A Single Dose, Open Label, Randomized Scintigraphic Study to Investigate the Gastrointestinal Behavior of 2 Triple Combination Products (Acetaminophen, Phenylephrine and Dextromethorphan) in Healthy Male Volunteers
Phase: PHASE1
Conditions: Common Cold
Sponsor: GlaxoSmithKline

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Protocol number 208821 
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CLINICAL PROTOCOL
A single dose, open label, randomized scintigraphic study 
to investigate the gastrointestinal behavior of 2 triple 
combination products (Acetaminophen, Phenylephrine and 
Dextromethorphan) in healthy male volunteers
Compound Name:  
Theraflu Daytime Severe Cold & 
Cough powder for oral solution
Theraflu ExpressMax Daytime Severe 
Cold and Cough Caplets
United States (US) Investigational 
New Drug (IND) Number:
N/A
European Clinical Trials Database 
(EudraCT) Number:
NA
Other Regulatory Agency Identified 
Number:
NA
Protocol Number:
 208821
Phase:
I

T herafl u Da yti me Se vere C ol d & C o u g h P o w der f or Oral S ol uti o n / T herafl u E x press Ma x Da yti me Se vere C ol d a n d C o u g h ca plets
Pr ot oc ol n u m ber 2 0 8 8 2 1 
Cli nical Pr ot oc ol  v 2. 0, 2 5 Ja n 2 0 1 8
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
Te m plate Versi o n Effecti ve: 2 2-J u n- 2 0 1 7
Pa ge 2  of 5 6
S p o n s or i nf or m ati o n
S p o ns or Le g al Re gistere d A d dress
Gl a x o S mit h Kli ne Rese arc h & De vel o p me nt 
Li mite d
9 8 0 Great West R oa d
Bre ntf or d
Mi d dlese x, T W 8 9 G S
U K
S p o ns or C o nt act A d dress
Cli nic al St u d y M a n a ger
Gla x o S mit h Kli ne C o ns u mer Healt hcare
St Ge or ge’s A ve n ue, We y bri d ge
S urre y, K T 1 3 0 D E
U K
Cli nic al Rese arc h Scie ntist
Gla x o S mit h Kli ne C o ns u mer Healt hcare
N o vartis C o ns u mer Healt h S. A. 
R o ute de l’ Etraz 2, 1 2 6 9 N y o n
S witzerla n d
P P D
P P D

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Document History
Document
Version Date
Summary of Changes 
Clinical Protocol, v2.0
(Amendment 1)
25-January-2018
Definition of Medical History 
added as a footnote to Table 1-1.
Clarification made to the 
following sections to ensure 
consistency that AEs are collected 
from Informed Consent.
1.
Section 6.2
2.
Section 6.2.2
3.
Section 6.2.1 
4.
Section 7.2.2
5.
Section 8.2.1
Clarification added to Section 
7.2.2 that the cardiovascular 
system will be included in the 
physical examination.
Correction of ‘tobacco’ spelling in 
Section 6.1
Clarification in Section 7.2.7 that 
CRF will capture both results and 
clinically significant findings of 
ECG’s 
Clinical Protocol, v1.0
(Original Protocol)
12-December-2017
Not applicable (N/A)
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc.  

T herafl u Da yti me Se vere C ol d & C o u g h P o w der f or Oral S ol uti o n / T herafl u E x press Ma x Da yti me Se vere C ol d a n d C o u g h ca plets
Pr ot oc ol n u m ber 2 0 8 8 2 1 
Cli nical Pr ot oc ol  v 2. 0, 2 5 Ja n 2 0 1 8
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
Te m plate Versi o n Effecti ve: 2 2-J u n- 2 0 1 7
Pa ge 4  of 5 6
P RI N CI P A L I N V E S TI G A T O R P R O T O C O L A G R E E M E N T P A G E

I c o nfir m a gree me nt t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol a n d a n y 
a me n d me nts a n d acc or di n g t o t he c urre nt I C H G C P g ui deli nes.

I ac k n o wle d ge t hat I a m res p o nsi ble f or o verall st u d y c o n d uct. I a gree t o pers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.

I a gree t o e ns ure t hat all ass ociates, c ollea g ues a n d e m pl o yees assisti n g i n t he c o n d uct of 
t he st u d y are i nf or me d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n place t o e ns ure site staff 
recei ves all a p pr o priate i nf or mati o n t hr o u g h o ut t he st u d y.

I a gree t o c o n d uct t his st u d y i n f ull c o nf or ma nce wit h t he la ws a n d re g ulati o ns of t he 
c o u ntr y i n w hic h t he researc h is c o n d ucte d a n d t he Declarati o n of Helsi n ki.
I n vesti gat or Na me:
Walter J. D oll
I n vesti gat or Q ualificati o ns:
P h. D., R. P h.
I n vesti gat or Si g nat ure:
Date of Si g nat ure/ A gree me nt:
D D/ M M M/ Y Y Y Y
P P D
P P D

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Protocol number 208821 
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Table of contents
Sponsor information ............................................................................................................2
Document History................................................................................................................3
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT PAGE ...............................4
Table of contents..................................................................................................................5
List of tables.........................................................................................................................9
SCHEDULE OF ACTIVITIES .........................................................................................10
1
INTRODUCTION .............................................................................................................12
1.1
Mechanism of Action/Indication ...........................................................................12
1.2
Background and Rationale.....................................................................................12
2
STUDY OBJECTIVES AND ENDPOINTS.....................................................................13
3
STUDY DESIGN AND SUBJECT POPULATION.........................................................14
4
SUBJECT SELECTION....................................................................................................14
4.1
Inclusion Criteria....................................................................................................15
4.2
Exclusion Criteria ..................................................................................................15
4.3
Randomization Criteria..........................................................................................17
4.4
Lifestyle Guidelines...............................................................................................17
4.4.1
Meals and Dietary Restrictions .............................................................17
4.4.2
Alcohol, Caffeine and Tobacco.............................................................18
4.4.3
Activity..................................................................................................18
4.4.4
Contraception ........................................................................................18
4.5
Screen Failures.......................................................................................................19
4.6
Sponsor’s Qualified Medical Personnel.................................................................20
5
STUDY TREATMENTS...................................................................................................20
5.1
Blinding and Allocation to Treatment/Randomization..........................................21
5.2
Breaking the Blind .................................................................................................21
5.3
Subject Compliance ...............................................................................................21
5.4
Investigational Product Supplies............................................................................21
5.4.1
Dosage Form and Packaging.................................................................21
5.4.2
Preparation and Dispensing...................................................................22
5.5
Administration .......................................................................................................22
5.5.1
Medication Errors..................................................................................23
5.6
Investigational Product Storage .............................................................................23
5.7
Investigational Product Accountability..................................................................24
5.7.1
Destruction of Investigational Product Supplies...................................24

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5.8
Concomitant Treatment(s) .....................................................................................25
5.9
Rescue Medication.................................................................................................25
6
STUDY PROCEDURES...................................................................................................25
6.1
Screening................................................................................................................25
6.2
Study Period 1........................................................................................................26
6.2.1
Visit 2: Day -1 .......................................................................................26
6.2.2
Visit 2: Day 1.........................................................................................27
6.3
Subject Withdrawal................................................................................................28
7
ASSESSMENTS................................................................................................................29
7.1
Efficacy..................................................................................................................29
7.2
Safety .....................................................................................................................29
7.2.1
Laboratory Tests....................................................................................29
7.2.2
Physical Examinations...........................................................................31
7.2.3
Height and Weight.................................................................................31
7.2.4
Blood Pressure and Pulse Rate..............................................................31
7.2.5
Respiratory Rate....................................................................................31
7.2.6
Temperature...........................................................................................31
7.2.7
Electrocardiogram .................................................................................32
7.3
Gamma Scintigraphy Measurements and Evaluations...........................................32
7.3.1
Scintigraphic Acquisition......................................................................32
7.3.2
Gamma Scintigraphy Data Analysis .....................................................33
7.3.3
Radioactivity Exposure .........................................................................33
7.4
Blood Volume........................................................................................................34
8
ADVERSE EVENT AND OTHER EVENTS OF SPECIAL INTEREST 
REPORTING.....................................................................................................................34
8.1
Definitions of Adverse Events and Serious Adverse Events.................................34
8.1.1
Adverse Event .......................................................................................34
8.1.2
Serious Adverse Event ..........................................................................35
8.2
Reporting Period ....................................................................................................36
8.2.1
Adverse Event .......................................................................................36
8.2.2
Serious Adverse Event ..........................................................................37
8.3
Reporting Procedures.............................................................................................37
8.3.1
Adverse Event .......................................................................................38
8.3.2
Serious Adverse Event ..........................................................................38

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8.3.3
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees.................................................................................39
8.4
Evaluating Adverse Events and Serious Adverse Events......................................39
8.4.1
Severity Assessment..............................................................................39
8.4.2
Causality Assessment............................................................................40
8.5
Withdrawal Due to an Adverse Event and Serious Adverse Events......................40
8.6
Pregnancy...............................................................................................................40
8.6.1
Time period for collecting pregnancy information ...............................40
8.6.2
Action to be taken if pregnancy occurs .................................................41
8.7
Follow-up of Adverse Events and Serious Adverse Events ..................................41
9
DATA MANAGEMENT ..................................................................................................42
9.1
Source Documents/ Data........................................................................................42
9.2
Case Report Form ..................................................................................................42
9.3
Data Handling ........................................................................................................43
9.3.1
Queries...................................................................................................43
9.4
External Data..........................................................................................................43
10 STATISTICAL CONSIDERATIONS AND DATA ANALYSES...................................44
10.1
Sample Size Determination....................................................................................44
10.2
Statistical Methods and Analytical Plan ................................................................44
10.2.1
Demographic and Baseline Characteristics...........................................44
10.2.2
Scintigraphy Analysis............................................................................44
10.2.3
Safety Analysis......................................................................................45
10.2.4
Definition of Analysis Populations .......................................................45
10.2.5
Exclusion of Data from Analysis ..........................................................45
10.2.6
Handling of Dropouts and Missing Data...............................................45
10.2.7
Interim Analysis ....................................................................................46
11 STUDY GOVERNANCE CONSIDERATIONS..............................................................46
11.1
Quality Control ......................................................................................................46
11.2
Quality Assurance..................................................................................................46
11.3
Regulatory and Ethical Considerations..................................................................47
11.3.1
Institutional Review Board/ Ethics Committee.....................................47
11.3.2
Ethical Conduct of the Study.................................................................47
11.3.3
Subject Information and Consent..........................................................47
11.3.4
Subject Recruitment ..............................................................................48

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11.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ...............................................................................................48
11.4
Posting of Information on Publicly Available Clinical Trial Registers.................48
11.5
Provision of Study Results to Investigators...........................................................49
11.6
Records Retention..................................................................................................49
11.7
Conditions for Terminating the Study ...................................................................50
11.8
Definition of Study End/ End of Study..................................................................50
12 REFERENCES ..................................................................................................................50
13 APPENDIX........................................................................................................................52
13.1
RADIATION DOSIMETRY.................................................................................52
13.2
RADIOLABELING PROCEDURE ......................................................................53
13.3
ABBREVIATION..................................................................................................54

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List of tables
Table 1-1
Schedule of Activities............................................................................10
Table 7-1
Laboratory Tests....................................................................................30
Table 7-2
Blood Volume .......................................................................................34
Table 13-1
Abbreviation..........................................................................................54

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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities, in order to conduct evaluations or assessments required to protect the 
well-being of the subject.
Table 1-1
Schedule of Activities
Screening
Study Period 1
Visit 1
Visit 2
Procedure/Assessment
Day -21 to Day -2
Day -1
Day 1
Informed consent
X
Inclusion/Exclusion criteria
X
X
Medical 
history 
/smoking 
historyh
X
X
Demographics 
X
Prior medications
X
X
Physical examination
Xc
Xc
Xc
Laboratory tests
X
Xd
Urine drug test
X
X
Height & weight
X
Xe
Breath Alcohol test
X
X
Urine Cotinine test
X
X
ECG
X
Scintigraphic imaginga
X
Vital signs 
(BP, PR, RR, oral 
temperature)
Xf
Xf
Xf
Mealsb
X
X
Randomization
X
Study treatment 
administration
X
Concomitant treatments
X
X
X
Adverse eventsg
X
X
X
Study conclusion
X
Abbreviations:  ECG = electrocardiogram; BP = blood pressure; PR = pulse rate, RR = respiratory rate
aScintigraphic acquisitions will be taken beginning after dose administration until 10 hours post-dose. 
b Subjects will be given a standard lunch 4 hours postdose, and a standard dinner at 10 hours post-dose.
c Full physical examination, on screening, on day -1, and brief physical examination on day 1 before randomization 
and another brief physical examination before discharge
dAfter final scintigraphic image is taken prior to dinner.

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e Only weight.
f Vital signs that will be performed at visit 1 and visit 2 (day -1): BP, RR PR and oral temperature.  At visit 2 (day 
1) vital signs that will be performed are only BP and PR and they will be done before randomization and after the 
last scintigraphic image.
g AEs (serious and non-serious) will be collected from the time the subject has signed the informed consent form 
until 5 days following last administration of the investigational product.
h Medical History recorded will be any existing or resolved condition that started prior to Informed Consent. 
Changes in medical history will be assessed at visit 2 (day-1)

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1
INTRODUCTION
The common cold is one of the most frequent human illnesses worldwide (Gwaltney 1994) and, 
although no cure exists, symptoms are treatable. Cold remedies and multi-symptom drug 
combinations are available in a variety of formats, including a hot drink.  Hot drink remedies 
are associated with greater comfort and provide active ingredients in solution. This may result 
in reaching the bloodstream faster and being bioavailable quicker than tablet formulations 
(Hodges 2014). 
Theraflu Daytime Severe Cold & Cough powder for oral solution and Theraflu ExpressMax 
Daytime Severe Cold and Cough caplets are among the commercially available multi-symptom 
formulations available on the market. Theraflu Daytime Severe Cold & Cough powder for oral 
solution contains acetaminophen, phenylephrine and dextromethorphan and is available in 
sachets for reconstitution with hot water. 
Given that absorption of these active ingredients from the stomach is negligible but is rapid and 
significant from the duodenum, (Hengstmann  1982)  (Prescott L. 1996) rapid gastric emptying 
(GE) is a key approach to reducing the delay between drug ingestion and onset of symptom 
control. This clinical study is designed to characterize the gastrointestinal transit of Theraflu 
Daytime Severe Cold & Cough powder for oral solution and Theraflu ExpressMax Daytime 
Severe Cold and Cough caplets using gamma scintigraphy.
External gamma scintigraphy has been used extensively as a noninvasive technique for 
assessing the in vivo performance of drug delivery systems.  It provides information on 
deposition, dispersion and movement of radiolabeled dosage forms.  In this study, gamma 
scintigraphy will be utilized to monitor gastric emptying and intestinal transit of a single 
radioactive marker by radiolabeling the drug formulation.
1.1
Mechanism of Action/Indication
Acetaminophen is an analgesic and antipyretic, its mechanism of action is believed to include 
inhibition of prostaglandin synthesis, primarily within the central nervous system. 
Phenylephrine is a sympathomimetic agent with mainly direct effects on adrenergic receptors 
producing nasal decongestion. Finally, dextromethorphan has an antitussive action, it controls 
cough spasms by depressing the medullary cough centre (GSK Global Data Sheet 2017).
1.2
Background and Rationale
This clinical study will be conducted to characterize the gastrointestinal transit of two multi-
symptoms formulations by inclusion of a radiolabel marker: Theraflu Daytime Severe Cold & 
Cough powder for oral solution and Theraflu ExpressMax Daytime Severe Cold and Cough 
caplets. This study will be the first study to investigate the time of onset and completion of 
gastric emptying as well as small intestine transit time of Theraflu Daytime Severe Cold & 

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Protocol number 208821 
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Cough powder for oral solution and Theraflu ExpressMax Daytime Severe Cold and Cough 
caplets.
2
STUDY OBJECTIVES AND ENDPOINTS
Objective(s)
Endpoint(s)
Gamma Scintigraphy Imaging
Characterize time to onset and time to 
completion 
of 
gastric 
emptying 
after 
administration of either Theraflu Daytime 
Severe Cold & Cough powder for oral 
solution to be reconstituted with 225 ml of 
hot water or Theraflu ExpressMax Daytime 
Severe Cold and Cough  caplets using gamma 
scintigraphic analysis. 
Mean time to onset of gastric emptying in 
healthy male volunteers who did not vomit 
shortly (within 60 minutes) after study drug 
administration, who have sufficient data to 
determine time to onset of gastric emptying 
and who had no major protocol deviations.  
Mean time to complete gastric emptying in 
healthy male volunteers who did not vomit 
shortly (within 60 minutes) after study drug 
administration, who have sufficient data to 
determine time to completion of gastric 
emptying and who had no major protocol 
deviations. 
Further 
characterize 
gastrointestinal 
emptying 
by 
calculating 
additional 
parameters such as but not limited to: a) 
GE25%, GE50%, GE90% values, b) the 
amount remaining in the stomach at 15, 30, 
45, 60, 75, 90, 105, 120, 180, 240 min; c) 
sectional areas under the gastric emptying 
curve and total AUC; and d) gastric emptying 
t1/2 values.
e) Small intestinal transit times which are 
calculated by determining the arrival time of 
the radioactive marker at the cecum / colon 
region and subtracting the gastric emptying 
value.
Safety
To evaluate safety of Theraflu Daytime 
Severe Cold & Cough powder for oral 
Safety assessments consists of monitoring 
and recording adverse events (AEs) and 
laboratory test

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solution and Theraflu ExpressMax Daytime 
Severe Cold and Cough caplets
3
STUDY DESIGN AND SUBJECT POPULATION
This will be an open label, randomized, single dose, parallel group gamma scintigraphy. 
Approximately, forty-two healthy male volunteers will be screened to allow a total of 28 healthy 
male volunteers to be randomized (14 subjects per treatment arm) in order to have 24 evaluable 
subjects (12 subjects per treatment arm). 
Subjects will be randomized to receive either a single dose of Theraflu Daytime Severe Cold & 
Cough powder for oral solution (Treatment A) or a single dose of Theraflu ExpressMax 
Daytime Severe Cold and Cough caplets (Treatment B) under fasted conditions:): 
Treatment A – 12 healthy male volunteers will be administered 1 sachet of Theraflu 
Daytime Severe Cold & Cough radiolabeled powder for oral solution (acetaminophen 650 mg 
+ phenylephrine 10 mg + 20 mg dextromethorphan) reconstituted with 225 mL of hot water
Treatment B – 12 healthy male volunteers will take 2 radiolabeled caplets of Theraflu 
ExpressMax Daytime Severe Cold and Cough (2 caplets each containing acetaminophen 325 
mg + phenylephrine 5 mg + 10 mg dextromethorphan) with 225 mL of room temperature non-
carbonated water.
The study will consist of screening visit (Visit 1), followed by a treatment visit (Visit 2). Visit 
2 includes two days: day -1 and day 1.
The screening visit will assess subject eligibility and consist of relevant medical examinations. 
On visit 2 (day -1) of the study, study participants will be admitted to the unit at approximately 
7 pm on the evening before study drug administration to ensure compliance with fasting 
conditions and will receive a standardized meal. Subjects are required to fast (nothing to eat or 
drink except room temperature non-carbonated water) from 10 hours prior until 4 hours after 
study drug administration. Water is permitted until 1 hour prior to investigational product 
administration, and no additional fluids until the lunch meal is served at approximately 4 hours 
post dose. 
Subjects will be given a standard lunch at 4h post-dose and a standard dinner at 10h post-dose 
on day 1. Subjects will be discharged from the unit after the last scintigraphic imaging is 
performed, blood sample for laboratory test is taken as well as a brief physical examination.
4
SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol. Healthy 

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male volunteers will be recruited. It is essential to ensure they do not suffer from any 
gastrointestinal disorders which could impact on the validity of the scintigraphy data. 
Vegetarians will be excluded from this study as there is evidence that the absorption of 
acetaminophen is impaired in this group of the population (Prescott, 1993). Female subjects 
will be similarly excluded; it has been observed that the menstrual cycle has been associated 
with changes in gastric emptying patterns (Wald, 1981). Subjects with allergies or intolerance 
to one or more ingredients of the standard meal will be excluded. Any subjects with a body 
mass index (BMI) higher than 30.5 kg/m2 will be excluded as shielding caused by bone, muscle, 
other organs and soft tissue will attenuate counts.
4.1
Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
Subjects must meet all the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document indicating that the 
subject has been informed of all pertinent aspects of the study before any assessment is 
performed.
2. Healthy male subjects who, at the time of screening, are between the ages of 21 and 45 
years, inclusive.
3. Subjects who are willing and able to comply with scheduled visits, treatment plan, bio-
imaging procedure, laboratory tests and other study procedures.
4. Healthy subjects which is defined as in general good physical health, as judged by the 
investigator and no clinically relevant abnormalities identified by a detailed medical history, 
full physical examination, including blood pressure and pulse rate measurement, 12-lead 
ECG or clinical laboratory tests. 
5. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
4.2
Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the study:
1. Subjects who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are GSK employees directly involved in the conduct of the 
study.
2. Participation in other studies involving investigational drug(s) within 30 days prior to 
study entry and/or during study participation.

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3. Acute or chronic medical or psychiatric condition or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
4. Known or suspected intolerance or hypersensitivity or contraindication to the study 
materials (or closely related compounds) or any of their stated ingredients. 
5. Subject with known allergy or intolerance to any of the contents of the standard meals.
6. Subject is vegetarian.
7. Unwilling or unable to comply with the Lifestyle guidelines described in this protocol. 
8. Use of prescription or non-prescription drugs and dietary supplements within 14 days or 5 
half-lives, whichever is longer, prior to the first dose of investigational product that are 
deemed by the investigator to have a potential impact on the study objectives results. 
9. Evidence or history of clinically significant laboratory abnormality, hematological, renal, 
endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease 
within the last 5 years that may increase the risk associated with study participation.
10. A positive urine drug screen, breath alcohol test or urine cotinine test during Screening or 
on Day -1 of the study. 
11. Any condition possibly affecting drug absorption (e.g., gastrectomy) 
12. A history of current or relevant previous non-self-limiting gastrointestinal disorders peptic 
ulcer disease and/or gastrointestinal bleeding. 
13. Currently suffering from disease known to impact gastric emptying, e.g. migraine, insulin-
dependent diabetes mellitus.
14. The subject has had radiation exposure from clinical trials, including from the present study, 
and from therapeutic or diagnostic exposure, but excluding background radiation, exceeding 
a target organ (colon) dose of 50 mSv (5 rems) from a single dose within the last 30 days or 
a cumulative dose of 150 mSv (15 rems) in the last 12 months. No subject whose occupation 
requires monitoring for radiation exposure will be enrolled in the study.
15. Subjects who have been exposed to ionising radiation in excess of 10 mSv (whole body 
effective dose) above background over the previous 3 years period as a result of 
occupational exposure or previous participation in research studies.  Clinically justified 
(therapeutic or diagnostic) exposures are not included in this calculation.
16. Renal disease or impaired renal function at screening as indicated by abnormal levels of 
serum creatinine or urea or the presence of clinically significant abnormal urinary 
constituents (e.g. albuminuria).  Minor deviations of laboratory values from the normal 
range are permitted, if judged by the investigator to have no clinical relevance.
17. History or current evidence of ongoing hepatic disease or impaired hepatic function at 
screening. A candidate will be excluded if more than one of the following lab value 
deviations are found: 1) AST/SGOT (≥ 1.2 ULN), ALT/SGPT (≥ 1.2 ULN), 2) GGT (≥ 
1.2 ULN), ALP (≥ 1.2 ULN), 3) total bilirubin (≥ 1.2 mg/dL) Minor deviations of 
laboratory values from the normal range are permitted, if judged by the investigator to 

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have no clinical relevance. Positive results in any of the virology tests for HIV-Ab, HCV-
Ab, HBsAg and HBc-Ab (Total).
18. Diagnosis of long QT syndrome or QTc > 450 msec for males at screening.
19. Subjects who were intending to father a child in the 3 months following the study.
20.  Subjects who were unwilling to follow contraception requirements described in section 
4.4.4.
21. Subject had any non-removable metal objects such as metal plates, screws etc. in their 
chest or abdominal area.
22. History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces 
(150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) 
within 6 months of Screening.
23. Smokers defined as the use of tobacco products (including but not limited to: electronic-
cigarettes, nicotine gums, nicotine lozenges, etc…) during the 6 months prior to screening 
or a positive urine cotinine test at screening.
24. Subject has consumed (eat or drink) grapefruit or grapefruit-related citrus fruits (e.g., 
Seville oranges, pomelos, pawpaw, dragon fruit, kiwi fruit, mango, passion fruit, 
pomegranate, rambutan, star fruit or products that contain these fruits) 14 days prior to the 
first dose of investigational product.
25. Subjects who have previously been enrolled in this study. 
4.3
Randomization Criteria
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria to take 1 sachet of Theraflu Daytime Severe Cold & Cough powder for oral solution or 
2 caplets of Theraflu ExpressMax Daytime Severe Cold and Cough. Randomization schedule 
will be generated by InVentiv Health Clinical (IHC).
4.4
Lifestyle Guidelines
4.4.1
Meals and Dietary Restrictions

Subjects must abstain from all food and drink (except water) at least 4 hours prior to 
any laboratory test evaluations and 10 hours prior to the administration of the 
investigational drug.  Water is permitted until 1 hour prior to investigational product 
administration. 

Water may be consumed without restriction beginning 4 hours after dosing.  
Non-caffeinated drinks (except grapefruit or grapefruit-related citrus fruit juices – see 
below) may be consumed with meals.

Lunch will be provided approximately 4 hours after dosing.

Dinner will be provided approximately 10 hours after dosing after the safety 
laboratory tests are performed.

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
Subjects will not be allowed to eat or drink grapefruit or grapefruit-related citrus fruits 
(e.g., Seville oranges, pomelos, pawpaw, dragon fruit, kiwi fruit, mango, passion fruit, 
pomegranate, rambutan, star fruit or products that contain these fruits) from 14 days 
prior to the first dose of investigational product until collection of the final 
scintigraphic image. 

While confined, the daily caloric intake per subject should not exceed approximately 
3200 kcal. 
4.4.2
Alcohol, Caffeine and Tobacco

Subjects will abstain from alcohol for 72 hours prior to admission to the clinical site 
and continue abstaining from alcohol until collection of the final scintigraphic image. 

Subjects will abstain from caffeine-containing products for 24 hours prior to 
admission to the clinical site until collection of the final scintigraphic image. 
Subjects are non-smokers for the last 6 months before the screening date and they will 
also abstain from the use of tobacco- or nicotine-containing products for 24 hours prior 
to admission to the clinical site and during confinement at the clinical site. 
4.4.3
Activity

Subjects will not be permitted to assume a fully recumbent position for 4 hours 
following dosing except during imaging and other required study procedures.

Subjects will abstain from strenuous exercise (e.g., heavy lifting, weight training, 
calisthenics, aerobics) for at least 24 hours before admission to the clinical site. 
Walking at a normal pace will be permitted.
4.4.4
Contraception
Male subjects able to father children and who are sexually active must agree to use a highly 
effective method of contraception consistently and correctly for the duration of the active study 
period and for at least 3 months after the last dose of investigational product.  Male subjects 
who are not sexually active but become active, must comply with the contraceptive 
requirements as described below .The investigator or his or her designee, in consultation with 
the subject, will confirm that the male subject and female partner of childbearing potential have 
selected an appropriate method of contraception for the individual subject from the permitted 
list of contraception methods (see below) and instruct the subject in its consistent and correct 
use during the informed consent discussion.  Subjects need to affirm that they meet the criteria 
for the correct use of at least 1 of the selected methods of contraception.  The investigator or 
his or her designee will discuss with the subject the need to use highly effective contraception 
consistently and correctly according to the schedule of activities and document such 
conversation in the subject’s chart.  In addition, the investigator or his or her designee will 
instruct the subject to call immediately if the selected contraception method is discontinued or 
if pregnancy is known or suspected in the subject’s partner. 

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Male subject or female partner of childbearing potential to use of one of the highly effective 
methods of contraception are those that, alone or in combination, result in a failure rate of less 
than 1% per year when used consistently and correctly (i.e., perfect use) and include the 
following:
1. Established use of oral, inserted, injected, transdermal, or implanted hormonal methods of 
contraception is allowed provided the subject plans to remain on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness as deemed appropriate by the investigator.
2. Correctly placed copper-containing intrauterine device (IUD). 
3. Male condom used WITH a spermicide (i.e., foam, gel, film, cream, or suppository). 
4. Male sterilization with documented absence of sperm in the post-vasectomy ejaculate.
5. Bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label). 
Female partners of non-childbearing potential must meet at least one of the following criteria 
(medical documentation must be provided):
a. Achieved postmenopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; status may be confirmed by having a serum follicle-stimulating hormone 
(FSH) level confirming the post-menopausal state;  
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
All other female partners (including females with tubal ligations) will be considered to be of 
childbearing potential.
Male subjects should not donate sperm for the duration of the study and for 3 months after the 
last investigational product dose. 
All sexually active male subjects must agree to prevent potential transfer of and exposure to 
drug through semen to their partners by using a condom consistently and correctly, beginning 
with the first dose of investigational product and continuing for at least 3 months after the last 
dose. 
4.5
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized. In order to ensure transparent reporting of screen failure subjects, 
a minimal set of screen failure information will include demography, screen failure details (e.g., 
withdrawal of consent), eligibility criteria, and any serious adverse events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) may not 
be re-screened.

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4.6
Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list and will be provided by the GSK CH Clinical 
Study Manager, which should be filed in the Investigator Site File.
The contact number can be used by investigational staff if they are seeking advice on medical 
questions or problems; however, it should be used only in the event that the established 
communication pathways between the investigational site and the study team are not 
available.  It is therefore intended to augment, but not replace, the established communication 
pathways between the investigational site and the study team for advice on medical questions 
or problems that may arise during the study.  The contact number is not intended for use by the 
subject directly, and if some subject calls that number, he or she will be directed back to the 
investigational site.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card contains, at 
a minimum, protocol identifiers, subject study numbers, contact information for the 
investigational site, and contact details in the event that the investigational site staff cannot be 
reached to provide advice on a medical question or problem identified from the subject’s 
healthcare professional other than the investigator.  
5
STUDY TREATMENTS
The healthy male individuals will be randomized to take either treatment A:  1 sachet of 
Theraflu Daytime Severe Cold & Cough powder (Berry flavor) - (acetaminophen 650mg + 
Dextromethorphan 20mg + Phenylephrine 10mg) or treatment B: 2 caplets of Theraflu 
ExpressMax Daytime Severe Cold and Cough. (each caplet contains: acetaminophen 325 mg + 
Dextromethorphan 10mg + Phenylephrine 5mg). Both products will be commercially sourced 
from local market.
For treatment A:  Individual Theraflu doses are prepared by pouring the contents of the sachet 
into a glass bottle (with cap) and 225 mL of hot, but not boiling water (approximately 90-95°C), 
will be added to the container and mixed to dissolve the contents of the sachet. The dissolved 
Theraflu solution will be allowed to cool to approximately 40 – 50°C. After cooling, a small 
volume (1 to 10 microliters) of 99mTc-DTPA will be added to the drug solution in the preceding 
steps to achieve a maximum of 108 µCi (4 MBq) per individual dose at the time of dosing. The 
container will be capped and maintained at a temperature between 35-45°C until administration. 
For Treatment B: Individual caplet doses are prepared by drilling a hole of approximately 1 
mm diameter and at a depth of approximately one-half of its thickness (~2-2.5 mm deep) into 
individual caplets.  99mTc-DTPA (dissolved in normal saline) will be added into the hole of each 
caplet as a low volume liquid (0.5-2.0 microliters) to achieve a maximum of 54 µCi (2 MBq) 
per individual caplet at the time of dosing (two caplets = 108 µCi (4 MBq) dose per assessment 
visit). The applied liquid will be allowed to air dry and the hole is then filled with the equivalent 

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powder blend from a crushed caplet such that the drug content will remain constant and the 
same for all caplets. The small surface area of the caplet that was altered may be sealed with an 
appropriate material if determined to be necessary. Radiolabeled caplets will be packaged as 
unit doses (2 caplets per container) and maintained at room temperature until administration.
A document describing the radiolabeling procedure of treatment A and B is detailed in 
Appendix 13.2 
For the purposes of this study, and per International Conference on Harmonization (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active ingredient 
being tested or used as a reference in a clinical trial, including a product with a marketing 
authorization when used or assembled (formulated or packaged) in a way different from the 
approved form, or when used for an unapproved indication, or when used to gain further 
information about an approved use (ICH E6 R2 1.33).
5.1
Blinding and Allocation to Treatment/Randomization
Treatments will be provided in an open-label manner.  The investigator’s knowledge of the 
treatment should not influence the decision to enroll a particular subject nor affect the order in 
which subjects are enrolled nor influence the scintigraphy outcomes. Subjects knowing the 
product they are taking will also not affect the scintigraphy outcomes.
GSK CH will provide a randomization schedule to the investigator and, in accordance with the 
randomization numbers, the subject will receive the study treatment regimen assigned to the 
corresponding randomization number.
5.2
Breaking the Blind
Not applicable to this study
5.3
Subject Compliance
Study treatment will be administered under the supervision of investigator site personnel. The 
emptiness of the mouth/tongue and containers will be checked after drug administration. A 
record of the administration of study formulations will be kept using the Dosing Accountability 
Log and the Case Report Form (CRF), any comments on the performance of this procedure 
should be recorded on the CRF. Any violation of compliance will require evaluation by the 
investigator and sponsor to determine if the subject will continue in the study.  
5.4
Investigational Product Supplies
5.4.1
Dosage Form and Packaging
Treatment A, Theraflu Daytime Severe Cold & Cough sachets (acetaminophen 650 mg + 
phenylephrine 10 mg + 20 mg dextromethorphan sachet) and treatment B, Theraflu ExpressMax 
Daytime Severe Cold and Cough caplets (each containing acetaminophen 325 mg + 

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phenylephrine 5 mg + 10 mg dextromethorphan) used in this study will be sourced 
commercially and supplied by GSK CH Global Clinical supply (GCS). 
Treatment A, Theraflu Daytime Severe Cold & Cough powder for oral solution will be supplied 
to the study site in the commercial secondary package containing 6 individual sachets. The 
commercial secondary package will be labeled specifically for this study. 
Treatment B, Theraflu ExpressMax Daytime Severe Cold and Cough caplets will be supplied 
to the study site in the commercial secondary package containing 20 caplets, 2-10 count Blister 
cards. The commercial secondary package will be labeled specifically for this study.
The commercial secondary package labels will include, but not limited to the following 
information: the study number, Treatment or Product name, Batch number, storage conditions, 
expiry date, the appropriate regulatory precautionary information, study site name and the 
sponsor name. 
The manufacturers package information on product drug facts, warnings, directions, expiry, lot 
and storage conditions will not be defaced by the study label. 
The study labels will be in accordance with all applicable regulatory requirements. Labeling 
will be carried out according to cGMP guidelines. Specific study label text for bulk supplies 
will be reviewed and approved internally by the GSK study team and GSK R&D Quality.
Bulk Packaging and labeling of the study products will be the responsibility of the Clinical 
Supply Department, GSKCH, Lincoln, NE, USA.
Care should be taken with the supplied products and their labels so that they are maintained in 
good condition.  It is important that all labels remain intact and legible for the duration of the 
study. The study labels are not to be removed or defaced.
Radiolabeling or individual dose labeling of the study treatments used in this study will be the 
responsibility of Scintipharma.
5.4.2
Preparation and Dispensing 
Radiolabeled Theraflu Daytime Severe Cold & Cough powder for oral solution and Theraflu 
ExpressMax Daytime Severe Cold and Cough caplets will be prepared, labeled and dispensed 
by qualified unblinded site personnel and checked by another independent individual at 
Scintipharma according to the dosage and administration instructions.
5.5
Administration
Following an overnight fast of least 10 hours, subjects will receive investigational product at 
approximately 8 am (plus or minus 2 hours).  Site personnel will administer investigational 
product as follows:
Treatment A: Hot radiolabeled Theraflu solution (225 mL) that will be prepared as described 
in section 5, will be allowed to cool sufficiently to be drinkable at a temperature between 35 

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and 45°C at time of dosing and then subjects will be instructed to consume the hot drink entirely 
within 30 seconds.
Treatment B: 2 radiolabeled caplets will be swallowed with 225 mL of non-carbonated room 
temperature water. All the water (225 ml) should be consumed within 30 seconds.  
Subjects will swallow the investigational product whole, and will not manipulate or chew the 
medication prior to swallowing.
In order to standardize the conditions for scintigraphic imaging, all subjects will be required to 
refrain from lying down (except when required for imaging) and will not be allowed to eat or 
drink beverages (including water) for the first 4 hours after dosing. 
5.5.1
Medication Errors
Medication errors may result, in this study, from the administration or consumption of: 

the wrong product,

by the wrong subject, 

at the wrong time, 

or at the wrong dosage strength (other examples of concern may be added based on 
the investigational product administration, such as inadvertent exposure).  
Such medication errors occurring to a study participant are to be captured in the CRF.  In the 
event of medication dosing error, the sponsor should be notified immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that 
do or do not involve the participating subject.
Whether or not a medication error is accompanied by an AE, as determined by the investigator, 
the medication error and, if applicable, any associated adverse event(s) is captured on AE CRF 
page.
5.6
Investigational Product Storage 
The investigator, or an approved representative, e.g., pharmacist, will ensure that all 
investigational products Theraflu Daytime Severe Cold & Cough powder for oral solution and 
Theraflu ExpressMax Daytime Severe Cold and Cough caplets are stored in a secured area with 
controlled access under required storage conditions and in accordance with applicable 
regulatory requirements and product label.  
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should be 

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captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure that ensures active daily evaluation for 
excursions should be available.  The operation of the temperature-monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure it 
is maintained in working order. 
Any excursions from the product-label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to the storage conditions as 
described in the labeling, as soon as possible.  Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the Sponsor.  
Once an excursion is identified, the investigational product must be quarantined and not used 
until the Sponsor provides documentation of permission to use the investigational product.  It 
will not be considered a protocol deviation if the sponsor approves the use of the investigational 
product after the temperature excursion.  Use of the investigational product prior to sponsor 
approval will be considered a protocol deviation.  Specific details regarding information the site 
should report for each excursion will be provided to the site. 
5.7
Investigational Product Accountability
All products supplied are for use only in this clinical study and should not be used for any other 
purpose.
Study treatments must be received by a designated person at the study sites, handled and stored 
safely and properly, and kept in a secured location to which only the staff have access. Upon 
receipt, all study treatments should be stored according to the instructions specified on the 
treatment labels. Clinical supplies are to be dispensed only in accordance with the protocol. 
Documentation provided with the shipment of study treatments is to be completed by the site 
designated receiver and must be completed and returned to the clinical supplies department as 
specified on the documentation. This documentation consists of a GSK shipping manifest and 
an environmental condition data logger and instruction sheet.  
The investigative site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All study drugs will be accounted for 
using a drug accountability form/record. 
The inventory must be available for inspection by the study monitor during the study. 
Monitoring of treatments accountability will be performed by the field monitor during site visits 
and at the completion of the study.
5.7.1
Destruction of Investigational Product Supplies 
At the termination of the study, all investigational study treatments shipped for this clinical trial 
will be sent by the site to a third-party vendor which will provide a record or certificate of 
destruction. At the conclusion of the study, the Principal Investigator or an appropriate designee, 
and a representative of GSK CH will inventory all used and unused investigational study 
treatment.  

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5.8
Concomitant Treatment(s)
Subjects will abstain from all concomitant treatments, except for those used for the treatment 
of AEs.
All concomitant treatments taken during the study must be recorded with indication, unit dose, 
daily dose, and start and stop dates of administration.  All subjects will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 30 days before the first dose of study investigational product will be 
documented as a prior treatment.  Treatments taken after the first dose of study investigational 
product will be documented as concomitant treatments.
5.9
Rescue Medication 
Not applicable to this study. 
6
STUDY PROCEDURES
6.1
Screening
Subjects will be screened within 21 days prior to administration of the investigational product 
to confirm that they meet the subject selection criteria for the study.  
The following procedures will be completed:

Obtain written informed consent and record in the CRF.

Review Inclusion and Exclusion criteria and record in the CRF.

Collect demography, including year of birth and record in the CRF.

Collect height and weight. The results for each measurement will be recorded in the 
CRF.

Obtain medical history as related to the inclusion/exclusion criteria, including any 
relevant medical or surgical history, allergies or drug sensitivity, history of illegal 
drug, tobacco and alcohol use. Significant findings that are present from Informed 
Consent must be included in the CRF.

Obtain complete medication history of all prescription or nonprescription drugs, and 
dietary and herbal supplements taken within 30 days prior to the planned first dose, 
and record in the CRF.

Obtain supine blood pressure (BP), pulse rate (PR), respiratory rate (RR) and oral 
body temperature. The results for each measurement will be recorded in the CRF.

Conduct full physical examination. Any clinically relevant findings will be noted in 
the medical history CRF page and enrollment will be based upon investigator 
judgement.

Collect single 12-lead electrocardiogram (ECG). Results and any clinically significant 
abnormalities found will be recorded on the CRF.

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
Following at least a 4-hour fast, collect blood and urine specimens for the following, 
and record in the CRF:
Collect urine for drug screening test. Result will be recorded in the CRF.
Collect urine for cotinine test. Result will be recorded in the CRF.
Perform alcohol breath test. Result will be recorded in the CRF
Laboratory test (hematology, clinical chemistry, urinalysis, virology (HIV 
antibodies, HBsAg, anti-HBc (Total), anti-HCV)).
Assess symptoms by spontaneous reporting of AEs and by asking the subjects to respond 
to a non-leading question such as “How do you feel?” Any finding will be recorded on 
CRF
To prepare for study participation, subjects will be instructed on the use of the Lifestyle 
Guidelines and Concomitant Treatment(s) sections of the protocol.
6.2
Study Period 1
For the study visits described below, when multiple procedures are scheduled at the same time 
point(s) relative to dosing, the following chronology of events should be adhered to, where 
possible.
6.2.1
Visit 2: Day -1 
Subjects will be admitted to the clinical site at approximately 7 pm prior to Day 1.  The 
following procedures will be completed following admission to the clinical site:

Review Inclusion and Exclusion criteria and record in the CRF.
Collect weight. The results for each measurement will be recorded in the CRF.
Obtain supine blood pressure (BP), pulse rate (PR), respiratory rate (RR) and oral body 
temperature. The results for each measurement will be recorded in the CRF.

Conduct full physical examination by trained medical personnel at the investigator 
site. Any clinically relevant findings will be noted in the CRF, in the AE section.

Collect urine for drug screening test. Results will be recorded on the CRF.

Collect urine for cotinine test. Result will be recorded on the CRF.

Perform alcohol breath test. Result will be recorded on the CRF

Review changes in the subject’s medical history including medication history since 
Screening.. If the medical history condition worsens, the event will be recorded in the 
CRF, in the AE section.
Assess symptoms by spontaneous reporting of AEs and by asking the subjects to respond 
to a non-leading question such as “How do you feel?” Any finding will be recorded in 
CRF

Collect concomitant medications and record in the CRF.

Provide standardized dinner at around 9 pm.

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Subjects will begin fasting at least 10 hours prior to dosing on Day 1.
6.2.2
Visit 2: Day 1
Prior to randomization, the following procedures will be completed:

Conduct brief physical examination by trained medical personnel at the investigator 
site. Any clinically relevant findings will be noted in the CRF, in the AE section.

Collect supine blood pressure and pulse rate. The results for each measurement will 
be recorded in the CRF.
Assess symptoms by spontaneous reporting of AEs and by asking the subjects to respond 
to a non-leading question such as “How do you feel?” Any finding will be recorded in 
the CRF

Randomization

Administer the investigational product (see Study Treatments and Administration 
Sections). 
After dosing, the following procedures will be completed:
Collect images: A total of 30 image acquisitions will be recorded as follows: Anterior 
supine images will be recorded as 60 second frame acquisitions and recorded at 0-15 
minutes (continuous imaging), 20, 25, 30, 35, 40, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 
2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8, 9 and 10 hrs. A window of ± 2 
minutes will be allowed for each imaging period up to 1 hour (inclusive) and ± 3 minutes 
after 1 hour. The time when each imaging acquisition sequence starts will be recorded 
in source documents as well as the total number of images that have been acquired. 
Additional images may be acquired at the discretion of the investigator.

Record changes in concomitant medication in the CRF.

Assess symptoms by spontaneous reporting of AEs and by asking the subjects to 
respond to a non-leading question such as “How do you feel?” Any finding will be 
recorded in the CRF.

Provide standardized lunch meal 4 hours post dose.

After the last scintigraphic image is performed (~10 hours post dose), collect vital signs 
(BP and PR), blood and urine for laboratory tests and record on the CRF. Conduct brief 
physical examination by trained medical personnel at the investigator site. Any 
clinically relevant findings will be noted in the AE CRF page.

Provide standardized dinner meal after laboratory tests are performed.

Discharge the subject after all study procedures and fill in study completion page of 
CRF.
If a subject has any clinically significant, study-related abnormalities at the conclusion of a 
scheduled inpatient portion of the study, the GSK CH medical monitor (or designated 
representative) should be notified and depending on the abnormality, the subject may be asked 
to remain at the clinical site until such abnormalities are deemed not clinically significant, or it 
is safe for outpatient follow-up.  If the subject is unable or unwilling to remain at the clinical 

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site and/or when outpatient follow-up is deemed appropriate, the GSK CH medical monitor (or 
designated representative) should be so notified, and the investigator should make every effort 
to arrange follow-up evaluations at appropriate intervals to document the course of the 
abnormalities.
6.3
Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or, behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures at a given study site.  
The following circumstances require discontinuation of study treatment and/or premature 
subject withdrawal:

Protocol violation that may impact the outcome of the subject’s safety

Withdrawal of informed consent

Vomiting shortly (within 60 minutes) after study drug administration

Subject lost to follow-up 

Death
If a subject is discontinued or prematurely withdraws from the study, reasons for 
discontinuation or withdrawal and associated date must be documented in the relevant section(s) 
of the CRF. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  The Investigator or site staff should attempt to contact the subject twice.  After two 
attempts, clinical site staff must send a registered letter.  If no response is received from the 
subject, the subject will be considered lost to follow up.  All attempts to contact the subject and 
information received during contact attempts must be documented in the CRF.  In any 
circumstance, every effort should be made to document subject outcome, if possible.  The 
investigator should inquire about the reason for withdrawal, request that the subject return for 
a final visit, if applicable, and follow-up with the subject regarding any unresolved AEs).
Lack of completion of all or any of the early termination procedures will not be viewed as 
protocol deviations so long as the subject’s safety was preserved.
If the subject withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations should be performed and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.

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7
ASSESSMENTS
Every effort should be made to ensure that protocol-required tests and procedures are completed 
as described.  However, it is anticipated that from time to time there may be circumstances, 
outside the control of the investigator that may make it unfeasible to perform the test.  In these 
cases, the investigator must take all steps necessary to ensure the safety and well-being of the 
subject.  When a protocol-required test cannot be performed, the investigator will document the 
reason for the missed test and any corrective and preventative actions that he or she has taken 
to ensure that required processes are adhered to as soon as possible.  The study team must be 
informed of these incidents in a timely manner.
7.1
Efficacy
Not applicable as there are no efficacy assessments.
7.2
Safety
The following safety assessments will be performed at times defined in the Study Procedures 
section of this protocol.  
7.2.1
Laboratory Tests 
Additional laboratory results may be reported on these samples as a result of the method of 
analysis or the type of analyzer used by the clinical laboratory; or as derived from calculated 
values.  These additional tests would not require additional collection of blood.  Unscheduled 
clinical labs may be obtained at any time during the study to assess any perceived safety 
concerns.
Blood and urine Human Biological Samples (HBS) will be collected for safety laboratory tests. 
The volume of individual blood samples collected will be up to 8.5 mL and the volume of 
individual urine samples collected will be up to 50 mL. All samples will be assigned unique 
tracking identifiers.
 
Samples (blood and urine) will be processed, labelled and couriered to the analytical laboratory 
the same day as collection. If a sample is collected and processed on a day when it cannot be 
couriered to the analytical laboratory, the sample will be processed and stored at conditions 
stated in the analytical laboratory sample manual.  Samples will be sent to and tested at Quest 
Diagnostics (1355 Mittel Blvd., Wood Dale, IL 60191, USA). Blood samples will be destroyed 
within 7 days of testing.
 
An aliquot of the urine sample will be taken for drug and cotinine testing at Scintipharma, Inc. 
(1721 Maywick View Lane, Lexington, KY 40504, USA).  Such aliquots will be disposed of in 
the sanitary sewer system within 7 days of testing. Empty urine containers and used test devices 
will be placed in medical waste and destroyed within 3 months of testing.

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All samples will be tracked from collection to destruction on a HBS Tracking Log.
Table 7-1
Laboratory Tests
Hematology
Chemistry
Urinalysis
Virology
Other
Hemoglobin
Hematocrit 
RBC count 
MCV
MCH
MCHC
MPV
Platelet count 
WBC count
Total 
neutrophils 
(Abs)
Eosinophils 
(Abs)
Monocytes 
(Abs) 
Basophils 
(Abs) 
Lymphocytes 
(Abs)
BUN/urea and 
Creatinine
Glucose (fasting) 
Calcium 
Magnesium 
Sodium 
Potassium 
Chloride
Total 
CO2(Bicarbonate)
 AST, ALT
Direct Bilirubin
Total Bilirubin
Alkaline 
phosphatase
Uric acid
Albumin
Total protein
GGT
PT/INR
pH
Glucose (qual) 
Protein (qual) 
Blood (qual) 
Ketones 
Nitrites
Leukocyte 
esterase 
Urine Bilirubin
Specific gravity
Microscopya
HIV-Ab 
HCV-Ab HBsAg 
and HBc-Ab 
(Total) 
Urine drug 
screenb
Breath alcohol
Urine cotinine
Definitions:  RBC= Red blood cell; MCV= Mean corpuscular volume; MCH= Mean corpusuclar 
hemoglobin; MCHC= Mean copusuclar hemoglobin concentration; MPV= Mean platelet volume; 
WBC= White blood cells; BUN=Blood urea nitrogen; HIV-Ab=Human Immunodeficiency Virus, HCV-
Ab=Antibodies Hepatitis C Virus, HBsAg=Surface antigen of Hepatitis B; b
AST= transaminase; ALT= alanine transaminase; PT/INR= prothrombin time/ international normalized 
ratio; GGT= Gamma-glutamyl transpeptidase.
a Only if urine dipstick is positive for blood, protein, nitrites or leukocyte esterase.
b Minimum requirement for drug testing includes: cocaine, THC, opiates/opiods, benzodiazepines and 
amphetamines; to be done at visit 1 and visit 2 (day-1)

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7.2.2
Physical Examinations 
Physical examinations may be conducted by a physician, trained physician's assistant, or nurse 
practitioner as acceptable according to local regulation.  A full physical examination will 
include head, ears, eyes, nose, mouth, skin, and lung examinations, lymph nodes, 
gastrointestinal, musculoskeletal, cardiovascular and neurological systems.  
The brief physical examination will be focused on general appearance, the respiratory and 
cardiovascular systems, as well as towards subject reported symptoms.
Any untoward findings identified on physical exams will be captured as an adverse event, if 
those findings meet the definition of an AE.
7.2.3
Height and Weight 
Height in centimeters (cm) and body weight in kilograms (kg) to the nearest 0.1 kilogram will 
be measured.
For measuring weight, a scale with appropriate range and resolution is used and must be placed 
on a stable, flat surface.  Subjects must remove shoes, bulky layers of clothing, and jackets so 
that only light clothing remains.  They must also remove the contents of their pockets and 
remain still during measurement of weight. 
7.2.4
Blood Pressure and Pulse Rate 
Additional collection times, or changes to collection times of blood pressure and pulse rate will 
be permitted, as necessary at the discretion of the investigator, to ensure appropriate collection 
of safety data.
Supine blood pressure will be measured with the subject’s arm supported at the level of the 
heart and recorded to the nearest mm Hg after approximately 5 minutes of rest.  The same arm 
(preferably the dominant arm) will be used throughout the study.  
The same properly sized and calibrated blood pressure cuff will be used to measure blood 
pressure each time. The use of an automated device for measuring BP and pulse rate is 
acceptable, although, when done manually, pulse rate will be measured in the brachial/radial 
artery for at least 30 seconds.  
7.2.5
Respiratory Rate
Respiratory rate will be measured after approximately 5 minutes rest in supine position by 
observing and counting the respirations of the subject for 30 seconds and multiplied by 2.  When 
blood pressure is to be taken at the same time, respiration measurement will be done during the 
5 minutes of rest and before blood pressure measurement.
7.2.6
Temperature
Temperature will be measured orally. 
No eating, drinking or smoking is allowed for 15 minutes prior to the measurement.

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7.2.7
Electrocardiogram
A standard 12 lead ECG will be performed at screening visit (Visit 1). Interpretation of the 
tracing must be made by a qualified physician or designee and documented on the ECG section 
of the CRF. Each ECG tracing should be labeled with the study number, subject initials, subject 
number, date, and kept in the source documents at the study site. Results and clinically 
significant abnormalities should be reported in the CRF. Clinically significant abnormalities 
should also be recorded on the AE CRF page at the baseline visit. Clinically significant findings 
must be discussed with the GSK CPL prior to enrolling the subject in the study.
Subjects should be in a quiet environment and not speak during the resting period or 
measurement.  Generally, ECGs should not be collected within 3 hours after food or beverage 
consumption.
7.3
Gamma Scintigraphy Measurements and Evaluations
7.3.1
Scintigraphic Acquisition
External gamma scintigraphy has been used extensively as a noninvasive technique for 
assessing the in vivo performance of drug delivery systems. In this study, gamma scintigraphy 
will be utilized to monitor gastric emptying and intestinal transit of a single radioactive marker 
by radiolabeling the drug formulation. The radioactive isotope technetium-99m DTPA (99mTc, 
t½ 6 hr, γ = 140 keV) is added to drug formulation before ingestion. All radiolabeled dosage 
forms will be assayed using a standardized dose calibrator to determine radioactive content. In 
vitro validation tests will be completed to verify that radiolabeling procedures of the caplet do 
not alter dosage form pharmaceutical characteristics. The radiolabeling procedure of the caplet 
will be described in a separate document that will be available before study start, i.e. before 
FSFV.  Since the 99mTc-DTPA is not absorbed, gastrointestinal transit can be monitored using 
a gamma camera that captures images at frequent intervals after administration. Scintigraphic 
imaging will be performed with subjects in the supine position. Except during imaging or while 
conducting other clinical procedures, subjects will remain in the upright position (seated, 
standing or walking) until at least four hours post dose. Subjects will undergo a series of 
consecutive anterior scintigraphic images, each of sixty seconds in duration on Day 1 of each 
period at 0-15 minutes (continuous) and at 20, 25, 30, 35, 40, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.25, 
2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8, 9 and 10 hrs. A window of ± 2 
minutes will be allowed for each imaging period up to 1 hour (inclusive) and ± 3 minutes after 
1 hour.
The drug formulation will be radiolabeled with not more than 108 µCi (4 MBq) of 99mTc-DTPA. 
Prior to ingesting the radiolabeled formulation, two removable external markers (2-3 
microcuries of technetium-99m) will be placed on each subject to facilitate consistent 
positioning underneath the gamma camera. The first marker will be placed on the right side of 
the subject’s chest (approximately at the fifth intercostal rib) and a second marker will be placed 
on the hip bone (approximately the left anterior superior ileac spine). The scintigraphy analysis 
software ScinWin (GammaForge, Louisville, KY) uses these markers to automatically align 
and register the images to the same relative position.  Variations in subject positioning or actual 

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subject movement are thereby corrected facilitating accurate image analysis. Scintigraphic 
imaging will begin immediately following ingestion of the radiolabeled drug formulation using 
a large field of view gamma camera (Siemens BasiCam) equipped with a low energy all-purpose 
parallel hole collimator.  The multi-channel analyzer will be set to 10-15% window and tuned 
to the 140 keV photopeak of 99mTc. 
Scintigraphic data will be recorded and stored electronically using ScinCam image acquisition 
software (GammaForge, Louisville, KY).
7.3.2
Gamma Scintigraphy Data Analysis
 Scintigraphic images will be analyzed in a time-lapse format. Regions of interest (ROI) will be 
drawn to include the stomach, proximal small intestine, distal small intestine and colon 
(SCINWIN, GammaForge, Louisville, KY). Each image will be corrected for radioactive decay 
and background radiation. The primary analysis will evaluate the gastric emptying time and 
first gastric emptying (or time to reach duodenum) and complete gastric emptying time. 
Parameters such as the following will be determined as necessary: time for half of the tracer to 
leave the stomach (T50% gastric emptying, GET50%), small intestine transit time (SITT50%), 
and time for half of the tracer to arrive at the colon (T50% colon arrival, ATC50%). 
7.3.3
Radioactivity Exposure
Each subject will receive a single dose of Treatment A or Treatment B containing the 
radioactive marker Tc-99m-DTPA. The maximum amount of radioactivity to be administered 
to each subject per dose (Treatment A or B) is 108 Ci (4.00 MBq) of 99mTc-DTPA on a 
single occasion. Treatment A will consist of a single dose of up to 108 Ci (4.00 MBq) of 99mTc-
DTPA and Treatment B will consist of two caplets containing up to 54 Ci (2.00 MBq) of 
99mTc-DTPA each for a total of up to 108 Ci (4.00 MBq) of 99mTc-DTPA.
The radiation dose from the administration of a 108 Ci total dose of 99mTc DTPA into the GI 
tract has been calculated (See Appendix 13.1). A total effective dose of up to 0.100 mSv (0.0100 
rems) will be administered.  The additional risk of developing a fatal malignancy as a result of 
this exposure has been estimated as approximately 1 in 200,000 for an adult in normal health. 
(ICRP 2007).
The National Council on Radiation Protection and Measurements (NCRP) indicates that the 
effective dose from natural background radiation which everyone receives per year (excluding 
radon) is about 1 mSv (0.1 rems).  The average annual effective dose from radon alone is 
estimated as 2 mSv (0.2 rems) per year.  The NCRP indicates that larger exposures to more 
limited groups of persons are not especially hazardous, provided they do not occur often to the 
same groups. The NCRP has recommended that the maximum permissible annual effective dose 
be 5 mSv (0.5 rems) for individuals with infrequent exposure to radioactivity (NCRP 1993). 
For workers who are occupationally exposed to radioactivity, the NCRP recommends that the 
effective dose in any 1 year should not exceed 50 mSv (5 rems), which is approximately 
500 times greater than the effective dose that each subject will receive in the present study. 

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The primary target organ (upper colon wall) will receive a maximum dose of 0.458 mSv (0.0458 
rems) for the entire study, which is approximately 100 times lower than the recommended 
maximum amount of radiation exposure to a target organ achieved after a single dose (50 mSv 
or 5 rems) of a radiopharmaceutical, and lower than the annual recommended amount of 
radiation exposure to a target organ (150 mSv or 15 rems), as specified in 21 CFR 361.1. 
To avoid recruitment of radiation workers or serial study volunteers, subjects who have been 
exposed to ionizing radiation exceeding an effective dose of 10 mSv (1 rem) above background 
over the previous 3 year period as a result of occupational exposure or previous participation in 
research studies, not including clinically justified (therapeutic or diagnostic) exposures, will be 
excluded. 
7.4
Blood Volume
The total blood sampling volume for each subject in this study is approximately 54 .5 mL.  The 
table below reflects approximate sample volumes needed for each measured endpoint.  The 
actual collection times of blood sampling may change, but the total blood volume collected will 
not increase.  Additional blood samples may be taken for safety assessments at the discretion 
of the investigator or GSK CH.
Table 7-2
Blood Volume
Sample Volume (mL)
Sample Type
Screening
Study Period
Total Volume (mL)
Safety Labs
33.5
21
54.5
This total volume does not include discarded blood from pre-draws used to remove fluid from flushed 
catheters, if applicable.  
8
ADVERSE EVENT AND OTHER EVENTS OF SPECIAL 
INTEREST REPORTING
8.1
Definitions of Adverse Events and Serious Adverse Events
8.1.1
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant, temporally associated 
with the use of an investigational or washout product or medical device, whether or not 
considered related to the investigational or washout product or medical device.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study treatment.
Events Meeting the AE Definition:  

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
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.
Events NOT meeting the AE definition: 

Any clinically significant abnormal laboratory findings (if applicable) 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 subject’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 subject’s 
condition. 

Medical or surgical procedure (e.g., endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g., appendicitis).

Situations where 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. 
8.1.2
Serious Adverse Event
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 any untoward medical occurrence at any dose that:

Results in death

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;

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
Requires inpatient hospitalization or prolongation of existing hospitalization 

In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred, or was necessary, the AE should be considered 
serious.

Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.

Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption

Results in congenital anomaly/birth defect

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 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.
8.2
Reporting Period
8.2.1
Adverse Event
AEs (serious and nonserious) will be collected from the signing the informed consent and until 
5 days following last administration of the investigational product. For studies that have a run-
in period or washout period, adverse events will be collected from the time the run-in or washout 
period begins. 
Medical occurrences that start after obtaining informed consent will be recorded on the AE 
section of the case report form (CRF) 

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8.2.2
Serious Adverse Event
SAEs assessed as related to study participation (e.g., investigational product, protocol 
mandated procedures, invasive tests, or change in existing therapy) or related to a GSK 
concomitant medication will be recorded from the time a subject provides informed consent, 
which is obtained prior to the subject’s participation in the study, i.e., prior to undergoing any 
study-related procedure and/or receiving investigational product and until 5 days following 
last administration of the investigational product.
SAEs assessed as not related to study participation (e.g., investigational product, protocol 
mandated procedures, invasive tests, or change in existing therapy) or not related to a GSK 
concomitant medication will be recorded from the signing of informed consent and until 5 days 
following last administration of the investigational product. 
8.3
Reporting Procedures
The investigator and any designees are responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up on 
AEs that are serious, considered related to the study treatment or the study, or that caused the 
participant to discontinue the study. 
The investigator is to report all directly observed AEs and all AEs reported by the study 
subject. In addition, each study subject will be questioned about AEs. 
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory, and diagnostics reports) related to the event.
The investigator or site staff will then record all relevant information regarding an AE/SAE 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 instance, all subject identifiers, with the exception of the subject number, will be blinded 
on the copies of the medical records prior to submission to GSK.
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information.  In such cases, the diagnosis will be documented as the 
AE/SAE and not the individual signs/symptoms. Clinical AEs will be described by diagnosis 
and not by symptoms when possible (e.g., upper respiratory tract infection, seasonal allergy, 
etc. instead of runny nose).
Medical conditions reported prior to the time period for reporting AEs/SAEs should be recorded 
as part of the subject’s medical history.

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AEs elicited by the investigator in a standard manner at the study visits should also be recorded 
in the AE section of the CRF. Care will be taken not to introduce bias when detecting AE and/or 
SAE. Open-ended and non-leading verbal questioning of the participant is the preferred method 
to inquire about AE occurrence.
8.3.1
Adverse Event
All AEs will be reported on the AE page(s) of the CRF by the investigator or site staff.  It should 
be noted that the form for collection of SAE information is not the same as the AE CRF.  Where 
the same data are collected, the forms must be completed in a consistent manner.  For example, 
the same AE term should be used on both forms.  AE should be reported using concise medical 
terminology on the CRF as well as on the form for collection of SAE information.
8.3.2
Serious Adverse Event
A paper copy of the SAE form provided in the investigator study master file should be 
completed as fully as possible. 
It is essential to enter the following information: 

Protocol and subject identifiers

Subject’s demography

Description of events, with diagnosis if available

Investigator opinion of relationship to study product 

Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and GSK CH 
assessment of the SAE report:

Date of onset of AE 

Date AE stopped, if relevant

Study product start date

Study product end date if relevant

Action taken on study product

Outcome if known
The SAE form, completed as fully as possible, must be e-mailed to the GSK CH Clinical 
Operations Safety Reporting email box with the study number and subject number in the subject 
line of the email immediately and under no circumstance should this exceed 24 hours after 
study site personnel learn of the event. The investigator will submit any updated SAE data to 
the sponsor, immediately and under no circumstance should this exceed 24 hours of it being 
available. The GSK CH Study Manager should also be notified of the situation by telephone or 
email.

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E m ail Seri o us A d verse E ve nts t o:
T he G S K C H St u d y Ma na ger or desi g nee will be res p o nsi ble f or f or war di n g t he S A E f or m t o 
t he Case 
Ma na ge me nt 
Gr o u p, 
Gl o bal Cli nical Safet y a n d P har mac o vi gila nce 
mail b o x 
(
).
T he i nitial re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q ueste d b y t he 
G S K C H st u d y ma na ger.
8. 3. 3 
S p o n s or’ s R e p orti n g R e q uir e m e nt s t o R e g ul at or y A ut h oriti e s a n d 
Et hi c s C o m mitt e e s
G S K has a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ut h orities a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n.  Pr o m pt 
n otificati o n of S A Es b y t he i n vesti gat or t o G S K is esse ntial s o t hat le gal o bli gati o ns a n d et hical 
res p o nsi bilities t o war ds t he safet y of s u bjects are met.
G S K will c o m pl y wit h c o u ntr y s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g t o 
t he re g ulat or y a ut h orit y, I R B/ E C a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x pecte d seri o us a d verse reacti o ns 
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o 
i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a S A E or ot her s pecific 
safet y i nf or mati o n e. g., s u m mar y or listi n g of S A E) fr o m t he s p o ns or will re vie w a n d t he n file 
it al o n g wit h t he I n vesti gat or’s Br oc h ure a n d will n otif y t he I R B/I E C, if a p pr o priate acc or di n g 
t o l ocal re q uire me nts.
8. 4 
E v al u ati n g A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s
8. 4. 1 
S e v erit y A s s e s s m e nt
T he i n vesti gat or or desi g nee will ma ke a n assess me nt of se verit y f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories:

Mil d:  A n e ve nt t hat is easil y t olerate d b y t he s u bject, ca usi n g mi ni mal disc o mf ort a n d 
n ot i nterferi n g wit h e ver y da y acti vities.

M o derate:  A n e ve nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or mal e ver y da y 
acti vities

P P D
Se vere:  A n e ve nt t hat pre ve nts n or mal e ver y da y acti vities. 
N ote: A n A E t hat is assesse d as se vere will n ot be c o nf use d wit h a n S A E. Se verit y is a cate g or y 
utilize d f or rati n g t he i nte nsit y of a n e ve nt; a n d b ot h A Es a n d S A Es ca n be assesse d as se vere. 
P P D

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For example, a headache may be severe (interferes significantly with the subject's usual function) 
but would not be classified as serious unless it met one of the criteria for SAEs, listed above. 
8.4.2
Causality Assessment
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 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. The 
investigator’s assessment of causality must be provided for all AEs (serious and non-serious); 
the investigator must record the causal relationship in the CRF, as appropriate, and report such 
an assessment in accordance with the SAE reporting requirements if applicable.
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. 
Generally, the facts (evidence) or arguments to suggest a causal relationship should be provided.
The investigator will use clinical judgment to determine the relationship and will also consult 
the Investigator Brochure (IB), Safety Statement and/or Product Information, for marketed 
products, in the determination of his/her assessment.  Alternative causes, such as underlying 
disease(s), concomitant therapy, other risk factors, and the temporal relationship of the event to 
the study product will be considered and investigated.
There may be situations when 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 prior to 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. 
8.5
Withdrawal Due to an Adverse Event and Serious Adverse 
Events
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, according 
to the definition of AE noted earlier, and recorded on the appropriate AE CRF.
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.6
Pregnancy
8.6.1
Time period for collecting pregnancy information
Pregnancy information on female partners of a male subject will attempt to be collected on all 
pregnancies reported 3 months following administration of any investigational product to the 
male subject. Information on pregnancy identified during the screening phase and prior to 
investigational product administration does not need to be collected.

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8. 6. 2  
A cti o n t o b e t a k e n if pr e g n a n c y o c c ur s
T he i n vesti gat or will atte m pt t o c ollect pre g na nc y i nf or mati o n o n a n y fe male part ner of a male 
s u bject, w h o bec o mes pre g na nt w hile partici pati n g i n t he st u d y after a d mi nistrati o n of t he 
i n vesti gati o nal pr o d uct a n d f or u p t o 3 m o nt hs after t he last d ose of t he i n vesti gati o nal pr o d uct. 
T he i n vesti gat or will rec or d pre g na nc y i nf or mati o n o n t he a p pr o priate f or m pr o vi de d b y G S K 
C H a n d s u b mit it t o G S K wit hi n 2 wee ks of lear ni n g of t he fe male part ner of t he male s u bject 
bec o mi n g pre g na nt. T he fe male part ner of a male s u bject will be f oll o we d t o deter mi ne t he 
o utc o me of t he pre g na nc y. I nf or mati o n o n t he stat us of t he m ot her a n d i nfa nt / ne o nate 
(i ncl u di n g c o nc o mita nt me dicati o ns ta ke n b y t he m ot her d uri n g t he pre g na nc y) will be 
f or war de d t o G S K. Ge nerall y, f oll o w- u p will be n o l o n ger t ha n 6 t o 8 wee ks f oll o wi n g t he 
esti mate d deli ver y date. A n y ter mi nati o n of t he pre g na nc y will be re p orte d.
W hile pre g na nc y itself is n ot c o nsi dere d t o be a n A E, a n y pre g na nc y c o m plicati o n or
electi ve ter mi nati o n f or me dical reas o ns will be rec or de d as a n A E or S A E as defi ne d i n 
Secti o n 8. 1.
A s p o nta ne o us a b orti o n is al wa ys c o nsi dere d t o be a n S A E a n d will be re p orte d as s uc h. A n 
S A E occ urri n g i n ass ociati o n wit h a pre g na nc y, br o u g ht t o t he i n vesti gat or’s atte nti o n after t he 
s u bject c o m plete d t he st u d y a n d c o nsi dere d b y t he i n vesti gat or as p ossi bl y relate d t o t he 
i n vesti gati o nal pr o d uct, m ust be pr o m ptl y f or war de d t o G S K. W hile t he i n vesti gat or is n ot 
o bli ge d t o acti vel y see k t his i nf or mati o n i n f or mer st u d y partici pa nts, he or s he ma y lear n of a n 
S A E t hr o u g h re p orti n g.
8. 7 
F oll o w- u p of A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s
P P D
After t he i nitial re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll o w u p wit h eac h s u bject 
a n d pr o vi de f urt her i nf or mati o n o n t he s u bject’s c o n diti o n.
All A Es/ S A Es will be f oll o we d u ntil res ol uti o n, u ntil t he c o n diti o n sta bilizes, u ntil t he e ve nt is 
ot her wise e x plai ne d, or u ntil t he s u bject is l ost t o f oll o w- u p.  
T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as ma y be i n dicate d or as re q ueste d b y G S K t o el uci date as 
f ull y as p ossi ble t he nat ure a n d/ or ca usalit y of t he A E or S A E. T his ma y i ncl u de a d diti o nal 
la b orat or y tests or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt h care pr ofessi o nals.
Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y c o m plete d C R F.
T he i n vesti gat or will s u b mit a n y u p date d S A E data t o G S K wit hi n 2 4 h o urs of recei pt of t he 
i nf or mati o n.
I n vesti gat ors are n ot o bli ge d t o acti vel y see k A Es or S A Es i n f or mer s u bjects.  H o we ver, if 
t he i n vesti gat or lear ns of a n y S A E, i ncl u di n g t he deat h, at a n y ti me after a s u bject has bee n 
disc har ge d fr o m t he st u d y, a n d c o nsi ders t he e ve nt reas o na bl y relate d t o t he i n vesti gati o nal 
pr o d uct or st u d y partici pati o n, t he i n vesti gat or will pr o m ptl y n otif y G S K b y e maili n g t he 
i nf or mati o n t o t he G S K C H Cli nical O perati o ns Safet y Re p orti n g e mail b o x (
). T he G S K C H St u d y Ma na ger or desi g nee will be res p o nsi ble f or 

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Te m plate Versi o n Effecti ve: 2 2-J u n- 2 0 1 7
Pa ge 4 2  of 5 6
f or war di n g t he i nf or mati o n t o t he Case Ma na ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d 
P har mac o vi gila nce gr o u p mail b o x at G S K (
).
T he i n vesti gat or will s u b mit a n y u p date d S A E data t o G S K wit hi n t he desi g nate d re p orti n g ti me 
fra mes.
9  
D A T A M A N A G E M E N T
As use d i n t his pr ot oc ol, t he ter m C R F s h o ul d be u n derst o o d t o refer t o eit her a pa per f or m or 
a n electr o nic data rec or d or b ot h, de pe n di n g o n t he data c ollecti o n met h o d use d i n t his st u d y. 
F or t his st u d y, s u bject data will be e ntere d i nt o a n electr o nic C R F, usi n g a vali date d data s yste m.
9. 1 
S o ur c e D o c u m e nt s/ D at a
T he s o urce d oc u me nts (e. g., h os pital rec or ds, cli nical a n d office c harts, la b orat or y n otes, 
me m ora n da, s u bjects’ diaries or e val uati o n c hec klists, p har mac y dis pe nsi n g rec or ds, rec or de d 
data fr o m a ut o mate d i nstr u me nts, micr ofic hes, p h ot o gra p hic ne gati ves, micr ofil m or ma g netic 
me dia, x-ra ys, s u bject files a n d rec or ds ke pt at t he p har mac y, at t he la b orat or y a n d at t he 
me dic o-tec h nical de part me nts i n v ol ve d i n t he cli nical st u d y) w hic h c o ntai n t he s o urce of data 
rec or de d i n t he C R F s h o ul d be s pecifie d i n Secti o n 6 .  T he C R F ca n be use d as a s o urce 
d oc u me nt at t he discreti o n of data ma na ge me nt.
Eac h s u bject will be assi g ne d a n d i de ntifie d b y a u ni q ue N u m ber. A n y refere nce ma de t o a n 
i n di vi d ual s u bject wit hi n t he st u d y m ust be d o ne usi n g t he u ni q ue Scree ni n g N u m ber.
9. 2  
C a s e R e p ort F or m
P P D
A C R F is a pri nte d, o ptical, or electr o nic d oc u me nt desi g ne d t o rec or d all of t he pr ot oc ol 
re q uire d i nf or mati o n t o be re p orte d t o t he s p o ns or o n eac h trial s u bject.
F or eac h s u bject w h o has gi ve n i nf or me d c o nse nt/asse nt a n d has bee n scree ne d, C R F m ust be 
c o m plete d a n d si g ne d b y t he Pri nci pal I n vesti gat or ( or a ut h orize d desi g nee) t o certif y t hat t he 
data are c o m plete a n d c orrect.  
Ma na ge me nt of cli nical data will be perf or me d i n acc or da nce wit h a p plica ble Ve n d or a n d G S K 
C H sta n dar ds, a n d data clea ni n g pr oce d ures t o e ns ure t he i nte grit y of t he data e. g. re m o vi n g 
err ors a n d i nc o nsiste ncies i n t he data. 
I n or der t o pr otect t he pri vac y of s u bjects, n o Pers o nall y I de ntifia ble I nf or mati o n ( PII) 
(i ncl u di n g t he s u bject's na me or i nitials or f ull birt h date) is t o be rec or de d i n t he C R F or as part 
of t he q uer y te xt.
All C R F pa ges s h o ul d be c o m plete d d uri n g a s u bject assess me nt w he n t he C R F has bee n 
desi g nate d as t he s o urce.  Data t hat is s o urce d else w here s h o ul d be e ntere d i nt o t he C R F i n a n 
a gree d u p o n ti mefra me bet wee n t he I n vesti gat or a n d S p o ns or.  
G S K C H will o btai n a n d retai n all C R Fs a n d ass ociate d st u d y data at t he c o m pleti o n of t he 
st u d y. 

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9.3
Data Handling
Documentation of all data management activities should allow step-by-step retrospective 
assessment of data quality and study performance. 
Any changes or corrections to data will be performed in the Electronic Data Capture (EDC) 
System, and it will include rationale for changes. The EDC system has an audit trail, which will 
provide a complete record of the changes and corrections endorsed by the Investigator.
AEs will be coded using MedDRA (Medical Dictionary for Regulatory Activities) and 
concomitant medications terms (if applicable) using an internal validated medication dictionary, 
GSK Drug.  
9.3.1
Queries
Programmed edit checks will be generated automatically, as the data is being entered into the 
system. Data Management will also run reports and listings on the CRF data, in addition to the 
queries already programmed and generated by the system, to raise manual queries as needed 
for site clarification or correction. The Clinical Dictionary Development and Management 
Group will raise queries as needed on safety data to code the terms (AEs and Drugs) 
appropriately. 
The study monitor at the study site will review the CRFs in accordance with the monitoring 
plan, and any queries will be generated in the EDC System to the Investigator or designee, 
enabling the errors to be addressed in parallel with Data Management review. The study monitor 
can also run reports and listings on the CRFs, to raise manual queries as needed for site 
clarification or correction.
9.4
External Data 
External Data are subject data obtained externally to the CRF. These data are generated from 
laboratory instruments, computers or other sources and then transcribed into a file and format 
agreed upon by GSK CH to identify the subject and time point referenced in the CRF and/or 
protocol. 
An agreed upon quality control process is performed against the transcribed data to the source 
to ensure the accuracy of the transcription. The transcribed data is transmitted in an agreed upon 
format to GSK CH. 
Reconciliation will be performed between the transcribed data and the clinical database to 
ensure subject and time point referenced in the Clinical Database match before Clinical 
Database Freeze (locking of the database) can occur.

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10
STATISTICAL CONSIDERATIONS AND DATA ANALYSES
10.1
Sample Size Determination
Since this study does not have any statistical power, formal sample size calculation has not been 
performed. It is planned to screen approximately 42 subjects to allow a total of 28 subject to be 
randomized to have at least 24 subjects evaluable (12 subject per arm). This is a sufficient 
number to provide descriptive statistics. 
10.2
Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the statistical 
analysis plan (SAP), which will be written following finalization of the protocol and prior to 
study analysis (as appropriate).
10.2.1
Demographic and Baseline Characteristics
Baseline data (i.e. the last available value prior to the start of the treatment phase), relevant 
screening data and demographic characteristics will be summarized for the safety population.
10.2.2
Scintigraphy Analysis
The scintigraphy variables are:

time to onset of gastric emptying for treatment arm A and B.

 time to completion of gastric emptying for treatment arm A and B.

GE25%, GE50%, GE90% values for each treatment A and B, 

 the amount remaining in the stomach at 15, 30, 45, 60, 75, 90, 105, 120, 180, 240 min 
for each Treatment arm A and B 

sectional areas under the gastric emptying curve and total AUC; and gastric emptying 
t1/2 values. 

small intestinal transit times for each treatment arm A and B.
The scintigraphy variables of scintigraphic analysis will be summarized by treatment arm using 
descriptive statistics (mean, minimum, median, maximum and standard deviation, CVs and 95% 
CI for the Means). There are no formal hypotheses being tested in this study.
10.2.2.1 Criteria for assessing Scintigraphy
Use the scintigraphic images to measure the gastric emptying time to onset and completion as 
for treatment arms A and B. 

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10.2.3
Safety Analysis
Safety variables will be summarized for the safety population.
Adverse Event:
Treatment Emergent AEs, i.e. AEs that are emergent or that worsen after the administration of 
treatment arm A or B, will be summarized by presenting, for each treatment, the number and 
percentage of subjects having any AE, any AE in each MedDRA System Organ Class (SOC) 
and having each individual AE. The subset of AEs suspected of a relationship to study drug will 
be presented similarly. All treatment-emergent AEs will also be tabulated by severity. Any other 
information collected (e.g. action taken, duration, outcome) will be listed. Each AE will be 
attributed to the treatment taken most recently before the onset of the AE.
Physical examination
Physical Examination data will be listed with abnormal values flagged.
Laboratory tests:
Laboratory data will be listed with abnormal values flagged.
10.2.3.1 Criteria for assessing safety
Laboratory tests and monitoring of AEs as well as brief physical examination outcomes will be 
used to assess the safety and tolerability of the study products
10.2.4
Definition of Analysis Populations
Scintigraphy analysis population will be conducted on all subjects who received the 
radiolabeled treatments arm A or B and who did not vomit shortly (within 60 minutes) after 
study drug administration, who have sufficient data to determine time to onset and completion 
of gastric emptying and who had no major protocol deviations.
The Safety population will include all subjects who receive a radiolabeled hot drink 
independently if they are included or not in the scintigraphy analysis.
10.2.5
Exclusion of Data from Analysis 
Exclusion of any data from the analyses will be determined during a Data Review Meeting prior 
to database lock. Any reasons for exclusion from an analysis population will be listed, if 
applicable.
10.2.6
Handling of Dropouts and Missing Data 
Subjects who drop out will not be replaced, i.e. their randomization number will not be re-used.

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10.2.7
Interim Analysis 
No interim analysis is planned for this study
11
STUDY GOVERNANCE CONSIDERATIONS
11.1
Quality Control 
In accordance with applicable regulations including GCP, and GSK procedures, GSK or 
designee (i.e. third party vendor) monitors will contact the site prior to the start of the study to 
review with the site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the source 
document.
GSK or designee will monitor the study and site activity to verify that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan on file at 
GSK CH. The investigator (or designee) agrees to allow the monitor direct access to all relevant 
documents and agrees to co-operate with the monitor to ensure that any problems detected in 
the course of these monitoring visits are resolved.
11.2
Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK may conduct 
a quality assurance assessment and/or audit of the site records, and the regulatory agencies may 
conduct a regulatory inspection at any time during or after completion of the study. 
In the event of an assessment, audit or inspection, the investigator (and institution) must agree 
to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant documents and 
to allocate their time and the time of their staff to discuss the conduct of the study, any 
findings/relevant issues and to implement any corrective and/or preventative actions to address 
any findings/issues identified.
The investigator(s) will notify GSK CH or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with GSK CH 
or its agents to prepare the study site for the inspection and will allow GSK CH or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly apply 
copies of the inspection finding to GSK CH or its agent. Before response submission to the 

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regulatory authority, the investigator will provide GSK CH or its agents with an opportunity to 
review and comment on responses to any such findings. 
The sponsor will be available to help investigators prepare for an inspection.
11.3
Regulatory and Ethical Considerations
11.3.1
Institutional Review Board/ Ethics Committee 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, investigator brochure/safety statement 
(including any updates) and other relevant documents, e.g., recruitment advertisements, if 
applicable, from the IRB/EC.  All correspondence with the IRB/EC should be retained in the 
investigator file.  Copies of IRB/EC approvals should be forwarded to GSK CH prior to the 
initiation of the study, and also when subsequent amendments to the protocol are made.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In that 
event, the investigator must notify the IRB/EC and GSK CH in writing immediately after the 
implementation.
11.3.2
Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical Research 
Involving Human Subjects (Council for International Organizations of Medical Sciences 2002), 
guidelines for GCP (ICH 1996 and revision 2), and the Declaration of Helsinki (World Medical 
Association 2013). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws.
11.3.3
Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names or 
other identifiable data in any reports, publications, or other disclosures, except where required 
by laws. 
When study data are compiled for transfer to GSK CH and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSK CH in order to de-identify study subjects. The use of 
initials should be avoided.  
The study site will maintain a confidential list of subjects who participated in the study, linking 
each subject’s numerical code to his or her actual identity.  In case of data transfer, GSK CH 
will maintain high standards of confidentiality and protection of subjects’ personal data 
consistent with applicable privacy laws.

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The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consent documents used during the informed consent process must be reviewed 
and approved by the sponsor, approved by the IRB/EC before use, and available for inspection.
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed.  The investigator will 
retain the original of each subject's signed informed consent document.
11.3.4
Subject Recruitment 
Advertisements approved by IRBs/ECs and investigator databases may be used as recruitment 
procedures.  Use of ethics committee approved, generic, prescreening questionnaire to assess 
basic subject characteristics to determine general eligibility for this study is allowed.  This 
generic questionnaire may be used by sites as a phone script and/or to review internal databases 
to identify subjects.  
GSK CH will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used. 
11.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP 
Within a GSK CH a serious breach is defined as a breach likely to affect to a significant degree 
the safety and rights of a subject or the reliability and robustness of the data generated in GSK 
CH- sponsored human subject research studies. 
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, GSK CH should be informed immediately. 
In addition, the investigator will inform GSK CH immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of any 
serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
11.4
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial registers 
before enrollment of subjects begins in accordance with applicable GSK processes.

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11.5
Provision of Study Results to Investigators
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  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.
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 results summary and for development of 
a manuscript for publication will be in accordance with GSK Policy.
A manuscript will be progressed for publication in the scientific literature if the results provide 
important scientific or medical knowledge.
11.6
Records Retention
Following closure of the study, the investigator must maintain all site study records (except for 
those required by local regulations to be maintained elsewhere), in a safe and secure location.  
The records (study/ site master file) must be maintained to allow easy and timely retrieval, when 
needed (e.g., for a GSK audit or regulatory inspection) and must be available for review in 
conjunction with assessment of the facility, supporting systems, and relevant site staff.
Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g., microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and accurate copy 
of the original and meet accessibility and retrieval standards, including re-generating a hard 
copy, if required.  Furthermore, the investigator must ensure there is an acceptable back-up of 
these reproductions and that an acceptable quality control process exists for making these 
reproductions.
The investigator must assure that the subject’s anonymity will be maintained.  On CRFs or other 
documents submitted to GSK CH, subjects should not be identified by their names or initials, 
but by an identification code. The investigator should keep a separate log of subjects’ codes, 
names and addresses.  Documents not for submission to GSK CH, e.g. subjects’ written consent 
forms, should be maintained by the investigator in strict confidence.
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained by the investigator for 25 years from the issue of the final Clinical Study Report (CSR)/ 
equivalent summary unless local regulations or institutional policies require a longer retention 
period. The minimum retention time will meet the strictest standard applicable to that site for 
the study, as dictated by any institutional requirements or local laws or regulations, GSK 
standards/procedures, and/or institutional requirements.  
No study document should be destroyed without a prior written agreement between GSK CH 
and the investigator. The investigator must notify GSK of any changes in the archival 

T herafl u Da yti me Se vere C ol d & C o u g h P o w der f or Oral S ol uti o n / T herafl u E x press Ma x Da yti me Se vere C ol d a n d C o u g h ca plets
Pr ot oc ol n u m ber 2 0 8 8 2 1 
Cli nical Pr ot oc ol  v 2. 0, 2 5 Ja n 2 0 1 8
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
Te m plate Versi o n Effecti ve: 2 2-J u n- 2 0 1 7
Pa ge 5 0  of 5 6
arra n ge me nts, i ncl u di n g, b ut n ot li mite d t o, arc hi val at a n off-site facilit y or tra nsfer of 
o w ners hi p of t he rec or ds i n t he e ve nt t he i n vesti gat or is n o l o n ger ass ociate d wit h t he site.
1 1. 7  
C o n diti o n s f or T er mi n ati n g t h e St u d y 
Pre mat ure ter mi nati o n of t his st u d y ma y occ ur beca use of a re g ulat or y a ut h orit y decisi o n, 
c ha n ge i n o pi ni o n of t he I R B/ E C, or i n vesti gati o nal pr o d uct safet y pr o ble ms, or at t he discreti o n 
of G S K C H.  
If a st u d y is pre mat urel y ter mi nate d, G S K C H will pr o m ptl y n otif y t he i n vesti gat or.  After 
n otificati o n, t he i n vesti gat or m ust pr o m ptl y c o ntact all partici pati n g s u bjects a n d s h o ul d ass ure 
a p pr o priate t hera p y/ f oll o w- u p f or t he s u bjects.  As directe d b y G S K C H, all st u d y materials 
m ust be c ollecte d a n d all C R Fs c o m plete d t o t he greatest e xte nt p ossi ble. W here re q uire d b y 
t he a p plica ble re g ulat or y re q uire me nts, G S K C H s h o ul d i nf or m t he re g ulat or y a ut h orit y(ies) 
a n d t he i n vesti gat or s h o ul d pr o m ptl y i nf or m t he I R B/ E C a n d pr o vi de t he I R B/ E C a detaile d 
writte n e x pla nati o n of t he ter mi nati o n or s us pe nsi o n. 
If t he I R B/ E C ter mi nates or s us pe n ds its a p pr o val/fa v ora ble o pi ni o n of a trial, t he i n vesti gat or 
s h o ul d pr o m ptl y n otif y t he G S K C H a n d pr o vi de G S K C H wit h a detaile d writte n e x pla nati o n 
of t he ter mi nati o n or s us pe nsi o n. U p o n c o m pleti o n or pre mat ure disc o nti n uati o n of t he st u d y, 
t he G S K C H m o nit or will c o n d uct site cl os ure acti vities wit h t he i n vesti gat or or site staff, as 
a p pr o priate, i n acc or da nce wit h a p plica ble re g ulati o ns i ncl u di n g G C P, a n d G S K C H Sta n dar d 
O perati n g Pr oce d ures
1 1. 8  
D efi niti o n of St u d y E n d/ E n d of St u d y 
St u d y E n d ( S E) date is defi ne d as t he date of t he last s u bject visit of t he last s u bject t o c o m plete 
t he st u d y ( L S L V).  
1 2  
R E F E R E N C E S
[ G walt ne y Jr J M, P hilli ps C D, Miller R D et al, ( 1 9 9 4)] C o m p ute d t o m o gra p hic st u d y of t he 
c o m m o n c ol d. N E n gl J Me d. 3 3 0( 1): 2 5 – 3 0.
[ H o d ges L A & H u g hes A & Tar gett D & D urca n M ( 2 0 1 4)] D oes a H ot Dri n k Pr o vi de Faster 
A bs or pti o n of Paraceta m ol T ha n a Ta blet? A P har mac osci nti gra p hic St u d y i n Healt h y Male 
V ol u nteers. P har m Res ( 2 0 1 4) 3 1: 2 0 7 8 – 2 0 8 5.
[ He n gst ma n n J H, G or o nz y J ( 1 9 8 2)] P har mac o ki netics of H- 3 P he n yle p hri ne i n Ma n. 
E ur o pea n J o ur nal of Cli nical P har mac ol o g y; 2 1 ( 4): 3 3 5- 3 4 1.
[ Presc ott L. Paraceta m ol (aceta mi n o p he n): a critical bi bli o gra p hic re vie w]. L o n d o n: Ta yl or & 
Fra ncis; 1 9 9 6. 
[ Presc ott L F, Y o o vat ha w or n K, Ma kara na n da K et al,  ( 1 9 9 3)]. I m paire d a bs or pti o n of
paraceta m ol i n ve getaria ns. Br J Cli n P h ar m ac ol 1 9 9 3; 3 6: 2 3 7- 2 4 0.
[ Wal d A, T hiel D H V, H oec hstetter et al, ( 1 9 8 1)].
C CI
 Gastr oi ntesti nal tra nsit: t he effect of

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the menstrual cycle. Gastroenterology 1981; 80:1497-1500.
 [National Council on Radiation Protection and Measurements (NCRP) (1993)]. Limitations 
of Exposure to Ionizing Radiation. NCRP Report No 116, Bethesda, MD; 1993]. NCRP 
Publications ISBN#0-929600-30-4.
[ICRP 103 (2007)] vol. 37, 2-4, 2007
[INTEGRATED ADDENDUM TO ICH E6(R1): GUIDELINE FOR GOOD CLINICAL 
PRACTICE E6(R2)]

T herafl u Da yti me Se vere C ol d & C o u g h P o w der f or Oral S ol uti o n / T herafl u E x press Ma x Da yti me Se vere C ol d a n d C o u g h ca plets
Pr ot oc ol n u m ber 2 0 8 8 2 1 
Cli nical Pr ot oc ol  v 2. 0, 2 5 Ja n 2 0 1 8
Gla x o S mit h Kli ne C o ns u mer Healt hcare C o nfi de ntial
Te m plate Versi o n Effecti ve: 2 2-J u n- 2 0 1 7
Pa ge 5 2  of 5 6
1 3  
A P P E N DI X
1 3. 1  
R A DI A TI O N D O SI M E T R Y
C CI
Ma xi m u m esti mate d ra diati o n d ose t o vari o us or ga ns fr o m t he oral a d mi nistrati o n of t he 
f oll o wi n g:

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13.2
RADIOLABELING PROCEDURE
The preparation of the radiolabeled doses will be documented in a detailed dose preparation 
record that is prepared by the study site and offered to the sponsor for review. Example step 
wise procedures are summarized in the following.
Treatment A: Theraflu Solution (will be prepared on visit 2 day 1, maximum 3 hours before 
administration)

Pour the drug powder contents from an individual sachet into a single glass bottle (with 
cap). Confirm transfer of material by weight.

Heat distilled drinking water to approximately 90-95°C and add 225 mL of the heated 
water to the bottle containing the drug powder (confirm the addition of the 225 mL of 
water by weight). Screw the cap onto the bottle and mix to dissolve the contents of the 
sachet. 

Allow the dissolved Theraflu solution to cool to approximately 40-50°C. 

After cooling, a small volume (1 to 10 microliters) of 99mTc-DTPA is added to the 
individual bottles containing the drug solution to achieve a maximum of 108 µCi (4 
MBq) per individual dose at the time of dosing. 

The container is capped, labeled for individual subject use and stored at a temperature 
between 35-45°C until administration.
Treatment B: Theraflu ExpressMax Daytime Severe Cold and Cough Caplet (will be prepared 
up to 18 hours before administration)

Individual caplets are radiolabeled by adding Tc-99m DTPA into approximately the 
center portion of the caplet.

The caplet is oblong, approximately 17.8 mm long, 7.4 mm wide, and 6.0 mm thick. 
The caplet weight is approximately 630 mg. One side the caplet is inscribed with 
“1143D” and the opposite side is blank and has no inscription.

The original caplet weight is determined. On the blank side inscribed, a hole, 
approximately 1 mm diameter is drilled to a depth of approximately one-half of the 
caplet’s thickness (~2-2.5 mm deep). After drilling, the caplet is re-weighed.

Tc-99m DTPA (dissolved in saline) is carefully pipetted into the hole as a low volume 
liquid (approximately 0.5 – 2 microliters) such that the maximum radioactive level does 
not exceed 54 µCi (2 MBq) per individual caplet at the time of dosing. The applied 
liquid is allowed to air dry at room temperature.

The hole is filled with the equivalent powder blend from a crushed caplet. The caplet 
weight is again recorded.

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
The surface area of the filled region of the caplet may be sealed with an appropriate 
material if determined to be necessary.

Radiolabeled caplets are packaged as unit doses (2 caplets per container), labeled for 
individual subject use and stored at room temperature until administration.  
The preparation of the radiolabeled doses will be documented in a detailed dose preparation 
record that is prepared by the study site and offered to the sponsor for review.
13.3
ABBREVIATION
The following is a list of abbreviations that may be used in the protocol. 
Table 13-1
Abbreviation
Abbreviation
Term
AE
adverse event
ALT
alanine transaminase
ALP
alkaline phosphatase
AST
aspartate transaminase
AUC
area under the curve
BMI
body mass index
BP
blood pressure
BPM
beats per minute
BUN
blood urea nitrogen
cGMP
Current good manufacturing practice
CRF
case report form
CV
Coefficient of variation
DCT
data collection tool
99mTc-DTPA
Technetium-99m-diethylene-triamine-pentaacetate
EC
ethics committee
ECG
electrocardiogram
EDC
Electronic data capture
EDTA
edetic acid (ethylenediaminetetraacetic acid)
FDA
Food and Drug Administration (United States)
FSFV
First subject first visit
FSH
follicle-stimulating hormone
GCC
Global Clinical Supplies
GCP
Good Clinical Practice
GE
Gastric emptying
GGT
gamma-glutamyl transpeptidase
GSK CH
GlaxoSmithKline Consumer Health
GSK CPL
GlaxoSmithKline Clinical Pharmacologist 

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Abbreviation
Term
hCG
human chorionic gonadotropin
HDL-C
high density lipoprotein cholesterol
HIV
human immunodeficiency virus
HIV-Ab
Human Immunodeficiency Virus antibody
HCV-Ab
Antibodies Hepatitis C Virus
HBcAg
Core antigen of Hepatitis B
HBsAg
Surface antigen of Hepatitis B
IB
investigator’s brochure
ICH
International Conference on Harmonisation
IHV
InVentiv Health Care
ID
identification
INR
international normalized ratio
IRB
institutional review board
IRC
internal review committee
IUD
intrauterine device
IUS
Intrauterine system
K2EDTA
dipotassium ethylene diamine tetraacetic acid
LDL-C
low density lipoprotein-cholesterol
LFT
liver function test
LSLV
last subject last visit 
MCH
Mean corpuscular hemoglobin
MCHC
Mean corpuscular hemoglobin concentration
MCV
Mean corpuscular volume
MedDRA
medical Dictionary for Regulatory Activities
mSv
millisievert 
N/A
not applicable
NCRP 
national council on radiation protection
PI
principal investigator
PR
pulse rate
PT
prothrombin time
QC
quality control
QTc
corrected QT
RBC
red blood cell
rem
roentgen equivalent man 
RNA
ribonucleic acid
RR
Respiratory rate 
SAE
serious adverse event
SCr
serum creatinine
SGOT
serum glutamic oxaloacetic transaminase

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Abbreviation
Term
SGPT
serum glutamic pyruvic transaminase
SOC
system organ class
SOP
standard operating procedure
SS
safety statement
T1/2
terminal half-life
THC
tetrahydrocannabinol
ULN
upper limit of normal
US
United States
USPI
United States package insert
WBC
white blood cell