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 Day2a | 12 | +0.23 | 12 | −0.59 | 12 | −0.73* | 10 | −0.64 | 11 | +0.26 |
| Δ Day7b | 12 | −1.71‡ | 12 | −0.11 | 12 | −2.87‡ | 10 | +0.31 | 11 | +0.41 |
| Δ Day14c | 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 Day2a | 12 | +0.20 | 12 | +0.08 | 12 | +0.40‡ | 10 | +0.08 | 11 | 0.00 |
| Δ Day7b | 12 | +0.25‡ | 12 | +0.12* | 12 | +0.28‡ | 10 | −0.02 | 11 | −0.05 |
| Δ Day14c | 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 1a | 12 | +45.2† | 9 | +76.3‡ | 11 | +64.0‡ | 9 | +53.8‡ | 11 | +5.6 |
| Δ Day 7b | 12 | +3.6 | 9 | +44.0 | 11 | +22.2 | 9 | +16.2 | 11 | +16.7 |
| Δ Day 14c | 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 1a | 12 | +9.2 | 9 | +9.7 | 11 | +2.9 | 9 | +5.2 | 11 | +8.6 |
| Δ Day 7b | 12 | +12.8 | 9 | +17.4* | 11 | +12.2 | 9 | +6.4 | 11 | +1.6 |
| Δ Day 14c | 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.