Perpetrator DDI Potential of Givinostat as Inhibitor and Inducer of CYP3A and P-gp Activity

10 mg/mL oral suspension. Givinostat 10 mg/ml oral suspension was administered once, in the morning, in Days 1, 2, 6, 7, 17 and 18), and twice a day (50 mg as oral suspension), in the morning and in the evening, from the Day 4 to Day 18. On Day 19, only the morning dose was administered.

Midazolam 1 mg/ml, solution for intravenous administration. Midazolam 1mg/ml IV, single dose, was administered on Days 1, 6 and 17, 1 hour after the planned morning time of givinostat administration. Midazolam IV were administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose.

"Dose: 2.5 mg oromucosal solution. Midazolam 2.5 mg single oral solution was administered on Days 2, 7 and 18, 1 hour after the planned morning time of givinostat administration.~Oral midazolam (and dabigatran etexilate) was administered following an overnight fasting of at least 8 hours and subjects remained fasted until at least 3 hours post-dose.~Oral midazolam (and dabigatran etexilate) was administered with 150 mL of water. Except for water given with the investigational products, no fluids were allowed from 1 hour before midazolam and dabigatran dosing until 2 hours postdose. Water was provided ad libitum at all other times. Midazolam (and dabigatran etexilate) were administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose."

"Dose: 75 mg; Dosage form: hard capsules On Days 1, 6 and 17, dabigatran etexilate 75 mg was administered (with midazolam 1mg IV) 1 hour after the planned morning time of givinostat administration.~Dabigatran etexilate (and midazolam) was administered following an overnight fasting of at least 8 hours and subjects remained fasted until at least 3 hours post-dose Oral dabigatran etexilate (and oral midazolam) was administered with 150 mL of water. Except for water given with the investigational products, no fluids were allowed from 1 hour before dabigatran (and midazolam) dosing until 2 hours postdose. Water was provided ad libitum at all other times. Dabigatran etexilate (and Midazolam) was administered with the subjects in a semi-recumbent position. Subjects remained semirecumbent until at least 3 hours post-dose."