Report NO9

Table of Contents

• 1 PK parameters
  • 1.1 PK Parameters of C1 plasma
    • 1.1.1 AUC_tEnd
    • 1.1.2 C_max
    • 1.1.3 C_tEnd
    • 1.1.4 t_max
    • 1.1.5 Total body clearance/F
    • 1.1.6 Vss (plasma)/F
• 2 Time profiles and residual plots
  • 2.1 Time profiles and residual plots for single IV administration
  • 2.2 Time profiles and residual plots for children_0_3y
  • 2.3 Time profiles and residual plots for children_3_6y
  • 2.4 Time profiles and residual plots for children_6_9y

1 PK parameters

1.1 PK Parameters of C1 plasma

1.1.1 AUC_tEnd

Figure 1-1: AUC_tEnd of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in logarithmic scale.

Figure 1-2: AUC_tEnd of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in linear scale.

Table 1-1: Population statistics summarizing AUC_tEnd of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y reported in [µg*h/l]

Population	N	5th pctl	25th pctl	50th pctl	75th pctl	95th pctl	Mean	SD	Geo Mean	Geo SD
single IV administration	10	8843.16	9408.69	11804.59	13514.22	16208.15	11945.12	2899.61	11645.31	1.27
children_0_3y	5	10180.61	11060.57	12511.74	16127.16	16812.38	13328.76	3096.21	13043.50	1.26
children_3_6y	5	12619.16	12676.50	12862.73	16120.44	17498.06	14421.39	2416.84	14267.25	1.18
children_6_9y	5	11633.07	13294.59	16361.30	16819.53	17066.94	14964.38	2593.43	14770.23	1.20

1.1.2 C_max

Figure 1-3: C_max of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in logarithmic scale.

Figure 1-4: C_max of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in linear scale.

Table 1-2: Population statistics summarizing C_max of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y reported in [µg/l]

Population	N	5th pctl	25th pctl	50th pctl	75th pctl	95th pctl	Mean	SD	Geo Mean	Geo SD
single IV administration	10	3302.16	3405.09	3757.09	4221.53	4473.51	3821.55	470.40	3795.86	1.13
children_0_3y	5	3106.38	3303.05	3395.22	3855.09	3948.88	3516.58	385.24	3499.75	1.12
children_3_6y	5	2812.86	2932.02	3303.99	3382.07	3415.62	3165.03	288.82	3154.20	1.10
children_6_9y	5	3124.12	3304.15	3562.26	3768.33	3921.70	3534.78	352.48	3520.56	1.11

1.1.3 C_tEnd

Figure 1-5: C_tEnd of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in logarithmic scale.

Figure 1-6: C_tEnd of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in linear scale.

Table 1-3: Population statistics summarizing C_tEnd of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y reported in [µg/l]

Population	N	5th pctl	25th pctl	50th pctl	75th pctl	95th pctl	Mean	SD	Geo Mean	Geo SD
single IV administration	10	293.81	311.03	406.87	459.20	552.40	404.54	102.70	393.41	1.28
children_0_3y	5	363.81	404.48	462.65	591.82	624.99	489.18	119.95	477.42	1.28
children_3_6y	5	479.32	481.84	482.89	617.71	664.82	547.54	93.29	541.48	1.18
children_6_9y	5	432.81	497.25	625.43	651.28	656.48	569.69	107.44	560.90	1.22

1.1.4 t_max

Figure 1-7: t_max of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in logarithmic scale.

Figure 1-8: t_max of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in linear scale.

Table 1-4: Population statistics summarizing t_max of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y reported in [h]

Population	N	5th pctl	25th pctl	50th pctl	75th pctl	95th pctl	Mean	SD	Geo Mean	Geo SD
single IV administration	10	0.05	0.05	0.05	0.05	0.05	0.05	0	0.05	1
children_0_3y	5	0.05	0.05	0.05	0.05	0.05	0.05	0	0.05	1
children_3_6y	5	0.05	0.05	0.05	0.05	0.05	0.05	0	0.05	1
children_6_9y	5	0.05	0.05	0.05	0.05	0.05	0.05	0	0.05	1

1.1.5 Total body clearance/F

Figure 1-9: Total body clearance/F of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in logarithmic scale.

Figure 1-10: Total body clearance/F of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in linear scale.

Table 1-5: Population statistics summarizing Total body clearance/F of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y reported in [ml/min/kg]

Population	N	5th pctl	25th pctl	50th pctl	75th pctl	95th pctl	Mean	SD	Geo Mean	Geo SD
single IV administration	10	0.00	0.00	0.01	0.01	0.01	0.01	0.00	0.01	1.87
children_0_3y	5	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	1.45
children_3_6y	5	0.00	0.00	0.01	0.01	0.01	0.00	0.00	0.00	1.18
children_6_9y	5	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	1.20

1.1.6 Vss (plasma)/F

Figure 1-11: Vss (plasma)/F of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in logarithmic scale.

Figure 1-12: Vss (plasma)/F of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y shown as box-whisker plot, which indicates the 5^th, 25^th, 50^th, 75^th, 95^th percentiles in linear scale.

Table 1-6: Population statistics summarizing Vss (plasma)/F of C1 plasma for single IV administration, children_0_3y, children_3_6y, children_6_9y reported in [ml/kg]

Population	N	5th pctl	25th pctl	50th pctl	75th pctl	95th pctl	Mean	SD	Geo Mean	Geo SD
single IV administration	10	1819.01	2163.69	2446.94	3208.77	3393.87	2596.60	628.35	2526.43	1.28
children_0_3y	5	1595.31	1681.41	2156.59	2466.16	2752.86	2140.50	525.87	2088.68	1.28
children_3_6y	5	1497.40	1610.20	2061.71	2069.03	2078.95	1858.31	295.18	1838.50	1.18
children_6_9y	5	1517.33	1529.82	1595.02	2005.10	2316.77	1807.77	384.74	1777.44	1.22

2 Time profiles and residual plots

2.1 Time profiles and residual plots for single IV administration

Figure 2-1: Time profiles for single IV administration. Time profiles are plotted in a linear scale.

Figure 2-2: Time profiles for single IV administration. Time profiles are plotted in a logarithmic scale.

2.2 Time profiles and residual plots for children_0_3y

Figure 2-3: Time profiles for children_0_3y. Time profiles are plotted in a linear scale.

Figure 2-4: Time profiles for children_0_3y. Time profiles are plotted in a logarithmic scale.

2.3 Time profiles and residual plots for children_3_6y

Figure 2-5: Time profiles for children_3_6y. Time profiles are plotted in a linear scale.

Figure 2-6: Time profiles for children_3_6y. Time profiles are plotted in a logarithmic scale.

2.4 Time profiles and residual plots for children_6_9y

Figure 2-7: Time profiles for children_6_9y. Time profiles are plotted in a linear scale.

Figure 2-8: Time profiles for children_6_9y. Time profiles are plotted in a logarithmic scale.