Table 1.

Summary of design of single-agent studies from which data were analyzed

Design (study number)Population (n)Dosing schedule*Study day for full PK samplingFull PK sampling time points post-dose (h)
Single-dose studies
R, DB, PC (001)Healthy volunteers (6)50 mg1Pre-dose (0), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 16, 24, 30, 36, 48
R, OL, three-way CO of sunitinib free base, l-malate salt, and the effect of food (004)Healthy volunteers (15)50 mg10, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 11, 12, 16, 24, 30, 36, 48, 72, 216
3 single doses (free base fasted; l-malate salt fasted; l-malate salt fed)
R, OL, two-way CO study with/without concomitant ketoconazole (009)Healthy volunteers (27)10 mg§10, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 30, 36, 48, 72, 120, 168, 216, 312, 408, 504
Ketoconazole: 400 mg p.o. qd ×7 d
OL, CO study with/without concomitant rifampin (1001)Healthy volunteers (25)50 mg10, 2, 4, 7, 8, 9, 12, 16, 24, 36, 48, 72, 144, 240, 288, 336, 408
Rifampin: 400 mg p.o. qd ×7 d
OL, dose escalation (006)AML (29)50-350 mg10, 4, 6, 8, 10, 12, 24, 48
Multiple-dose studies
OL, single-arm, NR, dose-escalating study of three treatment schedules (013)GIST (68, of which 18 with full PK)25, 50 or 75 mg qd (2/2, 4/2 or 2/1)Schedule 2/2
Cycle 1: 1, 140, 1, 4, 6, 8, 10, 12, 24, 48
Cycle 2: 14
Schedule 4/2
Cycle 1: 1 and 28As above
Cycle 2: 28
Schedule 2/1
Cycle 1: 1, 14As above
Cycle 2: 14
DB, PC, R (1004)GIST (154)50 mg qd (4/2)Schedule 4/2
Cycle 1: 1, 14, 28Trough sampling only
Additional cycles: 1, 28
OL, NR (1045)GIST (12)25, 50, 75 mg qd (4/2)Schedule 4/2
Cycle 1: 10, 1, 2, 4, 6, 8, 10
Cycle 1: 2, 7, 14, 210
Cycle 1: 280, 1, 2, 4, 6, 8, 10, 24, 48
OL, NR (014)mRCC (56)50 mg qd (4/2)Schedule 4/2
Cycles 1-4: 1, 14, 28Trough sampling only
Additional cycles: 1
OL, NR (1006)mRCC (92)50 mg qd (4/2)Schedule 4/2
Cycle 1: 1, 14, 28Cycles 2-4: 1, 28Trough sampling only
Additional cycles: 1
OL, NR, dose escalation (002)Solid tumor (27)25, 50, 75 or 100 mg qd or qod (4/2)Schedule 4/2
Cycle 1: 1 and 27 or 280, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 14, 16, 24
OL, NR, dose escalation (005)Solid tumor (41)50, 75 mg qd or qod (2/2 or 4/2)Schedule 2/2
Cycle 1: 1 and 13 or 140, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 20, 24, 48
Cycles 2 and 3: 13 or 14
Schedule 4/2
Cycle 1: 1 and 28As above
Cycles 2 and 3: 28
Schedule 4/2
Cycle 1: 140, 4, 6, 8, 10, 12, 24
OL, NR (016)Solid tumor (12)50 mg qd (2/1)Schedule 2/1
Cycle 1: 1 and 140, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 20, 24
Cycle 2: 14
Cycle 3: 14
OL, dose escalation (018)Solid tumor (26)50-175 mg loading dose on day 1; 50 mg qd (2/1)Schedule 2/1
Cycle 1: 10, 4, 6, 8, 10, 12, 24
Cycle 2: 1 and 14
Cycle 3: 14 (for >50 mg)
Cycle 1: 140, 4, 6, 8, 10, 12, 24, 72, 120
  • Abbreviations: CO, crossover; DB, double-blind; MD, multiple dose; mRCC, metastatic renal cell carcinoma; GIST, gastrointestinal stromal tumor; n, number of subjects evaluable for PK; NR, nonrandomized; OL, open-label; PC, placebo-controlled; p.o., oral; PK, pharmacokinetics; qd, everyday; qod, every other day; R, randomized; SD, single dose.

  • * Information provided: dose of sunitinib (in all studies sunitinib was administered in the form of l-malate salt capsules unless stated); frequency of dosing and dosing schedule (weeks on treatment/weeks off treatment).

  • Free base powder in bottle.

  • Free base and l-malate salt capsule.

  • § l-Malate salt powder in bottle.

  • Trough PK sampling was also done.