Clinical trial NCT03555890
Conditions: Rhinitis
Keywords: Oral disintegrating tablet Levocetirizine Immediate release tablet Bioequivalence Japanese subjects
Sponsor: GlaxoSmithKline
Start date: 2018-05-18; Completion date: 2018-09-17
Enrollment: 72 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This study will be an open-label, randomized 2-way cross-over study to evaluate bioequivalence study between levocetirizine ODT and levocetirizine IRT in healthy Japanese male subjects. Approximately 48 subjects will participate in this study to receive a single dose treatments of levocetirizine ODT 5 milligram (mg) or levocetirizine IRT 5 mg. In Part 1, subjects will randomized in 1:1 ratio (12 in each Period) in Period 1 and 2 to receive single dose of levocetirizine ODT 5 mg with water or single dose levocetirizine IRT 5 mg with water in fasted state. In this part, comparison of bioavailability of levocetirizine ODT and levocetirizine IRT when taken with water in the fasted state will be assessed. In Part 2, subjects will be randomized in 1:1 ratio (12 in each Period) in Period 1 and 2 to receive single dose levocetirizine ODT 5 mg without water or single dose levocetirizine IRT 5 mg with water in fasted state. In this part, comparison of bioavailability of levocetirizine ODT without water and levocetirizine IRT with water in the fasted state will be assessed. There will be at least a 5-day wash out period between the intervention periods. The duration of each subject's participation in each part will be approximately 7 weeks from screening to follow-up.

Detailed description:

Arms: arm 1: Subjects in Group A will be randomized to receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine ODT 5 mg with 150 mL water in fasted state in Period 2. arm 2: Subjects in Group B will be randomized to receive levocetirizine ODT 5 mg with 150 mL water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 2. arm 3: Subjects in Group C will be randomized to receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine ODT 5 mg without water in fasted state in Period 2. arm 4: Subjects in Group D will be randomized to receive levocetirizine ODT 5 mg without water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 2.
Interventions: intervention 1: Levocetirizine IRT 5 mg intervention 2: Levocetirizine ODT 5 mg
Intervention descriptions: intervention 1: Levocetirizine IRT will be available as film-coated tablets. Subjects will receive a single dose of 5 mg levocetirizine IRT. Subjects will receive levocetirizine IRT with 150 mL water in both Part (1 and 2). intervention 2: Levocetirizine ODT will be available as oral disintegrating tablet. Subjects will receive a single dose of 5 mg levocetirizine ODT. In Part 1, subjects will receive levocetirizine ODT with 150 mL water and in Part 2 subjects will receive levocetirizine ODT without water.

Protocol documents:
Prot_001.pdf: 
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TITLE PAGE 
Protocol Title: A single centre, single dose, open-label, randomized, 2-part, 2-way 
crossover study to determine the bioequivalence of levocetirizine oral disintegrating 
tablet given with water and without water compared to levocetirizine immediate release 
tablet in healthy Japanese male subjects  
 
Protocol Number: 204706 
Compound Number: 
Levocetirizine  
Study Phase: I 
Short Title: Bioequivalence study between levocetirizine oral disintegrating tablet and 
levocetirizine immediate release tablet  
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline K.K. (GSK) 
8-1, Akasaka 1-chome, Minato-ku, Tokyo, 107-0052, Japan 
Medical Monitor Name and Contact Information  
 
GlaxoSmithKline K.K. (GSK) 
Akasaka Intercity AIR, 8-1, Akasaka 1-chome, Minato-ku, Tokyo 107-0052 Japan 
Regulatory Agency Identifying Number(s): Not applicable 
Approval Date: 1-AUG-2018 
Copyright 2018 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
 
PPD


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SPONSOR SIGNATORY: 
 
 
Kosuke Kozaiwa,  
VP & Board of Director,  
Vice Head, Japan Development,  
GlaxoSmithKline K.K. 
 
Date 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 2 
1-AUG-2018 
2018N360906_02 
Amendment 1 
25-MAY-2018 
2018N360906_01 
Original Protocol 
20-APR-2018 
2018N360906_00 
 
Amendment 1: 1-AUG-2018 
Overall Rationale for the Amendment: for conducting the add-on subject study of Part 
2 
Section # and Name Description of Change 
Brief Rationale 
1.1.Synopsis 
To include the additional 
information of Part 2 
In order to conduct the add-on study for 
Part 2 
2.2.Background 
To include the additional 
information of Part 2 
In order to conduct the add-on study for 
Part 2 
4.1.Overall Design 
To include the additional 
information of Part 2 
In order to conduct the add-on study for 
Part 2 
9.2.3.Sample Size 
Re-estimation or 
Adjustment 
To include the additional 
information of Part 2 
In order to conduct the add-on study for 
Part 2 
 
 
Amendment 1: 25-MAY-2018 
Overall Rationale for the Amendment: Description maintenance 
Section # and Name Description of Change 
Brief Rationale 
9.1.Statistical 
Hypotheses 
Description maintenance 
In order to ensure consistency with 
statements in the statistical analysis plan 
9.4.1.PK Analyses 
Description maintenance 
In order to ensure consistency with 
statements in the statistical analysis plan 
 
 


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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1. 
Synopsis ....................................................................................................... 7 
1.2. 
Schedule of Activities (SoA) ........................................................................ 10 
2. 
INTRODUCTION .................................................................................................... 11 
2.1. 
Study Rationale .......................................................................................... 11 
2.2. 
Background ................................................................................................ 11 
2.3. 
Benefit/Risk Assessment ............................................................................ 12 
2.3.1. 
Risk Assessment ......................................................................... 12 
2.3.2. 
Benefit Assessment ..................................................................... 13 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 13 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 13 
4. 
STUDY DESIGN .................................................................................................... 14 
4.1. 
Overall Design ............................................................................................ 14 
4.2. 
Scientific Rationale for Study Design .......................................................... 15 
4.3. 
Justification for Dose .................................................................................. 16 
4.4. 
End of Study Definition ............................................................................... 16 
5. 
STUDY POPULATION ........................................................................................... 16 
5.1. 
Inclusion Criteria ......................................................................................... 16 
5.2. 
Exclusion Criteria ........................................................................................ 17 
5.3. 
Lifestyle Considerations .............................................................................. 19 
5.3.1. 
Meals and Dietary Restrictions .................................................... 19 
5.3.2. 
Caffeine, Alcohol and Tobacco .................................................... 19 
5.3.3. 
Activity ......................................................................................... 19 
5.4. 
Screen Failures........................................................................................... 19 
6. 
STUDY INTERVENTION ........................................................................................ 21 
6.1. 
Study Intervention(s) Administered ............................................................. 21 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 21 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 22 
6.4. 
Study Intervention Compliance ................................................................... 22 
6.5. 
Concomitant Therapy.................................................................................. 22 
6.6. 
Dose Modification ....................................................................................... 22 
6.7. 
Method of Treatment Assignment ............................................................... 22 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 23 
7.1. 
Discontinuation of Study Intervention .......................................................... 23 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 23 
7.1.2. 
QTc Stopping Criteria .................................................................. 23 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 24 
7.3. 
Lost to Follow-Up ........................................................................................ 24 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 25 
8.1. 
Safety Assessments ................................................................................... 25 
8.1.1. 
Physical Examinations ................................................................. 25 


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8.1.2. 
Vital Signs .................................................................................... 25 
8.1.3. 
ECG ............................................................................................. 26 
8.1.4. 
Clinical Safety Laboratory Assessments ...................................... 26 
8.2. 
Adverse Events and Serious Adverse Events ............................................. 26 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 27 
8.2.2. 
Method of Detecting AEs and SAEs ............................................. 27 
8.2.3. 
Follow-up of AEs and SAEs ......................................................... 27 
8.2.4. 
Regulatory Reporting Requirements for SAEs ............................. 28 
8.2.5. 
Pregnancy ................................................................................... 28 
8.3. 
Treatment of Overdose ............................................................................... 28 
8.4. 
Pharmacokinetics ....................................................................................... 29 
8.5. 
Palatability Assessment .............................................................................. 29 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 30 
9.1. 
Statistical Hypotheses................................................................................. 30 
9.2. 
Sample Size Determination ........................................................................ 30 
9.2.1. 
Sample Size Assumptions ........................................................... 30 
9.2.2. 
Sample Size Sensitivity ................................................................ 31 
9.2.3. 
Sample Size Re-estimation or Adjustment ................................... 31 
9.3. 
Populations for Analyses ............................................................................ 31 
9.4. 
Statistical Analyses ..................................................................................... 32 
9.4.1. 
PK Analyses ................................................................................ 32 
9.4.2. 
Safety Analyses ........................................................................... 33 
9.4.3. 
Exploratory analyses ................................................................... 34 
9.4.4. 
Interim Analyses .......................................................................... 34 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 35 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 35 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 35 
10.1.2. 
Financial Disclosure ..................................................................... 35 
10.1.3. 
Informed Consent Process .......................................................... 36 
10.1.4. 
Data Protection ............................................................................ 36 
10.1.5. 
Dissemination of Clinical Study Data ........................................... 36 
10.1.6. 
Data Quality Assurance ............................................................... 37 
10.1.7. 
Source Documents ...................................................................... 38 
10.1.8. 
Study and Site Closure ................................................................ 38 
10.1.9. 
Publication Policy ......................................................................... 38 
10.2. Appendix 2: Clinical Laboratory Tests ......................................................... 40 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 42 
10.3.1. 
Definition of AE ............................................................................ 42 
10.3.2. 
Definition of SAE .......................................................................... 43 
10.3.3. 
Recording and Follow-Up of AE and SAE .................................... 44 
10.3.4. 
Reporting of SAE to GSK ............................................................. 45 
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 47 
10.4.1. 
Contraception Guidance: ............................................................. 47 
10.4.2. 
Collection of Pregnancy Information: ........................................... 47 


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10.5. Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 49 
10.6. Appendix 6: Palatability Questionnaire ........................................................ 51 
10.7. Appendix 7: Country-specific requirements ................................................. 53 
10.8. Appendix 8: Abbreviations and Trademarks ................................................ 56 
11. REFERENCES ....................................................................................................... 58 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A single centre, single dose, open-label, randomized, 2-part, 2-way 
crossover study to determine the bioequivalence of levocetirizine oral disintegrating 
tablet given with water and without water compared to levocetirizine immediate release 
tablet in healthy Japanese male subjects 
Short Title: Bioequivalence study between levocetirizine oral disintegrating tablet and 
levocetirizine immediate release tablet 
Rationale: As a new dosage form of levocetirizine hydrochloride (hereafter 
levocetirizine) oral disintegrating tablet (ODT) is being developed for the purpose of 
boosting convenience and compliance for patients with allergic disease.  The primary 
objective of this study is to evaluate the bioequivalence between levocetirizine ODT and 
levocetirizine immediate release tablet (IRT) in healthy Japanese male subjects.   
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
• To evaluate the bioequivalence between 
levocetirizine ODT 5 mg (Test product) 
and levocetirizine IRT 5 mg (Reference 
product) in healthy Japanese male 
subjects. 
• Plasma pharmacokinetic (PK) parameters 
of levocetirizine: AUC(0-t) and Cmax 
Secondary 
• To assess the safety and tolerability 
following a single dose of levocetirizine 
5 mg when given as levocetirizine ODT 
and levocetirizine IRT in healthy 
Japanese male subjects. 
• Safety: Adverse events (AEs), changes 
from baseline in clinical laboratory tests, 
vital signs (blood pressure, pulse rate and 
body temperature), and 12-lead 
electrocardiogram (ECG) 
• Plasma PK parameters of levocetirizine: 
AUC(0-inf), tmax, t1/2, %AUCex, CL/F, 
Vz/F, kel and MRT 
Exploratory  
• To evaluate the palatability of 
levocetirizine ODT. 
• Palatability Questionnaire 
 


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Overall Design: This will be a single centre, single dose, open-label, randomized, 2-way 
crossover study in healthy Japanese male subjects.  This study consists of two parts: Part 
1 compares bioavailability of levocetirizine ODT and levocetirizine IRT taken with water 
in the fasted state, Part 2 compares bioavailability of levocetirizine ODT without water 
and levocetirizine IRT with water in the fasted state. 
In both parts (Part 1 and Part 2), subjects will have a screening visit within 30 days prior 
to the first dose of study intervention, two-way crossover intervention periods, and a 
follow-up 5-7 days after the last dose.  All subjects will be housed in the clinical research 
unit from Day -1 to 48 hours post-dose of each period for assessments. 
In both parts (Part 1 and Part 2), a total number of 24 subjects will be equally divided into 
two groups (12 subjects in each group).  All subjects will receive a single dose of 
levocetirizine 5 mg after an overnight fast (at least 10 hours) during the intervention 
period.  Subjects will be administered one intervention of either levocetirizine ODT 5 mg 
or levocetirizine IRT 5 mg in Period 1 and then receive the alternate intervention in 
Period 2.  There will be a washout period of at least 5 days between these periods.   
Disclosure Statement: This is an open-label, 2-part, 2-way crossover study.  
Number of Participants: 
Sufficient subjects will be randomized such that 24 evaluable subjects complete both Part 
1 and Part 2. There will be a total of 48 subjects in the 2 study parts. The definition of 
study complete is described in Section 4.4. 
If subjects prematurely discontinue the study, additional replacement subjects may be 
recruited and assigned to the same treatment sequence at the discretion of the Sponsor in 
consultation with the investigator. 
If bioequivalence could not be demonstrated in Part 1 and/or Part 2 because of an 
insufficient number of subjects, an add-on subject study was to be performed with 12 (6 
subjects in each group) or more subjects per part using the same methodology and 
according to the Japanese Guideline for Bioequivalence Studies of Generic Products 
[Japanese BE guideline, 2012]. 
Analyses of the Part 2 results indicated that BE was not demonstrated. Considering the 
possibility noted in the protocol of adding further subjects to meet the BE criteria, , an 
add-on study with the same design as Part 2 will be performed. An additional 24 subjects 
(12 subjects in each group) will be studied to increase the number of subjects to be 
included in the BE assessment. 
Intervention Groups and Duration: 
Subjects will participate either in Part 1 or Part 2, and receive the study interventions 
shown below. 
Part 1 (Dosing of levocetirizine ODT with water) 


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• Single dose of levocetirizine ODT 5 mg x 1 with 150 mL of water in the fasted 
state 
• Single dose of levocetirizine IRT 5 mg x 1 with 150 mL of water in the fasted 
state 
Group 
n 
Period 1 
Period 2 
A 
12 
Levocetirizine IRT 5 mg 
(with water) 
Levocetirizine ODT 5 mg 
(with water) 
B 
12 
Levocetirizine ODT 5 mg 
(with water) 
Levocetirizine IRT 5 mg 
(with water) 
 
Part 2 (Dosing of levocetirizine ODT without water) 
• Single dose of levocetirizine ODT 5 mg x 1 without water in the fasted state 
NOTE: ODT is placed on the subject's tongue, infiltrated with saliva, collapsed 
gently with the tongue, then swallowed with saliva without water. 
• Single dose of levocetirizine IRT 5 mg x 1 with 150 mL of water in the fasted 
state 
Group 
n 
Period 1 
Period 2 
C 
12 
Levocetirizine IRT 5 mg 
(with water) 
Levocetirizine ODT 5 mg 
(without water) 
D 
12 
Levocetirizine ODT 5 mg 
(without water) 
Levocetirizine IRT 5 mg 
(with water) 
 
Blood sampling for pharmacokinetic (PK) analysis will be performed prior to dosing and 
until 48 hours post-dose during each intervention period.  The duration of each subject’s 
participation in each part will be approximately 7 weeks from screening to follow-up. 
A palatability questionnaire will be administered to each subject following dosing of 
ODT treatments only. 
Data Monitoring Committee: No 


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1.2. 
Schedule of Activities (SoA) 
 
 
 
Procedure 
Screening2 
Part 1 and Part 2 Intervention period (Period 1 and Period 2) 
Follow-
up3 
Day -1 
Day 1 
Day 2 
Day 3 
Pre 
dose 
0 h 
0.25 h 0.5 h 
1 h 
1.5 h 
2 h 
3 h 
4 h 
6 h 
9 h 
12 h 
16 h 
24 h 36 h 
48 h 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to unit 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, Weight, Body 
mass index (BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
X 
X 
Serology test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory test1 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Vital signs 
X 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
X 
X 
PK blood sampling 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Study intervention 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Palatability 
questionnaire4 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs 
 
 
 
 
Discharge from unit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
1. 
Clinical laboratory test: haematology, clinical chemistry, and urinalysis  
2. 
Screening: up to 30 days prior to Day 1 of Period 1 
3. 
Follow-up: 5-7 days post dose of Period 2  
4. 
Palatability questionnaire will be administered to each subject within 10 minutes following dosing of ODT treatments only 


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2. 
INTRODUCTION 
Levocetirizine is one of the two enantiomers (R-enantiomer: levocetirizine, S-enantiomer: 
dextrocetirizine) of racemic cetirizine hydrochloride (hereafter cetirizine).  Levocetirizine 
has high affinity and selective antagonistic activity against histamine H1 receptors that is 
30-fold higher than that of dextrocetirizine [Yanai, 2011], and as an active component of 
cetirizine, exerts an inhibitory effect on eosinophil chemotaxis with negligible 
penetration into the central nervous system (CNS) due to a hydrophilic group. In view of 
these characteristics, levocetirizine is classified as a second generation antihistamine and 
considered to be a highly useful drug in the treatment of allergic diseases.   
2.1. 
Study Rationale 
The primary objective of this study is to evaluate the bioequivalence between 
levocetirizine ODT and levocetirizine IRT in healthy Japanese male subjects.   
2.2. 
Background 
In Japan, levocetirizine IRT (brand name: Xyzal® Tablets 5 mg) has been approved since 
October 2010 for the indications of allergic rhinitis, urticaria, eczema/dermatitis group, 
prurigo and cutaneous pruritus and used in adults and children aged between 7 and 15 
years.  In addition, levocetirizine syrup (brand name: Xyzal® Syrup 0.05%) has been 
approved since January 2014 to be used in children aged on or over 6 months and under 7 
years, on or over 7 and under 15 years and adults for the same indications. 
As a new dosage form of levocetirizine, the ODT is being developed for the purpose of 
boosting convenience and compliance for patients with allergic disease. 
To date, two clinical pharmacology studies comparing the same dose of levocetirizine 
contained in different formulations were conducted in healthy Japanese male subjects, 
confirming that levocetirizine exposure in plasma was equivalent between formulations 
when given as levocetirizine IRT 5 mg and as cetirizine IRT 10 mg [Ino, 2010], and 
when given as levocetirizine oral solution 5 mg and as cetirizine dry syrup 10 mg [Ino, 
2014].  In the safety endpoints of both studies, no adverse events (AEs) were reported, 
and no clinically significant abnormalities were observed for the results of the following 
examinations: vital signs, 12-lead electrocardiogram ECG), or clinical laboratory tests.  
Additional information can be found in the Xyzal® package inserts and the Japanese Drug 
Interview Form. 
Bioequivalence between levocetirizine ODT and levocetirizine IRT was evaluated in 48 
healthy Japanese male subjects (Part 1; 24 subjects, Part 2; 24 subjects) during May to 
June 2018, and statistical analyses were initially completed for Part 2. In Part 2, 23 
subjects completed the study and one subject withdrew from the study for personal 
reasons. While no adverse event was reported after dosing of levocetirizine IRT, 5 
adverse events were reported in 4 subjects who received levocetirizine ODT; Diarrhoea, 
Tonsillitis, Alanine aminotransferase (ALT) increased, Aspartate aminotransferase (AST) 
increased and Neck pain. ALT increased and AST increased, which were observed in one 
subject, were considered to be related to the study treatment by the investigator. Intensity 


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of tonsillitis was moderate, and intensity of the remaining AEs was mild. As BE was not 
demonstrated in Part 2, considering the possibility of adding further subjects to meet the 
BE criteria, an add-on study with the same design as Part 2 will be performed. An 
additional 24 subjects (12 subjects in each group).will be studied to increase the number 
of subjects to be included in the BE assessment. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected AEs associated with levocetirizine may be found in the Xyzal® 
package insert and Japanese Drug Interview Form. 
2.3.1. 
Risk Assessment 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
Investigational Product (IP) [e.g., Levocetirizine] 
Shock, Anaphylaxis 
Adverse reaction reports 
related to shock and 
anaphylaxis have been issued 
overseas and these events are 
also described in the Company 
Core Safety Information 
(CCSI). 
To ensure subjects’ safety 
during this study, safety 
monitoring will be performed as 
described in Section 8.1. 
The study is being run at a 
clinical pharmacology unit 
which has all relevant 
emergency services available.  
Convulsion 
Adverse reaction reports 
related to convulsion have 
been issued overseas and this 
event is also described in the 
CCSI. 
To ensure subjects’ safety 
during this study, safety 
monitoring will be performed as 
described in Section 8.1. 
The study is being run at a 
clinical pharmacology unit 
which has all relevant 
emergency services available. 
Hepatic dysfunction, Jaundice 
Adverse reaction reports 
related to hepatic dysfunction 
and jaundice have been issued 
overseas and these events are 
also described in the CCSI. 
Safety, and pre-defined 
stopping criteria are included in 
Section 7.1.  
To ensure subjects’ safety 
during this study, safety 
monitoring will be performed as 
described in Section 8.1. 
Subjects will not be discharged 
from the unit until the 
Investigator has reviewed all the 
available safety data. 
Thrombocytopenia 
Adverse reaction reports 
related to thrombocytopenia 
have been issued overseas. 
To ensure subjects’ safety 
during this study, safety 
monitoring will be performed as 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
described in Section 8.1. 
Subjects will not be discharged 
from the unit until the 
Investigator has reviewed all the 
available safety data. 
 
2.3.2. 
Benefit Assessment 
This study is being conducted in healthy Japanese male subjects with no significant 
medical history.  Subjects will not receive benefit from participation in this study.  
2.3.3. 
Overall Benefit: Risk Conclusion 
Pre-clinical and clinical data to date do not indicate that single dose levocetirizine at the 
exposure planned for this study is associated with excessive risks. 
 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
 
• 
To evaluate the bioequivalence between 
levocetirizine ODT 5 mg (Test product) and 
levocetirizine IRT 5 mg (Reference 
product) in healthy Japanese male 
subjects. 
• 
Plasma PK parameters of levocetirizine: 
AUC(0-t) and Cmax 
Secondary 
 
• 
To assess the safety and tolerability 
following a single dose of levocetirizine 5 
mg when given as levocetirizine ODT and 
levocetirizine IRT in healthy Japanese 
male subjects. 
• 
Safety: AEs, changes from baseline in 
clinical laboratory tests, vital signs (blood 
pressure, pulse rate and body 
temperature), and 12-lead ECG 
• 
Plasma PK parameters of levocetirizine: 
AUC(0-inf), tmax, t1/2, %AUCex, CL/F, 
Vz/F, kel and MRT 
Exploratory 
 
• 
To evaluate the palatability of levocetirizine 
ODT. 
• 
Palatability Questionnaire 
 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This will be a single centre, single dose, open-label, randomized, 2-way crossover study 
in healthy Japanese male subjects.  This study consists of two parts: Part 1 compares 
bioavailability of levocetirizine ODT and levocetirizine IRT taken with water in the 
fasted state, Part 2 compares bioavailability of levocetirizine ODT without water and 
levocetirizine IRT with water in the fasted state.   
In both parts (Part 1 and Part 2), subjects will have a screening visit within 30 days prior 
to the first dose of study intervention, two-way crossover intervention periods with at 
least a 5-day washout period, and a follow-up visit 5-7 days after the last dose.  All 
subjects will be housed in the clinical research unit from Day -1 to 48 hours post-dose of 
each period for assessments. 
In both parts (Part 1 and Part 2), a total number of 24 subjects will be equally divided into 
two groups (12 subjects in each group) and will be randomized in a 1:1 ratio (to one of 
two groups in each part).  Subjects will only participate in either Part 1 or Part 2.  All 
subjects will receive a single dose of levocetirizine 5 mg after an overnight fast (at least 
10 hours) during the intervention period as shown below. 
Part 1 (Dosing of levocetirizine ODT with water) 
• Single dose of levocetirizine ODT 5 mg x 1 with 150 mL of water in the fasted 
state 
• Single dose of levocetirizine IRT 5 mg x 1 with 150 mL of water in the fasted 
state 
Group 
n 
Period 1 
Period 2 
A 
12 
Levocetirizine IRT 5 mg 
(with water) 
Levocetirizine ODT 5 mg 
(with water) 
B 
12 
Levocetirizine ODT 5 mg 
(with water) 
Levocetirizine IRT 5 mg 
(with water) 
 
Part 2 (Dosing of levocetirizine ODT without water) 
• Single dose of levocetirizine ODT 5 mg x 1 without water in the fasted state 
NOTE: ODT is placed on the subject's tongue, infiltrated with saliva, collapsed 
gently with the tongue, then swallowed with saliva without water. 
• Single dose of levocetirizine IRT 5 mg x 1 with 150 mL of water in the fasted 
state 
Group 
n 
Period 1 
Period 2 
C 
12 
Levocetirizine IRT 5 mg 
(with water) 
Levocetirizine ODT 5 mg 
(without water) 


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D 
12 
Levocetirizine ODT 5 mg 
(without water) 
Levocetirizine IRT 5 mg 
(with water) 
 
Blood sampling for PK analysis will be performed prior to dosing and until 48 hours 
post-dose during each intervention period.  The duration of each subject’s participation in 
each part will be approximately 7 weeks from screening to follow-up. 
A palatability questionnaire will be administered to each subject following dosing of 
ODT treatments only. 
Sufficient subjects will be randomized such that 24 evaluable subjects complete both Part 
1 and Part 2. There will be a total of 48 subjects in the 2 study parts. The definition of the 
study complete is described in the Section 4.4. 
If subjects prematurely discontinue the study, additional replacement subjects may be 
recruited and assigned to the same treatment sequence at the discretion of the Sponsor in 
consultation with the investigator. 
If bioequivalence could not be demonstrated in Part 1 and/or Part 2 because of an 
insufficient number of subjects, an add-on subject study was to be performed with 12 (6 
subjects in each group) or more subjects per part using the same methodology and 
according to the Japanese BE guideline. 
Initial analyses demonstrated that BE was not demonstrated in Part 2. Considering the 
possibility noted in the protocol of adding further subjects to meet the BE criteria, an add-
on study with the same design as Part 2 will be performed. An additional 24 subjects (12 
subjects in each group) will be studied to increase the number of subjects to be included 
in the BE assessment. 
 
4.2. 
Scientific Rationale for Study Design 
This study is a 2-way crossover study to demonstrate the bioequivalence of levocetirizine 
following single oral doses of levocetirizine ODT 5 mg and levocetirizine IRT 5 mg in 
healthy Japanese male subjects.   
Aligned to the Japanese BE guideline, this study is single dose and study interventions 
will be given to healthy subjects with 150 mL of water after fasting for at least 10 hours. 
Fasting lasts for at least 4 hours post-dose. 
Current Japanese approval reviews of ODTs require that the bioequivalence studies are 
conducted both with and without water being given with the ODT.  Therefore this study 
evaluates single doses of levocetirizine ODT administered with water (Part 1) and 
without water (Part 2).   
In previous studies in healthy Japanese, the terminal phase t1/2 of levocetirizine reported 
was approximately 8 hours subjects [Ino, 2010, Ino, 2014].  Therefore, it was decided to 


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continue observation/examination of subjects for up to 48 hours after each dose of study 
intervention, to set the washout periods to be ≥5 days, and to set the follow-up visit to be 
at 5-7 days after the dose in Period 2 of both Part 1 and Part 2. 
4.3. 
Justification for Dose 
Levocetirizine IRT and dry syrup has been approved and marketed in Japan.  The 
recommended single dosage for Japanese adults is levocetirizine 5 mg (as levocetirizine 
hydrochloride), though this dosage may be increased up to 10 mg/day.  The Japanese BE 
guideline generally recommends that one dose unit or a clinical usual dose should be 
employed. Thus, 5 mg was the dose of levocetirizine ODT and levocetirizine IRT 
selected for evaluation in this study. 
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he has completed all phases of 
the study including the last follow-up visit. 
The end of the study is defined as the date of the last visit of the last participant in the 
study. 
 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Participant must be 20 to 55 years of age inclusive, at the time of signing the 
informed consent 
Type of Participant and Disease Characteristics 
2. Japanese participants who are overtly healthy as determined by medical evaluation 
including medical history, physical examination, laboratory tests, and cardiac 
monitoring 
Weight 
3. Body weight of ≥50 kg and body mass index (BMI) within the range of ≥18.5 and 
<25.0 kg/m2 
Sex 


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4. Male 
Contraceptive use should be consistent with local regulations regarding the methods of 
contraception for those participating in clinical studies 
a. Male Participants: 
Male participants are eligible to participate if they agree to the following during the 
intervention period and until the completion of follow-ups: 
• 
Refrain from donating sperm 
PLUS either: 
• 
Be abstinent from heterosexual or homosexual intercourse as their preferred and 
usual lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent 
OR 
• 
Must agree to use contraception/barrier as detailed below 
o Agree to use a male condom and female partner to use an additional 
highly effective contraceptive method with a failure rate of <1% per 
year as described in Appendix 4 when having sexual intercourse with a 
woman of childbearing potential who is not currently pregnant 
o Agree to use male condom when engaging in any activity that allows 
for passage of ejaculate to another person 
Tobacco 
5. Participants must be non-smokers 
Informed Consent 
6. Capable of giving signed informed consent as described in Appendix 1 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol 
5.2. 
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, haematological, or neurological disorders capable of significantly altering 
the absorption, metabolism, or elimination of drugs; constituting a risk when taking 
the study intervention; or interfering with the interpretation of data 
2. Abnormal blood pressure as determined by the investigator 
3. History of allergic rhinitis 


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4. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN) 
5. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones) 
7. QT interval correction (QTc) >450 msec 
NOTES: 
• 
The QTc is the QT interval corrected for heart rate according to Fridericia’s 
formula (QTcF) machine-read or manually over-read. 
• 
The specific formula that will be used to determine eligibility and 
discontinuation for an individual participant 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 participant from the trial. 
Prior/Concomitant Therapy 
8. Past or intended use of over-the-counter or prescription medication including 
vitamins, diet supplements (including St. John's wort), herbal medications within 14 
days prior to first dosing or 5 half-lives (whichever is longer). Specific medications 
listed in Section 6.5 may be allowed 
Prior/Concurrent Clinical Study Experience 
9. Exposure to more than 4 new chemical entities within 12 months prior to the first 
dosing day 
10. Current enrolment or past participation within 4 months prior to the first dosing day 
in this or any other clinical study involving an investigational study intervention or 
any other type of medical research (except for the participants with no study 
intervention administered during any of those enrolment or participation) 
Diagnostic Assessments 
11. The participant with positive serological test for syphilis (Rapid Plasma Reagin 
[RPR] and Treponema pallidum [TP] antibody tests), 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 moderate alcohol consumption within 6 months prior to the study 
participation defined as: 
• 
An average weekly intake of >14 units for males.  One unit is equivalent to 
360 mL of beer, 150 mL of wine or 45 mL of 80 proof distilled of spirits.  


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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 interventions, or components thereof, or drug or other 
allergy that, in the opinion of the investigator or Medical Monitor, contraindicates 
participation in the study 
16. History of donation of blood or blood products ≥400 mL within 3 months or 
≥200 mL within 1 month prior to the first dosing day 
5.3. 
Lifestyle Considerations 
5.3.1. 
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 
before the start of study intervention until after collection of the final PK sample. 
• 
Subjects will refrain from any food and drink (except water) at least 10 hours before 
dosing and 4 hours after dosing. 
• 
No water is allowed until 2 hours after dosing, water is allowed ad libitum at all 
other times. 
5.3.2. 
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 after collection of the final PK sample. 
• 
During each dosing session participants will abstain from alcohol for 24 hours before 
the start of dosing until after collection of the final PK sample.  
• 
Use of tobacco products will not be allowed from screening until after the final 
follow-up visit. 
5.3.3. 
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 the clinical studies (e.g., watching television, reading). 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. 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 serious adverse events 
(SAEs). 


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Individuals who do not meet the criteria for participation in this study (screen failure) 
may not be rescreened. 
 


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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
ARM Name 
Reference formulation 
Test formulation 
Intervention 
Name 
Levocetirizine IRT 5 mg 
Levocetirizine ODT 5 mg 
Dose 
Formulation 
Film-coated Tablets 
Oral Disintegrating Tablets 
Unit Dose 
Strength(s) 
5 mg 
5 mg  
Dosage Level(s) 
5 mg of single dose 
Part 1: with 150 mL water 
Part 2: with 150 mL water 
5 mg of single dose 
Part 1: with 150 mL water 
Part 2: without water  
Route of 
Administration 
Oral 
Oral 
 
Sourcing 
GSK 
Zensei Pharmaceutical Co., Ltd. 
Packaging and 
Labelling 
 
Study Intervention will be provided in 
container. Each container will be 
labelled as required per country 
requirement. 
Study Intervention will be provided in 
container. Each container will be 
labelled as required per country 
requirement. 
 
6.2. 
Preparation/Handling/Storage/Accountability 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labelled storage conditions with 
access limited to the investigator and authorized site staff. 


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3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention 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 
intervention are provided in the Study Reference Manual (SRM).  
• 
Under normal conditions of handling and administration, study intervention 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. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open label study. Subjects will be assigned to one of two groups in each part in 
accordance with the randomization schedule generated by the Biomedical Data Science 
Department at GSK, prior to the start of the study. 
6.4. 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention 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 
intervention 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 
intervention.  Study site personnel will examine each participant’s mouth to ensure that 
the study intervention was ingested. 
6.5. 
Concomitant Therapy 
Participants must abstain from taking prescription or non-prescription drugs (including 
vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a 
potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study 
intervention until completion of the follow-up visit, unless, in the opinion of the 
investigator and sponsor, the medication will not interfere with the study.  
6.6. 
Dose Modification 
This protocol allows no dose modification. 
6.7. 
Method of Treatment Assignment 
Subjects will be assigned to one of two groups in each part, in accordance with the 
randomization schedule generated by Biomedical Data Sciences Department at GSK, 
using validated internal software prior to the start of the study. 
 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
7.1.1. 
Liver Chemistry Stopping Criteria 
Study intervention 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*
 
Abbreviations: INR = international normalized ratio. 
Liver Safety Required Actions and Follow-up Assessments Section can be found in 
Appendix 5. 
7.1.2. 
QTc Stopping Criteria 
If the single QTc value meets either bulleted criterion, the additional double QTc values 
should be obtained over a brief (e.g., 5-10 minute) recording period. A subject that meets 
either bulleted criterion based on the average of triplicate ECG readings will be 
withdrawn from study intervention.   
• 
QTcF >500 msec 
 


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7.2. 
Participant Discontinuation/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, 
behavioural, compliance or administrative reasons.  
• 
The participant will be permanently discontinued both from the study 
intervention and from the study at that time. 
• 
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. 
7.3. 
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.  
 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA (Section 1.2).  
• 
Protocol waivers or exemptions are not allowed.  
• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• 
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. 
8.1. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.2). 
8.1.1. 
Physical Examinations 
• 
A complete 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 at the Screening. 
• 
Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
8.1.2. 
Vital Signs 
• 
Axillary temperature, pulse rate, and blood pressure will be assessed. 
• 
Blood pressure and pulse measurements will be assessed in the supine position 
with a completely automated device. Manual techniques will be used only if an 
automated device is not available. 


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• 
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). 
• 
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. 
8.1.3. 
ECG 
Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.2) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and QTcF. Refer to Section 7.1 for QTcF withdrawal criteria and additional QTcF 
readings that may be necessary. 
8.1.4. 
Clinical Safety Laboratory Assessments 
• 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and 
to the SoA (Section 1.2) 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 Case Report Form (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 (Section 1.2). 
8.2. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
The investigator and any qualified 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 intervention or the 
study, or that caused the subject to discontinue the study intervention (see Section 7).  


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8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of intervention until the follow-up visit 
at the time points specified in the SoA (Section 1.2). However, any SAEs 
assessed as related to study participation (e.g., study intervention, protocol-
mandated procedures, or invasive tests) or related to a GSK product will be 
recorded from the time a subject consents to participate in the study. 
• 
All AEs will be collected from the start of intervention until the follow-up visit 
at the time points specified in the SoA (Section 1.2). 
• 
Medical occurrences that begin before the start of study intervention 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 immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available. 
• 
All AEs related to Levocetirizine IRT 5 mg will be recorded and reported to the 
sponsor within 24 hours as indicated in Section 10.3.4. 
• 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. 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 considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor. 
8.2.2. 
Method of Detecting AEs and SAEs 
• 
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 3. 
• 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the subject is the preferred method 
to inquire about AE occurrence.  
8.2.3. 
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 will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is given in 
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8.2.4. 
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 intervention 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 intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Board (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 Investigator’s Brochure (IB) 
and will notify the IRB, if appropriate according to local requirements. 
8.2.5. 
Pregnancy 
• 
Details of all pregnancies in female partners of male participants will be collected 
after the start of study intervention and until at least 5 terminal half-lives after the 
last dose. 
• 
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 4. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE. 
8.3. 
Treatment of Overdose 
For this study, any dose of levocetirizine greater than 5 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 subject for AE/SAE and laboratory abnormalities until 
levocetirizine can no longer be detected systemically (at least 14 days). 
3. Obtain a plasma sample for PK analysis within 14 days from the date of the last dose 
of study intervention if requested by the Medical Monitor (determined on a case-by-
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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 subject. 
8.4. 
Pharmacokinetics 
• Blood samples of approximately 2 mL will be collected for measurement of 
plasma concentrations of levocetirizine at the times specified in the SoA 
(Section 1.2)  
• The actual date and time (24 h clock time) of each sample will be recorded. 
• Instructions for the collection and handling of biological samples will be provided 
by the sponsor.  
8.5. 
Palatability Assessment 
A palatability questionnaire will be administered to each subject within 10 minutes 
following dosing of ODT treatments only, see Appendix 6. Subjects will be given the 
questionnaire to read prior to receiving the ODT.  
 


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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
This study is designed to test the bioequivalence of levocetirizine ODT 5 mg (with water 
or without water) relative to levocetirizine IRT 5 mg. 
The null hypothesis is that the true ratio of the geometric mean of the levocetirizine ODT 
5mg (μtest) to the geometric mean of the levocetirizine IRT 5mg (μref), μtest/μref, for each 
primary PK endpoint (AUC(0-t) and Cmax of levocetirizine), is either less than or equal 
to 0.80 or greater than or equal to 1.25.  The alternative hypothesis is that the true ratio of 
the test treatment geometric mean to the reference treatment geometric mean is greater 
than 0.80 and less than 1.25.   
Symbolically, this is expressed as follows: 
H0: µtest/µref ≤0.80 or µtest/µref ≥1.25, 
i.e., treatments are not bioequivalent. 
Versus 
H1: 0.80< µtest/µref <1.25, 
i.e., treatments are bioequivalent. 
These hypotheses will be considered for levocetirizine ODT 5 mg with water or without 
water separately, relative to levocetirizine IRT 5 mg. 
For each PK parameters, designated as a primary endpoint (AUC(0-t) and Cmax), a two 
one-sided t-test (TOST) procedure [Schuirmann, 1987] with α = 0.05 for each one-sided 
test will be used to test this set of hypotheses.  This is equivalent to requiring that a 90% 
interval for the true ratio of levocetirizine ODT 5 mg to levocetirizine IRT 5 mg 
geometric means (µtest/µref) falls entirely within the range of 0.80 to 1.25.  A judgment by 
90% confidence interval (CI) will be conducted in this study. 
However, even though the confidence interval is not in the above range, test products are 
accepted as bioequivalent, if the geometric means (μtest/μref) falls within a range of 0.90 
to 1.11., which is in line with the Japanese BE GL. 
9.2. 
Sample Size Determination 
9.2.1. 
Sample Size Assumptions 
Sample size calculation is based on the within-subject estimates of variability (CVw%).  
CVw% of about 6% and 11% for AUC(0-48) and Cmax were observed, respectively, in a 
previous study in healthy Japanese male subjects (LOC116459). 


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Assuming CVw% of 22% (double of 11%) conservatively, it is estimated that sample size 
of 23 subjects will provide at least 90% power to demonstrate bioequivalence in each part.  
Considering the treatment assignment, a total of 24 healthy Japanese male subjects will 
be enrolled in each part of this study.  This calculation is based on TOST procedure with 
each type 1 error rate of 5% and assumes a true ratio of 1.00.  This procedure is 
corresponding to acceptance criteria for 90% CI. 
9.2.2. 
Sample Size Sensitivity 
Some sample size sensitivity calculations have been performed to assess robustness of 
sample size with deviations in the assumptions. 
Powers by changing assumptions in case of a sample size of 24 subjects are shown below. 
Geometric means 
ratio 
Within-subject CVw% 
17% 
20% 
23% 
26% 
0.95 
96.2% 
89.6% 
80.7% 
70.4% 
1.00 
99.5% 
96.7% 
90.2% 
80.0% 
1.05 
96.6% 
90.3% 
81.6% 
71.3% 
 
9.2.3. 
Sample Size Re-estimation or Adjustment 
Sample size re-estimation will not to be conducted in this study. However, after 
completing the study, if bioequivalence could not be demonstrated in Part 1 and/or Part 2 
because of an insufficient number of subjects, following the Japanese BE guideline, an 
add-on subject study could be performed in the same manner using not less than half the 
number of subjects in the initial study. The add-on subject study was to be performed 
using 12 (6 subjects in each group) or more subjects in each part.  
In Part 2, using 24 subjects the ratio of the geometric means for the AUC(0-t) of 
levocetirizine ODT 5 mg to levocetirizine IRT 5 mg was 0.964 and the 90%CI was 0.942 
to 0.987, which met the BE criteria. However, the ratio for Cmax was 0.828 and the 90% 
CI was 0.762 to 0.900, which did not meet the BE criteria. Therefore, BE was not 
demonstrated in Part 2 of the study. For Cmax, the f %CVw (16.6%) was smaller than the 
22% value expected at study planning. However, the ratio 0f 0.828 was different from 
unity, the assumption at the time of study planning. This may be the reason why BE was 
not shown in Part 2 of this study. Considering the possibility of meeting the BE criteria 
by adding further subjects an add-on study with the same design as Part 2 will be 
performed. An additional 24 subjects (12 subjects in each group) will be studied to 
increase the number of subjects to be included in the BE assessment. 
When an add-on subject study is conducted, the data of the two studies would be 
combined for analysis. 
9.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 


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Population 
Description 
Screened 
Consisting of all participants screened in the study. 
Screening Failure 
Participants who sign the ICF in the study but are never 
subsequently randomized. All participants who sign the ICF have 
the screening test in the study. 
Safety 
All randomized participants who take at least one dose of study 
treatment. Participants will be analyzed according to the treatment 
they actually received. 
PK 
This population is defined as all participants administered at least 
one dose of study treatment and who have blood for plasma drug 
concentration sample taken and analyzed. Participants will be 
analyzed according to the treatment they actually received. 
 
9.4. 
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. 
Final analysis will be performed for each part after completing the following procedures. 
1. All participants completed the study. 
2. All required database cleaning is completed and data management declares the 
final database release (DBR) and database freeze (DBF). 
For an add-on subject study, the procedures same as above will be performed. 
Statistical analysis will be performed for each part separately. 
Complete details of the planned statistical analyses will be provided in the Reporting and 
Analysis Plan (RAP). 
9.4.1. 
PK Analyses 
All PK analyses will be performed on the PK Population for each part (Part 1 and Part 2). 
Further details will be provided in the RAP. 
Statistical Analysis Methods 
Plasma Drug Concentrations: 
Plasma levocetirizine concentration-time data will be analysed by non-compartmental methods 
with WinNonlin (version 6.3 or higher). Calculations will be based on the actual sampling times 
recorded during the study.  


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PK Parameters: 
From the plasma concentration-time data, the following PK parameters will be determined, as 
data permit: AUC(0-t), Cmax, AUC(0-inf), Cmax, tmax, t1/2, %AUCex, CL/F, Vz/F, kel, and MRT. 
PK parameters 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 (SD), minimum, median, maximum, geometric mean with associated 95% CI, 
SD on log-scale and %CVb) will be calculated for each derived plasma PK parameter for each 
dose. 
 
Bioequivalence between Levocetirizine IRT 5 mg and Levocetirizine ODT 5 mg with and without 
water (Part 1 and Part 2): 
The bioequivalence in both parts (Part 1 and Part 2) will be evaluated according to the criteria 
described in the Japanese BE Guideline.  For both Part 1 and Part 2, after loge-transformation, 
AUC(0-t) and Cmax of levocetirizine 5 mg when given as ODT or IRT will be analyzed separately 
using mixed effects model fitting for intervention and period as fixed effects and subject as 
random effect.  The Kenward & Roger (KR) degrees of freedom approach will be used.  Point 
estimates and associated 90% CIs for the difference in means of two interventions [logμtest -
logμref] will be constructed using the residual variance.  These estimate values will then be 
exponentially back-transformed to provide point estimates and associated 90% CIs for the 
geometric mean ratio [μtest//μref]. 
In both parts (Part 1 and Part 2), the two interventions are considered to be bioequivalent, if the 
90% CIs of the geometric mean ratio of AUC(0-t) and Cmax are within the acceptable range “0.80 
- 1.25”. 
However, even though the confidence interval is not in the above range, test products are 
accepted as bioequivalent, if the geometric means (μtest/μref) falls within a range of 0.90 to 1.11., 
which is in line with the Japanese BE GL. 
The same analysis for AUC (0-t) and Cmax will be performed to evaluate bioequivalence of other 
reference PK parameters (AUC (0-inf), kel, MRT, tmax).  For tmax, however, the point estimate 
value of the median difference and the 90% CI will be calculated using the nonparametric 
Wilcoxon matched pair method (signed rank order method) (the difference is levocetirizine ODT 
5 mg - levocetirizine IRT 5 mg). 
 
9.4.2. 
Safety Analyses 
All safety analyses will be performed on the Safety Population.  
Statistical Analysis Methods 
AEs, clinical laboratory values, vital signs, ECG will be summarized by dose in each part. 
No formal statistical comparisons will be made for the safety data. 


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9.4.3. 
Exploratory analyses 
Exploratory analysis will be performed on the Safety Population.  
Statistical Analysis Methods 
Palatability questionnaire items will be summarized descriptively. Further details will be provided 
in the RAP. 
 
9.4.4. 
Interim Analyses 
No interim analysis is planned.


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
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 
• The study will be conducted in accordance with “the Ministerial 
Ordinance on the Standards for the Conduct of Clinical Trials of 
Medicinal Products (MHW Notification No.28 dated 27th March, 1997)” 
and the Pharmaceuticals and Medical Devices Act. 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, 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 Code of Federal Regulations (CFR), ICH guidelines, 
the IRB, European regulation 536/2014 for clinical studies (if applicable), 
and all other applicable local regulations 
10.1.2. 
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. 


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Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to 
the participant or his legally authorized representative 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 
informed consent that meets the requirements of 21 CFR 50, 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 or the participant’s 
legally authorized representative.  
• 
Participants who are rescreened are required to sign a new ICF. 
10.1.4. 
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. 
10.1.5. 
Dissemination of Clinical Study Data 
• 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the Clinical Study Report (CSR).  The 
investigator will be provided reasonable access to statistical tables, figures, and 
relevant reports and will have the opportunity to review the complete study 
results at a GSK site or other mutually-agreeable location. 


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• 
GSK will also provide the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study subjects, as appropriate. 
• 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 
• 
GSK intends to make anonymized patient-level data from this trial available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure the data 
provided by trial participants are used to maximum effect in the creation of 
knowledge and understanding. 
• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
10.1.6. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
(e)CRF unless transmitted to the sponsor or designee electronically (e.g., 
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.  
• 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
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 
CSR/ equivalent summary unless local regulations or institutional policies 


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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.  
10.1.7. 
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. 
10.1.8. 
Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. 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. 
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 intervention development 
10.1.9. 
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 


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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. 
 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 1 will be performed by the local laboratory.  
• 
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 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 1 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Haematology 
Platelet count  
RBC Indices: 
Mean corpuscular volume 
(MCV) 
Mean corpuscular 
haemoglobin (MCH) 
Mean corpuscular 
haemoglobin 
concentration (MCHC) 
Reticulocytes (‰) 
WBC count with 
differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red blood cells (RBC) 
count 
White blood cells 
(WBC) count 
Haemoglobin 
Haematocrit 
Clinical 
Chemistry1 
Blood urea 
nitrogen (BUN) 
Potassium 
Aspartate 
transaminase 
(AST) / Serum 
glutamic-oxaloacetic 
transaminase 
(SGOT) 
Total and direct 
bilirubin 
Creatinine 
Sodium 
ALT / Serum 
glutamic-pyruvic 
transaminase 
(SGPT) 
Total protein 
Glucose (fasting) Calcium 
Alkaline 
phosphatase 
Albumin 
Uric acid 
Triglyceride 
Total cholesterol 
Low density 
lipoprotein (LDL) 
cholesterol 
High density 
lipoprotein (HDL) 
cholesterol 
Lactate 
dehydrogenase 
(LDH) 
Gamma-
glutamyltransferase 
(GT) / Gamma 
glutamyl 
transpeptidase 
(GGT) 
Creatine kinase 
(CK) / Creatine 
phosphokinase 
(CPK) 
Amylase 
Chloride 
Inorganic phosphrus  
Routine 
Urinalysis 
• Specific gravity 


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Laboratory 
Assessments 
Parameters 
• 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 [PCP], 
Benzodiazepines [BZO], Cocaine [COC], Amphetamines [AMP], 
Tetrahydrocannabinol [THC], Opiates [OPI], Barbiturates [BAR], Trycyclic 
antidepressants [TCA]) 
• Serology (Syphilis [RPR & TP], HIV antigen/antibody, HTLV-1 antibody, 
HBsAg, and HCV 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 7.1 and Appendix 5.  All events of ALT ≥3 ×ULN and bilirubin ≥2 × ULN 
(>35% direct bilirubin) or ALT ≥3 × ULN 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). 


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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
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 intervention, whether or not considered related to 
the study intervention. 
• 
NOTE: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (haematology, 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 intervention 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 
intervention 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. 


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• 
Situations in which an untoward medical occurrence did not occur (social and/or 
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. 
 
10.3.2. 
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: 
o Results in death 
o 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. 
o 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 fulfils 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. 
o 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, diarrhoea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
o Is a congenital anomaly/birth defect 
o 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 
one of the other outcomes listed in the above definition. These events should usually 


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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. 
 
10.3.3. 
Recording and Follow-Up of 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 sufficient 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 
• 
The investigator is obligated to assess the relationship between study intervention 


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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 intervention 
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 make 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. 
 
 
10.3.4. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 


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• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
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 or to the 
Medical Monitor by telephone. 
• 
Contacts for SAE reporting can be found in Appendix 7. 
 
 
 


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10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information 
10.4.1. 
Contraception Guidance: 
Male participants 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Combined (oestrogen- 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.)  
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 the completion of the follow-ups. 
10.4.2. 
Collection of Pregnancy Information: 
Male participants with partners who become pregnant 
• 
Investigator will attempt to collect pregnancy information on any male participant’s 
female partner of a male study participant who becomes pregnant while participating 
in this study. This applies only to male participants who receive study intervention. 
• 
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.  
• 
The female 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. 


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• 
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 foetal 
status (presence or absence of anomalies) or indication for procedure.  


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10.5. 
Appendix 5: 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 intervention 
• 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 INR) and 
perform liver event follow-up assessments 
within 24 hours 
• 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 INR) and 
• 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 within 
24 hours of last dose4  
• Serum CPK and 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 acetaminophen, herbal remedies, 
other 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  
perform liver event follow-up assessments 
within 24-72 hours 
• Monitor subjects weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
total immunoglobulin G (IgG) or gamma 
globulins. 
• 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 intervention 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, which may 
indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); 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 (HBcAb); Hepatitis 
C ribonucleic acid (RNA); Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if 
unavailable, obtain heterophile antibody or monospot testing) and Hepatitis E IgM antibody. 
4. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention 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. 
 
 
 


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10.6. 
Appendix 6: Palatability Questionnaire 
The following questionnaire will be administered to each subject within 10 minutes 
following 5 mg dose of the Levocetirizine where it is given as an ODT.  
Subjects will be given the questionnaire to read prior to receiving this dose. 
 
Subject #: _________________________   Date: __________   Treatment: ______ 
 
1. Please briefly describe the taste of the product in your own words (one word, short 
phrase descriptions are acceptable). 
 
 
2. Please rate the palatability (acceptability of taste) of the product by checking a rating 
below. 
____ 1 = unacceptable (would not use product under any circumstances)  
____ 2 = neutral/acceptable 
____ 3 = very good 
 
3. Please check all the descriptors that apply to the product. 
______ Sweet 
______ Sour/tart 
______ Bitter 
______ Fruity 
______ Nutty 
______ Chalky 
______ Medicinal 
 
4. Please rate the mouth feel of the product by checking a rating below. 
_____ 1 = unacceptable (would not use product under any circumstances) 
_____ 2 = neutral/acceptable 
_____ 3 = very good 


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5. For each of the following attributes please circle the number that best describes your 
perception of each attribute.  
 
a. Sweetness 
Not Sweet 
Sweet 
Very Sweet 
 
 
 
1
2 
3 
4
5 
 
 
b. Sour/tartness 
Mild 
Average 
        Strong 
 
 
 
1
2
3 
4
5 
 
 
c. Bitterness  
Not bitter  
Bitter  
Very Bitter  
 
 
 
1
2
3 
4
5 
 
 


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10.7. 
Appendix 7: Country-specific requirements 
Sponsor Legal Registered Address 
GlaxoSmithKline K.K. 
8-1, Akasaka 1-chome Minato-ku, Tokyo 107-0052 Japan 
Study Director: Ryutaro Shimamura, Head, Medicines Development, Clinical 
Pharmacology Office 
Sponsor Contact Address 
Leading Author: 
 
GlaxoSmithKline K.K. 
Manager, Medicines Development, Clinical Pharmacology Office 
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 Office), 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) 
 (mobile: 
)  
Sponsor Medical Monitor/ Sponsor’s Medical Expert 
 
GlaxoSmithKline K.K. 
8-1, Akasaka 1-chome, Minato-ku, Tokyo 107-0052 Japan 
TEL: 
 (mobile)/
 (direct dialling) 
FAX: 
 
Medical Institution and Investigator:  
Masanari Shiramoto 
SOUSEIKAI Hakata Clinic 
6-18 Tenyamatchi, Hakata-ku, Fukuoka 812-0025 Japan 
TEL: 
  
FAX: 
 
Laboratories 
Clinical Laboratory: except HTLV-1 serology 
SOUSEIKAI Hakata Clinic 
Person in charge: 
 
6-18 Tenyamachi, Hakata-ku, Fukuoka 812-0025 Japan 
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TEL:
 
FAX: 
  
Clinical Laboratory: HTLV-1 serology (If subject meet Liver chemistry stopping criteria, 
include anti-nuclear antibody, anti-smooth muscle antibody, type 1 anti-liver kidney 
microsomal antibodies, and quantitative total IgG or gamma globulins, and viral hepatitis 
serology described in Appendix 5, but except HBsAg)  
LSI Medience Inc.  
Person in charge: 
 
30-1 Shimura 3-chome, Itabashi-ku, Tokyo 174-8555 Japan  
TEL: 
 
FAX: 
 
Pharmacokinetic Measurement Facilities 
Shin Nippon Biomedical Laboratories, Ltd  
Pharmacokinetics and Bioanalysis Center  
Person in charge: 
 
Minamiakasaka 16-1, Kainan City, Wakayama prefecture, 642-0017 Japan 
TEL : 
 
 
FAX : 
 
Pharmacokinetic Analyses 
Person in charge: 
 
GlaxoSmithKline K.K., Medicines Development, Clinical Pharmacology Office 
8-1, Akasaka 1-chome, Minato-ku, Tokyo 107-0052 Japan 
TEL: 
(direct dialling)  
FAX: 
 
Contract Research Organization 
Role: Study Monitoring 
Person in charge (Monitor Leader): 
 
Mediscience Planning Inc. 
8-10 Toranomon 2-chome, Minato-ku, Tokyo 105-0001 Japan 
TEL: 
 
FAX: 
 
Role: Medical Writing (Protocol & ICF) 
Person in charge: 
 
Mediscience Planning Inc. 
6-1 Hirano-machi 3-chome, Chuo-ku, Osaka 541-0046 Japan 
TEL: 
 
FAX: 
 
Role: Medical Writing (CSR) 
Person in charge: 
 
Mediscience Planning Inc. 
8-10 Toranomon 2-chome, Minato-ku, Tokyo 105-0001 Japan 
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TEL: 
 
FAX: 
 
Role: Data Loading 
Person in charge: 
 
Mediscience Planning Inc. 
2-1, Nihonbashi-hamacho 1-chome, Chuo-ku, Tokyo 103-0007 Japan 
TEL: 
 
FAX: 
 
Study Period 
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10.8. 
Appendix 8: Abbreviations and Trademarks 
Abbreviations 
AE(s) 
Adverse event(s) 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
AUC(0-48) 
Area under the concentration-time curve from time 0 to 48 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 the last 
measurable concentration 
%AUCex 
Percentage of AUC for time t to infinity by extrapolation to AUC(0-inf) 
BMI 
Body mass index 
CCSI 
Company Core Safety Information 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CL/F 
Apparent clearance following oral dosing 
Cmax 
Maximum observed concentration 
CPK 
Creatine phosphokinase 
(e)CRF 
(electronic) Case Report Form 
CSR 
Clinical Study Report 
%CVb 
Coefficient of variation between subjects 
CVw% 
Within-subject estimates of variability 
ECG 
Electrocardiogram 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline K.K. 
h 
Hour(s) 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HTLV-1 
Human T-cell lymphotropic virus type 1 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
INR 
International normalized ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IRT 
Immediate release tablet 
Japanese BE guideline 
Japanese Guideline for Bioequivalence Studies of Generic Products 
kel 
Elimination rate constant 
kg 
Kilogram 
LDH 
Lactate dehydrogenase 
Levocetirizine 
Levocetirizine hydrochloride 
mg 
Milligram 


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mL 
Millilitre 
MRT 
Mean residence time 
msec 
Millisecond 
m2 
Square metre 
ODT 
Oral disintegrating tablet 
pH 
Pondus Hydrogenii 
PK 
Pharmacokinetic(s) 
QTc 
QT interval correction 
QTcF 
QT interval corrected for heart rate according to Fridericia’s formula 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cells 
RPR 
Rapid Plasma Reagin 
SAE(s) 
Serious adverse event(s) 
SD 
Standard deviation 
SoA 
Schedule of Activities 
SRM 
Study Reference Manual 
t1/2 
Terminal half-life 
tmax 
Time to maximum observed concentration 
TOST 
Two one-sided t-test 
TP 
Treponema pallidum  
ULN 
Upper limit of normal 
Vz/F 
Apparent volume of distribution after oral administration 
WBC 
White blood cells 
μref 
The geometric mean of the reference product 
μtest 
The geometric mean of the test product 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
Xyzal 
 
WinNonlin 
 


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11. 
REFERENCES 
GlaxoSmithKline K.K. Drug Interview Form Xyzal® Tablets 5mg & Xyzal® Syrup 
0.05%. Mar-2017 (Version 9). 
GlaxoSmithKline K.K. Package insert Xyzal® Syrup 0.05%. Feb-2018 (Version 5). 
GlaxoSmithKline K.K. Package insert Xyzal® Tablets 5mg. Feb-2018 (Version 8). 
GlaxoSmithKline K.K. Document Number: 2011N128902_01. Study ID: LOC116459. 
Pharmacokinetic study of levocetirizine oral solution-An open-label, randomized, cross-
over study to evaluate the pharmacokinetics, the safety and tolerability of levocetirizine 
oral solution (5 mg) and cetirizine dry syrup (10 mg), following a single dose in Japanese 
healthy male subjects (protocol). 2012. 
Ino H, Hara K, Honma G, Doi Y, Fukase H. Comparison of levocetirizine 
pharmacokinetics after single doses of levocetirizine oral solution and cetirizine dry 
syrup in healthy Japanese male subjects. Journal of Drug Assessment 2014; 3: 38–42. 
Ino H, Nohda S, Miki S, Hara K, Hirama T. Comparisons of the Pharmacokinetics of 
Levocetirizine after Single Doses of Levocetirizine Hydrochloride and Cetirizine 
Hydrochloride in Healthy Japanese Male Subjects. Jpn J Clin Pharmacol Ther 2010; 
41(6): 309-315. 
Pharmaceutical and Food Safety Bureau, Evaluation and Licensing Division, Ministry of 
Health, Labour, and Welfare. Guideline for Bioequivalence Studies of Generic Products. 
Notification 0229 No.10. Feb-2012. 
Schuirmann DJ. A comparison of the Two One-Sided Tests Procedure and the Power 
Approach for assessing the equivalence of average bioavailability. Journal of 
Pharmacokinetics and Biopharmaceutics 1987; 15: 657-80. 
Yanai K, Zhang D, Tashiro M, Yoshikawa T, Naganuma F, Harada R, Nakamura T, 
Shibuya K, Okamura N. Positron emission tomography evaluation of sedative properties 
of antihistamines. Expert Opin. Drug Saf 2011;10: 613-622. 
 

SAP_000.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
204706
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for 204706:
A single centre, single dose, open-label, randomized, 2-part, 
2-way crossover study to determine the bioequivalence of 
levocetirizine oral disintegrating tablet given with water and 
without water compared to levocetirizine immediate release 
tablet in healthy Japanese male subjects
Compound Number 
:
GSK2074687 (Levocetirizine)
Effective Date 
:
15-MAY-2018
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Pharmacology Study Report for Protocol 204706.

This RAP is intended to describe the safety and pharmacokinetics analyses required 
for the study. 

This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s):
Approver
Date
Approval Method
Study statistician (Manager, Biostatistics Group 
1, Biomedical Data Sciences Department, Japan)
14-MAY-2018
eSignature
Pharmacokineticist (Staff, Clinical Pharmacology 
Office, Japan)
Copyright 2018 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
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RAP Team Approvals:
Approver
Date
Approval Method
14-MAY-2018
eSignature
CIL and OSL (Manager, Clinical Pharmacology 
Office, Medicines Development, Japan
15-MAY-2018
eSignature
DQL (Staff, Data Practice Group, Biomedical 
Data Sciences Department, Japan)
15-MAY-2018
eSignature
Clinical programmer (Manager, Statistical 
Programming & Reporting Group, Biomedical 
Data Sciences Department, Japan)
Clinical Statistics and Clinical Programming Line Approvals:
Approver
Date
Approval Method
14-MAY-2018
eSignature
Clinical Statistics Line approver (Associate 
Manager, Biostatistics Group 1, Biomedical Data 
Sciences Department, Japan)
14-MAY-2018
eSignature
Clinical Programming Line approver (Department 
Manager, Biomedical Data Sciences Department, 
Japan)
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TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................6
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 / Statistical Analyses .................................................8
3.
PLANNED ANALYSES ............................................................................................9
3.1.
Interim Analyses ...........................................................................................9
3.2.
Final Analyses ..............................................................................................9
4.
ANALYSIS POPULATIONS .....................................................................................9
4.1.
Protocol Deviations.......................................................................................9
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................10
5.1.
Study Treatment & Sub-group Display Descriptors.....................................10
5.2.
Baseline Definitions ....................................................................................10
5.3.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................11
6.
STUDY POPULATION ANALYSES .......................................................................11
7.
SAFETY ANALYSES .............................................................................................11
7.1.
Adverse Events Analyses ...........................................................................11
7.2.
Clinical Laboratory Analyses.......................................................................11
7.3.
Other Safety Analyses ................................................................................12
8.
PHARMACOKINETIC ANALYSES.........................................................................12
8.1.
Primary Pharmacokinetic Analyses.............................................................12
8.1.1.
Endpoint / Variables.....................................................................12
8.1.1.1.
Drug Concentration Measures....................................12
8.1.1.2.
Derived Pharmacokinetic Parameters.........................12
8.1.2.
Summary Measure ......................................................................12
8.1.3.
Population of Interest...................................................................12
8.1.4.
Strategy for Intercurrent (Post-Randomization) Events ................12
8.1.5.
Statistical Analyses / Methods .....................................................13
8.1.5.1.
Statistical Methodology Specification..........................13
8.2.
Secondary Pharmacokinetic Analyses........................................................14
8.2.1.
Endpoint / Variables.....................................................................14
8.2.1.1.
Drug Concentration Measures....................................14
8.2.1.2.
Derived Pharmacokinetic Parameters.........................14
8.2.2.
Summary Measure ......................................................................15
8.2.3.
Population of Interest...................................................................15
8.2.4.
Strategy for Intercurrent (Post-Randomization) Events ................15
8.2.5.
Statistical Analyses / Methods .....................................................15
8.2.5.1.
Statistical Methodology Specification..........................16
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9.
EXPLORATORY ANALYSES.................................................................................16
10. REFERENCES.......................................................................................................17
11. APPENDICES........................................................................................................18
11.1.
Appendix 1: Protocol Deviation Management .............................................18
11.2.
Appendix 2: Schedule of Activities ..............................................................19
11.2.1.
Protocol Defined Schedule of Events...........................................19
11.3.
Appendix 3: Assessment Windows .............................................................20
11.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................20
11.4.1.
Study Phases ..............................................................................20
11.4.2.
Treatment Emergent Flag for Adverse Events .............................20
11.5.
Appendix 5: Data Display Standards & Handling Conventions....................21
11.5.1.
Reporting Process .......................................................................21
11.5.2.
Reporting Standards....................................................................21
11.5.3.
Reporting Standards for Pharmacokinetic....................................22
11.6.
Appendix 6: Derived and Transformed Data ...............................................23
11.6.1.
General........................................................................................23
11.6.2.
Study Population..........................................................................23
11.6.3.
Safety ..........................................................................................23
11.6.4.
Pharmacokinetic ..........................................................................24
11.6.5.
Exploratory ..................................................................................24
11.7.
Appendix 7: Reporting Standards for Missing Data.....................................25
11.7.1.
Premature Withdrawals................................................................25
11.7.2.
Handling of Missing Data.............................................................25
11.7.2.1.
Handling of Missing and Partial Dates ........................25
11.7.2.2.
Handling of Missing for Statistical Analysis of 
BE ..............................................................................26
11.8.
Appendix 8: Values of Potential Clinical Importance ...................................27
11.8.1.
Laboratory Values........................................................................27
11.8.2.
ECG.............................................................................................28
11.8.3.
Vital Signs....................................................................................28
11.9.
Appendix 9: Abbreviations & Trade Marks ..................................................29
11.9.1.
Abbreviations...............................................................................29
11.9.2.
Trademarks .................................................................................30
11.10. Appendix 10: List of Data Displays..............................................................31
11.10.1. Data Display Numbering..............................................................31
11.10.2. Mock Example Shell Referencing ................................................32
11.10.3. Deliverables.................................................................................32
11.10.4. Part 1...........................................................................................33
11.10.4.1. Study Population Tables.............................................33
11.10.4.2. Safety Tables .............................................................34
11.10.4.3. Pharmacokinetic Tables .............................................35
11.10.4.4. Pharmacokinetic Figures ............................................37
11.10.4.5. Exploratory Tables......................................................38
11.10.4.6. ICH Listings................................................................38
11.10.4.7. Non-ICH Listings ........................................................42
11.10.5. Part 2...........................................................................................43
11.10.5.1. Study Population Tables.............................................43
11.10.5.2. Safety Tables .............................................................44
11.10.5.3. Pharmacokinetic Tables .............................................45
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11.10.5.4. Pharmacokinetic Figures ............................................47
11.10.5.5. Exploratory Tables......................................................48
11.10.5.6. ICH Listings................................................................48
11.10.5.7. Non-ICH Listings ........................................................52
11.11. Appendix 11: Example Mock Shells for Data Displays ................................53
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1.
INTRODUCTION
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Pharmacology Study Report for Protocol.
Revision Chronology:
Version 00
15-MAY-2018
Original
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: 20/Apr/2018).
2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints

To evaluate the bioequivalence 
between levocetirizine ODT (Orally 
Disintegrating Tablet) 5 mg (Test 
product) and levocetirizine IRT
(Immediate Release Tablet) 5 mg 
(Reference product) in healthy 
Japanese male subjects

Plasma PK parameters of levocetirizine: AUC(0-t) and 
Cmax
Secondary Objectives
Secondary Endpoints

To assess the safety and tolerability 
following a single dose of 
levocetirizine 5 mg when given as 
levocetirizine ODT and levocetirizine 
IRT in healthy Japanese male
subjects.

Adverse events (AEs), changes from baseline in clinical 
laboratory tests, vital signs (blood pressure, pulse rate 
and body temperature), and 12-lead electrocardiogram 
(ECG).

Plasma PK parameters of levocetirizine: AUC(0-inf), 
tmax, t1/2, %AUCex, CL/F, Vz/F, kel and MRT.
Exploratory Objectives
Exploratory Endpoints

To assess the palatability 
questionnaire

The palatability questionnaire
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2.3.
Study Design
Overview of Study Design and Key Features
Part 1 (Dosing of levocetirizine ODT with water)

Single dose of levocetirizine ODT 5 mg x 1 with 150 mL of water in the fasted state

Single dose of levocetirizine IRT 5 mg x 1 with 150 mL of water in the fasted state
Group
n
Period 1
Period 2
A
12
Levocetirizine IRT 5 mg
(with water)
Levocetirizine ODT 5 mg
(with water)
B
12
Levocetirizine ODT 5 mg
(with water)
Levocetirizine IRT 5 mg
(with water)
Part 2 (Dosing of levocetirizine ODT without water)

Single dose of levocetirizine ODT 5 mg x 1 without water in the fasted state

Single dose of levocetirizine IRT 5 mg x 1 with 150 mL of water in the fasted state
Group
n
Period 1
Period 2
C
12
Levocetirizine IRT 5 mg
(with water)
Levocetirizine ODT 5 mg
(without water)
D
12
Levocetirizine ODT 5 mg
(without water)
Levocetirizine IRT 5 mg
(with water)
Design
Features

This is a single centre, open-label, single dose, randomized, 2-way crossover study in 
healthy Japanese male subjects.

This study consists of two parts: Part 1 compares dosing of levocetirizine ODT and 
levocetirizine IRT taken with 150 mL water in the fasted state, Part 2 compares dosing 
of levocetirizine ODT without water and levocetirizine IRT with 150 mL water in the 
fasted state.

If subjects prematurely discontinue the study, additional replacement subjects may be 
recruited and assigned to the same treatment sequence at the discretion of the 
Sponsor in consultation with the investigator.

If bioequivalence cannot be demonstrated in Part 1 and/or Part 2 because of an 
insufficient number of subjects, an add-on subject study will be performed using 12 (6 
subjects in each group) or more subjects in each part.
Dosing

All subjects will receive a single dose of levocetirizine 5 mg after an overnight fast (at 
least 10 hours) during the intervention period
Time & 
Events

Refer to Appendix 2: Schedule of Activities.
Treatment 
Assignment

In both parts (Part 1 and Part 2), total number of 24 subjects will be equally divided 
into two groups (12 subjects in each group) and will be randomized in a 1:1 ratio to 
one of two groups in each part.

Subjects will participate either in Part 1 or Part 2 without overlapping.
Interim 
Analysis

No formal interim analyses are planned.
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2.4.
Statistical Hypotheses / Statistical Analyses
This study is designed to test the bioequivalence of levocetirizine ODT 5 mg (with water 
or without water) relative to levocetirizine IRT 5 mg.
The null hypothesis is that the true ratio of the geometric mean of the levocetirizine ODT
5mg (μtest) to the geometric mean of the levocetirizine IRT 5mg (μref), μtest/μref, for each 
primary PK endpoint (AUC(0-t) and Cmax of levocetirizine), is either less than or equal 
to 0.80 or greater than or equal to 1.25. The alternative hypothesis is that the true ratio of 
the test treatment geometric mean to the reference treatment geometric mean is greater 
than 0.80 and less than 1.25. 
Symbolically, this is expressed as follows:
H0: test/ref 0.80 or test/ref 1.25,
i.e., treatments are not bioequivalent.
Versus
H1: 0.80 < test/ref < 1.25,
i.e., treatments are bioequivalent.
These hypotheses will be considered for levocetirizine ODT 5 mg with water or without 
water separately, relative to levocetirizine IRT 5 mg.
For each PK parameter designated as a primary endpoint (AUC(0-t) and Cmax), a two 
one-sided t-test (TOST) procedure [Schuirmann, 1987] with =0.05 for each one-sided 
test will be used to test this set of hypotheses. This is equivalent to requiring that a 90% 
interval for the true ratio of levocetirizine ODT 5 mg to levocetirizine IRT 5 mg
geometric means (test/ref) falls entirely within the range of 0.80 to 1.25. A judgment by 
90% CI will be conducted in this study.
If the bioequivalence will not be shown above, ODT 5 mg will be accepted as 
bioequivalent where the point estimate for true ratio of levocetirizine ODT 5 mg to 
levocetirizine IRT 5 mg geometric mean (test/ref) of AUC(0-t) and Cmax are within 
0.90 - 1.11, according to the criteria described in the Japanese Guideline for 
Bioequivalence Studies of Generic Products (Japanese BE guideline) [Pharmaceutical
and Food Safety Bureau, Evaluation and Licensing Division, Ministry of Health, Labour, 
2012].
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3.
PLANNED ANALYSES
3.1.
Interim Analyses
No formal interim analyses are planned.
3.2.
Final Analyses
The final analyses will be performed after the completion of the following sequential 
steps in each part respectively:
1.
All participants have completed the study as defined in the protocol.
2.
All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management. 
3.
Randomization codes have been distributed according to RandAll NG procedures.
As for an add-on subject study, the same sequential step above will be conducted.
4.
ANALYSIS POPULATIONS
Population
Definition / Criteria
Analyses Evaluated
Screened

Consisting of all participants screened in the study.

Study Population
Screening Failure

Participants who sign the ICF in the study but are never 
subsequently randomized. All participants who sign the 
ICF have the screening test in the study.

Study Population
Safety

All randomized participants who take at least one dose 
of study treatment.

Participants will be analyzed according to the treatment 
they actually received.

Study Population

Safety

Palatability 
Questionnaire
Pharmacokinetic

This population is defined as all participants 
administered at least one dose of study treatment and 
who have blood for plasma drug concentration sample 
taken and analyzed.

Participants will be analyzed according to the treatment 
they actually received.

PK
Refer to Appendix 10: List of Data Displays which details the population used for each display.
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.
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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 
summary will be based on data as recorded on the inclusion/exclusion page of the eCRF.
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA
HANDLING CONVENTIONS
5.1.
Study Treatment & Sub-group Display Descriptors
Treatment
RandAll NG
Data Displays for Reporting 
Code
Description
Description
Order in TLF 
A
Levocetirizine ODT 5 mg
Levocetirizine ODT 5 mg
1
A
Levocetirizine IRT 5 mg
Levocetirizine IRT 5 mg
2
B
Levocetirizine IRT 5 mg
Levocetirizine IRT 5 mg
2
B
Levocetirizine ODT 5 mg
Levocetirizine ODT 5 mg
1
Randomized group (sequence) will be displayed as A or B for Part 1, and C (= A in 
RandAll NG) or D (= B in RandAll NG) for Part 2 according to the protocol.
5.2.
Baseline Definitions
Baseline to be used in analysis is pre-dose in each period. For all endpoints, the baseline 
value will be the latest pre-dose assessment with a non-missing value, including those 
from unscheduled visits.
Parameter
Study Assessments Considered as Baseline
Baseline Used in 
Data Display
Screening
Day -1
Day 1 (Pre-Dose)
Safety
Clinical Laboratory 
Test (Hematology, 
Clinical chemistry, and 
Urinalysis)
X
X
Day 1 (Pre Dose)
12 Lead ECG & Vital 
Signs
X
X
Day 1 (Pre Dose)
Data of height, weight and BMI for demographic characteristics will be from screening 
visit.
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Unless otherwise stated, if baseline data is missing, no derivation will be performed and 
baseline will be set to missing.
5.3.
Other Considerations for Data Analyses and Data Handling 
Conventions
Other considerations for data analyses and data handling conventions are outlined in the 
appendices:
Section
Component
11.3
Appendix 3: Assessment Windows
11.4
Appendix 4: Study Phases and Treatment Emergent Adverse Events
11.5
Appendix 5: Data Display Standards & Handling Conventions
11.6
Appendix 6: Derived and Transformed Data
11.7
Appendix 7: Reporting Standards for Missing Data
11.8
Appendix 8: Values of Potential Clinical Importance
6.
STUDY POPULATION ANALYSES
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic characteristics, prior and concomitant medications, and 
exposure will be based on GSK Core Data Standards. Details of the planned displays are 
presented in Appendix 10: List of Data Displays.
7.
SAFETY ANALYSES
The safety analyses will be based on the Safety population, unless otherwise specified.
7.1.
Adverse Events Analyses
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs)
and other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 10: List of Data Displays.
7.2.
Clinical Laboratory Analyses
Laboratory evaluations including the analyses of Chemistry laboratory tests, Hematology 
laboratory tests, Urinalysis, and liver function tests will be based on GSK Core Data 
Standards. The details of the planned displays are in Appendix 10: List of Data Displays.
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7.3.
Other Safety Analyses
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. The details of the 
planned displays are presented in Appendix 10: List of Data Displays.
8.
PHARMACOKINETIC ANALYSES
The PK analyses will be based on the Pharmacokinetic population, unless otherwise 
specified.
8.1.
Primary Pharmacokinetic Analyses
8.1.1.
Endpoint / Variables
8.1.1.1.
Drug Concentration Measures
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 11.5.3
Reporting Standards for Pharmacokinetic)
8.1.1.2.
Derived Pharmacokinetic Parameters
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin (version 6.3 or higher). All calculations of non-compartmental parameters 
will be based on actual sampling times. Pharmacokinetic parameters listed will be 
determined from the plasma concentration-time data, as data permits.
Parameter
Parameter Description
AUC (0-t)
(hr*ng/mL)
Area under the concentration-time curve from time zero time (pre-dose) to the time of last 
quantifiable concentration (AUC(0-t)) will be calculated by the linear trapezoidal method 
(i.e., Linear Trapezoidal Linear Interpolation calculation method in Phoenix WinNonlin).
Cmax
(ng/mL)
Maximum observed concentration will be obtained directly from the concentration-time data.
8.1.2.
Summary Measure
PK parameters of AUC(0-t) and Cmax are summary measures.
8.1.3.
Population of Interest 
The primary pharmacokinetic analyses will be based on the PK population, unless 
otherwise specified.
8.1.4.
Strategy for Intercurrent (Post-Randomization) Events
This section is not applicable, however, where a missing data for PK parameters will 
occur in a subject on period 1 or period 2, the subject data will be analyzed using the 
mixed effect model to evaluate the bioequivalence of PK parameter.
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8.1.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 8.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
8.1.5.1.
Statistical Methodology Specification
The following pharmacokinetic statistical analyses will only be performed if sufficient 
data is available (i.e. if participants have well defined plasma profiles).
Endpoint / Variables

AUC(0-t) and Cmax
Model Specification

Evaluation of BE will be performed for each part (Part 1 and Part 2) according to the criteria 
described in the Japanese BE Guideline.

After loge-transformation, primary PK parameter(s) of levocetirizine given as levocetirizine ODT 
5 mg or when given as levocetirizine IRT 5 mg will be analyzed using a mixed effects model 
fitting terms for treatment and period as fixed effects, also subjects as a random effect.

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 for the contrast (test-reference) 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 test/reference.

Two treatment are considered to be bioequivalent, if the 90% confidence intervals of the 
geometric mean ratio (test/ref) of AUC(0-t) and Cmax are within the acceptable range of 0.80 
– 1.25.

Estimates of within-subject variability (%CVw) for AUC (0-t) and Cmax of levocetirizine will also 
be provided.

The within-subject coefficients of variation (%CVw) for AUC(0-t) and Cmax 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

If the bioequivalence will not be shown above, ODT 5 mg will be accepted as bioequivalent to 
IRT 5mg where the following condition is satisfied.
o
Point estimate for geometric mean ratio (test/ref) of AUC(0-t) and Cmax are within 0.90 -
1.11.
Add-on subject study
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Endpoint / Variables

When an add-on subject study will be conducted, the data of two studies in each part would be 
combined for analysis.

ODT 5 mg will be accepted as bioequivalent if the following condition is satisfied under the total 
pooled sample size of the main and add-on subject according to the criteria described in the 
Japanese BE Guideline.
o
The 90% confidence intervals of the geometric mean ratio (test/ref) of AUC(0-t) and 
Cmax are within the acceptable range of 0.80 – 1.25.
o
If the bioequivalence will not be shown above, point estimate for geometric mean ratio 
(test/ref) of AUC(0-t) and Cmax are within 0.90 - 1.11.

After loge-transformation, primary PK parameter(s) of levocetirizine given as levocetirizine 
ODT 5 mg or when given as levocetirizine IRT 5 mg will be analyzed using a mixed effects 
model fitting terms for treatment, period and study (main or add-on subject study) as fixed 
effects, also subjects as a random effect.
8.2.
Secondary Pharmacokinetic Analyses
8.2.1.
Endpoint / Variables
8.2.1.1.
Drug Concentration Measures 
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 11.5.3
Reporting Standards for Pharmacokinetic)
8.2.1.2.
Derived Pharmacokinetic Parameters
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin (version 6.3 or higher). All calculations of non-compartmental parameters 
will be based on actual sampling times. Pharmacokinetic parameters listed will be 
determined from the plasma concentration-time data, as data permits.
Parameter
Parameter Description
AUC (0-inf) 
(hr*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) + C(t) / kel
%AUCex (%)
The percentage of AUC (0-inf) obtained by extrapolation (%AUCex) will be calculated as:
%AUCex = [AUC(0-inf) – AUC(0-t)] / AUC(0-inf) x 100
tmax (hr)
Time to first occurrence of Cmax will be obtained directly from the concentration-time data.
t1/2 (hr)
Apparent terminal phase half-life will be calculated as: 
t½ = ln2 / kel
tlast (hr)
The time of the last measurable (positive) concentration.
kel 
(lambda_z) 
(1/hr)
The first order rate constant associated with the terminal (log-linear) portion of the curve.
lambda_z
The lower limit on time for values to be included in the calculation of kel.
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Parameter
Parameter Description
lower (hr)
lambda_z
upper (hr)
The upper limit on time for values to be included in the calculation of kel.
#pts
The number of time points used in computing kel.
R-square
Square of the correlation coefficient.
CL/F (L/hr)
Apparent clearance following oral dosing will be calculated as:
CL/F = Dose / AUC (0-inf)
Vz/F (L)
Apparent volume of distribution following oral dosing will be calculated as:
Vz/F = Dose / kel * AUC(0-inf)
MRT (hr)
Mean residence time will be calculated as follows:
MRT = AUMC(0-inf) / AUC(0-inf)
NOTES:

Additional parameters may be included as required.

kel is the terminal phase rate constant.

C(t) is the last observed quantifiable concentration.

AUMC is area under the moment curve.
8.2.2.
Summary Measure
Derived PK parameters are shown in Section 8.2.1.2." Derived Pharmacokinetic 
Parameters" are summary measures.
8.2.3.
Population of Interest 
The secondary pharmacokinetic analyses will be based on the PK population, unless 
otherwise specified.
8.2.4.
Strategy for Intercurrent (Post-Randomization) Events
This section is not applicable, however, where a missing data for PK parameters will 
occur in a subject on period 1 or period 2, the subject data will be analyzed using the 
mixed effect model to evaluate the bioequivalence of PK parameter.
8.2.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 8.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
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8.2.5.1.
Statistical Methodology Specification
Endpoint / Variables

AUC(0-inf), tmax, kel, MRT
Model Specification

Same manner as Section 8.1.5.1. "Statistical Methodology Specification" for AUC(0-inf), kel, 
MRT.

tmax will be analyzed with the non-parametric Wilcoxon Matched Pairs Method (Signed Rank
Method) to compute point estimate and associated 90% confidence interval for the median 
difference, Levocetirizine ODT 5 mg – Levocetirizine IRT 5 mg, using normal approximation. 
Paired data of Levocetirizine ODT 5 mg and Levocetirizine IRT 5 mg will be used only and 
period effect will not be considered.
Add-on subject study

Same manner as Section 8.1.5.1. "Statistical Methodology Specification" for AUC(0-inf), kel, 
MRT.

tmax will be analyzed with the non-parametric Wilcoxon Matched Pairs Method (Signed Rank 
Method) to compute point estimate and associated 90% confidence interval for the median 
difference, Levocetirizine ODT 5 mg – Levocetirizine IRT 5 mg, using normal approximation. 
Paired data of Levocetirizine ODT 5 mg and Levocetirizine IRT 5 mg will be used only and 
period effect and study effect (main or add-on subject study) will not be considered.
9.
EXPLORATORY ANALYSES
The analysis of the palatability questionnaire will be based on the Safety population. The 
data will be summarized using descriptive statistics. All categorical responses will be 
summarized with counts and percentages. All ordinal data, e.g. ratings, will be 
summarized with mean, median, standard deviation, minimum, and maximum as well as 
counts and percentages of each rating. Palatability questionnaire data will also be listed.
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10.
REFERENCES
GlaxoSmithKline Document Numbers 2018N360906_00 Study Protocol of 204678. A 
single centre, single dose, 2 part, open-label, randomized, 2-way crossover study to 
determine the bioequivalence of levocetirizine oral disintegrating tablet given with water 
and without water compared to levocetirizine immediate release tablet in healthy 
Japanese male subjects (Effective date: 20-Apr-2018)
Pharmaceutical and Food Safety Bureau, Evaluation and Licensing Division, Ministry of 
Health, Labour, and Welfare. Guideline for Bioequivalence Studies of Generic Products.
Notification 0229 No.10. Feb-2012.
Schuirmann DJ. 1987. A comparison of the two one-sided tests procedure and the power 
approach for assessing the equivalence of average bioavailability. J Pharmacokinet and 
Biopharm, 15, 657-680.
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11.
APPENDICES
11.1.
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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11.2.
Appendix 2: Schedule of Activities
11.2.1.
Protocol Defined Schedule of Events
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11.3.
Appendix 3: Assessment Windows
Not applicable
11.4.
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events
11.4.1.
Study Phases
Assessments and events will be classified according to the time of occurrence relative to 
dosing by period.
Study Phase
Definition
Pre-Treatment 
Date <= Day -1 in Period 1
On-Treatment
Period 1: From Day 1 of Period 1 to Day 3 in Period 1.
Period 2: From Day 1 of Period 2 to Day 3 in Period 2.
Follow-Up
After Day 3 in Period 2.
11.4.2.
Treatment Emergent Flag for Adverse Events
Adverse events will be classified according to the time of occurrence relative to start 
and/or stop date of the study treatment by period.
Flag (Treatment 
State)
Definition
Pre-Treatment

AE Start Date < Study Treatment Start Date and Time in Period 1
On treatment
(Period 1)

Dosing Start Date and Time in Period 1 ≤ AE Start Date and Time < Study 
Treatment Start Date and Time in Period 2
On treatment
(Period 2)

Dosing Start Date and Time in Period 2 ≤ AE Start Date and Time < Follow-Up
Onset Time Since 
First Dose 
(Minute)

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 (if dosing Start Date 
and Time ≤ AE Onset Date and Time)

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
NOTES: 

If the study treatment stop date is missing, then the AE will be considered to be On-Treatment.

Time of study treatment dosing and start/stop time of AEs should be considered, if collected.

If AE onset time is missing, the duration will be calculated in days.
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11.5.
Appendix 5: Data Display Standards & Handling 
Conventions
11.5.1.
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
: N/A
HARP Compound
: N/A
Analysis Datasets 

Analysis datasets will be created according to Legacy GSK A&R dataset standards.
Generation of RTF Files

RTF files will be generated.
11.5.2.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx):

4.03 to 4.23: General Principles

5.01 to 5.08: Principles Related to Data Listings

6.01 to 6.11: Principles Related to Summary Tables

7.01 to 7.13: Principles Related to Graphics 
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected, unless otherwise stated.

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:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

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: 

Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the subject’s listings. 
Unscheduled Visits

Unscheduled visits will not be included in summary tables and/or figures.

All unscheduled visits will be included in listings.
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Descriptive Summary Statistics
Continuous Data
Refer to IDSL Statistical Principle 6.06.1
Categorical Data
N, n, frequency, %
Graphical Displays

Refer to IDSL Statistical Principals 7.01 to 7.13.
11.5.3.
Reporting Standards for Pharmacokinetic
Pharmacokinetic Concentration Data
PC Windows Non-
Linear (WNL) File
PC WNL file (CSV format) for the non-compartmental analysis by Clinical 
Pharmacology Office will be created according to GUI_51487. 
Note: Concentration values will be imputed as per GUI_51487.
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards.
Refer to IDSL Statistical Principle 6.06.1.
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only. 
Pharmacokinetic Parameter Derivation
PK Parameter to be 
Derived by 
Programmer
No PK parameters derived by programmer are planned.
Pharmacokinetic Parameter Data
Is NQ impacted PK 
Parameters Rule 
Being Followed
Yes, refer to Standards for Handling NQ Impacted PK Parameters in GUI_51487.
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards.
tmax will not be loge-transformed for summary statistics.
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11.6.
Appendix 6: Derived and Transformed Data
11.6.1.
General
Multiple Measurements at One Analysis 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.

Participants having both High and Low values for Normal Ranges at any post-baseline visit 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 First Dose Date:

Ref Date = Missing              → Study Day = Missing 

Ref Date < (Dosing Start Date) → Study Day = Ref Date – (Dosing Start Date)

Ref Data ≥ (Dosing Start Date) → Study Day = Ref Date – (Dosing Start Date) + 1    
11.6.2.
Study Population
Demographics
Age

GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed as 
follows:
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 date for age calculation will be from dosing start day.

Reference date for calculation of age at screening will be from informed consent date.

Analysis age group will be categorized (Years):
<=18, 19-64, 65-74, >=75

Age will be categorized for EudraCT:
Adults (18-64 years)
11.6.3.
Safety
Adverse Events
AE’S OF Special Interest
N/A
Laboratory Assessments
Haematology
Platelet Count, RBC Count, Haemoglobin, Hematocrit, RBC Indices (MCV, MCH, MCH, %Reticulocytes), 
WBC count with Differential (Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils)
Clinical Chemistry
BUN, Creatinine, Glucose (fasting), Potassium, Sodium, Calcium, Aspartate Aminotransferase (AST),
Alanine Aminotransferase (ALT), Alkaline phosphatise, Total and direct bilirubin, Total Protein
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Laboratory Assessments
Routine Urinalysis

Specific gravity, pH (assessed by dipstick)

Glucose, Protein, Blood, Ketones, Bilirubin, Urobilinogen by dipstick
ECG (12-lead ECG)
ECG findings, ECG values (Heart rate, PR interval, QRS duration, QT interval, and QTcF intervals)
Vital Signs
Pulse rate (Heart rate), Blood pressure (Systolic, Diastolic), Temperature
11.6.4.
Pharmacokinetic
PK parameters
Primary parameters
AUC(0-t), Cmax
Secondary parameters
AUC(0-inf), tmax, t1/2, %AUCex, CL/F, Vz/F, kel, MRT (tlast, lambda_z lower, lambda_z upper, #pts, R-
square will be listed only)
NQ, NC and ND

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.
11.6.5.
Exploratory
Palatability Questionnaire

Q1: to describe the taste of the product in subject's own words briefly

Q2: to rate the palatability (acceptability of taste)

Q3: to check all the descriptors (Sweet, Sour/tart, Bitter, Fruity, Nutty, Chalky, Medicinal)

Q4: to rate the mouth feel

Q5: to circle the number that best describes (5 score: Sweetness, Sour/tartness, Bitter)
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11.7.
Appendix 7: Reporting Standards for Missing Data
11.7.1.
Premature Withdrawals
Element
Reporting Detail
General

Subject study completion (i.e. as specified in the protocol) was defined as a subject has 
completed all phases of the study including the last follow-up visit as described in the 
protocol. 

Withdrawn subjects may be replaced in the study.

All available data from participants 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.
11.7.2.
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.
Outliers

Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report.
11.7.2.1.
Handling of Missing and Partial Dates
Element
Reporting Detail
General

Partial dates will be displayed as captured in subject listing displays.
Adverse 
Events

The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 
recorded for AE start and end dates; that is, the day of the month may be missing. In 
such a case, the following conventions will be applied for calculating the time to onset 
and the duration of the event:
o
Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used 
and hence the event is considered On-treatment as per Appendix 4: Study Phases 
and Treatment Emergent Adverse Events.
o
Missing Stop Day: Last day of the month will be used, unless this is after the stop 
date of study treatment; in this case the study treatment stop date will be used.

Completely missing start or end dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing.
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.
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11.7.2.2.
Handling of Missing for Statistical Analysis of BE
Element
Reporting Detail
Imputation

No imputation will be performed for missing data. 

Where a missing data for PK parameters (except for tmax) will occur in a subject on 
period 1 or period 2, the subject data will be analyzed using the mixed effect model to 
evaluate the bioequivalence of PK parameter
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11.8.
Appendix 8: Values of Potential Clinical Importance
11.8.1.
Laboratory Values
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
Note: ↓ indicates a negative direction of the change from baseline.
Clinical Chemistry
Laboratory Parameter
Units
Category
Clinical Concern Range
Low Flag (< x)
High Flag (>x)
Calcium
mmol/L
2
2.75
Creatinine
µmol/L
∆from BL
↑ 44.2
Glucose
mmol/L
3
9
Potassium
mmol/L
3
5.5
Sodium
mmol/L
130
150
Note: ↑indicates a positive direction of the change from baseline.
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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11.8.2.
ECG
ECG Parameter
Units
Clinical Concern Range
Lower
Upper
Absolute
Absolute QTc (QTcF) Interval
msec
> 450
Absolute PR Interval
msec
< 110
> 220
Absolute QRS Interval
msec
< 75
> 110
Change from Baseline
Increase from Baseline QTc
(QTcF)
msec
> 60
11.8.3.
Vital Signs
Vital Sign Parameter
(Absolute)
Units
Clinical Concern Range
Lower
Upper
Systolic Blood Pressure
mmHg
< 85
> 160
Diastolic Blood Pressure
mmHg
< 45
> 100
Heart Rate (Pulse Rate)
bpm
< 40
> 110
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11.9.
Appendix 9: Abbreviations & Trade Marks
11.9.1.
Abbreviations
Abbreviation
Description
AE
Adverse Event
A&R
Analysis and Reporting 
AUC
Area under concentration-time curve
AUC(0-inf)
Area under the concentration-time curve from time zero (pre-dose) extrapolated 
to infinite time
%AUCex
Percentage of AUC(0-inf) obtained by extrapolation
AUC(0-t)
Area under the concentration-time curve from pre-dose to last time of 
quantifiable concentration within a subject across all treatments
BE
Bioequivalence
BMI
Body mass index
CI
Confidence Interval
CIL
Clinical Investigation Leader
CL/F
Apparent clearance following oral dosing
Cmax
Maximum observed concentration 
CSR
Clinical Study Report
CVb / CVw
Coefficient of Variation (Between) / Coefficient of Variation (Within)
DBF
Database Freeze
DBR
Database Release
DQL
Data Quality Leader
ECG
Electrocardiogram
eCRF
Electronic Case Record Form
GSK
GlaxoSmithKline
ICF
Informed Consent Form
IDSL
Integrated Data Standards Library
IP
Investigational Product
LLQ
Lower Limit of Quantification
LS
Least Squar
MedDRA
Medical dictionary for regulatory activities
MSE
Mean Square Error
OSL
Operations and Science Leader
PCI
Potential Clinical Importance 
PDMP
Protocol Deviation Management Plan
PK
Pharmacokinetic
QC
Quality Control
QTcF
Frederica’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
SAC
Statistical Analysis Complete
SOP
Standard Operation Procedure
t1/2
Terminal phase half-life
tmax
Time of occurrence of Cmax
TOST
Two one-sided t-test
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Abbreviation
Description
Vz/F
Apparent volume of distribution after oral administration
11.9.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
None
SAS
WinNonlin
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11.10.
Appendix 10: List of Data Displays
11.10.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Part 1:
Section
Tables
Figures
Study Population
1.101 to 1.107
N/A
Safety
2.101 to 2.118
N/A
Pharmacokinetic
3.101 to 3.106
3.101 to 3.105
Exploratory
4.101
N/A
Section
Listings
ICH Listings
101 to 138
Other Listings
139
Part 2:
Section
Tables
Figures
Study Population
1.201 to 1.207
N/A
Safety
2.201 to 2.218
N/A
Pharmacokinetic
3.201 to 3.206
3.201 to 3.205
Exploratory
4.201
N/A
Section
Listings
ICH Listings
201 to 238
Other Listings
239
If an add-on subject study will be conducted, the data of two studies will be combined for 
analysis. The following numbering will be applied for RAP generated displays:
Part 1:
Section
Tables
Figures
Study Population
1.301 to 1.307
N/A
Safety
2.301 to 2.318
N/A
Pharmacokinetic
3.301 to 3.306
3.301 to 3.305
Explanatory
4.301
N/A
Section
Listings
ICH Listings
301 to 338
Other Listings
339
Part 2:
Section
Tables
Figures
Study Population
1.401 to 1.407
N/A
Safety
2.401 to 2.418
N/A
Pharmacokinetic
3.401 to 3.406
3.401 to 3.405
Explanatory
4.401
N/A
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Section
Listings
ICH Listings
401 to 438
Other Listings
439
11.10.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 11: 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
Exploratory
EXP_Fn
EXP_Tn
EXP_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’
11.10.3.
Deliverables
Delivery [Priority] [1]
Description
TR [X]
Topline Report
SAC [X]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort
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11.10.4.
Part 1
11.10.4.1. Study Population Tables
Study Population Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition 
1.101
Safety
CP_ES1
Summary of Subject Disposition (Part 1)
Completed or withdrawn and the reason for 
withdrawal.
SAC [1]
1.102
Screened
ES6
Summary of Screening Status and Reasons for 
Screen Failure (Part 1)
The number (%) of Randomized or screening 
failure subjects as the screening status, and the 
reason for screening failure.
SAC [1]
Protocol Deviation
1.103
Safety
DV1
Summary of Important Protocol Deviations (Part 1)
Data is from DV dataset.
SAC [1]
Study Populations
1.104
Safety
SP1
Summary of Study Populations (Part 1)
SAC [1]
Demographics
1.105
Safety
DM3
Summary of Demographic Characteristics (Part 1)
TR [2]
1.106
Screened
DM11
Summary of Age Ranges (Part 1)
Adults (18-64 years)
SAC [1]
1.107
Safety
DM5
Summary of Race and Racial Combinations (Part 1)
SAC [1]
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11.10.4.2. Safety Tables
Safety Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events
2.101
Safety
AE1CP
Summary of All Adverse Events by System Organ 
Class and Preferred Term (Part 1)
TR [2]
2.102
Safety
AE5A
Summary of All Adverse Events by System Organ 
Class and Maximum Intensity (Part 1)
SAC [1]
2.103
Safety
AE1CP
Summary of All Drug-Related Adverse Events by 
System Organ Class and Preferred Term (Part 1)
SAC [1]
2.104
Safety
AE5A
Summary of All Drug-Related Adverse Events by 
Maximum Intensity (Part 1)
SAC [1]
2.105
Safety
AE1CP
Summary of Serious Adverse Events by System 
Organ Class (Part 1)
SAC [1]
Labs
2.106
Safety
LB1
Summary of Chemistry Results (Part 1)
SAC [1]
2.107
Safety
LB1
Summary of Chemistry Changes from Baseline (Part 
1)
SAC [1]
2.108
Safety
LB4
Summary of Chemistry Data Shifts from Baseline with 
Respect to the Normal Range (Part 1)
Worst Case Post-Baseline is not needed
SAC [1]
2.109
Safety
LB1
Summary of Hematology Results (Part 1)
SAC [1]
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Safety Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.110
Safety
LB1
Summary of Hematology Changes from Baseline
(Part 1)
SAC [1]
2.111
Safety
LB4
Summary of Hematology Data Shifts from Baseline 
with Respect to the Normal Range (Part 1)
Worst Case Post-Baseline is not needed
SAC [1]
2.112
Safety
UR3b
Summary of Urinalysis (Glucose, Protein, Blood, 
Ketones) Data (Part 1)
SAC [1]
2.113
Safety
LB1
Summary of Urinalysis (Gravity and pH) (Part 1)
SAC [1]
ECGs
2.114
Safety
EG1
Summary of ECG Findings (Part 1)
SAC [1]
2.115
Safety
EG2
Summary of ECG Values (Part 1).
SAC [1]
2.116
Safety
EG2
Summary of Change from Baseline in ECG Values 
(Part 1). 
SAC [1]
Vital Signs 
2.117
Safety
VS1
Summary of Vital Signs (Part 1)
SAC [1]
2.118
Safety
VS1
Summary of Change from Baseline in Vital Signs 
(Part 1).
SAC [1]
11.10.4.3. Pharmacokinetic Tables
Pharmacokinetic Tables
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No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
PK Concentration Data
3.101
PK
PK01: PKCT1
Summary of Levocetirizine Plasma Concentration 
(ng/mL) (Part 1)
Summary statistics: N, n, Number of imputed, 
mean, 95% confidence interval, standard 
deviation, median, minimum, maximum
SAC [1]
Derived PK Parameters
3.102
PK
PK03: PKPT1
Summary of Levocetirizine Plasma Pharmacokinetic 
Parameters (non-transformed) (Part 1)
Summary statistics: N, n, Number of imputed, 
mean, 95% confidence interval, standard 
deviation, median, minimum, maximum
TR [2]
3.103
PK
PK05: PKPT3
Summary of Levocetirizine Plasma Pharmacokinetic 
Parameters (loge-transformed) (Part 1)
Summary statistics: N, n, Number of imputed, 
geometric mean, 95% confidence interval for the 
geometric mean, standard deviation of 
logarithmically transformed data (SD(logs)), 
coefficient of variation (%CVb).
tmax is not included in this table.
TR [2]
3.104
PK
Study Specific
(PK_T1)
Summary of Bioequivalence Analysis on 
Pharmacokinetic Parameters (AUC(0-t) and Cmax) 
(Part 1)
PK Parameters: AUC(0-t), Cmax
TR [2]
3.105
PK
Study Specific 
(PK_T1)
Summary of Bioequivalence Analysis on 
Pharmacokinetic Parameters (AUC(0-inf), kel, MRT)
(Part 1)
PK Parameters: AUC(0-inf), kel, MRT
TR [2]
3.106
PK
Study Specific 
(PK_T2)
Summary of Bioequivalence Analysis on 
Pharmacokinetic Parameters (tmax) (Part 1)
PK Parameter: tmax. Non-parametric Wilcoxon 
Matched Pairs Method for median difference.
TR [2]
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11.10.4.4. Pharmacokinetic Figures
Pharmacokinetic Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Individual Concentration Plots
3.101
PK
PK16b: 
PKCF1x
Individual Levocetirizine Plasma Concentration-Time 
Plots by Subject (Linear and Semi-Log) (Part 1)
Paginate by Subject.
Include line for LLQ along with footnote defining 
LLQ value (2.0 ng/mL)
SAC [1]
3.102
PK
PK16b: 
PKCF1x
Individual Levocetirizine Plasma Concentration-Time 
Plots by Treatment (Linear and Semi-Log) (Part 1)
Paginate by Treatment.
Include line for LLQ along with footnote defining 
LLQ value (2.0 ng/mL)
SAC [1]
Mean / Median Concentration Plots
3.103
PK
PK17: PKCF2
Mean (+SD) Levocetirizine Plasma Concentration-
Time Plots (Part 1)
1. Include the + SD bars at each time point.
2. X-axis displays planned relative time
3. Include line for LLQ along with footnote 
defining LLQ value (2.0 ng/mL)
TR [2]
3.104
PK
PK18: PKCF3
Median Levocetirizine Plasma Concentration-Time 
Plots (Part 1)
TR [2]
PK parameter Plots (Bioequivalence Analysis)
3.105
PK
Study Specific
(PK_F1)
Plot of Levocetirizine Treatment Ratio and 90% 
CI for Bioequivalence Analysis on PK 
Parameters (AUC(0-t) and Cmax) (Part 1)
PK Parameters: AUC(0-t), Cmax.
Plot the comparison on the Y-axis and Ratio on 
X axis.
TR [1]
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11.10.4.5. Exploratory Tables
Palatability Questionnaire Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Palatability Questionnaire Tables
4.101
Safety
Study Specific
(EXP_T1)
Summary of Palatability Questionnaire (Part 1)
Q2 to Q5.
Summary statistics and frequency count will be 
performed for all questions except for Q3 of 
frequency only.
SAC [1]
11.10.4.6. 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]
Randomisation
101
Safety
CP_TA2
Listing of Randomised and Actual Treatments (Part 1)
SAC [1]
Subject Disposition
102
Safety
CP_ES10x
Listing of Reasons for Premature Withdrawal (Part 1)
SAC [1]
103
Screening 
Failure
ES7
Listing of Reasons for Screening Failure (Part 1)
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
104
Safety
DV2
Listing of Subjects with Important Protocol Deviations
(Part 1)
SAC [1]
105
Screened
IE4
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations (Part 1)
SAC [1]
106 
Safety
Study Specific 
(SAFE_L1)
Listing of Subjects Excluded from PK Population
(Part 1)
SAC [1]
Demographics
107
Safety
DM4
Listing of Demographic Characteristics (Part 1)
Informed consent date is included.
SAC [1]
108
Screening 
Failure
DM2
Listing of Demographic Characteristics for Screening 
Failure Subjects (Part 1)
Informed consent date is included.
SAC [1]
109
Safety
DM10
Listing of Race (Part 1)
SAC [1]
110
Screening 
Failure
DM10
Listing of Race for Screening Failure Subjects (Part 
1)
SAC [1]
Medical Conditions
111
Screened
MH3
Listing of Medical Conditions (Part 1)
SAC [1]
Concomitant Medications
112
Screened
CP_CM4
Listing of Concomitant Medications (Part 1)
SAC [1]
113
Safety
CM6
Relationship between ATC Level 1, Ingredient and 
Verbatim Text (Part 1)
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure
114
Safety
EX4
Listing of Exposure (Part 1)
SAC [1]
Adverse Events
115
Safety
CP_AE9
Listing of All Adverse Event (Part 1)
TR [2]
116
Safety
CP_AE9
Listing of Serious Adverse Events (Part 1)
TR [2]
117
Screening 
Failure
CP_AE9
Listing of Serious Adverse Events for Screening 
Failure Subject (Part 1)
SAC [1]
118
Safety
CP_AE9
Listing of Adverse Events Leading to Discontinuation 
of Investigational Product or Withdrawal from Study
(Part 1)
SAC [1]
119
Safety
AE7
Listing of Subject Numbers for Individual Adverse 
Events (Part 1)
SAC [1]
120
Screened
AE2
Listing of Relationship between System Organ Class, 
Preferred Term and Verbatim Text (Part 1)
SAC [1]
LABS
121
Safety
CP_LB6
Listing of All Chemistry Data (Part 1)
Change from baseline is included.
SAC [1]
122
Safety
CP_LB6
Listing of All Chemistry Data for Subjects with 
Potential Clinical Importance (Part 1)
SAC [1]
123
Safety
CP_LB6
Listing of All Hematology Data (Part 1)
Change from baseline is included.
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
124
Safety
CP_LB6
Listing of All Hematology Data for Subjects with 
Potential Clinical Importance (Part 1)
SAC [1]
125
Safety
CP_LB6
Listing of Urinalysis (Gravity and pH) Data (Part 1)
SAC [1]
126
Safety
UR2b
Listing of Urinalysis (Glucose, Protein, Blood, 
Ketones, Bilirubin, Urobilinogen and microscopic 
examination) Data (Part 1)
SAC [1]
Vital Signs 
127
Safety
CP_VS5
Listing of All Vital Signs (Part 1)
SAC [1]
128
Safety
CP_VS5
Listing of Change from Baseline in Vital Signs (Part 
1)
SAC [1]
129
Safety
CP_VS5
Listing of All Vital Signs for Subjects with any Value of 
Potential Clinical Importance (Part 1)
SAC [1]
ECG
130
Safety
CP_EG6
Listing of ECG Findings (Part 1)
SAC [1]
131
Safety
CP_EG4
Listing of All ECG Values (Part 1)
SAC [1]
132
Safety
CP_EG4
Listing of Change from Baseline in ECG Values (Part 
1)
SAC [1]
133
Safety
CP_EG4
Listing of All ECG Values for Subjects with Any Value 
of Potential Clinical Importance (Part 1)
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Liver event
134
Safety
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting 
(Part 1)
SAC [1]
135
Safety
MH3
Listing of Medical Conditions for Subjects with Liver 
Stopping Events (Part 1)
SAC [1]
136
Safety
SU2
Listing of Substance Use for Subjects with Liver 
Stopping Events (Part 1)
SAC [1]
Pharmacokinetics
137
PK
PK08: PKCL1x
Listing of Levocetirizine Plasma Concentration (Part 
1)
SAC [1]
138
PK
PK14: PKPL1x
Listing of Levocetirizine Plasma Pharmacokinetic 
Parameters (Part 1)
SAC [1]
11.10.4.7. Non-ICH Listings
Non-ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Palatability Questionnaire
139
Safety
Study Specific 
(EXP_L1)
Listing of Palatability Questionnaire (Part 1)
SAC [1]
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11.10.5.
Part 2
11.10.5.1. Study Population Tables
Study Population Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition 
1.201
Safety
CP_ES1
Summary of Subject Disposition (Part 2)
Completed or withdrawn and the reason for 
withdrawal.
SAC [1]
1.202
Screened
ES6
Summary of Screening Status and Reasons for 
Screen Failure (Part 2)
The number (%) of Randomized or screening 
failure subjects as the screening status, and the 
reason for screening failure.
SAC [1]
Protocol Deviation
1.203
Safety
DV1
Summary of Important Protocol Deviations (Part 2)
Data is from DV dataset.
SAC [1]
Study Populations
1.204
Safety
SP1
Summary of Study Populations (Part 2)
SAC [1]
Demographics
1.205
Safety
DM3
Summary of Demographic Characteristics (Part 2)
TR [1]
1.206
Screened
DM11
Summary of Age Ranges (Part 2)
Adults (18-64 years)
SAC [1]
1.207
Safety
DM5
Summary of Race and Racial Combinations (Part 2)
SAC [1]
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11.10.5.2. Safety Tables
Safety Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events
2.201
Safety
AE1CP
Summary of All Adverse Events by System Organ 
Class and Preferred Term (Part 2)
TR [1]
2.202
Safety
AE5A
Summary of All Adverse Events by System Organ 
Class and Maximum Intensity (Part 2)
SAC [1]
2.203
Safety
AE1CP
Summary of All Drug-Related Adverse Events by 
System Organ Class and Preferred Term (Part 2)
SAC [1]
2.204
Safety
AE5A
Summary of All Drug-Related Adverse Events by 
Maximum Intensity (Part 2)
SAC [1]
2.205
Safety
AE1CP
Summary of Serious Adverse Events by System 
Organ Class (Part 2)
SAC [1]
Labs
2.206
Safety
LB1
Summary of Chemistry Results (Part 2)
SAC [1]
2.207
Safety
LB1
Summary of Chemistry Changes from Baseline (Part 
2)
SAC [1]
2.208
Safety
LB4
Summary of Chemistry Data Shifts from Baseline with 
Respect to the Normal Range (Part 2)
Worst Case Post-Baseline is not needed
SAC [1]
2.209
Safety
LB1
Summary of Hematology Results (Part 2)
SAC [1]
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Safety Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.210
Safety
LB1
Summary of Hematology Changes from Baseline
(Part 2)
SAC [1]
2.211
Safety
LB4
Summary of Hematology Data Shifts from Baseline 
with Respect to the Normal Range (Part 2)
Worst Case Post-Baseline is not needed
SAC [1]
2.212
Safety
UR3b
Summary of Urinalysis (Glucose, Protein, Blood, 
Ketones) Data (Part 2)
SAC [1]
2.213
Safety
LB1
Summary of Urinalysis (Gravity and pH) (Part 2)
SAC [1]
ECGs
2.214
Safety
EG1
Summary of ECG Findings (Part 2)
SAC [1]
2.215
Safety
EG2
Summary of ECG Values (Part 2).
SAC [1]
2.216
Safety
EG2
Summary of Change from Baseline in ECG Values 
(Part 2). 
SAC [1]
Vital Signs 
2.217
Safety
VS1
Summary of Vital Signs (Part 2)
SAC [1]
2.218
Safety
VS1
Summary of Change from Baseline in Vital Signs 
(Part 2).
SAC [1]
11.10.5.3. Pharmacokinetic Tables
Pharmacokinetic Tables
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No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
PK Concentration Data
3.201
PK
PK01: PKCT1
Summary of Levocetirizine Plasma Concentration 
(ng/mL) (Part 2)
Summary statistics: N, n, Number of imputed, 
mean, 95% confidence interval, standard 
deviation, median, minimum, maximum
SAC [1]
Derived PK Parameters
3.202
PK
PK03: PKPT1
Summary of Levocetirizine Plasma Pharmacokinetic 
Parameters (non-transformed) (Part 2)
Summary statistics: N, n, Number of imputed, 
mean, 95% confidence interval, standard 
deviation, median, minimum, maximum
TR [1]
3.203
PK
PK05: PKPT3
Summary of Levocetirizine Plasma Pharmacokinetic 
Parameters (loge-transformed) (Part 2)
Summary statistics: N, n, Number of imputed, 
geometric mean, 95% confidence interval for the 
geometric mean, standard deviation of 
logarithmically transformed data (SD(logs)), 
coefficient of variation (%CVb).
tmax is not included in this table.
TR [1]
3.204
PK
Study Specific
(PK_T1)
Summary of Bioequivalence Analysis on 
Pharmacokinetic Parameters (AUC(0-t) and Cmax) 
(Part 2)
PK Parameters: AUC(0-t), Cmax
TR [1]
3.205
PK
Study Specific 
(PK_T1)
Summary of Bioequivalence Analysis on 
Pharmacokinetic Parameters (AUC(0-inf), kel, MRT)
(Part 2)
PK Parameters: AUC(0-inf), kel, MRT
TR [1]
3.206
PK
Study Specific 
(PK_T2)
Summary of Bioequivalence Analysis on 
Pharmacokinetic Parameters (tmax) (Part 2)
PK Parameter: tmax. Non-parametric Wilcoxon 
Matched Pairs Method for median difference.
TR [1]
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11.10.5.4. Pharmacokinetic Figures
Pharmacokinetic Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Individual Concentration Plots
3.201
PK
PK16b: 
PKCF1x
Individual Levocetirizine Plasma Concentration-Time 
Plots by Subject (Linear and Semi-Log) (Part 2)
Paginate by Subject.
Include line for LLQ along with footnote defining 
LLQ value (2.0 ng/mL)
SAC [1]
3.202
PK
PK16b: 
PKCF1x
Individual Levocetirizine Plasma Concentration-Time 
Plots by Treatment (Linear and Semi-Log) (Part 2)
Paginate by Treatment.
Include line for LLQ along with footnote defining 
LLQ value (2.0 ng/mL)
SAC [1]
Mean / Median Concentration Plots
3.203
PK
PK17: PKCF2
Mean (+SD) Levocetirizine Plasma Concentration-
Time Plots (Part 2)
1. Include the + SD bars at each time point.
2. X-axis displays planned relative time
3. Include line for LLQ along with footnote 
defining LLQ value (2.0 ng/mL)
TR [1]
3.204
PK
PK18: PKCF3
Median Levocetirizine Plasma Concentration-Time 
Plots (Part 2)
TR [1]
PK parameter Plots (Bioequivalence Analysis)
3.205
PK
Study Specific
(PK_F1)
Plot of Levocetirizine Treatment Ratio and 90% CI for 
Bioequivalence Analysis on PK Parameters (AUC(0-t) 
and Cmax) (Part 2)
PK Parameters: AUC (0-t), Cmax.
Plot the comparison on the Y-axis and Ratio on 
X axis.
TR [1]
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11.10.5.5. Exploratory Tables
Palatability Questionnaire Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Palatability Questionnaire Tables
3.206
Safety
Study Specific 
(EXP_T1)
Summary of Palatability Questionnaire (Part 2)
Q2 to Q5.
Summary statistics and frequency count will be 
performed for all questions except for Q3 of 
frequency only.
SAC [1]
11.10.5.6. 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]
Randomisation
201
Safety
CP_TA2
Listing of Randomised and Actual Treatments (Part 2)
SAC [1]
Subject Disposition
202
Safety
CP_ES10x
Listing of Reasons for Premature Withdrawal (Part 2)
SAC [1]
203
Screening 
Failure
ES7
Listing of Reasons for Screening Failure (Part 2)
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
204
Safety
DV2
Listing of Subjects with Important Protocol Deviations
(Part 2)
SAC [1]
205
Screened
IE4
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations (Part 2)
SAC [1]
206 
Safety
Study Specific 
(SAFE_L1)
Listing of Subjects Excluded from PK Population
(Part 2)
SAC [1]
Demographics
207
Safety
DM4
Listing of Demographic Characteristics (Part 2)
Informed consent date is included.
SAC [1]
208
Screening 
Failure
DM2
Listing of Demographic Characteristics for Screening 
Failure Subjects (Part 2)
Informed consent date is included.
SAC [1]
209
Safety
DM10
Listing of Race (Part 2)
SAC [1]
210
Screening 
Failure
DM10
Listing of Race for Screening Failure Subjects (Part 
2)
SAC [1]
Medical Conditions
211
Screened
MH3
Listing of Medical Conditions (Part 2)
SAC [1]
Concomitant Medications
212
Screened
CP_CM4
Listing of Concomitant Medications (Part 2)
SAC [1]
213
Safety
CM6
Relationship between ATC Level 1, Ingredient and 
Verbatim Text (Part 2)
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure
214
Safety
EX4
Listing of Exposure (Part 2)
SAC [1]
Adverse Events
215
Safety
CP_AE9
Listing of All Adverse Event (Part 2)
TR [1]
216
Safety
CP_AE9
Listing of Serious Adverse Events (Part 2)
TR [1]
217
Screening 
Failure
CP_AE9
Listing of Serious Adverse Events for Screening 
Failure Subject (Part 2)
SAC [1]
218
Safety
CP_AE9
Listing of Adverse Events Leading to Discontinuation 
of Investigational Product or Withdrawal from Study
(Part 2)
SAC [1]
219
Safety
AE7
Listing of Subject Numbers for Individual Adverse 
Events (Part 2)
SAC [1]
220
Screened
AE2
Listing of Relationship between System Organ Class, 
Preferred Term and Verbatim Text (Part 2)
SAC [1]
LABS
221
Safety
CP_LB6
Listing of All Chemistry Data (Part 2)
Change from baseline is included.
SAC [1]
222
Safety
CP_LB6
Listing of All Chemistry Data for Subjects with 
Potential Clinical Importance (Part 2)
SAC [1]
223
Safety
CP_LB6
Listing of All Hematology Data (Part 2)
Change from baseline is included.
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
224
Safety
CP_LB6
Listing of All Hematology Data for Subjects with 
Potential Clinical Importance (Part 2)
SAC [1]
225
Safety
CP_LB6
Listing of Urinalysis (Gravity and pH) Data (Part 2)
SAC [1]
226
Safety
UR2b
Listing of Urinalysis (Glucose, Protein, Blood, 
Ketones, Bilirubin, Urobilinogen and microscopic 
examination) Data (Part 2)
SAC [1]
Vital Signs 
227
Safety
CP_VS5
Listing of All Vital Signs (Part 2)
SAC [1]
228
Safety
CP_VS5
Listing of Change from Baseline in Vital Signs (Part 
2)
SAC [1]
229
Safety
CP_VS5
Listing of All Vital Signs for Subjects with any Value of 
Potential Clinical Importance (Part 2)
SAC [1]
ECG
230
Safety
CP_EG6
Listing of ECG Findings (Part 2)
SAC [1]
231
Safety
CP_EG4
Listing of All ECG Values (Part 2)
SAC [1]
232
Safety
CP_EG4
Listing of Change from Baseline in ECG Values (Part 
2)
SAC [1]
233
Safety
CP_EG4
Listing of All ECG Values for Subjects with Any Value 
of Potential Clinical Importance (Part 2)
SAC [1]
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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Liver event
234
Safety
LIVER5
Listing of Liver Monitoring/Stopping Event Reporting 
(Part 2)
SAC [1]
235
Safety
MH3
Listing of Medical Conditions for Subjects with Liver 
Stopping Events (Part 2)
SAC [1]
236
Safety
SU2
Listing of Substance Use for Subjects with Liver 
Stopping Events (Part 2)
SAC [1]
Pharmacokinetics
237
PK
PK08: PKCL1x
Listing of Levocetirizine Plasma Concentration (Part 
2)
SAC [1]
238
PK
PK14: PKPL1x
Listing of Levocetirizine Plasma Pharmacokinetic
Parameters (Part 2)
SAC [1]
11.10.5.7. Non-ICH Listings
Non-ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Palatability Questionnaire
239
Safety
Study Specific 
(EXP_L1)
Listing of Palatability Questionnaire (Part 2)
SAC [1]
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11.11.
Appendix 11: Example Mock Shells for Data Displays
Study specific mock shells are shown only.
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Example: Study Specific (PK_T1)
                 Page 1 of n
Protocol: 204706
Population: PK
Table X.XX
Summary of Bioequivalence Analysis on Pharmacokinetic Parameters (AUC(0-t) and Cmax) (Part X)
Parameter
N
Treatment
n 
Geometric LS Mean
Ratio
[1]
90% CI of the 
Ratio
%CVw
[2]
AUC(0-t)
(hr*ng/mL)
xx
Levocetirizine 
ODT 5 mg 
xx
xxx.xx
xx.xx
(x.xxx, x.xxx)
xx.x
Levocetirizine 
IRT 5 mg
xx
xxx.xx
Cmax (ng/mL)
xx
Levocetirizine 
ODT 5 mg
xx
xxxx.xx
xx.xx
(xx.xxx, 
xx.xxx)
xx.x
Levocetirizine 
IRT 5 mg
xx
xxxx.xx
[1] Ratio = Geometric LS Mean of Levocetirizine ODT 5 mg / Geometric LS Mean of Levocetirizine IRT 5 mg
[2] %CVw = sqrt[exp(MSE) - 1] * 100
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Example: Study Specific (PK_T2)
                 Page 1 of n
Protocol: 204706
Population: PK
Table X.XX
Summary of Bioequivalence Analysis on Pharmacokinetic Parameters (tmax) (Part X)
Parameter
N
Treatment
n 
Median
n 
Median 
Difference
90% CI of the 
Difference
tmax (hr)
xx
Levocetirizine 
ODT 5 mg
xx
xxxx.xx
xx
xx.xx
(xx.xxx, 
xx.xxx)
Levocetirizine 
IRT 5 mg
xx
xxxx.xx
Note: tmax will be analyzed with the non-parametric Wilcoxon Matched Pairs Method (Signed Rank Method) to 
compute point estimate and associated 90% confidence interval for the median difference, Levocetirizine ODT 5 
mg – Levocetirizine IRT 5 mg, using normal approximation.
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Example: Study Specific (PK_F1)
                 Page 1 of n
Protocol: 204706
Population: PK
Figure X.XX
Plot of Levocetirizine Treatment Ratio and 90% CI for Bioequivalence Analysis on PK Parameters
(AUC(0-t) and Cmax) (Part X)
Note: Ratio = Geometric LS Mean of Levocetirizine ODT 5 mg / Geometric LS Mean of Levocetirizine IRT 5 mg
Ratio and 90% CI
AUC(0-t) (hr*ng/mL), Cmax (ng/mL)
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Example: Study Specific (EXP_T1)
                 Page 1 of n
Protocol: 204706
Population: Safety
Table X.XX
Summary of Palatability Questionnaire (Part X)
Questions
ODT 5mg
(N=XX)
Q2. Palatability Rate
n
XX
Mean
x.x
SD
x.xx
Median
x.x
Min.
x
Max.
x
n
x
1 Unacceptable
x (xx%)
2 Neutral/Acceptable
x (xx%)
3 Very good
x (xx%)
Q3. All Description 
Associated
n
x
Bitter
x (xx%)
Chalky
x (xx%)
Fruity
x (xx%)
Medicinal
x (xx%)
Nutty
x (xx%)
Sour
x (xx%)
Sweet
x (xx%)
Q4. Mouth Feel Rate, Q5a. Best Description (Sweetness), Q5b. Best Description 
(Sour/tartness), Q5c. Best Description (Bitter). Summary statistics and frequency 
count with % will be performed for all questions except for Q3.
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Example: Study Specific (EXP_L1)
                 Page 1 of n
Protocol: 204706
Population: SP
Listing X.XX
Listing of Subjects Palatability Questionnaire (Part X)
Treatment/
Site Id./
Unique Subject Id.
Age(y)/
Sex/ 
Race/
Assessor
Q1
Q2
Q3
Q4
Q5
a
b
c
Levocetirizine ODT 
5mg/
 
26/
Male/
White/
Subject
xxx
1:Unaccepta
ble
Sweet, 
Fruity
2:Neutral/Acc
eptable
1
1
3
Levocetirizine IRT 
5mg/
 
39/
Male/
White/
Subject
xxx
2:Neutral/A
cceptable
Bitter
3: Very good
3
2
1
Note:
Q1. Please briefly describe the taste of the product in your own words (one word, short phrase descriptions are acceptable)
Q2. Please rate the palatability (acceptability of taste) of the product by checking a rating.
Q3. Please check all the descriptors that apply to the product. (Multiple Answer allowed)
Q4. Please rate the mouth feel of the product by checking a rating.
Q5. Please circle the number that best describes your perception of each attribute: a=Sweetness b=Sour/tartness c=Bitter
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Example: Study Specific (SP_L1)
                 Page 1 of n
Protocol: 204706
Population: Safety
Listing X.XX
Listing of Subjects Excluded from PK population (Part X)
Treatment/
Site Id./
Unique Subject 
Id.
Age(y)/
Sex/ 
Race
PK 
Population
26/
Male/
White
N
39/
Male/
White
N
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PPD