Table 5. Pharmacokinetic parameters of OM following administration of 6 OM formulations in the fed state.
| Pharmacokinetic parameter | IR (n = 21) | MRT-F1 (n = 20) | MRT-F2 (n = 20) | MP (n = 21) | SCT-F1 (n = 22) | SCT-F2 (n = 22) |
|---|---|---|---|---|---|---|
| OM | ||||||
| AUClast (h×ng/mL) | 2,380 (433) | 2,420 (390) | 2,290 (520) | 1,620 (440) | 1,740 (492) | 2,070 (329) |
| AUC∞ (h×ng/mL) | 2,470 (464) | 2,540 (433) | 2,370 (582) | 1,690 (462) | 1,820 (529) | 2,150 (362) |
| Cmax (ng/mL) | 144 (39) | 70 (16) | 90 (20) | 50 (13) | 51 (15) | 79 (14) |
| tmax (h)a | 2.0 (1.0 – 8.0) | 6.0 (3.0 – 12.0) | 4.0 (2.0 – 8.0) | 8.0 (3.0 – 10.0) | 10.0 (4.0 – 12.0) | 6.0 (2.0 – 8.0) |
| CL/F (L/h) | 10.5 (2.0) | 10.1 (1.8) | 11.1 (2.7) | 15.9 (4.6) | 14.8 (4.3) | 12.0 (2.5) |
| t1/2,z (h) | 20.2 (3.6) | 20.6 (3.6) | 18.4 (4.6) | 19.0 (5.0) | 19.0 (3.9) | 19.5 (3.2) |
| M3 | ||||||
| Cmax (ng/mL) | 6.7 (3.0) | 4.6 (1.6) | 5.7 (1.6) | 3.5 (1.4) | 3.5 (1.5) | 5.0 (1.2) |
| AUClast (h×ng/mL) | 216 (60) | 216 (66) | 216 (59) | 146 (52) | 155 (59) | 198 (42) |
| M3:OM AUClast (h×ng/mL) | 9.2 (2.6) | 9.0 (2.5) | 9.6 (2.1) | 9.1 (2.4) | 8.9 (2.1) | 9.7 (1.8) |
| M4 | ||||||
| Cmax (ng/mL) | 2.0 (0.7) | 1.9 (0.8) | 1.9 (0.9) | 1.3 (0.6) | 1.4 (0.5) | 1.8 (0.6) |
| AUClast (h×ng/mL) | 69.2 (38.7) | 79.7 (37.7) | 59.2 (39.6) | 40.4 (30.2) | 46.6 (27.6) | 62.8 (27.6) |
| M4:OM AUClast (h×ng/mL) | 2.9 (1.6) | 3.3 (1.5) | 2.5 (1.6) | 2.4 (1.6) | 2.6 (1.3) | 3.0 (1.2) |
Data presented as mean (SD) unless otherwise specified. AUC = area under the curve; AUC∞ = AUC to infinity; AUClast = AUC to the time of last measureable concentration; CL/F = clearance; Cmax = maximum plasma concentration; IR = immediate release; MP = multiparticulate; MRT-F = matrix tablet; OM = omecamtiv mecarbil; SCT-F = swellable core tablet; t1/2z = half-life; tmax = time to reach Cmax. amedian (min–max).