an terminal half-life of VWF:RCo (range) 11 hours*
(3.5-33.6) 10 hours†
(2.8-28.3)
Median clearance (range) 3.1 mL/hr/kg
(1-16.6) 4.8 mL/hr/kg
(2.1-53)
Volume of distribution at steady state (range) 53 mL/kg
(29-141) 59 mL/kg
(32-290)
Median IVR for VWF:RCo activity (range) 2.4 IU/dL per IU/kg
(1.1-4.2) 1.9 IU/dL per IU/kg
(0.6-4.5)
The multimeric patterns of Humate-P in the US study, were measured in 13 subjects with type 3 VWD; 11 had absent or barely detectable multimers at baseline. Of those 11 subjects, all had some high molecular weight multimers present 24 hours after infusion of Humate-P. In the European study, infusion of Humate-P corrected the defect of the multimer pattern in subjects with types 2A and 3 VWD. High molecular weight multimers were detectable until at least 8 hours after infusion.
Based on the small sample size eva luation, it appears that age, sex, and type of VWD have no impact on the pharmacokinetics of VWF:RCo.
14CLINICAL STUDIES
Controlled clinical studies to eva luate the safety and efficacy of prophylactic dosing with Humate-P to prevent spontaneous bleeding have not been conducted in VWD subjects. Adequate data are not presently available on which to eva luate or to base dosing recommendations in this setting.
14.1Treatment of Bleeding Episodes in VWD
Clinical efficacy of Humate-P in the control of bleeding in subjects with VWD was determined by a retrospective review of clinical safety and efficacy data obtained from 97 Canadian VWD subjects who received product under an Emergency Drug Release Program. The dosage schedule and duration of therapy were determined by the medical practitioner.
There were 514 requests for product use for surgery, bleeding, or prophylaxis in the 97 subjects. Of these, Humate-P was not used in 151 cases, and follow-up safety and/or efficacy information was available for 303 (83%) of the remaining 363 requests. In many cases, Humate-P from a single request was used for several treatment courses in one subject. Therefore, there are more reported treatment courses than requests.
Humate-P was administered to 97 subjects in 530 treatment courses: 73 for surgery, 344 for treatment of bleeding, and 20 for prophylaxis of bleeding. The majority of the 93 "other" uses involved dental procedures, diagnostic procedures, prophylaxis prior to a procedure, or test doses.
Table 9 summarizes the dosing information (all subjects) for bleeding episodes.
Table 9: Dosing Information for Bleeding Episodes in VWD Type/Location of Bleeding Episode
Digestive System Nose+Mouth
+Pharynx Integument System Female
Genital System Musculo-skeletal
SD, standard deviation.
*
IU VWF:RCo/kg.
†
Number of infusions where the dose per kg body weight was available.
‡
Day 1, first treatment day.
No. of Subjects 14 29 11 4 22
Loading Dose Mean Dose (SD)* 62.1 (31.1) 66.9 (24.3) 73.4 (37.7) 88.5 (28.3) 50.2 (24.9)
No. of Infusions† 37 127 22 7 107
Maintenance Dose Mean Dose (SD)* 61.5 (38.0) 67.5 (22.4) 56.5 (63.3) 74.5 (17.7) 63.8 (28.8)
No. of Infusions† 250 55 4 15 121
No. of Treatment Days per Bleeding Episode Mean (SD)
No. of Events 4.6 (3.6)
49 1.4 (1.2)
130 1.1 (0.4)
22 2.8 (2.9)
9 2.0 (1.9)
108
No. of Infusions by Treatment Day
No. of Subjects 14 29 11 4 22
Day 1‡ Mean (SD)
No. of Events 1.2 (0.4)
49 1.1 (0.2)
130 1.0 (0.2)
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