Study to evaluate the effect of food and the effect of swallowing capsule whole versus sprinkling on apple sauce on the pharmacokinetics (PK)/bioavailability of palovarotene, and evaluate the effect of palovarotene on the PK of the CYP3A4 substrate midazolam.
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Maximum (peak) observed plasma drug concentration
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13.
Time to reach maximum (peak) (t max) observed plasma concentration following drug administration
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Area under the plasma concentration time (AUC 0-last) curve from time zero to the last quantifiable time point, calculated by linear-log trapezoidal summation
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Area under the plasma concentration time curve from time zero to infinity (AUC 0-infinity)
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Apparent terminal disposition rate constant/terminal rate constant yz
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Apparent terminal elimination half-life (t1/2)
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Apparent volume of distribution after oral administration (Vd/F)
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Apparent total clearance of the drug from plasma after oral administration (cLF)
Timeframe: Days 1, 2, 3, 6, 7, 8, 11, 12, 13
Area under the plasma concentration time curve from time zero to 24 hours only for DDI cohort
Timeframe: Days 1, 2, 15, 16
The last concentration before the next study drug administration at steady state for DDI cohort
Timeframe: Days 1, 2, 15, 16
Maximum (peak) observed plasma drug concentration at steady state for DDI cohort
Timeframe: Days 1, 2, 15, 16
Time to reach maximum (peak) observed plasma concentration following drug administration at steady state for DDI cohort
Timeframe: Days 1, 2, 15, 16
Minimum observed plasma concentration at steady state, taken as the lowest plasma concentration during dosing interval for DDI cohort
Timeframe: Days 1, 2, 15, 16
Accumulation ratio for DDI cohort
Timeframe: Days 1, 2, 15, 16