Table 1.

Axitinib Studies Included in the Population PK Analysis

Study no.	Design	Population (enrolled/analyzed, n)	Axitinib dose and regimen	PK sampling post-dosing (hour)
111	Phase I, OL, SA, dose-escalating	Patients with solid tumors (36/20a)	Tx 1: 5 mg bid, fed, 4-week cycles, Form IV Tx 2: 5 mg bid, fasted, 4-week cycles, Form IV Tx 3: 2 mg bid (day 1), 5 mg bid thereafter, fasted, 4-week cycles, Form IV	0 (pre-dose), 0.5, 1, 2, 4, 8, 12
25	Phase II, OL, SA	Cytokine-refractory mRCC patients (52/52)	5 mg bid, fasted, 4-week cycles, dose titration, Form IV	0 (pre-dose) and 1–2
318	Phase I, OL, SA, Japanese	Japanese patients with solid tumors (12/12)	5 mg single, then 5 mg bid, fed, 4-week cycles, dose titration, Form IV	0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 32 (following single-dose) 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12 (following continuous dosing)
46	Phase II, OL, SA	Sorafenib-refractory mRCC patients (62/59b)	5 mg bid, fed, 4-week cycles, dose titration, Form IV	0 (pre-dose) and 1–2
54	Phase II, OL, SA, Japanese	Japanese cytokine-refractory mRCC patients (64/64)	5 mg bid, fed, 4-week cycles, dose titration, Form IV	0 (pre-dose) and 1–2
639	SB, randomized, 2-way CO, DDI with ketoconazole	Healthy volunteers (35/32c)	5 mg, fasted, Form IV	0 (pre-dose), 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48
728	OL, food effect	Healthy volunteers (42/41d)	Tx 1: 5 mg, fasted, Form IV Tx 2: 5 mg, fed high fat, Form IV	0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48
8	OL, 2-way CO, F	Healthy volunteers (16/16)	Tx 1: 5 mg, fasted, Form IV Tx 2: 5 mg, fed moderate fat, Form IV Tx 3: 1 mg intravenous, fasted, Form IV	0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36
9	OL, randomized, CO, relative F	Healthy volunteers (40/20e)	5 mg, fasted, Form IV	0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36
10	OL, randomized, 2-sequence, 3-period CO, BE	Healthy volunteers (40/40)	5 mg, fasted, Form IV	0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32
1129	OL, 2-period, 2-Tx CO, DDI with rifampin, Caucasian and Japanese	Caucasian healthy volunteers (20/20) Japanese healthy volunteers (20/20)	5 mg, fasted, Form IV	0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32
12	OL, randomized, 4-sequence, 4-period CO, relative F	Healthy volunteers (56/54e)	Tx 1: 5 mg, fed moderate fat, Form IV Tx 2: 5 mg, fed moderate fat, Form XLI	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 32
1330	OL, PG, normal, mild to moderate hepatic impairment	Healthy volunteers (24/8f)	5 mg, fed moderate fat, Form IV	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16,24,36,48,96, 144
14	OL, randomized, 4-sequence, 4-period CO, relative bioavailability	Healthy volunteers (20/20)	5 mg, fed moderate fat, Form IV	0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16,24,36,48
15	OL, randomized, 2-sequence, 4-period CO bioequivalence	Healthy volunteers (68/68)	Tx 1: 5 mg, fasted, Form IV Tx 2: 5 mg, fasted, Form XLI	0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32
1640	OL, fixed-sequence, 3-period CO, Chinese	Healthy volunteers (14/14)	Single-dose 5, 7, and 10 mg with washout period, fed, Form XLI	0 (pre-dose), 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 32
1728	OL, randomized, 3-period CO food effect	Healthy volunteers (30/30)	Tx 1: 5 mg, fasted, Form XLI Tx 2: 5 mg, fed high fat, Form XLI Tx 3: 5 mg, fed moderate fat, Form XLI	0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 6, 8, 12, 16, 24

BE, bioequivalence; bid, twice daily; CO, crossover; DDI, drug–drug interaction; OL, open-label; PG, parallel-group; PK, pharmacokinetics; SA, single-agent; SB, single-blind; Tx, treatment. Reasons for excluding individual data from the analysis:

^aAxitinib starting dose higher than 5 mg bid.

^bLack of dose time data or only one measurable axitinib concentration.

^cDid not receive axitinib.

^dDid not complete the study.

^eReceived I mg axitinib dose in a spray-dried dispersion or self-emulsifying drug dispersion system.

^fHaving hepatic impairment based on Child-Pugh classification.