Table 1.

Study designs

Black highlight indicates midostaurin. Medium gray highlight indicates CYP3A4 inhibitor, inducer, or probe. Light gray highlight indicates placebo. Double vertical lines indicate the end of a given study

4β-HC 4β-hydroxycholesterol, 6β-HC 6β-hydroxycortisol, CYP3A4 cytochrome P450 3A4, PK pharmacokinetics

^aBlood samples for the determination of midostaurin PK were collected predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h after midostaurin dosing on day 6 (ketoconazole study) and day 9 (rifampicin study). In the rifampicin study, an additional sample was taken at 144 h after midostaurin dosing on day 9

^bOn days 4–6, blood samples were collected before the morning dose to measure ketoconazole levels

^cOn days 6, 9, and 14, blood samples were collected for rifampicin assessment before the evening rifampicin dose

^dOn days 1 (baseline), 9 (before midostaurin treatment), 11, and 15, levels of 4β-HC in plasma and the ratio of 6β-HC/cortisol in urine were assessed

^eBlood samples for PK determination of midostaurin and its metabolites (CGP62221 and CGP52421) were taken before the morning dose of midostaurin on days 4–6 and before midazolam administration on days 7 and 8

^fBlood samples for the determination of midazolam PK were collected before dose and at 0.25, 0.5, 1, 1.5, 1.75, 2, 3, 4, 6, 8, and 10 h after midazolam dosing on days 1, 3, and 8

^gBlood samples and urine samples were taken on days 1, 3, 6, 7, 8, and 9 to measure 4β-HC in plasma and the ratio of 6β-HC/cortisol in urine, respectively