Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced Cancer

In Part A, Period 1, patients will be administered a 3 drug cocktail of caffeine, omeprazole and midazolam on Day -8 followed by a washout period of at least 7 but no more than 14 days. In Part A, Period 2, AZD1775 capsules will be administered orally, 225 mg bid, until steady state for 2.5 days (total of 5 doses) and administered together with the cocktail on the morning of Day 3.

In Part A, Period 1, patients will be administered a 3 drug cocktail of caffeine, omeprazole and midazolam on Day -8 followed by a washout period of at least 7 but no more than 14 days. In Part A, Period 2, AZD1775 capsules will be administered orally, 225 mg bid, until steady state for 2.5 days (total of 5 doses) and administered together with the cocktail on the morning of Day 3.

In Part A, Period 1, patients will be administered a 3 drug cocktail of caffeine, omeprazole and midazolam on Day -8 followed by a washout period of at least 7 but no more than 14 days. In Part A, Period 2, AZD1775 capsules will be administered orally, 225 mg bid, until steady state for 2.5 days (total of 5 doses) and administered together with the cocktail on the morning of Day 3.

Patients should be administered Kytril (granisetron) 1 mg orally, under fasted conditions (-2 to 2 hours away from meals), 30 minutes prior to administration of the AZD1775 capsules with a small amount of water.

Multiple doses of 225 mg AZD1775, (3 x 75 mg, printed capsules) administered orally. The drug class of AZD1775 is Wee-1 kinase inhibitor.