This example assumes a design in which the applicant-defined protocol specifies the following information. All subjects are to be screened for 7 days prior to randomization into 6 protocol groups:

  • Group 1 is a control group of 20 subjects, 10 male and 10 female, dosed with vehicle once per day for 28 days.
  • Group 2 is a low-dose group of 20 subjects, 10 male and 10 female, dosed at 100 mg/kg with compound A once per day for 14 days and 100 mg/kg with compound B once per day for 14 days.
  • Group 3 is a high-dose group of 20 subjects, 10 male and 10 female, dosed at 500 mg/kg with compound A once per day for 14 days and 500 mg/kg with compound B once per day for 14 days.
  • Group 4 is a control group of 6 subjects, 3 male and 3 female, dosed with vehicle once per day for 28 days. This group will be subjected to blood sampling for the purpose of TK analysis, with samples taken on days 14, 21, and 28.
  • Group 5 is a low-dose group of 6 subjects, 3 male and 3 female, dosed at 100 mg/kg with compound A once per day for 14 days and 100 mg/kg with compound B once per day for 14 days. This group will be subjected to blood sampling for the purpose of toxicokinetic (TK) analysis, with samples taken on days 14, 21, and 28.
  • Group 6 is a high-dose group of 6 subjects, 3 male and 3 female, dosed at 500 mg/kg with compound A once per day for 14 days and 500 mg/kg with compound B once per day for 14 days. This group will be subjected to blood sampling for the purpose of TK analysis, with samples taken on days 14, 21, and 28.
Group
Number		Group LabelDose LevelNumber of Animals (both sexes combined)
Non-ToxicokineticToxicokinetic
1Group 1, ControlVehicle Control20-
2Group 2, 100 mg/kg A, B100 mg/kg/day A, B20-
3Group 3, 500 mg/kg A, B500 mg/kg/day A, B20-
4Group 4, ControlVehicle Control-6
5Group 5, 100 mg/kg A, B100 mg/kg/day A, B-6
6Group 6, 500 mg/kg A, B500 mg/kg/day A, B-6

There are no other experimental factors of interest specified in the study design.

Figure. Example Trial 3 Design
 

Trial Elements

The TK blood collection has no effect on the structure of the dosing elements.

te.xpt

te.xpt

RowSTUDYIDDOMAINETCDELEMENTTESTRLTEENRLTEDUR
1TDM3TESCRNScreenStart of Preexposure1 week after start of ElementP7D
2TDM3TETRT01Vehicle ControlFirst day of dosing with vehicle control28 days after start of ElementP28D
3TDM3TETRT02A100 mg/kg Compound A, once dailyFirst day of dosing with 100 mg/kg Compound A14 days after start of ElementP14D
4TDM3TETRT02B100 mg/kg Compound B, once dailyFirst day of dosing with 100 mg/kg Compound B14 days after start of ElementP14D
5TDM3TETRT03A500 mg/kg Compound A, once dailyFirst day of dosing with 500 mg/kg Compound A14 days after start of ElementP14D
6TDM3TETRT03B500 mg/kg Compound B, once dailyFirst day of dosing with 500 mg/kg Compound B14 days after start of ElementP14D
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Trial Arms

There are 3 trial arms on this study. The fact that some subjects are being selected for blood sampling is an experimental factor that is separate from the dosing; see the TS example. The applicant-defined protocol group numbering is also not addressed in the TA domain. Therefore, the TA dataset for this design is similar to that for Example 1, although the "branching" rule differs, due to the randomization procedure employed. In this case, the applicant considers all exposure elements for the study to be part of a single exposure epoch.

ta.xpt

ta.xpt

RowSTUDYIDDOMAINARMCDARMTAETORDETCDELEMENTTABRANCHEPOCH
1TDM3TA1Control1SCRNScreenRandomized to Group 1 or Group 4PRE-EXPOSURE
2TDM3TA1Control2TRT01Vehicle Control
EXPOSURE
3TDM3TA2100 mg/kg1SCRNScreenRandomized to Group 2 or Group 5PRE-EXPOSURE
4TDM3TA2100 mg/kg2TRT02A100 mg/kg Compound A, once daily
EXPOSURE
5TDM3TA2100 mg/kg3TRT02B100 mg/kg Compound B, once daily
EXPOSURE
6TDM3TA3500 mg/kg1SCRNScreenRandomized to Group 3 or Group 5PRE-EXPOSURE
7TDM3TA3500 mg/kg2TRT03A500 mg/kg Compound A, once daily
EXPOSURE
8TDM3TA3500 mg/kg3TRT03B500 mg/kg Compound B, once daily
EXPOSURE
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Trial Sets

In this case, there are 6 trial sets, corresponding to the following experimental factors: dosing level (3 separate dose levels) and whether the subjects will be used for TK analysis.

The applicant has chosen to provide the associated arm code, applicant-defined group code, group label, set label, dose level and units, control type, toxicokinetic description, and planned number of males and females for each set.

tx.xpt

tx.xpt

RowSTUDYIDDOMAINSETCDSETTXSEQTXPARMCDTXPARMTXVAL
1TDM3TX1Control Group, Vehicle Control, once daily1ARMCDArm Code1
2TDM3TX1Control Group, Vehicle Control, once daily2SPGRPCDApplicant-Defined Group Code1
3TDM3TX1Control Group, Vehicle Control, once daily3GRPLBLGroup LabelGroup 1, Control
3TDM3TX1Control Group, Vehicle Control, once daily4SETLBLSet LabelGroup 1, Control
4TDM3TX1Control Group, Vehicle Control, once daily5TRTDOSDose Level0
5TDM3TX1Control Group, Vehicle Control, once daily6TRTDOSUDose Unitsmg/kg/day
6TDM3TX1Control Group, Vehicle Control, once daily7TCNTRLControl TypeVEHICLE CONTROL
7TDM3TX1Control Group, Vehicle Control, once daily8TKDESCToxicokinetic DescriptionNON-TK
8TDM3TX1Control Group, Vehicle Control, once daily9PLANMSUBPlanned Number of Male Subjects10
9TDM3TX1Control Group, Vehicle Control, once daily10PLANFSUBPlanned Number of Female Subjects10
10TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily11ARMCDArm Code2
11TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily12SPGRPCDApplicant-Defined Group Code2
12TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily13GRPLBLGroup LabelGroup 2, 100 mg/kg A, B
13TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily14SETLBLSet LabelGroup 2, 100 mg/kg/day
14TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily15TRTDOSDose Level100
15TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily16TRTDOSUDose Unitsmg/kg/day
16TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily17TKDESCToxicokinetic DescriptionNON-TK
17TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily18PLANMSUBPlanned Number of Male Subjects10
18TDM3TX2Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily19PLANFSUBPlanned Number of Female Subjects10
19TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily20ARMCDArm Code3
20TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily21SPGRPCDApplicant-Defined Group Code3
21TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily22GRPLBLGroup LabelGroup 3, 500 mg/kg A, B
22TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily23SETLBLSet LabelGroup 3, 500 mg/kg/day
23TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily24TRTDOSDose Level500
24TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily25TRTDOSUDose Unitsmg/kg/day
25TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily26TKDESCToxicokinetic DescriptionNON-TK
26TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily27PLANMSUBPlanned Number of Male Subjects10
27TDM3TX3High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily28PLANFSUBPlanned Number of Female Subjects10
28TDM3TX4Control Group, Vehicle Control once daily, TK29ARMCDArm Code1
29TDM3TX4Control Group, Vehicle Control once daily, TK30SPGRPCDApplicant-Defined Group Code4
30TDM3TX4Control Group, Vehicle Control once daily, TK31GRPLBLGroup LabelGroup 4, Control
31TDM3TX4Control Group, Vehicle Control once daily, TK32SETLBLSet LabelGroup 4, Control - TK
32TDM3TX4Control Group, Vehicle Control once daily, TK33TRTDOSDose Level0
33TDM3TX4Control Group, Vehicle Control once daily, TK34TRTDOSUDose Unitsmg/kg/day
34TDM3TX4Control Group, Vehicle Control once daily, TK35TCNTRLControl TypeVEHICLE CONTROL
35TDM3TX4Control Group, Vehicle Control once daily, TK36TKDESCToxicokinetic DescriptionTK
36TDM3TX4Control Group, Vehicle Control once daily, TK37PLANMSUBPlanned Number of Male Subjects3
37TDM3TX4Control Group, Vehicle Control once daily, TK38PLANFSUBPlanned Number of Female Subjects3
38TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK39ARMCDArm Code2
39TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK40SPGRPCDApplicant-Defined Group Code5
40TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK41GRPLBLGroup LabelGroup 5, 100 mg/kg A, B
41TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK42SETLBLSet LabelGroup 5, 100 mg/kg/day - TK
42TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK43TRTDOSDose Level100
43TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK44TRTDOSUDose Unitsmg/kg/day
44TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK45TKDESCToxicokinetic DescriptionTK
45TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK46PLANMSUBPlanned Number of Male Subjects3
46TDM3TX5Low-Dose Group, 100 mg/kg Compound A, 100 mg/kg Compound B, once daily, TK47PLANFSUBPlanned Number of Female Subjects3
47TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK48ARMCDArm Code3
48TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK49SPGRPCDApplicant-Defined Group Code6
49TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK50GRPLBLGroup LabelGroup 6, 500 mg/kg A, B
50TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK51SETLBLSet LabelGroup 6, 500 mg/kg/day - TK
51TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK52TRTDOSDose Level500
52TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK53TRTDOSUDose Unitsmg/kg/day
53TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK54TKDESCToxicokinetic DescriptionTK
54TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK55PLANMSUBPlanned Number of Male Subjects3
55TDM3TX6High-Dose Group, 500 mg/kg Compound A, 500 mg/kg Compound B, once daily, TK56PLANFSUBPlanned Number of Female Subjects3
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