Table S1.

Clinical studies included in the population pharmacokinetic model

Study	Population	Design	Dasatinib dosing regimens	na	PK sampling schedule
CA180-002 (NCT00064233)1	CML(-CP, -AP, -BP) or Ph+ ALL resistant/intolerant to imatinib	Phase I, open-label, multicenter, dose-escalation study	15, 30, 50, 75, 105, 140, and 180 mg once daily (5 days on, 2 days off weekly dosing), 25, 35, 50, 70, 90, and 120 mg twice daily (5 days on, 2 days off weekly or continuous dosing)	83	Once daily (5 days on, 2 days off weekly dosing) Cycle 1, days 1, 5, and 26: predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 h (all days); 48 and 72 h (days 5 and 26 only) Twice daily (5 days on, 2 days off weekly dosing) Cycle 1, days 1, 5, and 26: predose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h (all days); 5 h (days 1 and 5 only); 24, 48, and 72 h (days 5 and 26 only) Twice daily (continuous daily dosing) Cycle 1, days 1 and 5, and Cycle 2, day 1: predose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h (all days); 5 h (Cycle 1, day 1 only); 24, 48, and 72 h (Cycle 1, day 8, and Cycle 2, day 1 only)
CA180-005 (START-A; NCT00101647)2	CML-AP resistant/intolerant to imatinib	Phase II, open-label, multicenter study	70 mg twice daily	41	First 15 treated patients Cycle 1, days 1 and 8: predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 10 h All subsequently treated patients Cycle 1, day 8: predose; between 0.5 h and 3 h
CA180-006 (START-B; NCT00101816)3	CML-BP (myeloid) resistant/intolerant to imatinib	Phase II open-label, multicenter study	70 mg twice daily	29	First 15 treated patients Cycle 1, days 1 and 8: predose; 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 10 h All subsequently treated patients Cycle 1, day 8: predose; between 0.5 h and 3 h
CA180-013 (START-C; NCT00101660)4	CML-CP resistant/intolerant to imatinib	Phase II, open-label, multicenter study	70 mg twice daily	144	Cycle 1, day 8: predose; between 0.5 h and 3 h; between 5 h and 8 h; between 12 h and the next dose
CA180-015 (START-L; NCT00101595)3	CML-BP (lymphoid) resistant/intolerant to imatinib	Phase II, open-label, multicenter study	70 mg twice daily	39	Cycle 1, day 8: predose; between 0.5 h and 3 h
CA180-017 (START-R; NCT00103844)5	CML-CP resistant to imatinib	Phase II, open-label, multicenter study	70 mg twice daily	78	Cycle 1, day 8: predose; between 0.5 h and 3 h; between 5 h and 8 h; between 12 h and the next dose
CA180-034 (NCT00123474)6,7	CML-CP resistant/intolerant to imatinib	Phase III, open-label, multicenter, doseoptimization study	50 or 70 mg twice daily, or 100 or 140 mg once daily	567	Day 15: predose; between 1 h and 3 h; between 5 h and 8 h Day 29: predose

Note:

^aPatients with PK samples included in the analysis.

Abbreviations: AP, accelerated phase; BP, blast phase; CML, chronic myeloid leukemia; CP, chronic phase; Ph+ ALL, Philadelphia chromosome–positive acute lymphoblastic leukemia; PK, pharmacokinetic.