Validation Study of Multiple Probe Compounds for Drug Interaction Evaluation

Caffeine dosed at 100 mg as probe for CYP1A2 pathway

Dosed at 4 mg as probe for CYP2C8 pathway

Dosed at 40 mg, probe for CYP2C9 pathway

Dosed at 20 mg, probe for CYP2C19 pathway

Dosed at 30 mg, probe for CYP2D6 pathway

Dosed at 3 mg for Part 1, Part 2 cohorts B and C and 1 mg for Part 2 Cohort A, probe drug for CYP3A4/5 pathway

Dosed at 10 mg, probe drug for OATP1B1 pathway

Dosed at 400 mg once-daily Day 1 through Day 9, inhibitor of CYP3A4

Dosed at 400 mg x 1 dose on day 1, 200 mg once daily on days 2 through 9, inhibitor of CYP2C9 pathway

Dosed at 600 mg x 1 dose on Day 1 and Day 8, inhibitor of OATP1B1 pathway

Dosed at 15 mg, probe drug for CYP2C8 pathway