Table 3.

Ralimetinib pharmacokinetic parameters of interest at the doses of interest

300 mg Q12H300 mg Q12H + tamoxifen420 mg Q12H
Day 1, n11621
Cmax (ng/mL)1,020 (58)1,810 (42)1,700 (71)
tmaxa (h)1.00 (0.98–3.00)0.74 (0.50–1.00)1.00 (0.50–8.00)
 AUC(0–8) ng·h/mL3,460 (51)4,500 (36)5,780 (57)
Day 14, n9d314e
Cmax (ng/mL)1,400 (81)1,700 (52)2,230 (53)
tmaxa (h)2.02 (1.00–11.72)0.98 (0.47–1.98)1.53 (0.5–4.00)
 AUC(0–8) ng·h/mL6,620 (85)6,910 (55)10,200 (55)
 AUC(0–24,ss)b ng·h/mL17,900 (85)16,600 (55)26,200 (57)
 CLss/F (L/h)33.6 (85)NC32.1 (57)
 Vss/F (L)2,130 (100)NC1,620 (165)
t1/2 (h)92.6 (46)NC77.4 (150)
 RAc1.89 (33)1.58 (59)1.79 (28)

Abbreviations: AUC(0-8) and AUC(0-24) area under the baseline corrected serum concentration versus time curve from time zero to 8 or 24 hours, respectively; CLss/F, apparent total body clearance at steady state after extravascular administration; Cmax, maximum plasma concentration; CV, coefficient of variation; h, hours; Q12H, every 12 hours; RA, accumulation ratio; t1/2, terminal half life; tmax, time to reach Cmax; Vss/F, apparent volume of distribution at steady state after extravascular administration; NC, not calculable due to sampling time.

  • aMedian (range).

  • bAUC(0-24,ss) represents the sum of AUC(0-12,ss) + AUC(0-12,ss).

  • cRA: accumulation ratio between day 1 and day 14 of cycle 1 (ratio of AUC[0-8] [Day 14]/AUC[0-8] [Day 1]).

  • dN = 8 for all parameters except t1/2. Excluded pharmacokinetic parameters other than t1/2 for one patient due to missing pharmacokinetic results at early sampling time points.

  • eN = 13 for all parameters except Cmax and tmax. Excluded pharmacokinetic parameters dependent on terminal phase estimation for one patient due to atypically high concentration results.