Pharmacokinetics
hypoglycemia
HYPOGLYCEMIA
Pharmacokinetic (non-food effect) analyses were performed on blood samples, which were collected pre-dose during treatment cycle 1 on days 1 and 5, and 1, 2, 4, 6, 8, 10 and 24 h after receiving the first adavosertib dose on days 1 and 5. Pre-dose samples were also collected on day 5 of treatment cycle 5.The area under the plasma concentration–time curve from time 0 to 10 h post-dose (AUCDose proportionality (non-food effect) of adavosertib AUCFor the preliminary food-effect analysis, blood samples were collected pre-dose and 1, 2, 4, 6, 8 and 10 h after receiving the first adavosertib dose during treatment cycle 1 on day 1 (fasted condition), and during treatment cycle 2 on day 1 (fed condition). Analyses were performed for the bid dosing schedules and RP2D only.For the fasted condition, patients were required to fast for at least 10 h prior to receiving adavosertib until 4 h post-dose. Patients were allowed glucose and/or juice if they had signs or symptoms of hypoglycemia after receiving adavosertib. Water was restricted from 1 h pre-dose until 1 h post-dose, except for the 240 mL of water administered with treatment.For the fed condition, patients fasted for at least 10 h prior to receiving adavosertib until 4 h post-dose, with the exception of a high-fat meal eaten in the 30 min before adavosertib administration. If the meal was not completed within 30 min, adavosertib was administered so long as 75% of the meal had been consumed within 45 min of starting the meal. The study was conducted using the Food and Drug Administration standard high-fat meal under fed conditions, which should have a total of 800 to 1000 kcal, with approximately 50% of the caloric content made up from fat [Natural log-transformed AUC and C