Aldosterone synthase inhibition: cardiorenal protection in animal disease models and translation of hormonal effects to human subjects

Table 3 Effect of LCI699 on plasma and urinary sodium and potassium (human study, multiple-dose phase)

	LCI699 0.5 mg		LCI699 1 mg		LCI699 3 mg		Eplerenone		Placebo
	n	Mean	n	Mean	n	Mean	n	Mean	n	Mean
Plasma sodium, mEq/L
Baseline	12	139.3	12	140.1	12	140.6	10	139.9	11	139.6
Δ Day2^a	12	+0.23	12	−0.59	12	−0.73*	10	−0.64	11	+0.26
Δ Day7^b	12	−1.71^‡	12	−0.11	12	−2.87^‡	10	+0.31	11	+0.41
Δ Day14^c	12	+0.41	12	−0.01	12	−0.45	10	−0.07	11	+0.35
Plasma potassium, mEq/L
Baseline	12	4.19	12	4.03	12	4.13	10	3.97	11	4.14
Δ Day2^a	12	+0.20	12	+0.08	12	+0.40^‡	10	+0.08	11	0.00
Δ Day7^b	12	+0.25^‡	12	+0.12*	12	+0.28^‡	10	−0.02	11	−0.05
Δ Day14^c	12	+0.05	12	−0.06	12	+0.22*	10	−0.09	11	−0.06
Urinary sodium, mEq/24 h
Baseline	12	52.3	9	109.3	11	60.7	9	66.5	11	70.1
Δ Day 1^a	12	+45.2^†	9	+76.3^‡	11	+64.0^‡	9	+53.8‡	11	+5.6
Δ Day 7^b	12	+3.6	9	+44.0	11	+22.2	9	+16.2	11	+16.7
Δ Day 14^c	12	−25.5	12	−3.6	12	−17.2	10	−24.0	9	−12.2
Urinary potassium, mEq/24 h
Baseline	12	38.7	9	42.5	11	49.1	9	46.4	11	44.8
Δ Day 1^a	12	+9.2	9	+9.7	11	+2.9	9	+5.2	11	+8.6
Δ Day 7^b	12	+12.8	9	+17.4*	11	+12.2	9	+6.4	11	+1.6
Δ Day 14^c	12	+20.2	12	+4.2	12	+37.6*	10	+3.7	9	+17.5

^aΔ values are comparisons of Day 1/Day 2–baseline (Day −1); ^bΔ values are comparisons of Day 7– baseline (Day −1); ^cΔ values are comparisons of Day 14– Day 7. Mean changes (last observation carried forward) were derived from an analysis of covariance model with baseline value as a covariate. Based on urinary electrolyte values obtained from placebo subjects on Day 7 and Day 14 respectively, the actual diet was ~95 ± 63 mEq Na⁺/46 ± 12 mEq K⁺ for the first week and ~86 ± 42 mEq Na⁺/69 ± 25 mEq K⁺ for the second week.
*P < 0.05, ^† P < 0.01, ^‡ P < 0.001 vs placebo.

ISSN: 1479-5876