Table 6.

Plasma OSI-906 pharmacokinetic parameters after single and multiple dosing (twice-daily regimen)

OSI-906 PK parameters following single oral administration (twice-daily regimen, day 1)
Dose (mg)204075150200
Evaluable, n533103
tmax (h)3.0 (2.0–4.0)2.0 (1.0–4.0)3.0 (2.0–4.0)2.1 (1.0–3.2)3.0 (1.2–3.2)
Cmax (ng/mL)242 (121–284)401 (395–659)762 (629–1,040)1,705 (869–3,090)2,050 (970–2,990)
AUCtau (ng × h/mL)830 (366–1,508)1,761 (1,093–1,804)3,601 (2,437–5,814)8,453 (2,557–11,795)12,508 (4,668–17,809)
AUCinf (ng × h/mL)861 (388–1,624)1,812 (1,098–1,815)4,240 (2,487–6,742)9,475 (2,649–12,411)9,680a (4,932–14,428)
CL/F (L/h)23,237 (12,319–51,536)22,077 (22,040–36,434)17,687 (11,124–30,265)15,839 (12,086–56,634)27,207a (13,862–40,552)
t1/2lambdaz (h)2.24 (1.64–3.06)1.65 (1.45–1.83)3.52 (1.80–4.10)2.93 (2.09–4.58)3.09 (2.55–6.58)
Vz/F (L)59,414 (39,865–227,717)58,429 (52,490–76,261)78,528 (65,576–89,724)77,780 (37,730–173,756)105,360a (61,701–149,020)
OSI-906 PK parameters following multiple oral administrations (twice-daily regimen, day 22)
Evaluable, n33391
tmax (h)2.0 (1.0–8.0)3.0 (3.0–4.0)6.0 (2.0–12.0)2.0 (1.0–3.1)1.1 (1.1–1.1)
Cmax (ng/mL)173 (110–451)489 (470–1,290)1,420 (944–2,370)3,110 (1,190–4,290)2,970 (2,970–2,970)
AUC0–tau (ng × h/mL)846 (616–1,542)1,996 (1,577–5,331)11,540 (3,408–18,256)25,280 (6,967–32,567)16,070 (16,070–16,070)
AUCinf (ng × h/mL)1,117a (645–1,589)3,566a (1,590–5,542)3,560b (3,560–3,560)24,747c (7,588–24,926)17,769 (17,669–17,669)
CL/F (L/h)23,642 (12,974–32,456)20,045 (7,503–25,362)6,499 (4,108–22,007)7,332d (5,425–21,531)12,446 (12,466–12,466)
t1/2lambdaz (h)2.49a (2.33–2.65)1.73a (1.35–2.10)2.66b (2.66–2.66)5.03e (2.93–8.85)3.23 (3.23–3.23)
Vz/F (L)83,741a (43,576–123,907)36,052a (22,767–49,336)84,306b (84,306–84,306)46,793c (44,950–91,032)58,058 (58,058–58,058)

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

Abbreviation: 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; PK, pharmacokinetic.

  • an = 2; bn = 1; cn = 3; dn = 4; en = 8.