Pharmacokinetic properties of Privigen^® in Japanese patients with primary immunodeficiency

Figures & data

Figure 1. Study overview. ^aSampling period for 3-weekly dosing regimen: sampling points included −60 minutes to −1 minute prior to infusion, 3–20 minutes post infusion, 24 ± 2 h, 3 ± 1 days, 7 ± 1 days, 10 ± 1 days, 14 ± 1 days, 21 ± 1 days post infusion; ^bsampling period for 4-weekly dosing regimen: sampling points were the same as for 3-weekly regimen^a plus 28 ± 2 days post infusion. IgG: immunoglobulin G; PK: pharmacokinetic.

Table 1. Baseline demographic characteristics of patients (PKAS).

Parameter	Privigen^® (N = 10)
Age, years
Mean (SD)	31.1 (16.9)
Median (range)	30.0 (9.0, 67.0)
Age categories, n (%)
2 to 11 years	1.0 (10.0)
12 to 17 years	0.0
18 to 64 years	8.0 (80.0)
65 to 84 years	1.0 (10.0)
Gender, n (%)
Female	2.0 (20.0)
Male	8.0 (80.0)
Race, n (%)
Japanese	10.0 (100.0)
Weight at Day 1,^a kg
Mean (SD)	60.3 (13.8)
Median (range)	62.1 (27.5, 78.9)
BMI, kg/m^2
Mean (SD)	22.1 (3.2)
Median (range)	21.4 (16.3, 28.3)
PID, n (%)
CVID	3.0 (30.0)
XLA	6.0 (60.0)
Other immunodeficiency	1.0 (10.0)
IgG level at time of first PID diagnosis,^b g/L
Mean (SD)	0.9 (1.1)
Median (range)	0.6 (0.1, 3.4)
Pre-study IgG trough level, g/L
Mean (SD)	8.9 (4.1)
Median (range)	7.5 (5.2, 18.4)

BMI: body mass index; CVID: common variable immunodeficiency; IgG: immunoglobulin G; PID: primary immunodeficiency; PKAS: pharmacokinetic analysis set; SD: standard deviation; XLA: X-linked agammaglobulinemia.

^a If weight on Day 1 was missing, the assessment at Screening is used

^b n = 8.

Table 2. Serum IgG PK parameters by dosing regimen (PKAS).

PK parameter	Privigen^® (N = 10)
	3-weekly infusions	4-weekly infusions
	(N = 2)	(N = 8)
AUC0–last (g*h/L)
Mean (SD)	5971 (NR)	6591 (2633)
Geometric mean (CV%)	5891 (NR)	6239 (34.50)
95% CI for the geometric mean	NR	4713–8258
Cmax (g/L)
Mean (SD)	16.60 (NR)	14.20 (5.53)
Geometric mean (CV%)	16.40 (NR)	13.40 (36.40)
95% CI for the geometric mean	NR	9.98–18.0
Cmin (g/L)
Mean (SD)	10.60 (NR)	8.53 (3.89)
Geometric mean (CV%)	10.30 (NR)	7.98 (37.40)
95% CI for the geometric mean	NR	5.90–10.80
Ctrough (g/L)
Mean (SD)	10.05 (NR)	7.96 (3.78)
Geometric mean (CV%)	9.89 (NR)	7.40 (38.92)
95% CI for the geometric mean	NR	5.41–10.14
CL (mL/h)
Mean (SD)	2.53 (NR)	2.53 (1.00)
Geometric mean (CV%)	2.49 (NR)	2.36 (42.20)
95% CI for the geometric mean	NR	1.68–3.31
dAUC (g*h/L/mg)^a
Mean (SD)	0.41 (NR)	0.46 (0.19)
Geometric mean (CV%)	0.40 (NR)	0.42 (42.20)
95% CI for the geometric mean	NR	0.30–0.59
Tmax (h)
Median	1.19	1.14
Min, Max	0.92, 1.47	0.62, 23.37

AUC_0–last: area under the concentration-time curve from time point zero to the last quantifiable time point; CI: confidence interval; CL: clearance; C_max: maximum serum IgG concentration; C_min: minimum serum IgG concentration; C_trough: trough IgG level prior to the next infusion during the wash-in/wash-out phase; CV: coefficient of variation; dAUC: dose-adjusted AUC_0–last; IgG: immunoglobulin G; NR: not reliable; PK: pharmacokinetic; PKAS: pharmacokinetic analysis set; SD: standard deviation; T_max: time to reach C_max.

PK parameters or statistics which could not be determined due to low number of patients (n = 2) are identified in the table by NR.

^a AUC values are dose-normalized on a per mg dose basis.

Figure 2. Mean (SD) serum IgG concentration-time data by dosing regimen (PKAS). The first two time points (60–1 minutes prior to infusion and 3–20 minutes post infusion) are presented on a different scale. Profiles are shifted for ease of comparison. IgG: immunoglobulin G; PKAS: pharmacokinetic analysis set; SD: standard deviation.