Table 3.
CHF6001 derived pharmacokinetic parameters following OD or BID administration (PK population)
| CHF6001 dose | Day | Pharmacokinetic parameter
|
|||||
|---|---|---|---|---|---|---|---|
| Cmax, pg/mL | tmax, h | AUC0–24 h or AUC0–12 h*, pg.h/mL | Weighted AUC**, pg.h/mL.µg | CL/F, mL/min | Racc | ||
|
| |||||||
| SDDPI | |||||||
| 100 µg OD (N=7) | 1 | 65.4 (28.9) | 1.5 (0.08, 2.0) | 796.3 (37.7) | |||
| 7 | 165.3 (33.8) | 1.0 (0.5, 2) | 2,304 (41.1) | 23.0 (41.1) | 723 (41.1) | 2.89 (16.6) | |
| 300 µg OD (N=8) | 1 | 178.6 (22.4) | 2.0 (1.0, 4) | 2,340 (24.5) | |||
| 7 | 410.0 (40.3) | 1.0 (1.0, 4) | 5,815 (44.7) | 19.4 (44.7) | 860 (44.7) | 2.49 (31.8) | |
| 600 µg OD (N=9) | 1 | 290.0 (22.3) | 1.5 (1.0, 6) | 4,240 (21.7) | |||
| 7 | 701.7 (24.7) | 2.0 (1.0, 4) | 10,460 (28.2) | 17.4 (28.2) | 956 (28.2) | 2.47 (20.2) | |
| 1,200 µg OD (N=9) | 1 | 628.3 (28.0) | 2.1 (2, 8) | 9,465 (26.4) | |||
| 7 | 1,689.9 (28.0) | 2.0 (1.5, 2) | 25,920 (26.6) | 21.6 (26.6) | 772 (26.6) | 2.74 (28.2) | |
| 1,600 µg OD (N=6) | 1 | 710.4 (41.5) | 2.0 (1.0, 2) | 10,640 (27.4) | |||
| 7 | 1,974.5 (29.0) | 2.0 (1.0, 2) | 29,310 (17.0) | 18.3 (17.0) | 910 (17.0) | 2.75 (16.5) | |
| MDDPI | |||||||
| 1,200 µg BID (N=9) | 1 | 547 (19.3) | 3.0 (1.0, 6) | 5,097 (22.5) | |||
| 14 | 3,652 (48.9) | 1.6 (1.0, 3) | 34,002 (50.7) | 28.3 (50.7) | 588 (50.7)a | 6.66 (38.4) | |
| 2,000 µg BID (N=9) | 1 | 928 (32.8) | 1.5 (1.5, 4) | 8,142 (34.4) | |||
| 14 | 5,447 (39.3) | 1.5 (1.0, 3) | 51,139 (39.0) | 25.6 (39.0) | 652 (39.0) | 6.28 (19.5) | |
| 2,400 µg BID (N=9) | 1 | 1,230 (33.3) | 3.0 (1.5, 4) | 11,633 (31.7) | |||
| 14 | 6,922 (34.1)a | 2.3 (1.0, 3)a | 61,909 (37.0)a | 25.8 (37.0) | 646 (37.0)a | 5.47 (36.6)a | |
Notes:
0–24 hours calculated for OD regimens and 0–12 hours calculated for BID regimens.
Calculated as AUC0–24 h divided by total daily dose for Study 1 and AUC0–12 h divided by half of the total daily dose in Study 2. Data are geometric mean (% coefficient of variation), except tmax which is median (range). PK population is defined as all subjects in the safety population who had at least one valid PK measurement and who had no major PK-related protocol deviations.
n=8.
Abbreviations: AUC0–12 h, area under the curve from administration to 12 post-dose; AUC0–24 h, area under the curve from administration to 24 hours post-dose; BID, twice daily; CL/F, clearance adjusted for absolute bioavailability; Cmax, maximum plasma concentration; MDDPI, study medication administered via multi-dose dry-powder inhaler; OD, once-daily; PK, pharmacokinetics; Racc, accumulation ratio; SDDPI, study medication administered via single-dose dry-powder inhaler; tmax, time to maximum concentration.