Clinical trial NCT03136380
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: healthy Japanese subjects CXCR2 inhibitor Danirixin
Sponsor: GlaxoSmithKline
Start date: 2017-05-10; Completion date: 2017-07-31
Enrollment: 34 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Danirixin is a selective chemokine receptor antagonist being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the study is to assess the safety, tolerability and pharmacokinetics (PK) in healthy Japanese subjects over the age of 65 years (inclusive). The study will be conducted in two parts: Part 1 will be a double blind, placebo-controlled, 3-period crossover, ascending single oral dose administration of GSK1325756H (Hydrobromide Salt Tablet Formulations of Danirixin) 10, 50 and 100 milligram (mg) in the fed condition. Part 2 will be an open label, 2-period crossover, single oral dose of GSK1325756H 50 mg in fed and fasted state. This study will provide an understanding of PK of hydrobromide salt of GSK1325756 in population of healthy elderly subjects and also contribute to the selection of appropriate dosing for Phase IIa study in Japan.

Detailed description:

Arms: arm 1: Subjects will receive GSK1325756H 10 mg in P-1, GSK1325756H 50 mg in P-2 and placebo in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period. arm 2: Subjects will receive GSK1325756H 10 mg in P-1, placebo in P-2 and GSK1325756H 100 mg in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period. arm 3: Subjects will receive placebo in P-1, GSK1325756H 50 mg in P-2 and GSK1325756H 100 mg in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period. arm 4: Subjects will receive GSK1325756H 50 mg after a low fat meal and fasted state respectively. There will be a washout period of at least 7 days between each treatment period. arm 5: Subjects will receive GSK1325756H 50 mg after a fasted state and a low fat meal respectively. There will be a washout period of at least 7 days between each treatment period.
Interventions: intervention 1: GSK1325756H intervention 2: Placebo
Intervention descriptions: intervention 1: Danirixin will be available as 10 and 50 milligram (mg) white film coated, round and oval tablets intended for oral administration. It will be administered with 240 mL of water. intervention 2: Subjects will receive visually matching danirixin placebo tablets. It will be administered with 240 mL of water.

Protocol documents:
Prot_000.pdf: 
2016N309585_02 
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GlaxoSmithKline group of companies 
 
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TITLE PAGE 
Protocol Title: A Single Centre, Double Blind (Sponsor Open), Placebo Controlled, 3-
Period Crossover,  Ascending Dose Study in Japanese Healthy Elderly Male Subjects to 
Evaluate the Safety, Tolerability and Pharmacokinetics of Danirixin in the Fed State 
(Part1) and an open label, 2-way crossover to evaluate food effect on the 
pharmacokinetics of Danirixin (Part2). 
Protocol Number: 206817  
Short Title: Phase I study of Danirixin in Japanese healthy elderly male subjects 
Compound Number: GSK1325756  
 
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline K.K. 
6-15, Sendagaya 4-chome, Shibuya-ku, Tokyo 151-8566 Japan 
Medical Monitor Name and Contact Information: 
 
GlaxoSmithKline K.K. 
6-15, Sendagaya 4-chome, Shibuya-ku, Tokyo 151-8566 Japan 
 
Regulatory Agency Identifying Number(s): Not applicable 
Approval Date: 8-MAY-2017 
Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
PPD


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SPONSOR SIGNATORY: 
 
 
Kihito Takahashi  
Vice President 
Development & Medical Affairs 
GlaxoSmithKline K.K. 
 
Date 
 
 


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TABLE OF CONTENTS 
PAGE 
1. 
SYNOPSIS ............................................................................................................... 5 
2. 
SCHEDULE OF ACTIVITIES (SOA) ......................................................................... 8 
3. 
INTRODUCTION .................................................................................................... 12 
3.1. 
Study Rationale .......................................................................................... 12 
3.2. 
Background ................................................................................................ 12 
3.3. 
Benefit/Risk Assessment ............................................................................ 13 
3.3.1. 
Risk Assessment ......................................................................... 14 
3.3.2. 
Benefit Assessment ..................................................................... 17 
3.3.3. 
Overall Benefit:Risk Conclusion ................................................... 17 
4. 
OBJECTIVES AND ENDPOINTS ........................................................................... 17 
5. 
STUDY DESIGN .................................................................................................... 17 
5.1. 
Overall Design ............................................................................................ 17 
5.2. 
Number of Participants ............................................................................... 19 
5.3. 
Participant and Study Completion ............................................................... 19 
5.4. 
Scientific Rationale for Study Design .......................................................... 19 
5.5. 
Dose Justification ........................................................................................ 20 
6. 
STUDY POPULATION ........................................................................................... 21 
6.1. 
Inclusion Criteria ......................................................................................... 21 
6.2. 
Exclusion Criteria ........................................................................................ 22 
6.3. 
Lifestyle Restrictions ................................................................................... 23 
6.3.1. 
Meals and Dietary Restrictions .................................................... 23 
6.3.2. 
Caffeine, Alcohol, and Tobacco ................................................... 24 
6.3.3. 
Activity ......................................................................................... 24 
6.4. 
Screen Failures........................................................................................... 24 
7. 
TREATMENTS ....................................................................................................... 24 
7.1. 
Treatments Administered ............................................................................ 25 
7.2. 
Dose Modification ....................................................................................... 26 
7.3. 
Method of Treatment Assignment ............................................................... 26 
7.4. 
Blinding ....................................................................................................... 26 
7.5. 
Preparation/Handling/Storage/Accountability .............................................. 26 
7.6. 
Treatment Compliance ................................................................................ 27 
7.7. 
Concomitant Therapy.................................................................................. 27 
7.8. 
Treatment after the End of the Study .......................................................... 28 
8. 
DISCONTINUATION CRITERIA ............................................................................. 28 
8.1. 
Discontinuation of Study Treatment ............................................................ 28 
8.1.1. 
Liver Chemistry Stopping Criteria ................................................ 28 
8.1.2. 
QTc Stopping Criteria .................................................................. 28 
8.2. 
Withdrawal from the Study .......................................................................... 29 
8.3. 
Lost to Follow Up ........................................................................................ 29 
9. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 29 
9.1. 
Adverse Events........................................................................................... 30 


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9.1.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 30 
9.1.2. 
Method of Detecting AEs and SAEs ............................................. 31 
9.1.3. 
Follow-up of AEs and SAEs ......................................................... 31 
9.1.4. 
Regulatory Reporting Requirements for SAEs ............................. 31 
9.1.5. 
Pregnancy ................................................................................... 31 
9.2. 
Treatment of Overdose ............................................................................... 32 
9.3. 
Safety Assessments ................................................................................... 32 
9.3.1. 
Physical Examinations ................................................................. 32 
9.3.2. 
Vital Signs .................................................................................... 32 
9.3.3. 
Electrocardiograms ...................................................................... 33 
9.3.4. 
Ophthalmic Examinations ............................................................ 33 
9.3.5. 
Clinical Safety Laboratory Assessments ...................................... 33 
9.4. 
Pharmacokinetics ....................................................................................... 33 
10. STATISTICAL CONSIDERATIONS ........................................................................ 34 
10.1. Sample Size Determination ........................................................................ 34 
10.1.1. 
Sample Size Assumptions ........................................................... 34 
10.1.2. 
Sample Size Sensitivity ................................................................ 34 
10.2. Populations for Analyses ............................................................................ 35 
10.3. Statistical Analyses ..................................................................................... 35 
10.3.1. 
Safety Analyses ........................................................................... 35 
10.3.2. 
Pharmacokinetic Analyses ........................................................... 35 
10.3.3. 
Interim Analyses .......................................................................... 36 
11. REFERENCES ....................................................................................................... 38 
12. APPENDICES ........................................................................................................ 39 
12.1. Appendix 1: Abbreviations and Trademarks ................................................ 39 
12.2. Appendix 2: Clinical Laboratory Tests ......................................................... 42 
12.3. Appendix 3: Study Governance Considerations .......................................... 44 
12.4. Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 48 
12.5. Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 53 
12.6. Appendix 6: Liver Safety: Required Actions and Follow up 
Assessments .............................................................................................. 55 
12.7. Appendix 7: Country-specific requirements ................................................. 57 
12.8. Appendix 8: Protocol Amendment History ................................................... 60 
 


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1. 
SYNOPSIS 
Protocol Title: A Single Centre, Double Blind (Sponsor Open), Placebo Controlled, 3-
Period Crossover,  Ascending Dose Study in Japanese Healthy Elderly Male Subjects to 
Evaluate the Safety, Tolerability and Pharmacokinetics of Danirixin in the Fed State 
(Part1) and an open label, 2-way crossover to evaluate food effect on the 
pharmacokinetics of Danirixin (Part2). 
 
Short Title: Phase I study of Danirixin in Japanese healthy elderly male subjects 
Rationale: The primary objective of this study is to assess the safety, tolerability and 
pharmacokinetics (PK) following single doses of GSK1325756H (Hydrobromide Salt 
Tablet Formulations of Danirixin) 10, 50 and 100 mg, and to investigate a potential food 
effect on PK of GSK1325756 following a single dose of GSK1325756H 50 mg in healthy 
Japanese subjects of over 65 years of age inclusive. This is the first study in which 
GSK1325756 will be administered in a Japanese population. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Part 1  
• To assess the safety, tolerability and 
PK following single doses of 
GSK1325756H 10, 50 and 100 mg in 
the fed state in healthy Japanese 
subjects of over 65 years of age 
inclusive. 
Part 2  
• To investigate the safety, tolerability 
and food effect on PK of GSK1325756 
following a single dose of 50 mg in the 
fed and fasted state, in healthy 
Japanese subjects of over 65 years of 
age inclusive. 
Part 1 and 2 
• 
Adverse events (AEs) 
• 
Change from baseline of clinical laboratory 
values, vital signs, and electrocardiogram 
(ECG) parameters 
• 
Blood concentration of GSK1325756 
• 
Cmax, AUC(0-t), AUC(0-inf), AUC(0-24), 
tmax, t1/2, tlag, tlast of the blood 
concentration of GSK1325756, as data 
permit 
 
Overall Design: This study consists of two parts; Part 1 is a double blind, placebo-
controlled, 3-period crossover, ascending dose, single oral administration in the fed 
condition and Part 2 is an open label, 2-way crossover, single oral dose in the fed and 
fasted state. After screening in each Part, subjects will be randomized and receive the 
treatments. A minimum 7-day wash-out period will occur between each treatment period. 


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Number of Participants: Sufficient participants will be randomised such that 
approximately 18 and 16 evaluable participants complete the study of Part 1 and Part 2, 
respectively. 
Treatment Groups and Duration: 
Subjects will be divided into the study of Part 1 and 2, and receive the following study 
treatment doses shown below;  
Part 1 
This is a double blind, placebo-controlled, 3-period crossover, ascending dose, single oral 
administration in the fed condition. After screening, during treatment periods 1 to 3, 
subjects will be randomized to receive:  
• GSK1325756H 10 mg , single dose, in the fed state  
• GSK1325756H 50 mg, single dose, in the fed state  
• GSK1325756H 100 mg, single dose, in the fed state, or 
• Placebo, single dose, in the fed state 
Subjects will have a screening visit within 30 days prior to the first dose of study. A 
minimum washout period of 7 days will be required between each treatment period. 
Subjects will receive three treatment periods in the study. Subjects will be housed in the 
Clinical Research Unit from Day -1 (the day before dosing) through Day 3 for Period 1 
and 2, and from Day -1 (the day before dosing) through Day 4 for Period 3. Subjects will 
return to the clinic 7 days (at least) after the previous administration day for Period 1 and 
2, and subjects will visit the unit on Day 8 (+/- 1 day) of the last dosing for Period 3 for 
follow-up. 
Group 
n 
Period 1 
Washout 
Period 2 
Washout 
Period 3 
A 
6 
10 mg 
at least 7 
days 
50 mg 
at least 7 
days 
Placebo 
B 
6 
10 mg 
Placebo 
100 mg 
C 
6 
Placebo 
50 mg 
100 mg 
 
Part 2 
This is an open label, 2-way crossover, single oral dose in the fed and fasted state study. 
After screening, subjects will be randomized and receive the treatments in the fed and 
fasted condition. 
Subjects will have a screening visit within 30 days prior to the first dose of study 
treatment, two treatment periods separated by at least 7 days, and follow-up. Subjects will 
be housed in the Clinical Research Unit from Day -1 (the day before dosing) through Day 
3 (for Period 1 and 2), and re-visit 7 (±1) days after the last dose of Period 2 for follow-
up. 


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Group 
n 
Period 1 
Washout 
Period 2 
D 
8 
50 mg, fed 
at least 7 days 
50 mg, fasted 
E 
8 
50 mg, fasted 
50 mg, fed 
 
 
 


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2. 
SCHEDULE OF ACTIVITIES (SOA) 
Table 1 
Time and Events Table 
Part 1, Period 1-2 
Day 
Screening 
Day-1 
Day 1 
Day 2 
Day 3 
Time post-dose 
Pre-
dose 
0 h 
0.25 
h 
0.5 h 
0.75 
h 
1 h 
2 h 
3 h 
4 h 
6 h 
8 h 
10 h 
12 h 
24 h 
48 h 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject demography 
/Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, Weight, BMI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serological test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
Vital signs (PR, BP, 
temp) 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
12-lead ECG 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
Ophthalmic examination 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs2 
<============================================================================================================> 
AEs2 
 
<===================================================================================> 
Con Med review 
<============================================================================================================> 
Hematology, clinical 
chemistry and urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK sampling 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Admission  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
1. 
Screening visit will occur only prior to the first dosing. Treatment Period 2 will occur after at least 7-days wash-out period. High fat meal will be started and completed before within 
30 minutes of GSK1325756H/Placebo dosing. 
2. 
All SAEs will be collected from the signing of the ICF until the follow-up visit at the time points specified. All AEs will be collected from the start of treatment until the follow-up visit 
at the time points specified (see Section 9.1 Adverse Events). 


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3. 
Ophthalmic examinations are conducted on the day between Screening and Day-1. However, it is not carried out for those who are ineligible due to other screening criteria. 
Part 1, Period 3 
Day 
Day-1 
Day 1 
Day 2 
Day 3 
Day 4 
Follow 
up 2,3 
Time post-dose 
Pre-
dose 
0 h 
0.25 
h 
0.5 
h 
0.75 
h 
1 h 
2 h 
3 h 
4 h 
6 h 
8 h 
10 h 
12 h 
24 h 
48 h 
60 h 
72 h 
Physical 
examination 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
 
X 
X 
Vital signs (PR, 
BP, temp) 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
 
X 
X 
12-lead ECG 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
 
X 
X 
Ophthaimic 
examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
SAEs 
<=================================================================================================================> 
AEs 
<=================================================================================================================> 
Con Med review 
<=================================================================================================================> 
Hematology, 
clinical chemistry 
and urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK sampling 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Admission  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
1. 
Treatment Period 3 will occur after at least 7-days wash-out period. High fat meal will be started and completed before within 30 minutes of GSK1325756/Placebo dosing. 
2. 
Follow up visit will occur after 7 days (+/- 1day) of the last dosing. 
3. 
In the case where the subject has discontinued the study prematurely, the assessments for follow up will be carried out. 
 
 
 
 


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Part 2, Period 1-2 
Day 
Screening 
Day-1 
Day 1 
Day 2 
Day 3 
Follow 
up3,5 
Time post-dose 
Pre-
dose 
0 h 
0.25 
h 
0.5 
h 
0.75 
h 
1 h 
2 h 
3 h 
4 h 
6 h 
8 h 
10 h 
12 h 
24 h 
48 h 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject demography 
/Medical history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, Weight, BMI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serological test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
X 
Vital signs (PR, BP, 
temp) 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
X 
12-lead ECG 
X 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
X 
Ophthalmic 
examination 
X6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
SAEs4 
<===============================================================================================================> 
AEs4 
 
<=======================================================================================> 
Con Med review 
<===============================================================================================================> 
Hematology, clinical 
chemistry and 
urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK sampling 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Admission  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
1. 
Screening visit will occur only prior to the first dosing. Treatment Period 2 will occur after at least 7-days wash-out period. 
2. 
For the fed condition, meal will be started and completed before within 30 minutes of GSK1325756H dosing. 
3. 
Follow up visit will occur after 7-days (+/- 1day) of the last dosing. 
4. 
All SAEs will be collected from the signing of the ICF until the follow-up visit at the time points specified. All AEs will be collected from the start of treatment until the follow-up 
visit at the time points specified (see Section 9.1.Adverse Events). 
5. 
In the case where the subject has discontinued the study prematurely, the assessments for follow up will be carried out. 
6. 
Ophthalmic examinations are conducted on the day between Screening and Day-1. However, it is not carried out for those who are ineligible due to other screening criteria. 


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• 
The timing and number of planned study assessments, including safety, tolerability, and PK assessments may be altered during 
the course of the study based on newly available data (e.g., to obtain data closer to the time of peak blood concentrations) to 
ensure appropriate monitoring.  
• 
Any changes in the timing or addition of time points for any planned study assessments must be documented and approved by 
the relevant study team member and then archived in the sponsor and site study files, but will not constitute a protocol 
amendment. The Institutional Review Board (IRB) will be informed of any safety issues that require alteration of the safety 
monitoring scheme or amendment of the Informed Consent Form (ICF). 


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3. 
INTRODUCTION 
GSK1325756 is a selective CXC chemokine receptor 2 (CXCR2) antagonist being 
developed as a potential anti-inflammatory agent for the treatment of chronic obstructive 
pulmonary disease (COPD) and evaluated for its potential to reduce pulmonary morbidity 
in hospitalized patients with viral respiratory tract infections.  
3.1. 
Study Rationale 
The primary objective of this study is to assess the safety, tolerability and PK following 
single doses of GSK1325756H 10, 50 and 100 mg (Part 1), and to investigate a potential 
food effect on PK of GSK1325756 following a single dose of GSK1325756H 50 mg in 
healthy Japanese subjects of over 65 years of age inclusive (Part 2). This is the first study 
in which GSK1325756 will be administered in a Japanese population. 
The current study will provide an understanding of the PK of the hydrobromide salt of 
GSK1325756 in a population of healthy elderly subjects. The effect of food on the PK of 
the GSK1325756H will also be addressed in this population based on PMDA’s advice. 
The outcome of this study will contribute to the selection of the most appropriate dosing 
regimen for Phase IIa study in Japan. 
3.2. 
Background 
GSK1325756 is a non-peptide, high affinity, selective, and reversible CXCR2 antagonist, 
which has demonstrated potent antagonism of CXCR2 activity both in vitro and in vivo 
in preclinical studies. There is a large body of evidence indicating that the chemokine 
receptor CXCR2 plays a pivotal role in neutrophil recruitment to the lung [Chapman, 
2009]. Expressed on the surface of neutrophils and several other cell types of 
hematopoietic and non-hematopoietic origin, the CXCR2 receptor binds ELR+ cytokines 
such as CXC chemokine ligand 8 (CXCL8) or interleukin-8 (IL-8). For neutrophils, 
chemokine binding to CXCR2 results in chemotaxis and cell activation, releasing of a 
number of inflammatory mediators and proteinases thought to contribute to the 
progressive fibrosis, airway stenosis, and destruction of the lung parenchyma 
characteristic of COPD. Lazaar and colleagues [Lazaar, 2011] demonstrated the ability 
for the CXCR2 antagonist, SB-656933, to reduce neutrophil recruitment into the lung in 
an experimental human model of lung inflammation. This evidence supports the strategy 
for selective antagonism of the interaction between CXCR2 and its various chemokine 
ligands as a mechanism for reducing neutrophil migration into the lung. 
As reported in the Investigator’s Brochure [GlaxoSmithKline Document Number 
YM2010/00163/07], in six completed studies using GSK1325756, 210 healthy non-
Japanese subjects have received either single doses of GSK1325756 up to 400 mg or 
repeat doses of 50 mg and 200 mg (once daily for 14 days). GSK1325756 has been well-
tolerated and most AEs were mild to moderate in intensity. The most commonly observed 
AEs were headache and diarrhea. There were no clinically significant changes in vital 
signs, ECG parameters or laboratory assessments at any oral or intravenous dose of 
GSK1325756. There were no severe or serious adverse events (SAE) reported. 


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The clinical trial in patients with COPD (200163) has been completed dosing but has not 
been reported. In Part A of the 200163 study, 9 COPD patients received GSK1325756 
50 mg or placebo bis in die (BID) for 14 days. One subject reported an SAE of worsening 
arthrosis that was not attributed to study drug by the investigator and the subject was not 
withdrawn from the study. No vital sign, ECG or safety laboratory abnormalities were 
reported as an AE in Part A. Part B of the COPD study has completed dosing. Subjects 
have received GSK1325756 75 mg (n = 45) or placebo (n = 48) BID for 52 weeks. 
Twenty subjects in Part B (10 in each treatment group) have reported 49 SAEs, the 
majority of which have been COPD exacerbations. Only two SAEs (both COPD 
exacerbations in subjects on placebo) were attributed to study drug by the investigator. 
There has been one death, in a subject who developed liver failure on placebo; this event 
was not attributed to the study drug by the investigator. 
GSK1325756 is in Phase II development as a novel, oral anti-inflammatory agent for the 
maintenance treatment of COPD and as a treatment for hospitalized influenza infection. 
More information about the non-clinical and clinical studies is available in the IB, 
including its Supplement [GlaxoSmithKline Document Number YM2010/00163/07]. 
3.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of GSK1325756 may be found in the IB. The 
following section outlines the risk assessment and mitigation strategy for this protocol: 
 


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3.3.1. 
Risk Assessment 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Impact – eligibility criteria 
Mitigation Strategy 
Investigational Product (IP) [e.g., GSK1325756] 
Reduction in peripheral blood 
neutrophil count 
 
Observed with other molecules 
with CXCR2 antagonist activity, 
including after single doses; has 
not been observed with GSK 
competitive reversible CXCR2 
antagonists elubrixin [Lazaar, 
2011] and GSK1325756 in healthy 
volunteers or COPD subjects, 
including elderly subjects, dosed 
with GSK1325756 up to one year. 
A subject’s peripheral blood 
neutrophil count must be within the 
normal range.  
 
 
Refer to Time and Events Table 
Section 2 for neutrophil  
monitoring. Any subject that has 
a peripheral blood neutrophil 
count of < 1.0 x 109 cells/L that is 
confirmed with repeat testing 
will be withdrawn from the study 
and monitored daily until the 
neutrophil count returns to the 
pre-dose value. 
Infection Risk  
Neutrophils are an important 
component of host defense and 
innate immunity. Inhibition of 
neutrophil migration and activation 
could impact host defense and 
innate immunity. 
No increase in pneumonia has 
been observed in COPD patients 
dosed for one year or in patients 
with influenza. 
A subject’s peripheral blood 
neutrophil count must be within the 
normal range.  
 
Careful monitoring of adverse 
events  
Testicular toxicity 
Testis and epididymal effects 
occurred in dogs following 6 or 7 
non-tolerated oral doses of 300 or 
1000 mg/kg/day following 
suspension dosing and at doses of 
Subjects who are able to follow the 
contraceptive guidance are 
eligible. 
Contraceptive guidance and 
collection of pregnancy information 
will be implemented as in 
Appendix 5. 
Subjects who are unable to follow 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Impact – eligibility criteria 
Mitigation Strategy 
30 mg/kg/day following 39 weeks 
of dosing. In rats, testicular 
changes and secondary effects on 
the epididymis occurred after 
administration of GSK1325756H at 
oral doses of 500 mg/kg/day 
following 4 weeks of dosing which 
were similar to those seen 
previously with GSK1325756B at 
equivalent exposures. 
There have been no reported 
testicular effects in clinical studies 
up to one year in duration. 
the contraceptive guidance are 
ineligible. 
Standard safety monitoring will be 
implemented. 
The potential risk of testicular 
injury is described in the ICF. 
From PK modeling, it is predicted 
that the risk of the exposure in 
subjects receiving 50 mg of 
GSK1325756H twice daily to 
exceed twice the AUC(0-24) of 
NOAEL for testicular influence is 
low. 
Photosensitivity 
The UV/visible spectrum for 
GSK1325756, exhibits an 
absorbance maximum at 323 nm, 
which is within the range of natural 
sunlight (290 – 700 nm). 
Concentrations of drug-related 
material observed in the uveal 
tract/retina and pigmented skin 
were highest at 6 hours after 
dosing (i.e., 13.1 and 3.59 µg 
equiv/g tissue, respectively), 
representing tissue:plasma 
radioactivity concentrations of 3.29 
and 0.9, respectively.  In addition 
there was evidence of retention of 
drug-related material in the uveal 
Subjects who are able to avoid 
direct exposure to sunlight are 
eligible. 
Avoid direct exposure to sunlight 
for as long as possible using a hat 
appropriate sunscreen treatment 
etc. 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Impact – eligibility criteria 
Mitigation Strategy 
tract/retina at 35 days following a 
single dose. 
Gastrointestinal (GI) effects 
(abdominal pain, diarrhoea) 
 
GI effects (e.g., erosion or 
ulceration) were observed in 
animal toxicology studies with 
GSK1325756B but not 
hydrobromide salt formulation.  
In one study CX3114922, 7 events 
of mild, self-limiting diarrhea were 
reported in 5 subjects receiving 
GSK1325756B. 
The safety margins between 
nonclinical NOAEL exposure levels 
and clinical exposure levels are 
currently considered sufficient to 
support long term clinical studies 
up to 75 mg BID. 
Closely monitor, paying particular 
attention to a possible association 
with GI effects, and collect 
information on and characterize GI 
effects. 
 


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3.3.2. 
Benefit Assessment 
There is no direct medical benefit to the subjects from taking part in this study. The 
information obtained from this study will contribute to the development of GSK1325756 
and may benefit patients in the future. The overall risk benefit balance is considered to be 
acceptable. 
3.3.3. 
Overall Benefit:Risk Conclusion 
Appropriate measures have been taken to minimize the risk to subjects in this study 
through eligibility criteria and consideration of burden relative to study procedures. It is 
acceptable to conduct this study in healthy elderly volunteers, because whilst they will 
receive no direct medical benefit, the risks from the study treatment and procedures are 
minimal. The study will be conducted in a fully equipped clinical research unit with 
access to hospital emergency facilities. 
4. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Part 1  
• To assess the safety, tolerability and 
PK following single doses of 
GSK1325756H 10, 50 and 100 mg in 
the fed state in healthy Japanese 
subjects of over 65 years of age 
inclusive. 
Part 2  
• To investigate the safety, tolerability 
and food effect on PK of GSK1325756 
following a single dose of 50 mg in the 
fed and fasted state, in healthy 
Japanese subjects of over 65 years of 
age inclusive. 
Part 1 and 2 
• 
AEs 
• 
Change from baseline of clinical laboratory 
values, vital signs, and ECG parameters 
• 
Blood concentration of GSK1325756 
• 
Cmax, AUC(0-t), AUC(0-inf), AUC(0-24), 
tmax, t1/2, tlag, tlast of the blood 
concentration of GSK1325756, as data 
permit 
5. 
STUDY DESIGN 
5.1. 
Overall Design 
This study consists of two parts; 
Part 1 
This is a double blind, placebo-controlled, 3-period crossover, ascending dose, single oral 
administration in the fed condition (high fat meal). During treatment periods 1 to 3, 
subjects will be randomized and receive the treatments:  


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• GSK1325756H 10 mg, single dose, in the fed state  
• GSK1325756H 50 mg, single dose, in the fed state  
• GSK1325756H 100 mg, single dose, in the fed state, or 
• Placebo, single dose, in the fed state 
Subjects will have a screening visit within 30 days prior to the first dose of study 
treatment. A minimum washout period of 7 days from the dose of GSK1325756 will be 
required between each treatment period. Subjects will receive three treatment periods in 
the study. Subjects will be housed in the Clinical Research Unit from Day -1 (the day 
before dosing) through Day 3 for Period 1 and 2, from Day -1 (the day before dosing) 
through Day 4 for Period 3. Subjects will return to the clinic 7 days (at least) after the 
previous administration day for Period 1 and 2, and subjects will visit the unit on Day 8 
(+/- 1 day) of the last dosing for Part 3 for follow-up. 
For each dosing period, the progress to the next period will be determined by GSK 
medical monitor and investigator based on the blinded safety profiles (AE, clinical 
laboratory values, vital signs and 12-lead ECG). Furthermore, for the progresses Period 2 
to Period 3, GSK medical monitor will determine the appropriateness of the progresses 
Period 2 to Period 3 based on the result of blood concentration of GSK1325756 assessed 
by the sponsor's person who is responsible for confirmation of concentration under 
unblind. 
Table 2 
Dose regimen for GSK1325756H or placebo 
Group 
n 
Period 1 
Washout 
Period 2 
Washout 
Period 3 
A 
6 
10 mg 
at least 7 
days 
50 mg 
at least 7 
days 
Placebo 
B 
6 
10 mg 
Placebo 
100 mg 
C 
6 
Placebo 
50 mg 
100 mg 
Part 2 
This is an open label, 2-way crossover, single oral dose in the fed (low fat meal) and 
fasted states. 
Subjects will have a screening visit within 30 days prior to the first dose of study 
treatment, two treatment periods separated by at least 7 days, and follow-up. Subjects will 
be housed in the Clinical Research Unit from Day -1 (the day before dosing) through Day 
3 (for Period 1 and 2), and re-visit 7 (±1) days after the last dose of Period 2 for follow-
up. 
The initiation of Part 2 will be determined by GSK medical monitor and investigator 
based on the review of the blinded safety (AE, clinical laboratory values, vital signs and 
12-lead ECG). Furthermore, GSK medical monitor will determine the appropriateness of 
the initiation of Part 2 based on the result of blood concentration of GSK1325756 


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assessed by the sponsor's person who is responsible for confirmation of concentration 
under unblind.. 
 
Table 3 
Dose regimen for GSK1325756H 
Group 
n 
Period 1 
Washout 
Period 2 
D 
8 
50 mg, fed 
at least 7 days 
50 mg, fasted 
E 
8 
50 mg, fasted 
50 mg, fed 
 
5.2. 
Number of Participants 
Part 1 and Part 2 
Sufficient participants will be randomised such that approximately 18 and 16 evaluable 
participants complete the study of each part. If subjects prematurely discontinue the study, 
additional subjects may be enrolled as replacement subjects and assigned to the same 
treatment sequence, if applicable, at the discretion of the sponsor in consultation with the 
investigator. 
5.3. 
Participant and Study Completion 
A participant is considered to have completed the study if he has completed all sessions 
of the study including the last visit or the last scheduled procedure shown in the Schedule 
of Activities. 
The end of the study is defined as the date of the last visit of the last participant in the 
study. 
5.4. 
Scientific Rationale for Study Design 
Part 1 
This part is a double-blind, randomized, placebo-controlled, dose escalating, crossover 
design to characterize the safety, tolerability, PK following single dose of GSK1325756H 
in healthy Japanese elders. This part will include a placebo control study, to allow for 
evaluation of adverse events attributable to treatment versus those independent of 
treatment. In this part, high fat meal will be given 30 minutes prior to dosing. 
With consideration for that it has been reported that majority of COPD population are 
elders [Fukuchi Y, 2004], healthy Japanese elders will be enrolled in this study to 
evaluate safety, tolerability and PK of GSK1325756, which enable comparison to the 
non-Japanese data in healthy elders from Study 201037. 


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In previous clinical studies GSK1325756 was very well tolerated. Since this study is the 
first study in Japanese subjects, this study adopts a cautious approach starting with a 
single administration of low dose level (10 mg) and will include rigorous safety 
monitoring to confirm the safety profile prior to moving to the next dose level. 
Since the terminal half-life was approximately 11-12 hours after 50 mg GSK1325756H 
both in fast and fed condition in the past study in non-Japanese (Study 201037), 3 days is 
considered to be sufficient for the evaluation of PK and safety in Period 1 and 2 (10 and 
50 mg) of Part 1 and 4 days in Period 3 (100 mg) of Part 1. The study plans follow up 
until at least 7 (±1) days after the last dose of each part. Assuming the half-life 
conservatively, 7 days is sufficient duration for the washout and the following up. 
Period 3 will occur based on the review of the blinded safety and PK concentration data 
from Period 2 of Part 1 (i.e., 50 mg single dose after intake of high fat meal) in 
consideration of safety. 
Since high fat meal was given in previously conducted study (Study 201037), high fat 
meal is also given in this study in order to enable to make a comparison between the 
exposure of Study 201037 and this study. 
Part 2 
Part 2 is 2 way complete crossover design to evaluate the food effect on PK of 
GSK1325756. In this part, low fat meal will be given 30 minutes prior to dosing. 
This part will occur based on the review of the blinded safety and PK concentration data 
from Period 2 of Part 1 (i.e., 50 mg single dose after intake of low fat meal) in 
consideration of safety. 
Since the terminal half-life was approximately 11-12 hours after 50 mg GSK1325756H 
both in fast and fed condition in the past study in non-Japanese (Study 201037), 3 days is 
considered to be sufficient for the evaluation of PK and safety of Part 2 (50 mg). The 
study plans follow up until at least 7 (±1) days after the last dose of each part. Assuming 
the half-life conservatively, 7 days is sufficient duration for the washout and the 
following up. 
5.5. 
Dose Justification 
Part 1 
To date, dose range of 10 to 400 mg of GSK1235756 including all proposed doses for 
this study are within the safe and well tolerated from previously investigated across the 
GSK1325756 programme in non-Japanese population. Study 201037 showed that 
systemic GSK1325756 exposure was higher following oral 50 mg GSK1325756H 
compared to GSK1325756B (free base of Danirixin) in fed conditions (84% increase in 
area under the concentration-time curve from time 0 to infinity [AUC(0-inf)], 92% 
increase in area under the concentration-time curve from time 0 to t [AUC(0-t)] and 76% 
increase in Maximum observed concentration [Cmax]). The oral 10 mg GSK1325756H 
dose is approximately equivalent to oral 20 mg GSK1325756B, based on the results of 


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Study 201037. The oral 50 mg GSK1325756H dose is selected to enable comparison with 
the non-Japanese PK data in Study 201037 and will be proposed dose level for Phase II 
study (Study 206818). In addition, since the oral 50 mg GSK1325756H is to be 
administrated twice daily in Phase II study, the 100 mg dose is selected as a top dose to 
investigate the higher systemic exposure than that of following 50 mg twice daily. 
The middle dose in this study, 50 mg will be 1/70 of the no observable adverse effect 
level (NOAEL) of 4 week rat study based on systemic blood exposure (Table below). 
The starting and top dose in this study (10 mg and 100 mg) is 1/5 and double of the 
middle dose (1/140 and 1/35 of the NOAEL), and has a sufficient safety margin.  
Species 
(Duration) 
Dose 
Sex 
Cmax 
AUC 
Exposure Ratio 
Rat 
(4 week) 
150 mg/kg/day 
[NOAEL] 
M 
61.9 
491 
71.7 
67.7 
F 
58.3 
567 
67.5 
78.2 
Human 
Single 
50 mg 
M/F 
0.863 
7.248 
- 
- 
Part 2 
Since the food effect was evaluated using 50 mg in the previous study (Study 201037), 
50 mg is chosen for the dose to evaluate the food effect on the single dose PK in Japanese 
population. 
6. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
6.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Participant must be over 65 years of age inclusive, at the time of signing the 
informed consent. 
Type of Participant and Disease Characteristics 
2. Participants who are overtly healthy as determined by medical evaluation including 
medical history, physical examination, laboratory tests, and ECG. A subject with a 
clinical abnormality or laboratory parameter(s) which is/are not specifically listed in 
the inclusion or exclusion criteria, outside the reference range for the population 
being studied may be included only if the investigator in consultation with the 
Medical Monitor if required agree that the finding is unlikely to introduce additional 
risk factors and will not interfere with the study procedures. 


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3. Participants whose peripheral blood neutrophil counts and hematocrit values are 
within normal range at screening visit. 
Weight 
4. Body weight ≥ 50 kg and body mass index (BMI) within the range 18.5 – 24.9 kg/m2 
(inclusive). 
Sex 
5. Japanese Male 
A male participant must agree to use contraception as detailed in Appendix 5 of this 
protocol during the treatment period and until follow up visit. 
Informed Consent 
6. Capable of giving signed informed consent as described in restrictions listed in the 
informed consent form (ICF). 
6.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrine, hematological, or neurological disorders capable of significantly altering 
the absorption, metabolism, or elimination of drugs; constituting a risk when taking 
the study treatment; or interfering with the interpretation of data 
2. Abnormal blood pressure as determined by the investigator 
3. Alanine Aminotransferase (ALT) > 1.5x upper limit of normal (ULN) 
4. Bilirubin > 1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin < 35%) 
5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones) 
6. QTcF > 450 msec 
NOTES: 
• 
The QTc is the QT interval corrected for heart rate according to Fridericia’s 
formula (QTcF), and/or another method, machine-read or manually over-read. 
• 
The specific formula that will be used to determine eligibility and 
discontinuation for an individual subject should be determined prior to initiation 
of the study. In other words, several different formulae cannot be used to 
calculate the QTc for an individual subject and then the lowest QTc value used 
to include or discontinue the subject from the trial. 


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• 
For purposes of data analysis, QTcF, another QT correction formula, or a 
composite of available values of QTc will be used as specified in the Reporting 
and Analysis Plan (RAP). 
Prior/Concomitant Therapy 
7. Past or intended use of over-the-counter or prescription medication including herbal 
medications and proton pump inhibitor (PPI) within 14 days prior to dosing. Specific 
medications listed in Section 7.7 may be allowed 
Prior/Concurrent Clinical Study Experience 
8. History of donation of blood or blood products ≥ 400 mL within 3 months or ≥ 
200 mL within 1 month prior to screening 
9. Exposure to more than 4 new chemical entities within 12 months prior to the first 
dosing day 
10. Current enrollment or past participation within the last 30 days before signing of 
consent in this clinical study involving an investigational study treatment or any 
other type of medical research 
Diagnostic assessments 
11. The subject with positive Serological test for syphilis (Rapid Plasma Reagin [RPR] 
and Treponema pallidum hemagglutination test [TPHA]), Human immunodeficiency 
virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C 
virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) 
antibody at screening 
12. Positive pre-study drug screen 
Other Exclusions 
13. Regular alcohol consumption within 6 months prior to the study defined as: 
• 
For an average weekly intake of > 14 units for males. One unit is equivalent to 
350 mL of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits 
14. Smoking or history or regular use of tobacco- or nicotine-containing products within 
6 months prior to screening 
15. Sensitivity to any of the study treatments, or components thereof, or drug or other 
allergy that, in the opinion of the investigator or medical monitor, contraindicates 
participation in the study 
6.3. 
Lifestyle Restrictions 
6.3.1. 
Meals and Dietary Restrictions 
• 
Refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice, 
pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices from 7 days prior to 


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the first dose of study medication until completion of all study procedures in each 
study period after the final dose. 
• 
No water is allowed at least 2 hours before and after dosing. Also, keep resting as 
much as possible in sitting or semi-sitting position. Water is allowed ad libitum at all 
other times. 
• 
Once in the clinical unit subjects will not be allowed to eat or drink anything other 
than provided by the study centre. 
6.3.2. 
Caffeine, Alcohol, and Tobacco 
• 
During each dosing session, participants will abstain from ingesting caffeine- or 
xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 24 
hours before the start of dosing until collection of the final PK and clinical laboratory 
sample. 
• 
During each dosing session, participants will abstain from alcohol for 24 hours 
before the start of dosing until collection of the final PK and clinical laboratory 
sample.  
• 
Participants will be instructed that use of nicotine-containing products (including 
nicotine patches) will not be permitted from the screening until collection of the final 
PK sample. 
6.3.3. 
Activity 
• 
Participants will abstain from strenuous exercise for 48 hours before each blood 
collection for clinical laboratory tests. Participants may participate in light 
recreational activities during studies (e.g., watching television, reading). 
• 
Participants will avoid a long direct exposure to sunlight for as long as possible using 
a appropriate sunscreen treatment etc. from the initiation of dosing to follow-up visit 
when participants will go outside. 
6.4. 
Screen Failures 
Screen failures are defined as participants who are screened in the clinical study but are 
not subsequently randomised. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any SAEs. 
7. 
TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 


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7.1. 
Treatments Administered 
Study Treatment 
Name: 
GSK1325756H 
Placebo 
Dosage formulation: 
 
GSK1325756H Tablets,10 mg are 
white film coated, round tablets 
intended for oral administration. 
GSK1325756H Tablets, 50 mg are 
white film coated, oval-shaped 
tablets intended for oral 
administration, 
White oval-shaped tablets which 
does not include GSK1325756H. 
Unit dose 
strength(s)/Dosage 
level(s): 
10 mg, 50 mg 
Not applicable 
Route of 
Administration:  
oral 
oral 
Dosing instructions: 
 
With food and 240 mL (8 oz) 
water, unless explicitly defined by 
protocol 
With food and 240 mL (8 oz) 
water, unless explicitly defined by 
protocol 
Manufacturer: 
GlaxoSmithKline 
GlaxoSmithKline 
Note: When 100 mg strength is administrated, subjects receive two doses of 50 mg 
strength. 
 
 


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7.2. 
Dose Modification 
No dose modification is planned. 
7.3. 
Method of Treatment Assignment 
On Day 1 of each Part, participants will be assigned a unique number (randomization 
number) in ascending numerical order. The randomization number encodes the 
participant’s assignment to one of the 3 sequences in Part 1 and one of the 2 sequences in 
Part 2, according to the randomization schedule generated prior to the study by the 
Biomedical Data Sciences Department at GSK. Participants will be randomized in a 1:1:1 
ratio to receive sequence (A:B:C) for Part 1, or will be randomized in a 1:1 ratio to 
receive sequence (D:E) for Part 2. Each participant will be dispensed blinded study 
treatment, labeled with his unique randomization number, throughout the study. 
7.4. 
Blinding 
Participants for Part 1 will be randomized to one of the treatment sequences, A, B or C. 
Participants for Part 2 will be randomized to one of the two sequences, D or E. 
Investigators, participants and sponsor will remain blinded to each participant’s assigned 
study treatment throughout the course of the study. Although investigational product 
administering physician will be able to know information on assignment of 
investigational product, the physician do not inform site staff who are not involved in 
investigational drug administration about the information of assignment. Also, he/she 
does not get involved in safety evaluation under blind. 
The sponsor's person who is responsible for confirmation of concentration will review 
blood drug concentration data under unblind. 
A participant will be withdrawn if the participant’s treatment code is unblinded by the 
investigator or treating physician. The primary reason for discontinuation (the event or 
condition which led to the unblinding) will be recorded in the case report form (CRF).  
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
treatment assignment for any participant with an SAE. If the SAE requires that an 
expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
report, identifying the participant’s treatment assignment, may be sent to investigators in 
accordance with local regulations and/or GSK policy. 
7.5. 
Preparation/Handling/Storage/Accountability 
No special preparation of study treatment is required. 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment. 
2. Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study treatments 


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must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study treatment 
are provided in the Study Reference Manual (SRM). 
• 
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff. 
• 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK. 
7.6. 
Treatment Compliance 
• 
When the individual dose for a participant is prepared from a bulk supply, the 
preparation of the dose will be confirmed by a second member of the study site staff.  
• 
The investigator nominates an investigational product administering physician, and 
the physician gives the study drug directly to the subject according to the 
administration instructions of the protocol. 
• 
When participants are dosed at the site, they will receive study treatment directly 
from the investigator or designee, under medical supervision. The date and time of 
each dose administered in the clinic will be recorded in the source documents. The 
dose of study treatment and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person 
administering the study treatment. Study site personnel will examine each 
participant’s mouth to ensure that the study treatment was ingested. 
7.7. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Participants must abstain from taking prescription or non-prescription drugs (including 
vitamins and dietary or herbal supplements) within 14 days before the start of study 


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treatment until completion of the follow-up visit, unless, in the opinion of the investigator 
and sponsor, the medication will not interfere with the study.  
7.8. 
Treatment after the End of the Study 
Subjects will not receive any additional treatment from GSK after completion of the 
study, because only healthy subjects are eligible for study participation. 
8. 
DISCONTINUATION CRITERIA 
8.1. 
Discontinuation of Study Treatment 
8.1.1. 
Liver Chemistry Stopping Criteria 
Study treatment will be discontinued for a participant if liver chemistry stopping criteria 
are met: 
Phase I Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
Continue Study Treatment 
Discontinue Study Treatment 
*INR value not applicable to subjects on anticoagulants 
ALT ≥3xULN 
No
Yes
Must refer to Liver Safety Required Actions and Follow up Assessments  section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*
 
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Appendix 6. 
8.1.2. 
QTc Stopping Criteria 
A subject that meets the bulleted criterion based on the average of triplicate ECG 
readings will be withdrawn from study treatment. 
• 
QTcF > 500 msec, 
• 
Change from baseline: QTc > 60 msec 


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8.1.3. 
Other criteria 
A subject that meets the bulleted criterion based on neutrophil counts will be withdrawn 
from study treatment. 
• 
Neutrophil count < 1.0 * 109/L 
8.2. 
Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his own request, or 
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, compliance or administrative reasons. 
• 
If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• 
If a participant withdraws from the study, he may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
• 
Refer to the SoA for data to be collected at the time of study discontinuation and 
follow-up and for any further evaluations that need to be completed. 
8.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  
9. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA.  
• 
Protocol waivers or exemptions are not allowed  


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• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study treatment. 
• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.  
• 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA. 
• 
The maximum amount of blood collected from each participant over the 
duration of the study, including any extra assessments that may be required, will 
not exceed 400 mL. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
9.1. 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 4. 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study (see Section 8).  
9.1.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the signing of the ICF until the follow-up visit 
at the time points specified in the SoA (Section 2). 
• 
All AEs will be collected from the start of treatment until the follow-up visit at 
the time points specified in the SoA (Section 2). 
• 
Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the CRF not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee within 24 
hours, as indicated in Appendix 4. The investigator will submit any updated 
SAE data to the sponsor within 24 hours of it being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, 
at any time after a participant has been discharged from the study, and he/she 


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considers the event to be reasonably related to the study treatment or study 
participation, the investigator must promptly notify the sponsor. 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 4. 
9.1.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
9.1.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs (as defined in Section 12.4) will be 
followed until the event is resolved, stabilized, otherwise explained, or the participant is 
lost to follow-up (as defined in Section 8.3). Further information on follow-up procedures 
is given in Appendix 4. 
9.1.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study treatment under clinical investigation are 
met.  
• 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
IRB, and investigators. 
• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary. 
• 
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAE) from the 
sponsor will review and then file it along with the IB and will notify the IRB, if 
appropriate according to local requirements. 
9.1.5. 
Pregnancy 
• 
Details of all pregnancies in female partners of male participants will be collected 
after the start of study treatment and until the end of the follow-up period. 
• 
If a pregnancy is reported, the investigator should inform GSK within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 5. 


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• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE. 
9.2. 
Treatment of Overdose 
For this study, any dose of GSK1325756H greater than 100 mg within a 24-hour time 
period will be considered an overdose. 
GSK does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for AE/SAE and laboratory abnormalities until 
GSK1325756 can no longer be detected systemically (at least 14 days). 
3. Obtain a blood sample for PK analysis within 14 days from the date of the last dose 
of study treatment if requested by the Medical Monitor (determined on a case-by-
case basis). 
4. Document the quantity of the excess dose as well as the duration of the overdosing in 
the CRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
9.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. 
9.3.1. 
Physical Examinations 
• 
Physical examination will include, at a minimum, assessments of the Skin, 
Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height 
and weight will also be measured and recorded. 
• 
Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
9.3.2. 
Vital Signs 
• 
Axillary temperature, pulse rate and blood pressure will be assessed. 
• 
Blood pressure and pulse measurements will be assessed (specify participant's 
position, if applicable) with a completely automated device. Manual techniques 
will be used only if an automated device is not available. 
• 
Blood pressure and pulse measurements should be preceded by at least 5 
minutes of rest for the participant in a quiet setting without distractions (e.g., 
television, cell phones). 


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• 
Single vital signs will be measured in a supine position after 5 minutes rest and 
will include temperature, systolic and diastolic blood pressure, and pulse rate.  
9.3.3. 
Electrocardiograms 
• 
Single 12-lead ECG will be obtained as outlined in the SoA (see Section 2) 
using an ECG machine that automatically calculates the heart rate and measures 
PR, QRS, QT, and QTc intervals. Refer to Section 8.1.2. for QTc withdrawal 
criteria and additional QTc readings that may be necessary. 
9.3.4. 
Ophthalmic Examinations 
• 
Fundus and slit-lamp examinations will be implemented as outlined in the SoA 
(see Section 2). 
9.3.5. 
Clinical Safety Laboratory Assessments 
• 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and 
to the SoA for the timing and frequency.  
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or medical monitor.  
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
• 
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA. 
• 
If laboratory values from non-protocol specified laboratory assessments 
performed at the institution’s local laboratory require a change in participant 
management or are considered clinically significant by the investigator (e.g., 
SAE or AE or dose modification), then the results must be recorded in the CRF.  
9.4. 
Pharmacokinetics 
Whole blood samples of approximately 1 mL will be collected for measurement of blood 
concentrations of GSK1325756 as specified in the SoA. Instructions for the collection 
and handling of biological samples will be provided in the SRM by the sponsor. The 
actual date and time (24-hour clock time) of each sample will be recorded. 


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10. 
STATISTICAL CONSIDERATIONS 
This is a Phase I study and the primary objective of this study is to assess the safety, 
tolerability and PK profile of single dose of GSK1325756H in healthy Japanese elderly 
subjects (Part 1). Also other primary objective of this study is to investigate food effect 
on PK of GSK1325756H 50 mg single dose in fed state and fasted state in healthy 
Japanese elderly subjects (Part 2). Where appropriate, the PK parameters will be 
summarized descriptively. 
10.1. 
Sample Size Determination 
10.1.1. 
Sample Size Assumptions 
Given that this is the first time for Japanese subjects that GSK1325756 has been 
administered, the primary objective of the study is to obtain a preliminary assessment of 
safety, tolerability and PK profile of the dose range selected and food effect. The sample 
size is based on feasibility where 18 healthy Japanese elderly subjects will be enrolled in 
Part 1, and 16 healthy Japanese elderly subjects will be enrolled in Part 2. Consideration 
has been given to the level of precision we would expect to achieve for the main PK 
parameters assuming the variability is the same as seen the previous GSK1325756 study. 
Part 1: 
Assuming a between subject coefficient of variance (CVb%) has been obtained from 
CX3114922 study that administered single dose of GSK1325756 100 mg in age of 65 to 
80 in fed state. The between subject CVb% observed for Cmax was estimated to be 
30.1% and AUC(0-t) was estimated to be 30.2%. Based on sample size of 12 subjects of 
GSK1325756 (10 mg, 50 mg, 100 mg), the CVb% of 30.2% provides a precision estimate 
for the upper limit value and lower limit value of a mean of 90% confidence interval (CI) 
of 16.6%  
Part 2: 
Based on sample size of 16 subjects, assuming a within-subject CVw% of 44.7% for 
ACU(0-t) and Cmax as observed in Study 201037, it is estimated that the lower and 
upper bounds of the 90% CI for the ratio of the food effect will be within +/- 30%. Hence, 
90% CI would be approximately (0.77, 1.30) if the estimated ratio of food effect is 1.0. 
10.1.2. 
Sample Size Sensitivity  
Part 1: 
Based on sample size of 12, if the between subject CVb% observed in the PK parameters 
is 10% and 20% greater between subject CVb% (33.2%, 36.2%), the precision estimate 
for the upper limit value and lower limit value of a mean of 90% CI will be 18.3% and 
20.0% respectively. 
Part 2: 


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Based on sample size of 16, assuming a 10% and 20% greater within subject CVw% 
(49.2%, 53.6%), the half-width of the 90% CI for the ratio of food effect means should be 
no more than 33% and 37% of the point estimates. Assuming an observed ratio of one, 
the corresponding 90% CI for the ratio of food effect means would be (0.75, 1.33) and 
(0.73, 1.37) respectively. 
10.2. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Screened  
Consisting of all subjects screened in the study. 
Screening Failure 
Subjects who screened in the study but are never subsequently 
randomised. All participants who sign the ICF have the screening 
test in the study. 
Safety 
All randomised participants who take at least one dose of study 
treatment. Participants will be analyzed according to the treatment 
they actually received. This population will be defined for each Part. 
PK 
This population is defined as all subjects administered at least one 
dose of study treatment and who have PK sample taken and 
analyzed. Participants will be analyzed according to the treatment 
they actually received. This population will be defined for each Part. 
10.3. 
Statistical Analyses 
This study will be presented in tabular and/or graphical format and summarized 
descriptively according to GSK’s Integrated Data Standards Library (IDSL) standards. 
Complete details of the planned statistical analyses will be provided in the RAP. 
10.3.1. 
Safety Analyses 
All safety analyses will be performed on the Safety Population.  
Statistical Analysis Methods 
AEs, clinical laboratory values, vital signs and ECG will be summarized by dose group by dose 
group in Part 1 and by fed state in Part 2. 
No formal statistical comparisons will be made for the safety data. 
10.3.2. 
Pharmacokinetic Analyses 
All PK analyses will be performed on the PK Population. 


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Statistical Analysis Methods 
Blood GSK1325756 concentration-time data will be analysed by non-compartmental methods with 
WinNonlin. Calculations will be based on the actual sampling times recorded during the study.  
From the blood concentration-time data, the following PK parameters will be determined, as data 
permit: AUC(0-t), AUC(0-24), AUC(0-inf), Cmax, tmax, apparent t1/2, Tlag and tlast. 
PK data will be presented in graphical and/or tabular form and will be summarised descriptively.  
Listings will be generated and summary statistics (n, arithmetic mean with associated 95% CI, 
standard deviation, minimum, median, maximum, geometric mean with associated 95% CI, SD on 
log-scale and %CVb or %CVw) will be calculated for each derived blood PK parameter for each 
group dose in each Part. 
 
Part 1: 
The PK-dose relationship will be examined graphically by plotting derived blood PK parameters 
(AUC(0-t) and Cmax) for each group dose. 
Dose proportionality for PK parameters (AUC(0-t) and Cmax) will be assessed by using a power 
model as described below: 
    log (PK parameter) = β0 + β1·log(dose) 
    where β0 is the intercept and β1 is the slope. 
 
Following loge-transformation, AUC(0-t) and Cmax will be separately analyzed using a power 
model with fixed effect terms for log-dose, as data permitted. Subjects will be assessed in model as 
random effect, and degree of freedom will use Kenward-Roger. Point estimates for the slopes of 
PK parameters and their associated 90% CIs will be constructed. 
 
Part 2: 
An estimation approach will be used to assess the food effect of GSK1325756 on primary PK 
parameters, where point estimates and corresponding 90% CIs will be constructed to provide a 
plausible range of values for the true comparisons of interest. 
To estimate the food effect on the primary PK endpoints, data from Period 1 and Period 2 will be 
used. Following loge-transformation, AUC(0-t) and Cmax of GSK1325756 will be separately 
analysed using a mixed effects model with fixed effect terms for regimen (the treatment variable 
can be applied as this contains whether the subject is on fed or fasted for that particular period) 
and period. Subject will be treated as a random effect in the model. 
The point estimates and their associated 90% CIs will then be backtransformed to provide point 
estimates (ratio) and 90% CIs for the adjusted geometric means of fed and fasted. 
10.3.3. 
Interim Analyses 
No formal statistical analysis is planned. 


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A blind review of preliminary safety data (AE, clinical laboratory values, vital signs, 
ECG) will be conducted after Period 1 and Period 2 in Part 1 Furthermore, .the sponsor's 
person who is responsible for confirmation of concentration will review blood 
concentration of GSK1325756 under unblind. 
After completion of Part 1, formal analysis for Part 1 is to be conducted. 


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11. 
REFERENCES 
Chapman RW, Phillipsa JE, Hipkina RW, Currana AK, Lundella D and Fine JS. CXCR2 
antagonists for the treatment of pulmonary disease. Pharmacol. Ther. 2009; 121(1): 55-68. 
Lazaar AL, Sweeney LE, MacDonald AJ, Alexis NE, Chen C, Deans A, Tal-Singer R. 
SB-656933, a novel CXCR2 selective antagonist, inhibits ex-vivo neutrophil activation 
and ozone-induced airway inflammation in humans. Br J Clin Pharm 72:282-293, 2011. 
Fukuchi Y, Nishimura M, Ichinose M, Adachi M, Nagai A, Kuriyama T, Takahashi K, 
Nishimura K, Ishioka S, Aizawa H, Zaher C. COPD in Japan: the Nippon COPD 
Epidemiology study. Respirology 2004; 9: 458-465. 
 


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12. 
APPENDICES 
12.1. 
Appendix 1: Abbreviations and Trademarks 
Abbreviations 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
AUC(0-24) 
Area under the concentration-time curve from time 0 to 24 hours 
AUC(0-inf) 
Area under the concentration-time curve from time 0 to infinity 
AUC(0-t) 
Area under the concentration-time curve from time 0 to t 
BID 
Bis in die 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Maximum observed concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
COPD 
chronic obstructive pulmonary disease 
CK (CPK) 
Creatine phosphokinase 
(e)CRF 
(electronic) Case report form 
CSR 
Clinical Study Report 
CV 
Coefficient of variance 
CXCL8 
CXC chemokine ligand 8 
CXCR2 
CXC chemokine receptor 2 
ECG 
Electrocardiogram 
e.g. 
exempli gratia 
GCP 
Good Clinical Practice 
GCSP 
Global Clinical Safety and Pharmacovigilance 
GGT 
Gamma-glutamyl transpeptidase 
GI 
Gastrointestinal 
GSK 
GlaxoSmithKline 
h/hrs 
Hour(s) 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
HPLC 
high performance liquid chromatography 
HTLV-1 
Human T-cell lymphotropic virus type 1 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 


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ICH 
International Conference on Harmonization 
IDSL 
Integrated Data Standards Library 
i.e. 
id est 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IL-8 
Interleukin-8 
INR 
International Normalized Ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
kg 
Kilogram 
LDH 
Lactate dehydrogenase 
LDL 
Low-density lipoprotein 
log 
Logarithm 
MCH 
Mean corpuscular hemoglobin 
MCV 
Mean corpuscular volume 
µg 
Microgram 
mg  
Milligram 
mL 
Milliliter 
MSDS 
Material Safety Data Sheet 
msec 
Millisecond 
nm 
Nanometer 
NOAEL 
No observable adverse effect level 
oz 
ounce 
pH 
Pondus Hydrogenii 
PK 
Pharmacokinetic(s) 
PMDA 
Pharmaceuticals and Medical Devices Agency 
PPI 
Proton pump inhibitor 
PR 
Pulse rate 
QTc 
QT interval corrected 
QTcF 
QT interval corrected for heart rate by Friderician formula 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cells 
RNA 
ribonucleic acid 
RPR 
Rapid Plasma Reagin 
SAE 
Serious adverse event 
SD 
Standard Deviation 
SoA 
Schedule of Activities 
SRM 
Study reference manual 
SUSAR 
suspected unexpected serious adverse reactions 
t1/2 
Terminal half-life 
TG 
Triglyceride 
tlag 
Lag time before observable concentration 
tlast 
Time to last quantifiable concentration 
tmax 
Time to maximum observed concentration 


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TPHA 
Treponema pallidum hemagglutination test 
ULN 
Upper limit of normal 
UV 
Ultraviolet 
WBC 
White blood cells 
WOCBP 
Women of Childbearing Potential 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
 
 
WinNonlin 
 
 
 
 
 
 
 


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12.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 4 will be performed by the local laboratory.  
• 
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 6 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
Table 4 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1 
BUN 
Potassium 
Aspartate 
Aminotransferase 
(AST) 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
Alanine 
Aminotransferase 
 (ALT) 
Total Protein 
 
Glucose (fasting) 
Calcium 
Alkaline 
phosphatase 
Albumin 
Uric acid 
TG 
Total Cholesterol 
LDL-cholesterol 
HDL-cholesterol 
LDH 
GGT 
CK (CPK) 
 
Amylase 
Chloride 
 Phosphorus 
Routine 
Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen by dipstick 
• Microscopic examination (if blood or protein is abnormal) 
Other 
Screening 
Tests 
• Urine drug screen (to include at minimum: Phencyclidines, 
Benzodiazepines, Cocaine, Amphetamines, Tetrahydrocannabinol, Opiates, 
Barbiturates and Trycyclic antidepressants 
• Serology (Syphilis [RPR & TPHA], HIV antigen/antibody, HBsAg, HCV 
antibody and HTLV-1 antibody) 
NOTES : 
1. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 8.1 and Appendix 6. All events of ALT ≥ 3 × ULN and bilirubin ≥ 2 × ULN (> 
35% direct bilirubin) or ALT ≥ 3 × ULN and international normalized ratio (INR) > 1.5, if INR measured, which may 
indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding studies of hepatic 


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impairment or cirrhosis). 
 
Laboratory/analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded. 


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12.3. 
Appendix 3: Study Governance Considerations 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines 
• 
Applicable International Conference on Harmonization (ICH) Good Clinical 
Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB by the 
investigator and reviewed and approved by the IRB before the study is initiated.  
• 
Any amendments to the protocol will require IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB 
• Notifying the IRB of SAE or other significant safety findings as required 
by IRB procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
Informed Consent Process 
• 
The investigator will explain the nature of the study to the participant and 
answer all questions regarding the study.  
• 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 


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informed consent that meets the requirements of local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB or study centre.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study.  
• 
A copy of the ICF(s) must be provided to the participant.  
• 
Participants who are rescreened are required to sign a new ICF. 
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred.  
• 
The participant must be informed that his personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant.  
• 
The participant must be informed that his medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by 
the sponsor, by appropriate IRB members, and by inspectors from regulatory 
authorities. 
Publication Policy 
• 
The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.  
• 
The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicentre studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 


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laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF.  
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• 
The investigator must permit study-related monitoring, audits, IRB review, and 
regulatory agency inspections and provide direct access to source data 
documents.  
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the sponsor. 
No records may be transferred to another location or party without written 
notification to the sponsor.  
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the CRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
• 
Definition of what constitutes source data can be found in the list of the source 
documents. 
Study and Site Closure 
Study sites will be closed upon study completion. A study site is considered closed when 
all required documents and study supplies have been collected and a study-site closure 
visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 


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Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB 
or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study treatment development 


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12.4. 
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of a study treatment, whether or not considered related to the 
study treatment. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment. 
 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not related 
to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 


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convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 


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one of the other outcomes listed in the above definition. These events should usually 
be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
 
Recording AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK/AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities. 
• 
Moderate: An event that causes sufficiently discomfort and interferes with normal 
everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilized for rating 
the intensity of an event; and both AE and SAE can be assessed as severe. 
• 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe. 
 
 
Assessment of Causality 


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• 
The investigator is obligated to assess the relationship between study treatment and 
each occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated. 
• 
The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always makes an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK with a copy of any post-mortem 
findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 


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Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the site will use 
the paper SAE data collection tool (see next section). 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
The investigator or medically-qualified sub-investigator must show evidence within 
the eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to IP/study participation (causality) within 72 hours of SAE 
entry into the eCRF. 
• 
After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form. 
• 
Contacts for SAE reporting can be found in Section 12.7. 
 
SAE Reporting to GSK via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the medical monitor. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in Section 12.7. 
 


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12.5. 
Appendix 5: Contraceptive Guidance and Collection of 
Pregnancy Information 
Contraception Guidance 
Male participants 
• 
Male participants with female partners of child-bearing potential are eligible to 
participate if they agree to ONE of the following during the protocol-defined 
time frame in Section 6.1:  
• Are abstinent from penile-vaginal intercourse as their usual and preferred 
lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent  
• Agree to use a male condom plus an additional method of contraception 
with a failure rate of < 1% per year as described in Table 5 when having 
penile-vaginal intercourse with a woman of childbearing potential  
• 
Men with a pregnant or breastfeeding partner must agree to remain abstinent 
from penile-vaginal intercourse or use a male condom during each episode of 
penile penetration during the protocol-defined time frame  
• 
Refrain from donating sperm for duration of study and until follow up visit 
Table 5 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of < 1% per year when used consistently and correctly.  
Combined (estrogen- and progestogen-containing ) hormonal contraception associated with inhibition 
of ovulationb  
• oral 
Highly Effective Methods That Are User Independent  
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.)  
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and 
the preferred and usual lifestyle of the participant.)  


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NOTES:  
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with 
local regulations regarding the use of contraceptive methods for participants in clinical studies.  
b. 
Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of the 
contraceptive method. In this case two highly effective methods of contraception should be utilized during the 
treatment period and until follow up visit corresponding to time needed to eliminate study treatment  
 
Collection of Pregnancy Information 
Male participants with partners who become pregnant 
• 
Investigator will attempt to collect pregnancy information on any female partner of a 
male study participant who becomes pregnant while participating in this study. 
• 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy.  
• 
Partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK. 
• 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure.  


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12.6. 
Appendix 6: Liver Safety: Required Actions and Follow up 
Assessments 
Phase I liver chemistry stopping criteria and required follow up assessments 
Liver Chemistry Stopping Criteria  
 
ALT-absolute 
 
ALT ≥ 3xULN 
If ALT ≥ 3xULN AND bilirubin1,2 ≥ 2xULN (> 35% direct bilirubin) or INR > 1.5, 
Report as an SAE. 
See additional Actions and Follow Up Assessments listed below 
Required Actions and Follow up Assessments  
Actions 
Follow Up Assessments 
• Immediately discontinue study treatment 
• Report the event to GSK within 24 hours 
• Complete the liver event CRF, and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2 
• Perform liver event follow up assessments  
• Monitor the subject until liver chemistries 
resolve, stabilise, or return to within baseline 
(see MONITORING below) 
MONITORING: 
If ALT ≥ 3xULN AND bilirubin ≥ 2xULN or 
INR > 1.5 
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 
24 hrs 
• Monitor subjects twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline 
• A specialist or hepatology consultation is 
recommended 
If ALT ≥ 3xULN AND bilirubin < 2xULN and 
INR ≤ 1.5: 
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
• Viral hepatitis serology3 
• Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend 
• Obtain blood sample for PK analysis, 
obtained within 24 hours of last dose4 
• Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH) 
• Fractionate bilirubin, if total bilirubin ≥ 
2xULN 
• Obtain complete blood count with 
differential to assess eosinophilia 
• Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form 
• Record use of concomitant medications on 
the concomitant medications report form 
including over the counter medications 
• Record alcohol use on the liver event 
alcohol intake case report form 
If ALT ≥ 3xULN AND bilirubin ≥ 2xULN or 
INR > 1.5: 
• Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 


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Liver Chemistry Stopping Criteria  
liver event follow up assessments within 24-
72 hrs 
• Monitor subjects weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
total immunoglobulin G (IgG) or gamma 
globulins 
• Serum acetaminophen adduct high 
performance liquid chromatography 
(HPLC) assay (quantifies potential 
acetaminophen contribution to liver injury 
in subjects with definite or likely 
acetaminophen use in the preceding week 
[James, 2009]. NOTE: not required in 
China 
• Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy CRF forms 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that subject if ALT ≥ 3xULN and bilirubin ≥ 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary bilirubin on 
dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. 
All events of ALT ≥ 3xULN and bilirubin ≥ 2xULN (> 35% direct bilirubin) or ALT ≥ 3xULN and INR > 1.5, if INR 
measured, which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold value stated will 
not apply to subjects receiving anticoagulants 
3. 
Includes: Hepatitis A immunoglobulin M (IgM) antibody; HBsAg and Hepatitis B Core Antibody (IgM); Hepatitis 
C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); Hepatitis E IgM antibody  
4. 
PK sample may not be required for subjects known to be receiving placebo or non-GSK comparator treatments.  
Record the date/time of the PK blood sample draw and the date/time of the last dose of study treatment prior to 
PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the subject’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the SRM. 
 
References 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784. 
 
 


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12.7. 
Appendix 7: Country-specific requirements 
SPONSOR INFORMATION 
Sponsor Legal Registered Address: 
GlaxoSmithKline K.K.  
6-15, Sendagaya 4-chome Shibuya-ku, Tokyo 151-8566 Japan 
Study Director: 
 Head, Medicines Development, Clinical 
Pharmacology & Science Promotion Office 
Sponsor Contact Address: 
Lead Author: 
 
Medicines Development, Clinical Pharmacology & Science Promotion Office 
GlaxoSmithKline K.K. 
TEL: 
 
FAX: 
 
Monitoring Leader: 
 
Manager, Medicines Development, Clinical Pharmacology & Science Promotion Office 
GlaxoSmithKline K.K. 
TEL: 
 
FAX: 
 
Sponsor’s Emergency Contact Information (10:00~18:00, Monday to Friday, except 
national holidays and year-end and new-year holidays); 
Medicines Development (Clinical Pharmacology), GlaxoSmithKline K.K. 
TEL: 
 (direct dialling) 
FAX: 
 
Contact Information at Night and on Holidays (Monday to Friday: 18:00~10:00, Saturday, 
Sunday, national holidays, year-end and new-year holidays) 
 (Cell Phone: 
  
 (Cell Phone: 
 
Sponsor’s Medical Monitor/Medical Expert 
 
GlaxoSmithKline K.K. (GSK) 
6-15, Sendagaya 4-chome Shibuya-ku, Tokyo 151-8566 Japan 
TEL: 
 
FAX: 
 
Sponsor’s person who is responsible for concentration confirmation 
 
GlaxoSmithKline 
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Stockley Partk, West, Uxbridge, Middleesex, UB11 1BT, UK 
TEL: 
 
Medical Institution and Investigator 
Koichi Nakamura, MD 
Clinical Research Tokyo Hospital 
87-4 Haramachi 3-chome, NT Bldg. 3F, Shinjuku-ku, Tokyo 162-0053 Japan 
TEL: 
 
FAX: 
 
Laboratories 
Clinical Laboratory Measurement Facilities 
Role: Clinical Laboratory Tests (except for infectious diseases) 
Person in charge: 
 
Clinical Research Tokyo Hospital 
87-4 Haramachi 3-chome, NT Bldg. 3F Shinjuku-ku, Tokyo 162-0053 Japan 
TEL: 
 
FAX: 
 
 
Role: Clinical Laboratory Tests (infectious diseases) 
Person in charge: 
 
Health Sciences Research Institute, Inc. 
106 Godo-cho, Hodogaya-ku, Yokohama, Kanagawa 240-0005 Japan 
TEL: 
 
FAX: 
 
 
Role: Ophthalmic Examinations 
Person in charge: 
 MD 
Yakuoji I Clinic 
70 Ichigayayakuoji-machi, Arusu Ichigayayakuoji 1F, Shinjuku-ku, Tokyo 162-0063 
Japan 
TEL: 
 
FAX: 
 
 
Pharmacokinetics Measurement Facilities 
Person in charge: 
 
Covance Laboratories Limited 
Otley Road, Harrogate, North Yorkshire, HG3 1PY, UK 
TEL: 
 
 
Contract research organization 
Role: Study Monitoring 
Person in charge: 
 
Mediscience Planning Inc. 
Toranomon 15 Mori Building, 2-8-10 Toranomon, Minato-ku, Tokyo 105-0001 Japan 
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TEL: 
 
FAX: 
 
Role: Medical Writing (Protocol & Informed Consent Form)  
Person in charge: 
 
Mediscience Planning Inc. 
Toranomon 15 Mori Building, 2-8-10 Toranomon, Minato-ku, Tokyo 105-0001 Japan 
TEL: 
 
FAX: 
 
Role: Medical Writing (Clinical Study Report)  
Person in charge: 
 
Mediscience Planning Inc. 
Toranomon 15 Mori Building, 2-8-10 Toranomon, Minato-ku, Tokyo 105-0001 Japan 
TEL: 
 
FAX: 
 
Role: Pharmacokinetic Parameter Derivation 
Person in charge: 
 
Mediscience Planning Inc. 
HF Nihonbashi-hamacho Bldg.2-1, Nihonbashi-hamacho 1-chome, Chuo-ku,  
Tokyo 103-0007 Japan 
TEL: 
 
FAX: 
 
Role: Data Loading 
Person in charge: 
 
Mediscience Planning Inc. 
HF Nihonbashi-hamacho Bldg.2-1, Nihonbashi-hamacho 1-chome, Chuo-ku,  
Tokyo 103-0007 Japan 
TEL: 
 
FAX: 
 
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12.8. 
Appendix 8: Protocol Amendment History 
Not applicable 
 
 

SAP_001.pdf: 
 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
206817 
 
1 
 
Division 
: Worldwide Development 
Information Type    : Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for Study 206817: A Single 
Centre, Double Blind (Sponsor Open), Placebo Controlled, 3-
Period Crossover, Ascending Dose Study in Japanese Healthy 
Elderly Male Subjects to Evaluate the Safety, Tolerability and 
Pharmacokinetics of Danirixin in the Fed State (Part1) and an 
open label, 2-way crossover to evaluate food effect on the 
pharmacokinetics of Danirixin (Part2). 
Compound Number  : GSK1325756 
Effective Date  
: 11-JUL-2017 
 
Description: 
• The purpose of this reporting and analysis plan (RAP) is to describe the planned 
analyses and output to be included in the clinical pharmacology study report for 
protocol 206817.  
• This RAP is intended to describe the safety, pharmacokinetics analyses required for 
the study.  
• This document will be provided to the study team members to convey the content of 
the statistical analysis complete (SAC) deliverable. 
 
Author’s Name and Functional Area:  
 
5-Jul-2017 
Biostatistics Group 1 Manager, Biomedical Data Sciences 
Department, Japan. 
 
5-Jul-2017 
Clinical Pharmacology & Science Promotion Office, Medicines 
Development, Japan. 
 
Approved:  
 
11-Jul-2017 
Department Manager, Biomedical Data Sciences Department, 
Japan. 
 
Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
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TABLE OF CONTENTS 
PAGE 
1. 
REPORTING & ANALYSIS PLAN SYNPOSIS ......................................................... 4 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 6 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 6 
2.2. 
Study Objective(s) and Endpoint(s)............................................................... 6 
2.3. 
Study Design ................................................................................................ 7 
2.4. 
Statistical Hypotheses................................................................................... 8 
3. 
PLANNED ANALYSES............................................................................................. 9 
3.1. 
Interim Analyses ........................................................................................... 9 
3.2. 
Final Analyses .............................................................................................. 9 
4. 
ANALYSIS POPULATIONS ..................................................................................... 9 
4.1. 
Protocol Deviations ..................................................................................... 10 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 10 
6. 
STUDY POPULATION ANALYSES ....................................................................... 11 
6.1. 
Overview of Planned Analyses ................................................................... 11 
7. 
SAFETY ANALYSES ............................................................................................. 12 
7.1. 
Overview of Planned Adverse Events Analyses .......................................... 12 
7.2. 
Overview of Planned Clinical Laboratory Analyses ..................................... 12 
7.3. 
Overview of Planned Other Safety Analyses ............................................... 13 
8. 
PHARMACOKINETIC ANALYSES ......................................................................... 14 
8.1. 
Overview of Planned Pharmacokinetic Analyses ........................................ 14 
8.2. 
Drug Concentration Measures .................................................................... 14 
8.3. 
Pharmacokinetic Parameters ...................................................................... 15 
8.3.1. 
Deriving Pharmacokinetic Parameters ......................................... 15 
8.3.2. 
Summary of Pharmacokinetic Parameters ................................... 17 
8.3.3. 
Statistical Analysis of Pharmacokinetic Parameters ..................... 17 
9. 
REFERENCES ....................................................................................................... 19 
10. APPENDICES ........................................................................................................ 20 
10.1. 
Appendix 1: Protocol Deviation Management ............................................. 21 
10.2. 
Appendix 2: Time & Events ......................................................................... 22 
10.3. 
Appendix 3: Treatment States and Phases ................................................. 25 
10.3.1. 
Treatment Phases ....................................................................... 25 
10.3.2. 
Treatment States ......................................................................... 25 
10.4. 
Appendix 4: Data Display Standards & Handling Conventions .................... 26 
10.4.1. 
Study Treatment & Sub-group Display Descriptors ...................... 26 
10.4.2. 
Sequence group Display Descriptors ........................................... 26 
10.4.3. 
Baseline Definition & Derivations ................................................. 27 
10.4.4. 
Reporting Process & Standards ................................................... 27 
10.5. 
Appendix 5: Derived and Transformed Data ............................................... 30 


 
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10.5.1. 
General ........................................................................................ 30 
10.5.2. 
Study Population .......................................................................... 30 
10.5.3. 
Safety .......................................................................................... 31 
10.5.4. 
Pharmacokinetics ........................................................................ 32 
10.6. 
Appendix 6: Premature Withdrawals & Handling of Missing Data ............... 33 
10.6.1. 
Premature Withdrawals ................................................................ 33 
10.6.2. 
Handling of Missing Data ............................................................. 33 
10.6.3. 
Handling of Partial Dates ............................................................. 33 
10.6.4. 
Handling of Missing Data for Statistical Analysis .......................... 33 
10.7. 
Appendix 7: Values of Potential Clinical Importance ................................... 34 
10.7.1. 
Laboratory Values (Healthy Volunteers) ...................................... 34 
10.7.2. 
ECG (Healthy Volunteers) ........................................................... 35 
10.7.3. 
Vital Signs (Healthy Volunteers) .................................................. 35 
10.8. 
Appendix 8 - Abbreviations & Trade Marks ................................................. 36 
10.8.1. 
Abbreviations ............................................................................... 36 
10.8.2. 
Trademarks ................................................................................. 37 
10.9. 
Appendix 9: List of Data Displays ............................................................... 38 
10.9.1. 
Data Display Numbering .............................................................. 38 
10.9.2. 
Mock Example Referencing ......................................................... 38 
10.9.3. 
Deliverable [Priority] ..................................................................... 38 
10.9.4. 
Study Population Tables .............................................................. 39 
10.9.5. 
Safety Tables ............................................................................... 41 
10.9.6. 
Pharmacokinetic Tables ............................................................... 44 
10.9.7. 
Pharmacokinetic Figures ............................................................. 45 
10.9.8. 
ICH Listings ................................................................................. 47 
10.10. Appendix 10: Example Mock Shells for Data Displays ................................ 53 
10.10.1. Study population .......................................................................... 53 
10.10.2. Safety population ......................................................................... 76 
10.10.3. PK population .............................................................................. 97 
11. REVISION HISTORIY .......................................................................................... 109 
 
 


 
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1. 
REPORTING & ANALYSIS PLAN SYNPOSIS 
Overview 
Key Elements of the Reporting and Analysis Plan  
Purpose 
• 
The purpose of this RAP is to describe the planned analyses and output to be included 
in the Clinical Study Report for Protocol 206817. 
Protocol 
• 
Reporting and Analysis Plan is based on original protocol (Dated:11-Apr-2017) for study 
GSK1325756 / 206817 [GlaxoSmithKline Document Number:2016N309585_0] 
Objectives 
Part 1 
• 
To assess the safety, tolerability and PK following single doses of GSK1325756H 10, 
50 and 100 mg in the fed state in healthy Japanese subjects of over 65 years of age 
inclusive. 
Part 2 
• 
To investigate the safety, tolerability and food effect on PK of GSK1325756 following a 
single dose of 50 mg in the fed and fasted state, in healthy Japanese subjects of over 
65 years of age inclusive. 
Endpoints 
Part 1 and 2. 
• 
Adverse events (AEs) 
• 
Change from baseline of clinical laboratory values, vital signs, and electrocardiogram 
(ECG) parameters 
• 
Blood concentration of GSK1325756 
• 
Cmax, AUC(0-t), AUC(0-inf), AUC(0-24), tmax, t1/2, tlag, tlast of the blood 
concentration of GSK1325756, as data permit 
Study 
Design 
This study consists of two parts. 
• 
Part 1 is a double blind, placebo-controlled, 3-period crossover, ascending dose, single 
oral administration in the fed condition 
• 
Part 2 is an open label, 2-way crossover, single oral dose in the fed and fasted state. 
Analysis 
Population 
• 
Screened: Consisting of all subjects screened in the study  
• 
Screening Failure: Subjects who screened in the study but are never subsequently 
randomized. 
• 
Safety: All randomized subjects who take at least one dose of study treatment. 
• 
Pharmacokinetic: This population is defined as all subjects administered at least one 
dose of study treatment and who have PK sample taken and analysed. 
Hypothesis 
• 
The objectives of this study are to evaluate safety and tolerability of GSK1325756 and 
to estimate GSK1325756 Pharmacokinetic parameters. No formal statistical hypotheses 
will be tested in Part 1 and Part 2. Descriptive statistics will be used to assess safety 
and tolerability objectives. An estimation approach will be used to address the 
pharmacokinetic study objectives, where point estimates and corresponding 90% 
confidence intervals will be constructed. 
Safety 
Analyses 
• 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively according to GSK’s Integrated Data Standards Library (IDSL) standards. 
Pharmacoki
netic 
Analyses 
• 
Individual GSK1325756 blood concentration-time profiles (by part, treatment and 
subject) and median/mean (±SD) profiles by part and treatment will be plotted and 
listed. Treatment indicates dose group in Part 1 and the fed and fasted condition in Part 
2. 
• 
Blood concentration time data for GSK1325756 will be analyzed by non-compartmental 
methods using WinNonlin and derived PK parameters graphically present, summarised 


 
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Overview 
Key Elements of the Reporting and Analysis Plan  
and listed. No formal statistical analyses will be conducted. 
• 
Statistical analyses will be carried out to explore the dose proportionality of 
GSK1325756 as assessed by AUC(0-t) and Cmax using the Power Model (Part 1). 
• 
Statistical analyses will be carried out to explore the food effect of GSK1325756 as 
assessed by AUC(0-t) and Cmax using a mixed effects mode (Part 2). 


 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol [Dated: 11/APR/2017]. 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Part 1 
• 
To assess the safety, tolerability and PK 
following single doses of GSK1325756H 10, 
50 and 100 mg in the fed state in healthy 
Japanese subjects of over 65 years of age 
inclusive. 
Part 2 
• 
To investigate the safety, tolerability and food 
effect on PK of GSK1325756 following a 
single dose of 50 mg in the fed and fasted 
state, in healthy Japanese subjects of over 65 
years of age inclusive. 
Part 1 and Part 2 
• 
Adverse events (AEs) 
• 
Change from baseline of clinical laboratory values, 
vital signs, and electrocardiogram (ECG) 
parameters 
• 
Blood concentration of GSK1325756 
• 
Cmax, AUC(0-t), AUC(0-inf), AUC(0-24), tmax, t1/2, 
tlag, tlast of the blood concentration of 
GSK1325756, as data permit 
 


 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
Subjects will be divided into Part 1 and 2, and receive the following study treatment 
doses shown in Table below. 
Part 1: 
Group 
n 
Period 1 
Washout 
Period 2 
Washout 
Period 3 
A 
6 
10 mg 
at least 7 
days 
50 mg 
at least 7 
days 
Placebo 
B 
6 
10 mg 
Placebo 
100 mg 
C 
6 
Placebo 
50 mg 
100 mg 
 
Part 2: 
Group 
n 
Period 1 
Washout 
Period 2 
D 
8 
50 mg, fed 
at least 7 
days 
50 mg, fasted 
E 
8 
50 mg, fasted 
50 mg, fed 
 
Design 
Features 
Part 1: This is a double blind, placebo-controlled, 3-period crossover, ascending 
dose, single oral administration in the fed condition. 
Part 2: This is an open label, 2-way crossover, single oral dose in the fed and 
fasted state study. 
Dosing 
Part 1: 
Subjects will have a screening visit within 30 days prior to the first dose of 
study. A minimum washout period of 7 days will be required between 
each treatment period. Subjects will receive three treatment periods in the 
study. Subjects will be housed in the Clinical Research Unit from Day -1 
(the day before dosing) through Day 3 for Period 1 and 2, and from Day -1 
(the day before dosing) through Day 4 for Period 3. Subjects will return to 
the clinic 7 days (at least) after the previous administration day for Period 
1 and 2, and subjects will visit the unit on Day 8 (+/- 1 day) of the last 
dosing for Period 3 for follow-up. 
 
Part 2: 
Subjects will have a screening visit within 30 days prior to the first dose of 
study treatment, two treatment periods separated by at least 7 days, and 
follow-up. Subjects will be housed in the Clinical Research Unit from Day 
-1 (the day before dosing) through Day 3 (for Period 1 and 2), and re-visit 
7 (±1) days after the last dose of Period 2 for follow-up. 
Treatment 
Assignment 
• 
Sufficient participants will be randomised such that approximately 18 
in Part 1and 16 in Part 2 evaluable participants complete the study of 


 
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Overview of Study Design and Key Features 
each part. 
• 
If participants prematurely discontinue the study, additional 
participants may be enrolled as replacement participants and assigned 
to the same treatment sequence, if applicable, at the discretion of the 
sponsor in consultation with the investigator. 
• 
On Day 1 of each Part, participants will be assigned a unique number 
(randomization number) in ascending numerical order. The 
randomization number encodes the participant’s assignment to one of 
the 3 sequences in Part 1 and one of the 2 sequences in Part 2, 
according to the randomization schedule generated prior to the study 
by the Biomedical Data Sciences Department at GSK. 
• 
Participants will be randomized in a 1:1:1 ratio to receive sequence 
(A:B:C) for Part 1, or will be randomized in a 1:1 ratio to receive 
sequence (D:E) for Part 2. 
• 
Each participant will be dispensed blinded study treatment, labeled 
with his unique randomization number, throughout the study. 
• 
Investigators, participants and sponsor will remain blinded to each 
participant’s assigned study treatment throughout the course of the 
study. For the concentration evaluation after Period 2 of Part 1, the 
pre-specified sponsor's person who is responsible for the confirmation 
of the concentration will review blood drug concentration data under 
unblended. 
Interim 
Analysis 
• 
No formal statistical analysis is planned. 
• 
A blind review of preliminary safety data (AE, clinical laboratory 
values, vital signs, ECG) and blood concentration will be conducted 
between Period 2 and Period 3 in Part 1 and prior to Part 2. 
• 
After completion of Part 1, formal analysis for Part 1 is to be 
conducted. 
 
2.4. 
Statistical Hypotheses 
The objectives of this study are to evaluate safety, tolerability and PK profile of single 
dose of GSK1325756H and to investigate food effect of PK profile of single dose of 
GSK1325756H in healthy Japanese elderly subjects. No formal statistical hypotheses will 
be tested in Part 1 and Part 2. Descriptive statistics will be used to assess safety and 
tolerability objectives. An estimation approach will be used to address the PK study 
objectives, where point estimates and corresponding 95% confidence intervals will be 
constructed, unless otherwise stated. 


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
No formal statistical analysis is planned. However, following Period 1 and Period 2 of 
Part 1, a blind review of preliminary safety data (AE, clinical laboratory values, vital 
signs, ECGs) will be conducted between Period 2 and Period 3 in Part 1 and prior to Part 
2. Furthermore, the sponsor's person who is responsible for the confirmation of the 
concentration will review blood drug concentration data under unblended. 
3.2. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the 
following sequential steps: 
1. All subjects in each part have completed the study as defined in the protocol. 
2. All required database cleaning activities in each part have been completed and final 
database release and database freeze has been declared by Data Management for each 
part. 
3. All criteria for unblinding the randomisation codes have been met for Part 1. 
4. Randomisation codes have been distributed according to RandAll NG procedures. 
After completion of Part 1, formal analysis for Part 1 is to be conducted. 
4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Endpoint(s) Evaluated 
Screened 
• Consisting of all subjects screened in the 
study. 
Note: This definition indicates the same 
meaning as ‘All subjects who have subject 
number’ in a programming point of view. 
• Study Population 
Screening Failure  
• Subjects who screened in the study but are 
never subsequently randomized. All 
participants who sign the ICF have the 
screening test in the study. 
Note: This definition indicates the same 
meaning as ‘Subjects who have subject 
number but are never subsequently 
randomized’ in a programming point of view. 
• Study Population 
Safety 
• All randomized subjects who take at least 
one dose of study treatment. Participants will 
be analyzed according to the treatment they 
actually received. 
• Study Population 
• Safety 
Pharmacokinetic 
• This population is defined as all subjects 
• PK 


 
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Population 
Definition / Criteria 
Endpoint(s) Evaluated 
administered at least one dose of study 
treatment and who have PK sample taken 
and analysed. Participants will be analyzed 
according to the treatment they actually 
received. 
4.1. 
Protocol Deviations 
• 
Important protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarised and listed. 
• 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations and deviations which may lead to exclusion from the analysis are 
captured and categorised on the protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of protocol deviations. 
• 
A separate listing of all inclusion/exclusion criteria deviations will also be provided. 
This will be based on data as recorded on the inclusion/exclusion page of the eCRF. 
 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
Table 1 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions. 
Table 1 
Overview of Appendices 
Section Component 
10.1 
Appendix 1: Protocol Deviation Management 
10.2 
Appendix 2: Time & Events 
10.3 
Appendix 3: Treatment States and Phases 
10.4 
Appendix 4: Data Display Standards & Handling Conventions 
10.5 
Appendix 5: Derived and Transformed Data 
10.6 
Appendix 6: Premature Withdrawals & Handling of Missing Data 
10.7 
Appendix 7: Values of Potential Clinical Importance 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Analyses 
The study population analyses will be based on the Safety Population, unless otherwise 
specified. These analyses will be performed in each part. 
Table 2 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 9: List of Data Displays. 
Table 2 
Overview of Planned Study Population Analyses 
Display Type 
Data Displays Generated 
Table 
Figure 
Listing 
Subject Disposition 
Subject Disposition and Reason for Study Withdrawal 
Y 
 
Y 
Screening Status and Reasons for Screen Failure 
Y 
 
Y 
Subjects for Whom the Treatment Blind was Broken 
 
 
Y 
Planned and Actual Treatments 
 
 
Y 
Protocol Deviations 
Important Protocol Deviations 
Y 
 
Y 
Inclusion/Exclusion Criteria Deviations 
 
 
Y 
Populations Analysed 
Study Populations 
Y 
 
 
Subjects Excluded from Any Population 
 
 
Y 
Demographic and Baseline Characteristics 
Demographic Characteristics 
Y 
 
Y 
Demographic Characteristics for Screening Failure 
 
 
Y 
Age Ranges 
Y 
 
 
Race and Racial Combinations 
Y 
 
Y 
Race and Racial Combinations for Screening Failure 
 
 
Y 
Medical Conditions and Concomitant Medications 
Medical Conditions 
 
 
Y 
Concomitant Medications 
 
 
Y 
Exposure and Treatment Compliance 
Exposure to Study Treatment 
 
 
Y 
Meal 
Meal start and end days/times on fed treatment 
 
 
Y 
NOTES: 
• 
Y = Yes display generated. 
 


 
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7. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety Population, unless otherwise specified. 
These analyses will be performed in each part. 
Adverse events occurred in washout period will be included in adverse events analyses 
for previous period. Also adverse events occurred in follow up period will be included in 
safety analyses for the last period. 
7.1. 
Overview of Planned Adverse Events Analyses 
Table 3 provides an overview of the planned adverse events analyses with full details of 
data displays being presented in Appendix 9: List of Data Displays. 
Table 3 
Overview of Planned Adverse Event Analyses 
Display Type 
Absolute 
Summary 
Individual 
T 
F 
L 
Adverse Events (AEs) 
All AEs by SOC and PT 
Y 
 
Y 
All AEs by Maximum Intensity 
Y 
 
 
Drug-Related AEs by SOC and PT 
Y 
 
 
Drug-Related AEs by Maximum Intensity 
Y 
 
 
Subject Numbers for Individual AEs 
 
 
Y 
Relationship Between AE SOCs, PT and Verbatim Text 
 
 
Y 
Serious and Other Significant AEs 
Serious AEs 
 
 
Y 
AEs Leading to Withdrawal from Study  
 
 
Y 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated, SOC = System Organ Class, PT = Preferred 
Term. 
• 
Summary = Represents TF related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data.  
 
7.2. 
Overview of Planned Clinical Laboratory Analyses 
Table 4 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 9: List of Data Displays. 
Table 4 
Overview of Planned Clinical Laboratory Analyses 
Display Type 
Absolute 
Change from BL 
Summary Individual Summary 
Individual 
T 
F 
L 
T 
F 
L 
Chemistry 
Chemistry Data 
Y 
 
Y 
Y 
 
Y 


 
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Display Type 
Absolute 
Change from BL 
Summary Individual Summary 
Individual 
T 
F 
L 
T 
F 
L 
Chemistry Results Relative to Normal Range 
 
 
 
Y 
 
 
All Chemistry Data for Subjects with any Value of 
Potential Clinical Concern/PCI 
 
 
Y 
 
 
Y 
Hematology 
Hematology Data 
Y 
 
Y 
Y 
 
Y 
Hematology Results Relative to Normal Range 
 
 
 
Y 
 
 
All Hematology Data for Subjects with any Value of 
Potential Clinical Concern/PCI 
 
 
Y 
 
 
Y 
Urinalysis 
Dipstick Data (Glucose, Protein, Blood, Ketones, 
Bilirubin, Urobilinogen) 
Y 
 
Y* 
 
 
 
Gravity and pH 
Y 
 
Y 
 
 
 
Hepatobiliary (Liver) 
Liver Monitoring/Stopping Event Reporting 
 
 
Y 
 
 
 
Medical Conditions for Subjects with Liver Stopping 
Events 
 
 
Y 
 
 
 
Substance Use for Subjects with Liver Stopping Events 
 
 
Y 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated, PCI = Potential Clinical Importance 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data.  
*: If blood or protein is abnormal, microscopic examination will be included. 
7.3. 
Overview of Planned Other Safety Analyses 
Table 5 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 9: List of Data Displays. 
Table 5 
Overview of Planned Other Safety Analyses 
Display Type 
Absolute 
Change from BL 
Summary Individual Summary 
Individual 
T 
F 
L 
T 
F 
L 
ECG 
ECG Findings 
Y 
 
Y 
 
 
 
ECG Values 
Y 
 
Y 
Y 
 
Y 
All ECG Values for Subjects with any Value of PCI 
 
 
Y 
 
 
 
Vital Signs 
Vitals Values 
Y 
 
Y 
Y 
 
Y 
All Vital Signs for Subjects with any Value of PCI 
 
 
Y 
 
 
 


 
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Display Type 
Absolute 
Change from BL 
Summary Individual Summary 
Individual 
T 
F 
L 
T 
F 
L 
Ophthalmic examinations 
Ophthalmic examinations 
 
 
Y 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated, PCI = Potential Clinical Importance 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 
 
8. 
PHARMACOKINETIC ANALYSES 
8.1. 
Overview of Planned Pharmacokinetic Analyses  
The pharmacokinetic (PK) analyses will be based on the Pharmacokinetic population, 
unless otherwise specified. These analyses will be performed in each part. 
Table 6 provides an overview of the planned analyses, with full details being presented in 
Appendix 9: List of Data Displays. 
Table 6 
Overview of Planned Pharmacokinetic Analyses 
Display Type 
Untransformed 
Log-Transformed 
Summary 
Individual 
Stats 
analysis 
Summary 
Individual 
F 
T 
F 
L 
 
F 
T 
F 
L 
Descriptive statistics 
Blood Drug Concentrations 
Y [1] [2] 
Y 
Y [1] 
Y 
 
 
 
 
 
Derived PK Parameters 
Y 
Y 
 
Y 
 
 
Y 
 
 
Statistical Analysis of PK Parameters 
Power model (Part 1) 
 
 
 
 
Y 
 
 
 
 
Food effect (Part 2) 
 
 
 
 
Y 
 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated. 
• 
Summary = Represents TFL related to any summaries (descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 
1. 
Linear and Semi-Log plots will be created on the same display. 
2. 
Separate Mean (+ SD) and Median plots will be generated. 
 
8.2. 
Drug Concentration Measures  
Blood concentrations of GSK1325756 will be listed and summarised by part, treatment 
and nominal time. Standard summary statistics will be calculated (i.e. mean, standard 
deviation, median, minimum and maximum). 


 
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Individual blood concentration-time profiles and median/mean profiles by treatment will 
be plotted. Each of the figures will contain one plot on the untransformed scale (i.e. a 
linear plot) and one plot on the log transformed scale (i.e. log-linear plot). 
Refer to Appendix 4: Data Display Standards & Handling Conventions (Section 10.4.4 
Reporting Process & Standards). 
8.3. 
Pharmacokinetic Parameters  
8.3.1. 
Deriving Pharmacokinetic Parameters 
• 
Derivation of pharmacokinetic parameters will be performed by, or under the direct 
auspices of, Clinical Pharmacology & Science Promotion Office, GlaxoSmithKline 
K.K. 
• 
Refer to Appendix 4: Data Display Standards & Handling Conventions (Section 
10.4.4 Reporting Process & Standards). 
• 
The pharmacokinetic parameters will be calculated by standard non-compartmental 
analysis using WinNonlin (version 6.3 or higher) 
• 
All calculations of non-compartmental parameters will be based on actual sampling 
times recorded during the study. 
• 
Pharmacokinetic parameters described in Table 7 will be determined from blood 
GSK1325756 concentration-time data, as data permits. 
 
Table 7 
Derived Pharmacokinetic Parameters 
Parameter 
Parameter Description 
AUC(0-24) 
(h*ng/mL) 
Area under the concentration-time curve will be calculated to fixed nominal time 24 
hours after administration (AUC(0-24)),using the combination of linear and logarithmic 
trapezoidal methods (i.e., Linear Up/Log Down calculation method in Phoenix 
WinNonlin Professional). 
If a sampling time deviation occurred at nominal time 24 hours after administration (and 
24 < t), AUC(0-24) will be calculated using the concentration at time 24 hours after 
administration post-dose estimated by the method of interpolation. 
If nominal time 24 hours after administration > t (or if the concentration at time 24 hours 
after administration was below then limit of quantification), then the concentration (y) at 
time 24 hours after administration is estimated using lambda_z and last observed Ct 
according to the formula: 
 
y=Ct(obser) x e-lambda_z(24-t) 
 
Then the following equation will be used to calculate (AUC(0-24)) where t is the time of 
last quantifiable blood concentration. 
 


 
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Parameter 
Parameter Description 
AUC(0-24) = AUC(0-t) + AUC(t-24) 
 
If lambda_z is not estimable, a partial AUC is not calculated (when 24 > t). 
AUC(0-t) 
(h*ng/mL) 
Area under the concentration-time curve from zero time (pre-dose) to the time of the 
last quantifiable concentration (AUC(0-t)) will be calculated by a combination of linear 
and logarithmic trapezoidal methods. The linear trapezoidal method will be employed 
for all incremental trapezoids arising from increasing concentrations and the logarithmic 
trapezoidal method will be used for those arising from decreasing concentrations (i.e., 
Linear Up/Log Down calculation method in Phoenix WinNonlin Professional). 
AUC(0-inf) 
(h*ng/mL) 
Area under the concentration-time curve from zero time (pre-dose) extrapolated to 
infinite time (AUC(0-inf)) will be calculated as follows:  
AUC(0-inf) = AUC(0-t) + Ct / lambda_z 
Cmax (ng/mL) 
Maximum observed concentration will be obtained directly from the concentration-time 
data. 
Tmax (h) 
Time to first occurrence of Cmax will be obtained directly from the concentration-time 
data. 
t1/2 (h) 
Terminal phase half-life will be calculated as follows: 
t1/2 = ln2 / lambda_z 
tlag (h) 
Lag time before observation of drug concentrations in sampled matrix. 
tlast (h) 
The time of the last measurable (positive) concentration. 
%AUCex (%) 
The area under the curve (AUC) from the last predicted non-zero concentration value 
to infinity as a percentage of the area under the curve extrapolated to infinity. 
lambda_z (/h) 
The first order rate constant associated with the terminal (log-linear) portion of the 
curve. 
lambda_z_lower 
(h) 
The lower limit on time for values to be included in the calculation of Lambda z. 
lambda_z_upper 
(h) 
The upper limit on time for values to be included in the calculation of Lambda z. 
#pts 
The number of time points used in computing Lambda z. 
R2 
The goodness of fit statistic for the terminal elimination phase. 
NOTES: 
• 
Additional parameters may be included as required. 
• 
Lambda_z is the terminal phase rate constant. 
• 
Ct is the last observed quantifiable concentration. 


 
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8.3.2. 
Summary of Pharmacokinetic Parameters 
• 
For each of these parameters, except for tmax, tlag and tlast, the following summary 
statistics will be calculated for each treatment: 
o Non-transformed: arithmetic mean, median, maximum, minimum, 95% 
confidence interval for the arithmetic mean and standard deviation 
o Loge-transformed: geometric mean, 95% confidence interval for the geometric 
mean, standard deviation of logarithmically transformed data and between 
geometric coefficient of variation (CVb (%))  
• 
Median, maximum, minimum, arithmetic mean, 95% confidence interval and 
standard deviation will be calculated for tmax, tlag and tlast. 
 
8.3.3. 
Statistical Analysis of Pharmacokinetic Parameters 
8.3.3.1. 
Dose proportionality 
For Part 1, the PK-dose relationship will be investigated graphically in order to assess 
dose proportionality of GSK1325756. Plots of AUC (0-t) and Cmax versus dose will be 
plotted. 
Also statistical analyses will be carried out to explore the dose proportionality of 
GSK1325756 as assessed by AUC(0-t) and Cmax, using the Power Model: 
loge (Yij) = μ + Si + β*loge (Dj) + εij 
  Yij: PK parameter (AUC(0-t), Cmax) on the jth dose for ith subject 
  μ: Overall mean (Intercept) 
  Si: Random effect for subject i following normal distribution N(0, σb2) 
  β: Slope for loge transformed dose 
  Dj: Dose (j=1:10mg, 2:50mg, 3:100mg) 
  εij: Random error following normal distribution N(0, σw2) 
Following loge-transformation, AUC (0-t) and Cmax will be separately analyzed, if data 
permitted. A mixed effect model will be fitted with the loge transformed dose and period 
as fixed effects. Subject will be fitted as a random effect. The Kenward & Roger (KR) 
degrees of freedom approach will be used. Point estimates and their associated 90% 
confidence intervals will be constructed. 
8.3.3.2. 
Food effect 
For Part 2, statistical analyses will be carried out to assess treatment (food effect) of 
GSK1325756 for AUC(0-t) and Cmax using Mixed effect model: 


 
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loge (Yij) = μ + Si + tj + pk + εij 
  Yij: PK parameter (AUC(0-t), Cmax) on the jth treatment for ith subject 
  μ: Overall mean (Intercept) 
  Si: Random effect for subject i following normal distribution N(0, σb2) 
  ti : Treatment effect (j=fasted, fed) 
  pk: Period effect (k=period 1, period 2) 
  εij: Random error following normal distribution N(0, σw2) 
Following loge-transformation, AUC (0-t) and Cmax will be separately analysed using a 
mixed effects model fitting terms for treatment and period as fixed effects, and subject as 
a random effect in order to assess food effect of GSK1325756 (Fed vs. Fasted). The 
Kenward & Roger (KR) degrees of freedom approach will be used. 
Point estimates for the adjusted means on the loge scale, the mean difference between 
treatments and associated 90% confidence interval will be constructed using the residual 
variance. The point estimate and confidence interval will then be exponentially back-
transformed to obtain adjusted (least square) geometric means for each treatment, and 
point estimates and associated 90% confidence interval for the ratio of fasted/fed. 
Estimates of within-subject variability (CVw (%)) for AUC (0-t) and Cmax will also be 
provided. CVw (%) will be calculated based on the loge-normal distribution where: 
    CVw (%)= SQRT(exp(MSE)-1) * 100. (MSE is the residual mean squared error 
from the model) 


 
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9. 
REFERENCES 
GlaxoSmithKline Document Numbers 2016N309585_01: Study Protocol of 206817. A 
Single Centre, Double Blind (Sponsor Open), Placebo Controlled, 3-Period Crossover, 
Ascending Dose Study in Japanese Healthy Elderly Male Subjects to Evaluate the Safety, 
Tolerability and Pharmacokinetics of Danirixin in the Fed State (Part1) and an open label, 
2-way crossover to evaluate food effect on the pharmacokinetics of Danirixin (Part2). 


 
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10. 
APPENDICES 
Section 
Appendix 
RAP Section 4 : Analysis Populations 
Section 10.1 
Appendix 1: Protocol Deviation Management 
RAP Section 5 : General Considerations for Data Analyses & Data Handling Conventions 
Section 10.2 
Appendix 2: Time and Events 
Section 10.3 
Appendix 3: Treatment States & Phases 
Section 10.4 
Appendix 4: Data Display Standards & Handling Conventions 
• Study Treatment 
• Baseline Definitions & Derivations 
• Reporting Process & Standards 
Section 10.5 
Appendix 5: Derived and Transformed Data 
• General 
• Study Population 
• Safety 
• Pharmacokinetics 
Section 10.6 
Appendix 6: Premature Withdrawals & Handling of Missing Data 
• General 
• Study Population & Safety 
Section 10.7 
Appendix 7: Values of Potential Clinical Importance 
• Laboratory Values 
• ECG 
• Vital Signs 
Other RAP Appendices 
Section 10.8 
Appendix 8: Abbreviations & Trade Marks 
Section 10.9 
Appendix 9: List of Data Displays 
Section 10.10 
Appendix 10: Example Mock Shells for Data Displays 
 


 
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10.1. 
Appendix 1: Protocol Deviation Management  
Details will be referred latest Protocol Deviation Management Plan and data handling 
will be decided prior to final data base release. 
 
 


 
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10.2. 
Appendix 2: Time & Events 
 
Part 1, Period 1-2 
 
 


 
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Part 1, Period 3 
 
 
 
 
 


 
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Part 2, Period 1-2 
 
 


 
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10.3. 
Appendix 3: Treatment States and Phases 
10.3.1. 
Treatment Phases 
Assessments and events will be classified according to the time of occurrence relative to 
the assessment date. 
Treatment Phase 
Definition 
Part 1: Period 1 
Assessment Date < Previous Day of Dosing Start Date in Period 2 (Part 1) 
Part 1: Period 2 
Previous Day of Dosing Start Date in Period 2 ≤ Assessment Date < Previous Day 
of Dosing Start Date in Period 3 (Part 1) 
Part 1: Period 3 
Previous Day of Dosing Start Date in Period 3 ≤ Assessment Date (Part 1) 
Part 2: Period 1 
Assessment Date < Previous Day of Dosing Start Date in Period 2 (Part 2) 
Part 2: Period 2 
Previous Day of Dosing Start Date in Period 2 ≤ Assessment Date (Part 2) 
 
10.3.2. 
Treatment States 
Assessments and events will be classified according to time of occurrence relative to the 
start and/or stop date of the study treatment. 
10.3.2.1. 
Treatment States for AE Data 
Treatment State 
Definition 
Pre-Treatment 
AE Start Date and Time < Dosing Start Date and Time 
Part 1: Period 1 
Dosing Start Date and Time in Period 1 ≤ AE Start Date and Time < Dosing Start 
Date and Time in Period 2 (Part 1) 
Part 1: Period 2 
Dosing Start Date and Time in Period 2 ≤ AE Start Date and Time < Dosing Start 
Date and Time in Period 3 (Part 1) 
Part 1: Period 3 
Dosing Start Date and Time in Period 3 ≤ AE Start Date and Time (Part 1) 
Part 2: Period 1 
Dosing Start Date and Time in Period 1 ≤ AE Start Date and Time < Dosing Start 
Date and Time in Period 2 (Part 2) 
Part 2: Period 2 
Dosing Start Date and Time in Period 2 ≤ AE Start Date and Time (Part 2) 
Onset Time Since 
First Dose (Minute) 
If Dosing Start Date and Time ˃ AE Onset Date and Time = AE Onset Date and 
Time – Dosing Start Date and Time 
If dosing Start Date and Time ≤ AE Onset Date and Time = AE Onset Date and 
Time - Dosing Start Date and Time +1 
Missing otherwise 
Onset Time Since 
Last Dose (Minute) 
AE Start Date and Time – Most Recent Treatment Start Date and Time + 1 
Duration (Minute)  
AE Resolution Date and Time – AE Onset Date and Time + 1 
Drug-related 
If relationship is marked ‘YES’ on eCRF 
 
 


 
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10.4. 
Appendix 4: Data Display Standards & Handling 
Conventions 
10.4.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
Part1 (Scedule1) 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description 
Order [1] 
P 
Placebo, Fed 
Placebo, Fed 
1 
X1 
GSK1325756H 10 mg, Fed 
GSK1325756H 10 mg, Fed 
2 
X2 
GSK1325756H 50 mg, Fed 
GSK1325756H 50 mg, Fed 
3 
X3 
GSK1325756H 100 mg, Fed 
GSK1325756H 100 mg, Fed 
4 
Part2 (Scedule2) 
X2 
GSK1325756H 50 mg, Fed 
GSK1325756H 50 mg, Fed 
1 
X4 
GSK1325756H 50 mg, Fasted 
GSK1325756H 50 mg, Fasted 
2 
NOTES: 
1. 
Order in which treatments are to be presented in Listings. Note that the order in which treatments are to be 
presented in Tables, active treatment (X1, X2, X3 in Part 1, X2, X4 in Part 2) is shown in the first and placebo (P in 
Part 1) in the second. 
 
10.4.2. 
Sequence group Display Descriptors 
Sequence Group Descriptions 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description [1] 
Order  
A 
X1/X2/P 
A 
1 
B 
X1/P/X3 
B 
2 
C 
P/X2/X3 
C 
3 
D 
X2/X4 
D 
4 
E 
X4/X2 
E 
5 
NOTES: 
1. 
Footnote will be added in displays as follows. 
A: 10mg (Fed) / 50mg (Fed) / Placebo (Fed), B: 10mg (Fed) / Placebo (Fed) / 100mg (Fed), C: Placebo (Fed) / 
50mg (Fed) / 100mg (Fed), D: 50mg (Fed) / 50mg (Fasted) , E: 50mg (Fasted) / 50mg (Fed) 
 
 


 
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10.4.3. 
Baseline Definition & Derivations 
10.4.3.1. 
Baseline Definitions 
Parameter 
Study Assessments Considered 
as Baseline 
Baseline Used in 
Data Display 
Screening 
Day -1 
Day 1   
(Pre-Dose) 
Safety 
12 Lead ECG & Vital Signs 
X 
X 
X 
Day 1 
(Pre Dose) 
Haematology  
X 
X 
 
Day -1 
Clinical Chemistry 
X 
X 
 
Day -1 
NOTES: 
• 
The baseline will be defined for each period in Part 1 and Part 2. 
10.4.3.2. 
Derivations and Handling of Missing Baseline Data 
Definition 
Reporting Details 
Change from Baseline 
= Post-Dose Visit Value – Baseline 
NOTES: 
• 
Unless otherwise specified, the baseline definitions specified in Section 10.4.3.1 Baseline Definitions will be used 
for derivations for endpoints / parameters and indicated on summaries and listings. 
• 
Unless otherwise stated, if baseline data is missing no derivation will be performed and will be set to missing. 
• 
The baseline definition will be footnoted on all change from baseline displays. 
 
10.4.4. 
Reporting Process & Standards 
Reporting Process 
Software 
• The currently supported versions of SAS software will be used. 
Reporting Area  
HARP 
Server 
: uk1salx00175 
HARP Area 
Part1:/arenv/arprod/gsk1325756/mid206817/primary_01 
Part2:/arenv/arprod/gsk1325756/mid206817/final_01 
QC 
Spreadsheet 
Part1:/arenv/arprod/gsk1325756/mid206817/primary_01/qc 
Part2:/arenv/arprod/gsk1325756/mid206817/final_01/qc 
Analysis Datasets  
• Analysis datasets will be created according to GSK IDSL A&R dataset standards 
Generation of RTF Files 
• N/A 
 
 


 
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Reporting Standards 
General 
• The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated: 
o 4.03 to 4.23: General Principles 
o 5.01 to 5.08: Principles Related to Data Listings 
o 6.01 to 6.11: Principles Related to Summary Tables 
o 7.01 to 7.13: Principles Related to Graphics  
Formats 
• All data will be reported according to the actual treatment the subject received unless 
otherwise stated. 
• GSK IDSL Statistical Principles (4.24) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected. 
• Numeric data will be reported at the precision collected on the eCRF. 
• The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
• Reporting for tables, figures and formal statistical analyses: 
o Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
o The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as appropriate. 
• Reporting for Data Listings: 
o Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1). 
o Unscheduled or unplanned readings will be presented within the subject’s listings. 
o Visits outside the protocol defined time-windows (i.e. recorded as protocol deviations) will 
be included in listings but omitted from figures, summaries and statistical analyses. 
Unscheduled Visits 
• Unscheduled visits will not be included in summary tables. 
• Unscheduled visits will not be included in figures. 
• All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Reporting of Pharmacokinetic Concentration Data 
Descriptive Summary 
Statistics 
Refer to IDSL Statistical Principle 6.06.1 
Assign zero to NQ values (Refer to GUI_51487 for further details) 


 
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Reporting Standards 
Reporting of Pharmacokinetic Parameters 
Descriptive Summary 
Statistics.           
(Log Transformed) 
N, n, geometric mean, 95% CI of geometric mean, standard deviation 
(SD) of logged data and between geometric coefficient of variation 
(CVb/w (%)) will be reported. 
CVb (%) = SQRT (exp(SD2) - 1) * 100  
(SD = SD of loge-transformed data) 
CVw (%) =SQRT (exp(MSE) - 1) * 100  
(MSE = mean square error from mixed effect model of loge-transformed data). 
Parameters Not Being 
Log Transformed   
tmax, tlag, tlast 
Parameters Not Being 
Summarised 
The following PK parameters will not be summarised but listed: %AUCex, 
lambda_z, lambda_z_lower, lambda_z_upper, #pts, R2. 
Graphical Displays 
• Refer to IDSL Statistical Principals 7.01 to 7.13. 
 


 
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10.5. 
Appendix 5: Derived and Transformed Data 
10.5.1. 
General 
Multiple Measurements at One Time Point 
• Mean of the measurements will be calculated and used in any derivation of summary statistics 
but if listed, all data will be presented. 
• If there are two values within a time window the value closest to the target day for that window 
will be used. If values are the same distance from the target, then the mean will be taken. 
• Subjects having both High and Low values for Normal Ranges at any post-baseline visits for 
safety parameters will be counted in both the High and Low categories of “Any visit post-
baseline” row of related summary tables. This will also be applicable to relevant Potential 
Clinical Importance summary tables. 
Study Day 
• Calculated as the number of days from start of dosing date: 
o 
Ref Date = Missing           → Study Day = Missing  
o 
Ref Date < of start of dosing Date → Study Day = Ref Date – of start of dosing Date     
o 
Ref Data ≥ of start of dosing Date → Study Day = Ref Date – (of start of dosing Date) + 1 
 
10.5.2. 
Study Population 
Demographics 
Age 
• GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed 
as: 
o 
Any subject with a missing day will have this imputed as day ‘15’. 
o 
Any subject with a missing date and month will have this imputed as ‘30th June’. 
• Birth date will be presented in listings as ‘YYYY’. 
• Reference will be Randomization date for Part 1 and Part 2 
• Reference date for calculation of age at screening will be from visit 1 (Screening visit) date, 
however this will be from screen failure date for a screen failure subject. 
• Analysis age group will be categorized (Years): 
   <=18, 19-64, 65-74, >=75 
• Age will be categorized for EudraCT: 
   <=17 years, 18-64 years, 65-84 years, >=85 years 
Body Mass Index (BMI) 
• Calculated as Weight (kg) / [Height (m)2] 
 


 
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10.5.3. 
Safety 
Laboratory Parameters 
• If a laboratory value which is expected to have a numeric value for summary purposes, has a 
non-detectable level reported in the database, where the numeric value is missing, but typically 
a character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the 
comment field) is present, the number of significant digits in the observed values will be used to 
determine how much to add or subtract in order to impute the corresponding numeric value.  
o Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01 
o Example 2: 1 Significant Digit   =  ‘> x’ becomes x + 0.1 
o Example 3: 0 Significant Digits = ‘< x’ becomes x – 1 
 
Laboratory Assessments 
Haematology 
Platelet Count, RBC Count, Haemoglobin, Hematocrit, RBC Indices (MCV, 
MCH, %Reticulocytes), WBC count with Differential (Neutrophils, 
Lymphocytes, Monocytes, Eosinophils, Basophils) 
Clinical Chemistry 
BUN, Creatinine, Glucose (fasting), Uric acid, HDL-cholesterol, Amylase, 
Potassium, Sodium, Calcium, TG, LDH, Chloride, Aspartate Aminotransferase 
(AST), Alanine Aminotransferase (ALT), Alkaline phosphatise, Total 
Cholesterol, GGT, Phosphorus, Total and direct bilirubin, Total Protein, 
Albumin, LDL-cholesterol, CK (CPK) 
Routine Urinalysis 
• Specific gravity, pH (assessed by dipstick) 
• glucose, protein, blood, ketones, bilirubin, urobilinogen by dipstick 
• Microscopic examination (if blood or protein is abnormal) 
 
ECG (12-lead ECG) 
ECG findings, ECG values (Heart rate, PR interval, QRS duration, QT interval and QTcF intervals) 
 
Vital Signs 
Pulse rate, Blood pressure (Systolic, Diastolic),Temperature 
 
Ophthalmic examinations 
Ophthalmic examinations 
 


 
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10.5.4. 
Pharmacokinetics 
PK Parameters 
• If one or more non-quantifiable (NQ) values occur in a profile before the first measurable 
concentration, they will be assigned a value of zero concentration. For linear plots, zero 
concentration value(s) before the first measurable concentration will be included in the plot. For 
log-linear plots, zero concentration value(s) before the first measurable concentration will be 
assigned a missing value. 
• If a single NQ value occurs between measurable concentrations in a profile, the NQ should 
generally be set to missing in the derivation of pharmacokinetic parameters, statistical analysis, 
and the individual subject plots. 
• If two or more NQ values occur in succession between measurable concentrations, the profile 
will be deemed to have terminated at the last measurable concentration prior to these NQs. 
For the purpose of individual subject plots, these NQs will be set to 0, and the subsequent 
measurable concentrations will be retained. For the derivation of pharmacokinetic parameters, 
these NQs and any subsequent measurable concentrations will be set to missing. 
• NQs which occur after the last measurable concentration will be omitted (set to missing) in the 
derivation of pharmacokinetic parameters and from the individual subject plots. 
• Individual’s PK parameters reported as 'NC' (Not Calculable) or 'ND' (Not Determined) will be 
included in listings but omitted (set to missing) from figures, summaries and statistical 
analyses. 
 
 
 


 
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10.6. 
Appendix 6: Premature Withdrawals & Handling of Missing 
Data 
10.6.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• Subject study completion was defined as a participant has completed all periods 
of the study including the last visit or the last scheduled procedure (Follow-up) 
for each period as described in the protocol. 
• Withdrawn subjects maybe replaced in the study. 
• All available data from subjects who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, 
unless otherwise specified. 
 
10.6.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument: 
o These data will be indicated by the use of a “blank” in subject listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table. 
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
 
10.6.3. 
Handling of Partial Dates 
Element 
Reporting Detail 
Concomitant 
Medications 
• Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. 
• The recorded partial date will be displayed in listings. 
 
10.6.4. 
Handling of Missing Data for Statistical Analysis 
Element 
Reporting Detail 
Imputation 
• No imputation will be performed for missing data 
 
 


 
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10.7. 
Appendix 7: Values of Potential Clinical Importance 
10.7.1. 
Laboratory Values (Healthy Volunteers) 
Haematology 
Laboratory Parameter 
 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Hematocrit  
Ratio of 1 
Male 
 
0.54 
Female 
 
0.54 
∆ from BL 
↓0.075 
 
Hemoglobin  
g/L 
 
Male 
 
180 
Female 
 
180 
∆ from BL 
↓25 
 
Lymphocytes  
x109/ L 
 
0.8 
 
Neutrophil Count  
x109/ L 
 
1.5 
 
Platelet Count  
x109/ L 
 
100 
550 
While Blood Cell Count (WBC) 
x109/ L 
 
3 
20 
 
Clinical Chemistry 
Laboratory Parameter 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Albumin  
G/L 
 
30 
 
Calcium 
mmol/L 
 
2 
2.75 
Creatinine 
µmol/L 
∆ from BL 
 
↑ 44.2 
Glucose 
mmol/L 
 
3 
9 
Phosphorus 
mmol/L 
 
0.8 
1.6 
Potassium 
mmol/L 
 
3 
5.5 
Sodium 
mmol/L 
 
130 
150 
 
Liver Function 
Test Analyte 
Units 
Category 
Clinical Concern Range 
ALT/SGPT  
U/L 
High 
≥ 2x ULN 
AST/SGOT  
U/L 
High 
≥ 2x ULN 
AlkPhos  
U/L 
High 
≥ 2x ULN 
T Bilirubin  
µmol/L 
High 
≥ 1.5xULN 
T. Bilirubin + ALT 
µmol/L 
High 
1.5xULN T. Bilirubin 
 
+ 
U/L 
≥ 2x ULN ALT 
 
 
 
 
 


 
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10.7.2. 
ECG (Healthy Volunteers) 
ECG Parameter 
Units 
Clinical Concern Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
 
> 450 [1] 
Absolute PR Interval 
msec 
< 110 [1] 
> 220 [1] 
Absolute QRS Interval 
msec 
< 75 [1] 
> 110 [1] 
Change from Baseline 
Increase from Baseline QTc 
msec 
> 60 [1] 
 
NOTES: 
1. 
Represent standard ECG values of PCI for HV studies 
 
10.7.3. 
Vital Signs (Healthy Volunteers) 
Vital Sign Parameter 
(Absolute) 
Units 
Clinical Concern Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
bpm 
< 40 
> 110 
 
 
 


 
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10.8. 
Appendix 8 - Abbreviations & Trade Marks 
10.8.1. 
Abbreviations 
Abbreviation 
Description 
AE 
Adverse Event 
A&R 
Analysis and Reporting 
AUC(0-24) 
Area under the concentration-time curve from pre-dose to 24 hours 
AUC(0-inf) 
Area under the concentration-time curve from time zero (pre-dose) 
extrapolated to infinite time 
AUC(0-t) 
Area under the concentration-time curve from time zero (pre-dose) to 
last time of quantifiable concentration within a subject across all 
treatments 
BMI 
Body mass index 
BP 
Blood pressure 
CI 
Confidence Interval 
Cmax 
Maximum observed concentration  
CSR 
Clinical Study Report 
CVb 
Coefficient of variation (Between) 
CVw 
Coefficient of Variation (Within) 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
GSK 
GlaxoSmithKline 
HR 
Heart rate 
hrs 
Hours 
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
LLN 
Lower Limit of Normal 
LLQ 
Lower Limit of Quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
MG 
Milligrams 
msec 
Milliseconds 
PDMP 
Protocol Deviation Management Plan 
PK 
Pharmacokinetic 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
RAP 
Reporting and Analysis Plan 
SAC 
Statistical Analysis Complete 
SAE 
Serious Adverse Event(s) 
SAS 
Statistical Analysis Software 
SD 
Standard Deviation 
ULN 
Upper Limit of Normal 
SOP 
Standard Operation Procedure 
t1/2 
Terminal half-life 
Tmax 
Time to maximum observed blood drug concentration 
TFL 
Tables, Figures & Listings 


 
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10.8.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None 
 
SAS 
 
 
WinNonlin 
 


 
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10.9. 
Appendix 9: List of Data Displays 
10.9.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.14 
N/A 
Safety 
2.1 to 2.34 
N/A 
Pharmacokinetic 
3.1 to 3.8 
3.1 to 3.10 
Section 
Listings 
ICH Listings 
1 to 70 
Other Listings 
N/A 
 
10.9.2. 
Mock Example Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided in Appendix 10: Example Mock Shells for Data Displays. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
NOTES:  
• 
Indicate display is Non-Standard in the ‘IDSL/TST ID / Example Shell’ or ‘Programming Notes’ column. 
 
10.9.3. 
Deliverable [Priority] 
Delivery [Priority] [1] 
Description 
PR [1] 
Primary Report (Part 1 only) 
SAC [2] 
Statistical Analysis Complete (Part 2 only) 
NOTES:  
1. 
Indicates priority (i.e. order) in which displays will be generated for the reporting effort. 
 


 
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10.9.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
Safety 
CP_ES1 
Summary of Subject Disposition (Part 1) 
Completed or withdrawn and the 
reason for withdrawal. 
PR [1] 
1.2. 
Safety 
ES4 
Summary of Subject Disposition at each period (Part 1) 
Completed or withdrawn at each period. 
PR [1] 
1.3. 
Safety 
CP_ES1 
Summary of Subject Disposition (Part 2) 
Completed or withdrawn and the 
reason for withdrawal. 
SAC [2] 
1.4. 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure 
The number (%) of Randomized or 
screening failure subjects as the 
screening status, and the reason for 
screening failure. 
SAC [2] 
Protocol Deviation 
1.5. 
Safety 
DV1 
Summary of Important Protocol Deviations (Part 1) 
Data is from DV1 dataset. 
PR [1] 
1.6. 
Safety 
DV1 
Summary of Important Protocol Deviations (Part 2) 
Data is from DV1 dataset. 
SAC [2] 
Population Analysed 
1.7. 
Safety 
SP1 
Summary of Study Populations (Part 1) 
Only PK population (Yes or No) is 
summarized. 
PR [1] 
1.8. 
Safety 
SP1 
Summary of Study Populations (Part 2) 
Only PK population (Yes or No) is 
summarized. 
SAC [2] 
Demographic and Baseline Characteristics 
1.9. 
Safety 
DM3 
Summary of Demographic Characteristics (Part 1) 
 
PR [1] 
1.10. 
Safety 
DM3 
Summary of Demographic Characteristics (Part 2) 
 
SAC [2] 
1.11. 
Screened 
DM11 
Summary of Age Ranges (Part 1) 
<=17 years, 18-64 years, 65-84 years, 
>=85 years 
PR [1] 


 
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Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.12. 
Screened 
DM11 
Summary of Age Ranges (Part 2) 
<=17 years, 18-64 years, 65-84 years, 
>=85 years 
SAC [2] 
1.13. 
Safety 
DM5 
Summary of Race and Racial Combinations (Part 1) 
 
PR [1] 
1.14. 
Safety 
DM5 
Summary of Race and Racial Combinations (Part 2) 
 
SAC [2] 
 
 
 
 


 
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10.9.5. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
2.1.  
Safety 
AE1 
Summary of All Adverse Events by System Organ Class and 
Preferred Term (Part 1) 
 
PR [1] 
2.2.  
Safety 
AE5A 
Summary of All Adverse Events by Maximum Intensity (Part 1) 
 
PR [1] 
2.3.  
Safety 
AE1 
Summary All Drug-Related Adverse Events by System Organ 
Class and Preferred Term (Part 1) 
 
PR [1] 
2.4.  
Safety 
AE5A 
Summary All Drug-Related Adverse Events by Maximum 
Intensity (Part 1) 
 
PR [1] 
2.5.  
Safety 
AE1 
Summary of All Adverse Events by System Organ Class and 
Preferred Term (Part 2) 
 
SAC [2] 
2.6.  
Safety 
AE5A 
Summary of All Adverse Events by Maximum Intensity (Part 2) 
 
SAC [2] 
2.7.  
Safety 
AE1 
Summary All Drug-Related Adverse Events by System Organ 
Class and Preferred Term (Part 2) 
 
SAC [2] 
2.8.  
Safety 
AE5A 
Summary All Drug-Related Adverse Events by Maximum 
Intensity (Part 2) 
 
SAC [2] 
Laboratory: Chemistry  
2.9.  
Safety 
LB1 
Summary of Chemistry (Part 1) 
 
PR [1] 
2.10. 
Safety 
LB1 
Summary of Chemistry Changes from Baseline (Part 1) 
 
PR [1] 
2.11. 
Safety 
LB4 
Summary of Chemistry Data Shifts from Baseline with Respect 
to the Normal Range (Part 1) 
 
PR [1] 
2.12. 
Safety 
LB1 
Summary of Chemistry (Part 2) 
 
SAC [2] 
2.13. 
Safety 
LB1 
Summary of Chemistry Changes from Baseline (Part 2) 
 
SAC [2] 


 
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Safety: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.14. 
Safety 
LB4 
Summary of Chemistry Data Shifts from Baseline with Respect 
to the Normal Range (Part 2) 
 
SAC [2] 
Laboratory: Hematology 
2.15. 
Safety 
LB1 
Summary of Hematology (Part 1) 
 
PR [1] 
2.16. 
Safety 
LB1 
Summary of Hematology Changes from Baseline (Part 1) 
 
PR [1] 
2.17. 
Safety 
LB4 
Summary of Hematology Data Shifts from Baseline with Respect 
to the Normal Range (Part 1) 
 
PR [1] 
2.18. 
Safety 
LB1 
Summary of Hematology (Part 2) 
 
SAC [2] 
2.19. 
Safety 
LB1 
Summary of Hematology Changes from Baseline (Part 2)  
 
SAC [2] 
2.20. 
Safety 
LB4 
Summary of Hematology Data Shifts from Baseline with Respect 
to the Normal Range (Part 2) 
 
SAC [2] 
Laboratory: Urinalysis 
2.21. 
Safety 
UR3b 
Summary of Urinalysis Data (Glucose, Protein, Blood, Ketones, 
Bilirubin, Urobilinogen) (Part 1) 
 
PR [1] 
2.22. 
Safety 
LB1 
Summary of Urinalysis Data (Specific Gravity and pH) (Part 1) 
 
PR [1] 
2.23. 
Safety 
UR3b 
Summary of Urinalysis Data (Glucose, Protein, Blood, Ketones, 
Bilirubin, Urobilinogen) (Part 2) 
 
SAC [2] 
2.24. 
Safety 
LB1 
Summary of Urinalysis Data (Specific Gravity and pH) (Part 2) 
 
SAC [2] 
ECG 
2.25. 
Safety 
EG1 
Summary of ECG Findings (Part 1) 
 
PR [1] 
2.26. 
Safety 
EG2 
Summary of ECG Value (Part 1) 
 
PR [1] 
2.27. 
Safety 
EG2 
Summary of Change from Baseline in ECG Values (Part 1) 
 
PR [1] 
2.28. 
Safety 
EG1 
Summary of ECG Findings (Part 2) 
 
SAC [2] 


 
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Safety: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.29. 
Safety 
EG2 
Summary of ECG Value (Part 2) 
 
SAC [2] 
2.30. 
Safety 
EG2 
Summary of Change from Baseline in ECG Values by Visit (Part 
2) 
 
SAC [2] 
Vital Signs 
2.31. 
Safety 
VS1 
Summary of Vital Signs (Part 1) 
 
PR [1] 
2.32. 
Safety 
VS1 
Summary of Change from Baseline in Vital Signs (Part 1) 
 
PR [1] 
2.33. 
Safety 
VS1 
Summary of Vital Signs (Part 2) 
 
SAC [2] 
2.34. 
Safety 
VS1 
Summary of Change from Baseline in Vital Signs (Part 2) 
 
SAC [2] 
 


 
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10.9.6. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Part 1 
3.1.  
PK 
PK01: pkct1 
Summary of GSK1325756 Blood Concentration (Part 1) 
 
PR [1] 
3.2.  
PK 
PK03: pkpt1 
Summary of GSK1325756 Pharmacokinetic Parameters (non-
transformed) (Part 1) 
 
PR [1] 
3.3.  
PK 
PK05: pkpt3 
Summary of GSK1325756 Pharmacokinetic Parameters (loge-
transformed) (Part 1) 
 
PR [1] 
3.4.  
PK 
Study Specific 
(PK_T1) 
Analysis of Power Model Analysis for GSK1325756 Dose 
Proportionality of Pharmacokinetic Parameters (AUC(0-t), 
Cmax) (Part 1) 
Parameter, Effect, n, Point estimate of 
Slope, SE, 90% CI 
PR [1] 
Part 2 
3.5.  
PK 
PK01: pkct1 
Summary of GSK1325756 Blood Concentration (Part 2) 
 
SAC [2] 
3.6.  
PK 
PK03: pkpt1 
Summary of GSK1325756 Pharmacokinetic Parameters (non-
transformed) (Part 2) 
 
SAC [2] 
3.7.  
PK 
PK05: pkpt3 
Summary of GSK1325756 Pharmacokinetic Parameters (loge-
transformed) (Part 2) 
 
SAC [2] 
3.8.  
PK 
Study Specific 
(PK_T2) 
Analysis of food effect for Pharmacokinetic Parameters (AUC(0-
t), Cmax) (Part 2) 
n, Geometric mean of Fasted and Fed, 
ratio (Fasted/Fed), 90% CI and CVw(%) 
SAC [2] 
 


 
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10.9.7. 
Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Part 1 
3.1.  
PK 
PK16b: pkcf1x 
Individual GSK1325756 Blood Concentration-Time Plots by 
Subject (Part 1) 
By Subject (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
PR [1] 
3.2.  
PK 
PK24: pkcf6 
Individual GSK1325756 Blood Concentration-Time Plots by 
treatment (Part 1) 
By Treatment (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
PR [1] 
3.3.  
PK 
Study Specific 
(PK_F1) 
Mean (+SD) GSK1325756 Blood Concentration-Time Plots (Part 
1) 
Unit of x-axis is Hours 
PR [1] 
3.4.  
PK 
PK18: pkcf3 
Median GSK1325756 Blood Concentration-Time Plots (Part 1) 
Unit of x-axis is Hours 
PR [1] 
3.5.  
PK 
PK28 
Plot of GSK1325756 Treatment and PK Parameters (AUC (0-t), 
Cmax) (Part 1) 
 
PR [1] 
Part 2 
3.6.  
PK 
PK16b: pkcf1x 
Individual GSK1325756 Blood Concentration-Time Plots by 
Subject (Part 2) 
By Subject (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
SAC [2] 
3.7.  
PK 
PK24: pkcf6 
Individual GSK1325756 P Blood Concentration-Time Plots by 
Treatment (Part 2) 
By Treatment (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
SAC [2] 
3.8.  
PK 
Study Specifics 
(PK_F1) 
Mean (+SD) GSK1325756 Blood Concentration-Time Plots (Part 
2) 
Unit of x-axis is Hours 
SAC [2] 
3.9.  
PK 
PK18: pkcf3 
Median GSK1325756 Blood Concentration-Time Plots (Part 2) 
Unit of x-axis is Hours 
SAC [2] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.10. 
PK 
PK28 
Plot of GSK1325756 Treatment and PK Parameters (AUC(0-t), 
Cmax) (Part 2) 
 
SAC [2] 
 


 
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10.9.8. 
ICH Listings 
Note: ‘Inv.’ in the standard displays will be replaced to ‘Centre’. 
ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
Screening 
Failure 
ES7 
Listing of Reasons for Screen Failure 
 
PR [1] 
2.  
Safety 
CP-ES10x 
Listing of Reasons for Study Withdrawal (Part 1) 
 
PR [1] 
3.  
Safety 
CP-ES10x 
Listing of Reasons for Study Withdrawal (Part 2) 
 
SAC [2] 
4.  
Safety 
BL2 
Listing of Subjects for Whom the Treatment Blind was Broken 
(Part 1) 
 
PR [1] 
5.  
Safety 
TA2 
Listing of Planned and Actual Treatments (Part 1) 
 
PR [1] 
6.  
Safety 
TA2 
Listing of Planned and Actual Treatments (Part 2) 
 
SAC [2] 
Protocol Deviations 
7.  
Safety 
DV2 
Listing of Important Protocol Deviations (Part 1) 
Column for Treatment Sequence/Period 
of Protocol deviation will be displayed 
after Centre./Subj. 
Period day will be displayed in the 
same column of Date of 
Deviation/Study day. 
PR [1] 
8.  
Safety 
DV2 
Listing of Important Protocol Deviations (Part 2) 
 
SAC [2] 
9.  
Screened 
IE4 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
 
SAC [2] 
Populations Analysed 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
10.  
Safety 
Study Specifics 
(POP_L1) 
Listing of Subjects Excluded from PK Population (Part 1) 
 
PR [1] 
11.  
Safety 
Study Specifics 
(POP_L1) 
Listing of Subjects Excluded from PK Population (Part 2) 
 
SAC [2] 
Demographic and Baseline Characteristics 
12.  
Safety 
DM4 
Listing of Demographic Characteristics (Part 1) 
“Age at Screening” is added. 
PR [1] 
13.  
Safety 
DM4 
Listing of Demographic Characteristics (Part 2) 
“Age at Screening” is added. 
SAC [2] 
14.  
Screening 
Failure 
DM4 
Listing of Demographic Characteristics for Screening Failure 
Subjects 
 
SAC [2] 
15.  
Safety 
DM10 
Listing of Race (Part 1) 
 
PR [1] 
16.  
Safety 
DM10 
Listing of Race (Part 2) 
 
SAC [2] 
17.  
Screening 
Failure 
DM10 
Listing of Race for Screening Failure Subjects 
Treatment is not needed to display. 
SAC [2] 
Medical Conditions and Concomitant Medications 
18.  
Screened 
MH3 
Listing of Medical Conditions 
 
PR [1] 
19.  
Safety 
CM5 
Listing of Concomitant Medications (Part 1) 
 
PR [1] 
20.  
Safety 
CM5 
Listing of Concomitant Medications (Part 2) 
 
SAC [2] 
Exposure and Treatment Compliance 
21.  
Safety 
EX4 
Listing of Exposure Data (Part 1) 
 
PR [1] 
22.  
Safety 
EX4 
Listing of Exposure Data (Part 2) 
 
SAC [2] 
Meal 
23.  
Safety 
CP_ML1x 
Listing of Dosing Times, Meal Start and End Times on Fed 
Treatment Days (Part 1) 
 
PR [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
24.  
Safety 
CP_ML1x 
Listing of Dosing Times, Meal Start and End Times on Fed 
Treatment Days (Part 2) 
 
SAC [2] 
Adverse Events 
25.  
Safety 
AE9CP 
Listing of All Adverse Events (Part 1) 
 
SAC [1] 
26.  
Safety 
AE9CP 
Listing of All Adverse Events (Part 2) 
 
SAC [2] 
27.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events (Part 
1) 
 
PR [1] 
28.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events (Part 
2) 
 
SAC [2] 
29.  
Screened 
AE2 
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text 
 
SAC [2] 
Serious and Other Significant Adverse Events 
30.  
Safety 
AE9CP 
Listing of Serious Adverse Events (Part 1) 
 
PR [1] 
31.  
Safety 
AE9CP 
Listing of Serious Adverse Events (Part 2) 
 
SAC [2] 
32.  
Screening 
Failure 
AE9CP 
Listing of Serious Adverse Events for Screening Failure Subject 
Treatment is not needed to display. 
SAC [2] 
33.  
Safety 
AE9CP 
Listing of Adverse Events Leading to Withdrawal from Study 
(Part 1) 
 
PR [1] 
34.  
Safety 
AE9CP 
Listing of Adverse Events Leading to Withdrawal from Study 
(Part 2) 
 
SAC [2] 
Laboratory (Chemistry Data) 
35.  
Safety 
CP_LB6 
Listing of All Chemistry Data (Part 1) 
Change from baseline is included. 
PR [1] 
36.  
Safety 
CP_LB6 
Listing of All Chemistry Data (Part 2) 
Change from baseline is included. 
SAC [2] 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
37.  
Safety 
CP_LB6 
Listing of All Chemistry Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
 
PR [1] 
38.  
Safety 
CP_LB6 
Listing of All Chemistry Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2) 
 
SAC [2] 
Laboratory (Hematology Data) 
39.  
Safety 
CP_LB6 
Listing of All Hematology Data (Part 1) 
Change from baseline is included. 
PR [1] 
40.  
Safety 
CP_LB6 
Listing of All Hematology Data (Part 2) 
Change from baseline is included. 
SAC [2] 
41.  
Safety 
CP_LB6 
Listing of All Hematology Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
 
PR [1] 
42.  
Safety 
CP_LB6 
Listing of All Hematology Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2) 
 
SAC [2] 
Laboratory (Urinalysis Data) 
43.  
Safety 
UR2b 
Listing of All Urinalysis Dipstick Data (Glucose, Protein, Blood, 
Ketones, Bilirubin, Urobilinogen) (Part 1) 
Time will be displayed after ‘Date’. 
PR [1] 
44.  
Safety 
CP_LB6 
Listing of Urinalysis Data (Gravity and pH) (Part 1) 
 
PR [1] 
45.  
Safety 
UR2b 
Listing of All Urinalysis Dipstick Data (Glucose, Protein, Blood, 
Ketones, Bilirubin, Urobilinogen) (Part 2) 
Time will be displayed after ‘Date’. 
SAC [2] 
46.  
Safety 
CP_LB6 
Listing of Urinalysis Data (Gravity and pH) (Part 2) 
 
SAC [2] 
Hepatobiliary (Liver) 
47.  
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting (Part 1) 
Column for Treatment/Period will be 
displayed after the column for 
Age/Sex/Race Detail. 
PR [1] 
48.  
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting (Part 2) 
 
SAC [2] 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
49.  
Safety 
MH3 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (Part 1) 
 
PR [1] 
50.  
Safety 
MH3 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (Part 2) 
 
SAC [2] 
51.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events (Part 1) 
 
PR [1] 
52.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events (Part 2) 
 
SAC [2] 
ECG 
53.  
Safety 
CP_EG4 
Listing of All ECG Values (Part 1) 
 
PR [1] 
54.  
Safety 
CP_EG4 
Listing of All ECG Values (Part 2) 
 
SAC [2] 
55.  
Safety 
CP_EG4 
Listing of Change from Baseline in ECG Values (Part 1) 
 
PR [1] 
56.  
Safety 
CP_EG4 
Listing of Change from Baseline in ECG Values (Part 2) 
 
SAC [2] 
57.  
Safety 
CP_EG6 
Listing of ECG Findings (Part 1) 
 
PR [1] 
58.  
Safety 
CP_EG6 
Listing of ECG Findings (Part 2) 
 
SAC [2] 
59.  
Safety 
CP_EG4 
Listing of All ECG Data for Subjects with Any Value of Potential 
Clinical Importance (Part 1) 
 
PR [1] 
60.  
Safety 
CP_EG4 
Listing of All ECG Data for Subjects with Any Value of Potential 
Clinical Importance (Part 2) 
 
SAC [2] 
Vital Signs 
61.  
Safety 
CP_VS5 
Listing of All Vital Signs (Part 1) 
Change from baseline is included. 
PR [1] 
62.  
Safety 
CP_VS5 
Listing of All Vital Signs (Part 2) 
Change from baseline is included. 
SAC [2] 
63.  
Safety 
CP_VS5 
Listing of All Vital Signs Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
 
PR [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
64.  
Safety 
CP_VS5 
Listing of All Vital Signs Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2) 
 
SAC [2] 
Others 
65.  
Safety 
Study Specifics 
(SAFE_L1) 
Listing of Ophthalmic examinations (Part 1) 
 
PR [1] 
66.  
Safety 
Study Specifics 
(SAFE_L1) 
Listing of Ophthalmic examinations (Part 2) 
 
SAC [2] 
PK 
67.  
PK 
PK08: pkcl1x 
Listing of GSK1325756 Blood Concentration (Part 1) 
 
PR [1] 
68.  
PK 
PK08: pkcl1x 
Listing of GSK1325756 Blood Concentration (Part 2) 
 
SAC [2] 
69.  
PK 
Study Specifics 
(PK_L1) 
Listing of GSK1325756 Pharmacokinetic Parameters (Part 1) 
 
PR [1] 
70.  
PK 
Study Specifics 
(PK_L1) 
Listing of GSK1325756 Pharmacokinetic Parameters (Part 2) 
 
SAC [2] 
 


 
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10.10. 
Appendix 10: Example Mock Shells for Data Displays 
10.10.1. 
Study population 
Example CP_ES1 (XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
(N=100) 
Completion Status 
 
  Completed 
 50 (50%) 
  Withdrawn 
 50 (50%) 
 
 
Primary*/subreason^ for withdrawal 
 
  Adverse event 
 10 (10%) 
    Elevated ALT levels 
  2  (2%) 
    Severe vomiting 
  5  (5%) 
  Lack of efficacy 
  0 
  Protocol deviation 
  0 
  Subject reached stopping criteria 
 10 (10%) 
    CD4 levels below continuation threshold 
 10 (10%) 
  Study closed/terminated 
  0 
  Lost to follow-up 
  0 
  Investigator discretion 
  0 
  Withdrew consent  
 30 (30%) 
    Burden of procedures 
 10 (10%) 
    Pursue alternative treatment 
 20 (20%) 
    Other 
  0 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: ES4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Phase 
 
 
Not Randomized 
(N=10) 
 
Placebo 
(N=100) 
Curitol 
 10mg 
(N=100) 
Screening 
Entered 
 10(100%) 
100(100%) 
100(100%) 
 
Completed 
  0  
100(100%) 
100(100%) 
 
Withdrawn 
 10(100%) 
  0  
  0  
 
 
 
 
 
Double blind 
Entered 
 
100(100%) 
100(100%) 
 
Completed 
 
 50 (50%) 
 50 (50%) 
 
Withdrawn 
 
 50 (50%) 
 50 (50%) 
 
 
 
 
 
Follow-up 
Entered 
 
 50 (50%) 
 50 (50%) 
 
Completed 
 
 50 (50%) 
 50 (50%) 
 
Withdrawn 
 
  0  
  0  
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm


 
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Example: ES6 (SF for CONSORT) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Screened 
Subjects 
(N=100) 
Screening Status 
 
  ENROLLED 
 50 (50%) 
  FAILED 
 50 (50%) 
 
 
Reason(s) for Failure  
 
  DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 25 (25%) 
  STUDY CLOSED/TERMINATED  
  5  (5%) 
  PHYSICIAN DECISION 
 10 (10%) 
  PROTOCOL DEVIATION 
 10 (10%)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: CP_ES10x 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre 
ID/ 
Subj. 
Treatment 
Sequence/ 
Period of  
Withdrawal 
Last  
Treatment 
Before  
Withdrawal 
Date of  
Withdrawal/ 
Study Day of  
Withdrawal/ 
Period Day 
of 
Withdrawal 
Primary Reason 
for Withdrawal 
Subreason for 
Withdrawal 
Date of Last 
Contact/ 
Study Day of 
Last Contact 
xxxxxx/ 
xxx 
PAB/ 
Period 1 
A 
DDMMMYYYY/ 
xx/ 
x 
Adverse Event 
Elevated ALT levels 
DDMMMYYYY/ 
x 
xxxxxx/ 
xxx 
BPC/ 
Period 2 
B 
DDMMMYYYY/ 
x/ 
x 
 
 
DDMMMYYYY/ 
x 
 
 
 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: ES7 (for SF) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID/ 
Subj. 
Date of 
Screen 
Failure 
Reason Term(s) for Screen Failure 
xxxxxx/ 
xxx 
DDMMMYYYY 
DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 
 
 
xxxxxx/ 
xxx 
DDMMMYYYY 
PHYSICIAN DECISION 
DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 
 
 
xxxxxx/ 
xxx 
DDMMMYYYY 
DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 
DDMMMYYYY 
PHYSICIAN DECISION 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: BL2 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID Subj. 
Sequence/ 
Treatment 
when Blind 
broken 
Date 
Blind 
Broken 
Time 
Blind 
Broken 
 
Study 
Day 
Period 
Day 
 
 
Reason 
 
 
 
 
 
 
 
 
xxxxxx 
xxxx 
PBC/ 
Treatment A 
DDMMMYYYY 
hh:ss 
xx 
x 
Other: PT REQUESTED TO KNOW 
FOR MEDICAL REASONS 
 
 
 
 
 
 
 
 
xxxxxx 
xxxx 
APC/ 
Treatment C 
DDMMMYYYY 
hh:ss 
xx 
xx 
Medical Emergency 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: TA2 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Country: Canada 
Centre ID: 
 
Investigator:
 
Subject 
ID 
Randomization 
Number 
Randomization Date 
Period 
Randomization 
Treatment 
Actual Treatment 
Deviation 
01JAN08 
1 
Curital 10mg 
Curital 10mg 
 
 
2 
Placebo 
Placebo 
 
 
3 
Placebo 
No treatment 
Y 
 
4 
Curital 20mg 
No treatment 
Y 
 
 
 
 
 
03JAN08 
1 
Curital 20mg 
Curital 20mg 
 
 
2 
Placebo 
Placebo 
 
 
3 
Curital 10mg 
Curital 10mg 
 
 
4 
Placebo 
Placebo 
 
 
 
 
 
 
01FEB08 
1 
Placebo 
Placebo 
 
 
2 
Curital 10mg 
Curital 10mg 
 
 
3 
Placebo 
Placebo 
 
 
4 
Curital 20mg 
Curital 10mg 
Y 
 
 
 
 
 
15FEB08 
1 
Curital 10mg 
Curital 10mg 
 
 
2 
Placebo 
Placebo 
 
 
 
 
3 
Placebo 
Placebo 
 
 
 
 
4 
Curital 10mg 
Curital 20mg 
Y 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
PPD
PPD
PPD


 
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Example: IE4 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID Subj. 
Treatment 
sequence 
Type 
Criterion 
 
 
 
 
 
xxxxxx 
xxx 
APC 
INCLUSION 
Is the subject 18 years of age or older? 
 
 
 
 
 
xxxxxx 
xxx 
PAB 
EXCLUSION 
Has the subject had an asthma episode(s) 
requiring intubation associated with 
hypercapnia, respiratory arrest, or hypoxic 
seizures within 12 months prior to Visit 1? 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DV1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Category/Coded Term 
Total 
(N=200) 
 
 
Any important protocol deviations 
60 (30%) 
 
 
Informed consent 
10 (5%) 
WRONG INFORMED CONSENT/ASSENT VERSION SIGNED  
10 (5%) 
 
 
Eligibility criteria not met 
14 (7%) 
 
 
Not withdrawn after developing withdrawal criteria 
18 (9%) 
Not discontinued from study treatment 
10 (5%) 
Not withdrawn from study 
 8 (4%) 
 
 
EXCLUDED MEDICATION, VACCINE OR DEVICE 
 4 (2%) 
   MEDICATION, EXCLUDED BY THE PROTOCOL, WAS ADMINISTERED 
 4 (2%) 
 
 
Assessment or time point completion 
 2 (1%) 
   OUT OF WINDOW EFFICACY ASSESSMENT 
 2 (1%) 
 
 
WRONG STUDY TREATMENT/ADMINISTRATION/DOSE 
 4 (2%) 
  STUDY TREATMENT NOT ADMINISTERED PER PROTOCOL 
 2 (1%) 
  EXPIRED STUDY TREATMET ADMINISTERED 
 2 (1%) 
 
 
Failure to report SAFETY EVENTS PER Protocol 
 8 (5%) 
SAE NOT REPORTED WITHIN THE EXPECTED TIME FRAME 
 4 (2%) 
LIVER FUNCTION ABNORMALITIES PER PROTOCOL  
 4 (2%) 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
62 
 
Example: DV2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
Deviation Requires Exclusion from 
Site Id./ 
 
Date of 
Deviation/ 
Category/ 
Coded Term 
Term 
Intent to 
Treat 
Population 
Safety 
Population 
Per 
Protocol 
Population 
 
28 
ILURE TO REPORT SAFETY 
EVENTS PER PROTOCOL / 
SAE NOT REPORTED 
WITHIN THE EXPECTED 
TIME FRAME 
SAE OF FEVER 
WITH SEVERE 
CHILLS 
REQUIRING IV 
HYDRATION WAS 
NOT REPORTED 
TO GSK WITHIN 
24 HOURS.  
 
 
 
 
31 
ELIGIBILITY CRITERIA 
NOT MET / ELIGIBILITY 
CRITERIA NOT MET 
SUBJECT SCREEN 
FAILED BUT WAS 
RANDOMIZED IN 
ERROR. 
 
 
Y 
Y 
 
1 
WRONG STUDY TREATMENT/ 
ADMINISTRATION/DOSE / 
STUDY TREATMENT NOT 
ADMINISTERED PER 
PROTOCOL 
SUBJECT MISSED 
WEEK 8 
TREATMENT  
 
 
 
 
 
 
2 
WRONG STUDY TREATMENT/ 
ADMINISTRATION/DOSE / 
STUDY TREATMENT NOT 
ADMINISTERED PER 
PROTOCOL 
INTERRUPTION 
OF IP FOR 
GREATER THAN 
20 PERCENT OF 
TIME 
 
 
 
Y 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
63 
 
Example: SP1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Population 
No Treatment 
(N=50) 
Placebo 
(N=xxx) 
Treatment 1 
(N=200) 
Treatment 2 
(N=250) 
Total 
(N=500) 
 
 
 
 
 
 
Screened 
50 (100%) 
xx (xxx%) 
200 (100%) 
250 (100%) 
500 (100%) 
Enrolled 
10  (20%) 
xx (xxx%) 
200 (100%) 
250 (100%) 
460  (92%) 
Randomized 
 5  (10%) 
xx (xx%) 
200 (100%) 
250 (100%) 
455  (91%) 
Safety 
 
xx (xx%) 
195  (98%) 
245  (98%) 
440  (88%) 
PK 
 
xx (xx%) 
200 (100%) 
250 (100%) 
455  (91%) 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
64 
 
Example: POP_L1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx (Randomised subjects) 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID/ 
Subj. 
Treatment 
sequence 
PK 
population 
 
 
 
xxxxxx/ 
xxx 
ABC 
Y 
 
 
 
xxxxxx/ 
xxx 
CBA 
Y 
 
 
 
xxxxxx/ 
xxx 
BAC 
Y 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
65 
 
Example: DM3 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
 
(N=100) 
 
 
Sex 
 
  n 
  100 
  F 
   50  (50%) 
  M 
   50  (50%) 
 
 
Age (YEARS)[1] 
 
  n 
  100 
  Mean 
   50.0 
  SD 
   10.00 
  Median 
   50.0 
  Min. 
   18 
  Max. 
   65 
 
 
Age Group(YEARS)[1] 
 
  <=18 
    5   (5%) 
  19-64 
   50  (50%) 
  >=65 
   45  (45%) 
 
 
Ethnicity 
 
  n 
  100 
  HISPANIC OR LATINO 
   10  (10%) 
  NOT HISPANIC OR LATINO 
   90  (90%) 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
66 
 
Example: DM3 (continued) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
 
(N=100) 
 
 
Race Detail 
 
  AMERICAN INDIAN OR ALASKA NATIVE 
 1   (1%) 
  ASIAN - CENTRAL/SOUTH ASIAN HERITAGE 
 3   (3%) 
  ASIAN - EAST ASIAN HERITAGE 
 4   (4%) 
  ASIAN – JAPANESE HERITAGE 
 3   (3%) 
  ASIAN - SOUTH EAST ASIAN HERITAGE 
 1   (1%) 
  BLACK OR AFRICAN AMERICAN 
 2   (2%) 
  NATIVE 
HAWAIIAN 
OR 
OTHER 
PACIFIC 
ISLANDER  
59  (59%) 
  WHITE – ARABIC/NORTH AFRICAN HERITAGE 
26  (26%) 
  WHITE 
– 
WHITE/CAUSASIAN/EUROPEAN 
HERITAGE  
 1   (1%) 
  MIXED ASIAN RACE 
 1   (1%) 
  MIXED WHITE RACE 
 1   (1%) 
  MULTIPLE 
 1   (1%) 
 
 
Height (cm) 
 
  n 
  100 
  Mean 
  150.0 
  SD 
   10.00 
  Median 
   50.0 
  Min. 
   18 
  Max. 
   65 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
67 
 
Example: DM3 (continued) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
 
(N=100) 
 
 
Weight (kg) 
 
  n 
  100 
  Mean 
   50.0 
  SD 
   10.00 
  Median 
   50.0 
  Min. 
   18 
  Max. 
   65 
 
 
Options (units) 
 
 
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
68 
 
Example: DM4 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID/ 
Subj. 
Treatment 
Sequence 
Partial 
Date of 
Birth 
Age 
(YEARS)
[1] 
Sex 
Ethnicity 
Height 
 (cm) 
Weight 
 (kg) 
Option 
(unit) 
 
 
 
 
 
 
 
 
 
xxxxxx/ 
xxx 
ABC 
--MMYYYY 
xx 
F 
HISPANIC OR LATINO 
xxx 
xx 
 
 
 
 
 
 
 
 
 
 
xxxxxx/ 
xxx 
BCA 
--MMYYYY 
xx 
M 
NOT HISPANIC OR LATINO 
xxx 
xx 
 
 
 
 
 
 
 
 
 
 
xxxxxx/ 
xxx 
CAB 
----YYYY 
xx 
M 
NOT HISPANIC OR LATINO 
xxx 
xx 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
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Example: DM5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Treatment A 
Treatment B 
Total 
 
 
(N=XXX) 
(N=XXX) 
(N=XXX) 
 
 
 
 
 
Race n 
  100 
  100 
  200 
 
African American/African Heritage 
   30  (30%) 
   30  (30%) 
   60  (30%) 
 
American Indian or Alaskan Native 
    0    
    0    
    0    
 
Asian 
   15  (15%) 
   15  (15%) 
   30  (15%) 
 
Central/South Asian Heritage 
    3   (3%) 
    3   (3%) 
    6   (3%) 
 
Japanese/East Asian Heritage/South 
East Asian Heritage 
   11  (11%) 
   11  (11%) 
   22  (11%) 
 
Mixed Asian Heritage 
    1   (1%) 
    1   (1%) 
    2   (1%) 
 
Native Hawaiian or other Pacific 
Islander 
   10  (10%) 
   10  (10%) 
   20  (10%) 
 
White 
   35  (35%) 
   35  (35%) 
   70  (35%) 
 
Native Hawaiian or other Pacific 
Islander & American Indian or Alaskan 
Native 
    2   (2%) 
    2   (2%) 
    4   (4%) 
 
White & African American/African 
Heritage 
    3   (3%) 
    3   (3%) 
    6   (3%) 
 
White & Asian 
    5   (5%) 
    5   (5%) 
   10   (5%) 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
70 
 
Example: DM11 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
No Treatment Total 
 
(N=1) 
(N=201) 
 
 
 
Age Ranges [1] 
 
 
In utero                
   0        
 4   (2%) 
Preterm newborn infants (gestational age <37 
weeks) 
   0        
 2   (1%) 
Newborns (0-27 days) 
   0        
 6   (3%) 
Infants and toddlers (28 days-23 months) 
   0        
 8   (4%) 
Children (2-11 years) 
   0        
 6   (3%) 
Adolescents (12-17 years) 
   0        
 2   (1%) 
Adult (18-64 years)      
   0        
118  (59%) 
>=65-84 years        
   0        
52  (26%) 
>=85 years       
  1 (100%) 
 3   (1%) 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
71 
 
Example: DM10 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre 
ID 
Subj. 
Treatment 
sequence 
Race 
 
Race Detail 
 
 
 
 
 
xxxxxx xxx 
ABC 
BLACK OR AFRICAN AMERICAN 
BLACK OR AFRICAN AMERICAN 
 
xxx 
BCA 
Mixed race 
ASIAN - EAST ASIAN HERITAGE 
ASIAN – JAPANESE HERITAGE 
 
xxx 
CAB 
WHITE – ARABIC/NORTH AFRICAN 
HERITAGE 
WHITE – ARABIC/NORTH AFRICAN 
HERITAGE  
 
xxx 
ABC 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAGE 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAGE 
 
 
 
 
 
xxxxxx xxx 
ABC 
Mixed race 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAG 
ASIAN – JAPANESE HERITAGE 
 
xxx 
BCA 
NATIVE HAWAIIAN OR OTHER PACIFIC 
ISLANDER 
NATIVE HAWAIIAN OR OTHER PACIFIC 
ISLANDER 
 
 
 
 
 
 
xxx 
CAB 
BLACK OR AFRICAN AMERICAN  
BLACK OR AFRICAN AMERICAN  
 
xxx 
ABC 
WHITE - ARABIC/NORTH AFRICAN 
HERITAGE 
WHITE - ARABIC/NORTH AFRICAN 
HERITAGE 
 
 
 
 
 
xxxxxx xxx 
BCA 
AMERICAN INDIAN OR ALASKA NATIVE 
AMERICAN INDIAN OR ALASKA NATIVE 
 
xxx 
CAB 
Mixed race 
BLACK OR AFRICAN AMERICAN 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAGE 
 
 
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
72 
 
Example: MH3 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv. 
 
Subject 
Treatment 
Sequence 
 
Classification 
 
Condition 
 
Status 
 
 
 
 
AB 
Hepatobiliary 
HEPATITIS A 
Current 
 
Psychiatric 
PARANOIA COMBINED WITH MANIA. Past 
 
 
 
 
AB 
Eye 
ASTIGMATISM 
Current 
 
 
 
 
BA 
Metabolism and nutrition 
RICKETS 
Current 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
73 
 
Example: CM5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
 
 
Inv./ 
Subj./ 
Seq 
 
Treat- 
ment/ 
Period 
ATC Level 1/  
Ingredient/ 
Verbatim Text/ 
Indication 
Dose/     
Units/ 
Freq/     
Route 
Start 
Date/Time  
Study Day/ 
Period Day 
Stop 
Date/Time  
Study Day/ 
Period Day 
 
Started 
Pre- 
Trial? 
 
Ongoing 
Medi-
cation? 
 
 
 
 
 
 
ABC 
Tmt A/ 
Per 1 
Endocrine & metabolic/  
Fluticasone propionate/ 
FLIXOTIDE/ 
Asthma 
2/  
MG/ 
2XD/ 
IH 
 
12:30/ 
15/ 
7 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
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Example: EX4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre 
ID  
Subj. Treatment 
Start 
Date/ 
Start Time 
of Dose 
Stop Date/ 
Stop Time 
of Dose 
Duration 
(days) 
Dose  
Dose 
Unit  
Formulat
ion/ 
Route 
Freque
ncy 
Cumulat
ive 
Dose 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxx 
Treatment A  DDMMMYYYY/ 
hh:ss 
DDMMMYYYY/ 
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
Placebo 
DDMMMYYYY/ 
hh:ss 
 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
Treatment C DDMMMYYYY/ 
hh:ss 
DDMMMYYYY/ 
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
 
 
 
 
 
 
 
 
 
 Placebo 
DDMMMYYYY/ 
hh:ss 
DDMMMYYYY/ 
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
Treatment B  
 
 
 
 
 
 
 
 
Treatment C DDMMMYYYY/ 
hh:ss 
DDMMMYYYY/ 
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
 
 
 
 
 
 
 
 
 
  Treatment A  DDMMMYYYY/ 
hh:ss 
DDMMMYYYY/ 
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
Treatment B DDMMMYYYY/ 
hh:ss 
DDMMMYYYY/ 
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
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Example: CP_ML1x 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Cohort 
(Optional) 
Investigator 
OR 
Centre ID 
(Optional) 
Subj. Treatment 
Meal type 
(Optional) 
Period 
(Optional) 
/Visit 
Visit 
Date 
Dose 
Time 
Meal 
Start 
Time 
Meal End 
Time 
(Optional) 
Meal ended 
within 20 
minutes of 
Meal Start  
Time 
(Optional)  
Time from 
Start of 
Meal to 
Dosing 
(min)  
(Optional)
 
 
 
 
 
 
 
 
 
 
 
 
1 
50mg 
GSK123456 
High-fat 
breakfast 
Period 
2/Day 4 
8:13 7:30 
7:41 
Y 
43 
 
25mg 
GSK123456 
High-fat 
breakfast 
Period 
2/Day 4 
8:12 7:28 
7:42 
Y 
44 
 
10mg 
GSK123456 
High-fat 
breakfast 
Period 
2/Day 4 
8:10 7:27 
7:35 
Y 
43 
 
 
 
 
 
 
 
 
 
2 
50mg 
GSK123456 
High-fat 
breakfast 
Period 
2/Day 4 
8:09 7:28 
7:50 
N 
41 
 
50mg 
GSK123456 
High-fat 
breakfast 
Period 
2/Day 4 
8:11 7:30 
7:41 
Y 
41 
 
25mg 
GSK123456 
High-fat 
breakfast 
Period 
2/Day 4 
8:09 7:25 
7:42 
Y 
44 
 
10mg 
GSK123456 
High-fat 
breakfast 
Period 
2/Day 4 
8:10 7:27 
7:36 
Y 
43 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
 
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
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10.10.2. 
Safety population 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
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Example: AE1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
System Organ Class 
  Preferred Term 
Placebo 
(N=78) 
Drug A 
(N=78) 
Drug B 
(N=78) 
ANY EVENT 
58 (74%) 
64 (82%) 
64 (85%) 
 
 
 
 
Gastrointestinal disorders 
 
 
 
Any event 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Dyspepsia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Nausea 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Vomiting Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Constipation 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Diarrhoea Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Toothache 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Abdominal Pain Upper 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Dry Mouth 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Flatulence 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Gastrointestinal Upset 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Haemorrhoids 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Loose Stools 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Abdominal Pain Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Faecal Incontinence 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Gastritis Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Lip Disorder Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Lip Dry 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Stomach Discomfort 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
Nervous system disorders 
 
 
 
Any event 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Headache 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Dizziness 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Extrapyramidal Disorder 
xx (xx%) 
xx (xx%) 
xx (xx%) 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
78 
 
Example: AE5A 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Treatment: Treatment A (N=200) 
System Organ Class 
Preferred Term 
MILD 
MODERATE 
SEVERE 
MODERATE 
/SEVERE 
UNKNOWN 
Total 
 
 
 
 
 
 
 
ANY EVENT 
30 (15%) 
40 (20%) 
40 (20%) 
80 (40%) 
 1 (<1%) 
151 (76%) 
 
 
 
 
 
 
 
Cardiovascular 
 
 
 
 
 
 
  Any Event 
20 (10%) 
40 (20%) 
40 (20%) 
80 (40%) 
 0 
140 (70%) 
  Hypertension 
 0 
20 (10%) 
20 (10%) 
20 (10%) 
 0 
 40 (20%) 
  Syncope 
 0 
 0 
 0 
0 
 0 
  0 
  Hypotension 
20 (10%) 
 0 
 0 
40 (20%) 
 0 
 60 (30%) 
 
 
 
 
 
 
 
Nervous system 
disorders 
10  (5%) 
 0 
 0 
 0 
 1 (<1%) 
 11  (6%) 
  Any Event 
10  (5%) 
 0 
 0 
 0 
 1 (<1%) 
 11  (6%) 
  Dizziness 
10  (5%) 
 0 
 0 
 0 
 1 (<1%) 
 11  (6%) 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
79 
 
Example: LB1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Test (units)           
 
 
Treatment    
 
 
N    
 
Planned  
Time 
 
 
n   
 
 
Mean 
 
 
     SD   
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
Alkaline Phosphatase 
Trt A  
202  Week  8     
150   
 2.1 
 7.95 
1 
 -25 
 32 
(IU/L)                        
 
Week 12     
133   
 0.4 
10.05 
1 
 -64 
 33 
 
  
  
Week 24     
 55    -1.6 
18.22 
0  -339 
 44 
 
 
 
 
 
 
 
 
 
 
 
Trt B 
220  Week  8     
150   
 2.1 
 7.95 
1 
 -25 
 32 
 
 
    
Week 12     
133   
 0.4 
10.05 
1 
 -64 
 33 
 
 
   
Week 24     
 55    -1.6 
18.22 
0  -339 
 44 
 
 
 
 
 
 
 
 
 
 
Alanine Aminotransferase 
(IU/L)  
Trt A 
202  Week  8     
150   
-1.2 
16.32 
0 
-320 
38 
 
 
     Week 12     
133   
0.7 
10.55 
1 
-64 
32 
 
 
   
Week 24     
 55   
-3.3 
29.50 
0  -235  
36 
 
 
 
 
 
 
 
 
 
 
 
Trt B 
220  Week  8     
150   
-1.2 
16.32 
0 
-320 
38 
 
 
   
Week 12     
133   
0.7 
10.55 
1 
-64 
32 
 
 
  
Week 24     
 55   
-3.3 
29.50 
0  -235 
36 
 
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
80 
 
Example: LB4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Test= Alanine Aminotransferase (IU/L), Treatment=Treatment A 
 
 
 
 
 
 
Time Period Value 
Planned 
Time 
 
N 
 
n 
Baseline 
Value 
 
High 
 
Normal 
 
Low 
 
Total 
 
 
 
 
 
 
 
 
Week 1 
100 
100 
High 
  0 
  1   (1%) 
  3   (3%) 
  4   (4%) 
 
 
 
Normal  
 10  (10%) 
 84  (84%) 
  2   (2%) 
 96  (96%) 
 
 
 
Low 
  0 
  0 
  0 
  0 
 
 
 
Total 
 10  (10%) 
 85  (85%) 
  5   (5%) 
100 (100%) 
 
 
 
 
 
 
 
 
Week 4 
100 
100 
High 
  0 
  1   (1%) 
  3   (3%) 
  4   (4%) 
 
 
 
Normal 
 10  (10%) 
 84  (84%) 
  2   (2%) 
 96  (96%) 
 
 
 
Low 
  0 
  0 
  0 
  0 
 
 
 
Total 
 10  (10%) 
 85  (85%) 
  5   (5%) 
100 (100%) 
 
 
 
 
 
 
 
 
Worst Case  
Post-Baseline 
100 
100 
High 
  0 
  1   (1%) 
  3   (3%) 
  4   (4%) 
 
 
 
Normal 
 10  (10%) 
 84  (84%) 
  2   (2%) 
 96  (96%) 
 
 
 
Low 
  0 
  0 
  0 
  0 
 
 
 
Total 
 10  (10%) 
 85  (85%) 
  5   (5%) 
100 (100%) 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
81 
 
Example: UR3b 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Test 
Period/Planned 
Relative Time 
Result 
Treatment A  
(N=100) 
Treatment B 
(N=100) 
 
 
 
 
 
Urine General 
Dipstick 
SCREENING/ 
SCREENING 
Positive 
   30  (30%) 
   60  (60%) 
 
 
Negative 
   40  (40%) 
   30  (30%) 
 
 
No Result 
   30  (30%) 
   10  (10%) 
 
 
 
 
 
 
PERIOD 1/DAY 1 
Positive 
   40  (40%) 
   50  (50%) 
 
 
Negative 
   30  (30%) 
   40  (40%) 
 
 
No Result 
   30  (30%) 
   10  (10%) 
 
 
 
 
 
Urine Occult Blood 
(Dipstick) 
SCREENING/ 
SCREENING 
None 
   40  (40%) 
   40  (40%) 
 
 
Trace 
   25  (25%) 
   25  (25%) 
 
 
1+ 
   10  (10%) 
   15  (15%) 
 
 
2+ 
    0    
    0    
 
 
3+ 
    0    
    0    
 
 
No Result 
   10  (10%) 
   20  (20%) 
 
 
 
 
 
 
PERIOD 1/DAY 1 
None 
   40  (40%) 
   40  (40%) 
 
 
Trace 
   30  (30%) 
   30  (30%) 
 
 
1+ 
    5   (5%) 
    5   (5%) 
 
 
2+ 
    2   (2%) 
    4   (4%) 
 
 
3+ 
    0    
    0    
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
82 
 
Example: EG1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Treatment A 
Treatment B 
  
(N=157) 
(N=160) 
  
 
 
Time Period 1 
 
 
  n 
156  
160  
  Normal  
 81  (52%) 
 90  (56%) 
  Abnormal, not clinically significant 
 75  (48%) 
 69  (43%) 
  Abnormal, clinically significant 
  0  
  1  (<1%) 
   
 
 
Time Period 2 
 
 
  n  
117  
123  
  Normal 
 50  (43%) 
 67  (54%) 
  Abnormal, not clinically significant 
 64  (55%) 
 55  (45%) 
  Abnormal, clinically significant  
  2   (2%) 
  1  (<1%) 
   
 
 
  n  
117  
122  
  Clinically significant change from baseline  
  2   (2%) 
  1  (<1%) 
  Not a clinically significant change 
115  (98%) 
121 (>99%) 
  Not applicable 
  0 
  0 
 
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83 
 
Example: EG1 (continued) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Treatment A 
Treatment B 
  
(N=157) 
(N=160) 
  
 
 
Any time post-baseline 
 
 
  n  
117  
123  
  Normal 
 50  (43%) 
 67  (54%) 
  Abnormal, not clinically significant 
 65  (56%) 
 55  (45%) 
  Abnormal, clinically significant  
  2   (2%) 
  1  (<1%) 
  No result (not available) 
  0 
  0 
   
 
 
  n  
117  
122  
  Clinically significant change from baseline  
  2   (2%) 
  1  (<1%) 
  Not a clinically significant change 
115  (98%) 
121 (>99%) 
  Not applicable 
  0 
  0 
 
 
 
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206817 
 
 
 
84 
 
Example: EG2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
Treatment 
 
 
N 
Planned Relative  
Time 
 
 
n 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
Heart Rate  
Trt A 
200 Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 (bpm) 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
 
 
 
 
 
 
 
 
 
 
Trt B 
200 Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
 
 
 
 
 
 
 
 
 
PR Interval 
Trt A 
200 Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 (msec) 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
 
 
 
 
 
 
 
 
 
 
Trt B 
200 Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
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85 
 
Example: VS1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
Treatment 
 
 
N 
Planned 
Relative Time 
 
 
n 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
Systolic BP 
Trt A 
200 
Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 (mmHg) 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
 
 
 
 
 
 
 
 
 
 
Trt B 
200 
Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
 
 
 
 
 
 
 
 
 
Diastolic BP 
Trt A 
200 
Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 (mmHg) 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
 
 
 
 
 
 
 
 
 
 
Trt B 
200 
Time 1 
200 
91.6 
11.32 
90.0 
68 
140 
 
 
 
Time 2 
190 
92.4 
 9.83 
90.0 
70 
122 
 
 
 
Time 3 
186 
92.6 
10.87 
89.0 
72 
125 
 
 
 
 
 
 
 
 
 
 
 
 
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206817 
 
 
 
86 
 
Example: AE7 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
System Organ Class 
  Preferred Term              
 
Treatment 
No. 
with 
Event Unique Subject Id. 
 
 
 
Gastrointestinal disorders 
  Dyspepsia 
Placebo 
 
 9 
 
Treatment A 
11 
 
Treatment B 
 4 
 
 
 
  Nausea 
Placebo 
 
 6 
 
Treatment A 
 8 
 
Treatment B 
 4 
 
 
 
 
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PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
87 
 
Example: AE9CP 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Site 
Id./ 
Unique 
Subject 
Id./ 
/Arm 
 
 
 
Treatme
nt/ 
Period 
Age(YEARS)/ 
Sex/ 
Race 
Detail/ 
Weight 
(kg) 
 
 
 
System Organ Class/ 
Preferred Term/ 
VERBATIM TEXT 
 
Outcome/ 
Onset Datetime/ 
Datetime of 
Resolution/ 
Duration 
Time since 
Study 1st 
Dose/ 
Period 1st 
Dose/  
Last Dose  
Maximum  
Intensity/ 
Maximum 
Grade/ 
Serious/ 
Withdrawal  
 
Frequency/ 
Action Taken/ 
Relation to 
Study 
Treatment 
 
 
 
 
 
 
 
AB-BA-
BA 
Tmt A/ 
Per 1 
57/ 
F/ 
ASIAN - 
JAPANESE 
HERITAGE/ 
62.0 
Gastrointestinal 
Disorders/ 
Internal spasm/ 
ENTERO - SPASM 
RECOVERED/RESOLVE
D/ 
T06:05/ 
T09:35/ 
22d 13h 6m 
31d 26h 4m/ 
31d 26h 4m/ 
-29d 7h 0m 
MILD/ 
1 
N/ 
N 
INTERMITTENT/ 
DOSE REDUCED/ 
Y 
 
 
 
 
 
 
 
 
 
Tmt B/ 
Per 2 
65/ 
M/ 
MIXED WHITE 
RACE/ 
75.0 
Musculoskeletal and 
connective tissue 
disorders/ 
Arthralgia/ 
PAIN IN RIGHT 
SHOULDER 
RECOVERED/RESOLVE
D/ 
T05:50/ 
T21:55/ 
71d 9h 45m 
83d 1h 12m/ 
83d 1h 12m/ 
-17d 2h 5m  
MODERATE/ 
2/ 
N/ 
N 
SINGLE EVENT/ 
DOSE NOT 
CHANGED/ 
N 
 
 
 
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PPD
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PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
88 
 
Example: AE2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
System Organ Class 
Preferred Term 
Verbatim Text 
Blood and lymphatic system 
Lymphadenopathy 
ENLARGED LYMPH NODE 
disorders 
 
 
 
 
 
Cardiac disorders 
Palpitations 
CLOGGED EARS WITH EAR WAX 
 
Ear pain 
EARACHES IN BOTH EARS 
 
 
RIGHT EAR PAIN 
 
Tinnitus 
RINGING IN RIGHT EAR 
 
 
 
Eye disorders 
Asthenopia 
TIRED EYES 
 
Conjunctivitis 
BILATERAL ACUTE CONJUNCTIVITIS 
 
 
CONJUNCTIVITIS 
 
Dry eye nos 
DRY EYES 
 
Eye redness 
REDDENED EYES 
 
Vision blurred 
BLURRED VISION 
 
 
BLURRY VISION 
 
 
WORSENING OF BLURRED VISION 
 
 
 
Gastrointestinal disorders 
Abdominal pain nos 
ABDOMEN PAIN 
 
Abdominal pain upper 
MID-EPIGASTRIC AREA PAIN 
 
 
STOMACH ACHE 
. 
. 
. 
. 
. 
. 
 
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89 
 
Example: CP_LB6 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj./ 
Seq 
 
Age(y)/  
Sex/  
Race 
 
Treat- 
ment/ 
Period 
 
 
Lab test 
(units) 
 
Planned 
Relative 
Time 
 
 
 
Date/Time 
Study 
Day/ 
Period 
Day 
 
 
Converted Data 
 
 
Flag[1] 
Value 
Normal Range 
NR CI BL 
 
 
 
 
 
 
 
 
 
 
 
63/  
Trt A/ 
Alk Phos 
(U/L) 
Screening   
 
12:05 
-1/-1   64.00 
 32.0- 92.0 
 
 
 
Male/ 
Per 1 
 
Week 12      
 
13:45 
85/85 
 84.00 
 32.0- 92.0 
    
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT (U/L) 
Screening   
 
13:32 
-1/-1   29.00 
 10.0- 40.0       
 
 
 
 
 
 
Week 12      
 
09:55 
85/85 
 70.00 
 10.0- 40.0      H 
H 
H 
 
 
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PPD
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PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
90 
 
Example: UR2b 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv. 
 
Subject 
 
Treatment 
 
Period 
 
Visit 
 
Sample Date 
Study 
Day 
Period 
Day 
Urinalysis 
Test 
 
Result 
 
 
 
 
 
 
 
 
 
 
Trt A 
1 
1 
1 
1 
Blood 
++ or 2+ 
Trt B 
2 
8 
137 
1 
Blood 
+ or 1+ 
 
 
 
 
 
 
 
Trt B 
1 
1 
1 
1 
Blood 
+ or 1+ 
 
 
 
 
 
 
 
Protein 
+++ or 3+ 
 
 
Trt A 
2 
8 
137 
1 
Blood 
+ or 1+ 
 
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PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
91 
 
Example: LIVER5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Treatment: Treatment A 
 
 
Site Id./ 
Unique Subject 
Id. 
 
 
Age(YEARS)/ 
Sex/ 
Race Detail 
 
 
 
Maximum Status of 
the Liver Event 
 
 
Date First 
Detected/ 
Study Day 
Time  
Since 
First 
Dose 
(days) 
Time 
Since 
Last 
Dose 
(days) 
 
Restart/Re-
challenge After 
Stopping Criteria 
Was Met 
 
 
 
Resolved?/ 
Date 
resolved 
 
 
 
 
 
 
 
63/ 
M/ 
WHITE - 
WHITE/CAUSAS
IAN/EUROPEAN 
HERITAGE 
LIVER MONITORING 
CRITERIA 
 
101 
 
 101  
 1  
N 
Y/ 
2010-02-19 
 
 
 
 
 
 
 
61/ 
F/ 
ASIAN - 
JAPANESE 
HERITAGE  
LIVER EVENT 
STOPPING CRITERIA 
68 
  68  
 1  
Y 
Y/ 
2010-04-10 
 
LIVER EVENT 
STOPPING CRITERIA 
134 
 134  
 7  
N 
N 
 
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PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
92 
 
Example: SU2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
Treat- 
ment 
 
 
 
Inv./ 
Subj.  
 
 
 
 
Visit 
 
 
 
Study 
Day 
 
 
Assess- 
ment 
Date 
 
 
 
Smoking 
History 
 
 
 
Cur-rently 
Smoke 
 
 
Last 
Smoked 
Smoked 
Since 
Last 
Visit 
Days 
Smoked 
Since 
Last 
Visit 
 
 
 
Years 
Smoked 
 
 
Ciga-
rettes 
/day 
 
 
Smoki
ng 
Pack 
Years
* 
 
 
 
 
 
 
 
 
 
 
 
 
Trt A 
Visit 1 
1 
Never 
No 
 
No 
Zero 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit 1 
1 
Current Yes 
 
Yes 
A few 
   5 
   20 
5 
 
 
 
 
 
 
 
 
 
 
 
Trt B 
Visit 1 
1 
Former 
No 
31DEC1
990 
No 
Zero 
  18 
   30 
27 
 
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PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
93 
 
Example: CP_EG4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj. 
/Seq. 
 
Age 
(y)/ 
Sex/ 
Race 
 
Treat- 
ment/ 
Period 
 
Planned 
Relative 
Time 
 
 
ECG  
Date/Time 
 
Study 
Day 
/Period 
Day 
Actual  
Relative 
Time 
(optional) 
 
Heart 
Rate 
(bpm) 
 
PR 
Int. 
(msec
) 
 
QRS 
Dur. 
(mse
c) 
 
RR 
Int. 
(msec) 
 
QT 
Int. 
(msec) 
 
 
QTcB 
(msec) 
 
 
QTcF 
(msec) 
 
/AB 
65/ 
White/ 
Female 
Trt A/ 
Per 1 
Time 1 
 
14:00 
1/1 
-30m 
60 L 
150 
350 
750 
450 
520 
495 
 
 
 
Time 2 
 
15:00 
7/7 
26m 
80 
150 
350 
750 
450 
520 
495 
 
 
Trt B/ 
Per 2 
Time 1 
 
19:00 
14/1 
-30m 
80 
150 
390 
H 
750 
450 
520 
495 
 
 
 
Time 2 
20:00 
21/7 
26m 
80 
150 
350 
750 
450 
520 
495 
 
 
 
 
 
 
 
 
 
 
 
 
 
/BA 
58 
Male/ 
White/ 
 
Trt A/ 
Per 2 
Time 1 
 
14:00 
1/1 
-30m 
80 
90 L 350 800 H 
450 
520 
495 
 
 
 
Time 2 
 
15:00 
7/7 
26m 
80 
150 
350 
750 
450 
520 
495 
 
 
 
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PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
94 
 
Example: CP_EG6 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj./ 
Seq. 
 
Age (y)/ 
Sex/ 
Race 
 
Treat- 
ment/ 
Period 
Planned  
Relative  
Time/ECG  
Date/Time 
Study 
Day/ 
Period 
Day 
 
 
 
ECG Finding 
Clinically 
Significant 
Change from 
Baseline? 
 
 
Clinically  
Significant Abnormality 
 
 
 
 
 
 
 
 
 
A/B 
65/ 
Female/ 
White 
Trt A/ 
Per 1 
Visit 1/ 
 
/14:00 
 
1/1 
Normal 
 
 
 
 
 
Visit 2/ 
/12:00 
 
4/4 
Abnormal–not 
clinically 
significant 
No 
 
 
 
Trt B/ 
Per 2 
Visit 3/ 
/19:00 
 
8/1 
Abnormal–
clinically 
significant 
 
Sinus tachycardia 
 
 
 
Visit 4/ 
/13:00 
 
12/4 
No result (not 
available) 
 
 
B/A 
58 
Male/ 
White 
Trt B/ 
Per 1 
Visit 1/ 
/14:00 
 
16/1 
Abnormal–
clinically 
significant 
 
Ectopic ventricular 
 beats 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
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PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
95 
 
Example: CP_VS5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj./ 
Seq. 
 
Age(y)/ 
Sex/ 
Race 
 
Treat-
ment/ 
Period 
 
Planned 
Relative 
Time 
 
 
Actual 
Date/Time 
 
 
Study Day/ 
Period Day 
Systolic 
 Blood 
Pressure 
(mmHg) 
Diastolic 
 Blood 
Pressure  
(mmHg) 
 
Vital Sign 
3 
(units) 
23/ 
Tmt B/ 
Time 1 
 
1/1 
  190 H 
   60  
   xx H 
Male/ 
Per 1 
Time 2 
 
5/5 
   95 
   50 L 
   xx H 
B/C/A 
White 
 
Time 3 
 
10/10 
   95 
   60  
   xx  
 
 
Tmt C/ 
Time 1 
 
15/1 
  185 H 
   90 H 
   xx H 
 
 
Per 2 
Time 2 
 
20/5 
   95 
   50 
   xx H 
 
 
Time 3 
 
25/10 
   95 
   60  
   xx  
 
 
Tmt A/ 
Time 1 
 
30/1 
  200 H 
   45 L 
   xx H 
 
 
Per 3 
Time 2 
 
35/5 
   95 
   60 
   xx H 
 
 
 
Time 3 
 
40/10 
   95 
   85 H 
   xx  
 
 
 
 
 
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PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
96 
 
Example: SAFE_L1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Inv./ 
Subj./ 
Seq. 
Age(y)/ 
Sex/ 
Race 
Treat-ment/ 
Period 
Planned 
Relative 
Time 
Actual 
Date/Time 
Study Day/ 
Period Day 
Location/ 
Category 
Test type 
Side 
Test 
Result 
23/ 
Tmt B/ 
Time 1 
1/ 
Eye/ 
Indirect 
fundoscopic 
exam 
Left 
Normal 
Male/ 
Period x 
 
1 
Ophthalmological 
examination 
 
Right xxxxx 
B/C/A 
White 
 
 
 
 
Slit lamp 
Left 
xxxxxx 
 
 
 
 
 
 
 
Right xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Time 2 
5/ 
 
xxxxxxxxxx 
xxxxx xxxxxxx 
 
 
 
 
5 
 
 
xxxxx xxxxxxx 
 
 
 
 
 
 
xxxxxxxxxx 
xxxxx xxxxxxx 
 
 
 
 
 
 
 
xxxxx xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
Tmt C/ 
Time 1 
15/ 
 
xxxxxxxxxx 
xxxxx xxxxxxx 
 
 
Period 2 
 
1 
 
 
xxxxx xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
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PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
97 
 
10.10.3. 
PK population 
Example: PK01 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Treatmen
t 
 
 
N 
{Add.  
time 
var.} 
Planned  
Relative 
Time 
 
 
n 
 
No. 
Imputed 
 
 
Mean 
 
{95% CI 
(Lower,Upper)} 
 
 
SD 
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
 
 
50mg 
24  
Pre-dose 24  20 
xxxx.x (xxxx.x,xxxx.x)  
xxxx.x 
xxxx 
xxxx 
 
 
 
30 min 
24   1 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
1 hr 
23   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
2 hr 
24   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
100mg 
24  
Pre-dose 24   3 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
30 min 
21   0  
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
1 hr 
21   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
2 hr 
21   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
200mg 
24  
Pre-dose 24   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
30 min 
23   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
1 hr 
24   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
2 hr 
24   0 
xxxx.x (xxxx.x,xxxx.x) xx.xx 
xxxx.x 
xxxx 
xxxx 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
98 
 
Example: PK03 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Parameter 
 
 
Treatment 
 
 
N 
{Additio
nal  
time 
variable
s} 
 
 
n 
 
 
 Mean 
 
{95% CI 
(Lower,Upper)
} 
 
 
SD 
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
 
AUC(0-t) 
(units) 
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
14 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
100mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
14 
23 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
Cmax (units) 
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
14 
23 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
100mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
14 
21 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
99 
 
Example: PK05 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Parameter 
 
 
Treatment 
 
 
N 
{Additiona
l 
time 
variables} 
 
 
n 
 
Geom. 
Mean 
 
95% CI 
(Lower,Upper) 
 
 
SD 
(logs) 
 
 
{%CVb} 
AUC(0-t) 
(units) 
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
14 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
100mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
14 
23 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
200mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
14 
21 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
 
 
 
 
 
 
Cmax 
(units) 
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
14 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
100mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
14 
23 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
200mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
14 
21 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
100 
 
Example: PK_T1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Parameter 
Effect 
n 
Slope Point 
Estimate 
SE 
90% CI 
Parameter1 (unit) Log(dose levels) 
xx 
xxx 
xxx 
(xx,xx) 
Parameter2 (unit) Log(dose levels) 
xx 
xxx 
xxx 
(xx,xx) 
. 
. 
. 
. 
. 
. 
 
. 
. 
. 
. 
. 
. 
. 
. 
. 
 
 
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Example: PK_T2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Parameter 
Treatment 
N 
n 
Geometric LS Mean 
Ratio (Fasted/Fed) 
90% CI 
CVw(%)[1] 
Parameter1 (unit) 
Trt1 
xx 
xx 
xxx 
Xxx 
(xx,xx) 
xx 
 
Trt2 
xx 
xx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
Parameter2 (unit) 
Trt1 
xx 
xx 
xxx 
xxx 
(xx,xx) 
xx 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
ParameterX (unit) 
xx 
xx 
xx 
xxx 
xxx 
(xx,xx) 
xx 
 
 
 
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Example: PK16b 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
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Example: PK24 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
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Example: PK18 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
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Example: PK_F1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
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Example: PK28 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
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Example: PK08 (pkcl1x) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
{Inv./} 
Subj. 
 
{Age(y)/ 
Sex/ 
Race} 
 
 
Period
/Tmt. 
 
 
 
Date 
Study 
Day / 
Period 
Day 
 
Planned 
Relative 
Time 
 
 
Actual 
time 
 
 
Time dev. 
(units) 
 
Actual 
Relative 
Time 
 
 
Concentration  
(units) 
 
 
 
 
 
 
 
 
36/ 
M/ 
Mixed Race 
1/ 
50mg 
1/1 
 pre-dose 11:55 
  0 
0h 0m 0s  
  123 
 
 
 
  5m 
12:05 
  0 
0h 5m 0s 
 1434 
 
 
 
  1h 
13:00 
  0 
1h 0m 0s 
   NQ (<0.23) 
 
 
 
  1h 30m  13:30 
  0 
1h 30m 0s    30 
 
 
 
   
 
 
 
 
 
2/ 
100mg 
17/1 
 pre-dose 11:57 
  0 
0h 0m 0s  
  435 
 
 
 
  5m 
12:10 
  0.83 
0h 10m 0s 34566  
 
 
 
  1h 
12:56 
 -0.67 
0h 56m 0s  3452 
 
 
 
  1h 30m  13:30 
  0 
1h 30m 0s    30 
 
 
 
 
 
 
 
 
33/ 
M/ 
Mixed Race 
1/ 
50mg 
1/1 
 pre-dose 11:58 
  0 
0h 0m 0s  
 2345 
 
 
 
 
 
  5m 
12:04 
 -0.17 
0h 4m 0s 
  234 
 
 
 
 
 
  1h 
12:35 
  0.83 
1h 0m 0s 
   NR 
 
 
 
 
 
  1h 30m  13:30 
  0 
1h 30m 0s    30 
 
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PPD
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Example: PK_L1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
{Inv./} 
Subj. 
{Age(y)/ 
Sex/ 
Race} 
 
Parameter 
(units) 
 
Period/ 
Tmt. 
 
 
Value 
 
 
 
 
36/ 
M/ 
Mixed Race 
Parameter1(unit) 
1/ 
50mg 
xx.xx 
 
 
2/ 
100mg 
xx.xx 
 
 
 
 
 
Parameter2(unit) 
1/ 
50mg 
xx 
 
 
2/ 
100mg 
xx 
 
 
 
 
29/ 
M/ 
Mixed Race 
Parameter1(unit) 
1/ 
100mg 
xx.xx 
 
 
 
2/ 
50mg 
xx.xx 
 
 
 
 
 
 
 
Parameter2(unit) 
1/ 
100mg 
xx 
 
 
 
 
 
 
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11. 
REVISION HISTORIY 
Version 
Date 
Amendment 
00 
11-Jul-2017 
Issued version 00 
 


 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
206817 
 
1 
 
Division 
: Worldwide Development 
Information Type    : Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for Study 206817: A Single 
Centre, Double Blind (Sponsor Open), Placebo Controlled, 3-
Period Crossover, Ascending Dose Study in Japanese Healthy 
Elderly Male Subjects to Evaluate the Safety, Tolerability and 
Pharmacokinetics of Danirixin in the Fed State (Part1) and an 
open label, 2-way crossover to evaluate food effect on the 
pharmacokinetics of Danirixin (Part2). 
Compound Number  : GSK1325756 
Effective Date  
: 26-JUL-2017 
 
Description: 
 The purpose of this reporting and analysis plan (RAP) is to describe the planned 
analyses and output to be included in the clinical pharmacology study report for 
protocol 206817.  
 This RAP is intended to describe the safety, pharmacokinetics analyses required for 
the study.  
 This version includes amendments to the originally approved RAP. 
 This document will be provided to the study team members to convey the content of 
the statistical analysis complete (SAC) deliverable. 
 
Author’s Name and Functional Area:  
 
21-Jul-2017 
Biostatistics Group 2 Associate Manager, Biomedical Data 
Sciences Department, Japan. 
 
21-Jul-2017 
Clinical Pharmacology & Science Promotion Office, Medicines 
Development, Japan. 
 
Approved:  
 
26-Jul-2017 
Department Manager, Biomedical Data Sciences Department, 
Japan. 
 
Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
PPD
PPD
PPD


 
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TABLE OF CONTENTS 
PAGE 
1. 
REPORTING & ANALYSIS PLAN SYNPOSIS ........................................................... 4 
1.1. 
RAP Amendments ........................................................................................... 5 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................... 6 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................. 6 
2.2. 
Study Objective(s) and Endpoint(s) ................................................................ 6 
2.3. 
Study Design.................................................................................................... 7 
2.4. 
Statistical Hypotheses ..................................................................................... 8 
3. 
PLANNED ANALYSES ................................................................................................ 9 
3.1. 
Interim Analyses .............................................................................................. 9 
3.2. 
Final Analyses ................................................................................................. 9 
4. 
ANALYSIS POPULATIONS ........................................................................................ 9 
4.1. 
Protocol Deviations ........................................................................................ 10 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ........................................................................................................ 10 
6. 
STUDY POPULATION ANALYSES .......................................................................... 11 
6.1. 
Overview of Planned Analyses ...................................................................... 11 
7. 
SAFETY ANALYSES ................................................................................................. 12 
7.1. 
Overview of Planned Adverse Events Analyses ........................................... 12 
7.2. 
Overview of Planned Clinical Laboratory Analyses ...................................... 12 
7.3. 
Overview of Planned Other Safety Analyses ................................................ 13 
8. 
PHARMACOKINETIC ANALYSES ........................................................................... 14 
8.1. 
Overview of Planned Pharmacokinetic Analyses ......................................... 14 
8.2. 
Drug Concentration Measures ...................................................................... 15 
8.3. 
Pharmacokinetic Parameters ........................................................................ 15 
8.3.1. 
Deriving Pharmacokinetic Parameters .......................................... 15 
8.3.2. 
Summary of Pharmacokinetic Parameters .................................... 17 
8.3.3. 
Statistical Analysis of Pharmacokinetic Parameters ..................... 17 
9. 
REFERENCES .......................................................................................................... 20 
10.  APPENDICES ............................................................................................................ 21 
10.1. 
Appendix 1: Protocol Deviation Management ............................................... 22 
10.2. 
Appendix 2: Time & Events ........................................................................... 23 
10.3. 
Appendix 3: Treatment States and Phases .................................................. 26 
10.3.1. 
Treatment Phases .......................................................................... 26 
10.3.2. 
Treatment States ............................................................................ 26 
10.4. 
Appendix 4: Data Display Standards & Handling Conventions .................... 27 
10.4.1. 
Study Treatment & Sub-group Display Descriptors ...................... 27 
10.4.2. 
Sequence group Display Descriptors ............................................ 27 
10.4.3. 
Baseline Definition & Derivations ................................................... 28 
10.4.4. 
Reporting Process & Standards .................................................... 28 


 
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10.5. 
Appendix 5: Derived and Transformed Data ................................................. 31 
10.5.1. 
General ........................................................................................... 31 
10.5.2. 
Study Population ............................................................................ 31 
10.5.3. 
Safety ............................................................................................. 32 
10.5.4. 
Pharmacokinetics ........................................................................... 33 
10.6. 
Appendix 6: Premature Withdrawals & Handling of Missing Data ................ 34 
10.6.1. 
Premature Withdrawals .................................................................. 34 
10.6.2. 
Handling of Missing Data ............................................................... 34 
10.6.3. 
Handling of Partial Dates ............................................................... 34 
10.6.4. 
Handling of Missing Data for Statistical Analysis .......................... 34 
10.7. 
Appendix 7: Values of Potential Clinical Importance .................................... 35 
10.7.1. 
Laboratory Values (Healthy Volunteers)........................................ 35 
10.7.2. 
ECG (Healthy Volunteers) ............................................................. 36 
10.7.3. 
Vital Signs (Healthy Volunteers) .................................................... 36 
10.8. 
Appendix 8 - Abbreviations & Trade Marks .................................................. 37 
10.8.1. 
Abbreviations ................................................................................. 37 
10.8.2. 
Trademarks .................................................................................... 38 
10.9. 
Appendix 9: List of Data Displays.................................................................. 39 
10.9.1. 
Data Display Numbering ................................................................ 39 
10.9.2. 
Mock Example Referencing ........................................................... 39 
10.9.3. 
Deliverable [Priority] ....................................................................... 39 
10.9.4. 
Study Population Tables ................................................................ 40 
10.9.5. 
Safety Tables ................................................................................. 42 
10.9.6. 
Pharmacokinetic Tables ................................................................. 45 
10.9.7. 
Pharmacokinetic Figures ............................................................... 46 
10.9.8. 
ICH Listings .................................................................................... 48 
10.10.  Appendix 10: Example Mock Shells for Data Displays ................................. 54 
10.10.1.  Study population ............................................................................ 54 
10.10.2.  Safety population ........................................................................... 79 
10.10.3.  PK population ............................................................................... 100 
 
 
 


 
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1. 
REPORTING & ANALYSIS PLAN SYNPOSIS 
Overview 
Key Elements of the Reporting and Analysis Plan  
Purpose 
 
The purpose of this RAP is to describe the planned analyses and output to be included 
in the Clinical Study Report for Protocol 206817. 
Protocol 
 
Reporting and Analysis Plan is based on original protocol (Dated:11-Apr-2017) for study 
GSK1325756 / 206817 [GlaxoSmithKline Document Number:2016N309585_01] 
Objectives 
Part 1 
 
To assess the safety, tolerability and PK following single doses of GSK1325756H 10, 
50 and 100 mg in the fed state in healthy Japanese subjects of over 65 years of age 
inclusive. 
Part 2 
 
To investigate the safety, tolerability and food effect on PK of GSK1325756 following a 
single dose of 50 mg in the fed and fasted state, in healthy Japanese subjects of over 
65 years of age inclusive. 
Endpoints 
Part 1 and 2. 
 
Adverse events (AEs) 
 
Change from baseline of clinical laboratory values, vital signs, and electrocardiogram 
(ECG) parameters 
 
Blood concentration of GSK1325756 
 
Cmax, AUC(0-t), AUC(0-inf), AUC(0-24), tmax, t1/2, tlag, tlast of the blood 
concentration of GSK1325756, as data permit 
Study 
Design 
This study consists of two parts. 
 
Part 1 is a double blind, placebo-controlled, 3-period crossover, ascending dose, single 
oral administration in the fed condition 
 
Part 2 is an open label, 2-way crossover, single oral dose in the fed and fasted state. 
Analysis 
Population 
 
Screened: Consisting of all subjects screened in the study  
 
Screening Failure: Subjects who screened in the study but are never subsequently 
randomized. 
 
Safety: All randomized subjects who take at least one dose of study treatment. 
 
Pharmacokinetic: This population is defined as all subjects administered at least one 
dose of study treatment and who have PK sample taken and analysed. 
Hypothesis 
 
The objectives of this study are to evaluate safety and tolerability of GSK1325756 and 
to estimate GSK1325756 Pharmacokinetic parameters. No formal statistical hypotheses 
will be tested in Part 1 and Part 2. Descriptive statistics will be used to assess safety 
and tolerability objectives. An estimation approach will be used to address the 
pharmacokinetic study objectives, where point estimates and corresponding 90% 
confidence intervals will be constructed. 
Safety 
Analyses 
 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively according to GSK’s Integrated Data Standards Library (IDSL) standards. 
Pharmacoki
netic 
Analyses 
 
Individual GSK1325756 blood concentration-time profiles (by part, treatment and 
subject) and median/mean (±SD) profiles by part and treatment will be plotted and 
listed. Treatment indicates dose group in Part 1 and the fed and fasted condition in Part 
2. 
 
Blood concentration time data for GSK1325756 will be analyzed by non-compartmental 
methods using WinNonlin and derived PK parameters graphically present, summarised 


 
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and listed. No formal statistical analyses will be conducted. 
 
Statistical analyses will be carried out to explore the dose proportionality of 
GSK1325756 as assessed by AUC(0-t) and Cmax using the Power Model (Part 1). 
 
Statistical analyses will be carried out to explore the food effect of GSK1325756 as 
assessed by AUC(0-t) and Cmax using a mixed effects mode (Part 2). 
1.1. 
RAP Amendments 
Revision chronology: 
RAP Section 
Amendment Details 
Reporting and Analysis Plan_206817_Final [11-Jul-2017 
Reporting and Analysis Plan_206817_Final_Amend 1 [DD-Jul-2017] 
1.1 RAP Amendments 
 
added the section 
10.9.1. Data Display 
Numbering 
 
corrected number of ICH Listings 
10.9.3. Deliverable 
[Priority] 
 
deleted "(Part 2 only)" for SAC [2] 
10.9.4. Study Population 
Tables 
 
deleted "(Yes or No)" in the Programing Notes for No. 1.7 and No. 1.8 
10.9.6. Pharmacokinetic 
Tables 
 
added unit in the title for No. 3.1 and No. 3.5 
10.9.8. ICH Listings 
 
corrected "Deliverable [Priority]" column for No. 1, No. 18, and No. 26 
 
added " Listing of Relationship between ATC Level 1, Ingredient and 
Verbatim Text" as No. 21 
 
corrected the title for No. 44 and No. 46 
 
corrected "IDSL / TST ID / Example Shell" column for No. 70 and No. 71 
10.10.1. Study population 
 
added CM6 
10.10.3. PK population 
 
deleted "(unit)" in "Parameter" column for PK_T1 
 
deleted PK_L1 
 
added PK14 
11. Revision History 
 
deleted the section 
 


 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol [Dated: 11/APR/2017]. 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Part 1 
 
To assess the safety, tolerability and PK 
following single doses of GSK1325756H 10, 
50 and 100 mg in the fed state in healthy 
Japanese subjects of over 65 years of age 
inclusive. 
 
Part 2 
 
To investigate the safety, tolerability and food 
effect on PK of GSK1325756 following a 
single dose of 50 mg in the fed and fasted 
state, in healthy Japanese subjects of over 65 
years of age inclusive. 
Part 1 and Part 2 
 
Adverse events (AEs) 
 
Change from baseline of clinical laboratory values, 
vital signs, and electrocardiogram (ECG) 
parameters 
 
Blood concentration of GSK1325756 
 
Cmax, AUC(0-t), AUC(0-inf), AUC(0-24), tmax, t1/2, 
tlag, tlast of the blood concentration of 
GSK1325756, as data permit 
 
 


 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
Subjects will be divided into Part 1 and 2, and receive the following study treatment 
doses shown in Table below. 
Part 1: 
Group 
n 
Period 1 
Washout
Period 2 
Washout
Period 3 
A 
6 
10 mg 
at least 7 
days 
50 mg 
at least 7 
days 
Placebo 
B 
6 
10 mg 
Placebo 
100 mg 
C 
6 
Placebo 
50 mg 
100 mg 
 
Part 2: 
Group 
n 
Period 1 
Washout 
Period 2 
D 
8 
50 mg, fed 
at least 7 
days 
50 mg, fasted 
E 
8 
50 mg, fasted 
50 mg, fed 
 
Design 
Features 
Part 1: This is a double blind, placebo-controlled, 3-period crossover, 
ascending dose, single oral administration in the fed condition. 
Part 2: This is an open label, 2-way crossover, single oral dose in the fed 
and fasted state study. 
Dosing 
Part 1: 
Subjects will have a screening visit within 30 days prior to the first dose of 
study. A minimum washout period of 7 days will be required between 
each treatment period. Subjects will receive three treatment periods in the 
study. Subjects will be housed in the Clinical Research Unit from Day -1 
(the day before dosing) through Day 3 for Period 1 and 2, and from Day -1 
(the day before dosing) through Day 4 for Period 3. Subjects will return to 
the clinic 7 days (at least) after the previous administration day for Period 
1 and 2, and subjects will visit the unit on Day 8 (+/- 1 day) of the last 
dosing for Period 3 for follow-up. 
 
Part 2: 
Subjects will have a screening visit within 30 days prior to the first dose of 
study treatment, two treatment periods separated by at least 7 days, and 
follow-up. Subjects will be housed in the Clinical Research Unit from Day 
-1 (the day before dosing) through Day 3 (for Period 1 and 2), and re-visit 
7 (±1) days after the last dose of Period 2 for follow-up. 


 
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Overview of Study Design and Key Features 
Treatment 
Assignment 
 
Sufficient participants will be randomised such that approximately 18 
in Part 1and 16 in Part 2 evaluable participants complete the study of 
each part. 
 
If participants prematurely discontinue the study, additional 
participants may be enrolled as replacement participants and assigned 
to the same treatment sequence, if applicable, at the discretion of the 
sponsor in consultation with the investigator. 
 
On Day 1 of each Part, participants will be assigned a unique number 
(randomization number) in ascending numerical order. The 
randomization number encodes the participant’s assignment to one of 
the 3 sequences in Part 1 and one of the 2 sequences in Part 2, 
according to the randomization schedule generated prior to the study 
by the Biomedical Data Sciences Department at GSK. 
 
Participants will be randomized in a 1:1:1 ratio to receive sequence 
(A:B:C) for Part 1, or will be randomized in a 1:1 ratio to receive 
sequence (D:E) for Part 2. 
 
Each participant will be dispensed blinded study treatment, labeled 
with his unique randomization number, throughout the study. 
 
Investigators, participants and sponsor will remain blinded to each 
participant’s assigned study treatment throughout the course of the 
study. For the concentration evaluation after Period 2 of Part 1, the 
pre-specified sponsor's person who is responsible for the confirmation 
of the concentration will review blood drug concentration data under 
unblended. 
Interim 
Analysis 
 
No formal statistical analysis is planned. 
 
A blind review of preliminary safety data (AE, clinical laboratory 
values, vital signs, ECG) and blood concentration will be conducted 
between Period 2 and Period 3 in Part 1 and prior to Part 2. 
 
After completion of Part 1, formal analysis for Part 1 is to be 
conducted. 
 
2.4. 
Statistical Hypotheses 
The objectives of this study are to evaluate safety, tolerability and PK profile of single 
dose of GSK1325756H and to investigate food effect of PK profile of single dose of 
GSK1325756H in healthy Japanese elderly subjects. No formal statistical hypotheses will 
be tested in Part 1 and Part 2. Descriptive statistics will be used to assess safety and 
tolerability objectives. An estimation approach will be used to address the PK study 
objectives, where point estimates and corresponding 95% confidence intervals will be 
constructed, unless otherwise stated. 


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
No formal statistical analysis is planned. However, following Period 1 and Period 2 of 
Part 1, a blind review of preliminary safety data (AE, clinical laboratory values, vital 
signs, ECGs) will be conducted between Period 2 and Period 3 in Part 1 and prior to Part 
2. Furthermore, the sponsor's person who is responsible for the confirmation of the 
concentration will review blood drug concentration data under unblended. 
3.2. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the 
following sequential steps: 
1. All subjects in each part have completed the study as defined in the protocol. 
2. All required database cleaning activities in each part have been completed and final 
database release and database freeze has been declared by Data Management for each 
part. 
3. All criteria for unblinding the randomisation codes have been met for Part 1. 
4. Randomisation codes have been distributed according to RandAll NG procedures. 
After completion of Part 1, formal analysis for Part 1 is to be conducted. 
4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Endpoint(s) Evaluated 
Screened 
 Consisting of all subjects screened in the 
study. 
Note: This definition indicates the same 
meaning as ‘All subjects who have subject 
number’ in a programming point of view. 
 Study Population 
Screening Failure  
 Subjects who screened in the study but are 
never subsequently randomized. All 
participants who sign the ICF have the 
screening test in the study. 
Note: This definition indicates the same 
meaning as ‘Subjects who have subject 
number but are never subsequently 
randomized’ in a programming point of view. 
 Study Population 
Safety 
 All randomized subjects who take at least 
one dose of study treatment. Participants will 
be analyzed according to the treatment they 
actually received. 
 Study Population 
 Safety 


 
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Population 
Definition / Criteria 
Endpoint(s) Evaluated 
Pharmacokinetic 
 This population is defined as all subjects 
administered at least one dose of study 
treatment and who have PK sample taken 
and analysed. Participants will be analyzed 
according to the treatment they actually 
received. 
 PK 
4.1. 
Protocol Deviations 
 
Important protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarised and listed. 
 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations and deviations which may lead to exclusion from the analysis are 
captured and categorised on the protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of protocol deviations. 
 
A separate listing of all inclusion/exclusion criteria deviations will also be provided. 
This will be based on data as recorded on the inclusion/exclusion page of the eCRF. 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
Table 1 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions. 
Table 1 
Overview of Appendices 
Section Component 
10.1 
Appendix 1: Protocol Deviation Management 
10.2 
Appendix 2: Time & Events 
10.3 
Appendix 3: Treatment States and Phases 
10.4 
Appendix 4: Data Display Standards & Handling Conventions 
10.5 
Appendix 5: Derived and Transformed Data 
10.6 
Appendix 6: Premature Withdrawals & Handling of Missing Data 
10.7 
Appendix 7: Values of Potential Clinical Importance 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Analyses 
The study population analyses will be based on the Safety Population, unless otherwise 
specified. These analyses will be performed in each part. 
Table 2 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 9: List of Data Displays. 
Table 2 
Overview of Planned Study Population Analyses 
Display Type 
Data Displays Generated 
Table 
Figure 
Listing 
Subject Disposition 
Subject Disposition and Reason for Study Withdrawal 
Y 
 
Y 
Screening Status and Reasons for Screen Failure 
Y 
 
Y 
Subjects for Whom the Treatment Blind was Broken 
 
 
Y 
Planned and Actual Treatments 
 
 
Y 
Protocol Deviations 
Important Protocol Deviations 
Y 
 
Y 
Inclusion/Exclusion Criteria Deviations 
 
 
Y 
Populations Analysed 
Study Populations 
Y 
 
 
Subjects Excluded from Any Population 
 
 
Y 
Demographic and Baseline Characteristics 
Demographic Characteristics 
Y 
 
Y 
Demographic Characteristics for Screening Failure 
 
 
Y 
Age Ranges 
Y 
 
 
Race and Racial Combinations 
Y 
 
Y 
Race and Racial Combinations for Screening Failure 
 
 
Y 
Medical Conditions and Concomitant Medications 
Medical Conditions 
 
 
Y 
Concomitant Medications 
 
 
Y 
Exposure and Treatment Compliance 
Exposure to Study Treatment 
 
 
Y 
Meal 
Meal start and end days/times on fed treatment 
 
 
Y 
NOTES: 
 
Y = Yes display generated. 
 


 
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7. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety Population, unless otherwise specified. 
These analyses will be performed in each part. 
Adverse events occurred in washout period will be included in adverse events analyses 
for previous period. Also adverse events occurred in follow up period will be included in 
safety analyses for the last period. 
7.1. 
Overview of Planned Adverse Events Analyses 
Table 3 provides an overview of the planned adverse events analyses with full details of 
data displays being presented in Appendix 9: List of Data Displays. 
Table 3 
Overview of Planned Adverse Event Analyses 
Display Type 
Absolute 
Summary 
Individual 
T 
F 
L 
Adverse Events (AEs) 
All AEs by SOC and PT 
Y 
 
Y 
All AEs by Maximum Intensity 
Y 
 
 
Drug-Related AEs by SOC and PT 
Y 
 
 
Drug-Related AEs by Maximum Intensity 
Y 
 
 
Subject Numbers for Individual AEs 
 
 
Y 
Relationship Between AE SOCs, PT and Verbatim Text 
 
 
Y 
Serious and Other Significant AEs 
Serious AEs 
 
 
Y 
AEs Leading to Withdrawal from Study  
 
 
Y 
NOTES: 
 
T = Table, F = Figures, L = Listings, Y = Yes display generated, SOC = System Organ Class, PT = Preferred 
Term. 
 
Summary = Represents TF related to any summaries (i.e. descriptive statistics) of the observed raw data. 
 
Individual = Represents FL related to any displays of individual subject observed raw data.  
 
7.2. 
Overview of Planned Clinical Laboratory Analyses 
Table 4 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 9: List of Data Displays. 


 
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Table 4 
Overview of Planned Clinical Laboratory Analyses 
Display Type 
Absolute 
Change from BL 
Summary
Individual
Summary 
Individual
T 
F 
L 
T 
F 
L 
Chemistry 
Chemistry Data 
Y 
 
Y 
Y 
 
Y 
Chemistry Results Relative to Normal Range 
 
 
 
Y 
 
 
All Chemistry Data for Subjects with any Value of 
Potential Clinical Concern/PCI 
 
 
Y 
 
 
Y 
Hematology 
Hematology Data 
Y 
 
Y 
Y 
 
Y 
Hematology Results Relative to Normal Range 
 
 
 
Y 
 
 
All Hematology Data for Subjects with any Value of 
Potential Clinical Concern/PCI 
 
 
Y 
 
 
Y 
Urinalysis 
Dipstick Data (Glucose, Protein, Blood, Ketones, 
Bilirubin, Urobilinogen) 
Y 
 
Y* 
 
 
 
Gravity and pH 
Y 
 
Y 
 
 
 
Hepatobiliary (Liver) 
Liver Monitoring/Stopping Event Reporting 
 
 
Y 
 
 
 
Medical Conditions for Subjects with Liver Stopping 
Events 
 
 
Y 
 
 
 
Substance Use for Subjects with Liver Stopping Events 
 
 
Y 
 
 
 
NOTES: 
 
T = Table, F = Figures, L = Listings, Y = Yes display generated, PCI = Potential Clinical Importance 
 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
 
Individual = Represents FL related to any displays of individual subject observed raw data.  
*: If blood or protein is abnormal, microscopic examination will be included. 
7.3. 
Overview of Planned Other Safety Analyses 
Table 5 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 9: List of Data Displays. 


 
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Table 5 
Overview of Planned Other Safety Analyses 
Display Type 
Absolute 
Change from BL 
Summary
Individual
Summary 
Individual
T 
F 
L 
T 
F 
L 
ECG 
ECG Findings 
Y 
 
Y 
 
 
 
ECG Values 
Y 
 
Y 
Y 
 
Y 
All ECG Values for Subjects with any Value of PCI 
 
 
Y 
 
 
 
Vital Signs 
Vitals Values 
Y 
 
Y 
Y 
 
Y 
All Vital Signs for Subjects with any Value of PCI 
 
 
Y 
 
 
 
Ophthalmic examinations 
Ophthalmic examinations 
 
 
Y 
 
 
 
NOTES: 
 
T = Table, F = Figures, L = Listings, Y = Yes display generated, PCI = Potential Clinical Importance 
 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
 
Individual = Represents FL related to any displays of individual subject observed raw data. 
8. 
PHARMACOKINETIC ANALYSES 
8.1. 
Overview of Planned Pharmacokinetic Analyses 
The pharmacokinetic (PK) analyses will be based on the Pharmacokinetic population, 
unless otherwise specified. These analyses will be performed in each part. 
Table 6 provides an overview of the planned analyses, with full details being presented in 
Appendix 9: List of Data Displays. 


 
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Table 6 
Overview of Planned Pharmacokinetic Analyses 
Display Type 
Untransformed 
Log-Transformed 
Summary 
Individual 
Stats 
analysis
Summary 
Individual 
F 
T 
F 
L 
 
F 
T 
F 
L 
Descriptive statistics 
Blood Drug Concentrations 
Y [1] [2] 
Y 
Y [1] 
Y 
 
 
 
 
 
Derived PK Parameters 
Y 
Y 
 
Y 
 
 
Y 
 
 
Statistical Analysis of PK Parameters 
Power model (Part 1) 
 
 
 
 
Y 
 
 
 
 
Food effect (Part 2) 
 
 
 
 
Y 
 
 
 
 
NOTES: 
 
T = Table, F = Figures, L = Listings, Y = Yes display generated. 
 
Summary = Represents TFL related to any summaries (descriptive statistics) of the observed raw data. 
 
Individual = Represents FL related to any displays of individual subject observed raw data. 
1. 
Linear and Semi-Log plots will be created on the same display. 
2. 
Separate Mean (+ SD) and Median plots will be generated. 
8.2. 
Drug Concentration Measures 
Blood concentrations of GSK1325756 will be listed and summarised by part, treatment 
and nominal time. Standard summary statistics will be calculated (i.e. mean, standard 
deviation, median, minimum and maximum). 
Individual blood concentration-time profiles and median/mean profiles by treatment will 
be plotted. Each of the figures will contain one plot on the untransformed scale (i.e. a 
linear plot) and one plot on the log transformed scale (i.e. log-linear plot). 
Refer to Appendix 4: Data Display Standards & Handling Conventions (Section 10.4.4 
Reporting Process & Standards). 
8.3. 
Pharmacokinetic Parameters 
8.3.1. 
Deriving Pharmacokinetic Parameters 
 
Derivation of pharmacokinetic parameters will be performed by, or under the direct 
auspices of, Clinical Pharmacology & Science Promotion Office, GlaxoSmithKline 
K.K. 
 
Refer to Appendix 4: Data Display Standards & Handling Conventions (Section 
10.4.4 Reporting Process & Standards). 
 
The pharmacokinetic parameters will be calculated by standard non-compartmental 
analysis using WinNonlin (version 6.3 or higher) 
 
All calculations of non-compartmental parameters will be based on actual sampling 
times recorded during the study. 
 
Pharmacokinetic parameters described in Table 7 will be determined from blood 
GSK1325756 concentration-time data, as data permits. 


 
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Table 7 
Derived Pharmacokinetic Parameters 
Parameter 
Parameter Description 
AUC(0-24) 
(h*ng/mL) 
Area under the concentration-time curve will be calculated to fixed nominal time 24 
hours after administration (AUC(0-24)),using the combination of linear and logarithmic 
trapezoidal methods (i.e., Linear Up/Log Down calculation method in Phoenix 
WinNonlin Professional). 
If a sampling time deviation occurred at nominal time 24 hours after administration (and 
24 < t), AUC(0-24) will be calculated using the concentration at time 24 hours after 
administration post-dose estimated by the method of interpolation. 
If nominal time 24 hours after administration > t (or if the concentration at time 24 hours 
after administration was below then limit of quantification), then the concentration (y) at 
time 24 hours after administration is estimated using lambda_z and last observed Ct 
according to the formula: 
 
y=Ct(obser) x e-lambda_z(24-t) 
 
Then the following equation will be used to calculate (AUC(0-24)) where t is the time of 
last quantifiable blood concentration. 
 
AUC(0-24) = AUC(0-t) + AUC(t-24) 
 
If lambda_z is not estimable, a partial AUC is not calculated (when 24 > t). 
AUC(0-t) 
(h*ng/mL) 
Area under the concentration-time curve from zero time (pre-dose) to the time of the 
last quantifiable concentration (AUC(0-t)) will be calculated by a combination of linear 
and logarithmic trapezoidal methods. The linear trapezoidal method will be employed 
for all incremental trapezoids arising from increasing concentrations and the logarithmic 
trapezoidal method will be used for those arising from decreasing concentrations (i.e., 
Linear Up/Log Down calculation method in Phoenix WinNonlin Professional). 
AUC(0-inf) 
(h*ng/mL) 
Area under the concentration-time curve from zero time (pre-dose) extrapolated to 
infinite time (AUC(0-inf)) will be calculated as follows:  
AUC(0-inf) = AUC(0-t) + Ct / lambda_z 
Cmax (ng/mL) 
Maximum observed concentration will be obtained directly from the concentration-time 
data. 
Tmax (h) 
Time to first occurrence of Cmax will be obtained directly from the concentration-time 
data. 
t1/2 (h) 
Terminal phase half-life will be calculated as follows: 
t1/2 = ln2 / lambda_z 
tlag (h) 
Lag time before observation of drug concentrations in sampled matrix. 


 
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Parameter 
Parameter Description 
tlast (h) 
The time of the last measurable (positive) concentration. 
%AUCex (%) 
The area under the curve (AUC) from the last predicted non-zero concentration value 
to infinity as a percentage of the area under the curve extrapolated to infinity. 
lambda_z (/h) 
The first order rate constant associated with the terminal (log-linear) portion of the 
curve. 
lambda_z_lower 
(h) 
The lower limit on time for values to be included in the calculation of Lambda z. 
lambda_z_upper 
(h) 
The upper limit on time for values to be included in the calculation of Lambda z. 
#pts 
The number of time points used in computing Lambda z. 
R2 
The goodness of fit statistic for the terminal elimination phase. 
NOTES: 
 
Additional parameters may be included as required. 
 
Lambda_z is the terminal phase rate constant. 
 
Ct is the last observed quantifiable concentration. 
 
8.3.2. 
Summary of Pharmacokinetic Parameters 
 
For each of these parameters, except for tmax, tlag and tlast, the following summary 
statistics will be calculated for each treatment: 
o Non-transformed: arithmetic mean, median, maximum, minimum, 95% 
confidence interval for the arithmetic mean and standard deviation 
o Loge-transformed: geometric mean, 95% confidence interval for the geometric 
mean, standard deviation of logarithmically transformed data and between 
geometric coefficient of variation (CVb (%))  
 
Median, maximum, minimum, arithmetic mean, 95% confidence interval and 
standard deviation will be calculated for tmax, tlag and tlast. 
 
8.3.3. 
Statistical Analysis of Pharmacokinetic Parameters 
8.3.3.1. 
Dose proportionality 
For Part 1, the PK-dose relationship will be investigated graphically in order to assess 
dose proportionality of GSK1325756. Plots of AUC (0-t) and Cmax versus dose will be 
plotted. 


 
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Also statistical analyses will be carried out to explore the dose proportionality of 
GSK1325756 as assessed by AUC(0-t) and Cmax, using the Power Model: 
loge (Yij) = μ + Si + β*loge (Dj) + εij 
  Yij: PK parameter (AUC(0-t), Cmax) on the jth dose for ith subject 
  μ: Overall mean (Intercept) 
  Si: Random effect for subject i following normal distribution N(0, σb2) 
  β: Slope for loge transformed dose 
  Dj: Dose (j=1:10mg, 2:50mg, 3:100mg) 
  εij: Random error following normal distribution N(0, σw2) 
Following loge-transformation, AUC (0-t) and Cmax will be separately analyzed, if data 
permitted. A mixed effect model will be fitted with the loge transformed dose and period 
as fixed effects. Subject will be fitted as a random effect. The Kenward & Roger (KR) 
degrees of freedom approach will be used. Point estimates and their associated 90% 
confidence intervals will be constructed. 
8.3.3.2. 
Food effect 
For Part 2, statistical analyses will be carried out to assess treatment (food effect) of 
GSK1325756 for AUC(0-t) and Cmax using Mixed effect model: 
loge (Yij) = μ + Si + tj + pk + εij 
  Yij: PK parameter (AUC(0-t), Cmax) on the jth treatment for ith subject 
  μ: Overall mean (Intercept) 
  Si: Random effect for subject i following normal distribution N(0, σb2) 
  ti : Treatment effect (j=fasted, fed) 
  pk: Period effect (k=period 1, period 2) 
  εij: Random error following normal distribution N(0, σw2) 
Following loge-transformation, AUC (0-t) and Cmax will be separately analysed using a 
mixed effects model fitting terms for treatment and period as fixed effects, and subject as 
a random effect in order to assess food effect of GSK1325756 (Fed vs. Fasted). The 
Kenward & Roger (KR) degrees of freedom approach will be used. 
Point estimates for the adjusted means on the loge scale, the mean difference between 
treatments and associated 90% confidence interval will be constructed using the residual 
variance. The point estimate and confidence interval will then be exponentially back-
transformed to obtain adjusted (least square) geometric means for each treatment, and 
point estimates and associated 90% confidence interval for the ratio of fasted/fed. 


 
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Estimates of within-subject variability (CVw (%)) for AUC (0-t) and Cmax will also be 
provided. CVw (%) will be calculated based on the loge-normal distribution where: 
    CVw (%)= SQRT(exp(MSE)-1) * 100. (MSE is the residual mean squared error 
from the model) 


 
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9. 
REFERENCES 
GlaxoSmithKline Document Numbers 2016N309585_01: Study Protocol of 206817. A 
Single Centre, Double Blind (Sponsor Open), Placebo Controlled, 3-Period Crossover, 
Ascending Dose Study in Japanese Healthy Elderly Male Subjects to Evaluate the Safety, 
Tolerability and Pharmacokinetics of Danirixin in the Fed State (Part1) and an open label, 
2-way crossover to evaluate food effect on the pharmacokinetics of Danirixin (Part2). 


 
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10. 
APPENDICES 
Section 
Appendix 
RAP Section 4 : Analysis Populations 
Section 10.1 
Appendix 1: Protocol Deviation Management 
RAP Section 5 : General Considerations for Data Analyses & Data Handling Conventions 
Section 10.2 
Appendix 2: Time and Events 
Section 10.3 
Appendix 3: Treatment States & Phases 
Section 10.4 
Appendix 4: Data Display Standards & Handling Conventions 
 Study Treatment 
 Baseline Definitions & Derivations 
 Reporting Process & Standards 
Section 10.5 
Appendix 5: Derived and Transformed Data 
 General 
 Study Population 
 Safety 
 Pharmacokinetics 
Section 10.6 
Appendix 6: Premature Withdrawals & Handling of Missing Data 
 General 
 Study Population & Safety 
Section 10.7 
Appendix 7: Values of Potential Clinical Importance 
 Laboratory Values 
 ECG 
 Vital Signs 
Other RAP Appendices 
Section 10.8 
Appendix 8: Abbreviations & Trade Marks 
Section 10.9 
Appendix 9: List of Data Displays 
Section 10.10 
Appendix 10: Example Mock Shells for Data Displays 
 


 
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10.1. 
Appendix 1: Protocol Deviation Management 
Details will be referred latest Protocol Deviation Management Plan and data handling 
will be decided prior to final data base release. 
 
 


 
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10.2. 
Appendix 2: Time & Events 
 
Part 1, Period 1-2 
 
 


 
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Part 1, Period 3 
 
 
 
 
 


 
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Part 2, Period 1-2 
 
 


 
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10.3. 
Appendix 3: Treatment States and Phases 
10.3.1. 
Treatment Phases 
Assessments and events will be classified according to the time of occurrence relative to 
the assessment date. 
Treatment Phase 
Definition 
Part 1: Period 1 
Assessment Date < Previous Day of Dosing Start Date in Period 2 (Part 1) 
Part 1: Period 2 
Previous Day of Dosing Start Date in Period 2 ≤ Assessment Date < Previous Day 
of Dosing Start Date in Period 3 (Part 1) 
Part 1: Period 3 
Previous Day of Dosing Start Date in Period 3 ≤ Assessment Date (Part 1) 
Part 2: Period 1 
Assessment Date < Previous Day of Dosing Start Date in Period 2 (Part 2) 
Part 2: Period 2 
Previous Day of Dosing Start Date in Period 2 ≤ Assessment Date (Part 2) 
 
10.3.2. 
Treatment States 
Assessments and events will be classified according to time of occurrence relative to the 
start and/or stop date of the study treatment. 
10.3.2.1. 
Treatment States for AE Data 
Treatment State 
Definition 
Pre-Treatment 
AE Start Date and Time < Dosing Start Date and Time 
Part 1: Period 1 
Dosing Start Date and Time in Period 1 ≤ AE Start Date and Time < Dosing Start 
Date and Time in Period 2 (Part 1) 
Part 1: Period 2 
Dosing Start Date and Time in Period 2 ≤ AE Start Date and Time < Dosing Start 
Date and Time in Period 3 (Part 1) 
Part 1: Period 3 
Dosing Start Date and Time in Period 3 ≤ AE Start Date and Time (Part 1) 
Part 2: Period 1 
Dosing Start Date and Time in Period 1 ≤ AE Start Date and Time < Dosing Start 
Date and Time in Period 2 (Part 2) 
Part 2: Period 2 
Dosing Start Date and Time in Period 2 ≤ AE Start Date and Time (Part 2) 
Onset Time Since 
First Dose (Minute) 
If Dosing Start Date and Time ˃ AE Onset Date and Time = AE Onset Date and 
Time – Dosing Start Date and Time 
If dosing Start Date and Time ≤ AE Onset Date and Time = AE Onset Date and 
Time - Dosing Start Date and Time +1 
Missing otherwise 
Onset Time Since 
Last Dose (Minute) 
AE Start Date and Time – Most Recent Treatment Start Date and Time + 1 
Duration (Minute)  
AE Resolution Date and Time – AE Onset Date and Time + 1 
Drug-related 
If relationship is marked ‘YES’ on eCRF 
 
 


 
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10.4. 
Appendix 4: Data Display Standards & Handling 
Conventions 
10.4.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
Part1 (Scedule1) 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description 
Order [1] 
P 
Placebo, Fed 
Placebo, Fed 
1 
X1 
GSK1325756H 10 mg, Fed 
GSK1325756H 10 mg, Fed 
2 
X2 
GSK1325756H 50 mg, Fed 
GSK1325756H 50 mg, Fed 
3 
X3 
GSK1325756H 100 mg, Fed 
GSK1325756H 100 mg, Fed 
4 
Part2 (Scedule2) 
X2 
GSK1325756H 50 mg, Fed 
GSK1325756H 50 mg, Fed 
1 
X4 
GSK1325756H 50 mg, Fasted 
GSK1325756H 50 mg, Fasted 
2 
NOTES: 
1. 
Order in which treatments are to be presented in Listings. Note that the order in which treatments are to be 
presented in Tables, active treatment (X1, X2, X3 in Part 1, X2, X4 in Part 2) is shown in the first and placebo (P in 
Part 1) in the second. 
 
10.4.2. 
Sequence group Display Descriptors 
Sequence Group Descriptions 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description [1] 
Order  
A 
X1/X2/P 
A 
1 
B 
X1/P/X3 
B 
2 
C 
P/X2/X3 
C 
3 
D 
X2/X4 
D 
4 
E 
X4/X2 
E 
5 
NOTES: 
1. 
Footnote will be added in displays as follows. 
A: 10mg (Fed) / 50mg (Fed) / Placebo (Fed), B: 10mg (Fed) / Placebo (Fed) / 100mg (Fed), C: Placebo (Fed) / 
50mg (Fed) / 100mg (Fed), D: 50mg (Fed) / 50mg (Fasted) , E: 50mg (Fasted) / 50mg (Fed) 
 
 


 
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10.4.3. 
Baseline Definition & Derivations 
10.4.3.1. 
Baseline Definitions 
Parameter 
Study Assessments Considered 
as Baseline 
Baseline Used in 
Data Display 
Screening
Day -1
Day 1   
(Pre-Dose)
Safety 
12 Lead ECG & Vital Signs 
X 
X 
X 
Day 1 
(Pre Dose) 
Haematology  
X 
X 
 
Day -1 
Clinical Chemistry 
X 
X 
 
Day -1 
NOTES: 
 
The baseline will be defined for each period in Part 1 and Part 2. 
10.4.3.2. 
Derivations and Handling of Missing Baseline Data 
Definition 
Reporting Details 
Change from Baseline
= Post-Dose Visit Value – Baseline
NOTES: 
 
Unless otherwise specified, the baseline definitions specified in Section 10.4.3.1 Baseline Definitions will be used 
for derivations for endpoints / parameters and indicated on summaries and listings. 
 
Unless otherwise stated, if baseline data is missing no derivation will be performed and will be set to missing. 
 
The baseline definition will be footnoted on all change from baseline displays. 
 
10.4.4. 
Reporting Process & Standards 
Reporting Process 
Software 
 The currently supported versions of SAS software will be used. 
Reporting Area  
HARP 
Server 
: uk1salx00175 
HARP Area 
Part1:/arenv/arprod/gsk1325756/mid206817/primary_01 
Part2:/arenv/arprod/gsk1325756/mid206817/final_01 
QC 
Spreadsheet 
Part1:/arenv/arprod/gsk1325756/mid206817/primary_01/qc 
Part2:/arenv/arprod/gsk1325756/mid206817/final_01/qc 
Analysis Datasets  
 Analysis datasets will be created according to GSK IDSL A&R dataset standards 
Generation of RTF Files 
 N/A 
 
 


 
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Reporting Standards 
General 
 The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated: 
o 4.03 to 4.23: General Principles 
o 5.01 to 5.08: Principles Related to Data Listings 
o 6.01 to 6.11: Principles Related to Summary Tables 
o 7.01 to 7.13: Principles Related to Graphics  
Formats 
 All data will be reported according to the actual treatment the subject received unless 
otherwise stated. 
 GSK IDSL Statistical Principles (4.24) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected. 
 Numeric data will be reported at the precision collected on the eCRF. 
 The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
 Reporting for tables, figures and formal statistical analyses: 
o Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
o The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as appropriate.
 Reporting for Data Listings: 
o Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1). 
o Unscheduled or unplanned readings will be presented within the subject’s listings. 
o Visits outside the protocol defined time-windows (i.e. recorded as protocol deviations) will 
be included in listings but omitted from figures, summaries and statistical analyses. 
Unscheduled Visits 
 Unscheduled visits will not be included in summary tables. 
 Unscheduled visits will not be included in figures. 
 All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Reporting of Pharmacokinetic Concentration Data 
Descriptive Summary 
Statistics 
Refer to IDSL Statistical Principle 6.06.1 
Assign zero to NQ values (Refer to GUI_51487 for further details) 


 
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Reporting Standards 
Reporting of Pharmacokinetic Parameters 
Descriptive Summary 
Statistics.           
(Log Transformed) 
N, n, geometric mean, 95% CI of geometric mean, standard deviation 
(SD) of logged data and between geometric coefficient of variation 
(CVb/w (%)) will be reported. 
CVb (%) = SQRT (exp(SD2) - 1) * 100  
(SD = SD of loge-transformed data) 
CVw (%) =SQRT (exp(MSE) - 1) * 100  
(MSE = mean square error from mixed effect model of loge-transformed data). 
Parameters Not Being 
Log Transformed   
tmax, tlag, tlast 
Parameters Not Being 
Summarised 
The following PK parameters will not be summarised but listed: %AUCex, 
lambda_z, lambda_z_lower, lambda_z_upper, #pts, R2. 
Graphical Displays 
 Refer to IDSL Statistical Principals 7.01 to 7.13. 


 
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Reporting Standards 
10.5. 
Appendix 5: Derived and Transformed Data 
10.5.1. 
General 
Multiple Measurements at One Time Point 
 Mean of the measurements will be calculated and used in any derivation of summary statistics 
but if listed, all data will be presented. 
 If there are two values within a time window the value closest to the target day for that window 
will be used. If values are the same distance from the target, then the mean will be taken. 
 Subjects having both High and Low values for Normal Ranges at any post-baseline visits for 
safety parameters will be counted in both the High and Low categories of “Any visit post-
baseline” row of related summary tables. This will also be applicable to relevant Potential 
Clinical Importance summary tables. 
Study Day 
 Calculated as the number of days from start of dosing date: 
o 
Ref Date = Missing           → Study Day = Missing  
o 
Ref Date < of start of dosing Date → Study Day = Ref Date – of start of dosing Date     
o 
Ref Data ≥ of start of dosing Date → Study Day = Ref Date – (of start of dosing Date) + 1 
 
10.5.2. 
Study Population 
Demographics 
Age 
 GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed 
as: 
o 
Any subject with a missing day will have this imputed as day ‘15’. 
o 
Any subject with a missing date and month will have this imputed as ‘30th June’. 
 Birth date will be presented in listings as ‘YYYY’. 
 Reference will be Randomization date for Part 1 and Part 2 
 Reference date for calculation of age at screening will be from visit 1 (Screening visit) date, 
however this will be from screen failure date for a screen failure subject. 
 Analysis age group will be categorized (Years): 
   <=18, 19-64, 65-74, >=75 
 Age will be categorized for EudraCT: 
   <=17 years, 18-64 years, 65-84 years, >=85 years 
Body Mass Index (BMI) 
 Calculated as Weight (kg) / [Height (m)2] 
 


 
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10.5.3. 
Safety 
Laboratory Parameters 
 If a laboratory value which is expected to have a numeric value for summary purposes, has a 
non-detectable level reported in the database, where the numeric value is missing, but typically 
a character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the 
comment field) is present, the number of significant digits in the observed values will be used to 
determine how much to add or subtract in order to impute the corresponding numeric value.  
o Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01 
o Example 2: 1 Significant Digit   =  ‘> x’ becomes x + 0.1 
o Example 3: 0 Significant Digits = ‘< x’ becomes x – 1 
 
Laboratory Assessments 
Haematology 
Platelet Count, RBC Count, Haemoglobin, Hematocrit, RBC Indices (MCV, 
MCH, %Reticulocytes), WBC count with Differential (Neutrophils, 
Lymphocytes, Monocytes, Eosinophils, Basophils) 
Clinical Chemistry 
BUN, Creatinine, Glucose (fasting), Uric acid, HDL-cholesterol, Amylase, 
Potassium, Sodium, Calcium, TG, LDH, Chloride, Aspartate Aminotransferase 
(AST), Alanine Aminotransferase (ALT), Alkaline phosphatise, Total 
Cholesterol, GGT, Phosphorus, Total and direct bilirubin, Total Protein, 
Albumin, LDL-cholesterol, CK (CPK) 
Routine Urinalysis 
 Specific gravity, pH (assessed by dipstick) 
 glucose, protein, blood, ketones, bilirubin, urobilinogen by dipstick 
 Microscopic examination (if blood or protein is abnormal) 
 
ECG (12-lead ECG) 
ECG findings, ECG values (Heart rate, PR interval, QRS duration, QT interval and QTcF intervals) 
 
Vital Signs 
Pulse rate, Blood pressure (Systolic, Diastolic),Temperature 
 
Ophthalmic examinations 
Ophthalmic examinations 
 


 
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10.5.4. 
Pharmacokinetics 
PK Parameters 
 If one or more non-quantifiable (NQ) values occur in a profile before the first measurable 
concentration, they will be assigned a value of zero concentration. For linear plots, zero 
concentration value(s) before the first measurable concentration will be included in the plot. For 
log-linear plots, zero concentration value(s) before the first measurable concentration will be 
assigned a missing value. 
 If a single NQ value occurs between measurable concentrations in a profile, the NQ should 
generally be set to missing in the derivation of pharmacokinetic parameters, statistical analysis, 
and the individual subject plots. 
 If two or more NQ values occur in succession between measurable concentrations, the profile 
will be deemed to have terminated at the last measurable concentration prior to these NQs. 
For the purpose of individual subject plots, these NQs will be set to 0, and the subsequent 
measurable concentrations will be retained. For the derivation of pharmacokinetic parameters, 
these NQs and any subsequent measurable concentrations will be set to missing. 
 NQs which occur after the last measurable concentration will be omitted (set to missing) in the 
derivation of pharmacokinetic parameters and from the individual subject plots. 
 Individual’s PK parameters reported as 'NC' (Not Calculable) or 'ND' (Not Determined) will be 
included in listings but omitted (set to missing) from figures, summaries and statistical 
analyses. 
 
 
 


 
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10.6. 
Appendix 6: Premature Withdrawals & Handling of Missing 
Data 
10.6.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
 Subject study completion was defined as a participant has completed all periods 
of the study including the last visit or the last scheduled procedure (Follow-up) 
for each period as described in the protocol. 
 Withdrawn subjects maybe replaced in the study. 
 All available data from subjects who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, 
unless otherwise specified. 
 
10.6.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
 Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument: 
o These data will be indicated by the use of a “blank” in subject listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table. 
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
 
10.6.3. 
Handling of Partial Dates 
Element 
Reporting Detail 
Concomitant 
Medications 
 Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. 
 The recorded partial date will be displayed in listings. 
 
10.6.4. 
Handling of Missing Data for Statistical Analysis 
Element 
Reporting Detail 
Imputation 
 No imputation will be performed for missing data 
 
 


 
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10.7. 
Appendix 7: Values of Potential Clinical Importance 
10.7.1. 
Laboratory Values (Healthy Volunteers) 
Haematology 
Laboratory Parameter 
 
Units 
Category
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Hematocrit  
Ratio of 1
Male 
 
0.54 
Female 
 
0.54 
∆ from BL 
↓0.075 
 
Hemoglobin  
g/L 
 
Male 
 
180 
Female 
 
180 
∆ from BL 
↓25 
 
Lymphocytes  
x109/ L 
 
0.8 
 
Neutrophil Count  
x109/ L 
 
1.5 
 
Platelet Count  
x109/ L 
 
100 
550 
While Blood Cell Count (WBC) 
x109/ L 
 
3 
20 
 
Clinical Chemistry 
Laboratory Parameter 
Units 
Category
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Albumin  
G/L 
 
30 
 
Calcium 
mmol/L 
 
2 
2.75 
Creatinine 
µmol/L 
∆ from BL
 
↑ 44.2 
Glucose 
mmol/L 
 
3 
9 
Phosphorus 
mmol/L 
 
0.8 
1.6 
Potassium 
mmol/L 
 
3 
5.5 
Sodium 
mmol/L 
 
130 
150 
 
Liver Function 
Test Analyte 
Units 
Category
Clinical Concern Range 
ALT/SGPT  
U/L 
High 
 2x ULN 
AST/SGOT  
U/L 
High 
 2x ULN 
AlkPhos  
U/L 
High 
 2x ULN 
T Bilirubin  
µmol/L 
High 
 1.5xULN 
T. Bilirubin + ALT 
µmol/L 
High 
1.5xULN T. Bilirubin 
 
+ 
U/L 
 2x ULN ALT 
 
 
 
 
 


 
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10.7.2. 
ECG (Healthy Volunteers) 
ECG Parameter 
Units 
Clinical Concern Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
 
> 450 [1] 
Absolute PR Interval 
msec 
< 110 [1] 
> 220 [1] 
Absolute QRS Interval 
msec 
< 75 [1] 
> 110 [1] 
Change from Baseline 
Increase from Baseline QTc 
msec 
> 60 [1] 
 
NOTES: 
1. 
Represent standard ECG values of PCI for HV studies 
 
10.7.3. 
Vital Signs (Healthy Volunteers) 
Vital Sign Parameter 
(Absolute) 
Units 
Clinical Concern Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
bpm 
< 40 
> 110 
 
 
 


 
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10.8. 
Appendix 8 - Abbreviations & Trade Marks 
10.8.1. 
Abbreviations 
Abbreviation 
Description 
AE 
Adverse Event 
A&R 
Analysis and Reporting 
AUC(0-24) 
Area under the concentration-time curve from pre-dose to 24 hours 
AUC(0-inf) 
Area under the concentration-time curve from time zero (pre-dose) 
extrapolated to infinite time 
AUC(0-t) 
Area under the concentration-time curve from time zero (pre-dose) to 
last time of quantifiable concentration within a subject across all 
treatments 
BMI 
Body mass index 
BP 
Blood pressure 
CI 
Confidence Interval 
Cmax 
Maximum observed concentration 
CSR 
Clinical Study Report 
CVb 
Coefficient of variation (Between) 
CVw 
Coefficient of Variation (Within) 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
GSK 
GlaxoSmithKline 
HR 
Heart rate 
hrs 
Hours 
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
LLN 
Lower Limit of Normal 
LLQ 
Lower Limit of Quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
MG 
Milligrams 
msec 
Milliseconds 
PDMP 
Protocol Deviation Management Plan 
PK 
Pharmacokinetic 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
RAP 
Reporting and Analysis Plan 
SAC 
Statistical Analysis Complete 
SAE 
Serious Adverse Event(s)
SAS 
Statistical Analysis Software 
SD 
Standard Deviation 
ULN 
Upper Limit of Normal 
SOP 
Standard Operation Procedure 
t1/2 
Terminal half-life 
Tmax 
Time to maximum observed blood drug concentration 
TFL 
Tables, Figures & Listings 


 
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10.8.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None 
 
SAS 
 
 
WinNonlin 
 


 
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10.9. 
Appendix 9: List of Data Displays 
10.9.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.14 
N/A 
Safety 
2.1 to 2.34 
N/A 
Pharmacokinetic 
3.1 to 3.8 
3.1 to 3.10 
Section 
Listings 
ICH Listings 
1 to 71 
Other Listings 
N/A 
 
10.9.2. 
Mock Example Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided in Appendix 10: Example Mock Shells for Data Displays. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
NOTES:  
 
Indicate display is Non-Standard in the ‘IDSL/TST ID / Example Shell’ or ‘Programming Notes’ column. 
 
10.9.3. 
Deliverable [Priority] 
Delivery [Priority] [1] 
Description 
PR [1] 
Primary Report (Part 1 only) 
SAC [2] 
Statistical Analysis Complete 
NOTES:  
1. 
Indicates priority (i.e. order) in which displays will be generated for the reporting effort. 
 


 
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10.9.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
Safety 
CP_ES1 
Summary of Subject Disposition (Part 1) 
Completed or withdrawn and the 
reason for withdrawal. 
PR [1] 
1.2. 
Safety 
ES4 
Summary of Subject Disposition at each period (Part 1) 
Completed or withdrawn at each period.
PR [1] 
1.3. 
Safety 
CP_ES1 
Summary of Subject Disposition (Part 2) 
Completed or withdrawn and the 
reason for withdrawal. 
SAC [2] 
1.4. 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure 
The number (%) of Randomized or 
screening failure subjects as the 
screening status, and the reason for 
screening failure. 
SAC [2] 
Protocol Deviation 
1.5. 
Safety 
DV1 
Summary of Important Protocol Deviations (Part 1) 
Data is from DV1 dataset. 
PR [1] 
1.6. 
Safety 
DV1 
Summary of Important Protocol Deviations (Part 2) 
Data is from DV1 dataset. 
SAC [2] 
Population Analysed 
1.7. 
Safety 
SP1 
Summary of Study Populations (Part 1) 
Only PK population is summarized. 
PR [1] 
1.8. 
Safety 
SP1 
Summary of Study Populations (Part 2) 
Only PK population is summarized. 
SAC [2] 
Demographic and Baseline Characteristics 
1.9. 
Safety 
DM3 
Summary of Demographic Characteristics (Part 1) 
 
PR [1] 
1.10. 
Safety 
DM3 
Summary of Demographic Characteristics (Part 2) 
 
SAC [2] 
1.11. 
Screened 
DM11 
Summary of Age Ranges (Part 1) 
<=17 years, 18-64 years, 65-84 years, 
>=85 years 
PR [1] 
1.12. 
Screened 
DM11 
Summary of Age Ranges (Part 2) 
<=17 years, 18-64 years, 65-84 years, 
>=85 years 
SAC [2] 


 
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Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
1.13. 
Safety 
DM5 
Summary of Race and Racial Combinations (Part 1) 
 
PR [1] 
1.14. 
Safety 
DM5 
Summary of Race and Racial Combinations (Part 2) 
 
SAC [2] 
 
 
 
 


 
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10.9.5. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
2.1.  
Safety 
AE1 
Summary of All Adverse Events by System Organ Class and 
Preferred Term (Part 1) 
 
PR [1] 
2.2.  
Safety 
AE5A 
Summary of All Adverse Events by Maximum Intensity (Part 1) 
 
PR [1] 
2.3.  
Safety 
AE1 
Summary All Drug-Related Adverse Events by System Organ 
Class and Preferred Term (Part 1) 
 
PR [1] 
2.4.  
Safety 
AE5A 
Summary All Drug-Related Adverse Events by Maximum 
Intensity (Part 1) 
 
PR [1] 
2.5.  
Safety 
AE1 
Summary of All Adverse Events by System Organ Class and 
Preferred Term (Part 2) 
 
SAC [2] 
2.6.  
Safety 
AE5A 
Summary of All Adverse Events by Maximum Intensity (Part 2) 
 
SAC [2] 
2.7.  
Safety 
AE1 
Summary All Drug-Related Adverse Events by System Organ 
Class and Preferred Term (Part 2) 
 
SAC [2] 
2.8.  
Safety 
AE5A 
Summary All Drug-Related Adverse Events by Maximum 
Intensity (Part 2) 
 
SAC [2] 
Laboratory: Chemistry  
2.9.  
Safety 
LB1 
Summary of Chemistry (Part 1) 
 
PR [1] 
2.10. 
Safety 
LB1 
Summary of Chemistry Changes from Baseline (Part 1) 
 
PR [1] 
2.11. 
Safety 
LB4 
Summary of Chemistry Data Shifts from Baseline with Respect 
to the Normal Range (Part 1) 
 
PR [1] 
2.12. 
Safety 
LB1 
Summary of Chemistry (Part 2) 
 
SAC [2] 
2.13. 
Safety 
LB1 
Summary of Chemistry Changes from Baseline (Part 2) 
 
SAC [2] 


 
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Safety: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
2.14. 
Safety 
LB4 
Summary of Chemistry Data Shifts from Baseline with Respect 
to the Normal Range (Part 2) 
 
SAC [2] 
Laboratory: Hematology 
2.15. 
Safety 
LB1 
Summary of Hematology (Part 1) 
 
PR [1] 
2.16. 
Safety 
LB1 
Summary of Hematology Changes from Baseline (Part 1) 
 
PR [1] 
2.17. 
Safety 
LB4 
Summary of Hematology Data Shifts from Baseline with Respect 
to the Normal Range (Part 1) 
 
PR [1] 
2.18. 
Safety 
LB1 
Summary of Hematology (Part 2) 
 
SAC [2] 
2.19. 
Safety 
LB1 
Summary of Hematology Changes from Baseline (Part 2)  
 
SAC [2] 
2.20. 
Safety 
LB4 
Summary of Hematology Data Shifts from Baseline with Respect 
to the Normal Range (Part 2) 
 
SAC [2] 
Laboratory: Urinalysis 
2.21. 
Safety 
UR3b 
Summary of Urinalysis Data (Glucose, Protein, Blood, Ketones, 
Bilirubin, Urobilinogen) (Part 1) 
 
PR [1] 
2.22. 
Safety 
LB1 
Summary of Urinalysis Data (Specific Gravity and pH) (Part 1) 
 
PR [1] 
2.23. 
Safety 
UR3b 
Summary of Urinalysis Data (Glucose, Protein, Blood, Ketones, 
Bilirubin, Urobilinogen) (Part 2) 
 
SAC [2] 
2.24. 
Safety 
LB1 
Summary of Urinalysis Data (Specific Gravity and pH) (Part 2) 
 
SAC [2] 
ECG 
2.25. 
Safety 
EG1 
Summary of ECG Findings (Part 1) 
 
PR [1] 
2.26. 
Safety 
EG2 
Summary of ECG Value (Part 1) 
 
PR [1] 
2.27. 
Safety 
EG2 
Summary of Change from Baseline in ECG Values (Part 1) 
 
PR [1] 
2.28. 
Safety 
EG1 
Summary of ECG Findings (Part 2) 
 
SAC [2] 


 
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Safety: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
2.29. 
Safety 
EG2 
Summary of ECG Value (Part 2) 
 
SAC [2] 
2.30. 
Safety 
EG2 
Summary of Change from Baseline in ECG Values by Visit (Part 
2) 
 
SAC [2] 
Vital Signs 
2.31. 
Safety 
VS1 
Summary of Vital Signs (Part 1) 
 
PR [1] 
2.32. 
Safety 
VS1 
Summary of Change from Baseline in Vital Signs (Part 1) 
 
PR [1] 
2.33. 
Safety 
VS1 
Summary of Vital Signs (Part 2) 
 
SAC [2] 
2.34. 
Safety 
VS1 
Summary of Change from Baseline in Vital Signs (Part 2) 
 
SAC [2] 
 


 
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10.9.6. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Part 1 
3.1.  
PK 
PK01: pkct1 
Summary of GSK1325756 Blood Concentration (ng/mL) (Part 1)
 
PR [1] 
3.2.  
PK 
PK03: pkpt1 
Summary of GSK1325756 Pharmacokinetic Parameters (non-
transformed) (Part 1) 
 
PR [1] 
3.3.  
PK 
PK05: pkpt3 
Summary of GSK1325756 Pharmacokinetic Parameters (loge-
transformed) (Part 1) 
 
PR [1] 
3.4.  
PK 
Study Specific 
(PK_T1) 
Analysis of Power Model Analysis for GSK1325756 Dose 
Proportionality of Pharmacokinetic Parameters (AUC(0-t), 
Cmax) (Part 1) 
Parameter, Effect, n, Point estimate of 
Slope, SE, 90% CI 
PR [1] 
Part 2 
3.5.  
PK 
PK01: pkct1 
Summary of GSK1325756 Blood Concentration (ng/mL) (Part 2)
 
SAC [2] 
3.6.  
PK 
PK03: pkpt1 
Summary of GSK1325756 Pharmacokinetic Parameters (non-
transformed) (Part 2) 
 
SAC [2] 
3.7.  
PK 
PK05: pkpt3 
Summary of GSK1325756 Pharmacokinetic Parameters (loge-
transformed) (Part 2) 
 
SAC [2] 
3.8.  
PK 
Study Specific 
(PK_T2) 
Analysis of food effect for Pharmacokinetic Parameters (AUC(0-
t), Cmax) (Part 2) 
n, Geometric mean of Fasted and Fed, 
ratio (Fasted/Fed), 90% CI and CVw(%)
SAC [2] 
 


 
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10.9.7. 
Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
Part 1 
3.1.  
PK 
PK16b: pkcf1x 
Individual GSK1325756 Blood Concentration-Time Plots by 
Subject (Part 1) 
By Subject (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
PR [1] 
3.2.  
PK 
PK24: pkcf6 
Individual GSK1325756 Blood Concentration-Time Plots by 
treatment (Part 1) 
By Treatment (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
PR [1] 
3.3.  
PK 
Study Specific 
(PK_F1) 
Mean (+SD) GSK1325756 Blood Concentration-Time Plots (Part 
1) 
Unit of x-axis is Hours 
PR [1] 
3.4.  
PK 
PK18: pkcf3 
Median GSK1325756 Blood Concentration-Time Plots (Part 1) 
Unit of x-axis is Hours 
PR [1] 
3.5.  
PK 
PK28 
Plot of GSK1325756 Treatment and PK Parameters (AUC (0-t), 
Cmax) (Part 1) 
 
PR [1] 
Part 2 
3.6.  
PK 
PK16b: pkcf1x 
Individual GSK1325756 Blood Concentration-Time Plots by 
Subject (Part 2) 
By Subject (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
SAC [2] 
3.7.  
PK 
PK24: pkcf6 
Individual GSK1325756 P Blood Concentration-Time Plots by 
Treatment (Part 2) 
By Treatment (Linear and Semi-Log). 
Actual time is used. 
Unit of x-axis is Hours. 
SAC [2] 
3.8.  
PK 
Study Specifics 
(PK_F1) 
Mean (+SD) GSK1325756 Blood Concentration-Time Plots (Part 
2) 
Unit of x-axis is Hours 
SAC [2] 
3.9.  
PK 
PK18: pkcf3 
Median GSK1325756 Blood Concentration-Time Plots (Part 2) 
Unit of x-axis is Hours 
SAC [2] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
3.10. 
PK 
PK28 
Plot of GSK1325756 Treatment and PK Parameters (AUC(0-t), 
Cmax) (Part 2) 
 
SAC [2] 
 


 
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10.9.8. 
ICH Listings 
Note: ‘Inv.’ in the standard displays will be replaced to ‘Centre’. 
ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
Screening 
Failure 
ES7 
Listing of Reasons for Screen Failure 
 
SAC [2] 
2.  
Safety 
CP-ES10x 
Listing of Reasons for Study Withdrawal (Part 1) 
 
PR [1] 
3.  
Safety 
CP-ES10x 
Listing of Reasons for Study Withdrawal (Part 2) 
 
SAC [2] 
4.  
Safety 
BL2 
Listing of Subjects for Whom the Treatment Blind was Broken 
(Part 1) 
 
PR [1] 
5.  
Safety 
TA2 
Listing of Planned and Actual Treatments (Part 1) 
 
PR [1] 
6.  
Safety 
TA2 
Listing of Planned and Actual Treatments (Part 2) 
 
SAC [2] 
Protocol Deviations 
7.  
Safety 
DV2 
Listing of Important Protocol Deviations (Part 1) 
Column for Treatment Sequence/Period 
of Protocol deviation will be displayed 
after Centre./Subj. 
Period day will be displayed in the 
same column of Date of 
Deviation/Study day. 
PR [1] 
8.  
Safety 
DV2 
Listing of Important Protocol Deviations (Part 2) 
 
SAC [2] 
9.  
Screened 
IE4 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations  
 
SAC [2] 
Populations Analysed 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
10.  
Safety 
Study Specifics 
(POP_L1) 
Listing of Subjects Excluded from PK Population (Part 1) 
 
PR [1] 
11.  
Safety 
Study Specifics 
(POP_L1) 
Listing of Subjects Excluded from PK Population (Part 2) 
 
SAC [2] 
Demographic and Baseline Characteristics 
12.  
Safety 
DM4 
Listing of Demographic Characteristics (Part 1) 
“Age at Screening” is added. 
PR [1] 
13.  
Safety 
DM4 
Listing of Demographic Characteristics (Part 2) 
“Age at Screening” is added. 
SAC [2] 
14.  
Screening 
Failure 
DM4 
Listing of Demographic Characteristics for Screening Failure 
Subjects 
 
SAC [2] 
15.  
Safety 
DM10 
Listing of Race (Part 1) 
 
PR [1] 
16.  
Safety 
DM10 
Listing of Race (Part 2) 
 
SAC [2] 
17.  
Screening 
Failure 
DM10 
Listing of Race for Screening Failure Subjects 
Treatment is not needed to display. 
SAC [2] 
Medical Conditions and Concomitant Medications 
18.  
Screened 
MH3 
Listing of Medical Conditions  
 
 
SAC [2] 
19.  
Safety 
CM5 
Listing of Concomitant Medications (Part 1) 
 
PR [1] 
20.  
Safety 
CM5 
Listing of Concomitant Medications (Part 2) 
 
SAC [2] 
21.  
Screened 
CM6 
Listing of Relationship between ATC Level 1, Ingredient and 
Verbatim Text 
 
SAC [2] 
Exposure and Treatment Compliance 
22.  
Safety 
EX4 
Listing of Exposure Data (Part 1) 
 
PR [1] 
23.  
Safety 
EX4 
Listing of Exposure Data (Part 2) 
 
SAC [2] 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
Meal 
24.  
Safety 
CP_ML1x 
Listing of Dosing Times, Meal Start and End Times on Fed 
Treatment Days (Part 1) 
 
PR [1] 
25.  
Safety 
CP_ML1x 
Listing of Dosing Times, Meal Start and End Times on Fed 
Treatment Days (Part 2) 
 
SAC [2] 
Adverse Events 
26.  
Safety 
AE9CP 
Listing of All Adverse Events (Part 1) 
 
PR [1] 
27.  
Safety 
AE9CP 
Listing of All Adverse Events (Part 2) 
 
SAC [2] 
28.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events (Part 
1) 
 
PR [1] 
29.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events (Part 
2) 
 
SAC [2] 
30.  
Screened 
AE2 
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text 
 
SAC [2] 
Serious and Other Significant Adverse Events 
31.  
Safety 
AE9CP 
Listing of Serious Adverse Events (Part 1) 
 
PR [1] 
32.  
Safety 
AE9CP 
Listing of Serious Adverse Events (Part 2) 
 
SAC [2] 
33.  
Screening 
Failure 
AE9CP 
Listing of Serious Adverse Events for Screening Failure Subject 
Treatment is not needed to display. 
SAC [2] 
34.  
Safety 
AE9CP 
Listing of Adverse Events Leading to Withdrawal from Study 
(Part 1) 
 
PR [1] 
35.  
Safety 
AE9CP 
Listing of Adverse Events Leading to Withdrawal from Study 
(Part 2) 
 
SAC [2] 
Laboratory (Chemistry Data) 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
36.  
Safety 
CP_LB6 
Listing of All Chemistry Data (Part 1) 
Change from baseline is included. 
PR [1] 
37.  
Safety 
CP_LB6 
Listing of All Chemistry Data (Part 2) 
Change from baseline is included. 
SAC [2] 
38.  
Safety 
CP_LB6 
Listing of All Chemistry Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
 
PR [1] 
39.  
Safety 
CP_LB6 
Listing of All Chemistry Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2) 
 
SAC [2] 
Laboratory (Hematology Data) 
40.  
Safety 
CP_LB6 
Listing of All Hematology Data (Part 1) 
Change from baseline is included. 
PR [1] 
41.  
Safety 
CP_LB6 
Listing of All Hematology Data (Part 2) 
Change from baseline is included. 
SAC [2] 
42.  
Safety 
CP_LB6 
Listing of All Hematology Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
 
PR [1] 
43.  
Safety 
CP_LB6 
Listing of All Hematology Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2) 
 
SAC [2] 
Laboratory (Urinalysis Data) 
44.  
Safety 
UR2b 
Listing of All Urinalysis Dipstick and Microscopy Data(Part 1) 
Time will be displayed after ‘Date’. 
PR [1] 
45.  
Safety 
CP_LB6 
Listing of Urinalysis Data (Gravity and pH) (Part 1) 
 
PR [1] 
46.  
Safety 
UR2b 
Listing of All Urinalysis Dipstick and Microscopy Data (Part 2) 
Time will be displayed after ‘Date’. 
SAC [2] 
47.  
Safety 
CP_LB6 
Listing of Urinalysis Data (Gravity and pH) (Part 2) 
 
SAC [2] 
Hepatobiliary (Liver) 
48.  
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting (Part 1) 
Column for Treatment/Period will be 
displayed after the column for 
Age/Sex/Race Detail. 
PR [1] 
49.  
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting (Part 2) 
 
SAC [2] 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
50.  
Safety 
MH3 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (Part 1) 
 
PR [1] 
51.  
Safety 
MH3 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events (Part 2) 
 
SAC [2] 
52.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events (Part 1) 
 
PR [1] 
53.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events (Part 2) 
 
SAC [2] 
ECG 
54.  
Safety 
CP_EG4 
Listing of All ECG Values (Part 1) 
 
PR [1] 
55.  
Safety 
CP_EG4 
Listing of All ECG Values (Part 2) 
 
SAC [2] 
56.  
Safety 
CP_EG4 
Listing of Change from Baseline in ECG Values (Part 1) 
 
PR [1] 
57.  
Safety 
CP_EG4 
Listing of Change from Baseline in ECG Values (Part 2) 
 
SAC [2] 
58.  
Safety 
CP_EG6 
Listing of ECG Findings (Part 1) 
 
PR [1] 
59.  
Safety 
CP_EG6 
Listing of ECG Findings (Part 2) 
 
SAC [2] 
60.  
Safety 
CP_EG4 
Listing of All ECG Data for Subjects with Any Value of Potential 
Clinical Importance (Part 1) 
 
PR [1] 
61.  
Safety 
CP_EG4 
Listing of All ECG Data for Subjects with Any Value of Potential 
Clinical Importance (Part 2) 
 
SAC [2] 
Vital Signs 
62.  
Safety 
CP_VS5 
Listing of All Vital Signs (Part 1) 
Change from baseline is included. 
PR [1] 
63.  
Safety 
CP_VS5 
Listing of All Vital Signs (Part 2) 
Change from baseline is included. 
SAC [2] 
64.  
Safety 
CP_VS5 
Listing of All Vital Signs Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
 
PR [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell
Title  
Programming Notes 
Deliverable 
[Priority] 
65.  
Safety 
CP_VS5 
Listing of All Vital Signs Data for Subjects with Any Value of 
Potential Clinical Importance (Part 2) 
 
SAC [2] 
Others 
66.  
Safety 
Study Specifics
(SAFE_L1) 
Listing of Ophthalmic examinations (Part 1) 
 
PR [1] 
67.  
Safety 
Study Specifics
(SAFE_L1) 
Listing of Ophthalmic examinations (Part 2) 
 
SAC [2] 
PK 
68.  
PK 
PK08: pkcl1x 
Listing of GSK1325756 Blood Concentration (Part 1) 
 
PR [1] 
69.  
PK 
PK08: pkcl1x 
Listing of GSK1325756 Blood Concentration (Part 2) 
 
SAC [2] 
70.  
PK 
PK14: pkpl1x 
Listing of GSK1325756 Pharmacokinetic Parameters (Part 1) 
 
PR [1] 
71.  
PK 
PK14: pkpl1x 
Listing of GSK1325756 Pharmacokinetic Parameters (Part 2) 
 
SAC [2] 
 


 
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10.10. 
Appendix 10: Example Mock Shells for Data Displays 
10.10.1. 
Study population 


 
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Example CP_ES1 (XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
(N=100) 
Completion Status 
 
  Completed 
 50 (50%) 
  Withdrawn 
 50 (50%) 
 
 
Primary*/subreason^ for withdrawal 
 
  Adverse event 
 10 (10%) 
    Elevated ALT levels 
  2  (2%) 
    Severe vomiting 
  5  (5%) 
  Lack of efficacy 
  0 
  Protocol deviation 
  0 
  Subject reached stopping criteria 
 10 (10%) 
    CD4 levels below continuation threshold 
 10 (10%) 
  Study closed/terminated 
  0 
  Lost to follow-up 
  0 
  Investigator discretion 
  0 
  Withdrew consent  
 30 (30%) 
    Burden of procedures 
 10 (10%) 
    Pursue alternative treatment 
 20 (20%) 
    Other 
  0 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: ES4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Phase 
 
 
Not Randomized 
(N=10) 
 
Placebo 
(N=100) 
Curitol 
 10mg 
(N=100) 
Screening 
Entered 
 10(100%) 
100(100%) 
100(100%) 
 
Completed 
  0  
100(100%) 
100(100%) 
 
Withdrawn 
 10(100%) 
  0  
  0  
 
 
 
 
 
Double blind 
Entered 
 
100(100%) 
100(100%) 
 
Completed 
 
 50 (50%) 
 50 (50%) 
 
Withdrawn 
 
 50 (50%) 
 50 (50%) 
 
 
 
 
 
Follow-up 
Entered 
 
 50 (50%) 
 50 (50%) 
 
Completed 
 
 50 (50%) 
 50 (50%) 
 
Withdrawn 
 
  0  
  0  
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm


 
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Example: ES6 (SF for CONSORT) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Screened 
Subjects 
(N=100) 
Screening Status 
 
  ENROLLED 
 50 (50%)
  FAILED 
 50 (50%)
 
 
Reason(s) for Failure  
 
  DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 25 (25%)
  STUDY CLOSED/TERMINATED  
  5  (5%) 
  PHYSICIAN DECISION 
 10 (10%)
  PROTOCOL DEVIATION 
 10 (10%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: CP_ES10x 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre 
ID/ 
Subj. 
Treatment 
Sequence/ 
Period of  
Withdrawal 
Last  
Treatment 
Before  
Withdrawal
Date of  
Withdrawal/ 
Study Day of 
Withdrawal/ 
Period Day 
of 
Withdrawal 
Primary Reason 
for Withdrawal 
Subreason for 
Withdrawal 
Date of Last 
Contact/ 
Study Day of 
Last Contact 
xxxxxx/ 
xxx 
PAB/ 
Period 1 
A 
DDMMMYYYY/ 
xx/ 
x 
Adverse Event 
Elevated ALT levels 
DDMMMYYYY/ 
x 
xxxxxx/ 
xxx 
BPC/ 
Period 2 
B 
DDMMMYYYY/ 
x/ 
x 
 
 
DDMMMYYYY/ 
x 
 
 
 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: ES7 (for SF) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID/ 
Subj. 
Date of 
Screen 
Failure 
Reason Term(s) for Screen Failure 
xxxxxx/ 
xxx 
DDMMMYYYY 
DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 
 
 
xxxxxx/ 
xxx 
DDMMMYYYY 
PHYSICIAN DECISION 
DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 
 
 
xxxxxx/ 
xxx 
DDMMMYYYY 
DID NOT MEED INCLUSION/EXCLUSION CRITERIA 
 
DDMMMYYYY 
PHYSICIAN DECISION 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: BL2 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID Subj. 
Sequence/ 
Treatment 
when Blind 
broken 
Date 
Blind 
Broken 
Time 
Blind 
Broken 
 
Study 
Day 
Period 
Day 
 
 
Reason 
 
 
 
 
 
 
 
 
xxxxxx 
xxxx 
PBC/ 
Treatment A
DDMMMYYYY 
hh:ss 
xx 
x 
Other: PT REQUESTED TO KNOW 
FOR MEDICAL REASONS 
 
 
 
 
 
 
 
 
xxxxxx 
xxxx 
APC/ 
Treatment C
DDMMMYYYY 
hh:ss 
xx 
xx 
Medical Emergency 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: TA2 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Country: Canada 
Centre ID: 
 
Investigator:
 
Subject 
ID 
Randomization 
Number 
Randomization Date 
Period 
Randomization 
Treatment 
Actual Treatment 
Deviation 
 
01JAN08 
1 
Curital 10mg 
Curital 10mg 
 
 
 
2 
Placebo 
Placebo 
 
 
 
3 
Placebo 
No treatment 
Y 
 
 
4 
Curital 20mg 
No treatment 
Y 
 
 
 
 
03JAN08 
1 
Curital 20mg 
Curital 20mg 
 
 
 
2 
Placebo 
Placebo 
 
 
 
3 
Curital 10mg 
Curital 10mg 
 
 
 
4 
Placebo 
Placebo 
 
 
 
 
01FEB08 
1 
Placebo 
Placebo 
 
 
 
2 
Curital 10mg 
Curital 10mg 
 
 
 
3 
Placebo 
Placebo 
 
 
 
4 
Curital 20mg 
Curital 10mg 
Y 
 
 
 
15FEB08 
1 
Curital 10mg 
Curital 10mg 
 
 
 
2 
Placebo 
Placebo 
 
 
 
 
3 
Placebo 
Placebo 
 
 
 
 
4 
Curital 10mg 
Curital 20mg 
Y 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
PPD
PPD
PPD


 
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Example: IE4 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID Subj. 
Treatment 
sequence 
Type 
Criterion 
 
 
 
 
 
xxxxxx 
xxx 
APC 
INCLUSION 
Is the subject 18 years of age or older? 
 
 
 
 
 
xxxxxx 
xxx 
PAB 
EXCLUSION 
Has the subject had an asthma episode(s) 
requiring intubation associated with 
hypercapnia, respiratory arrest, or hypoxic 
seizures within 12 months prior to Visit 1? 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DV1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Category/Coded Term 
Total 
(N=200) 
 
 
Any important protocol deviations 
60 (30%) 
 
 
Informed consent 
10 (5%) 
WRONG INFORMED CONSENT/ASSENT VERSION SIGNED  
10 (5%) 
 
 
Eligibility criteria not met 
14 (7%) 
 
 
Not withdrawn after developing withdrawal criteria 
18 (9%) 
Not discontinued from study treatment 
10 (5%) 
Not withdrawn from study 
 8 (4%) 
 
 
EXCLUDED MEDICATION, VACCINE OR DEVICE 
 4 (2%) 
   MEDICATION, EXCLUDED BY THE PROTOCOL, WAS ADMINISTERED 
 4 (2%) 
 
 
Assessment or time point completion 
 2 (1%) 
   OUT OF WINDOW EFFICACY ASSESSMENT 
 2 (1%) 
 
 
WRONG STUDY TREATMENT/ADMINISTRATION/DOSE 
 4 (2%) 
  STUDY TREATMENT NOT ADMINISTERED PER PROTOCOL 
 2 (1%) 
  EXPIRED STUDY TREATMET ADMINISTERED 
 2 (1%) 
 
Failure to report SAFETY EVENTS PER Protocol 
 8 (5%) 
SAE NOT REPORTED WITHIN THE EXPECTED TIME FRAME 
 4 (2%) 
LIVER FUNCTION ABNORMALITIES PER PROTOCOL  
 4 (2%) 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DV2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Deviation Requires Exclusion from
Site Id./ 
 
Date of 
Deviation/ 
Category/ 
Coded Term
Term 
Intent to 
Treat 
Population
Safety 
Population
Per 
Protocol 
Population
28 
ILURE TO REPORT SAFETY 
EVENTS PER PROTOCOL / 
SAE NOT REPORTED 
WITHIN THE EXPECTED 
TIME FRAME 
SAE OF FEVER 
WITH SEVERE 
CHILLS 
REQUIRING IV 
HYDRATION WAS 
NOT REPORTED 
TO GSK WITHIN 
24 HOURS. 
 
 
 
31 
ELIGIBILITY CRITERIA 
NOT MET / ELIGIBILITY 
CRITERIA NOT MET 
SUBJECT SCREEN 
FAILED BUT WAS 
RANDOMIZED IN 
ERROR. 
 
 
Y 
Y 
1 
WRONG STUDY TREATMENT/ 
ADMINISTRATION/DOSE / 
STUDY TREATMENT NOT 
ADMINISTERED PER 
PROTOCOL 
SUBJECT MISSED 
WEEK 8 
TREATMENT  
 
 
 
 
 
2 
WRONG STUDY TREATMENT/ 
ADMINISTRATION/DOSE / 
STUDY TREATMENT NOT 
ADMINISTERED PER 
PROTOCOL 
INTERRUPTION 
OF IP FOR 
GREATER THAN 
20 PERCENT OF 
TIME 
 
 
Y 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm
PPD
PPD
PPD
PPD
PPD


 
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Example: SP1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Population 
No Treatment 
(N=50) 
Placebo 
(N=xxx) 
Treatment 1 
(N=200) 
Treatment 2 
(N=250) 
Total 
(N=500) 
 
 
 
 
 
 
Screened 
50 (100%) 
xx (xxx%)
200 (100%) 
250 (100%) 
500 (100%) 
Enrolled 
10  (20%) 
xx (xxx%)
200 (100%) 
250 (100%) 
460  (92%) 
Randomized 
 5  (10%) 
xx (xx%) 
200 (100%) 
250 (100%) 
455  (91%) 
Safety 
 
xx (xx%) 
195  (98%) 
245  (98%) 
440  (88%) 
PK 
 
xx (xx%) 
200 (100%) 
250 (100%) 
455  (91%) 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: POP_L1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx (Randomised subjects) 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID/
Subj. 
Treatment 
sequence 
PK 
population 
 
 
 
xxxxxx/ 
xxx 
ABC 
Y 
 
 
 
xxxxxx/ 
xxx 
CBA 
Y 
 
 
 
xxxxxx/ 
xxx 
BAC 
Y 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DM3 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
 
(N=100) 
 
 
Sex 
 
  n 
  100 
  F 
   50  (50%) 
  M 
   50  (50%) 
 
 
Age (YEARS)[1] 
 
  n 
  100 
  Mean 
   50.0 
  SD 
   10.00 
  Median 
   50.0 
  Min. 
   18 
  Max. 
   65 
 
 
Age Group(YEARS)[1] 
 
  <=18 
    5   (5%) 
  19-64 
   50  (50%) 
  >=65 
   45  (45%) 
 
 
Ethnicity 
 
  n 
  100 
  HISPANIC OR LATINO 
   10  (10%) 
  NOT HISPANIC OR LATINO 
   90  (90%) 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DM3 (continued) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
 
(N=100) 
 
 
Race Detail 
 
  AMERICAN INDIAN OR ALASKA NATIVE 
 1   (1%) 
  ASIAN - CENTRAL/SOUTH ASIAN HERITAGE 
 3   (3%) 
  ASIAN - EAST ASIAN HERITAGE 
 4   (4%) 
  ASIAN – JAPANESE HERITAGE 
 3   (3%) 
  ASIAN - SOUTH EAST ASIAN HERITAGE 
 1   (1%) 
  BLACK OR AFRICAN AMERICAN 
 2   (2%) 
  NATIVE 
HAWAIIAN 
OR 
OTHER 
PACIFIC 
ISLANDER  
59  (59%) 
  WHITE – ARABIC/NORTH AFRICAN HERITAGE 
26  (26%) 
  WHITE 
– 
WHITE/CAUSASIAN/EUROPEAN 
HERITAGE  
 1   (1%) 
  MIXED ASIAN RACE 
 1   (1%) 
  MIXED WHITE RACE 
 1   (1%) 
  MULTIPLE 
 1   (1%) 
 
 
Height (cm) 
 
  n 
  100 
  Mean 
  150.0 
  SD 
   10.00 
  Median 
   50.0 
  Min. 
   18 
  Max. 
   65 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DM3 (continued) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Total 
 
(N=100) 
 
 
Weight (kg) 
 
  n 
  100 
  Mean 
   50.0 
  SD 
   10.00 
  Median 
   50.0 
  Min. 
   18 
  Max. 
   65 
 
 
Options (units) 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DM4 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre ID/ 
Subj. 
Treatment 
Sequence 
Partial 
Date of 
Birth 
Age 
(YEARS)
[1] 
Sex 
Ethnicity 
Height
 (cm) 
Weight
 (kg) 
Option 
(unit)
 
 
 
 
 
 
 
 
 
xxxxxx/ 
xxx 
ABC 
--MMYYYY 
xx 
F 
HISPANIC OR LATINO 
xxx
xx
 
 
 
 
 
 
xxxxxx/ 
xxx 
BCA 
--MMYYYY 
xx 
M 
NOT HISPANIC OR LATINO 
xxx
xx
 
 
 
 
 
 
xxxxxx/ 
xxx 
CAB 
----YYYY 
xx 
M 
NOT HISPANIC OR LATINO 
xxx
xx
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DM5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Treatment A
Treatment B
Total
 
(N=XXX) 
(N=XXX)
(N=XXX)
 
Race n 
 100 
 100
 200
African American/African Heritage
  30  (30%)
  30  (30%)
  60  (30%)
American Indian or Alaskan Native
   0    
   0   
   0   
Asian 
  15  (15%)
  15  (15%)
  30  (15%)
Central/South Asian Heritage
   3   (3%)
   3   (3%)
   6   (3%)
 
Japanese/East Asian Heritage/South 
East Asian Heritage
   11  (11%) 
   11  (11%) 
   22  (11%) 
Mixed Asian Heritage
   1   (1%)
   1   (1%)
   2   (1%)
 
Native Hawaiian or other Pacific 
Islander 
   10  (10%) 
   10  (10%) 
   20  (10%) 
White 
  35  (35%)
  35  (35%)
  70  (35%)
 
Native Hawaiian or other Pacific 
Islander & American Indian or Alaskan 
Native 
    2   (2%) 
    2   (2%) 
    4   (4%) 
 
White & African American/African 
Heritage 
    3   (3%) 
    3   (3%) 
    6   (3%) 
White & Asian
   5   (5%)
   5   (5%)
  10   (5%)
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DM11 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
No Treatment
Total 
 
(N=1) 
(N=201) 
 
 
 
Age Ranges [1] 
 
 
In utero                
   0        
 4   (2%) 
Preterm newborn infants (gestational age <37 
weeks) 
   0        
 2   (1%) 
Newborns (0-27 days) 
   0        
 6   (3%) 
Infants and toddlers (28 days-23 months) 
   0        
 8   (4%) 
Children (2-11 years) 
   0        
 6   (3%) 
Adolescents (12-17 years) 
   0        
 2   (1%) 
Adult (18-64 years)      
   0        
118  (59%) 
>=65-84 years        
   0        
52  (26%) 
>=85 years      
 1 (100%)
3   (1%)
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: DM10 (for XO studies) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre 
ID 
Subj. 
Treatment 
sequence 
Race 
 
Race Detail 
 
 
 
 
 
xxxxxx
xxx 
ABC 
BLACK OR AFRICAN AMERICAN 
BLACK OR AFRICAN AMERICAN 
 
xxx 
BCA 
Mixed race 
ASIAN - EAST ASIAN HERITAGE 
ASIAN – JAPANESE HERITAGE 
 
xxx 
CAB 
WHITE – ARABIC/NORTH AFRICAN 
HERITAGE 
WHITE – ARABIC/NORTH AFRICAN 
HERITAGE  
 
xxx 
ABC 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAGE 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAGE 
 
 
 
 
 
xxxxxx
xxx 
ABC 
Mixed race 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAG 
ASIAN – JAPANESE HERITAGE 
 
xxx 
BCA 
NATIVE HAWAIIAN OR OTHER PACIFIC 
ISLANDER 
NATIVE HAWAIIAN OR OTHER PACIFIC 
ISLANDER 
 
 
 
 
 
 
xxx 
CAB 
BLACK OR AFRICAN AMERICAN  
BLACK OR AFRICAN AMERICAN  
 
xxx 
ABC 
WHITE - ARABIC/NORTH AFRICAN 
HERITAGE 
WHITE - ARABIC/NORTH AFRICAN 
HERITAGE 
 
 
 
 
 
xxxxxx
xxx 
BCA 
AMERICAN INDIAN OR ALASKA NATIVE 
AMERICAN INDIAN OR ALASKA NATIVE 
 
xxx 
CAB 
Mixed race 
BLACK OR AFRICAN AMERICAN 
WHITE – WHITE/CAUSASIAN/EUROPEAN 
HERITAGE 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
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Example: MH3 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv. 
 
Subject 
Treatment 
Sequence 
 
Classification 
 
Condition 
 
Status 
 
 
 
 
AB 
Hepatobiliary 
HEPATITIS A 
Current 
 
Psychiatric 
PARANOIA COMBINED WITH MANIA.
Past 
 
 
 
 
 
AB 
Eye 
ASTIGMATISM 
Current 
 
 
 
 
BA 
Metabolism and nutrition 
RICKETS 
Current 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
75 
 
Example: CM5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
 
 
Inv./ 
Subj./ 
Seq 
 
Treat- 
ment/ 
Period 
ATC Level 1/  
Ingredient/ 
Verbatim Text/ 
Indication 
Dose/     
Units/ 
Freq/     
Route 
Start 
Date/Time  
Study Day/ 
Period Day 
Stop 
Date/Time  
Study Day/ 
Period Day 
 
Started 
Pre- 
Trial? 
 
Ongoing 
Medi-
cation? 
 
 
 
 
 
 
 
 
ABC 
Tmt A/ 
Per 1 
Endocrine & metabolic/  
Fluticasone propionate/ 
FLIXOTIDE/ 
Asthma 
2/  
MG/ 
2XD/ 
IH 
12:30/ 
15/ 
7 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
76 
 
Example: CM6 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
 
ATC Level 1 
Ingredient 
Verbatim Text 
 
 
 
Endocrine & metabolic 
Fluticasone Propionate 
FLIXOTIDE 
 
Prednisolone 
PREDNISOLONE 
 
 
 
 
 
 
Drugs acting via the nervous 
system 
Paracetamol 
PANADOL  
CHILDREN'S PANADOL 1-5YERS 
 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
77 
 
 
Example: EX4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Centre 
ID  
Subj. Treatment 
Start 
Date/ 
Start Time 
of Dose 
Stop Date/
Stop Time 
of Dose 
Duration 
(days) 
Dose  
Dose 
Unit  
Formulat
ion/ 
Route 
Freque
ncy 
Cumulat
ive 
Dose 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxx 
Treatment A  DDMMMYYYY/
hh:ss 
DDMMMYYYY/
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
Placebo 
DDMMMYYYY/
hh:ss 
 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
Treatment C
DDMMMYYYY/
hh:ss 
DDMMMYYYY/
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
 
 
 
 
 
 
 
 
 
   Placebo 
DDMMMYYYY/
hh:ss 
DDMMMYYYY/
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
Treatment B
 
 
 
 
 
 
 
 
 
Treatment C
DDMMMYYYY/
hh:ss 
DDMMMYYYY/
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
 
 
 
 
 
 
 
 
 
 Treatment A  DDMMMYYYY/
hh:ss 
DDMMMYYYY/
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
Treatment B
DDMMMYYYY/
hh:ss 
DDMMMYYYY/
hh:ss 
xx 
xx 
mg 
Tablet/ 
Oral 
1xday 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
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Example: CP_ML1x 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Cohort 
(Optional)
Investigator 
OR 
Centre ID 
(Optional) 
Subj.
Treatment
Meal type 
(Optional)
Period 
(Optional) 
/Visit
Visit 
Date
Dose 
Time
Meal 
Start 
Time
Meal End Time 
(Optional) 
Mea
wit
min
Mea
(Op
 
 
 
1 
50mg 
GSK123456
High-fat 
breakfast
Period 
2/Day 4 
8:13
7:30
7:41
Y 
 
25mg 
GSK123456
High-fat 
breakfast
Period 
2/Day 4 
8:12
7:28
7:42
Y 
 
10mg 
GSK123456
High-fat 
breakfast
Period 
2/Day 4 
8:10
7:27
7:35
Y 
 
 
 
 
 
2 
50mg 
GSK123456
High-fat 
breakfast
Period 
2/Day 4 
8:09
7:28
7:50
N 
 
50mg 
GSK123456
High-fat 
breakfast
Period 
2/Day 4 
8:11
7:30
7:41
Y 
 
25mg 
GSK123456
High-fat 
breakfast
Period 
2/Day 4 
8:09
7:25
7:42
Y 
 
10mg 
GSK123456
High-fat 
breakfast
Period 
2/Day 4 
8:10
7:27
7:36
Y 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
79 
 
 
10.10.2. 
Safety population 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
80 
 
Example: AE1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
System Organ Class 
  Preferred Term 
Placebo 
(N=78) 
Drug A 
(N=78) 
Drug B 
(N=78) 
ANY EVENT 
58 (74%) 
64 (82%) 
64 (85%) 
 
 
 
 
Gastrointestinal disorders 
 
 
 
Any event 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Dyspepsia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Nausea 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Vomiting Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Constipation 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Diarrhoea Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Toothache 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Abdominal Pain Upper 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Dry Mouth 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Flatulence 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Gastrointestinal Upset 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Haemorrhoids 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Loose Stools 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Abdominal Pain Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Faecal Incontinence 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Gastritis Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Lip Disorder Nos 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Lip Dry 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  Stomach Discomfort 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
Nervous system disorders 
 
 
 
Any event 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Headache 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Dizziness 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Extrapyramidal Disorder 
xx (xx%) 
xx (xx%) 
xx (xx%) 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
81 
 
Example: AE5A 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Treatment: Treatment A (N=200) 
System Organ Class 
Preferred Term 
MILD 
MODERATE 
SEVERE 
MODERATE 
/SEVERE 
UNKNOWN 
Total 
 
 
 
 
 
 
 
ANY EVENT 
30 (15%) 
40 (20%) 
40 (20%) 
80 (40%) 
 1 (<1%) 
151 (76%) 
 
 
 
 
 
 
 
Cardiovascular 
 
 
 
 
 
 
  Any Event 
20 (10%) 
40 (20%) 
40 (20%) 
80 (40%) 
 0 
140 (70%) 
  Hypertension 
 0 
20 (10%) 
20 (10%) 
20 (10%) 
 0 
 40 (20%) 
  Syncope 
 0 
 0 
 0 
0 
 0 
  0 
  Hypotension 
20 (10%) 
 0 
 0 
40 (20%) 
 0 
 60 (30%) 
 
 
 
 
 
 
 
Nervous system 
disorders 
10  (5%) 
 0 
 0 
 0 
 1 (<1%) 
 11  (6%) 
  Any Event 
10  (5%) 
 0 
 0 
 0 
 1 (<1%) 
 11  (6%) 
  Dizziness 
10  (5%) 
 0 
 0 
 0 
 1 (<1%) 
 11  (6%) 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
82 
 
Example: LB1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Test (units)           
 
 
Treatment    
 
 
N   
 
Planned  
Time
 
 
n   
Mean 
 
 
    SD  
Median 
Min. Max. 
 
Alkaline Phosphatase
Trt A 
202  Week  8    
150   
2.1 
7.95 
1
-25 
32 
(IU/L)                       
Week 12    
133   
0.4 
10.05 
1
-64 
33 
Week 24    
 55   
-1.6 
18.22 
0
-339 
44 
 
Trt B
220  Week  8    
150   
2.1 
7.95 
1
-25 
32 
  
Week 12    
133   
0.4 
10.05 
1
-64 
33 
 
Week 24    
 55   
-1.6 
18.22 
0
-339 
44 
 
Alanine Aminotransferase
(IU/L) 
Trt A 
202  Week  8     
150   -1.2 
16.32 
0
-320 
38 
   
Week 12    
133   
0.7 
10.55 
1
-64 
32 
 
Week 24    
 55   
-3.3 
29.50 
0
-235  
36 
 
Trt B
220 Week  8    
150   -1.2 
16.32 
0
-320 
38 
 
Week 12    
133   
0.7 
10.55 
1
-64 
32 
Week 24    
 55   
-3.3 
29.50 
0
-235 
36 
 
 
 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
83 
 
Example: LB4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Test= Alanine Aminotransferase (IU/L), Treatment=Treatment A 
 
 
 
 
 
Time Period Value
Planned 
Time
 
N 
 
n
Baseline 
Value
 
High
 
Normal
 
Low
 
Total
 
 
Week 1 
100
100
High
 0
  1   (1%)
 3   (3%)
 4   (4%)
 
Normal 
10  (10%)
 84  (84%)
 2   (2%)
96  (96%)
 
Low
 0
  0 
 0
 0
 
Total
10  (10%)
 85  (85%)
 5   (5%)
100 (100%)
 
 
Week 4 
100
100
High
 0
  1   (1%)
 3   (3%)
 4   (4%)
 
Normal
10  (10%)
 84  (84%)
 2   (2%)
96  (96%)
 
Low
 0
  0 
 0
 0
 
Total
10  (10%)
 85  (85%)
 5   (5%)
100 (100%)
 
 
Worst Case  
Post-Baseline 
100 
100 
High 
  0 
  1   (1%) 
  3   (3%) 
  4   (4%) 
 
Normal
10  (10%)
 84  (84%)
 2   (2%)
96  (96%)
 
Low
 0
  0 
 0
 0
 
Total
10  (10%)
 85  (85%)
 5   (5%)
100 (100%)
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
84 
 
Example: UR3b 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Test 
Period/Planned 
Relative Time
Result
Treatment A 
(N=100) 
Treatment B
(N=100) 
Urine General 
Dipstick 
SCREENING/ 
SCREENING 
Positive 
   30  (30%) 
   60  (60%) 
 
Negative 
  40  (40%)
  30  (30%)
 
No Result 
  30  (30%)
  10  (10%)
 
 
PERIOD 1/DAY 1
Positive 
  40  (40%)
 50  (50%)
 
 
Negative 
   30  (30%) 
   40  (40%) 
 
 
No Result 
   30  (30%) 
   10  (10%) 
Urine Occult Blood 
(Dipstick) 
SCREENING/ 
SCREENING 
None 
   40  (40%) 
   40  (40%) 
 
 
Trace 
   25  (25%) 
   25  (25%) 
 
1+
  10  (10%)
  15  (15%)
 
 
2+ 
    0    
    0    
 
3+
   0   
   0   
No Result 
  10  (10%)
  20  (20%)
 
PERIOD 1/DAY 1 
None 
   40  (40%) 
   40  (40%) 
 
 
Trace 
   30  (30%) 
   30  (30%) 
1+
   5   (5%)
   5   (5%)
 
 
2+ 
    2   (2%) 
    4   (4%) 
3+
   0   
   0   
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
85 
 
Example: EG1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Treatment A 
Treatment B 
  
(N=157) 
(N=160) 
  
 
 
Time Period 1 
 
 
  n 
156  
160  
  Normal  
 81  (52%) 
 90  (56%) 
  Abnormal, not clinically significant 
 75  (48%) 
 69  (43%) 
  Abnormal, clinically significant 
  0  
  1  (<1%) 
   
 
 
Time Period 2 
 
 
  n  
117  
123  
  Normal 
 50  (43%) 
 67  (54%) 
  Abnormal, not clinically significant 
 64  (55%) 
 55  (45%) 
  Abnormal, clinically significant  
  2   (2%) 
  1  (<1%) 
   
 
 
  n  
117  
122  
  Clinically significant change from baseline  
  2   (2%) 
  1  (<1%) 
  Not a clinically significant change 
115  (98%) 
121 (>99%) 
  Not applicable 
  0 
  0 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
86 
 
Example: EG1 (continued) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Treatment A 
Treatment B 
  
(N=157) 
(N=160) 
  
 
 
Any time post-baseline 
 
 
  n  
117  
123  
  Normal 
 50  (43%) 
 67  (54%) 
  Abnormal, not clinically significant 
 65  (56%) 
 55  (45%) 
  Abnormal, clinically significant  
  2   (2%) 
  1  (<1%) 
  No result (not available) 
  0 
  0 
   
 
 
  n  
117  
122  
  Clinically significant change from baseline  
  2   (2%) 
  1  (<1%) 
  Not a clinically significant change 
115  (98%) 
121 (>99%) 
  Not applicable 
  0 
  0 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
87 
 
Example: EG2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
Treatment
 
 
N
Planned Relative 
Time 
 
 
n
 
 
Mean
 
 
SD
 
 
Median
 
 
Min.
 
 
Max.
 
 
 
Heart Rate  
Trt A 
200
Time 1
200
91.6
11.32
90.0
68
140
 (bpm)
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
 
 
 
Trt B 
200
Time 1
200
91.6
11.32
90.0
68
140
 
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
 
 
PR Interval 
Trt A 
200
Time 1
200
91.6
11.32
90.0
68
140
 (msec)
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
 
 
 
Trt B 
200
Time 1
200
91.6
11.32
90.0
68
140
 
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
88 
 
Example: VS1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
Treatment
 
 
N
Planned 
Relative Time 
 
 
n
 
 
Mean
 
 
SD
 
 
Median
 
 
Min.
 
 
Max.
 
 
 
Systolic BP 
Trt A
200
Time 1
200
91.6
11.32
90.0
68
140
 (mmHg)
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
 
 
 
Trt B
200
Time 1
200
91.6
11.32
90.0
68
140
 
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
 
 
Diastolic BP 
Trt A
200
Time 1
200
91.6
11.32
90.0
68
140
 (mmHg)
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
 
 
 
Trt B
200
Time 1
200
91.6
11.32
90.0
68
140
 
 
Time 2
190
92.4
9.83
90.0
70
122
 
 
Time 3
186
92.6
10.87
89.0
72
125
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
89 
 
Example: AE7 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
System Organ Class 
 Preferred Term             
 
Treatment
No. 
with 
Event Unique Subject Id.
Gastrointestinal disorders 
  Dyspepsia 
Placebo 
 
 9 
 
Treatment A 
11 
 
Treatment B 
 4 
  Nausea 
Placebo 
 
 6 
 
Treatment A 
 8 
 
Treatment B 
 4 
 
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PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
90 
 
Example: AE9CP 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Site 
Id./ 
Unique 
Subject 
Id./ 
/Arm
 
 
 
Treatme
nt/ 
Period 
Age(YEARS)/
Sex/ 
Race 
Detail/ 
Weight 
(kg) 
 
 
 
System Organ Class/ 
Preferred Term/ 
VERBATIM TEXT 
 
Outcome/ 
Onset Datetime/ 
Datetime of 
Resolution/ 
Duration 
Time since 
Study 1st 
Dose/ 
Period 1st 
Dose/  
Last Dose  
Maximum  
Intensity/ 
Maximum 
Grade/ 
Serious/ 
Withdrawal  
 
Frequency/ 
Action Taken/
Relation to 
Study 
Treatment 
 
AB-BA-
BA 
Tmt A/ 
Per 1 
57/ 
F/ 
ASIAN - 
JAPANESE 
HERITAGE/ 
62.0 
Gastrointestinal 
Disorders/ 
Internal spasm/ 
ENTERO - SPASM 
RECOVERED/RESOLVE
T06:05/
T09:35/
22d 13h 6m 
31d 26h 4m/
31d 26h 4m/
-29d 7h 0m 
MILD/ 
1 
N/ 
N 
INTERMITTENT/
DOSE REDUCED/
Y 
 
 
 
Tmt B/ 
Per 2 
65/ 
M/ 
MIXED WHITE 
RACE/ 
75.0 
Musculoskeletal and 
connective tissue 
disorders/ 
Arthralgia/ 
PAIN IN RIGHT 
SHOULDER
RECOVERED/RESOLVE
T05:50/
T21:55/
71d 9h 45m 
83d 1h 12m/
83d 1h 12m/
-17d 2h 5m  
MODERATE/ 
2/ 
N/ 
N 
SINGLE EVENT/
DOSE NOT 
CHANGED/ 
N 
 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
91 
 
Example: AE2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
System Organ Class 
Preferred Term
Verbatim Text
Blood and lymphatic system
Lymphadenopathy
ENLARGED LYMPH NODE
disorders
 
Cardiac disorders 
Palpitations
CLOGGED EARS WITH EAR WAX
 
Ear pain
EARACHES IN BOTH EARS
 
RIGHT EAR PAIN
 
Tinnitus
RINGING IN RIGHT EAR
 
Eye disorders
Asthenopia
TIRED EYES
 
Conjunctivitis
BILATERAL ACUTE CONJUNCTIVITIS
 
CONJUNCTIVITIS
 
Dry eye nos
DRY EYES
 
Eye redness
REDDENED EYES
 
Vision blurred
BLURRED VISION
 
BLURRY VISION
 
WORSENING OF BLURRED VISION
 
Gastrointestinal disorders
Abdominal pain nos
ABDOMEN PAIN
 
Abdominal pain upper
MID-EPIGASTRIC AREA PAIN
 
STOMACH ACHE
. 
.
.
. 
.
.
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
92 
 
Example: CP_LB6 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj./ 
Seq 
 
Age(y)/  
Sex/  
Race 
 
Treat- 
ment/ 
Period 
 
 
Lab test 
(units) 
 
Planned 
Relative 
Time 
 
 
 
Date/Time 
Study 
Day/ 
Period 
Day 
 
 
Converted Data 
 
 
Flag[1] 
Value 
Normal Range 
NR
CI
BL
 
 
 
 
 
 
 
 
 
 
 63/  
Trt A/ 
Alk Phos 
(U/L) 
Screening   
 
12:05 
-1/-1   64.00 
 32.0- 92.0 
 
 
 
Male/ 
Per 1 
 
Week 12      
13:45 
85/85 
 84.00 
 32.0- 92.0 
    
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT (U/L) 
Screening   
 
13:32 
-1/-1   29.00 
 10.0- 40.0      
 
 
 
 
 
 
Week 12      
09:55 
85/85 
 70.00 
 10.0- 40.0      H 
H 
H 
 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
93 
 
Example: UR2b 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv. 
 
Subject 
 
Treatment 
 
Period 
 
Visit 
 
Sample Date 
Study 
Day 
Period 
Day 
Urinalysis 
Test 
 
Result 
 
 
 
 
 
 
 
 
 
 
Trt A 
1 
1 
1 
1 
Blood 
++ or 2+ 
Trt B 
2 
8 
137 
1 
Blood 
+ or 1+ 
 
 
 
 
 
 
 
Trt B 
1 
1 
1 
1 
Blood 
+ or 1+ 
 
 
 
 
 
 
 
Protein 
+++ or 3+ 
 
 
Trt A 
2 
8 
137 
1 
Blood 
+ or 1+ 
 
USER ID: directory/program.sas DDMMMYYYY hh:mm 
PPD
PPD


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
94 
 
Example: LIVER5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Treatment: Treatment A 
 
 
Site Id./ 
Unique Subject 
Id. 
 
 
Age(YEARS)/ 
Sex/ 
Race Detail 
 
 
 
Maximum Status of 
the Liver Event 
 
 
Date First 
Detected/ 
Study Day 
Time  
Since 
First 
Dose 
(days) 
Time 
Since 
Last 
Dose 
(days)
 
Restart/Re-
challenge After 
Stopping Criteria 
Was Met 
 
 
 
Resolved?/ 
Date 
resolved
 
 
 
 
 
 
 
63/ 
M/ 
WHITE - 
WHITE/CAUSAS
IAN/EUROPEAN 
HERITAGE 
LIVER MONITORING 
CRITERIA 
101 
 
 101  
 1  
N 
Y/ 
2010-02-19 
 
 
 
 
 
 
 
61/ 
F/ 
ASIAN - 
JAPANESE 
HERITAGE  
LIVER EVENT 
STOPPING CRITERIA 
68 
  68  
 1  
Y 
Y/ 
2010-04-10 
 
 
LIVER EVENT
STOPPING CRITERIA 
134 
 134  
 7  
N 
N 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
95 
 
Example: SU2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
Treat-
ment 
 
 
 
Inv./ 
Subj.  
 
 
 
 
Visit 
 
 
 
Study 
Day 
 
 
Assess-
ment 
Date 
 
 
 
Smoking 
History
 
 
 
Cur-rently 
Smoke 
 
 
Last 
Smoked
Smoked 
Since 
Last 
Visit 
Days 
Smoked 
Since 
Last 
Visit 
 
 
 
Years 
Smoked 
 
 
Ciga-
rettes 
/day 
 
 
Smoki
ng 
Pack 
Years
*
 
 
Trt A 
Visit 1 
1 
Never 
No 
 
No 
Zero 
 
 
 
 
 
 
Visit 1 
1 
Current
Yes 
 
Yes 
A few 
   5 
   20 
5 
 
Trt B 
Visit 1 
1 
Former 
No 
31DEC1
990 
No 
Zero 
  18 
   30 
27 
 
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CONFIDENTIAL 
 
 
 
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96 
 
Example: CP_EG4 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj. 
/Seq. 
 
Age 
(y)/ 
Sex/ 
Race
 
Treat- 
ment/ 
Period 
 
Planned 
Relative 
Time 
 
 
ECG  
Date/Time 
 
Study 
Day 
/Period 
Day
Actual  
Relative 
Time 
(optional) 
 
Heart
Rate 
(bpm)
 
PR 
Int.
(msec
)
 
QRS
Dur.
(mse
c)
 
RR 
Int. 
(msec)
 
QT 
Int.
(msec)
 
 
QTcB
(msec)
 
 
QTcF
(msec)
/AB 
65/ 
White/ 
Female 
Trt A/ 
Per 1 
Time 1 
14:00 
1/1 
-30m 
60 L 
150
350
750 
450 
520 
495 
 
 
 
Time 2 
15:00 
7/7 
26m 
80 
150
350
750 
450 
520 
495 
 
 
Trt B/ 
Per 2 
Time 1 
19:00 
14/1 
-30m 
80 
150
390 
H 
750 
450 
520 
495 
 
 
 
Time 2 
20:00 
21/7 
26m 
80 
150
350
750 
450 
520 
495 
 
 
 
/BA 
58 
Male/ 
White/ 
Trt A/ 
Per 2 
Time 1 
14:00 
1/1 
-30m 
80 
90 L
350
800 H
450 
520 
495 
 
 
 
Time 2 
15:00
7/7 
26m 
80 
150
350
750 
450 
520 
495 
 
 
 
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CONFIDENTIAL 
 
 
 
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97 
 
Example: CP_EG6 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj./ 
Seq. 
 
Age (y)/ 
Sex/ 
Race
 
Treat- 
ment/ 
Period
Planned  
Relative  
Time/ECG  
Date/Time
Study 
Day/ 
Period 
Day
 
 
 
ECG Finding 
Clinically 
Significant 
Change from 
Baseline?
 
 
Clinically  
Significant Abnormality
 
 
 
A/B 
65/ 
Female/ 
White 
Trt A/ 
Per 1 
Visit 1/ 
/14:00 
1/1 
Normal 
 
 
 
 
 
Visit 2/ 
 
/12:00 
4/4 
Abnormal–not 
clinically 
significant 
No 
 
 
 
Trt B/ 
Per 2 
Visit 3/ 
/19:00 
8/1 
Abnormal–
clinically 
significant 
 
Sinus tachycardia 
 
 
 
Visit 4/ 
/13:00 
12/4 
No result (not 
available) 
 
 
B/A 
58 
Male/ 
White 
Trt B/ 
Per 1 
Visit 1/ 
 
/14:00 
16/1 
Abnormal–
clinically 
significant 
 
Ectopic ventricular 
 beats 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
98 
 
Example: CP_VS5 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Inv./ 
Subj./ 
Seq. 
 
Age(y)/ 
Sex/ 
Race 
 
Treat-
ment/ 
Period 
 
Planned 
Relative 
Time 
 
 
Actual 
Date/Time 
 
 
Study Day/ 
Period Day 
Systolic 
 Blood 
Pressure 
(mmHg) 
Diastolic 
 Blood 
Pressure  
(mmHg) 
 
Vital Sign 
3 
(units) 
 
23/ 
Tmt B/ 
Time 1 
1/1 
  190 H 
   60  
   xx H 
Male/ 
Per 1 
Time 2 
5/5 
   95 
   50 L 
   xx H 
B/C/A 
White 
 
Time 3 
10/10 
   95 
   60  
   xx  
 
 
Tmt C/ 
Time 1 
15/1 
  185 H 
   90 H 
   xx H 
 
 
Per 2 
Time 2 
20/5 
   95 
   50 
   xx H 
 
 
Time 3 
25/10 
   95 
   60  
   xx  
 
 
Tmt A/ 
Time 1 
30/1 
  200 H 
   45 L 
   xx H 
 
 
Per 3 
Time 2 
35/5 
   95 
   60 
   xx H 
 
 
 
Time 3 
40/10 
   95 
   85 H 
   xx  
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
99 
 
Example: SAFE_L1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Inv./ 
Subj./ 
Seq. 
Age(y)/ 
Sex/ 
Race 
Treat-ment/
Period 
Planned 
Relative 
Time 
Actual 
Date/Time
Study Day/
Period Day
Location/ 
Category 
Test type 
Side 
Test 
Result 
 23/ 
Tmt B/ 
Time 1 
1/ 
Eye/ 
Indirect 
fundoscopic 
exam 
Left 
Normal 
Male/ 
Period x 
 
1 
Ophthalmological 
examination 
 
Right
xxxxx 
B/C/A 
White 
 
 
 
 
Slit lamp 
Left 
xxxxxx 
 
 
 
 
 
 
 
Right
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Time 2
5/ 
 
xxxxxxxxxx 
xxxxx
xxxxxxx
 
 
 
 
5 
 
 
xxxxx
xxxxxxx
 
 
 
 
 
 
xxxxxxxxxx 
xxxxx
xxxxxxx
 
 
 
 
 
 
 
xxxxx
xxxxxxx
 
 
 
 
 
 
 
 
 
 
 
Tmt C/ 
Time 1
15/ 
 
xxxxxxxxxx 
xxxxx
xxxxxxx
 
 
Period 2 
 
1 
 
 
xxxxx
xxxxxxx
 
 
 
 
 
 
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
100 
 
 
10.10.3. 
PK population 


 
CONFIDENTIAL 
 
 
 
206817 
 
 
 
101 
 
Example: PK01 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Treatmen
t 
 
 
N 
{Add.  
time 
var.} 
Planned  
Relative 
Time 
 
 
n 
 
No. 
Imputed
 
 
Mean 
 
{95% CI 
(Lower,Upper)} 
 
 
SD 
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
 
 
50mg 
24
 
Pre-dose 24  20 
xxxx.x (xxxx.x,xxxx.x)
 
xxxx.x 
xxxx 
xxxx 
 
 
 
30 min 
24   1 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
1 hr 
23   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
2 hr 
24   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
100mg 
24
 
Pre-dose 24   3 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
30 min 
21   0  
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
1 hr 
21   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
2 hr 
21   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
200mg 
24
 
Pre-dose 24   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
30 min 
23   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
1 hr 
24   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
 
 
2 hr 
24   0 
xxxx.x (xxxx.x,xxxx.x)
xx.xx 
xxxx.x 
xxxx 
xxxx 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
102 
 
Example: PK03 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Parameter 
 
 
Treatment
 
 
N 
{Additio
nal  
time 
variable
s} 
 
 
n 
 
 
 Mean 
 
{95% CI 
(Lower,Upper)
} 
 
 
SD 
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
 
AUC(0-t) 
(units) 
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
14 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
100mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
14 
23 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
Cmax (units) 
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
14 
23 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
100mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x 
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
14 
21 
xxxx.xx 
(xxxx.xx,xxxx
.xx) 
xx.xx
x
xxxx.xx 
xxxx.x
xxxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
103 
 
Example: PK05 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
Parameter 
 
 
Treatment 
 
 
N 
{Additiona
l 
time 
variables} 
 
 
n 
 
Geom. 
Mean 
 
95% CI 
(Lower,Upper) 
 
 
SD 
(logs)
 
 
{%CVb} 
AUC(0-t) 
(units)
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
14
24
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
 
 
 
 
 
 
 
 
100mg 
24
1
24
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
 
 
14 
23 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
200mg 
24
1
24
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
14
21
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
 
 
 
 
 
 
 
 
Cmax 
(units)
50mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
14
24
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
 
100mg 
24 
1 
24 
xxxx.xx 
(xxxx.xx,xxxx.xx) 
xx.xxx 
xx.xx 
 
14
23
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
200mg 
24
1
24
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
14
21
xxxx.xx
(xxxx.xx,xxxx.xx)
xx.xxx
xx.xx
 
 
 
 
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CONFIDENTIAL 
 
 
 
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Example: PK_T1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Parameter 
Effect 
n Slope Point 
Estimate 
SE 
90% CI 
Parameter1 
Log(dose levels) 
xx
xxx 
xxx 
(xx,xx) 
Parameter2 
Log(dose levels) 
xx
xxx 
xxx 
(xx,xx) 
. 
. 
. 
. 
. 
. 
 
. 
. 
. 
. 
. 
. 
. 
. 
. 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
105 
 
Example: PK_T2 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Table x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Parameter 
Treatment
N 
n 
Geometric LS Mean 
Ratio (Fasted/Fed)
90% CI 
CVw(%)[1]
Parameter1 (unit) 
Trt1 
xx 
xx 
xxx 
Xxx 
(xx,xx)
xx 
 
Trt2 
xx 
xx 
xxx 
 
 
 
 
 
Parameter2 (unit) 
Trt1 
xx 
xx 
xxx 
xxx 
(xx,xx)
xx 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
. 
ParameterX (unit) 
xx 
xx 
xx 
xxx 
xxx 
(xx,xx)
xx 
 
 
 
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CONFIDENTIAL 
 
 
 
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Example: PK16b 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
107 
 
Example: PK24 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
108 
 
Example: PK18 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
109 
 
Example: PK_F1 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
110 
 
Example: PK28 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Figure x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
111 
 
Example: PK08 (pkcl1x) 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
{Inv./} 
Subj.
 
{Age(y)/ 
Sex/ 
Race} 
 
 
Period
/Tmt.
 
 
 
Date
Study 
Day / 
Period 
Day
 
Planned 
Relative 
Time
 
 
Actual 
time 
 
 
Time dev.
(units)
 
Actual 
Relative 
Time
 
 
Concentration 
(units)
 
 
36/ 
M/ 
Mixed Race 
1/ 
50mg 
1/1 
 pre-dose
11:55 
  0 
0h 0m 0s  
  123 
 5m
12:05 
 0
0h 5m 0s
1434
 1h
13:00 
 0
1h 0m 0s
  NQ (<0.23)
 1h 30m 
13:30 
 0
1h 30m 0s
  30
 
 
2/
100mg
17/1 
 pre-dose
11:57 
  0 
0h 0m 0s  
  435 
 5m
12:10 
 0.83
0h 10m 0s
34566 
 1h
12:56 
-0.67
0h 56m 0s
3452
 1h 30m 
13:30 
 0
1h 30m 0s
  30
33/ 
M/ 
Mixed Race 
1/ 
50mg 
1/1 
 pre-dose
11:58 
  0 
0h 0m 0s  
 2345 
 
 
 5m
12:04 
-0.17
0h 4m 0s
 234
 
 
 1h
12:35 
 0.83
1h 0m 0s
  NR
 
 
 1h 30m 
13:30 
 0
1h 30m 0s
  30
 
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CONFIDENTIAL 
 
 
 
206817 
 
 
 
112 
 
Example: PK14 
Protocol: GSK123456                                                                                     Page 1 of n 
Population: xxxxx 
Listing x.x 
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
{Inv./} 
Subj. 
{Age(y)/ 
Sex/ 
Race} 
 
Period/
Tmt.
 
AUC(0-inf) 
(units)
 
AUC(0-t) 
(units) 
 
Cmax 
(units)
 
t1/2 
(units)
 
tmax 
(units)
 
36/ 
M/ 
Mixed Race
1/ 
50mg 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
2/ 
100mg
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
33/ 
M/ 
Mixed Race
1/ 
50mg 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
2/ 
100mg
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
24/ 
M/ 
Mixed Race
1/ 
50mg 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
2/ 
100mg
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
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