Table 2.

Pharmacokinetic parameters for each drug alone and in combination

Parameter	Study 1		Study 2		Study 3
	Esaxerenone 2.5 mg		Amlodipine 2.5 mg		Digoxin 0.25 mg/day
	Alone (n = 22)	+ Amlodipine 10 mg/day (n = 22)	Alone (n = 18)	+ Esaxerenone 5 mg/day (n = 18)	Alone (n = 19)	+ Esaxerenone 5 mg/day (n = 19)
Cmax, ng/mL	35.5 ± 6.3	33.9 ± 5.0	2.09 ± 0.47	2.28 ± 0.46	1.54 ± 0.53	1.77 ± 0.73
Ctrough, ng/mL	–	–	–	–	0.533 ± 0.089	0.583 ± 0.116
AUClast, ng·h/mL	560 ± 106	644 ± 111	87.2 ± 22.3	102 ± 20	–	–
AUCinf, ng·h/mL	575 ± 111	674 ± 127	102 ± 29	122 ± 29	–	–
AUCtau, ng·h/mL	–	–	–	–	15.3 ± 2.5	16.5 ± 3.3
tmax, ha	2.00 (1.00–4.00)	2.50 (1.50–4.00)	5.00 (3.00–9.00)	6.00 (5.00–7.00)	1.50 (0.50–4.00)	1.00 (0.50–3.00)
t1/2, h	18.5 ± 3.2	20.9 ± 3.1	40.5 ± 6.8	43.5 ± 6.7	NA	NA
CL/F, L/h	4.49 ± 0.79	3.83 ± 0.67	26.8 ± 8.9	21.8 ± 5.9	–	–
CLss/F, L/h	–	–	–	–	16.8 ± 3.2	15.8 ± 3.5

Unless stated otherwise, values are means±standard deviations

NA, not assessable because the elimination rate constant was not appropriately estimated

AUC_inf area under the plasma concentration–time curve up to infinity, AUC_last AUC up to the last quantifiable time, AUC_tau AUC over the dosing interval, CL/F apparent total body clearance, CL_ss/F apparent total body clearance at steady state, C_max peak plasma concentration, C_trough trough plasma concentration, t_1/2 terminal elimination half-life, t_max time to reach maximum plasma concentration

^aMedian value (range)