Table 6. The food effect on the pharmacokinetic parameters of omecamtiv mecarbil following administration of 6 formulations.
| IR | MRT-F1 | MRT-F2 | MP | SCT-F1 | SCT-F2 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fasting (n = 20) |
Fed (n = 21) |
Fasting (n = 21) |
Fed (n = 20) |
Fasting (n = 20) |
Fed (n = 20) |
Fasting (n = 19) |
Fed (n = 21) |
Fasting (n = 21) |
Fed (n = 22) |
Fasting (n = 21) |
Fed (n = 22) |
|
| AUClast LSGM | 2,372 | 2,351 | 1,855 | 2,256 | 2,097 | 2,343 | 1,492 | 1,571 | 1,331 | 1,719 | 1,950 | 2,094 |
| NF/fasting (90% CI) | 0.99 (0.93 – 1.05) | 1.22 (1.14 – 1.29) | 1.12 (1.05 – 1.19) | 1.05 (0.99 – 1.12) | 1.29 (1.22 – 1.37) | 1.07 (1.01 – 1.14) | ||||||
| AUC∞ LSGM | 2,473 | 2,447 | 1,937 | 2,346 | 2,191 | 2,422 | 1,564 | 1,648 | 1,400 | 1,807 | 2,024 | 2,169 |
| Fed/fasting (90% CI) | 0.99 (0.93 – 1.05) | 1.21 (1.14 – 1.29) | 1.11 (1.04 – 1.17) | 1.05 (0.99 – 1.12) | 1.29 (1.22 – 1.37) | 1.07 (1.01 – 1.14) | ||||||
| Cmax LSGM | 253 | 139 | 55.1 | 65.5 | 76.8 | 88.9 | 57.8 | 48.3 | 33.1 | 50.1 | 62.3 | 81.1 |
| Fed/fasting (90% CI) | 0.55 (0.49 – 0.62) | 1.19 (1.06 – 1.33) | 1.16 (1.03 – 1.29) | 0.84 (0.75 – 0.94) | 1.51 (1.36 – 1.69) | 1.30 (1.17 – 1.45) | ||||||
| tmax | 0.5 | 2.0 | 3.0 | 6.0 | 2.0 | 4.0 | 4.0 | 8.0 | 10.0 | 10.0 | 6.0 | 6.0 |
| Median p-valuea | < 0.0001 | 0.0184 | 0.0116 | 0.0002 | 0.0522 | 0.3173 | ||||||
AUC = area under the curve; AUC∞ = AUC to infinity; AUClast = AUC to the time of last measureable concentration; CI = confidence interval; Cmax = maximum plasma concentration; IR = immediate-release tablet; LSGM = least squares geometric mean; MP = multiparticulate; MRT-F = matrix tablet; NF = nonfasting; SCT-F = swallowable core tablet; tmax = time to reach Cmax. ap value represents the difference in medians between fasting and nonfasting.