Table 4. Pharmacokinetic parameters of OM following administration of 6 formulations in the fasting state.
| Pharmacokinetic parameter | IR (n = 20) | MRT-F1 (n = 21) | MRT-F2 (n = 20) | MP (n = 19) | SCT-F1 (n = 21) | SCT-F2 (n = 21) |
|---|---|---|---|---|---|---|
| OM | ||||||
| AUClast (h×ng/mL) | 2,390 (385) | 2,030 (432) | 2,080 (623) | 1,520 (284) | 1,390 (489) | 1,970 (436) |
| AUC∞ (h×ng/mL) | 2,490 (432) | 2,150 (489) | 2,170 (663) | 1,590 (310) | 1,470 (541) | 2,060 (483) |
| Cmax (ng/mL) | 262 (81) | 60 (17) | 78 (23) | 61 (21) | 34 (10) | 62 (16) |
| tmax (h)a | 0.5 (0.5 – 1.0) | 3.0 (1.0 – 12.0) | 2.0 (1.0 – 10.0) | 4.0 (1.0 – 6.0) | 10.0 (4.0 – 25.0)* | 6.0 (2.0 – 10.0)* |
| CL/F (L/h) | 10.3 (1.7) | 12.3 (3.0) | 12.5 (3.7) | 16.4 (4.3) | 19.2 (6.5) | 12.9 (3.4) |
| t1/2,z (h) | 19.6 (4.2) | 21.4 (3.4) | 18.5 (4.8) | 20.0 (4.4) | 19.7 (4.4) | 20.5 (3.8) |
| Frel to IR (AUC∞)b | – | 0.79 (0.72 – 0.86) | 0.87 (0.80 – 0.95) | 0.64 (0.58 – 0.70) | 0.58 (0.53 – 0.63) | 0.82 (0.75 – 0.90) |
| M3 | ||||||
| Cmax (ng/mL) | 7.5 (2.2) | 3.9 (1.1) | 5.1 (1.5) | 4.7 (3.4) | 2.5 (0.8) | 4.2 (1.1) |
| AUClast (h×ng/mL) | 217 (53) | 186 (61) | 196 (61) | 144 (40) | 120 (55) | 185 (36) |
| M3:OM AUClast (h×ng/mL) | 9.1 (1.8) | 9.1 (2.3) | 9.7 (2.4) | 9.5 (2.1) | 8.5 (2.1) | 9.7 (2.0) |
| M4 | ||||||
| Cmax (ng/mL) | 2.4 (0.9) | 1.6 (0.6) | 1.7 (0.8) | 1.4 (0.6) | 1.0 (0.3) | 1.6 (0.7) |
| AUClast (h×ng/mL) | 70.7 (37.8) | 65.6 (35.6) | 57.7 (36.6) | 43.4 (28.6) | 32.6 (21.4) | 61.0 (35.1) |
| M4:OM AUClast (h×ng/mL) | 3.0 (1.6) | 3.1 (1.4) | 2.7 (1.5) | 2.7 (1.8) | 2.1 (1.2) | 3.1 (1.6) |
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; CI = confidence interval; CL/F = clearance; Cmax = maximum plasma concentration; Frel = relative bioavailability; IR = immediate release; MP = multiparticulate; MRT-F = matrix tablet; OM = omecamtiv mecarbil; SCT-F = swallowable core tablet; tmax = time to reach Cmax; t1/2z = half-life; tmax = time to reach Cmax. *p < 0.046 vs. IR; analyzed using a mixed-effect model, with treatment, study period, and sequence as fixed effects, and subject with in each sequence as a random effect. amedian (min – max); bgeometric mean (90% CI).