Table 3.

Total and unbound plasma anticoagulant PK parameters on day 6: edoxaban and D21-2393

PK parameter	Andexanet alfa dose (n = 6/cohort)			Placebo* (n = 8)
	Cohort 1 (600-mg bolus)	Cohort 2 (800/8 × 60 min)	Cohort 3 (800-mg bolus)
Total edoxaban, mean ± SD
Cmax, ng/mL	1420 ± 384	1720 ± 327	1240 ± 225	212 ± 62.1
C3.03,† ng/mL	1450 ± 424	1680 ± 340	NA	164 ± 91.4‡
C5.03,§ ng/mL	NA	NA	1200 ± 228	94.9 ± 14.9ǁ
Tmax,¶ h (range)	3.1 (3.04, 3.21)	3.3 (3.05, 3.27)	5.2 (5.03, 5.40)	2.0 (1.00, 2.47)
AUC0-24, ng • h/mL	3550 ± 970	4950 ± 1050	3280 ± 438	1520 ± 358
CL/F, L/h	17.9 ± 4.24	12.6 ± 2.80	18.6 ± 2.33	41.3 ± 8.77
t1/2, h	15.4 ± 6.24	9.3 ± 2.90	13.3 ± 4.14	9.5 ± 4.20
Unbound edoxaban, mean ± SD
Pre–andexanet alfa/placebo	130 ± 52.9	114 ± 37.1	63.6 ± 13.3	125 ± 57.5‡
C3.03,† ng/mL	59.6 ± 33.1§	41.1 ± 19.7	NA	103 ± 55.4‡
C5.03,§ ng/mL	NA	NA	15.1 ± 7.52	65.6 ± 10.5ǁ
Total D21-2393, mean ± SD
Cmax, ng/mL	61.9 ± 11.9	85.3 ± 53.7	45.6 ± 12.3	14.4 ± 5.43
C3.03,† ng/mL	60.0 ± 14.8¶	75.6 ± 46.1	NA	14.5 ± 5.48#
C5.03,§ ng/mL	NA	NA	43.2 ± 13.2	5.00 ± 1.63ǁ
Tmax,¶ h (range)	3.2 (3.05, 4.02)	3.3 (3.25, 3.30)	5.2 (5.03, 5.54)	2.2 (2.00, 3.00)
AUC0-24, ng • h/mL	205 ± 47.9	290 ± 191	164 ± 38.0	98.6 ± 34.5
t1/2, h	10.4 ± 4.77§	8.4 ± 2.53	12.8 ± 4.83	8.7 ± 3.35
Unbound D21-2393, mean ± SD
Pre–andexanet alfa/placebo	5.9 ± 3.03	7.5 ± 2.82	3.6 ± 1.25	7.7 ± 2.89#
C3.03,† ng/mL	3.07 ± 1.07¶	2.7 ± 0.96§	Not applicable	7.8 ± 4.26#
C5.03,§ ng/mL	NA	NA	0.73 ± 0.32	2.7 ± 0.98ǁ

C_5.03, concentration at 5.03 hours postdose; NA, not available.

^*Pooled placebo subjects from cohorts 1 to 3.

^†Anticoagulant plasma concentration measured 2 minutes after the end of the andexanet alfa bolus dose (3.03 hours after edoxaban dosing).

^‡N = 5.

^§Anticoagulant plasma concentration measured 2 minutes after the end of the andexanet alfa bolus dose (5.03 hours after edoxaban dosing).

^ǁN = 3.

^¶Median (minimum, maximum); time relative to edoxaban dosing.

^#N = 4.