This is a single center, non-randomized, open-label, fixed sequence study to investigate the effect of multiple oral dosing of LEO 32731 (up-titrated), on CYP3A activity in healthy male subjects using midazolam as a probe CYP3A substrate. The study will be conducted in two seamless parts: Part I - Maximal Tolerated Dose (MTD) Part II - Drug-Drug Interaction with midazolam
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Nuvisan GmbH
Neu-Ulm, Germany
Pharmacokinetic (PK) parameters of midazolam AUC0-t
PK parameters AUC0-t will be analyzed on Day -1 and Day 17.
Time frame: Day -1 and Day 17
Pharmacokinetic (PK) parameters of midazolam Cmax
PK parameter Cmax will be analyzed on Day -1 and Day 17.
Time frame: Day -1 and Day 17
AUC0-t midazolam
PK parameters of midazolam on Day 4 and Day 7 will only be calculated if relevant differences are seen in midazolam PK parameters between Day -1 and Day 17.
Time frame: Day 4 and Day 7
AUC0-inf of midazolam
PK parameters of midazolam on Day 4 and Day 7 will only be calculated if relevant differences are seen in midazolam PK parameters between Day -1 and Day 17.
Time frame: Day 4 and Day 7
Cmax of midazolam
PK parameters of midazolam on Day 4 and Day 7 will only be calculated if relevant differences are seen in midazolam PK parameters between Day -1 and Day 17.
Time frame: Day 4 and Day 7
AUC0-inf of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Time frame: Day -1 and Day 17
Tmax of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Time frame: Day -1 and Day 17
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t1/2 of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Time frame: Day -1 and Day 17
CL/F of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Time frame: Day -1 and Day 17
Vz/F of midazolam
Further PK parameters (AUC0-inf, tmax, t1/2, CL/F and Vz/F) of midazolam on Days -1 and 17 (if applicable these parameters will be calculated on Day 4 and Day 7, too).
Time frame: Day -1 and Day 17