22 1.0 (0.0)
9 1.0 (0.1)
108
No. of Subjects 13 9 3 1 15
Day 2 Mean (SD)
No. of Events 1.2 (0.6)
41 1.3 (0.5)
12 1.0 (0.0)
3 1.0 (-)
1 1.2 (0.5)
26
No. of Subjects 12 6 - 2 10
Day 3 Mean (SD)
No. of Events 1.5 (0.8)
25 1.4 (0.7)
9 -
- 1.0 (0.0)
3 1.2 (0.4)
18
14.2Prevention of Excessive Bleeding During and After Surgery in VWD
Two prospective, open-label, non-controlled, multicenter clinical studies, one in the US and one in Europe, investigated the safety and hemostatic efficacy of Humate-P in subjects with VWD undergoing surgery.
• US clinical study – The primary objective of this study was to demonstrate the safety and hemostatic efficacy of Humate-P in preventing excessive bleeding in adult and pediatric subjects with VWD undergoing surgery. The 35 subjects (21 female and 14 male) ranged in age from 3 to 75 years (mean 32.9); seven were age 15 or younger and two were age 65 or older. Twelve subjects had type 1 VWD, two had type 2A, three had type 2B, five had type 2M, and 13 had type 3. Twenty-eight of the surgical procedures were classified as major (e.g., orthopedic joint replacement, intracranial surgery, multiple tooth extractions, laparoscopic cholecystectomy), four as minor (e.g., placement of intravenous access device), and three subjects had oral surgery3. Seven of the 13 subjects with type 3 VWD had major surgery.
The first 15 subjects received a loading dose of Humate-P corresponding to 1.5 times the "full dose" (defined as the dose predicted to achieve a peak VWF:RCo level of 100 International Units (IU)/dL as determined by each subject's calculated IVR and baseline VWF:RCo level); the loading dose did not vary with the type of surgery performed (i.e., major, minor, or oral). The remaining 20 subjects were dosed based on individual pharmacokinetic assessments and target peak VWF:RCo levels of 80 to 100 International Units (IU)/dL for major surgery and 50 to 60 International Units (IU)/dL for minor or oral surgery, respectively. All 35 subjects received initial maintenance doses corresponding to 0.5 times the full dose at intervals of 6, 8, or 12 hours after surgery as determined by their individual half-lives for VWF:RCo; subsequent maintenance doses were adjusted based on regular measurements of trough VWF:RCo and FVIII:C levels. The median duration of treatment was 1 day (range: 1 to 2 days) for oral surgery, 5 days (range: 3 to 7 days) for minor surgery, and 5.5 days (range: 2 to 26 days) for major surgery.
• European clinical study –The primary objective of this study was to assess the ability of Humate-P to effectively correct the coagulation defect in subjects with VWD undergoing elective surgery, as demonstrated by an increase in VWF:RCo and FVIII, a shortening of the prolonged bleeding time, and the prevention and/or cessation of excessive bleeding. This study did not have a pre-stated hypothesis to eva luate hemostatic efficacy. The 27 subjects (18 females and nine males) ranged in age from 5 to 81 years (median age: 46 years); one was age 5, and five were older than 65. Ten subjects had type 1 VWD, nine had type 2A, one had type 2M, and seven had type 3. Sixteen of the surgical procedures were classified as major (orthopedic joint replacement, hysterectomy, multiple tooth extractions, laparoscopic adnexectomy, laparoscopic cholecystectomy, and basal cell carcinoma excision). Six of the seven subjects with type 3 VWD had major surgery.
Dosing was individualized based on a pha |
