Table 4.
Serum PK parameters of BITS7201A for Part A: SC and IV cohorts
| Parameter | Statistics | Cohort A 30-mg SC | Cohort B 90-mg SC | Cohort C 300-mg SC | Cohort D 300-mg IV | Cohort E 750-mg IV |
|---|---|---|---|---|---|---|
| AUC0-t (day×ng/mL) | GM mean (CV%) | 110,457.2 (41.0) | 370,913.6 (41.3) | 1,207,764.9 (30.1) | 1,176,030.6 (37.3) | 3,455,348.1 (13.6) |
| AUC0-∞ (day×ng/mL) | GM mean (CV%) | 141,766.6 (35.4)a | 389,887.4 (43.5) | 1,347,765.9 (32.2) | 1,240,187.8 (38.6) | 3,793,134.2 (18.4) |
| AUC% extrap. (%) | Mean (CV%) | 11.09 (19.1)a | 4.82 (66.4) | 10.24 (53.6) | 5.12 (69.5) | 8.70 (75.1) |
| Cmax (ng/mL) | GM mean (CV%) | 2861.3 (37.2) | 9564.4 (38.1) | 39,204.9 (35.6) | 77,684.8 (29.8)b | 203,937.4 (10.3) |
| tmax (day) | Median (range) | 6.973 (3.96–13.96) | 6.961 (3.99–28.04) | 5.495 (3.96–14.02) | 0.021 (0.02–0.08)b | 0.052 (0.02–0.08) |
| kel (1/day) | Mean (CV%) | 0.02732 (7.9)a | 0.04404 (23.1) | 0.03192 (45.4) | 0.03972 (27.7) | 0.03232 (37.0) |
| t1/2 (day) | Mean (CV%) | 25.50 (8.1)a | 16.42 (22.1) | 24.40 (30.7) | 18.60 (27.0) | 23.73 (33.2) |
| CL/F (SC) or CL (IV) (L/day) | Mean (CV%) | 0.2187 (25.5)a | 0.2478 (39.2) | 0.2452 (57.3) | 0.2719 (62.2) | 0.2007 (19.1) |
| V/F (SC) or CL (IV) (L) | Mean (CV%) | 7.932 (21.0)a | 5.663 (37.7) | 7.531 (15.6) | 6.956 (55.1) | 6.562 (20.7) |
CV coefficient of variation, GM mean geometric mean, IV intravenous, SC subcutaneous
an = 5; the terminal elimination phase could not be characterized for 1 subject in Cohort A because the time spanned was less than twice the estimated t1/2
bn = 7; one subject discontinued early and was included in Cmax and tmax calculations, but was excluded from summary statistics
AUC0-t area under the concentration-time curve from time 0 to the last quantifiable concentration, AUC0-∞ AUC from time 0 to infinity, AUC% extrap AUC extrapolated to infinity as a percentage of total AUC, CL clearance (for IV doses), CL/F apparent clearance (for SC doses), Cmax maximum serum concentration, CV coefficient of variation, GM mean geometric mean, IV intravenous, kel elimination rate constant, SC subcutaneous, tmax time to maximum serum concentration, t1/2 half-life, V volume of distribution (for IV doses), V/F apparent volume of distribution (for SC doses)