FIGURE 1.

Summary of PBPK modeling strategy. Treatment A: single dose of milademetan 100 mg on study day 1 administered under fasted conditions; treatment B: itraconazole 200 mg twice daily on study day 8 and 200 mg once daily on study days 9 through 20 administered under fasted conditions and single dose of milademetan 100 mg on study day 14 administered 1 h post itraconazole dose; treatment C: posaconazole 200 mg three times daily on study days 8 through 20 administered with a full meal and single dose of milademetan 100 mg on study day 14 administered 2 h post posaconazole dose. ADME, absorption, distribution, metabolism, and excretion; AUCR, area under the concentration‐time curve ratio; CYP3A, cytochrome P3A; f_mCYP3A4, fraction metabolized by CYP3A4; PBPK, physiologically based pharmacokinetics