TABLE 1

Summary statistics of pharmacokinetic parameters for apalutamide, M3, M4, and 14C-apalutamide in plasma and blood. Geometric mean (% CV) data are presented, except for Tmax for which median (minimum–maximum) data are presented

AnalyteCmaxTmaxaAUC0-tAUC0-inft1/2FCLVd
µg/mlhh/µg per milliliterhl/hl
Part A—bioavailability study, N = 6
 Apalutamide3.25 (12.2)1.01 (1.00–1.50)185 (16.2)200 (14.5)175 (19.0)1.11 (2.1)N.D.N.D.
 M30.302 (20.0)265.84 (144.00–313.70)183 (10.6)199 (12.0)248 (23.7)N.D.N.D.N.D.
 M4b0.0662 (33.2)3.00 (2.00–6.00)8.83 (52.0)N.D.N.D.N.D.N.D.N.D.
 14C-apalutamide0.00235 (25.3)0.23 (0.08–0.42)0.0699 (19.7)0.0719 (19.7)170 (23.3)N.D.1.33 (15.0)326 (17.0)
 DN 14C-apalutamide5.64 (25.3)N.D.168 (19.7)173 (19.7)N.D.N.D.N.D.N.D.
Part B—AME study, N = 6
 Apalutamide3.18 (14.5)1.50 (1.00–2.02)175 (23.5)185 (22.1)148 (22.0)N.D.N.D.N.D.
 M30.322 (21.9)204.00 (120.00–240.00)169 (14.0)186 (12.2)225 (23.4)N.D.N.D.N.D.
 M4b0.0717 (19.4)3.00 (2.00–6.00)11.1 (39.0)N.D.N.D.N.D.N.D.N.D.
 Total 14Cc2.82 (25.9)1.25 (0.50–2.00)413 (10.2)418 (10.5)257 (11.6)N.D.N.D.N.D.
 Total 14C (blood)c,d2.34 (19.1)1.00 (1.00–1.00)133 (11.1)N.D.N.D.N.D.N.D.N.D.

  • CL, clearance; DN, dose normalized to 240 mg; F, absolute bioavailability; N, number of subjects; N.D., not determined; t1/2, terminal half-life; Vd, volume of distribution.

  • ↵a For 14C-apalutamide, Tmax was measured relative to the start of the intravenous infusion at 2 h after oral dosing.

  • ↵b Geometric mean AUC0–inf and t1/2 could not be reliably determined.

  • ↵c For total 14C in plasma and blood, the units for Cmax (µg Eq/ml), AUC0–t (h/µg Eq per milliliter), and AUC0–inf (h/µg Eq per milliliter) differed from the units shown above.

  • ↵d For total 14C in blood, AUC0–t was calculated up to time t = 168 h.