Statistical analyses
EVENTS
No formal sample size estimation was conducted. Based on an estimate of within-patient standard deviation of 0.294 and assuming a true interaction effect of 100%, it was estimated that 20 evaluable patients would provide 80% power to show that the 90% confidence interval (CI) for the adavosertib effect lies entirely below 2.67, i.e. it would rule out a 167% increase of exposure in the presence of adavosertib. The number of patients was based on careful clinical consideration to gain adequate information on the primary endpoints while exposing as few patients as possible to study procedures. Enrollment of approximately 30 patients, with a target of 20 evaluable patients, was considered adequate and sufficient to meet the objectives of this study.The safety analysis set included all patients who received at least one dose of study treatment (adavosertib or probe cocktail drugs). Patients were evaluated according to the treatment received. A treatment-emergent AE was defined as an AE with its start date and time on or after the first dose of probe cocktail on day − 8 up to and including 30 days after the last dose date of adavosertib, or, for pre-existing pre-treatment AEs, the date on which they worsened in severity after the first dose of study treatment. The PK analysis set included all dosed patients who had at least one quantifiable plasma concentration for any of the cocktail drugs (or metabolites) or adavosertib collected post-dose without protocol deviations or events that could affect the PK analysis.PK parameters were derived using non-compartmental methods with PhoenixResults for AUC