Comparison of FVIII pharmacokinetic analyses at baseline and at end of phase 1 (week 13 after infusion of vector hFVIII(V))
. | Dose, TU . | . | . | . | . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
. | 2.8 × 107, n = 3 . | 9.2 × 107, n = 3 . | 2.2 × 108, n = 2* . | 4.4 × 108, n = 3 . | 8.8 × 108, n = 1 . | Overall, n = 12 . | ||||
| AUC† (% FVIII/h)/(IU/kg) baseline | 39 ± 21 | 40 ± 7 | 59 | 44 ± 9 | 24.7 | 43 ± 14 | ||||
| AUC, wk 13 | 47 ± 26 | 53 ± 3 | 63 | 39 ± 21 | 21.0 | 49 ± 17 | ||||
| % change from baseline‡ | 21.1 | 32.4 | 7.7 | 7.4 | -14.9 | 15.4 (P = .04)§ | ||||
| T1/2, h, baseline | 13.8 ± 3.3 | 16.9 ± 1.5 | 18.5 | 15.9 ± 2.3 | 9.3 | 15.5 ± 3.1 | ||||
| T1/2, h, wk 13 | 16.8 ± 5.2 | 23.5 ± 2.9 | 20.2 | 15.9 ± 0.6 | 11.7 | 18.4 ± 4.7 | ||||
| % change from baseline‡ | 21.9 | 38.9 | 9.3 | -0.3 | 25.8 | 18.6 (P = .02)§ | ||||
| Cmax†, % FVIII/(IU/kg) baseline | 2.1 ± 0.4 | 2.1 ± 0.3 | 2.3 ± 0.2 | 2.4 ± 0.6 | 2.3 | 2.2 ± 0.4 | ||||
| Cmax, wk 13 | 2.2 ± 0.5 | 2.5 ± 0.4 | 2.3 ± 0.3 | 2.6 ± 0.4 | 1.8 | 2.4 ± 0.4 | ||||
| % change from baseline‡ | 4.7 | 21.0 | 0.1 | 10.7 | -20.9 | 7.1 (P = .18)§ | ||||
. | Dose, TU . | . | . | . | . | . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
. | 2.8 × 107, n = 3 . | 9.2 × 107, n = 3 . | 2.2 × 108, n = 2* . | 4.4 × 108, n = 3 . | 8.8 × 108, n = 1 . | Overall, n = 12 . | ||||
| AUC† (% FVIII/h)/(IU/kg) baseline | 39 ± 21 | 40 ± 7 | 59 | 44 ± 9 | 24.7 | 43 ± 14 | ||||
| AUC, wk 13 | 47 ± 26 | 53 ± 3 | 63 | 39 ± 21 | 21.0 | 49 ± 17 | ||||
| % change from baseline‡ | 21.1 | 32.4 | 7.7 | 7.4 | -14.9 | 15.4 (P = .04)§ | ||||
| T1/2, h, baseline | 13.8 ± 3.3 | 16.9 ± 1.5 | 18.5 | 15.9 ± 2.3 | 9.3 | 15.5 ± 3.1 | ||||
| T1/2, h, wk 13 | 16.8 ± 5.2 | 23.5 ± 2.9 | 20.2 | 15.9 ± 0.6 | 11.7 | 18.4 ± 4.7 | ||||
| % change from baseline‡ | 21.9 | 38.9 | 9.3 | -0.3 | 25.8 | 18.6 (P = .02)§ | ||||
| Cmax†, % FVIII/(IU/kg) baseline | 2.1 ± 0.4 | 2.1 ± 0.3 | 2.3 ± 0.2 | 2.4 ± 0.6 | 2.3 | 2.2 ± 0.4 | ||||
| Cmax, wk 13 | 2.2 ± 0.5 | 2.5 ± 0.4 | 2.3 ± 0.3 | 2.6 ± 0.4 | 1.8 | 2.4 ± 0.4 | ||||
| % change from baseline‡ | 4.7 | 21.0 | 0.1 | 10.7 | -20.9 | 7.1 (P = .18)§ | ||||
FVIII value at one hour for subject no. 02002 was treated as an outlier.
Cmax and AUC were normalized for dose of FVIII administered in international units (IU) per kilogram (kg) of body weight.
Calculated as a percent increase from baseline. Calculations were performed prior to rounding off.
P value (2-tail) calculated using a 2-sided paired t test.