Table 1.
Dosing scheme and pharmacokinetics parameters of tirasemtiv (Part A).
| Treatment periods* | 20 mg† | 40 mg† | 80 mg† | 160 mg† | 320 mg† | 640 mg† | 1000 mg† | 1250 mg† | 640 mg‡ | 1000 mg‡ | 1500 mg‡ | 2000 mg‡ | 2500 mg‡ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cohort 1 | X | X | |||||||||||
| Cohort 2 | X | X | |||||||||||
| Cohort 3 | X | X | |||||||||||
| Cohort 4 | X | X | |||||||||||
| Cohort 5 | X | X | |||||||||||
| Cohort 6 | X | X | |||||||||||
| Cohort 7 | X | ||||||||||||
| Pharmacokinetics parameters (mean ± SEM) | |||||||||||||
| Cmax (µg/ml) | 0.55 ± 0.13 | 1.27 ± 0.22 | 1.40 ± 0.23 | 4.08 ± 0.79 | 7.16 ± 2.51 | 7.80 ± 1.54 | 14.1 ± 6.45 | 12.7 ± 1.12 | 14.0 ± 2.68 | 20.7 ± 1.50 | 20.5 ± 2.77 | 29.2 ± 3.79 | 24.6 ± 2.97 |
| AUC24h (h/µg/ml) | 6.26 ± 2.61 | 16.7 ± 2.88 | 20.2 ± 4.52 | 65.7 ± 11.9 | 114 ± 39.9 | 136 ± 24.2 | 237 ± 102 | 232 ± 12.9 | 196 ± 20.7 | 305 ± 29.5 | 309 ± 15.5 | 463 ± 60.1 | 420 ± 30.9 |
| tmax (h) | 4.50 ± 0.54 | 4.83 ± 0.41 | 5.66 ± 2.16 | 5.83 ± 2.04 | 4.50 ± 0.54 | 11.8 ± 6.40 | 12.8 ± 8.73 | 11.5 ± 1.11 | 4.83 ± 0.75 | 4.50 ± 1.51 | 5.33 ± 2.34 | 5.80 ± 2.38 | 6.67 ± 2.58 |
*
Eight subjects per cohort were assigned randomly to placebo (n = 2) or active (n = 6) treatments; 1 subject in cohort 6 withdrew consent and was replaced. All other subjects completed the indicated dosing period.
†
Doses were administered as solid in capsule with a matched placebo.
‡
Doses were administered as a suspension in OraBlend with a matched placebo.