Table 5.

Plasma OSI-906 pharmacokinetic parameters after multiple dosing (once-daily regimen, day 22)

Dose (mg)10204075150300400450
Evaluable, n23333332
tmax (h)2.5 (2.0–3.0)2.0 (2.0–2.0)3.0 (2.0–4.1)3.0 (2.1–5.8)3.9 (3.0–6.0)4.0 (3.1–5.9)5.9 (2.2–8.0)4.1 (4.0–4.1)
Cmax (ng/mL)57.5 (40.4–74.6)171 (163–212)639 (473–642)1,000 (684–1,250)1,570 (1,120–1,860)8,450 (4,440–13,600)4,180 (1,420 to −4,450)3,565 (2,820–4,310)
AUC0–tau (ng × h/mL)253 (210–295)658 (655–865)3,312 (2,365–3,878)6,063 (5,969–6,220)13,306 (6,890–15,774)85,212 (19,348–180,665)31,091 (8,690–83,533)54,684 (36,481–72,886)
AUCinf (ng × h/mL)243 (206–279)663 (658–871)3,359 (2,383–4,028)6,259 (5,987–6,505)13,839 (6,900–15,097)52,474 (19,352–85,597)20,219 (9,021–31,418)NCa
CL/F (L/h)40,701 (33,842–47,559)30,398 (23,132–30,525)12,079 (10,314–16,910)12,369 (12,058–12,566)11,273 (9,631–21,711)9,513 (3,521–15,505)12,866 (4,789–46,029)NCa
t1/2lambdaz (h)2.13 (1.68–2.58)3.28 (2.99–3.58)3.88 (3.07–5.15)4.05 (3.20–5.12)3.96 (2.52–4.41)2.69 (1.69–15.5)3.93 (3.32–4.53)10.1 (9.71–10.4)
Vz/F (L)120,545 (115,309–125,780)131,814 (109,596–156,858)74,991 (67,594–76,595)72,250 (58,059–89,033)71,802 (55,067–79,150)25,705 (13,656–37,754)181,317 (61,554–301,080)NCa

NOTE: Data for all patients who had sufficient pharmacokinetic sampling associated with the OSI-906 doses (pharmacokinetic analysis set).

Abbreviations: tmax, time to reach observed concentration; AUCtau, area under the concentration-time curve during the time interval between consecutive dosing; AUCinf, area under the concentration-time curve from the time of dosing up to infinity with extrapolation of terminal phase; t1/2lambaz, terminal elimination half-life; NC, not calculated.