Descriptive statistics for pharmacokinetics parameters of AUC0-t AUC0-inf Cmax

The MEANS Procedure

Treat Variable N Mean Median Minimum Maximum Range Std Dev Coeff of Variation
1
AUC0_T
AUC0_INF
Cmax
30
30
30
2.997
3.029
1.205
3.071
3.088
1.235
2.416
2.466
0.581
3.317
3.330
1.631
0.901
0.864
1.051
0.251
0.242
0.246
8.358
7.994
20.446
2
AUC0_T
AUC0_INF
Cmax
30
30
30
2.994
3.023
1.146
3.057
3.092
1.212
2.247
2.271
0.475
3.433
3.441
1.495
1.186
1.170
1.020
0.258
0.250
0.233
8.612
8.281
20.303


Levene test for homogeneity of variance AUC0-t AUC0-inf Cmax

The GLM Procedure

Levene's Test for Homogeneity of AUC0_T Variance
ANOVA of Absolute Deviations from Group Means
Source DF Sum of Squares Mean Square F Value Pr > F
Treat 1 0.000581 0.000581 0.02 0.8807
Error 58 1.4828 0.0256    

Levene's Test for Homogeneity of AUC0_INF Variance
ANOVA of Absolute Deviations from Group Means
Source DF Sum of Squares Mean Square F Value Pr > F
Treat 1 0.000482 0.000482 0.02 0.8893
Error 58 1.4293 0.0246    

Levene's Test for Homogeneity of Cmax Variance
ANOVA of Absolute Deviations from Group Means
Source DF Sum of Squares Mean Square F Value Pr > F
Treat 1 0.000068 0.000068 0.00 0.9583
Error 58 1.4393 0.0248    


Levene test for homogeneity of variance AUC0-t AUC0-inf Cmax

The GLM Procedure

Level of
Treat		 N AUC0_T AUC0_INF Cmax
Mean Std Dev Mean Std Dev Mean Std Dev
1 30 2.99721767 0.25051324 3.02924723 0.24216113 1.20483802 0.24634523
2 30 2.99436099 0.25788211 3.02310097 0.25033165 1.14613410 0.23270268


Normality test for AUC0-T AUC0-inf Cmax

Obs PK Treat Test Statistics pValue Result
1 AUC0_T 1 Shapiro-Wilk 0.897 0.007 NonNormal
2 AUC0_T 2 Shapiro-Wilk 0.914 0.018 NonNormal
3 AUC0_INF 1 Shapiro-Wilk 0.893 0.006 NonNormal
4 AUC0_INF 2 Shapiro-Wilk 0.901 0.009 NonNormal
5 Cmax 1 Shapiro-Wilk 0.929 0.045 NonNormal
6 Cmax 2 Shapiro-Wilk 0.933 0.058 Normal


Studentized Residuals Test of Outlier Analysis for AUC0-T AUC0-INF Cmax

Obs subject AUCT_RATIO AUCINF_RATIO Cmax_Ratio Residuals CookD Outlier
1 1 1.1906 1.1847 1.1588 0.79223 0.04560 No
2 2 0.7304 0.7518 1.1348 -0.94455 0.05764 No
3 3 0.9553 0.9643 0.9245 -0.12068 0.00083 No
4 4 0.9499 0.9489 0.9120 -0.15508 0.00122 No
5 5 0.9097 0.9142 1.0625 -0.31663 0.00450 No
6 6 0.9835 0.9856 0.8761 -0.06117 0.00015 No
7 7 1.6950 1.6911 2.1269 2.50638 0.22008 No
8 8 0.9768 0.9804 0.9745 -0.11480 0.00041 No
9 9 0.5463 0.5619 0.6063 -1.68073 0.07768 No
10 10 1.0068 0.9885 1.0003 -0.03601 0.00003 No
11 11 0.8456 0.8528 0.9886 -0.62869 0.00874 No
12 12 1.7981 1.7540 1.7056 2.76631 0.15438 No
13 13 0.9061 0.9036 0.9310 -0.44000 0.00363 No
14 14 0.9982 0.9954 1.2138 -0.12553 0.00028 No
15 15 0.9641 0.9745 1.0317 -0.26192 0.00119 No
16 16 1.0670 1.0652 0.9286 0.09055 0.00014 No
17 17 0.9862 0.9867 0.8030 -0.21266 0.00080 No
18 18 0.9983 0.9936 1.5211 -0.18439 0.00064 No
19 19 0.4464 0.4669 0.4569 -2.17448 0.09539 No
20 20 1.2579 1.2326 1.2723 0.71610 0.01134 No
21 21 0.8376 0.8313 1.1134 -0.80748 0.01600 No
22 22 0.9628 0.9936 0.8755 -0.37347 0.00384 No
23 23 0.9705 0.9585 1.1134 -0.36181 0.00406 No
24 24 1.5444 1.5285 1.5729 1.70470 0.10181 No
25 25 1.0521 1.0576 1.0705 -0.09746 0.00038 No
26 26 1.1121 1.1601 1.2781 0.10669 0.00051 No
27 27 1.0490 1.0263 1.0236 -0.14032 0.00100 No
28 28 1.2291 1.2258 1.0134 0.51066 0.01495 No
29 29 0.9069 0.9234 1.1653 -0.70269 0.03190 No
30 30 1.3101 1.3086 1.2255 0.79073 0.04543 No


Analysis of Variance (ANOVA)for AUC0-T AUC0-INF Cmax

The GLM Procedure

Class Level Information
Class Levels Values
Subject 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Sequence 2 1 2
Per 2 1 2
Treat 2 1 2

Number of Observations Read 60
Number of Observations Used 60


Analysis of Variance (ANOVA)for AUC0-T AUC0-INF Cmax

The GLM Procedure
 
Dependent Variable: AUC0_T

Source DF Sum of Squares Mean Square F Value Pr > F
Model 31 2.65922359 0.08578141 2.20 0.0188
Error 28 1.08944078 0.03890860    
Corrected Total 59 3.74866437      

R-Square Coeff Var Root MSE AUC0_T Mean
0.709379 6.584329 0.197253 2.995789

Source DF Type I SS Mean Square F Value Pr > F
Treat 1 0.00012241 0.00012241 0.00 0.9557
Per 1 0.03165406 0.03165406 0.81 0.3748
Sequence 1 0.73998261 0.73998261 19.02 0.0002
Subject*Sequence 28 1.88746451 0.06740945 1.73 0.0760

Source DF Type III SS Mean Square F Value Pr > F
Treat 1 0.00012241 0.00012241 0.00 0.9557
Per 1 0.03165406 0.03165406 0.81 0.3748
Sequence 1 0.73998261 0.73998261 19.02 0.0002
Subject*Sequence 28 1.88746451 0.06740945 1.73 0.0760

Tests of Hypotheses Using the Type III MS for Subject*Sequence as an Error Term
Source DF Type III SS Mean Square F Value Pr > F
Sequence 1 0.73998261 0.73998261 10.98 0.0026


Analysis of Variance (ANOVA)for AUC0-T AUC0-INF Cmax

The GLM Procedure
 
Dependent Variable: AUC0_INF

Source DF Sum of Squares Mean Square F Value Pr > F
Model 31 2.50943838 0.08094963 2.25 0.0167
Error 28 1.00905876 0.03603781    
Corrected Total 59 3.51849714      

R-Square Coeff Var Root MSE AUC0_INF Mean
0.713213 6.273145 0.189836 3.026174

Source DF Type I SS Mean Square F Value Pr > F
Treat 1 0.00056665 0.00056665 0.02 0.9011
Per 1 0.02715348 0.02715348 0.75 0.3928
Sequence 1 0.69730046 0.69730046 19.35 0.0001
Subject*Sequence 28 1.78441779 0.06372921 1.77 0.0688

Source DF Type III SS Mean Square F Value Pr > F
Treat 1 0.00056665 0.00056665 0.02 0.9011
Per 1 0.02715348 0.02715348 0.75 0.3928
Sequence 1 0.69730046 0.69730046 19.35 0.0001
Subject*Sequence 28 1.78441779 0.06372921 1.77 0.0688

Tests of Hypotheses Using the Type III MS for Subject*Sequence as an Error Term
Source DF Type III SS Mean Square F Value Pr > F
Sequence 1 0.69730046 0.69730046 10.94 0.0026


Analysis of Variance (ANOVA)for AUC0-T AUC0-INF Cmax

The GLM Procedure
 
Dependent Variable: Cmax

Source DF Sum of Squares Mean Square F Value Pr > F
Model 31 2.19798105 0.07090261 1.68 0.0853
Error 28 1.18396997 0.04228464    
Corrected Total 59 3.38195103      

R-Square Coeff Var Root MSE Cmax Mean
0.649915 17.49338 0.205632 1.175486

Source DF Type I SS Mean Square F Value Pr > F
Treat 1 0.05169225 0.05169225 1.22 0.2783
Per 1 0.01436216 0.01436216 0.34 0.5647
Sequence 1 0.47100779 0.47100779 11.14 0.0024
Subject*Sequence 28 1.66091885 0.05931853 1.40 0.1879

Source DF Type III SS Mean Square F Value Pr > F
Treat 1 0.05169225 0.05169225 1.22 0.2783
Per 1 0.01436216 0.01436216 0.34 0.5647
Sequence 1 0.47100779 0.47100779 11.14 0.0024
Subject*Sequence 28 1.66091885 0.05931853 1.40 0.1879

Tests of Hypotheses Using the Type III MS for Subject*Sequence as an Error Term
Source DF Type III SS Mean Square F Value Pr > F
Sequence 1 0.47100779 0.47100779 7.94 0.0088


Analysis of Variance (ANOVA)for AUC0-T AUC0-INF Cmax

The GLM Procedure

Level of
Treat		 N AUC0_T AUC0_INF Cmax
Mean Std Dev Mean Std Dev Mean Std Dev
1 30 2.99721767 0.25051324 3.02924723 0.24216113 1.20483802 0.24634523
2 30 2.99436099 0.25788211 3.02310097 0.25033165 1.14613410 0.23270268

Level of
Per		 N AUC0_T AUC0_INF Cmax
Mean Std Dev Mean Std Dev Mean Std Dev
1 30 2.97282049 0.26786549 3.00490069 0.26160213 1.16001450 0.27846530
2 30 3.01875817 0.23753073 3.04744751 0.22793746 1.19095762 0.19642004

Level of
Sequence		 N AUC0_T AUC0_INF Cmax
Mean Std Dev Mean Std Dev Mean Std Dev
1 30 3.10684357 0.18362267 3.13397797 0.17495261 1.26408702 0.19804870
2 30 2.88473510 0.26463251 2.91837023 0.25821353 1.08688510 0.24729348


Analysis of Variance (ANOVA)for AUC0-T AUC0-INF Cmax

The GLM Procedure
Least Squares Means

Treat AUC0_T LSMEAN Standard Error H0:LSMEAN=0 H0:LSMean1=LSMean2
Pr > |t| Pr > |t|
1 2.99721767 0.03601324 <.0001 0.9557
2 2.99436099 0.03601324 <.0001  

Treat AUC0_INF LSMEAN Standard Error H0:LSMEAN=0 H0:LSMean1=LSMean2
Pr > |t| Pr > |t|
1 3.02924723 0.03465920 <.0001 0.9011
2 3.02310097 0.03465920 <.0001  

Treat Cmax LSMEAN Standard Error H0:LSMEAN=0 H0:LSMean1=LSMean2
Pr > |t| Pr > |t|
1 1.20483802 0.03754315 <.0001 0.2783
2 1.14613410 0.03754315 <.0001  


Non Parametric Analysis of Tmax

The Mixed Procedure

Model Information
Data Set WORK.EE
Dependent Variable Tmax1
Covariance Structure Diagonal
Estimation Method REML
Residual Variance Method Profile
Fixed Effects SE Method Model-Based
Degrees of Freedom Method Residual

Class Level Information
Class Levels Values
Subject 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Treat 2 1 2
Per 2 1 2
Sequence 2 1 2

Dimensions
Covariance Parameters 1
Columns in X 7
Columns in Z 0
Subjects 1
Max Obs Per Subject 60

Number of Observations
Number of Observations Read 60
Number of Observations Used 60
Number of Observations Not Used 0

Covariance Parameter Estimates
Cov Parm Estimate
Residual 0.3868

Fit Statistics
-2 Res Log Likelihood 118.0
AIC (smaller is better) 120.0
AICC (smaller is better) 120.0
BIC (smaller is better) 122.0

Type 3 Tests of Fixed Effects
Effect Num DF Den DF F Value Pr > F
Treat 1 56 0.17 0.6811
Per 1 56 0.31 0.5788
Sequence 1 56 0.17 0.6811

Estimates
Label Estimate Standard Error DF t Value Pr > |t| Alpha Lower Upper
T vs R 0.06633 0.1606 56 0.41 0.6811 0.1 -0.2023 0.3349

Least Squares Means
Effect Treat Estimate Standard Error DF t Value Pr > |t| Alpha Lower Upper
Treat 1 2.4113 0.1136 56 21.24 <.0001 0.1 2.2214 2.6013
Treat 2 2.4777 0.1136 56 21.82 <.0001 0.1 2.2877 2.6676

Differences of Least Squares Means
Effect Treat _Treat Estimate Standard Error DF t Value Pr > |t| Alpha Lower Upper
Treat 1 2 -0.06633 0.1606 56 -0.41 0.6811 0.1 -0.3349 0.2023


Schuirmann two-one sided test for AUC0-T AUC0-INF Cmax

Obs PK n T1 P1 T2 P2 TCritV
1 AUC0-T 30 4.43736 0.0001 -4.32518 0.0001 1.70113
2 AUC0-INF 30 4.67783 0.0000 -4.42704 0.0001 1.70113
3 Cmax 30 5.30839 0.0000 -3.09707 0.0022 1.70113


Confidence Interval and Geometric Mean Ratio for AUC0-T AUC0-INF Cmax

Obs PK N Geometric_Mean_Ratio Lower UPPER Confidence_Level BE_Range Assessment
1 AUC0-T 30 100.286 91.9631 109.362 90 80-125 BE
2 AUC0-INF 30 100.617 92.5672 109.366 90 80-125 BE
3 Cmax 30 106.046 96.8879 116.070 90 80-125 BE


Arithmetic Mean and Coefficient of Variation for Tmax

The MEANS Procedure

Analysis Variable : Tmax1
Treat Mean Median Coeff of Variation
1 2.411 2.330 24.525
2 2.478 2.500 25.643


Variability with Sample_Size and power For Pharmacokinetics Parameters AUC0-T AUC0-INF Cmax

Obs N PK CVintra CVinter Intraclass_Correlation Power Sample_Size
1 30 AUC0-T 19.919 11.980 0.268 92.8261 Sufficient
2 30 AUC0-INF 19.157 11.809 0.278 94.8975 Sufficient
3 30 Cmax 20.781 9.248 0.168 72.7879 Not Suffic