Post on 19-Feb-2016
14 TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN THE TEXT
14.1 Demographic Data
14.1.1 Summary of Demographic Data
(A05000_dem_Cohort 1)
(A05000_dem_Cohort 2)
14.1.2 Study Conduct Data
14.1.2.1 Earliest and Latest Subject Visit/Contact Date
(A01100_studydates_Cohort 1)
(A01100_studydates_Cohort 2)
14.1.2.2 Subject Disposition - Treatment Phase
(A02200_disptreat_Cohort 1)
(A02200_disptreat_Cohort 2)
14.2 Pharmacokinetic Data: Summary Tables and Figures
14.2.1 Pharmacokinetic Data: Summary Figures
0
2
4
6
8
10
12
14
0 4 8 12 16 20 24Hour (hr)
Day=Day 1
Day=Day 1 Error
Day=Day 14
Day=Day 14 Error
TRT_ARM=1
Figure 1 Mean Plasma CAS Concentration vs Time Plot (CAS Alone)
0
2
4
6
8
10
12
0 4 8 12 16 20 24Hour (hr)
Day=Day 1
Day=Day 1 Error
Day=Day 14
Day=Day 14 Error
TRT_ARM=2
Figure 2 Mean Plasma CAS Concentrations vs. Time Plot (CAS + POS)
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
0 2 4 6 8 10 12Hour (hr)
Day=1
Day=1 Error
Day=14
Day=14 Error
Figure 3 Mean Plasma POS Concentration vs. Time Plot (CAS + POS)
1
2
3
4
5
11 12 13 14 15Day
TRT_ARM=1
Figure 4 Mean (SD) of Trough Plasma CAS Concentrations on Days 12-14 (Cohort 1, Treatment Arm 1)
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
11 12 13 14 15Day
TRT_ARM=2
Figure 5 Mean (SD) of Trough Plasma CAS Concentrations on Days 12-14 (Cohort 1, Treatment Arm 2)
2000
3000
4000
5000
11 12 13 14 15Day
Cohort=1
Figure 6 Mean (SD) of Trough Plasma POS Concentrations on Days 12-14 (Cohort 1, Treatment Arm 2)
Figure 7 Mean Plasma MICA Concentrations vs. Time Plot (MICA Alone)
Figure 8 Mean Plasma MICA Concentration vs. Time plot (MICA + POS)
0
500
1000
1500
2000
2500
3000
3500
4000
4500
0 2 4 6 8 10 12Hour (hr)
Day=1
Day=1 Error
Day=7
Day=7 Error
Figure 9 Mean (SD ) of Plasma POS Concentrations on Day 1 and Day 7 (Cohort 2, Treatment Arm 2)
3
4
5
6
4 5 6 7 8Day
Treatment_Arm=1
Figure 10 Mean (SD) of Trough Plasma MICA Concentrations on Days 5 -7 (Cohort 2, Treatment Arm 1)
Figure 11 Mean (SD) of Trough Plasma MICA Concentrations on Days 5 -7 (Cohort 2, Treatment Arm 2)
Figure 12 Mean (SD) of Trough Plasma POS Concentrations on Days 5 -7 (Cohort 2, Treatment Arm 2)
14.2.2 Pharmacokinetic Data: Summary Tables
Table 1 Mean and Other Descriptive Statistics of Plasma Concentrations of CAS (ug/ml)Protocol No. P04931
Subject #. Hour (hr)
0.00 1.00 1.25 1.50 2.00 3.00 4.00 5.00 6.00 8.00 12.00 16.00 20.00 24.00
N 16 16 16 16 16 16 16 16 16 16 16 15 16 16
Mean 0.0 11.8 10.5 9.1 8.0 6.7 5.9 5.3 5.5 4.8 3.4 2.5 2.1 1.7
SD 0.0 1.5 1.2 1.1 1.5 1.1 1.0 0.8 1.2 0.8 0.8 0.5 0.5 0.3
Min 0.0 10.1 8.3 6.9 5.8 5.1 4.6 3.6 3.3 3.0 1.8 1.6 1.4 1.3
Median 0.0 11.7 10.4 9.0 7.5 6.7 5.8 5.3 6.0 5.0 3.5 2.7 2.1 1.7
Max 0.0 15.0 12.7 11.2 10.9 9.3 7.6 7.2 6.9 5.9 4.6 3.6 3.1 2.4
CV% M 12.5 11.8 12.2 18.5 17.0 17.4 14.3 20.8 16.2 24.2 19.4 23.8 18.7
*M=MissingSource Data: Section 16.1.9.2.1- Table 1
Table 2 Mean and Other Descriptive Statistics of Plasma Concentrations of CAS (g/mL) versus Time (Treatment Arm 1, Day 14)Protocol No. P04931
Hour (hr)
0.00 1.00 1.25 1.50 2.00 3.00 4.00 5.00 6.00 8.00 12.00 16.00 20.00 24.00
N 16 16 16 16 16 16 16 16 16 16 16 16 16 16
Mean 1.6 9.6 9.1 7.9 7.1 6.2 5.5 5.2 5.0 4.2 3.2 2.3 1.9 1.7
SD 0.5 1.3 1.3 1.4 1.2 0.9 0.9 1.2 0.8 0.7 0.6 0.5 0.4 0.4
Min 0.7 7.6 6.8 5.4 5.0 4.7 4.2 3.5 3.9 3.2 2.2 1.5 0.7 1.1
Median 1.6 9.9 9.2 8.1 7.1 6.2 5.7 5.5 5.1 4.0 3.3 2.4 1.9 1.7
Max 2.5 11.4 11.2 9.8 8.9 7.7 6.9 7.4 6.9 5.4 4.1 2.9 2.4 2.3
CV% 27.8 13.2 14.3 17.6 16.4 15.2 15.6 22.5 16.7 16.0 19.0 21.3 22.6 20.4
Source Data: Section 16.1.9.2.1- Table 2
Table 3 Mean and Other Descriptive Statistics of Plasma Concentrations of CAS ( g/mL) versus (Treatment Arm 2, Day 1)
Protocol No. P04931Subject #. Hour (hr)
N 19 19 19 19 19 19 19 19 19 19 19 19 19 19
Mean 0.0 10.8 9.1 8.4 6.8 5.9 5.3 4.8 5.0 4.0 3.2 2.2 2.0 1.6
SD 0.0 1.1 1.4 1.3 1.2 0.8 0.9 0.9 1.1 1.0 0.8 0.4 0.5 0.4
Min 0.0 8.7 6.9 6.2 4.9 4.6 3.4 3.4 3.3 2.3 2.0 1.6 1.2 1.1
Median 0.0 11.2 9.2 8.5 6.9 6.1 5.4 4.5 4.8 4.0 3.0 2.2 2.0 1.5
Max 0.0 13.3 12.3 11.0 9.1 7.1 7.4 6.5 6.7 6.0 4.6 3.1 3.2 2.5
CV% M 10.6 15.2 15.8 18.1 13.4 16.6 18.3 21.6 25.7 24.1 19.3 26.5 26.9
*M=MissingSource Data: Section 16.1.9.2.1- Table 3
Table 4 Mean and Other Descriptive Statistics of Plasma Concentrations of CAS (g/mL) versus Time (Treatment Arm 2, Day 14)Protocol No. P04931
Subject # Hour (hr)
0.00 1.00 1.25 1.50 2.00 3.00 4.00 5.00 6.00 8.00 12.00 16.00 20.00 24.00
N 15 15 15 15 15 15 15 15 15 15 15 15 15 15
Mean 2.2 8.5 8.1 7.5 6.4 5.9 5.4 5.1 4.7 4.0 3.2 2.4 2.0 1.7
SD 2.5 1.4 1.2 1.3 1.2 1.0 1.1 0.7 0.8 0.7 0.6 0.4 0.4 0.3
Min 1.0 6.4 6.5 6.0 4.5 4.1 3.9 3.7 3.6 2.9 2.3 1.7 1.4 1.1
Median 1.6 8.0 7.7 7.0 6.2 5.8 5.5 5.1 4.7 3.9 3.3 2.4 2.1 1.7
Max 11.3 10.7 10.7 9.9 9.0 8.1 7.9 6.0 6.0 5.6 4.7 3.1 2.6 2.1
CV% 113.0 16.6 14.7 16.9 18.1 16.5 19.6 13.3 17.5 18.3 19.9 18.4 19.5 18.2
Source Data: Section 16.1.9.2.1- Table 4
Table 5 Mean and Other Descriptive Statistics of Plasma PK Parameters of CAS (Treatment Arm 1, Day 1)Protocol No. P04931
Cmax
(g/mL)
Tmax
(hr)
AUC()
(gh/mL)
N 16 16 16
Mean 11.9 1.05 96
SD 1.4 0.10 12
Min 10.1 1.00 73
Median 11.8 1.00 98
Max 15.0 1.25 117
CV% 11.9 9.6 12.7
Geometric Mean 11.8 1.04 95
Source Data: Section 16.1.9.2.1- Table 5
Table 6 Mean and Other Descriptive Statistics of Plasma PK Parameters of CAS (Treatment Arm 1 , Day 14)Protocol No. P04931
Cmax
(g/mL)
Tmax
(hr)
AUC()
(ghr/mL)
Cmin
(ug/mL)
CLss
(mL/hr)
Vss
(mL)
N 16 16 16 16 16 16
Mean 9.8 1.08 87 1.5 588 9769
SD 1.2 0.12 13 0.4 96 2192
Min 7.6 1.00 64 0.7 472 6237
Median 10.0 1.00 88 1.5 571 9298
Max 11.4 1.25 106 2.3 783 14855
CV% 12.3 11.1 15.1 27.4 16.4 22.4
Geometric Mean 9.7 1.07 86 1.4 581 9547
Source Data: Section 16.1.9.2.1- Table 6
Table 7 Mean and Other Descriptive Statistics of Plasma PK Parameters of CAS (Treatment Arm 2, Day 1)Protocol No. P04931
Cmax
(g/mL)
Tmax
(hr)AUC()
(gh/mL)
N 19 19 19
Mean 10.9 1.05 86
SD 1.1 0.13 12
Min 8.7 1.00 70
Median 11.2 1.00 83
Max 13.3 1.50 108
CV% 10.5 12.7 13.5
Geometric Mean 10.8 1.05 85
Source Data: Section 16.1.9.2.1- Table 7
Table 8 Mean and Other Descriptive Statistics of Plasma PK Parameters of CAS (Treatment Arm 2 , Day 14)Protocol No. P04931
Cmax
(g/mL)
Tmax
(hr)
AUC()
(ghr/mL)
Cmin
(ug/mL)
CLss
(mL/hr)
Vss
(mL)
N 15 15 15 15 15 15
Mean 8.8 1.05 85 1.6 603 9915
SD 1.3 0.33 14 0.3 97 1716
Min 7.3 0.00 66 1.0 455 6422
Median 8.1 1.00 87 1.6 575 10444
Max 11.3 1.50 110 2.0 758 11905
CV% 15.2 31.4 15.9 17.7 16.1 17.3
Geometric Mean 8.7 *M 84 1.5 596 9763
*M=Missing
Source Data: Section 16.1.9.2.1- Table 8
Table 9 Mean and Other Descriptive Statistics of Plasma Concentrations of POS (ng/mL) versus Time (Cohort 1, Arm 2, Day 1)
Protocol No. P04931Hour
0 1 3 4 5 6 8 12
N 19 19 19 19 19 19 19 19
Mean 0.0 26.3 309 470 616 584 554 553
SD 0.0 15.6 148 210 233 209 166 138
Min 0.0 9.9 163 197 293 255 283 260
Median 0.0 21.9 275 476 596 592 530 538
Max 0.0 60.9 707 943 1210 1160 1040 833
CV% *M 59.4 47.9 44.7 37.9 35.8 30.0 24.9
*M=Missing
Source Data: Section 16.1.9.2.1- Table 9
Table 10 Mean and Other Descriptive Statistics of Plasma Concentrations of POS (ng/mL) versus Time (Cohort 1, Arm 2, Day 14)
Protocol No. P04931Hour
0 1 3 4 5 6 8 12
N 15 15 15 15 15 15 15 15
Mean 3039 2745 3039 3196 3536 3179 2978 3088
SD 1189 1178 1007 990 1261 1223 1125 1242
Min 1500 1290 1400 1540 1920 1570 1380 1580
Median 2810 2580 3040 3230 3350 3040 2920 2930
Max 6610 6280 5700 5630 7160 6570 6310 6650
CV% 39.1 42.9 33.1 31.0 35.7 38.5 37.8 40.2
Source Data: Section 16.1.9.2.1- Table 10
Table 11 Mean and Other Descriptive Statistics of Plasma PK Parameters of POS (Cohort 1, Arm 2, Day 1)Protocol No. P04931
POS PK Parameters Cohort 1, Arm 2, Day 1
Cmax (ng/mL) Tmax (hr) AUC() (ng•hr/mL)
N 19 19 19
Mean 674 7.63 5231
SD 193 3.45 1535
Min 293 4.00 2563
Median 624 5.00 4926
Max 1210 12.0 9630
CV% 28.6 45.2 29.3
Geometric Mean 648 6.96 5031
Source Data: Section 16.1.9.2.1- Table 11
Table 12 Mean and Other Descriptive Statistics of Plasma PK Param eters of POS (Cohort 1, Arm 2, Day 14)Protocol No. P04931
Cmax (ng/mL) Tmax (hr) AUC() (ng•hr/mL)
N 15 15 15
Mean 3588 5.80 36807
SD 1251 2.60 13541
Min 1920 3.00 17900
Median 3430 5.00 36215
Max 7160 12.00 76150
CV% 34.9 44.8 36.8
Geometric Mean 3413 5.42 34820
Source Data: Section 16.1.9.2.1- Table 12
Table 13 Mean and O ther Descriptive Statistics of CAS ( g/mL) Trough Concentrations (Cohort 1, Treatment Arm 1)
Protocol No. P04931Day 12 Day 13 Day 14
N 16 16 16
Mean 1.9 1.7 1.6
SD 0.5 0.4 0.5
Min 1.1 0.7 0.7
Median 1.8 1.7 1.6
Max 2.6 2.5 2.5
CV% 25.3 26.6 27.8
Source Data: Section 16.1.9.2.1- Table 13
Table 14 Mean and O ther Descriptive Statistics of CAS ( g/mL) Trough Concentrations (Cohort 1, Treatment Arm 2)
Protocol No. P04931Day 12 Day 13 Day 14
N 15 15 15
Mean 2.0 1.7 2.2
SD 0.6 0.5 2.5
Min 1.3 1.1 1.0
Median 2.0 1.5 1.6
Max 3.1 2.6 11.3
CV% 28.4 31.5 113
Source Data: Section 16.1.9.2.1- Table 14
Table 15 Mean and O ther Descriptive Statistics of POS (ng/mL) Trough Concentrations (Cohort 1, Treatment Arm 2)
Protocol No. P04931Day
12 13 14
N 15 15 15
Mean 3023 3055 3039
SD 1240 1275 1189
Min 1270 1280 1500
Median 2940 3020 2810
Max 6500 6750 6610
CV% 41.0 41.7 39.1
Source Data: Section 16.1.9.2.1- Table 15
Table 16 Mean and Other Descriptive Statistics of Plasma MICA (g/mL) Concentrations (Treatment Arm 1, Day 1)Protocol No. P04931
Hour
0.00 1.00 1.25 1.50 2.00 3.00 4.00 5.00 6.00 8.00 12.00 16.00 20.00 24.00
N 16 16 16 16 16 16 16 16 16 16 16 16 16 16
Mean 0.00 11.62 10.41 9.58 8.64 7.80 7.25 6.73 6.29 5.57 4.46 3.51 2.83 2.52
SD 0.00 2.27 2.06 1.71 1.64 1.53 1.26 1.36 1.21 1.22 0.84 0.70 0.58 0.57
Min 0.00 7.01 5.60 5.42 4.74 4.49 4.42 3.72 3.69 2.82 2.60 1.86 1.57 1.43
Median 0.00 12.11 11.21 9.97 9.35 8.30 7.81 7.10 6.62 5.91 4.73 3.65 2.91 2.56
Max 0.00 15.10 13.22 11.60 10.80 9.66 8.60 8.30 7.73 7.03 5.61 4.26 3.64 3.35
CV% M 19.5 19.8 17.9 19.0 19.6 17.4 20.2 19.2 21.8 18.7 20.0 20.5 22.6
*M=Missing
Source Data: Section 16.1.9.2.1- Table 16
Table 17 Mean and Other Descriptive Statistics of Plasma MICA (g/mL) Concentrations (Treatment Arm 1, Day 7)Protocol No. P04931
Hour
0.00 1.00 1.25 1.50 2.00 3.00 4.00 5.00 6.00 8.00 12.00 16.00 20.00 24.00
N 15 15 15 15 15 15 15 15 15 15 15 15 15 15
Mean 4.35 15.63 14.34 13.56 12.79 11.48 10.84 9.92 9.57 8.52 7.13 5.81 4.72 4.34
SD 0.97 2.63 2.29 2.13 2.13 2.06 2.05 1.77 1.86 1.44 1.44 1.33 1.00 0.92
Min 3.06 11.52 10.27 10.00 9.42 7.93 7.79 7.26 6.88 6.40 5.49 3.90 3.30 3.29
Median 3.87 16.14 14.68 13.99 12.85 11.43 10.65 9.66 9.31 7.94 6.45 5.51 4.42 3.92
Max 5.91 19.77 17.66 16.68 15.56 14.67 13.70 12.15 12.75 10.76 9.83 8.06 6.23 5.96
CV% 22.3 16.8 16.0 15.7 16.7 17.9 18.9 17.8 19.5 16.9 20.2 22.9 21.2 21.3
Source Data: Section 16.1.9.2.1- Table 17
Table 18 Mean and other Descriptive Statistics of Plasma MICA (g/mL) Concentrations (Treatment Arm 2, Day 1)Protocol No. P04931
Hour
0 1 1.25 1.5 2 3 4 5 6 8 12 16 20 24
N 16 16 16 16 16 16 16 16 16 16 16 16 16 16
Mean 0.00 12.76 10.95 10.22 9.09 8.34 7.73 7.01 6.65 5.87 5.02 3.66 3.08 2.67
SD 0.00 1.64 1.53 1.35 1.02 1.02 1.05 0.87 0.90 0.58 0.62 0.48 0.33 0.31
Min 0.00 10.17 8.45 7.94 7.37 6.81 5.93 5.85 5.30 5.02 4.24 2.91 2.67 2.09
Median 0.00 13.15 11.01 9.96 9.02 8.31 7.74 6.93 6.52 5.71 4.88 3.58 3.02 2.65
Max 0.00 15.63 13.89 12.30 10.98 10.48 9.75 8.95 8.29 6.79 6.46 4.58 3.75 3.30
CV% M 12.9 14.0 13.2 11.3 12.2 13.6 12.5 13.5 9.8 12.3 13.0 10.7 11.5
*M=Missing
Source Data: Section 16.1.9.2.1- Table 18
Table 19 Mean and Other Descriptive Statistics of Plasma MICA (g/mL) Concentrations (Treatment Arm 2, Day 7)Protocol No. P04931
Hour
0.00 1.00 1.25 1.50 2.00 3.00 4.00 5.00 6.00 8.00 12.00 16.00 20.00 24.00
N 16 16 16 16 16 16 16 16 16 16 16 16 16 16
Mean 4.84 16.23 15.28 14.35 13.45 11.88 11.22 10.73 9.91 9.15 8.41 6.39 5.08 4.59
SD 0.61 2.34 2.34 1.76 1.89 1.78 1.67 1.63 1.66 1.30 1.26 1.13 0.66 0.62
Min 3.47 11.99 11.01 11.17 10.22 8.42 8.20 8.39 7.10 6.28 5.83 3.31 3.38 3.01
Median 4.81 16.22 15.10 13.91 13.63 11.78 11.25 10.45 9.52 9.06 8.22 6.58 5.11 4.53
Max 6.09 21.02 19.01 17.10 17.22 14.93 13.97 13.47 12.65 11.34 10.54 8.41 6.19 6.06
CV% 12.6 14.4 15.3 12.3 14.0 15.0 14.9 15.2 16.7 14.2 14.9 17.6 13.0 13.6
Source Data: Section 16.1.9.2.1- Table 19
Table 20 Mean and Other Descriptive Statistics of Plasma MICA PK Parameters (Treatment Arm 1, Day 1)Protocol No. P04931
Cmax
g/mL
Tmax
hr
AUC()
ghr/mL
N 16 16 16
Mean 11.67 1.02 116.1
SD 2.24 0.06 22.3
Min 7.01 1.00 65.0
Median 12.11 1.00 120.6
Max 15.10 1.25 141.8
CV% 19.2 6.2 19.2
Geometric Mean 11.45 1.01 113.8
Source Data: Section 16.1.9.2.1- Table 20
Table 21 Mean and Other Descriptive Statistics of Plasma MICA PK Parameters (Treatment Arm 1, Day 7)Protocol No. P04931
Cmax
g/mL
Tmax
hr
AUC()
ghr/mL
Cmin
g/mL
CLss
mL/hr
Vss
mL
N 15 15 15 15.00 15 15
Mean 15.63 1.00 182 4.25 853 18260
SD 2.63 0.00 34 0.92 161 3182
Min 11.52 1.00 137 3.06 664 13915
Median 16.14 1.00 168 3.81 894 17912
Max 19.77 1.00 226 5.63 1095 24512
CV% 16.8 0.0 18.5 21.6 19 17.4
Geometric Mean 15.41 1.00 179 4.16 839.4 18014
Source Data: Section 16.1.9.2.1- Table 21
Table 22 Mean and Other Descriptive Statistics of Plasma MICA PK Parameters (Treatment Arm 2, Day 1)Protocol No. P04931
Cmax
g/mL
Tmax
hr
AUC()
ghr/mL
N 16 16 16
Mean 12.76 1.00 124.4
SD 1.64 0.00 13.7
Min 10.17 1.00 104.8
Median 13.15 1.00 123.6
Max 15.63 1.00 152.9
CV% 12.9 0.0 11.0
Geometric Mean 12.66 1.00 123.7
Source Data: Section 16.1.9.2.1- Table 22
Table 23 Mean and Other Descriptive Statistics of Plasma MICA PK Parameters (Treatment Arm 2, Day 7)Protocol No. P04931
Cmax
g/mL
Tmax
hr
AUC()
ghr/mL
Cmin
g/mL
CLss
mL/hr
Vss
mL
N 16 16 16 16.00 16 16
Mean 16.26 1.03 197 4.57 777 16715
SD 2.35 0.09 27 0.63 118 2918
Min 11.99 1.00 135 3.01 627 11622
Median 16.34 1.00 193 4.53 777 17309
Max 21.02 1.25 239 6.06 1111 21610
CV% 14.4 8.3 13.6 13.8 15 17.5
Geometric
Mean
16.10 1.03 195 4.53 769.8 16467
Source Data: Section 16.1.9.2.1- Table 23
Table 24 Mean and O ther Descriptive Statistics of Plasma Concentrations of POS (ng/mL) versus Time (Cohort 2, Treatment Arm 2, Day 1)
Protocol No. P04931Hour
0 1 3 4 5 6 8 12
N 16 16 16 16 16 16 16 16
Mean 0.4 25.9 241.1 392.3 554.7 574.6 555.8 683.2
SD 1.4 17.9 101.7 143.7 194.8 182.0 168.8 208.1
Min 0.0 8.8 125.0 207.0 269.0 284.0 240.0 306.0
Median 0.0 18.5 206.5 369.0 571.0 533.5 559.5 671.5
Max 5.7 75.5 486.0 694.0 912.0 856.0 839.0 1110.0
CV% 400.0 69.1 42.2 36.6 35.1 31.7 30.4 30.5
Source Data: Section 16.1.9.2.1- Table 24
Table 25 Mean and O ther Des criptive Statistics of Plasma Concentrations of POS (ng/mL) versus Time (Cohort 2, Treatment Arm 2, Day 7)
Protocol No. P04931Hours
0 1 3 4 5 6 8 12
16 16 16 16 16 16 16 16
Mean 2620.6 2344.4 2593.1 2723.8 2888.1 2646.9 2604.4 2886.3
SD 1049.3 791.2 948.8 928.9 1275.7 984.6 887.4 1130.1
Min 1200.0 1040.0 1330.0 1230.0 1340.0 1190.0 1200.0 1110.0
Median 2450.0 2275.0 2300.0 2435.0 2625.0 2455.0 2530.0 2725.0
Max 5630.0 4080.0 4870.0 4460.0 6750.0 5280.0 4500.0 5500.0
CV% 40.0 33.7 36.6 34.1 44.2 37.2 34.1 39.2
Source Data: Section 16.1.9.2.1- Table 25
Table 26 Mean and Other Descriptive Statistics of POS PK Parameters (Cohort 2, Treatment Arm 2, Day 1)Protocol No. P04931
Cmax (ng/mL) Tmax (hr) AUC() (ng•hr/mL)
N 16 16 16
Mean 734 8.75 5243
SD 209 3.44 1416
Min 306 5.00 2453
Median 764.5 10.0 4952
Max 1110 12.0 7379
CV% 28.5 39.3 27.0
Geometric Mean 701 8.07 5043
Source Data: Section 16.1.9.2.1- Table 26
Table 27 Mean and Other Descriptive Statistics of POS PK Parameters (Cohort 2, Treatment Arm 2, Day 7)Protocol No. P04931
Cmax Tmax AUC()
(ng/mL) (hr) (ng•hr/mL)
N 16 16 16
Mean 3153 7.6 31884
SD 1320 4.2 11389
Min 1340 0.0 14330
Median 2740 5.0 29808
Max 6750 12.0 59870
CV% 41.9 54.6 35.7
Geometric Mean 2927 M 30050
*M=Missing
Source Data: Section 16.1.9.2.1- Table 27
Table 28 Mean and O ther Descriptive Stat istics of Trough MICA Plasma Concentrations ( g/mL) ( Cohort 2, Treatment Arm 1)
Protocol No. P04931Day
5 6 7
N 16.00 16.00 16.00
Mean 4.23 4.27 4.82
SD 0.58 0.49 0.68
Min 3.20 3.35 3.74
Median 4.30 4.18 5.01
Max 4.93 5.00 5.91
CV% 13.71 11.47 14.18
Source Data: Section 16.1.9.2.1- Table 28
Table 29 Mean and O ther Descriptive Statistics of Trough MICA Plasma Concentrations ( g/mL) ( Cohort 2, Treatment Arm 2)
Protocol No. P04931Day
5 6 7
N 15.00 15.00 15.00
Mean 4.19 4.30 4.37
SD 0.99 0.88 0.93
Min 2.79 3.19 3.06
Median 4.30 4.25 4.28
Max 6.43 5.92 6.09
CV% 23.61 20.48 21.17
Source Data: Section 16.1.9.2.1- Table 29
Table 30 Mean and O ther Descriptive Statistics of Plasma Trough Concentrations (ng/mL) of POS (Cohort 2, Treatment Arm 2)
Protocol No. P04931Day
5 6 7
N 16 16 16
Mean 2374 2427 2621
SD 769 815 1049
Min 1220 1130 1200
Median 2345 2450 2450
Max 4100 4190 5630
CV% 32.4 33.6 40.0
Source Data: Section 16.1.9.2.1- Table 30
14.3 Safety Data
14.3.1 Displays of Adverse Events
14.3.1.1 Summary of Treatment-Emergent Adverse Events
(B01000_ae_Cohort 1)
(B01000_ae_Cohort 2)