Bioequivalence 1011 BE (fasted) - CIC 36/35 BE shown 250 mg – (250 mg) versus IRT doses 36/35 BE (fasted) - CIC BE shown 250 mg – versus PIC doses Food Effect (250 1011 Food Effect - CIC Food decreases BA by ~ mg) fast/fed 14%. Mass balance (250 1009 14C 6/6 PKs and ADME mg) crizotinib investigated. PK Drug-Drug 1015 Ketoconazole / 15 Systemic exposure Interaction Crizotinib increased. Table 1 continued: Submitted clinical studies with clinical pharmacology data; n = subjects entered/evaluated. Topic Primary Aim n Comment Patients with advanced cancer single and multiple dose studies – Single and 1001 Phase I, open-label, n=208 Comprehensive PK multiple dose; single-arm efficacy (total) data in patients with and safety in patients advanced cancer; Various QD and with advanced dose-escalation BID cancer. (n=37), and RP2D Asian versus cohorts (n=171; 250 non-Asian; mg BID) including ALK+ NSCLC group (n=119). PK interaction; Food effect Trough 1005 Phase II, open-label, n=136 Limited data only. concentrations single-arm, efficacy only and safety in patients with ALK+ advanced NSCLC. Population-PK Structural PK N=250; Covariates weight, sex, Study population 3184 race, and ECOG status variability in CL and crizotinib as predictors of CL/F, Vd; effects of H2 weight as a predictor of V 2/F, Q/F, and
Bioequivalence (250 mg) 1011 BE (fasted) - CIC versus IRT BE (fasted) - CIC versus PIC 36/35 36/35 BE shown – 250 mg doses BE shown – 250 mg doses Food Effect (250 mg) 1011 Food Effect - CIC fast/fed Food decreases BA by ~ 14%. Mass balance (250 mg) 1009 14C crizotinib 6/6 PKs and ADME investigated. PK Drug-Drug Interaction 1015 Ketoconazole / Crizotinib 15 Systemic exposure increased. Table 1 continued: Submitted clinical studies with clinical pharmacology data; n = subjects entered/evaluated. Topic Primary Aim n Comment Patients with advanced cancer – single and multiple dose studies Single and multiple dose; Various QD and BID Asian versus non-Asian; PK interaction; Food effect 1001 Phase I, open-label, single-arm efficacy and safety in patients with advanced cancer. n=208 (total) Comprehensive PK data in patients with advanced cancer; dose-escalation (n=37), and RP2D cohorts (n=171; 250 mg BID) including ALK+ NSCLC (n=119). Trough concentrations only 1005 Phase II, open-label, single-arm, efficacy and safety in patients with ALK+ advanced NSCLC. n=136 Limited data only. Population-PK Study Structural PK population variability in CL and Vd; effects of H2 N=250; 3184 crizotinib Covariates weight, sex, race, and ECOG status as predictors of CL/F, weight as a predictor of V 2/F, Q/F, and group
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