3 changes (ie, >3.0 ULN)
AST or ALT	Grade 3 changes in ALT or AST (ie, >5.0 ULN)
Renal function	Creatinine values of grade 3 changes (ie, >5.0 ULN) eGRF—grade 3 changes (ie, <30.0 mL/min)
Δ⁹-Tetrahydrocannabinol
Somnolence	Richmond Agitation and Sedation Scale score indicating significant impairment to participant’s ability to perform daily tasks (as outlined by scores in online supplemental table 1).

AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBD, cannabidiol; eGFR, estimated glomerular filtration rate; INR, international normalised ratio; ULN, upper limit of normal.