Clinical trial NCT03005067
Conditions: Common Cold
Sponsor: GlaxoSmithKline
Start date: 2016-12-29; Completion date: 2017-06-07
Enrollment: 171 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will be conducted in adult participants with symptoms of common cold assessing if 1146A nasal spray reduces the severity of symptoms of the common cold compared to placebo. The study will also evaluate the safety of 1146A compared to placebo.

Detailed description:
This will be a multi-center, randomized, parallel-group, double blind, 2-arm, placebo controlled study to evaluate the efficacy and safety of 1146A in adult participants with symptomatic common cold in an outpatient setting.

Arms: arm 1: Participants will be administered test product (nasal spray) containing carbomer 980 gel. Three actuations per nostril per dose will be applied, each actuation will be 140µL (microliters) i.e. equivalent to 140mg. arm 2: Participants will be administered reference product (nasal spray) containing vehicle without carbomer 980. Three actuations of placebo nasal spray per nostril per dose; each actuation will be 140µL.
Interventions: intervention 1: Carbomer 980 (1146A) intervention 2: Placebo
Intervention descriptions: intervention 1: Test product containing carbomer 980 gel intervention 2: Reference product containing vehicle without carbomer 980 gel

Protocol documents:
Prot_000.pdf: 
Clinical Protocol
205684
 
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2
CONFIDENTIAL
SUMMARY INFORMATION
Title:
A Randomized, Parallel-Group, Placebo-Controlled, 
Double-BlindStudy to Evaluate the Efficacy and 
Safety of 1146A Nasal Spray in Adult Subjects with 
Symptoms of Common Cold 
Protocol Number:
205684
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)
184 Liberty Corner Road, Warren, NJ 07059 USA
Tel: 
Product Name:
1146A(Carbopol®980 Gel Nasal Spray)
Development Phase:
Phase II/III
Expert Advice Outside of Normal 
Working Hours:
Tel: 
Key Protocol Authors:
PRIMARY CONTACT
Clinical Study Manager:
184 Liberty Corner Road
Warren, NJ 07059 USA
Tel:
Fax: 
Biostatistician:
St. George’s Avenue, Weybridge, 
Surrey184 LIBERTY CORNER ROAD
WARREN, NJ 07059 USA
KT13 0DE, UK
Tel: 
 
Clinical Lead:
 PharmD
184 Liberty Corner Road, Warren, NJ 
07059 USA
Tel:
Other Protocol Authors:
Clinical Supplies:
 
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Data Manager:
Medical Expert:
, MD
Principal Investigator:
Multicenter
Study Site Name & Address:
Multicenter
Study Site Telephone Number:
Multicenter
Analytical Laboratory:
Attn: Specimen Mgmt/
PPD Bioanalytical Lab
2244 Dabney Road
Richmond, VA 23230-3323
United States
Tel: 
Fax: 
Regulatory Agency IdentifierNumber 
(if applicable):
 
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4
PRINCIPAL INVESTIGATORPROTOCOL AGREEMENT 
PAGE
I confirm agreement to conduct the study in compliance with the protocol and 
any amendments and according to the current ICH GCP guidelines.
I acknowledge that I am responsible for overall study conduct. I agree to 
personally conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the 
conduct of the study are informed about their obligations. Mechanisms are in 
place to ensure site staff receives all appropriate information throughout the 
study.
I agree toconduct this study in full conformance with the laws and regulations 
of the country in which the research is conducted and the Declaration of 
Helsinki.
InvestigatorName:
InvestigatorQualifications:
InvestigatorSignature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
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Table of Contents
SUMMARY INFORMATION...............................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE..............................................................................4
PROCESS FOR AMENDING THE PROTOCOL...............10
PROTOCOL AMENDMENT PAGE....................................11
SCHEDULE OF EVENTS.....................................................14
PROTOCOL SYNOPSIS FOR STUDY 205684...................16
1. INTRODUCTION...............................................................26
2. OBJECTIVES AND ENDPOINTS....................................27
3. STUDY PLAN.....................................................................28
3.1. Study Design.......................................................................28
3.2. Subject Restrictions...........................................................33
3.3. Type and Planned Number of Subjects............................34
3.4. Study Design and Dose Justification.................................35
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA........................................36
4.1. Inclusion Criteria...............................................................36
4.2. Exclusion Criteria..............................................................37
4.3. Screening/ Baseline Failures..............................................39
4.4. Women of Childbearing Potential Definition...................40
4.5. Withdrawal/ Stopping Criteria.........................................40
4.6. Subject Replacement..........................................................41
4.7. Subject and Study Completion..........................................41
5. PRODUCT INFORMATION.............................................42
5.1. Study Product.....................................................................42
 
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5.2. Dose Schedule.....................................................................43
5.2.1. Instructions for use of the medical device........................43
5.2.2. Dosing................................................................................44
5.3. Dose Modification..............................................................45
5.4. Product Compliance..........................................................45
5.5. Precautions.........................................................................45
5.6. Overdose.............................................................................45
5.7. Rescue Therapy..................................................................46
5.8. ProductAssignment...........................................................46
5.8.1. Randomization..................................................................46
5.8.2 Blinding...............................................................................47
5.8.3 Code Breaks........................................................................47
5.9. Packaging and Labelling...................................................48
5.9.1. Accountability of Product.................................................48
5.9.2. Storage of Product............................................................49
6. STUDY ASSESSMENTS AND PROCEDURES..............49
6.1. Visit 1 –Screening Visit (Day 1)........................................50
6.1.1. Informed Consent.............................................................50
6.1.2. Demographics....................................................................50
6.1.3. Medical History and Prior Medication............................50
6.1.4. Physical Examination........................................................51
6.1.5. Vital Sign Assessments......................................................51
6.1.6. Nasal Examination............................................................52
6.1.7. Self-Assessment of Common Cold Signs & Symptoms by 
Subjects.............................................................................52
6.1.8. Pregnancy Test..................................................................53
6.1.9. Urine Drug Screening Test...............................................53
6.1.10. Inclusion/Exclusion Criteria...........................................53
6.1.11. Randomization................................................................54
6.1.12. Safety Monitoring............................................................54
 
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6.2. Visit 1 -Treatment Phase Visit (Day 1)............................54
6.2.1. Dispense E-diary...............................................................54
6.2.2. Self-Assessment of Common Cold Symptoms.................54
6.2.3. Nasal Swab Sample...........................................................54
6.2.4. Study Treatment Dispensation, Priming of 1stDevice, and 
Instructions for Use..........................................................55
6.2.5. FirstAdministration of Study Treatment........................55
6.2.6. Safety Monitoring.............................................................55
6.2.7. Concomitant Medication..................................................55
6.2.8. Instructions for Treatment Continuation at Home.........56
6.3. Treatment Continuation and at Home Procedures (Days 2-
7).......................................................................................56
6.3.1. Self-Assessment of Common Cold Symptoms by Subjects
............................................................................................56
6.3.2. Administration of Study Treatment.................................56
6.3.3. Safety Monitoring.............................................................56
6.3.4. Concomitant Medication..................................................56
6.4. Visit 2 –End of Study /Early Termination (Day 8)..........57
6.4.1. Self-Assessment of Common Cold Symptoms.................57
6.4.2. Physical Examination........................................................57
6.4.3. Vital Sign Assessments......................................................57
6.4.4. Nasal Examination............................................................57
6.4.5. Pregnancy Test..................................................................57
6.4.6. Return of Study Treatment Devices and Subject E-diary
............................................................................................57
6.4.7. Concomitant Medication..................................................58
6.4.8. Safety Monitoring.............................................................58
6.4.9. Early Termination/ Premature Subject Withdrawal......58
6.4.10. Study Conclusion.............................................................58
7. SAFETY ASSESSMENTS..................................................59
 
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7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................59
7.1.1. Adverse Events..................................................................59
7.1.2. Serious Adverse Events.....................................................60
7.2. Recording Adverse Events and Serious Adverse Events.61
7.3. Evaluating Adverse Events and Serious Adverse Events61
7.4. Reporting Adverse Events and Serious Adverse Events..62
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................64
7.6. Collection of PregnancyInformation................................65
7.6.1. Time Period for Collecting of Pregnancy Information...65
7.6.2. Action to be Taken if Pregnancy Occurs.........................66
8. DATA MANAGEMENT....................................................66
8.1. Source Documents/ Data....................................................66
8.2. Electronic Case Report Form............................................67
8.3. Data Handling....................................................................67
8.3.1. Data Queries......................................................................68
8.4. Processing Patient Reported Outcomes............................68
8.5. External Data.....................................................................68
9. STATISTICALCONSIDERATIONS AND DATA 
ANALYSES....................................................................69
9.1 Sample Size Determination.................................................69
9.2. General Considerations.....................................................70
9.2.1. Definition of Analysis Populations...................................70
9.2.2. Exclusion of Data from Analysis......................................70
9.2.3. Criteria for Assessing Efficacy.........................................71
9.2.4. Criteria for Assessing Safety............................................71
9.2.5. Handling of Dropouts and Missing Data.........................71
9.2.6. Other Issues.......................................................................72
 
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9.3. Statistical Methods and Analytical Plan...........................72
9.3.1. Demographic and Baseline Characteristics.....................73
9.3.2. Primary Analysis...............................................................73
9.3.3. Secondary Analyses...........................................................74
9.3.4. Safety Analyses..................................................................74
9.3.5. Other Analyses..................................................................75
10. STUDY GOVERNANCE CONSIDERATIONS.............76
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................76
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................76
10.3. Quality Control (Study Monitoring)...............................76
10.4. Quality Assurance............................................................77
10.5. Conditions for Terminating the Study............................77
10.6. Records Retention............................................................78
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................79
11. REFERENCES..................................................................81
12. APPENDICES...................................................................83
12.1. Appendix 1 -Abbreviations.............................................83
12.2. Appendix 2 -Subject Instructions for Use......................85
 
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10
PROCESS FOR AMENDING THE PROTOCOL
Protocol modifications to ongoing studies which could potentially adversely affect the 
safety of subjects or which alter the scope of the investigation, the scientific quality of 
the study, the experimental design, dosages, duration of therapy, assessment 
variables, the number of subjects treated, or subject selection criteria are considered 
major/substantial amendments and must be made only after appropriate consultation 
between an appropriate representative of GSKCH and the Investigator.
Details of amendments to the protocols should be recorded on the following page. 
Protocol modifications must be prepared by a representative of GSKCH. All changes 
must be justified in the Reason for Amendment section of the following Protocol 
Amendment Page. Approval of amendments will be made by the original protocol 
signatories or their appropriate designees.
All major/substantial protocol modifications must be reviewed and approved by the 
appropriate IRBin accordance with local requirements, before the revised editioncan 
be implemented. 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IRBas per country specific requirements. In some countries pre-approval of a minor 
amendment is not required and will just be held on file by the sponsor and 
Investigator.
 
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PROTOCOL AMENDMENT PAGE
Details of all amendments should be recorded in the table below. Affected sections should be listed in the table; the actual 
amendment/ change should be made in the relevant section of the main protocol. 
To highlight the change, the following features will be used: 
To addtext: Use of CAPITAL LETTERS, BOLD AND UNDERLINE
To delete text:Use of Strikethrough e.g. strikethrough
Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for Amendment
Other 
Documents 
Requiring 
Amendment
Section(s) Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:1
Non-Substantial/Minor    During application, the 
device should be held 
between the index and 
middle fingers, not the index 
and ring fingers.  
Informed 
Consent   
Yes No
Safety 
Statement     
Yes No
CRF                       
Yes No
Appendix 2-Subject 
Instructions for Use, 
Step 5; Section 
5.2.1. 
Signature:
Protocol 
Version 
No.:1.02.0
Substantial/ Major           
Date:
Amendment 
No.:2
Non-Substantial/Minor    The head should be tilted 
forward slightly when 
inserting the nasal applicator 
into the nostril. 
Informed 
Consent   
Yes No
Safety 
Statement     
Yes No
CRF                       
Yes No
Appendix 2-Subject 
Instructions for Use, 
Step 5; Section 
5.2.1.
Signature:
Protocol 
Version 
No.:2.03.0
Substantial/ Major           
Date:
 
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Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for Amendment
Other 
Documents 
Requiring 
Amendment
Section(s)Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:3.0
Non-Substantial/Minor    1. The eligibility criteria for 
common cold symptom 
onset was changed from 
48 hours to 72 hours
2. A recent history of 
alcohol or other 
substance abuse within 
the past 5 years was 
changed to 1 year
3. Clarified how urine drug 
screen results would be 
documented in the CRF
4. Additional wording 
included regardingthe 
statistical impact of 
subjects with common 
cold between >48 and 
<72 hours and that it 
mightbe reviewed 
5. Date and time of 
symptom onset will be 
captured in the CRF
Informed 
Consent   
Yes No
Safety 
Statement     
Yes 
No
CRF                       
Yes 
No
1. Schedule of 
Events, Protocol 
Synopsis, Section 
3.1 Study Design, 
Section 3.3 Type 
and Planned 
Number of 
Subjects, Section 
4.1 Inclusion 
Criteria-6, Section 
6.1.7 Self-
Assessment of 
Common Cold 
Signs & 
Symptoms by 
Subjects
2. Section 4.2. 
Exclusion criteria-
6A
3. Section 6.1.9 
Urine Drug 
Screening Test
4. Protocol Synopsis, 
9.3.2 Primary 
Analysis
5. Section 6.1.7 Self-
Signature:
Protocol 
Version 
No.:4.0
Substantial/ Major           
Date:
 
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Assessment of 
Common Cold 
Signs & 
Symptoms by 
Subjects
Amendment 
No.:4
Non-Substantial/Minor    1. Sample size has been 
lowered due to recent 
awareness of publications 
with studies employing 
the use of products with 
similar purported 
mechanisms of actions
2. Clarification that freezer 
temperatures can be 
below -70°C
Informed 
Consent   
Yes No
Safety 
Statement     
Yes 
No
CRF                       
Yes 
No
1. Protocol Synopsis, 
Section 3.1 Study 
Design, Section 
3.3 Type and 
Planned Number 
of Subjects, 
Section 9.1 
Sample Size 
Determination, 
Section 11 
References
2. Section 6.2.3 
Nasal Swab 
Sample
Signature:
Protocol 
Version No.:
5.0
Substantial/ Major           
Date:
 
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SCHEDULE OF EVENTS
PROCEDURE
VISIT 1
(Day 1)
AT HOME 
PROCEDURES
(Days 2-7)
VISIT 2
(Day 8)
a
Screening
Treatment Phase
End of study 
or early 
termination
Written informed consent
X
Demographic data
X
Medical history
X
Record prior & concomitant medications 
and non-drug treatments/ procedures
X
X
X
X
Common cold symptom assessmentb
X
Vital signsc
X
X
Physical examination
X
X
Nasal examination 
X
X
Urine drug screen
X
Urine pregnancy testd
X
X
Inclusion/exclusion criteria
X
RANDOMIZATIONe
X
Dispense & train subjects on e-diary 
X
Self-assessment of common cold 
symptoms in subject e-diaryf
X
X
X
Nasal swab sampleg
X
Instruct subjects on proper use of study 
treatmenth
X
Dispense & prime 1ststudy device 
X
Study treatmentadministrationi
X
X
Collect subject e-diary
X
SAE and AEassessmentandrecordingj
X
X
X
X
Study conclusionk
X
a.
Subjects who discontinue study treatmentbefore completing the study and those who prematurely 
withdraw from the study for any reason should undergo end of study visit procedures in-clinic as 
soon as possible.
b.
Subjectswill self-evaluate and grade their common cold symptoms using a 4-point scale(See 
Section 6.1.7.for more details). Only subjects meeting all eligibility criteria including the following 
criteria will be enrolled into the study: 
1.
Aconfirmed common cold diagnosis with symptoms <4872 hours;
2.
TSS >9 (baseline sum of the 8 common cold symptoms described in Section 6.1.7.);
3.
Score >1 for at least one of the following symptoms: sore throat, runny nose, or blocked 
nose.
 
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The Investigatorwill confirm a common cold diagnosis.This will be collected in thecase report 
form (CRF). 
c.
Vitals will include blood pressure, pulse rate, respiratory rate, oral body temperature and height and 
weight measurements. Height and weight will only be collected during Screening.
d.
Only female subjects of childbearing potential.
e.
Site staff will stratify and randomize eligible subjects to one of the two treatment arms by 
contactinginteractive response technology (IRT).
f.
Self-assessment of common cold symptoms using a 4-point scale (See Section 6.1.7. for more 
details) will be recorded in the subject e-diary immediately prior to the first dose at Baseline, 
immediately prior to each subsequent dose, and the morning of Day 8upon awakening.
g.
Nasal swab samplewill be obtainedfrom each subject after randomization and self-assessment of 
common cold symptoms mentioned above for possible future virological analysis. 
h.
Independentsite personnel,who will have no other responsibilities during the study,will then 
instruct subjects on proper use, priming and administration technique of study treatment. Subjects 
will be instructed to dose for the full seven days irrespective of symptom resolution to avoid 
inappropriate discontinuation due to misinterpretation of reduced symptomatology as a result of the 
fluctuation of symptoms that occurs with a common cold. Subjects will also be instructed to change 
to a new study treatmentdevice every 2 days and to prime the new device prior to the morning 
dose. 
i.
Dosing administration is 3 actuations per nostril per dose, four times a day for 7 days.  Subjects will 
beinstructed to alternate nostrils after each actuation.  First administration of study treatmentwill 
occur at the study site by independent site personnel supervisionthatwill have no other 
responsibilities during the study; first dosing can occur any time prior to 13:00. Subject
randomizationwill be stratified by dosing time on Day 1 by those study subjects receiving first 
dose of study treatmentbetween the hours of 8:00-11:00 and those receiving first dose of study 
treatmentbetween the hours 11:01-13:00.  On Day 1, subjects dosing between 8:00-11:00 will dose 
every 4 hours ± 30 minutes for 4 dosesand subjects dosing between 11:01-13:00 will dose every 4 
hours± 30 minutesfor 3 doses.On Days 2-7 all subjects will administer their initial morning dose 
immediately following recording of their common cold symptom assessment at 07:00 ±2 hours and 
the remaining 3 doses every 4 hours ± 30 minutes. Dosing times and number of actuations will be 
recorded in subject’s e-diary.
j.
Any serious adverse event assessed as related to study participation that occurs subsequent to the 
signing of informed consent and any adverse event that occurs subsequent to the first dose will be 
recorded.
k.
Study conclusion will occurat the Investigator’s discretion once all study procedures are complete.
 
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PROTOCOL SYNOPSIS FOR STUDY 205684
Brief Summary
This study,to be conducted in adult subjects with symptoms of common cold, is 
designed to assess if 1146A nasal spray reduces the severity of symptoms of the 
common coldcompared to placebo.The study will alsoevaluate thesafety of 1146A
compared to placebo.
The study will be conducted at multiplesitesand will be funded by GlaxoSmithKline 
Consumer Healthcare (GSKCH).
Objectives and Endpoints
Objectives
Endpoints
Primary
To assess the efficacy of 1146A 
in reducing the severity of nasal 
symptomson days 1-4, using the 
average nasal symptom score, 
compared to placebo in adult 
subjects with the common cold
Average nasal symptom score 
Days 1-4(ANSS 
1-4)
Secondary
Efficacy
To assess the efficacy of 1146A 
in reducing the severity of nasal 
symptoms on days 1-7, using the 
average nasalsymptom score, 
compared to placebo in adult 
subjects with the common cold
Average nasal symptom score 
Days 1-7(ANSS 
1-7)
To assess the efficacy of 1146A 
in reducing the severity of 
symptomson days 1-4 and days 
1-7, using the total symptom 
score, compared to placebo in 
adult subjects with the common 
cold 
Average total symptom score 
Days 1-4(ATSS 
1-4)
Average total symptom score 
Days 1-7(ATSS 
1-7)
Safety
Adverse events
Spontaneous and solicited adverse 
events and serious adverse events
Exploratory
To assess the efficacy of 1146A 
in reducing the severity of 
Individual & composite total 
symptom scores [nasal symptom 
 
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individual symptoms, using the 
individual symptom score, 
compared to placebo in adult 
subjects with the common cold 
score (NSS) and total symptom 
score (TSS)] Days 1-7
Study Design
Overall Design
This is a multi-center, randomized, parallel-group, double blind, 2-arm, placebo-
controlled study to evaluate the efficacy and safety of 1146A ( 
 carbomer 980 gel 
nasal spray) in adult subjects with symptomatic common coldin an outpatient setting. 
At Screening (Day1, Visit 1), subjects with symptoms consistent with symptomatic 
common cold of a ≤4872hourduration will provide written informed consent to be 
enrolled into the study. During this visit,subjects will undergo eligibility screening, 
which includes: assessment of common cold symptoms and diagnosis by the 
Investigator;review of demographics, medical and medication history; vital sign 
assessments (blood pressure, pulse rate, respiratory rate,oral body temperature, 
height and weight measurements); physical examination;Investigator-led nasal 
examination; urine pregnancy test (only female subjectsof childbearing potential); 
and urine drug screen.
Only subjects meeting all eligibility criteria including the following symptomatic 
common cold symptoms will be enrolled into the study: 
1. A confirmed common cold diagnosis with symptoms <4872hours; 
2. TSS >9 (baseline sum of the 8 common cold symptoms described in 
Section6.1.7.);
3. Score >1 for at least one of the following symptoms: sore throat, runny 
nose, or blocked nose). 
Approximately 300170eligible subjectswill be stratified and randomized to 
treatment with 1146A nasal spray or placebo (vehicle, nasal spray) in a 1:1 ratio at 
multiplesites. All sites should make an effort to enroll approximately equal number 
of males and females into the study.The study siteswill stratify and randomize 
qualified subjects using IRT.
Study site personnel will dispense and train subjects on the e-diaryandsubjects will 
then perform their baseline self-assessment of commoncold symptomsin their e-
 
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diary. Independentsite personnel, who will have no other responsibilities during the 
study,will then instruct subjects on proper use, priming andadministration technique 
of study treatment. Subjects will be instructed to dose for the full seven days 
irrespective of symptom resolution to avoid inappropriate discontinuation due to 
misinterpretation of reduced symptomatology as a result of the fluctuation of 
symptoms that occurs with a common cold. Subjects will also be instructed to change 
to a new study treatmentdeviceevery 2 days and to prime the new deviceprior to the 
morning dose. The independent site personnel will then dispensethe devices and 
demonstrate how to primethe devices by priming the first device. They will then 
monitor eligiblesubjectswhile thesubjectadministersthe first dose of study 
treatment. 
Study treatmentwill be administered via a nasal spray device (1 dose =3 actuations
per nostril, each actuation is 140L). Dosing administration is 3 actuations per nostril 
per dose, four times a day for 7 days(except for Day 1 where subjects in the 2
ndstrata 
will receive 3 doses).  Subjects will be instructed to alternate nostrils after each 
actuation.  First administration of study treatmentwill occur at the study site by 
independent site personnel supervision; first dosing can occur any time prior to 13:00. 
Subjectrandomizationwill be stratified by dosing time on Day 1 by those study 
subjects receiving first dose of study treatmentbetween the hours of: 8:00-11:00 and 
those receiving first dose of study treatmentbetween the hours 11:01-13:00.  On Day 
1, subjects dosing between 8:00-11:00 will dose every 4 hours± 30 minutesfor 4 
doses and subjects dosing between 11:01-13:00 will dose every 4 hours ± 30 minutes
for 3 doses. 
On Days 2-7 all subjects will administer their initial morning dose immediately 
following recording of their common cold symptom assessment at 07:00 ±2 hours and 
the remaining 3 doses every 4 hours ± 30 minutes. 
Dosing times and number ofactuations will be recorded in the subject’s e-diary. 
Subjects will be instructed not to take any additional cough/cold medications, 
including but not limited to, prescription, over-the-counter (OTC), non-
drug/nutritional supplement, or proceduresthroughout the study.Subjects will be 
instructed to use acetaminophen/paracetamolover other OTC medications, but should 
try to avoid use if possible. See Section 3.2 and 4.2 for more detail. 
Subjects will self-evaluate the severity of the following common cold 
signs/symptoms before each dose and record their assessment in the e-diary: 
headache, muscle ache, chills, sore throat, blocked nose, runny nose, cough, and 
sneezing. Subjects will assess symptom severity on a 4-point scale (0=none, 1=mild, 
2=moderate, 3=severe)at baseline and 4 times a day (except for Day 1 where subjects 
 
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in the 2
ndstrata will receive 3 doses) through Day 7 immediately prior to each dose of 
nasal spray and record the scores in the e-diary. Safety will be assessed by occurrence 
of adverse events.
Upon awakening on the morning of Day 8, subjects will complete a self-assessment 
of common cold symptoms in the e-diary.Subjects will be instructed to return to the 
study siteson Day 8 (End of study/Visit 2). An Investigator-led nasal examination,
physical examination and vital signs will be repeated during thisvisit. A repeat urine 
pregnancy test will be performed on all female subjects of child bearing potential. 
Adverse events and the use of concomitant medications will be recorded by the 
subjectsin e-diariesandmonitoredby the site personnelthroughout the study.
Subjectswho discontinue study treatmentprior to Day 7 and those who prematurely 
withdraw from the study for any reason will be instructed to return to the site as soon 
as possible to undergo end ofstudy assessments, and then be discharged from the 
study.
 
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Visit 1 –Screening Visit(Day 1)
The following assessments will be conductedby study site staff:
1. Obtain written informed consent from each subject.
2. Collect demographic data and medical and medication history (previous and 
concomitant diseases, and pre-study and ongoing concomitant medications, 
non-drug concomitant treatments/procedures).
3. Instruct and monitor subjects as they perform aself-assessment of common 
cold symptoms using a 4-point grading scale. This will be recordedin the 
CRF by site personnel. The Investigatorwill confirm the common cold 
diagnosis and only subjects meeting all eligibility criteria and the following 
criteria will be enrolled into the study (See Section 6.1.7.for more detail):
i.A confirmed common cold diagnosis with symptoms <4872 
hours; 
ii.TSS >9 (baseline sum of the 8 common cold symptoms described 
in Section6.1.7.);
iii.Score >1 for at least one of the following symptoms: sore throat, 
runny nose, or blocked nose.
4. Perform physical examination (including ocular, oropharyngeal and chest 
examination); vital sign measurements (blood pressure, pulse, respiration rate, 
oral body temperature, and height and weight measurements).
5. Perform nasal examination by Investigator(for eligibility assessment). See 
Section 6.1.6. for details. 
6. Perform urine drug screen.
7. Perform urinepregnancy test infemale subjectsof childbearing potential.
8. Eligibility assessment based on inclusion/exclusion criteria.
9. Stratify and randomize qualified subjects by contacting IRT (will also provide 
subject/kit number).
10.Monitor for serious adverse events (SAEs)and record any SAEs in CRF.
 
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Visit 1 –Treatment PhaseVisit (Day 1)
1. Dispense and train subject on e-diary.
2. Subjects perform baseline self-assessment of common cold symptoms in e-
diary.
3. A nasal swab sample will be taken for possible future virological analysis. 
4.Independent site personnel, who will have no other responsibilities during the 
study,will instruct subjects on proper use, priming and administration
techniqueof study treatment. Subjects will be instructed to dose for the full 7 
days irrespective of symptom resolution to avoid inappropriate 
discontinuation due to misinterpretation of reduced symptomatology as a 
result of the fluctuation of symptoms that occurs with a common cold. 
Subjects will also be instructed to change to a new study treatmentdevice
every 2 days and to prime the new deviceprior to the morning dose. 
5. Independent site personnel will dispense the devices and demonstrate how to 
prime the devices by priming the first device.
6. Eligible subjectadministration ofthe firstdose of study treatmentat the site
by independent site personnel supervisionthat will have no other 
responsibilities during the study,and can occur any time prior to 13:00. 
Subjectrandomizationwill be stratified by dosing time on Day 1 by those 
study subjects receiving first dose of study treatmentbetween the hours of 
8:00-11:00 and those receiving first dose of study treatmentbetween the hours 
11:01-13:00.  On Day 1, subjects dosing between 8:00-11:00 will dose every 4 
hours ± 30 minutes for 4 doses and subjects dosing between 11:01-13:00 will 
dose every 4 hours± 30 minutesfor 3 doses. Dosing time and number of 
actuations will be recorded in the e-diary. 
7. Monitor for SAEs/adverse events (AEs).
8. Record changes in concomitant medication or non-drug treatments/procedures
in the e-diary.
Treatment Continuation and Subject Daily-Conduct (Days 2-7)
The following assessments will be conductedby study subjects every  day on Days 2-
7:
1. Subjectself-assessment ofcommon cold symptoms in e-diary immediately 
prior to dosing.
2. Subjects will administer their initial morning dose immediately following 
recording of their common cold symptom assessment at 07:00 ±2 hours and 
the remaining 3 doses every 4 hours ± 30 minutes. Dosing time and number of 
actuations will be recorded in the e-diary. 
3. Change study treatmentdevices every 2 daysprior to the morning dose.
4. AE recording in the e-diary.
5. Record changes in concomitant medication or non-drug treatments/procedures
 
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in the e-diary
Visit 2-End of Study Or Early Termination (Day 8)
1. Subjectself-assessment of common cold symptoms in e-diary upon 
awakening on the morning of Day 8.
The following assessments will be conductedby appropriately trained study site staff:
2. Vital signs measurements(blood pressure, pulse, respiration rate and oral 
body temperature).
3. Physical examination.
4. Nasal examinationby Investigator.
5. Urine pregnancy test infemale subjects of childbearing potential.
6. Collection ofsubject e-diary.
7. Recording ofany changes in concomitant medication or non-drug 
treatments/proceduresin the CRF.
8. Monitoring and recording of any SAEs and AEs.
9. Recording offinal status of subject and discharge from the study site at the 
Investigator’s discretion once all study procedures are complete.
Type and Planned Number of Subjects
A SUFFICIENT NUMBER OF SUBJECTS WILL BE SCREENED TO 
ENROLLapproximately 300170eligible subjects(approximately equal number of 
males and females)experiencing common cold symptoms for ≤4872hours;TSS >9 
and ascore >1 for at least one of the following symptoms: sore throat, runny nose, or 
blocked nose; and who are otherwise in good health,will be stratified and randomized
to ensure 274 evaluable subjects complete the entire study(approximately 137 
evaluable subjects per treatment arm).Subject randomization will be stratified by 
centerand by dosing time on Day 1.
Diagnosis and Main Criteria for Inclusion
Subjects must understand the study procedures and provide written informed 
consent before any assessment is performed; willing and able to complete all 
required assessments
Male or female, aged 18 to 75 years
Experiencing common cold symptoms(see Section 6.1.7. for details)for 
≤4872hoursand who are otherwise in good general and mental health
Free of concomitant treatment that could interfere with the interpretation of 
the study results as determined by the Investigator
 
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Product Information
Test Product
Reference Product
Product Name 
1146A formulation 
( 
 carbomer980 gel) 
nasal spray
Placebo
(vehicle without carbomer 
980) nasal spray
Product Formulation 
Code (MFC)
Dose
Apply dose by alternating 
nostrils. 3 actuations of the 
1146A nasal spray 
formulation per nostril per 
dose; 
each actuationis 140µL, 
equivalent to 140mg.
Apply dose by alternating 
nostrils. 3 actuations of 
placebo nasal spray per 
nostril per dose; 
each actuation is 140µL.
Route of 
Administration
Intranasal administration 
Intranasal administration
Dosing Instructions
Firstdosing can occur any 
time prior to 13:00. Subject
randomizationwill be 
stratified by dosing time on 
Day 1 by those study 
subjects receiving first dose 
of study treatmentbetween 
the hours of: 8:00-11:00 
and those receiving first 
dose of study treatment
between the hours 11:01-
13:00.  On Day 1, subjects 
dosing between 8:00-11:00 
will dose every 4 hours ± 
30 minutes for 4 doses and 
subjects dosing between 
11:01-13:00 will dose 
every 4 hours ± 30 minutes 
for 3 doses. On Days 2-7 
all subjects will administer 
their initial morning dose at 
07:00 ±2 hours and the 
remaining 3 doses every 4 
hours ± 30 minutes.
Subjects should blow their 
First dosing can occur any 
time prior to 13:00. Subject
randomizationwill be 
stratified by dosing time on 
Day 1 by those study 
subjects receiving first dose 
of study treatmentbetween 
the hours of: 8:00-11:00 
and those receiving first 
dose of study treatment
between the hours 11:01-
13:00.  On Day 1, subjects 
dosing between 8:00-11:00 
will dose every 4 hours ± 
30 minutes for 4 doses and 
subjects dosing between 
11:01-13:00 will dose 
every 4 hours± 30 minutes
for 3 doses. On Days 2-7 
all subjects will administer 
their initial morning dose at 
07:00 ±2 hours and the 
remaining 3 doses every 4 
hours ± 30 minutes.
Subjects should blow their 
 
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nose prior to dosing and 
alternate actuations to each 
nostril.For each actuation 
subjects should insert the 
nozzle into the nostril, fully 
depress the pump and 
inhale gently. This should 
be repeated in the alternate 
nostril until 3 actuations per 
nostril have been 
completed. Refer to 
Appendix 2, Subject 
Instructions for Use for 
further details.
nose prior to dosing and 
alternate actuations to each 
nostril.For each actuation 
subjects should insert the 
nozzle into the nostril, fully 
depress the pump and 
inhale gently. This should 
be repeated in the alternate 
nostril until 3 actuations per 
nostril have been 
completed. Refer to 
Appendix 2, Subject 
Instructions for Use for 
further details.
Statistical Methods
Primary analysis: The nasal symptom score (NSS) for a subject and time point 
will be calculated as the sum score of the nasal symptoms (blocked nose, runny 
nose, and sneezing) at a time point. The primary efficacy endpoint is average NSS 
on Days 1to 4(ANSS1-4). A subject’s ANSS1-4is calculated as the mean of the 4 
daily NSS across study days 1 to 4, excluding the baseline NSS on Day 1. The 
ANSS1-4will be summarized by means of descriptive statistics by treatment arm. 
For the difference of the ANSS1-4between the two treatment arms, the mean and 
the 95% confidence interval for the mean will be derived.The adjusted means of 
the ANSS1-4in both treatment arms will be compared using an analysis of 
covariance (at a significance level of 0.05), withfactors for treatment group,
centerand Day 1 dosing time stratification,and the Baseline NSS as a covariate.
THE IMPACT OF SUBJECTS WITH ONSET OF SYMPTOMS OF 
COMMON COLD BETWEEN > 48 AND ≤ 72 HOURS WILL BE 
REVIEWED IF THERE AREMORE THAN 10% OF SUCH SUBJECTS 
IN THE PRIMARY ANALYSISPOPULATION. TIME OF ONSET OF 
SYMPTOMS OF COMMON COLD MAYBE ADJUSTED FOR IN THE 
MODEL AND/OR JUST A SUMMARY OFTHE PRIMARY ENDPOINT
WILL BE PROVIDED FOR THIS SUBSET OF SUBJECTS.
The average nasal symptom score over Days 1to 7(ANSS
1-7) will be derived as 
the mean of all NSS across study Days 1to 7and will be summarized and 
analyzed in the same manner as ANSS
1-4.
The average total symptom scores ATSS1-4will be derived as the mean of all TSS 
across study Days 1 to 4 and will be summarized and analyzed in the same 
manner as ANSS1-4.
The average total symptom scores ATSS1-7will be derived as the mean of all TSS 
across study Days 1 to 7 and will be summarized and analyzed in the same 
manner as ANSS1-7.
 
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Safety variables (incidence of adverse events, and changes in vital signs) will be 
summarized descriptively.
Exploratory endpoints: Mean daily nasal symptom score (MDNSS), mean daily 
total symptom score (MDTSS), and mean daily individual symptom scores
(MDISS) and theirrespective changesfrom baselinewill be summarized by 
descriptive statistics by treatment arm and day.
The course of each of the 8common cold symptoms across the treatment period 
will be summarized using frequency tables by treatment arm and day.
 
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1. INTRODUCTION
The common cold is part of life, with most adults having 2-3 symptomatic infections 
per year, and children having a much higher incidence [Simasek, 2007]. Over $3 
billion are spent on over-the-counter (OTC) cough and cold remedies each year in the 
US [Boujaoude and Pratter, 2010]. Treatment options for the common cold focus on 
symptom control. For example, intranasal or oral decongestants are effective to 
improve nasal patency and thus relieve congestion [Sperber, 1989], first generation 
antihistamines reduce sneezing (Gwaltney 1997), ipratropium reduces rhinorrhea 
[Hayden 1996]and non-steroidal anti-inflammatory drugs (NSAIDS)may reduce 
fever and sore throat [Sperber, 1992]. Antitussives and mucolytics are often used to 
ameliorate cough and promoteexpectoration [Singh, 2013].
As the common cold is manifest through a plethora of symptoms, not all of which are 
displayed by each sufferer, there is a need for treatment options which are not 
specificallysymptom related. Agents such as zinc, used as a preventative, given 
within 24 hours of symptom onset, have been shown to reduce the severity and 
duration of symptoms [Singh, 2013]. Various nasal sprays that do not contain 
pharmacologically active ingredients are available as physical barriers to prevent
viruses interacting with nasal epithelium cells but little clinical data exist to support a 
benefit[Hull,2007].
The pathophysiological processes that cause symptoms of the common cold continue 
to be explored. The fundamental premise was established in 1982 when it was 
proposed that these symptoms are mediated through the release of inflammatory 
substances by the host in response to infection and that direct viral cytopathology is 
of lesser importance [Turner 1982]. More recently confirmatory evidence ofthe role 
of the immune response to symptomatology has been demonstrated for rhinoviruses, 
which are the predominant cause of the common cold [Proud,2008]. Once activated 
the humoral immune response continues irrespective of viral presence [Kennedy,
2012]so the target of minimizing the symptom complex must concentrate on 
containing the immune system responses while not interfering with the required 
antiviral activity. In addition to the barrier approach cited above[Hull,2007], 
prevention of viral attachment to nasal epithelial cells via the Intercellular Adhesion 
Molecule 1 (ICAM-1)receptor, the mechanism by which the virus gains access to the 
cell to allow replication, has been explored. Tremacamara, a recombinant soluble 
ICAM-1, was shown to be effective in reducing the symptoms of experimental 
common colds [Turner,1999]. A novel approach to minimizing an upper respiratory 
tract infection is to combine a barrier effect with an activity which prevents 
rhinovirus from binding to ICAM-1 receptors.
1146Acontains carbomer 980, one of a series of anionic, synthetic, high molecular 
weight, non-linear polymers of acrylic acid [ACT, 1982]. 
 
 
 
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 Carbomers inhibit human rhinovirus 
replication by a dual mode of action.First, above concentrations of 0.1% w/w 
carbomer 980 forms a viscous gel, which acts as a physical barrier.Second, 
carbomers are anionic and are believed to readily associate with the cationic binding 
sites on HRV which prevents viral interactions with the nasal epithelial cells via the 
cell surface receptors. Therefore, by preventing interaction with the cell surface 
receptors, the virus is prevented from entering the cell[Kennedy, 2012]. 
Carbomer 980 and 940 are used in ophthalmics, topicals, drugs, cosmetics, nasal 
moisturizing gel (Ocean Nasal Moisturizer Gel®-concentration unknown) and 
toothpaste [Lubrizol, 2010]and are generally regarded as safe. 
2. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To assess the efficacy of 1146A 
in reducing the severity of nasal 
symptomson days 1-4, using the 
average nasal symptom score, 
compared to placebo in adult 
subjects with the common cold
Average nasal symptom score 
Days 1-4(ANSS 
1-4)
Secondary
Efficacy
To assess the efficacy of 1146A 
in reducing the severity of nasal 
symptoms on days 1-7, using the 
average nasalsymptom score, 
compared to placebo in adult 
subjects with the common cold
Average nasal symptom score 
Days 1-7(ANSS 
1-7)
To assess the efficacy of 1146A 
in reducing the severity of 
symptomson days 1-4 and days 
1-7, using the total symptom 
score, compared to placebo in 
adult subjects with the common 
cold 
Average total symptom score 
Days 1-4(ATSS 
1-4)
Average total symptom score 
Days 1-7(ATSS 
1-7)
Safety
Adverse events
Spontaneous and solicited adverse 
eventsand serious adverse events
 
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Exploratory
To assess the efficacy of 1146A 
in reducing the severity of 
individual symptoms, using the 
individual symptom score, 
compared to placebo in adult 
subjects with the common cold 
Individual & composite  total 
symptomscores (NSS and TSS) 
Days 1-7
3. STUDY PLAN
3.1. Study Design
Overall Design
This is a multi-center, randomized, parallel-group, double blind, 2-arm, placebo-
controlled study to evaluate the efficacy and safety of 1146A ( 
 carbomer980 gel 
nasal spray) in adult subjects with symptomatic common cold in an outpatient setting. 
At Screening (Day 1, Visit 1), subjects with symptoms consistent with symptomatic 
common cold of ≤4872hour duration will provide written informed consent to be 
enrolled into the study. During this visit,subjects will undergo eligibility screening, 
which includes: assessment of common cold symptoms and diagnosis by the 
Investigator; review of demographics, medical and medication history; vital sign 
assessments (blood pressure, pulse rate, respiratory rate, oral body temperature, 
height and weight measurements); physical examination; Investigator-led nasal 
examination; urine pregnancy test (only female subjects of childbearing potential); 
and urine drug screen.
Only subjects meeting all eligibility criteria including the following symptomatic 
common cold symptoms will be enrolled into the study: 
1. A confirmed common cold diagnosis with symptoms <4872hours; 
2. TSS >9 (baseline sum of the 8 common cold symptoms described in 
Section6.1.7.);
3. Score >1 for at least one of the following symptoms: sore throat, runny 
nose, or blockednose.
Approximately 300170eligible subjects (approximatelyequal numbers of males and 
females) will be randomized to treatment with 1146A nasal spray or placebo (vehicle, 
nasal spray) in a 1:1 ratio at multiplesites. All sites should make an effort to enroll 
approximately equal number of males and females into the study. The study sites will
 
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stratified and randomize eligible subjects using IRT.
Study site personnel willdispense and train subjects on the e-diaryand subjects will 
then perform their baseline self-assessment of common cold symptoms in their e-
diary. A nasal swab sample will be taken for possible futurevirological analysis. An 
independent site personnel, who will have no other responsibilities during the study,
will then instruct subjects on proper use, priming and administration technique of 
study treatment. Subjects will be instructed to dose for the full seven days irrespective 
of symptom resolution to avoid inappropriate discontinuation due to misinterpretation 
of reduced symptomatology as a result of the fluctuation of symptoms that occurs 
with a common cold. Subjects will also be instructed to change to a new study 
treatmentdeviceevery 2 days and to prime the new deviceprior to the morning dose. 
The independent site personnel will then dispense the devicesand demonstrate how to 
prime the devices by primingthe first device.  They will then monitor eligible 
subjects while the subjectadministersthe first dose of study treatment. 
Study treatmentwill be administered via a nasal spray device (1 dose =3 actuations 
per nostril, each actuation is 140L). Dosingadministration is 3 actuations per nostril 
per dose, four times a day for 7 days(except for Day 1 where subjects in the 2
ndstrata 
will receive 3 doses).  Subjects will be instructed to alternate nostrils after each 
actuation.  First administration of study treatmentwill occur at the study site by 
independent site personnel supervisionthatwill have no other responsibilities during 
the study; first dosing can occur any time prior to 13:00. 
Subjectrandomizationwill be stratified by dosing time on Day1 by those study 
subjects receiving first dose of study treatmentbetween the hours of: 8:00-11:00 and 
those receiving first dose of study treatmentbetween the hours 11:01-13:00.  On Day 
1, subjects dosing between 8:00-11:00 will dose every 4 hours ± 30 minutes for 4 
doses and subjects dosing between 11:01-13:00 will dose every 4 hours ± 30 minutes 
for 3 doses. 
On Days 2-7 all subjects will administer their initial morning dose immediately 
following recording of their common cold symptom assessment at 07:00 ±2 hours and 
the remaining 3 doses every 4 hours ± 30 minutes. 
Dosing times and number of actuations will be recorded in subject’s e-diary. Subjects 
will be instructed not to take any additional cough/cold medications, including but not 
limited to, prescription, OTC, non-drug/nutritional supplement, or procedures 
throughout the study. Subjects will be instructed to use acetaminophen/paracetamol
over other OTC medications, but should try to avoid use if possible. See Section 3.2 
and 4.2 for more detail. 
 
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Subjects will self-evaluate the severity of the following common cold 
signs/symptoms before each dose and record their assessment in the e-diary:
headache, muscle ache, chills, sore throat, blocked nose, runny nose, cough, and 
sneezing. Subjects will assess symptom severity on a 4-point scale (0=none, 1=mild, 
2=moderate, 3=severe)at baseline and 4 times a day (except for Day 1 where subjects 
in the 2
ndstrata will receive 3 doses) through Day 7 immediately prior to each dose of 
nasal spray and record the scores in the e-diary. Safety will be assessed by occurrence 
of adverse events.
Upon awakening on the morning of Day 8, subjects will complete a self-assessment 
of common cold symptoms in the e-diary.Subjects will be instructed to return to the 
study sites on Day 8 (End of study/Visit 2). Nasal examination, physical examination 
and vital signs will be repeated during this visit. A repeat urine pregnancy test will be 
performed on all female subjects of child bearing potential. Adverse events and the 
useof concomitant medications will be recorded by the subjects in e-diaries and 
monitored by the site personnel throughout the study.
Subjects who discontinue study treatmentprior to Day 7 and those who prematurely 
withdraw from the study for any reason will be instructed to return to the site as soon 
as possible to undergo all end of study assessments, and then be discharged from the 
study.
 
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Visit 1 –Screening Visit (Day 1)
The following assessments will be conducted by study site staff:
1. Obtain written informed consent from each subject.
2. Collect demographic data and medical and medication history (previous and 
concomitant diseases, and pre-study and ongoing concomitant medications, 
non-drug concomitant treatments/procedures).
3. Instruct and monitor subjects as they perform a self-assessment of common 
cold symptoms using a 4-point grading scale. This will be recorded in the 
CRF by site personnel. The Investigatorwill confirm the common cold 
diagnosis and only subjects meeting all eligibility criteria and the following 
criteria will be enrolled into the study (See Section 6.1.7. for more detail):
i.
A confirmed common cold diagnosis with symptoms <4872
hours; 
ii.
TSS >9 (baseline sum of the 8 common cold symptoms 
described in Section 6.1.7.);
iii.
Score >1 for at least one of the following symptoms: sore throat, 
runny nose, or blocked nose.
4. Perform physical examination (including ocular, oropharyngeal and chest 
examination); vital sign measurements (blood pressure, pulse, respiration rate, 
oral body temperature, and height and weight measurements). 
5. Perform nasal examination by Investigator(for eligibility assessment). See 
Section 6.1.6. for details. 
6. Perform urine drug screen.
7. Perform urinepregnancy test in female subjects of childbearing potential.
8. Eligibility assessment based on inclusion/exclusion criteria.
9. Stratify and randomize eligiblesubjects usingIRT (will also provide 
subject/kit number). 
10.Monitor for SAEsand record any SAEs in CRF.
 
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Visit 1 –Treatment PhaseVisit (Day 1)
1. Dispense and train subject on the e-diary. 
2. Subjects perform baseline self-assessment of common cold symptoms in e-
diary.
3. A nasal swabsample will be taken for possible future virological analysis. 
4.Independent site personnel, who will have no other responsibilities during the 
study, will instruct subjects on proper use, priming and administration 
technique of study treatment. Subjects will be instructed to dose for the full 
seven days irrespective of symptom resolution to avoid inappropriate 
discontinuation due to misinterpretation of reduced symptomatology as a 
result of the fluctuation of symptoms that occurs with a common cold. 
Subjects will also be instructed to change to a new study treatmentdevice
every 2 days and to prime the new deviceprior to the morning dose. 
5. Independent site personnel will dispense the devices and demonstrate how to 
prime the devices by priming the first device. 
6. Eligible subject administration of the first dose of study treatmentat the site 
by independent site personnel supervision that will have no other 
responsibilities during the study, and can occur any time prior to 13:00. 
Subjectrandomizationwill be stratified by dosing time on Day 1 by those 
study subjects receiving first dose of study treatmentbetween the hours of 
8:00-11:00 and those receiving first dose of study treatmentbetween the hours 
11:01-13:00.  On Day 1, subjects dosing between 8:00-11:00 will dose every 4 
hours ± 30 minutes for 4 doses and subjects dosing between 11:01-13:00 will 
dose every 4 hours ± 30 minutes for 3 doses. Dosing time and number of 
actuations will be recorded in the e-diary. 
7. Monitor for SAEs/AEs.
8. Record changes in concomitant medication or non-drug treatments/procedures
in the e-diary.
Treatment Continuation and Subject Daily-Conduct (Days 2-7)
The following assessments will be conducted by study subjects every  day on Days 2-
7:
1. Subjectself-assessment of common cold symptoms in e-diary immediately 
prior to dosing.
2. Subjects will administer their initial morning dose immediately following 
recording of their common cold symptom assessment at 07:00 ±2 hours and 
the remaining 3 doses every 4 hours ± 30 minutes. Dosing time and number of 
actuations will be recorded in the e-diary. 
3. Change study treatmentdevices every 2 days prior to the morning dose.
4. Adverse event recording in the e-diary.
5. Record changes in concomitant medication or non-drugtreatments/procedures
 
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in the e-diary.
Visit 2 -End of Study Or Early Termination (Day 8)
1. Subjectself-assessment of common cold symptoms in e-diary upon 
awakening on the morning of Day 8.
The following assessments will be conducted by appropriately trained study site staff:
2. Vital signs measurements (blood pressure, pulse, respiration rate and oral 
body temperature).
3. Physical examination.
4. Nasal examinationby Investigator.
5. Urine pregnancy test in female subjects of childbearing potential).
6. Collection of subject e-diary.
7. Recording of any changes in concomitant medication or non-drug 
treatments/proceduresin the CRF.
8. Monitoring and recording of any adverse eventsand serious adverse events. 
9. Recording of final status of subject and discharge from the study sites at the 
Investigator’s discretion once all study procedures are complete
3.2. Subject Restrictions
Lifestyle/ Dietary
None
Medications and Treatments
During the entire study (screening –end of study):
A. Subjects are not permitted use of any medication other than the allocated 
study treatmentand medications to treat chronic, controlled diseases (see 
Section 4.2, Number 3 for details). In addition, subjects should also refrain 
from non-drug concomitant treatment or proceduresthat may interfere with 
study treatment. In case subjects use any concomitant medication that could 
interfere with the interpretation of the study results, they will be discontinued 
from the study. 
B. Intranasal sprays including saline or decongestants within 24 hours.
C. Intranasal steroids within the past 14 days.
D. Expectorants, mucolytics, or antitussives within the past 12 hours.
E. Cough/throat lozenges, menthol chest rub, menthol vaporizersor honey within 
6 hours.
 
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F. Non-steroidal anti-inflammatory drug (NSAID), or acetyl salicylic acid within 
the past 12 hours (immediate release) and 24 hours (sustained release). 
Acetaminophen/paracetamol may be used occasionally for fever or headache, 
but subjects should be instructed to try to avoid use if possible. 
G. Oral decongestants within 12 hours for short-acting and 24 hours for long-
acting. 
H. Long acting antihistamines (cetirizine, fexofenadine, hydroxyzine, and 
loratadine) within 5 days.
I. Short acting antihistamines (e.g., chlorpheniramine, brompheniramine, 
diphenhydramine), clemastine, long acting forms of chlorpheniramine within  
2 days.
J. Asthma medications with the exception of beta-agonists. Subject should be on 
a stable dose (7 days) within 24 hours.
K. Herbal OTC medicines for cough/cold (e.g., echinacea, garlic supplements, 
etc.) for 24 hours.
L. Systemic corticosteroids, immunomodulators within 3 months.
M. Antibiotics within the past 14 days.
N. A flu shot within the past 48 hours.
O. Use of Tamiflu®(oseltamivir) or Relenza
®(zanamivir) within the last 7 days.
P. Other investigational drugs or devices.
Q. Any other treatment the Investigatordeems unacceptable for this study.
3.3. Type and Planned Number of Subjects
A SUFFICIENT NUMBER OF SUBJECTS WILL BE SCREEN IN ORDER TO 
ENROLLapproximately 300170male andfemale subjects(all site will be instructed 
to enroll approximatelyequal numbersof males and females)will be randomizedto 
ensure 274 subjects (137 subjects per treatment arm) complete the study. Eligible 
subjects will beaged18 to 75 years,in good general health and experiencing 
symptomatic common cold symptomsfor ≤4872hours. 
Symptomatic common cold isdefined as:
TSS >9 (baseline sum of the 8 common cold symptoms described in Section
6.1.7.)AND
 
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Score >1 for at least one of the following symptoms: sore throat, runny nose, 
or blockednose.
To participate, each subject must meet all study Inclusion and none of the Exclusion 
criteriaat Screening/Baseline visit (Visit 1)prior to randomization.See Section 4.1.
and 4.2.for details on Inclusion and Exclusion criteria.
3.4. Study Design and Dose Justification
The target population is symptomatic subjects with the common cold. These subjects 
are studied in the outpatient setting and efficacy is monitored by the subjects’ 
evaluations of specific symptoms. Safety is evaluated by subject reported adverse 
events.
While common cold symptoms manifest for 7-10 days, the most severe symptoms 
typically present within the first 4 days of symptom onset, thus the primary endpoint 
will focus on nasal symptoms score on Days 1 through 4. 
Intranasally administered 1146A formulation containing carbomer 980 (Carbopol® 
980) stabilized with buffers will be compared to placebo. The individual components 
of 1146Aare used as excipients in pharmaceutical and cosmetic preparations. The 
safety of carbomers was assessed by American College of Toxicologyin 1982 and 
reevaluated in 2002; the conclusion was that carbomers are safe for use in humans 
[ACT, 1982;ACT, 2002].
Tolerability and safety of the intranasal formulation has been demonstrated in rats,
but no published literature was found on 
 carbomer 980 administered 
intranasally and used four times daily over 7 days.
 
 
The concentration of carbomer selected is based on invitrodata (
 carbomer 
980), which has demonstrated the ability to entrap common cold viruses. The 
rationale for the dose and regimen is to maximize the coverage of the nasal 
epithelium commensurate with consumer acceptability. The maximum frequency of 
use and volume of application are based on the regimen for competitive products 
(Vick’s First Defense is 2-3 sprays 4 times daily approximately 4 hours apart)[Vicks 
First Defence Nasal Spray, 2014].
 
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4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, adverse 
events, and other pertinent information on the GSK investigational product or other 
study treatment that may impact subject eligibility is provided in the Investigator
Brochure (IB).
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential.
4.1. Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
1. CONSENT
Demonstrates understanding of the study procedures, restrictions and willingness to 
participate as evidenced by voluntary written informed consent and has received a 
signed and dated copy of the informed consent form. 
2. AGE
Aged between18to 75 yearsinclusive.
3. GENDER
Male or female.
4. GENERAL HEALTH
Good general and mental health with, in the opinion of the Investigatoror medically 
qualified designee no clinically significant and relevant abnormalities in medical 
history or upon physicaland Investigator-led nasalexamination.
5. CONTRACEPTION
Females of childbearing potential (refer to Section 4.4.) who are, in the opinion of the 
Investigator, practicinga reliable method of contraception. Adequate contraception is 
defined as abstinence, oral contraceptive, either combined or progestogen alone OR 
 
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injectable progestogen OR implants of levonorgestrel OR estrogenic vaginal ring OR 
percutaneous contraceptive patches OR intrauterine device or intrauterinesystem OR 
double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] 
plus spermicidal agent [foam, gel, film, cream, suppository]) OR male partner 
sterilization prior to the female subject
's entry into the study, and this male is the sole 
partner for that subject.
6. STUDY SPECIFIC
Investigatorconfirmed diagnosis of symptomatic common cold with an onset of 48
72hours prior to randomization. Symptomatic common cold isdefined asTSS > 9 
AND a score >1 for at least one of the following symptoms: sore throat, runny nose, 
orblocked nose.
4.2. Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. PREGNANCY
Women who have a positive urine pregnancy test
2. BREAST-FEEDING
Women who are breast-feeding
3. CONCURRENT MEDICATION/ MEDICAL HISTORY
During the entire study (Screening –last subject visit):
A. Subjects who have used medications or therapies that could interfere with 
study evaluations and have not had the proper washout period (see Section 
3.2.) from these medications or therapies or are anticipated to require any 
concomitant intranasal medication during that period or at any time 
throughout the study.
B. Nasal disease(s) likely to affect deposition of intranasal medication, such as 
chronic sinusitis, rhinitis medicamentosa, clinically significant polyposis, or 
clinically significant nasal structuralabnormalities.
C. Nasal surgery or sinus surgery within the previous year.
D. Any condition that prohibits the subject from actuating nasal spray devices 
(severe rheumatoid arthritis; deformed hands and fingers; missing fingers).
 
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E. Clinically relevant abnormal physical findings which, in the opinion of the 
Investigatoror sponsor’s medical monitor, would interfere with the objectives 
of the study or that may preclude compliance with the study procedures.
F. Uncontrolled cardiovascular, pulmonary, renal, hepatic, gastrointestinal, 
hematological, endocrine, metabolic, autoimmune, neurological, psychiatric 
or other diseases at screeningthat would interfere with the study in the 
opinion of the Investigator.
G. Subjects with seasonal allergic rhinitis if randomization occursduring their 
expected allergy seasonor perennial allergic rhinitis.
H. Severe COPD, persistent asthma, or recent COPD/asthma exacerbation.
I. An inability to comprehend and satisfactorily use the measurement 
instruments as determined by the study sites staff on screening.
J. Subjects with a fever >38° C (100.4° F).
K. Frequent uses of analgesics (i.e. havetaken an analgesic for pain in headache 
and pain in muscle/joints for >1doses per week on average over the past 6 
months).
4. ALLERGY/ INTOLERANCE
A. Known or suspected intolerance or hypersensitivity to any of the study 
treatments,excipients or investigationaldevice materialor to medications of 
similar chemical classes.
B. Any history of drug hypersensitivityor other significant allergic diathesisthat 
could affect study participation.
C. Known or suspected contraindications, including history of allergy or 
photosensitivity to study treatment/s.
5. CLINICAL STUDY/ EXPERIMENTAL PRODUCT
A. Participation in another clinical study (including cosmetic studies) or receipt 
of an investigational drug within 30 days of the screening visitor 5 half-lives 
of enrollment, whichever is longer.
B. Previous participation in this study(i.e. subjects cannot be re-screened or 
randomized).
6. SUBSTANCE ABUSE
A. Recent history (within the last 51years) of alcohol or other substance abuse.
B. Positive urine drug screen. 
 
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7. PERSONNEL
A. An employee of the sponsor or the study sitesor members of their immediate 
family.
B. Persons directly or indirectly involved in the execution of this protocol, 
including employees of the contract research organization (CRO) and persons 
related to them.
8. DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
A. On nasal examinationby Investigator, the presence of nasal disease likely to 
affect deposition of intranasal treatment or any superficial or moderate nasal 
mucosal erosion, nasal mucosal ulceration, or nasal septum perforation at the 
screening visit.
B. Subjectswith difficulty in using the nasal spray applicator.
C. “Vulnerable” individual (as defined by the IRBe.g. incarcerated person).
D. Any condition not identified in the protocol that in the opinion of the 
Investigatorwould confound the evaluation and interpretation of the study 
data or may put the subject at risk.
4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study but are 
never subsequently randomized.
The following information is to be collected for screen failures:
Screening number
Date of screening
Date of informed consent
Age
Race
Ethnicity
Gender
Primary reason for screen failure
Occurrence of Serious Adverse Events (SAE); adverse events that are not 
SAEs will be followed by the Investigatorand collected only in the source 
data
Re-screening of subjects is notallowed in this study.
 
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4.4. Women of Childbearing Potential Definition
Female subjects of non-childbearing potential must meet at least one of thefollowing
criteria:
1. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
2. Have medically confirmed ovarian failure;
3. Have undergone a documented tubal ligation;
4. Have had 12 months of natural (spontaneous) amenorrhea with an appropriate 
clinical profile (e.g. age appropriate, history ofvasomotor symptoms).
All other female subjects (including those that do not have a documented 
hysterectomy, tubal ligation, bilateral oophorectomy and/or ovarian failure) will be 
considered to be of childbearing potential.
4.5. Withdrawal/ Stopping Criteria
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the Investigatorfor ethical, safety, 
behavioral or administrative reasons. If a subject withdraws or is withdrawn from the 
study, all human biological samples collected before they left will be analyzed and 
reported unlessthe subject requests otherwise. A subject may request for their human 
biological samples to be destroyed. In these cases, the Investigatormust document 
this in the site study records and the samples should not be used for any further 
research.
The following circumstances require discontinuation of study treatment and/or 
premature subject withdrawal:
Subject did not meet study criteria
Protocol violationthat may impact the outcome of the study and/or subject’s 
safety
Withdrawal of informed consent
Unblinding of the subject 
Subject lost to follow-up
Pregnancy
Death
Use of disallowed concomitant medications (see Section 3.2.)
If the reason for removal of a subject from the study is an AE or an abnormal 
laboratory test result, the principal specific event or test will be recorded on the 
 
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electronic case report form (CRF). If a subject is withdrawn from the study because 
of a product limiting AE, thorough efforts should be clearly made to document the 
outcome. Any AEs ongoing at the final visit will be followed up until resolved, the 
condition stabilizes, is otherwise explained, or the subject is lost to follow-up.
The following actions must be taken in relation to a subject who fails to attend the 
clinic for a required study visit:
The site must attempt to contact the subject and re-schedule the missed visit as 
soonas possible. 
The site must counsel the subject on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the subject wishes to 
and/or should continue in the study. 
In cases where the subject is deemed ‘lost to follow up’, the Investigatoror 
designee must make every effort to regain contact with the subject (where 
possible, at least2 telephone calls). The contact attempt should be 
documented in the subject’s record. 
Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost 
to Follow-up”.
All subjects will not be permitted any use of disallowed concomitant 
medications. The subject will be discontinued from study treatment if the 
subject takes more than one dose of disallowed concomitant medications. All 
medications, procedures and significant non-drug therapies (including 
physical therapy and blood transfusions) administered after the subject starts 
study treatmentmust be listed in the CRF.
4.6. Subject Replacement
Subjects who withdraw from the study post-randomization willnotbe replaced.
4.7. Subject and Study Completion
A subject is considered completed after completion of the 7 days of dosing and the 
final assessments conducted on Day 8.
The study is considered completed after all randomized subjects have either 
completed all study proceduresor have been discontinued from the study.
The end of the study is defined as the date of the last subject’s last visit.
 
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5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product 
Reference Product 
Product Name 
1146Aformulation 
( 
 carbomer 980 gel) 
nasal spray
Placebo(vehicle without 
carbomer 980) nasal spray
Product 
Formulation Code 
(MFC)
Dose
Apply dose by alternating
nostrils. 3 actuations of the 
1146A nasal spray 
formulation per nostril per 
dose; each actuation is 
140µL, (equivalent to 
140mg).
Apply dose by alternating
nostrils. 3 actuations of 
placebo nasal spray per 
nostril per dose;each 
actuation is 140µL.
Route of 
Administration
Intranasal administration 
Intranasal administration
Dosing Instructions
First dosing can occur any 
time prior to 13:00. Subject
randomizationwill be 
stratified by dosing time on 
Day 1 by those study 
subjects receiving first dose 
of study treatmentbetween 
the hours of: 8:00-11:00 and 
those receiving first dose of 
study treatmentbetween the 
hours 11:01-13:00.  On Day 
1, subjects dosing between 
8:00-11:00 will dose every 
4 hours ± 30 minutes for 4 
doses and subjects dosing 
between 11:01-13:00 will 
dose every 4 hours ± 30 
minutes for 3 doses. On 
Days 2-7 all subjects will 
administer their initial 
First dosing can occur any 
time prior to 13:00. Subject
randomizationwill be 
stratified by dosing time on 
Day 1 by those study 
subjects receiving first dose 
of study treatmentbetween 
the hours of: 8:00-11:00 and 
those receiving first dose of 
study treatmentbetween the 
hours 11:01-13:00.  On Day 
1, subjects dosing between 
8:00-11:00 will dose every 
4 hours ± 30 minutes for 4 
doses and subjects dosing 
between 11:01-13:00 will 
dose every 4 hours ± 30 
minutes for 3 doses. On 
Days 2-7 all subjects will 
administer their initial 
 
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morning dose at 07:00 ±2 
hours and the remaining 3 
doses every 4 hours ± 30 
minutes.
Subjects should blow their 
nose prior to dosing and 
alternate actuations to each 
nostril. For each actuation 
subjects should insert the 
nozzle into the nostril, fully 
depress the pump and inhale 
gently. This should be 
repeated in the alternate 
nostril until 3 actuations per 
nostril have been 
completed. Refer to 
Appendix 2, Subject 
Instructions for Use for 
further details.
morning dose at 07:00 ±2 
hours and the remaining 3 
doses every4 hours ± 30 
minutes.
Subjects should blow their 
nose prior to dosing and 
alternate actuations to each 
nostril. For each actuation 
subjects should insert the 
nozzle into the nostril, fully 
depress the pump and inhale 
gently. This should be 
repeated in thealternate 
nostril until 3 actuations per 
nostril have been 
completed. Refer to 
Appendix 2, Subject 
Instructions for Use for 
further details.
 
 
 
Both products are filled into 10 mL amber colored glass devices fitted with an Aptar 
FreepodM pump. The pump is made of high-density polyethylene (HDPE), low-
density polyethylene (LDPE), polypropylene and stainless steel parts and is fitted into 
the glass device. The pump delivers a spray of 140mcL (equivalent to 140 mg) per 
actuation with a precision of +15%.
5.2. Dose Schedule
5.2.1. Instructions for use of the medical device
During the 7 days of treatment each subject will receive in total 27-28 doses
(depending on Day 1 dosing time strata). Therefore, a kit containing 5devices for the 
7 days of dosing (4 as treatment and1 as a reserve device) will be allocated to the 
subject. Subjects will use a devicefor 2 days and then start a new device. 
All study treatmentwill be administered by the subject following the instructions for 
use below. The first administration will take place at the study sites under supervision 
of an independent study personnel(who will have no other responsibilities during the 
study)on a one-on-one session with the subject in a private room. Prior to the first 
 
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dose the independent study personnel will prime the 
devicein the presence of the 
subject as theyexplain the priming instructions below. 
Instructions for use (by an independent site personnel):
On Day 1, subjects dosing between 8:00-11:00 will dose every 4 hours ± 30 
minutes for 4 doses and subjects dosing between 11:01-13:00 will dose every 
4 hours ± 30 minutes for 3 doses. All subjects will be instructed to administer 
4 doses on Days 2-7. 
Dose for the full seven days irrespective ofsymptom resolution.
Change to a new study treatmentdeviceevery 2 days and prime the new 
device
prior to the morning dose.
Blow nose to clear nostrils prior to dosing. 
Subjects will be instructed to complete all 6 actuations (3 in each nostril) of 
studytreatmentwithin 2 minutes. 
To spray, hold the devicewith thumb at the base and nozzle between the index 
and ringMIDDLE fingers. Without tiltingTILT the headFORWARD 
SLIGHTLY, insert nozzle into the nostril. Fully depress the pump rim with a 
firm and even stroke and inhale gently.
Alternate actuations to each nostril
Wipe the nozzle clean and dry after each usedefined as 6 actuations.
See Appendix 2 for more details. 
Priming instructions: 
The devicewill be removed from the kit prior to using it for the first time and will be 
primed prior to first useas indicated below:
Shake the devicewell(only prior to priming, not prior to each use). 
Point the spray tip away from you.
Remove the protective cap and prime the pump by depressing the pump firmly 
10 times. Now the pump is ready to use.
5.2.2. Dosing
Dosing administration is 3 actuations per nostril per dose, four times a day for 7 days
(except for Day 1 where subjects in the 2
ndstrata will receive 3 doses).  Subjects will 
be instructed to alternate nostrils after each actuation.  First administration of study 
treatmentwill occur at the study site by independent site personnel supervision; first 
dosing can occur any timeprior to 13:00. 
 
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Subjectrandomizationwill be stratified by dosing time on Day 1 by those study 
subjects receiving first dose of study treatmentbetween the hours of: 8:00-11:00 and 
those receiving first dose of study treatmentbetween the hours 11:01-13:00.  On Day 
1, subjects dosing between 8:00-11:00 will dose every 4 hours ± 30 minutes for 4 
doses and subjects dosing between 11:01-13:00 will dose every 4 hours ± 30 minutes 
for 3 doses. 
On Days 2-7 all subjects will administer their initial morning dose immediately 
following recording of their common cold symptom assessment at 07:00 ±2 hours and 
the remaining 3 doses every 4 hours ± 30 minutes. 
Dosing times (time that first actuation is administered) and number of actuations will 
be recorded insubject’s e-diary.
5.3. Dose Modification
No dose modification is permitted in this study.
5.4. Product Compliance
Treatment compliance is assessed by the recording of dosing times and number of 
actuations in the subject e-diary.
5.5. Precautions
No special precautions are necessary provided the study is carried out in accordance 
with this protocol. 
5.6. Overdose
An overdose is a deliberate or inadvertent administration of a product at a dose higher 
than specified in the protocol.
Overdose is not likely to occur in this study. Limited quantities of the product will be 
supplied, and closely monitored by the site for each subject.
Overdose per se is not an AE. However, any clinical sequelae of an overdose should 
be reported as an AE (and serious adverse event [SAE], if appropriate). For reporting, 
follow the AE and SAE reporting instructionsprovided in Section 7.4.
 
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5.7. Rescue Therapy
No rescue therapy is required in this studyas the common cold is a self-limiting 
disease.
5.8. Product Assignment
A unique screening number will identify each subject screened for study 
participation. Screening numbers will be assigned in ascending numerical order as 
each subject signs their consent form. Only the assigned screening number should be 
entered in the field labelled “Subject ID” on the CRF. Once assigned to a subject, a
screening number will not be reused. 
5.8.1.Randomization
This study will use validated interactive response technology (IRT).  The IRT system 
will be set-up, validatedand administered by the CRO in accordance with the 
Sponsor approved protocol. The randomization scheduleand treatment kit schedule 
will begenerated under the responsibility of the CROand uploaded into the validated 
IRT system. The randomization schedule will be set up using the method of randomly 
permuted blocks with a fixed block size. 
The IRT system will randomize and stratify by site and by dosing time on Day 1. The 
maximum number of subjects each site can randomize will be capped at 45 (15% of 
the target number of randomized subjects). This is to ensure that the study population 
is reasonably distributed across as many sites as possible, and not dominated by one 
or two sites providing the majority of subjects. The IRT system will generate an 
initial shipment and re-supply shipments of numbered treatment kits for each 
treatment arm to the sites as subjectsare enrolled. 
All subjects that have signed an Informed Consent Form will be assigned anIRT 
generated subject number. The site will log into the IRT system and enter the required 
subject information; the IRT system will then assign a subject number, the subject 
will then meet the inclusion criteria and be enrolled or not meet inclusion criteria and 
excluded from the study. Those subjects excluded from the study will be recorded as 
Screen Failed in the IRT system.
Subjects who meet all inclusion criteria will be assigned by IRT to one of two 
treatment arms (1146A or placebo) in a 1:1 allocation ratio using the method of 
randomly permuted blocks with a fixed block size in accordance with the stratified 
randomization schedule. All site personnel will be blinded to the treatment 
 
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allocations. Sponsor and CRO personnel who may influence study outcomes are kept 
blinded to the treatment allocations. 
When a treatment arm is assigned to a subject, the IRT system will assign a 
randomization number to the subject and atreatment kit from the assigned arm that 
was previously allocatedby the IRT system and shipped to the site. The treatment kit 
the IRT system assigns to the subject will then be dispensed to the subject. The site 
will enter the IRT generated subject number, randomization number and treatment kit 
number into the sites log.
If a subject fails to be randomized for any reason, the subject number and the reason 
for not being randomized will be entered in the sites log. 
5.8.2 Blinding
The subjects, Investigatorand site staff, study statistician and other employees of the 
Sponsor who may influence study outcomes are blinded to the product allocation of 
subjects until database lock.Independent site personnel will be responsible for 
preparing study treatment, training the subject on the proper use of study treatment
andpriming the firstdevice. The independent site personnel will also monitor the 
subject as they administer their first dose. The independent site personnel will not be 
otherwise involved in the study.  
5.8.3 Code Breaks
The blind must only be broken at the conclusion of the studywith permission given 
by the Sponsoror in an emergency where it is essential to know which product a 
subject received in order to give the appropriate medical care. Most often, study 
treatmentdiscontinuation and knowledge of the possible treatment assignments are 
sufficient to treat a study subject who presents with an emergency condition.
If the Investigator, or designee, feels breaking the code is required, the Sponsor
should be consulted first, unless the delay would endanger the subject’s health. The 
date, time the code was broken, and reason for breaking the code must be recorded 
and signed. In the event that a code break is required, the GSK Clinical Study 
Manager (CSM) and the monitor must be informed within 24 hours. The unblinded 
treatment code should not be recorded in the CRF.
It is the Investigator’s responsibility to ensure that there is a procedure in place to 
allow access to acode break which will be providedin case of emergencythrough the 
IRT system. The Investigatorwill inform the subject how to contact his/her backup in 
cases of emergency when he/she is unavailable. Study treatments also must be 
 
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discontinued for any subject whose treatment code has been broken inadvertently or 
for any emergency or non-emergency reason.
5.9. Packaging and Labelling
The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department, 
GSKCH.
Clinical Supplieswill be responsible for supplying kitscontaining 5devices (4 as 
treatment and 1 as a reserve device) of test and reference products for the 7 days of 
dosing to be allocated to the subject. Subjects will use a devicefor 2 days (42-48 
actuationsdepending on Day1 dosing time strata) and then start a new deviceprior to 
the morning dose.All other study related items will be supplied by the CRO to the 
sites in their commercial packaging for dispensing by site staff as required. 
Both products will be supplied in identical 10 mL amber colored glass devices fitted 
with an applicator pump in order to maintain the study
 blind. Each devicewill bear a 
study label. Each subject will receive a labelled pack containing 5devices for the 
duration of the study. 
Each study label will contain, but not be limited to, protocol number, storage 
conditions, and caution statement. Subjects will be provided with an emergency 
contact card with study site telephone number and contact information.Each subject 
carton will bear a uniquely numbered 2-part label. Immediately before dispensing 
study treatmentto the subject, sitestaff will detach the outer part of the label from the 
packaging and affix it to the source document forthat subject number.
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. Subjects should be instructed to not remove or deface 
any part of the study label, and to not discard any study 
devices.
5.9.1. Accountability of Product
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 
 
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instructions specified on the treatmentlabels. Clinical supplies are to be dispensed 
only in accordance with the protocol.
The Investigatoror designee will maintain a full record of study product 
accountability. Subject Investigational Product Accountability Recordsmust be kept 
current and will contain the following information:
The identification of the subject to whom the study product was dispensed.
The date(s) and quantity of the study product dispensed to the subject.
The date(s) and quantity of the study product returned by the subject (if 
applicable).
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 trial.
At the end of the study, study product supplies will be verified by the monitor. Study 
product supplies will then be either collected by the study monitor or returned by the 
Investigatoror designee to the GSKCH Clinical Supplies Department or designated 
vendor. 
5.9.2. Storage of Product
Study product supplies must be received by a designated person at the study site, 
handled and stored safely and properly, stored in compliance with the label 
requirements in a secure locationto which only designated staff have access.
6. STUDY ASSESSMENTS AND PROCEDURES
This section lists the procedures and parameters of each planned study assessment. 
The exact timing of each assessment is listed in the Schedule of Events section.
Adherence to the study design requirements, including all assessments and 
procedures are essential and required for study conduct.
 
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6.1. Visit 1 –ScreeningVisit(Day 1)
6.1.1. Informed Consent
The Investigator, or designee, must obtain written (signed and dated by the subject) 
informed consent from each subject participating in this study after adequate 
explanation of the aims, methods, objectives, and potential hazards of the study.
The Investigator, or designee, must also explain to the subjects that they are 
completely free to refuse to enter the study or to withdraw from it at any time. 
Appropriate forms for documenting a written consent will be provided by the 
Investigator. The Investigator, or designee, should sign and date the consent form to 
confirm that the consent process was completed correctly. The subjectwill be 
provided with a copy of their signed and dated consent form and any other written 
information which they should be instructed to retain.
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each
ongoing subject should receive a copy of this new information and be re-consented 
into the study. Subjects or should be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded in the CRF.
6.1.2. Demographics
The following demographic parameters will be captured by the Investigatoror 
designee and recorded in the CRF: age, gender,raceand ethnicity.
6.1.3. Medical History and PriorMedication
Medical history will be assessed as related to the inclusion/exclusion criteria by the 
Investigatoror medically qualified designee. Details of any relevant medical or 
surgical history, including allergies or drug sensitivity, will be recorded in the CRF. 
Wherever possible, diagnoses and not symptoms will be recorded. Any medication 
and non-drug therapies/procedures taken in the 90 days prior to the Screening Visit 
will also be recorded. Relevant history will be recorded in the CRF.
Significant findings that are present before signing informed consent form must be 
included in the CRF. Significant findings made after signing informed consent form 
which meet the definition of an SAE must be recorded on the Adverse Event CRF 
page. Refer Section 7.1 for information on definition of adverse event and serious 
adverse event.
 
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6.1.4. Physical Examination
A complete physical examination will be performed at Screening (Visit 1, Day 1)for 
eligibility. It will include examination of general appearance, skin, neck (including 
thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, and 
extremities, vascular and neurological. 
Information for all physical examination findings must be included in the source 
documentation at the study sites. 
Any significant new findings made after signing informed consent form which meet 
the definition of an AE must be recorded on the Adverse Event CRF page. Refer 
Section 7.1 for information on definition of adverse event and serious adverse event.
6.1.5. Vital Sign Assessments
Vital signs assessmentswill be made which include blood pressure (BP), pulserate, 
respiration rate, oral body temperature, and height and weight.Subjects will be 
included into the study at the Investigator’s discretion. 
After the subject has been sitting for approximately 5 minutes, systolic and diastolic 
BP will be measured three times using an automated validated device, e.g. OMRON, 
with an appropriately sized cuff. The repeat sitting measurements will be made at 1-2 
minute intervals and the mean/average of the three measurements will be used. The 
results for each individual’s measurements will be recorded in the CRF. If the cuff 
sizes available are not large enough for the subject
's arm circumference, a 
sphygmomanometer with an appropriately sized cuff may be used.
The respiration rate is the number of breaths a person takes per minute. The rate is 
usually measured when a person is at rest and simply involves counting the number of 
breaths for one minute by counting how many times the chest rises.
Reference range for vital signs are as follows: oral body temperature between 35.0 ºC 
and 37.5 ºC; systolic BP between 90 and 140 mmHg; diastolic BP between 55 and 
90mmHg; pulse rate between 50 and 100 bpm; and respiration rate between 12 and 
20 breaths per minute.
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. Height in 
 
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centimeters (cm) and body weight in kilograms (kg) (to the nearest 0.1 kilogram) will 
be measured.
6.1.6. Nasal Examination
Nasal examination will be performed for eligibility. The Investigatorwill use a nasal 
speculum or the end of an otoscope to perform a thorough examination of the nasal 
mucosal surfaces for presence of nasal diseases likely to affect deposition of 
intranasal treatmentor any superficial or moderate nasal mucosal erosion, nasal 
mucosal ulceration, or nasal septum perforation. 
Any clinically relevant findings will be noted in the medical history CRF page and
enrollment will be based upon investigator judgement. 
6.1.7. Self-Assessment of Common Cold Signs & Symptoms by Subjects
Common cold signs and symptoms will be self-evaluated by the subject at Screening 
before the first dosing and will be documented in the source document and recorded 
in the CRF. 
In order to qualify each subject for eligibility, the Investigatorwill verbally confirm 
with the subject that the onset of any common cold symptoms occurred within 4872
hours of randomization. THE DATE AND TIME OFSYMPTOM ONSET WILL 
BE CAPTURED IN THE CRF.The investigator will also ensure that the subject 
has a symptomatic commoncold, whichis defined as TSS >9 (baseline sum of the 8 
common cold symptoms described below),AND a score >1 for at least one of the 
following symptoms: sore throat, runny nose,or blocked nose. 
The following are the symptoms of common cold and their severity grading:
Nasal symptoms:
runny nose
blocked nose
sneezing
Other symptoms
headache
muscle ache
chills
sore throat
cough
 
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Each individual sign/symptom will be scored using the following 4 point scale:
0 = absent symptoms (no sign/symptom evident)
1 = mild symptoms (sign/symptom clearly present, but minimal awareness; 
easily tolerated)
2 = moderate symptoms (definite awareness of sign/symptom that is 
bothersome but tolerable)
3 = severe symptoms (sign/symptom that is hard to tolerate; causes 
interference with activities of daily living and/or sleeping)
6.1.8. Pregnancy Test
All women of childbearing potential will have a urine pregnancy test. It will be 
conducted at the site using a urine dipstick. A positive urine pregnancy test 
disqualifies a subject from the study.Results from the pregnancy test will be recorded 
in the CRF. See Section 7.7 for more information. 
6.1.9. Urine Drug Screening Test
Urine will be collected at screening to perform urine drug test(urine dipstick). Urine 
will be tested for the following drugs or illicit substances: barbiturates, 
benzodiazepines, amphetamines, METHAMPHETAMINES, 3,4-
METHYLENEDIOXYMETHAMPHETAMINE (MDMA),cocaine, opiates,
OXYCODONE, METHADONEand cannabis. In case of a positive finding at the 
screening visits or any substance class, the subject must be excluded from 
participation in the study.Results will be recorded in the CRF. IF THE URINE 
DRUG SCREEN YIELDS APOSITIVE RESULT FOR 
METHAMPHETAMINE, 3,4-METHYLENEDIOXYMETHAMPHETAMINE 
(MDMA), OR AMPHETAMINES,THE SUBJECT WILL BE CONSIDERED 
AS HAVING POSITIVE RESULT FOR AMPHETAMINES. IF THE URINE 
DRUG SCREEN YIELDS APOSITIVE RESULT FOR OPIATES, 
OXYCODONE, OR METHADONE, THE SUBJECT WILL BE CONSIDERED 
AS HAVING POSITIVE RESULT FOR OPIATES.
6.1.10. Inclusion/Exclusion Criteria
The Investigator/delegatereviews the inclusion/exclusion criteria and various 
screening assessments and decides the eligibility of the subjectprior to 
randomization. In that context, good general health (confirmed by vital signs, 
physical examinationand nasal examination) and absence of any condition not 
identified in the protocol that in the opinion of the Investigatorwould confound the 
 
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evaluation and interpretation of the study data or may put the subject at risk will be 
checked and reviewed.
6.1.11. Randomization
The study sites will contact IRT to stratify and randomize the eligiblesubject to one 
of the two treatment arms (1146A or placebo), and receive the subject randomization 
numberand product kit number. The randomization number will be entered in the 
CRF. See Section 5.8.1 for details on the randomization.
6.1.12. Safety Monitoring
The occurrence of any SAEs related to study participation will be recorded, beginning 
at the time the subject provides written informed consent. This information should be 
recorded in the Investigator’s source documents. SAEsmust be reported to GSK. All 
SAEs will be treated appropriately and the action taken to treat the SAE should be 
recorded on the AdverseEvent CRF page. See Section 7.2.for further details.
6.2. Visit 1 -Treatment Phase Visit (Day 1)
6.2.1. DispenseE-diary
The site will dispense e-diary and instruct and train subjects on completion of the 
e-diary.
6.2.2. Self-Assessment of Common Cold Symptoms 
Subjects will perform a self-assessment of common cold symptoms prior to dosing
(see Section 6.2.5.) and record it in the e-diary. See Section 6.1.7 for details on 
Common Cold Symptoms and the severity grading.
6.2.3. Nasal Swab Sample 
A nasal swab sample will be taken for possible futurevirological analysis. 
Experienced site staff will collect a posterior nasopharangeal sample by inserting a 
Copan FLOQSwab (Copan Diagnostics, Corona, CA) into one nostril. The swab will 
be insertedposteriorallyapproximately equidistant from the subject’s nose to the ear 
and held in place for 10 seconds to allow absorption of secretions. Gently rotate swab 
2-3 times and then gently remove swab and place in labeled vials containing 
Universal Transport Media (Copan Diagnostics, Corona, CA). Ensure the swab is 
placed all the way to the bottom of the tube, break swab applicator shaft at the 
specified molded breakpoint, replace cap and screw on securely. Sample vials will be 
stored at OR BELOW-70°C and shipped on dryice to a diagnostic laboratory for 
possible future analysis.
 
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6.2.4. Study TreatmentDispensation, Priming of 1stDevice, and 
Instructions for Use
Independent site personnel, who will have no other responsibilities during the study, 
will dispense study treatmentaccording to IRT randomization and instruct the subject 
on proper use of study treatment. Subjects will be instructed to dose for the full seven 
days irrespective of symptom resolution to avoid inappropriate discontinuation due to 
misinterpretation of reduced symptomatology as a result of the fluctuation of 
symptoms that occurs with a common cold. 
Subjects will be instructed to change to a new study treatmentdeviceevery 2 days (48 
actuations) on Days 3, 5 and 7, and to prime the new deviceprior to the morning dose. 
The independent site personnel will then dispense the devices and demonstrate how to 
prime the devices by priming the first device.  See Section 5.2.for details on Dose 
Schedule.
6.2.5. First Administration of Study Treatment
The first dose of study treatmentwill be administered by the subject at the site with 
independent site personnel supervisionand can occur any time prior to 13:00. Subject
randomizationwill be stratified by dosing time on Day 1 by those study subjects 
receiving first dose of study treatmentbetween the hours of: 8:00-11:00 and those 
receiving first dose of study treatmentbetween the hours 11:01-13:00.  On Day 1, 
subjects dosing between8:00-11:00 will dose every 4 hours ± 30 minutes for 4 doses 
and subjects dosing between 11:01-13:00 will dose every 4 hours ± 30 minutes for 3 
doses. The time of dosing and the number of actuations will be recorded in the 
subject’s e-diaryby site personnel.Refer to Section 5.1.or Appendix 2 for further 
details.
6.2.6. Safety Monitoring
The occurrence of any SAEs related to study participation will be recorded beginning 
at the time the subject provides written informed consent. AEs and SAEs will be 
collected from the start of the investigational product. This information should be 
recorded in the Investigator’s source documents or in the subject’s e-diary if they are 
not at the study site. If the AE meets the criteria of an SAE, it must be reported to 
GSK. All adverse events will be treated appropriately and the action taken to treat the 
AE should be recorded on the Adverse Event CRF page. See Section 7.2.for further 
details.
6.2.7. Concomitant Medication
Any changes in concomitant medication or non-drug treatments/procedures will be 
recorded in subject’s e-diaryand will also be captured in the CRF. There will be a 
 
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specific question asking about acetaminophen/paracetamol and all other concomitant 
medication usage prior to each dose of study treatment. 
6.2.8. Instructions for Treatment Continuation at Home
The independentsite personnel will instruct subjects on proper use and continuation 
of study treatment,change of devices, completion of e-diary, reporting of incidence of 
AEs to site,andself-assessment of common cold symptoms to be followed until Day 
7.
6.3. Treatment Continuation and at HomeProcedures (Days2-7)
6.3.1. Self-Assessment of Common Cold Symptoms by Subjects
Subjects will perform self-assessment of common cold symptoms immediately prior 
to each dosingand record itin the e-diary. See Section 6.1.7for details on Common 
Cold Symptoms and the severity grading.
6.3.2. Administration of Study Treatment
Subjects will be instructed to continue dosing of study treatmentat home. Doses will 
be administered four times a day. Subjects will administer initial morning dose 
immediately following recording of their common cold symptom assessment at 07:00 
±2 hours and the remaining 3 doses every 4 hours ± 30 minutes. The time of dosing 
and the number of actuations will be recorded in their e-diary. Refer to Section 5.1 or 
Appendix 2 for further details.
6.3.3. Safety Monitoring
The occurrence of any SAEs related to study participation will be recorded beginning 
at the time the subject provides written informed consent. AEs and SAEs will be 
collected from the start of the investigational product. This information should be 
recorded in the Investigator’s source documents or in the subject’s e-diary if they are 
not at the study site. If the AE meets the criteria of an SAE, it must be reported to 
GSK. All adverse events will be treated appropriately and the action taken to treat the 
AE should be recorded on the Adverse Event CRF page. See Section 7.2 for further 
details.
6.3.4. Concomitant Medication
Any changes in concomitant medication or non-drug treatments/procedures will be 
recorded in subject’s e-diaryand will also be captured in the CRF. There will be a 
specific question asking about acetaminophen/paracetamol and all other concomitant 
medication usage prior to each dose of study treatment.
 
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6.4. Visit 2 –End of Study/Early Termination (Day 8)
6.4.1. Self-Assessment of Common Cold Symptoms 
Upon awakening on Day 8, subjects will perform a self-assessment of common cold 
symptoms and record it in the e-diary. See Section 6.1.7. for details on Common Cold 
Symptoms and the severity grading.
6.4.2. Physical Examination
A complete physical examination will be performed (Visit 2, Day 8). Refer to Section 
6.1.4.above for details on physical examination. Information for all physical 
examination findings must be included in the source documentation at thestudy sites. 
Any significant new findings made after signing informed consent form which meet 
the definition of an Adverse Event (AE) must be recorded on the Adverse Event CRF 
page. Refer Section 7.1.for information on definition of adverse event and serious 
adverse event.
6.4.3. Vital Sign Assessments
Vital signs assessmentswill be made which include blood pressure (BP), pulse, 
respiration rate and oral body temperature.The results for each individual’s 
measurements will be recorded in the CRF. See Section 6.1.5.above for further 
details.
6.4.4. Nasal Examination
Nasal examination will be performed(Visit 2, Day 8). The Investigatorwill perform a 
thorough examination of the nasal mucosal surfaces for presence of nasal diseases 
likely to affect deposition of intranasal treatmentor any superficial or moderate nasal 
mucosal erosion, nasal mucosal ulceration, or nasal septum perforation. Any 
clinically relevant (new or worsening) findings will be noted in the adverseevent 
CRF page.
6.4.5. Pregnancy Test
All women of childbearing potential will have a urine pregnancy test. It will be 
conducted at the site using a urine dipstick. Results from the pregnancy test will be 
recorded in the CRF.See Section 7.7. for more information.
6.4.6. Return of Study TreatmentDevices and Subject E-diary
The site personnel will collect the subject e-diary and all used and unused study 
treatmentfrom the subjects. Comments related to breakage, replacement of devices
and treatment compliance(visual verification) willbe recorded in the CRF.
 
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6.4.7. Concomitant Medication
Any changes in concomitant medication or non-drug treatments/procedures will be 
recordedin the CRF. 
6.4.8. Safety Monitoring
The occurrence of any SAEsrelated tostudy participation will be recorded beginning 
at the time the subject provides written informed consent. AEs and SAEs will be 
collected from the start of the investigational product. This information should be 
recorded in the Investigator’s source documents or in the subject’s e-diary if they are 
not at the study site. If the AE meets the criteria of an SAE, it must be reported to 
GSK. All adverse events will be treated appropriately and the action taken to treat the 
AE should be recorded on the Adverse Event CRF page. See Section 7.2. for further 
details.
6.4.9. Early Termination/ Premature Subject Withdrawal 
Subjects may voluntarily discontinue study treatment for any reason at any time. 
Study treatments also must be discontinued for any subject whose treatment code has 
been broken inadvertently or for any emergency or non-emergency reason. If 
premature withdrawal occurs for any reason, the Investigatormust determine the 
primary reason for a subject’s premature withdrawal from the study
 and record this 
information in the CRF. Subjects, who discontinue study treatmentbefore completing 
the study and those who prematurely withdraw from the study for any reason, should 
undergo final visit procedures (Visit 2, Day 8) as soon as possible.
6.4.10. Study Conclusion
Subjects will be evaluated to determine if they completed all study procedures or if 
they were discontinued from the study early. If the subject discontinued at any point 
during the study, the primary reason for withdrawal should be recorded in the CRF by 
selecting one of the options below.
Subject did not meet study criteria
Protocol violation
Withdrawal of informed consent
Unblinding of the subject 
Subject lost to follow-up
Pregnancy
Death
Other
The site personnel will contact IRT to close out of the subject. Subject will be 
discharged.
 
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7. SAFETY ASSESSMENTS
7.1. Definitions of an Adverse Event and Serious Adverse Event 
7.1.1. Adverse Events
The Investigatoror site staff will be responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE.
Adverse Event Definition:
An AE is any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use of an investigational 
or washout product, whether or not considered related to the investigational or 
washout product.
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 an investigational or 
washout product.
Events meeting AE definition include:
Any abnormal laboratory test results (if applicable) or other safety 
assessments, including those that worsen from baseline, and felt to be 
clinically significant in the medical and scientific judgment of the 
Investigator.
Exacerbation of a chronic or intermittent pre-existing condition including 
either an increase in frequency and/or intensity of the condition.
New condition(s) detected or diagnosed after study product administration 
even though it may have been present prior to the start of the study.
Signs, symptoms, or the clinical sequelae of a suspected interaction.
Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
study product or a concomitant medication (overdose per se will not be 
reported as an AE/SAE).
Events NOT meeting definition of an AE include:
Any clinically significant abnormal laboratory findings (if applicable) or other 
abnormal safety assessments which are associated with the underlying disease, 
unless judged by the Investigatorto be more severe than expected for the 
subject’s condition. 
The disease/disorder/ condition being studied or expected progression, signs, 
 
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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): the condition 
that leads to the procedure is an AE.
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.
7.1.2. Serious Adverse Events
Serious Adverse Event is defined as any untoward medical occurrence that, at 
any dose:
A. Results in death
B. Is life-threatening
NOTE: The term 
'life-threatening
' in the definition of 
'serious
' refers to an 
event in which the subject was at risk of death at the time of the event. It does 
not refer to an event, which hypothetically might have caused death, if it were 
more severe.
C. Requires hospitalization or prolongation of existing hospitalization
NOTE: In general, hospitalization signifies that the subject 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 out-patient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious.
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
D. Results in disability/incapacity
NOTE: The term disability means a substantial disruption of a person’s ability 
to conduct normal life functions.
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
E. Is a congenital anomaly/birth defect
F. Other Situations
Medical or scientific judgment should be exercised in deciding 
whether reporting is appropriate in other situations, such as important 
 
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medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the subject or may 
require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be 
considered serious.
Examples of such events are 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 drugabuse or reports of 
spontaneous abortion.
7.2. Recording Adverse Events and Serious Adverse Events
Recording of adverse events and serious adverse events:
The Investigatoror site staff will be responsible for detecting, documenting 
and reporting events that meet the definition of an AE or SAE.The 
Investigatoror site staff will then record all relevant information regarding an 
AE/SAE in the CRF.
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 Investigatorwill 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).
AEs will be collected from the start of the investigational product and until 5 
daysfollowing last administration of the study product.
SAEs will be collected over the same time period as stated above for AEs. 
However, any SAEs assessed as relatedto 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 consents to participate in the study up to 
and including any follow-up contact.
Medical conditions reported prior to the time period for reporting AEs/SAEs 
should be recorded as part of the subject’s medical history.
7.3. Evaluating Adverse Events and Serious Adverse Events
Assessment of Intensity:
The Investigatoror designee will make an assessment of intensity for each AE and 
 
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SAE reported during the study and will assign it to one of the following categories:
Mild: An event that is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
Moderate: An event that is sufficiently discomforting to interfere with normal 
everyday activities
Severe: An event that prevents normal everyday activities. -an AE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe.
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality:
The Investigatoris obligated to assess the relationship between study product 
and the occurrence of each AE/SAE.
A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.
The Investigatorwill use clinical judgment to determine the relationship.
Alternative causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the 
event to the study product will be considered and investigated.
The Investigatorwill also consult the InvestigatorBrochure (IB) and/or 
Product Information, for marketed products, in the determination of his/her 
assessment.
For each AE/SAE the Investigatormust document in the medical notes 
(source document) or CRF that he/she has reviewed the AE/SAE and has 
provided an assessment of causality.
There may be situations when an SAE has occurred and the Investigatorhas 
minimal information to include in the initial report to GSK. However, it is 
very important that the Investigatoralways make an assessment of 
causality for every event prior to the initial transmission of the SAE data 
to GSK.
The Investigatormay change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.
The causality assessment is one of the criteria used when determining 
regulatory reporting requirements.
7.4. Reporting Adverse Events and Serious Adverse Events
AE Reporting to GSKCH:
AEs will be recorded in the AE section of the CRF. 
Medical conditions recorded by the subject on a diary
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document that meet the definition of an AE must also be recorded in the AE 
section of the CRF, if not previously well-characterized by the Investigatorin 
the subject’s medical history. 
AEs elicited by the Investigatorin a standard manner at the study visits should 
also be recorded in the AE section of the CRF. The Investigatoror designee 
must ask the subject the following question during each visit including any 
follow-up visits: “Have you felt unwell, experienced any symptoms or taken 
any medication (since your last visit) (today) (since your last dose) (since the 
last session)?”
The medically qualified Investigatorshould review adverse events in a timely 
manner; this review should be documented in writing in the source document 
or in the CRF. 
After the study is completed at a given site, and the site has received their 
study data on Compact Discs (CDs), the electronic data collection tool will be 
removed from the internet to prevent the entry of new data or changes to 
existing data.
SAE Reporting to GSKCH:
A paper copy of the SAE form provided in the Investigatorstudy master file should 
be completed as fully aspossible. 
It is essential to enter the following information: 
Protocol and subject identifiers
Subject’s demography
Description of events, with diagnosis if available
Investigatoropinion of relationship to study product (see Section 8.3.)
Criterion forseriousness.
The following are desirable and are of particular relevance for Investigatorand 
GSKCH 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 faxed to PPD within 24 
hoursof awareness at the following fax number:
SAE Contact Information
PPD Hotline: 
PPD Fax: 
 
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PPD will then emailthe SAE form to the Case Management Group, Global Clinical 
Safety and Pharmacovigilanceat GSK, with copy to the appropriate GSKCH Study 
Manager as soon as possible, but not later than 1 business day after study site 
personnel learn of the event. The GSKCH Study Manager will be responsible for 
forwarding the SAE form to the Medical Director responsible for the study and other 
GSKCH personnel as appropriate via email.
The initial report will be followed up with more information as relevant, or as 
requestedby the GSKCH study manager.
7.5. Follow-up of Adverse Events and Serious Adverse Events
Follow-up of AEs and SAEs:
After the initial report, the Investigatoris required to proactively follow up 
with each subject and provide further information on the subject’s condition.
All AEs/SAEs will be followed until resolution, until the condition stabilizes, 
until the event is otherwise explained, or until the subjectis lost to follow-up. 
The Investigatoris obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as may be indicated or as 
requested by GSK to elucidate as fully as possible the nature and/or causality 
of the AE or SAE.
Investigators are not obliged to actively seek AEs or SAEs in former subjects. 
However, if the Investigatorlearns of any SAE, including the death, at any 
time after a subject has been discharged from the study, and considers the 
event reasonably related to the investigational product or study participation, 
the Investigatorwill promptly notify GSKCH.
The Investigatorwill submit any updated SAE data to GSK within the 
designated reporting time frames.
 
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Regulatory and ethics reporting requirements for SAEs:
The Investigatorwill promptly report all SAEs to GSKCH within the 
designated reporting timeframes (within 24 hours of learning of the event). 
GSKCH has a legal responsibility to notify, as appropriate, the local 
regulatory authority and other regulatory authorities about the safety of a 
product under clinical investigation. Prompt notification of SAEs by the 
Investigatorto GSKCH is essential so that legal obligations and ethical 
responsibilities towards the safety of subjects are met.
GSKCH will comply with country specific regulatory requirements relating to 
safety reporting to the regulatory authority, IRB and Investigators.
Investigatorsafety reports are prepared according to GSKCH policy and are 
forwarded to Investigators as necessary. An Investigatorsafety report is 
prepared for a SAE(s) that is both attributable to investigational product and 
unexpected. The purpose of the report is to fulfill specific regulatory and GCP 
requirements, regarding the product under investigation.
An Investigatorwho receives an Investigatorsafety report describing a 
SAE(s) or other specific safety information (e.g., summary of listing of SAEs) 
from GSKCH will file it with the InvestigatorBrochure (or safety statement) 
and will notify the IRB, if appropriateaccording to local requirements.
7.6. Collection of Pregnancy Information
7.6.1.Time Period for Collecting of Pregnancy Information
Collection of Pregnancy Information:
Pregnancy information will be collected on all pregnancies reported following 
administration of any investigational product. Information on pregnancy 
identified during the screening phase and prior to investigational product 
administration does not need to be collected.
 
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7.6.2. Action to be Taken if Pregnancy Occurs
Action to be Taken:
The investigator will collect pregnancy information on any subject who 
becomes pregnant while participating in the study after administration of the 
investigational product. The investigator will record pregnancy information on 
the appropriate form and submit it to PPDwithin 2 weeks of learning of the 
subject becoming pregnant. The subject will be followed to determine the 
outcome of the pregnancy. Information on the status of the mother and infant / 
neonate (including concomitant medications taken by the mother during the 
pregnancy) will be forwarded to PPD. Generally, follow-up will be no longer 
than 6 to 8 weeks following the estimated delivery date. Any termination of 
the pregnancy will be reported.Like with SAE and Incident Forms, PPD will 
then email the pregnancy form to the Case Management Group, Global 
Clinical Safety and Pharmacovigilance at GSK. 
While pregnancy itself is not considered to be an AE, any pregnancy 
complication or elective termination for medical reasons will be recorded as 
an AE orSAE.
A spontaneous abortion is always considered to be an SAE and will be 
reported as such. An SAE occurring in association with a pregnancy, brought 
to the investigator’s attention after the subject completed the study and 
considered by the investigator as possibly related to the investigational 
product, must be promptly forwarded to GSK.
While the investigator is not obliged to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous 
reporting.
If thesubject becomes pregnant during the study they should be withdrawn 
from the study and this should be recorded in the appropriate section of the 
CRF. 
8. DATA MANAGEMENT
For this study subject data will be entered into an electronic case report form, using a
CRO
's validated data system.
8.1. Source Documents/ Data
The source documents (e.g. hospital records, clinical and office charts, laboratory 
notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, subject files and records kept at the 
pharmacy, at the laboratory and at the medico-technical departments involved in the 
 
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clinical study) which contain the source of data recorded in the CRF should be 
specified. In some cases the e-diarycan be used as a source document.
Each subject will be assigned and identified by a unique Screening Number. Any 
reference made to an individual subject within the study must be done using the 
unique Screening Number.
8.2. Electronic Case Report Form
A CRF is a printed, optical, or electronic document designed to record all of the 
protocol required information to be reported to the sponsor on each trial subject.
For each subject who has given informed consent and has been screened, CRF must 
be completed and signed by the Principal Investigator(or authorized designee) to 
certify that the data are complete and correct.
Management of clinical data will be performed in accordance with applicable CRO 
standards and data cleaning procedures to ensure the integrity of the data e.g. 
removing errors and inconsistencies in the data. 
In order to protect the privacy of subjects,no Personally Identifiable Information 
(PII) (including the subject
's name or initials or birth date) is to be recorded in the 
CRF or as part of the query text.
Adverse events and concomitant medications terms (if applicable) will be coded 
using MedDRA (Medical Dictionary for Regulatory Activities) and an internal 
validated medication dictionary, GSKDrugrespectively. 
All CRF pages must be completed during a subject assessment when the CRF has 
been designated as the source. Data that is sourced elsewhereshould be entered into 
the CRF in an agreed upon timeframe between the Investigatorand Sponsor. 
At completion of the study report, all CRF data(including queries, query responses 
and audit trails) will be transmitted in an agreed upon format to GSKCH via secured 
web portal or CD/DVD via mail carrier with tracking capabilities. 
8.3. 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, 
 
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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.
8.3.1. Data 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 (Adverse Events and Drugs) are reported appropriately. 
The study monitor atthe study siteswill review the CRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigatoror designee, enabling the errors to be addressed in parallel with Data 
Management review. Monitor can also run reports and listings on the CRFs, to raise 
manual queries as needed for site clarification or correction.
8.4. Processing Patient Reported Outcomes
Patient reported outcome (PRO) data will be collected directly into an electronic diary 
(e-diaries).AEs and concomitant medications entered into the e-diary will be 
transcribed into the eCRF.Data from the e-diaries will be extracted and loaded in a 
secured web portal,for the CROhandling Data Managementto perform necessary 
reconciliationwith the study data in the Clinical Data Management system. The 
process for reconciliation will be handled the same way as external data below. The
e-diary datawill eventually be merged with the Study Data sets.
8.5. External Data
External Data are subject data obtained externally to the CRF. These data are 
generated from laboratory instruments, computers, e-diariesor other sources and then 
transcribed into a file and format agreed upon by CRO 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. 
Proper 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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9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
This section provides the key features of the planned data analysis. The data analysis 
will be performed in accordance with the ICH E9 Guidelines. 
9.1 Sample Size Determination
There is no previous experience and data with 1146A in the common cold setting and 
literature on products similar to 1146A and their efficacy on common cold symptoms 
is sparse.However, one paper was considered useful to be taken as basis for the 
sample size estimation.In aprevious study (Hull et al, 2007), a nasal irrigation spray, 
designed to deliver a low pH gel to the nasal cavity was compared to placebo. That 
study had a comparable scenario in terms of the form (spray) of the study product and 
regarding the endpoint as the current study. That study measured the cold severity for 
the 7 days of dosing, defined as the mean of the average of total symptom severity 
scores at 9:00 across the 7 days of dosing and of average of total symptom severity 
scores at 21:00 across the 7 days of dosing. The total symptom severity score was 
calculated per assessment by summing the severity scores across the 5 symptoms 
sore/scratchy throat, runny nose, blocked nose, cough, and tired/run down feeling 
(each scored using a 4-point scale 0 = absent, 1= mild, 2 = moderate, and 3=severe). 
The mean score of the average of the total symptom severity score reported for 
placebo was 0.8 with a standard deviation of 0.4 (n=85).Although the endpoint used 
in the Hull study differs slightly from the endpoint(s) in the current studyand it was 
calculated over a longer time period (7 days as opposed to 4 days in the current 
study), it is assumed that the placebo result and the variability reported in the Hull 
study are indicative for the severity of cold symptoms in such setting and for 
comparable severity endpoints.
UPON REVIEWOF THEMOST RECENT LITERATURE (FAZEKAS ET AL 
2012, LUDWIG ET AL 2013 AND ECCLES ET AL 2015), SIMILAR STUDIES 
EMPLOYING THE USE OF NASAL SPRAY PRODUCTSWITH A SIMILAR 
PURPORTED MECHANISM OF ACTION HAD SAMPLE SIZES BETWEEN 
153 AND 211. THEREFORE, AN APPROXIMATE SAMPLE SIZE OF 170 (85 
SUBJECTS IN EACH TREATMENT GROUP) IS CONSIDERED
SUFFICIENT FOR THIS STUDY. 
A SUFFICIENT NUMBER OF SUBJECTS WILL BE SCREENED TO 
ENROLL APPROXIMATELY 170 SUBJECTS. 
 
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A sample sizeof 274subjects (137 subjects per arm) will achieve 80% power to 
reject the null hypothesis of equal means in both arms for the average nasal symptom 
score when the mean difference is 17% (e.g. 0.136when the placebo mean score 
result is 0.8) with a common standard deviation of 0.40 and with a significance level 
(alpha) of 0.05using a two-sided two-sample equal-variance t-test. Considering a 
dropout rate of approximately 10%, 300 subjects will have to be recruited to have274 
evaluable subjects.
NQuery Advisor 7.0 Software was used to calculate the sample size.
9.2. General Considerations
9.2.1. Definition of Analysis Populations
The following analysis populations are defined:
The Intent-to-Treat (ITT) population will consist of all randomized subjects.
A modified ITT population will consist ofsubjects who
-received at least one dose of study treatment
-have at least one post-baseline efficacy assessment 
The Safety population (SAF) will include all randomized subjects who received at 
least one dose of study treatment.
The Per-Protocol (PP) population will be determined from compliance during 
days 1 to 4, since this is the period of the primary efficacy evaluation. Protocol 
deviations leading to the exclusion ofsubjects from the PP population will 
include:
-subjects who complete less than 80% or more than 120% of their target number 
of actuations over Days 1 to 4 
-subjects who miss 2 or more doses on any one day during Days 1 to 4
-subjects who miss a totalof 4 or more of their doses during Days 1 to 4
-subjects who miss more than 1 nasal assessment on any one day duringDays 1 
to4.
Other reasons for exclusion from the PP population will be detailed in the 
statistical analysis plan(SAP).
9.2.2. Exclusionof Data from Analysis
 
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Exclusion of any data from the analyses will be determined during a BlindData 
Review Meeting prior to database lock. Any reasons for exclusion from an analysis 
population will be listed, if applicable.
9.2.3. Criteria for Assessing Efficacy
The primary efficacy criterion is the difference in the mean of the average nasal
symptom score of the two treatments armson Days 1to 4.At each assessment, the 
individual nasal symptom scores (blocked nose,runny nose,and sneezing) will be 
summed to provide the NSS. On each day, the NSS scores at each assessment 
(excluding the baseline NSS on Day 1) will be averaged (mean) to provide a daily 
NSS. A subject’s average nasal symptom score on Days 1to 4(ANSS
1-4) is 
calculated as the mean of these dailysum scores for the nasal symptoms  across the 
Days 1to 4.
The investigational product will be considered effective if the mean ANSS1-4in the 
active treatment arm is at least 17% lower than in the placebo arm.
9.2.4. Criteria for Assessing Safety
Safety is assessed by comparing the incidence of adverse events between treatment 
arms.
It is expected that the findings in both treatment arms are comparable. 
9.2.5. Handling of Dropouts and Missing Data
Dropouts will not be replaced and for the primary analysis, missing data after dropout 
will not be imputed.
For data that is missing at intermediate assessments from subjects who still continue 
in the study, the fact that these subjects remain in the study and provide data at 
subsequent assessments supports the assumption that the mechanism for the missing 
data atthese intermediate assessments is unlikely to be related to either their 
randomized treatmentor the condition under study. Therefore, missing common cold 
symptom scores between two non-missing symptom scores will be imputed by the 
mean of the last available and the next available symptom score.
In the event that more than 10% of subjects do not complete the first 4 days of 
treatment (i.e. the period over which the primary endpoint is evaluated) or if there is a 
differential drop-out rate between the treatment groups, sensitivity analyses using 
 
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different imputation methods for data that is missing post-discontinuationwill be 
performed. These sensitivity analyses will be detailed in the SAP.
Subjects will be instructed not to take any additional cough/cold medications, 
including but not limited to, prescription,OTC, non-drug/nutritional supplement, or 
procedures throughout the study. Subjects will be instructed to use 
acetaminophen/paracetamol over other OTC medications, but should try to avoid use 
if possible. In the event that a subject uses any additional cough/cold medication
(including acetaminophen/paracetamol), its usage (time and reason for use) will be 
recorded in the e-diary. The primary analysis (modified ITT) will use the recorded 
cold symptom scores, irrespective of other cough/cold medication usage.The number 
of subjects using other cough/cold medications and frequency of use will be 
summarized by treatment group. Additional sensitivity analyses will be performed 
whereby cold symptom assessments made within 4 hours after the use of any other
cough/cold medication are set to missing and various methods used to impute these 
values. The imputation methods used will (a) reflect the fact that the true cold 
symptom score,had alternative medication not been used, would have been at least as 
severe as the cold symptom scoreprior to the use of the alternativemedication, and 
(b) to ensure the imputed values do not introduce a bias in favor of the test product. 
Missing data imputations will be applied throughout the assessment period (day 1 to 
day 8). Furtherdetails of the imputation methods will be provided in the SAP.  
9.2.6. Other Issues
None
9.3. Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the SAP, 
which will be written following finalization of the protocol and prior to study 
unblinding.
A review of the study data will be conducted before the study is unblinded, and any 
decisions made at that meeting leading to changes in the statistical analyses, e.g., 
additional outcomes and analysis populations, exclusion of subjects or data from 
analysis, will be documented in the SAP. Any changes in the statistical analysis that 
must be made after the study is unblinded will be documented separately and 
described in clinical study report.
Continuous data will be summarized by descriptive statistics showing the number of 
subjects (N), the mean, standard deviation (SD), median and minimum and 
 
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maximum. Categorical data will be summarized by frequency tables showing the 
number and percentage of subjects falling into each category. All study data will be 
listed.
Unless stated otherwise, for a parameter the Baseline value is the value of the last 
valid measurement/assessment prior to the first dose of study treatment.
9.3.1. Demographic and Baseline Characteristics
Demographic and other baseline data will be summarized descriptively overall and by 
treatment arm and by gender (and overall) for the Safety population.
9.3.2. Primary Analysis
The nasal symptom score (NSS) for a subject and time point will be calculated as the 
sum score of the nasal symptoms (blocked nose,runny nose,and sneezing) at that
time point.
The primary efficacy endpoint isaverage nasal symptom score on Days 1 to 4
(ANSS
1-4). At each assessment, the individual nasal symptom scores will be summed 
to provide the NSS. On each day, the NSS scores at each assessment (excluding the 
baseline NSS on Day 1) will be averaged (mean) to provide a daily NSS. A subject’s 
ANSS1-4is calculated as the mean of thesedaily NSS across study Days 1 to 4.
The ANSS1-4will be summarized by means of descriptive statistics by treatment arm.
For the differenceof the ANSS1-4between the two treatment arms, the mean and the 
95% confidence interval for the mean will be derived. If deemed appropriate, 
descriptive statistics might be further broken down by center,genderand/or Day 1 
dosing time stratification. The means of the ANSS1-4in both treatment arms will be 
compared using an analysis of covariance (at a significance level of 0.05), with
factors for treatment,centerand Day 1 dosing time stratification,and Baseline NSS 
(Day 1 prior to the first dose) as a covariate.The primary analysis will be done for the
modifiedITT population.
THE IMPACT OF SUBJECTS WITH ONSET OF SYMPTOMS OF 
COMMON COLD BETWEEN > 48 AND ≤ 72 HOURS WILL BE REVIEWED 
IF THERE AREMORE THAN 10% OF SUCH SUBJECTS IN THE 
PRIMARY ANALYSIS POPULATION. TIME OF ONSET OF SYMPTOMS 
OF COMMON COLD MAYBE ADJUSTED FOR IN THE MODEL AND/OR 
JUST A SUMMARY OF THE PRIMARY ENDPOINT WILL BE PROVIDED 
FOR THIS SUBSET OF SUBJECTS.
 
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9.3.3. Secondary Analyses
If more than 20%of the symptom scores in the calculation of the ANSS1-4for an
analysis population are missing, the summaries and analyses described for the 
ANSS1-4in Section 9.3.2 will be repeated for that analysis population on the ANSS1-4
calculatedwithout imputation of missing symptom scores(i.e. observed case 
analysis).In addition, the analysis described in Section 9.3.2 will be repeated for the 
PPpopulation. Depending on the amount of missing data, further sensitivity analyses 
deemednecessary upon blind review of study data may be performed, and these will 
be detailed in the SAP.
Likewise, average nasal symptom score over Days 1to 7(ANSS1-7) will be derived as 
the mean of the dailyNSS across study Days 1to 7, average total symptom scores 
ATSS1-4will be derived as the mean of the dailyTSS across study Days 1 to 4, and 
average total symptom scores ATSS1-7will be derived as the mean of the dailyTSS 
across study Days 1 to 7. The ANSS1-7,ATSS1-4,and ATSS1-7 will be summarized 
and analyzed in the same manner as ANSS1-4.
9.3.4. Safety Analyses
Safety variables (incidence of adverse events, and vital signs) will be summarized for 
the Safety population. All tables will be presented by treatment arm.
Treatment emergent adverse events, i.e. AEs that start or worsen during the treatment 
period(on or after first study treatmentadministration), will be summarized by 
presenting the number and percentage of subjects having any AE, any AE in each 
MedDRA System Organ Class (SOC) and having each individual AE (using 
MedDRA preferred term). The subset of AEs suspected of a relationship to study
 
treatmentwill be presented similarly. All treatment-emergent AEs will also be 
tabulated by severity. Any other information collected (e.g. action taken, duration, 
outcome) will belisted. 
For the summary by severity, subjects who have multiple occurrences of the same AE 
will be classified according to the worst reported severity of the AE. Similarly, for the 
summary by treatmentrelationship, the AE will be classified according to the closest 
relationship.
Vital signs (blood pressure, pulse, respirationrate, and body temperature) and their 
change from baseline will be summarized with descriptive statistics. 
 
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9.3.5. Other Analyses
9.3.5.1. Treatment Exposure and Treatment Compliance
Study treatmentexposure and treatment compliance will be summarized descriptively 
by treatment arm for the Safety population, including the following summaries:
Number of subjects who took study treatmentby study day (frequency table)
Total number of administrations (frequency table)
Total dose and average daily dose received
Treatment compliance (frequency table)
9.3.5.2. Use of Concomitant Medication
Use of concomitant medication will be summarized by medication classes (levels 1 
and 2) of the Anatomical Therapeutic Chemical (ATC) classification system and by 
treatment arm.
9.3.5.3. Exploratory Analysis
All exploratory analysis below will be done for the modified ITT population.
The mean dailyNSS (MDNSS) per study day will be derived as the mean of a 
subject’s NSS scores per study day. The MDNSS and its change from baselinewill be 
summarized by descriptive statistics by treatment arm and day. NSS and MDNSS will 
be displayed graphically as line graphs showing the mean +/-SE within each 
treatment arm over time.
Likewise, the mean dailytotal symptom score (MDTSS) per day will be calculated. 
The MDTSS and its change from baselinewill be summarized by descriptive 
statistics by treatment arm and day. TSS and MDTSS will be displayed graphically as 
line graphs showing the mean +/-SE within each treatment arm over time.
Finally, for each symptom, the mean daily individual symptom scores(MDISS) per 
day will be calculated. The MDISS and change from baseline will be summarized by 
descriptive statistics by treatment arm and day. Individual symptom scores and 
MDISS will be displayed graphically as line graphs showing the mean +/-SE within 
each treatment arm over time.  
The course of each of the 8common cold symptoms across the treatment period will 
be summarized using frequency tables by treatment arm and day.
 
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10. STUDY GOVERNANCE CONSIDERATIONS
10.1. Posting of Information on Publicly Available Clinical Trials 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
10.2. Regulatory and Ethical Considerations, Including the Informed 
Consent
The study will be conducted in accordance with all applicable regulatory 
requirements, and with GSK policy.
The study will also be conducted in accordance with ICH Good Clinical Practice 
(GCP), all applicable subject privacy requirements, and the guiding principles of the 
current version of the Declaration of Helsinki. This includes, but is not limited to, the 
following:
Before initiating a trial, the Investigator/institution should have written and 
dated approval/favorable opinion from the IRB for the trial protocol 
(including amendments), written informed consent form, consent form 
updates, subject recruitmentprocedures (e.g., advertisements), Investigator
brochure/ safety statement (including any updates) and any other written 
information to be provided to subjects. A letter or certificate of approval will 
be sent by the Investigatorto the sponsor prior to initiation of the study, and 
also when subsequent amendments to the protocol are made.
Signed informed consent to be obtained for each subject before participation 
in the study (and for amendments as applicable)
Investigatorreporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IRB)
GSK will provide full details of the above procedures, either verbally, in 
writing, or both.
10.3. Quality Control (Study Monitoring)
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.
 
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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 PPD. 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.
10.4. 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 theirstaff 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 sponsor will be available to help Investigators prepare for an inspection.
10.5. Conditions for Terminating the Study
Upon completion or premature discontinuation of the study, the GSKCH monitor will 
conduct site closure activities with the Investigatoror site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSKCH Standard 
Operating Procedures.
Both GSKCH and the Investigatorreserve the right to temporarily suspend or 
prematurely discontinue this study at any time for reasons including, but not limited 
 
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to, safety or ethical issuesor severe non-compliance. For multicenter studies (if 
applicable), this can occur at one or more or at all sites.
If the trial is prematurely terminated or suspended for any reason, the Investigatorsite 
should promptly inform the trial subjects and should assure appropriate therapy/ 
follow-up for the subjects. Where required by the applicable regulatory requirements, 
GSKCH should inform the regulatory authority(ies). 
In addition: 
If the Investigatorterminates or suspends a trial without prior agreement of 
GSKCH, the Investigatorsite should promptly inform the sponsor and the 
IRB, and should provide the sponsor and the IRB a detailed written 
explanation of the termination or suspension.
If the GSKCH terminates or suspends a trial, the Investigatorshould promptly 
inform the IRB and provide the IRB a detailed written explanation of the 
termination or suspension. 
If the IRB terminates or suspends its approval/favorable opinion of a trial, the 
Investigatorshould promptly notify the GSKCH and provide GSKCH with a 
detailed written explanation of the termination or suspension.
10.6. Records Retention
Following closure of the study, the Investigatormust 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 Investigatormust 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 Investigatormust ensure there 
is an acceptable back-up of these reproductions and that an acceptable quality control 
process exists for making these reproductions.
 
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The Investigatormust assure that the subject’s anonymity will be maintained. On 
CRFs or other documents submitted to GSKCH, subjects should not be identified by 
their names or initials, but by an identification code. The Investigatorshould keep a 
separate log of subjects’ codes, names and addresses. Documents not for submission 
to GSKCH, e.g. subjects’ written consent forms, should be maintained by the 
Investigatorin strict confidence.
GSK will inform the Investigatorof the time period for retaining these records to 
comply with all applicable regulatory requirements (GSKCH recommends that 
documents be kept for 10years). The Investigatoris also required to keep subject 
identification codes on file for at least 15 years after completion or discontinuation of 
the study. 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 destroy
ed without a prior written agreement between 
GSKCH and the Investigator. The Investigatormust notify GSK of any changes in the 
archival arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the Investigatoris no longer 
associated with the site.
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an Investigatorsignatory will 
be identified for the approval of the clinical study report. The Investigatorwill 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 Investigatorwith the full summary of the study results. The 
Investigatoris 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.
 
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A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
 
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11. REFERENCES
American College of Toxicology (ACT).Final report on the safety assessment of 
carbomers -934, -910, -934P, -940, -941 and -962. Elder RL, editor. Int. J. 
Toxicology.1982;1:109-141, DOI: 10.3109/10915818209013151.
American College of Toxicology (ACT). Final report on the safety assessment of 
acrylates copolymer and 33 related cosmetic ingredients. Andersen FA, editor. 
International Journal of Toxicology. 2002;21Suppl 3:1-50.
BoujaoudeZC, PratterMR. Clinical approach to acute cough. Lung. 2010 Jan;188 
Suppl 1:S41-6. DOI: 10.1007/s00408-009-9170-6. E pub 2009 Aug 22.
ECCLESR., ET AL. EFFICACY AND SAFETY OF IOTA-CARRAGEENAN 
NASA SPRAY VERSUS PLACEBO IN EARLY TREATMENT OF THE 
COMMON COLD IN ADULTS: THE ICC TRIAL. RESPIRATORY 
RESEARCH. 2015;16:121
FAZEKAS T., ET AL. LESSONS LEARNED FROM A DOUBLE-BLIND 
RANDOMIZED PLACEBO-CONTROLLED STUDY WITH A IOTA-
CARRAGEENAN NASAL SPRAY AS MEDICAL DEVICE IN CHILDREN 
WITH ACUTE SYMPTOMS OF COMMON COLD. BMC 
COMPLEMENTARY AND ALSTRENATIVE MEDICINE. 2012; 12:147
[Gwaltney JM Jr., and Druce HM. (1997)]. Efficacy of brompheniramine maleate for 
the treatment of rhinovirus colds. Clinical Infectious Diseases. 25:1188-1194.
Hayden FG, Diamond L, Wood PB, Korts DC, Wecker MT. Effectiveness and safety 
of intranasal ipratropium bromide in common colds. A randomized, double-blind, 
placebo-controlled trial. Ann Intern Med. 1996 Jul 15;125:89-97.
Hull D, Rennie P, Noronha A, PooreC, Harrington N, Fearnley V, et al.Effects of 
Creating a Non-Specific, Virus-Hostile Environment in the Nasopharynx on Specific 
Symptoms and Duration of Common Cold. Acta Otorhinolaryngol Ital. 2007;27:73-
77.
Kennedy JL, Turner RB, Braciale T, HeymannPW, Borish L. Pathogenesis of 
rhinovirus infection. Curr Opin Virol.2012;2(3):287-293.
Lubrizol.Formulating Toothpaste Using Carbopol® Polymer[Internet].2010 [cited 
2014 Oct 30]. Available from:http://www.lubrizol.com/Life-
Science/Documents/Pharmaceutical/Bulletins/Bulletin-24---Formulating-Toothpaste-
Using-Carbopol-Polymer.pdf.
LUDWIG M, ET AL. EFFICACY OF A CARRAGEENAN NASAL SPRAY IN 
PATIENTS WITH COMMON COLD:A RANDOMIZED CONTROLLED 
TRIAL. RESPIRATORY RESEARCH. 2013; 14:124
Proud D,Turner R, Winther B, Wiehler S, Tiesman J, Reichling T, et al.Gene 
Expression Profiles during InVivo Human Rhinovirus Infection-Insights into the 
Host Response. Am J Respir Crit Care Med. 2008;178(9):962–968.
Sperber SJ, Sorrentino JV, Riker DK, Hayden FG. Evaluation of an alpha agonist 
alone and in combination with a nonsteroidal antiinflammatory agent in the treatment 
of experimental rhinovirus colds. Bull N Y Acad Med. 1989 Jan;65(1):145-60.
 
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Sperber SJ, Hendley JO, Hayden FG, Riker DK, Sorrentino JV, Gwaltney JM Jr. 
Effects of naproxen on experimental rhinovirus colds. A randomized, double-blind, 
controlled trial. Ann Intern Med. 1992 Jul 1;117(1):37-41.
[Simasek M and Blandino DA] Treatment of the common cold. Amer. Fam. 
Physician, 2007, 75 (4): 515-20.
Singh M, Das RR; Zinc for the common cold. Cochrane Database Syst Rev. 
2013Jun18;6:CD001364. DOI: 10.1002/14651858.CD001364.pub4.
Turner RB, Hendley JO, Gwaltney JM Jr.Shedding of infected ciliated epithelial 
cells in rhinovirus colds. J Infect Dis.1982;145(6):940-953.
Turner RB. Efficacy of Tremacamara, a soluble intercellular adhesion molecule 1, for 
experimental rhinovirus infection. JAMA. 1999;281(19):1797-1804.
Vicks First Defence Nasal Spray, Package Information. Proctor &Gamble [Internet]. 
2014 [cited 2015 Nov 30]. Available from:http://www.vicks.co.uk/products/cold-
intervention/vicks-first-defence-nasal-spray/.
 
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12. APPENDICES
12.1. Appendix 1 -Abbreviations
AE
Adverse event
ATC
Anatomical therapeutic chemical
ANSS 1-7
Average nasal symptom score days 1-7
ANSS 1-4
Average nasal symptom score days 1-4
ATSS 1-7
Average total symptom scores over days 1-7
ATSS 1-4
Average total symptom scores over days 1-4
BP
Blood pressure
°C
Degrees Celsius
CD
Compact Disc
COPD
Chronic obstructive pulmonary disease
CRF
Case report form
CRO
Contract research organization
CSM
Clinical study manager
EDC
Electronic data capture
GCP
Good clinical practice
GSKCH
GlaxoSmithKline Consumer Healthcare
HDPE
High-density polyethylene
HRVs
Human rhinoviruses
IB
Investigator brochure
ICAM-1
Intercellular adhesion molecule 1
ICH
International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human 
Use
IRB
Institutional review board
IRT
Interactive response technology
ITT
Intention to treat
LDPE
Low-density polyethylene
MDISS
Mean daily individual symptom score
MDNSS
Mean dailynasal symptom score
MDTSS
Mean dailytotal symptom score
NSAID
Non-steroidal anti-inflammatory
NSS
Nasal symptom score
OTC
Over-the-counter
PII
Personally identifiable information
PP
Per protocol
PRO
Patient reported outcome
SAE
Serious adverse event
 
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SAP
Statistical analysis plan
SD
Standard deviation
SE
Standard error
SOC
System organ class
TSS 1-7
Total symptom score days 1-7
TSS 1-4
Total symptom score days 1-4
Trademark Information
Trademarks not owned by the GlaxoSmithKline group of companies:
Carbopol
 
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SAP_001.pdf: 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... IV 
1. 
INTRODUCTION ............................................................................................................. 1 
2. 
OBJECTIVES .................................................................................................................... 2 
2.1 PRIMARY OBJECTIVE ........................................................................................................... 2 
2.2 SECONDARY OBJECTIVES .................................................................................................... 2 
2.3 EXPLORATORY OBJECTIVES ................................................................................................ 2 
3. 
INVESTIGATIONAL PLAN ........................................................................................... 2 
3.1. OVERALL STUDY DESIGN AND PLAN ................................................................................... 2 
3.2. STUDY ENDPOINTS .............................................................................................................. 5 
3.3. TREATMENTS ....................................................................................................................... 6 
3.4. DOSE ADJUSTMENT/MODIFICATIONS .................................................................................. 6 
4. 
GENERAL STATISTICAL CONSIDERATIONS ........................................................ 6 
4.1. DEFINITION OF BASELINE AND STUDY DAY ........................................................................ 7 
4.2. SAMPLE SIZE ....................................................................................................................... 7 
4.3. RANDOMIZATION, STRATIFICATION, AND BLINDING ........................................................... 7 
4.4. ANALYSIS POPULATION ....................................................................................................... 7 
4.4.1. 
Intent-to-Treat (ITT) Population ................................................................................. 8 
4.4.2. 
Modified Intent-to-Treat (mITT) Population .............................................................. 8 
4.4.3. 
Safety (SAF) Population ............................................................................................. 8 
4.4.4. 
Per Protocol (PP) Population .................................................................................... 8 
5. 
SUBJECT DISPOSITION ................................................................................................ 9 
5.1. DISPOSITION ........................................................................................................................ 9 
5.2. PROTOCOL DEVIATIONS .................................................................................................... 10 
6. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................. 10 
6.1. DEMOGRAPHICS ................................................................................................................ 10 
6.2. BASELINE DISEASE CHARACTERISTICS .............................................................................. 11 
6.3. MEDICAL HISTORY ............................................................................................................ 11 
6.4. INCLUSION AND EXCLUSION CRITERIA .............................................................................. 11 
7. 
TREATMENTS AND MEDICATIONS ....................................................................... 11 
7.1. PRIOR AND CONCOMITANT MEDICATIONS ......................................................................... 11 
7.2. STUDY TREATMENTS ......................................................................................................... 13 
7.2.1. 
Extent of Exposure .................................................................................................... 14 
7.2.2. 
Treatment Compliance and Modifications ................................................................ 14 
8. 
EFFICACY ANALYSIS ................................................................................................. 15 
8.1. PRIMARY EFFICACY ENDPOINT ......................................................................................... 15 
8.1.1. 
Primary Analysis ....................................................................................................... 15 
8.1.2. 
Data Imputation ........................................................................................................ 16 
8.1.3. 
Sensitivity Analysis for Primary Endpoint ................................................................ 16 
8.1.4. 
Secondary Analysis for Primary Endpoint ............................................................... 17 


8.1.5. 
Adjustment of Covariates .......................................................................................... 17 
8.2. 
SECONDARY EFFICACY ENDPOINT .................................................................................... 18 
8.3. 
OTHER EFFICACY ENDPOINTS........................................................................................... 18 
8.3.1. 
Exploratory Analysis ................................................................................................. 18 
9. 
SAFETY ANALYSIS ...................................................................................................... 18 
9.1. ADVERSE EVENTS ............................................................................................................. 19 
9.1.1. 
Incidence of Adverse Events ..................................................................................... 19 
9.1.2. 
Relationship of Adverse Events to Study Drug ......................................................... 19 
9.1.3. 
Severity of Adverse Event .......................................................................................... 20 
9.1.4. 
Serious Adverse Events ............................................................................................. 20 
9.1.5. 
Adverse Events Leading to Study Discontinuation ................................................... 20 
9.1.6. 
Death ......................................................................................................................... 20 
9.2. CLINICAL LABORATORY EVALUATIONS ........................................................................... 20 
9.2.1. 
Urinalysis .................................................................................................................. 21 
9.3. VITAL SIGN MEASUREMENTS ........................................................................................... 21 
9.4. PHYSICAL EXAMINATION ................................................................................................. 21 
9.5. NASAL EXAMINATION ...................................................................................................... 22 
10. 
REFERENCES ................................................................................................................ 22 
11. 
APPENDICES .................................................................................................................. 24 


List of Abbreviations 
 
 
AE 
Adverse event 
ATC 
Anatomical therapeutic chemical 
ANSS1-7 
Average nasal symptom score days 1-7 
ANSS1-4 
Average nasal symptom score days 1-4 
ATSS1-7 
Average total symptom scores over days 1-7 
ATSS1-4 
Average total symptom scores over days 1-4 
°C 
Degrees Celsius 
CRF 
Case report form 
GSKCH 
GlaxoSmithKline Consumer Healthcare 
IBHRVs 
Human rhinoviruses 
ICAM-1 
Intercellular adhesion molecule 1 
ICH 
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
IRT 
Interactive response technology 
ITT 
Intention to treat 
LOCF 
Last observation carried forward 
MDISS 
Mean daily individual symptom score 
MDNSS 
Mean daily nasal symptom score 
MDTSS 
Mean daily total symptom score 
mITT 
Modified Intention to treat 
NSAID 
Non-steroidal anti-inflammatory 
NSS 
Nasal symptom score 
OTC 
Over-the-counter 
PP 
Per protocol 
PRO 
Patient reported outcome 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SOC 
System organ class 
TSS1-7 
Total symptom score days 1-7 
TSS1-4 
Total symptom score days 1-4 


 
1. Introduction 
The common cold is part of life, with most adults having 2-3 symptomatic infections per 
year, and children having a much higher incidence [Simasek, 2007]. Treatment options for 
the common cold focus on symptom control. For example, intranasal or oral decongestants 
are effective to improve nasal patency and thus relieve congestion [Sperber, 1989], first 
generation antihistamines reduce sneezing (Gwaltney 1997), ipratropium reduces 
rhinorrhea [Hayden 1996] and NSAIDS may reduce fever and sore throat [Sperber, 1992]. 
Antitussives and mucolytics are often used to ameliorate cough and promote expectoration 
[Singh, 2013]. 
 
As the common cold is manifest through a plethora of symptoms, not all of which are 
displayed by each sufferer, there is a need for treatment options which are not specifically 
symptom related. Various nasal sprays that do not contain pharmacologically active 
ingredients are available as physical barriers to prevent viruses interacting with nasal 
epithelium cells but little clinical data exist to support a benefit [Hull, 2007]. 
 
The pathophysiological processes that cause symptoms of the common cold continue to be 
explored. The fundamental premise was established in 1982 when it was proposed that 
these symptoms are mediated through the release of inflammatory substances by the host 
in response to infection and that direct viral cytopathology is of lesser importance [Turner 
1982]. In addition to the barrier approach cited above [Hull, 2007], prevention of viral 
attachment to nasal epithelial cells via the Intercellular Adhesion Molecule 1 (ICAM-1) 
receptor, the mechanism by which the virus gains access to the cell to allow replication, 
has been explored. Tremacamara, a recombinant soluble ICAM-1, was shown to be 
effective in reducing the symptoms of experimental common colds [Turner, 1999]. A 
novel approach to minimizing an upper respiratory tract infection is to combine a barrier 
effect with an activity which prevents rhinovirus from binding to ICAM-1 receptors. 
 
1146A contains carbomer 980, one of a series of anionic, synthetic, high molecular 
weight, 
non-linear polymers of acrylic acid [ACT, 1982]. 
 
 
 
 Carbomers inhibit human rhinovirus replication by a dual mode of action. First, 
above concentrations of 0.1% w/w carbomer 980 forms a viscous gel, which acts as a 
physical barrier. Second, carbomers are anionic and are believed to readily associate with 
the cationic binding sites on HRV which prevents viral interactions with the nasal 
epithelial cells via the cell surface receptors. Therefore, by preventing interaction with the 
cell surface receptors, the virus is prevented from entering the cell [Kennedy, 
2012]. 
 
Carbomer 980 and 940 are used in ophthalmics, topicals, drugs, cosmetics, nasal 
moisturizing gel (Ocean Nasal Moisturizer Gel®- concentration unknown) and toothpaste 
[Lubrizol, 2010] and are generally regarded as safe.
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2. Objectives 
 
This study, to be conducted in adult subjects with symptoms of common cold, is designed 
to assess if 1146A nasal spray reduces the severity of symptoms of the common cold 
compared to placebo. The study will also evaluate the safety of 1146A compared to 
placebo. 
 
2.1 Primary Objective 
 
• To assess the efficacy of 1146A in reducing the severity of nasal symptoms on 
days 
1-4, using the average nasal symptom score, compared to placebo in adult subjects 
with the common cold 
 
2.2 Secondary Objectives 
 
• Efficacy: 
o To assess the efficacy of 1146A in reducing the severity of nasal 
symptoms 
on days 1-7, using the average nasal symptom score, compared to placebo 
in adult subjects with the common cold 
 
o To assess the efficacy of 1146A in reducing the severity of symptoms on 
days 1-4 and days 1-7, using the total symptom score, compared to 
placebo 
in adult subjects with the common cold 
• Safety: 
o Adverse events 
 
2.3 Exploratory Objectives 
 
• To assess the efficacy of 1146A in reducing the severity of individual symptoms, 
using the individual symptom score, compared to placebo in adult subjects with the 
common cold 
 
3. Investigational Plan 
 
3.1. Overall Study Design and Plan 
This is a multi-center, randomized, parallel-group, double blind, 2-group, placebo- 
controlled study to evaluate the efficacy and safety of 1146A formulation  
 carbomer 
980 gel nasal spray) in adult subjects with symptomatic common cold in an outpatient 
setting.
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At Screening (Day 1, Visit 1), subjects with symptoms consistent with symptomatic 
common cold of a ≤ 72 hour duration will provide written informed consent to be enrolled 
into the study. During this visit, subjects will undergo eligibility screening, which includes: 
assessment of common cold symptoms and diagnosis by the Investigator; review of 
demographics, medical and medication history; vital sign assessments (blood pressure, 
pulse rate, respiratory rate, oral body temperature, height and weight measurements); 
physical examination; Investigator-led nasal examination; urine pregnancy test (only 
female subjects of childbearing potential); and urine drug screen. 
Eight common cold symptoms are defined as follows: 
Nasal symptoms: 
• runny nose 
• blocked nose 
• sneezing 
 
Other symptoms 
• headache 
• muscle ache 
• chills 
• sore throat 
• cough 
Each individual sign/symptom will be scored using the following 4 point scale: 
0 = absent symptoms (no sign/symptom evident) 
1 = mild symptoms (sign/symptom clearly present, but minimal awareness; easily 
tolerated) 
2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but 
tolerable) 
3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with 
activities of daily living and/or sleeping) 
Only subjects meeting all eligibility criteria including the following symptomatic common 
cold symptoms will be enrolled into the study: 
1. A confirmed common cold diagnosis with symptoms <72 hours; 
2. Total Symptom Score (TSS) > 9 (baseline sum of the 8 common cold 
symptoms); 
3. Score >1 for at least one of the following symptoms: sore throat, runny nose, or 
blocked nose. 


 
Approximately 170 eligible subjects will be stratified and randomized to treatment with 
1146A nasal spray or placebo (vehicle, nasal spray) in a 1:1 ratio at multiple sites. All sites 
should make an effort to enroll approximately equal number of males and females into the 
study. The study sites will stratify and randomize qualified subjects using Interactive 
Response Technology (IRT). 
 
Study site personnel will dispense and train subjects on the e-diary and subjects will then 
perform their baseline self-assessment of common cold symptoms in their e-diary. 
 
Study treatment will be administered via a nasal spray device (1 dose =3 actuations per 
nostril, each actuation is 140L). Dosing administration is 3 actuations per nostril per dose, 
four times a day for 7 days (except for Day 1 where subjects in the 2nd strata will receive 3 
doses). Subjects will be instructed to alternate nostrils after each actuation. First 
administration of study treatment will occur at the study site by independent site personnel 
supervision; first dosing can occur any time prior to 13:00. 
 
Subject randomization will be stratified by dosing time on Day 1 by those study subjects 
receiving first dose of study treatment between the hours of: 8:00-11:00 and those 
receiving first dose of study treatment between the hours 11:01-13:00. On Day 1, subjects 
dosing between 8:00-11:00 will dose every 4 hours ± 30 minutes for 4 doses and subjects 
dosing between 11:01-13:00 will dose every 4 hours ± 30 minutes for 3 doses. 
 
On Days 2-7 all subjects will administer their initial morning dose immediately following 
recording of their common cold symptom assessment at 07:00 ±2 hours and the remaining 
3 doses every 4 hours ± 30 minutes. 
 
Dosing times and number of actuations will be recorded in the subject’s e-diary. Subjects 
will be instructed not to take any additional cough/cold medications, including but not 
limited to, prescription, over-the-counter (OTC), non-drug/nutritional supplement, or 
procedures throughout the study. Subjects will be instructed to use 
acetaminophen/paracetamol over other OTC medications, but should try to avoid use if 
possible. 
 
Subjects will self-evaluate the severity of the following common cold signs/symptoms 
before each dose and record their assessment in the e-diary: headache, muscle ache, chills, 
sore throat, blocked nose, runny nose, cough, and sneezing. Subjects will assess symptom 
severity on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe) at baseline and 4 times 
a day (except for Day 1 where subjects in the 2nd strata will receive 3 doses) through Day 7 
immediately prior to each dose of nasal spray and record the scores in the e-diary. Safety 
will be assessed by occurrence of adverse events. 


 
Upon awakening on the morning of Day 8, subjects will complete a self-assessment of 
common cold symptoms in the e-diary. Subjects will be instructed to return to the study 
sites on Day 8 (End of study/Visit 2). An Investigator-led nasal examination, physical 
examination and vital signs will be repeated during this visit. A repeat urine pregnancy test 
will be performed on all female subjects of child bearing potential. Adverse events and the 
use of concomitant medications will be recorded by the subjects in e-diaries and monitored 
by the site personnel throughout the study. 
 
Subjects who discontinue study treatment prior to Day 7 and those who prematurely 
withdraw from the study for any reason will be instructed to return to the site as soon as 
possible to undergo end of study assessments, and then be discharged from the study. 
 
3.2. Study Endpoints 
 
3.2.1. Efficacy Endpoint 
 
3.2.1.1 Primary Efficacy Endpoint 
 
The nasal symptom score (NSS) for a subject and time point will be calculated as 
the sum score of the nasal symptoms (blocked nose, runny nose, and sneezing) at 
that time point. The primary efficacy endpoint is average nasal symptom score 
across Days 1 to 4 (ANSS1-4). 
 
3.2.1.2 Secondary Efficacy Endpoint 
 
The secondary efficacy endpoints are as follows: 
 
• average nasal symptom score Days 1-7 (ANSS1-7), derived as the mean of the daily 
NSS across study Days 1 to 7. 
• average total symptom score Days 1-4 (ATSS 1-4), derived as the mean of the daily 
TSS across study Days 1 to 4. 
• average total symptom score Days 1-7 (ATSS 1-7), derived as the mean of the daily 
TSS across study Days 1 to 7. 
 
 
3.2.2. Exploratory Efficacy Endpoints 
 
• Individual & composite  total symptom scores (NSS and TSS) Days 1-7 
 
3.2.3. Safety Endpoints 
 
• Spontaneous and solicited adverse events and serious adverse events 


 
 
 
3.3. Treatments 
 
The study treatment is called 1146A formulation ( 
 carbomer 980 gel) nasal spray. The 
control is called placebo (vehicle without carbomer 980) nasal spray. Subjects will apply 
the dose by alternating nostrils. Both treatments will be administered via a nasal spray 
device (1 dose =3 actuations per nostril, each actuation is 140L). Dosing administration is 
3 actuations per nostril per dose, four times a day for 7 days (except for Day 1 where 
subjects in the 2
nd  strata will receive 3 doses). 
 
3.4. Dose Adjustment/Modifications 
 
No dose modification is permitted in this study. 
 
4. General Statistical Considerations 
 
Continuous data will be summarized by descriptive statistics showing the number of 
subjects (N), the mean, standard deviation (SD), median and minimum and maximum. 
Categorical data will be summarized by frequency tables showing the number and 
percentage of subjects falling into each category. When count data are presented, the 
percentage will be suppressed when the count is zero in order to draw attention to the non- 
zero counts. The denominator for all percentages will be the number of subjects in that 
treatment within the analysis set of interest, unless otherwise specified. 
 
For the summary statistics of all numerical variables unless otherwise specified, minimum 
and maximum will be displayed to the same level of precision as reported. Mean and 
median will be displayed to one level of precision greater than the data collected. Standard 
deviation will be displayed to two levels of precision greater than the data collected. P- 
values will be rounded to three decimal places. If a p-value is less than 0.001 it will be 
reported as “<0.001.” If a p-value is greater than 0.999 it will be reported as “>0.999.” 
Data will be displayed in all listings sorted by treatment group. 
 
Unless otherwise specified, baseline will be defined as the last non-missing evaluation 
prior to or on the date that the first dose of treatment is taken. The study day will be 
calculated as assessment date - first dose date of double-blind study drug + 1. 
 
All analyses will be conducted using SAS Version 9.3 or higher. 
 
A two-sided test for primary analysis of the primary efficacy endpoint will be used at a 
Type I error rate of 0.05 for comparison between active group (i.e., 1146A formulation) 
and control group. The p-values reported for sensitivity analyses of the primary efficacy
CCI
 


 
endpoint and statistical analyses of the secondary efficacy endpoints and the exploratory 
efficacy endpoints will not be adjusted for multiplicity and will be considered nominal. 
 
4.1. Definition of Baseline and Study Day 
 
Baseline is defined as the latest assessment prior to the first dose of treatment on Day 1, 
i.e., Day 1 Assessment 1. If a baseline measurement is missing or the subject receives the 
first dose prior to Day 1 Assessment 1, and a Screening value is available, the Screening 
value is utilized as the baseline. For assessments on or after Day 1, the study day will be 
calculated as assessment date – date of treatment (Day 1) + 1. For assessment prior to Day 
1, the study day will be calculated as assessment date – date of treatment (Day 1). 
 
4.2. Sample Size 
 
Upon review of the most recent literature (Fazekas et al 2012, Ludwig et al 2013, and 
Eccles et al 2015), similar studies employing the use of nasal spray products with a similar 
purported mechanism of action had sample sizes between 153 and 211. Therefore, an 
approximate sample size of 170 (85 subjects in each treatment group) is considered 
sufficient for this study. 
A sufficient number of subjects will be screened to enroll approximately 170 subjects. 
 
4.3. Randomization, Stratification, and Blinding 
 
Subjects will be assigned to one of two treatment groups (1146A or placebo) using the 
method of randomly permuted blocks with a fixed block size in accordance with the 
stratified randomization schedule. The sites will not receive the randomization schedule, 
but will be assigned blocks of randomization numbers generated from the IRT system. All 
site personnel will be blinded to the treatment allocations. GSK and PPD personnel who 
may influence study outcomes are kept blinded to the treatment allocations. 
 
Subjects who meet all inclusion and exclusion criteria will be randomized to one of the two 
treatment groups (1146A or placebo) in a 1:1 allocation ratio. The IRT system will 
randomize and stratify by site and by dosing time on Day 1. The maximum number of 
subjects each site can randomize will be capped at 26 (15% of the target number of 
randomised subjects). This is to ensure that the study population is reasonably distributed 
across as many sites as possible, and not dominated by one or two sites providing the 
majority of subjects. 
 
4.4. Analysis Population 
 
The following analysis populations are defined: 


 
4.4.1. Intent-to-Treat (ITT) Population 
Intent-to-Treat (ITT) population will consist of all randomized subjects. 
 
In the event there is a discrepancy between treatment received and randomized treatment, 
all subjects in the ITT set will be analyzed according to the treatment they were 
randomized to receive and not according to what they actually received. 
 
4.4.2. Modified Intent-to-Treat (mITT) Population 
The mITT population includes  subjects who received at least one dose of study 
medication and have at least one post-baseline efficacy assessment. The mITT will be used 
for all primary, secondary and exploratory efficacy analyses. 
 
In the event there is a discrepancy between treatment received and randomized treatment, 
all subjects in the mITT population will be analyzed according to the treatment they were 
randomized to receive and not according to what they actually received. 
 
4.4.3. Safety (SAF) Population 
The SAF population will include all randomized subjects who received at least one dose of 
study medication. 
 
All subjects in the SAF population will be analyzed according to the treatment actually 
received and not according to the treatment they were randomized to receive, in the event 
there is a discrepancy. The SAF population is used to tabulate all of the safety endpoints. 
 
4.4.4. Per Protocol (PP) Population 
 
The Per-Protocol (PP) population will be determined from compliance during Days 1 to 4, 
since this is the period of the primary efficacy evaluation. 
 
Any randomized subjects who violated the following inclusion or exclusion criteria will be 
reviewed on a case by case basis to determine whether they should be excluded from the 
PP population. 
In addition, any subjects who violated the following criteria will be excluded from the PP 
population. 
a. Subjects who complete less than 80% or more than 120% of their target 
number of actuations over Days 1 to 4 
b. Subjects who miss 2 or more doses on any one day during Days 1 to 4 
c. Subjects who miss a total of 4 or more of their doses during Days 1 to 4 


 
d. Subjects who miss more than 1 nasal assessment on any one day during 
Days 1 to 4. 
e. Dosing outside of allowable time window (2 or more times on any day 
during Days 1-4) 
f. 
Use of prohibited medications during Days 1 to 4 as listed in the protocol 
g. Dosing more than 5 minutes prior to self-assessments of symptoms using  
the eDiary device at home. This is because dosing time is entered manually 
and can only allow entrance in the increments of 5 minutes. The manual 
time to be entered has to be in the past. Since the time for dosing has to be  
in the past and only in 5 minute increments, subjects may have entered a 
time for dosing that is earlier than automatic time for symptoms 
assessments. 
 
Analysis on the PP population will be used as a supplement to the mITT analysis and will 
be performed for the primary efficacy endpoint average nasal symptom score Days 1-4 
(ANSS1-4) and the secondary efficacy endpoint average total symptom score Days 1-4 
(ATSS 1-4). 
 
 
5. Subject Disposition 
 
5.1. Disposition 
 
Subject disposition will be summarized for the population of all screened subjects by 
treatment group and overall. A disposition of subjects includes the number and percentage 
of subjects for the following categories: subjects randomized, subjects who completed the 
study, subjects who discontinued from the study, subjects in the ITT population, subjects 
in mITT population, subjects in the SAF population, and subjects in the PP population. All 
percentages will be based on the number of subjects randomized. 
 
The number and percentage of subjects’ study completion/termination status and the 
categories of study completion/termination status will be displayed in the order they are 
displayed in the CRF as follows: 
 
• Subject did not meet study criteria 
• Protocol violation 
• Withdrawal of informed consent 
• Unblinding of the subject 
• Subject lost to follow-up 
• Pregnancy 
• Death 


 
• Adverse event 
• Other 
 
Subject disposition data will also be presented in a listing. A listing of screen fail subjects 
will be also provided. Screen failures are defined as subjects who did not meet one or 
more criteria required for participation in a trial. 
 
 
5.2. Protocol Deviations 
Protocol deviation is defined as non-compliance with the protocol/ICH-GCP which may 
impact subject rights, safety or well-being, or the integrity of the data: 
 
• Significant Deviation: Non-compliance with the protocol/ICH-GCP which 
significantly impacts subject rights, safety or well-being, or the integrity of the 
data. 
• Non-Significant Deviation - Non-compliance with the protocol/ICH-GCP which 
does not significantly impact subject rights, safety or well-being, or the integrity of 
the data. 
 
The significant protocol deviations are defined in Appendix C by the study team and will 
be finalized before database lock. 
 
All protocol deviations including protocol deviations leading to exclusion from the Per 
Protocol population will be presented in a listing. The subject data listing will be sorted by 
site, subject number, and treatment group. Potentially important protocol deviations will be 
summarized in the clinical study report. 
 
6. Demographics and Baseline Characteristics 
 
6.1. Demographics 
The following demographic parameters will be captured by the Investigator or designee 
and recorded in the CRF: age (years), gender, race and ethnicity. 
Age (years) will be summarized using descriptive statistics. The number and percentage of 
subjects by age category (<65 vs. ≥65), gender (Male, Female), race (White, Black or 
African American, Asian, American Indian or Alaska Native, Native Hawaiian or Other 
Pacific Islander, other), and ethnicity (Hispanic or Latino, Not Hispanic or Latino) will 
also be reported. 
 
Demographic characteristics will be summarized descriptively by treatment group and 
overall for the Safety population. The demographic characteristics will also be summarized 


 
by center as a subgroup. Percentages will be based on the total number of subjects in the 
Safety population.  Subject demographic data will also be presented in a listing. 
 
6.2. Baseline Disease Characteristics 
 
Baseline characteristics will be summarized descriptively by treatment group and overall 
for the Safety population. Baseline characteristics will also be summarized by center as a 
subgroup. Baseline characteristics include the following: 
 
• Total Symptom Score (TSS) 
• Severity grading of the symptoms common cold as follows: 
 
Nasal symptoms: 
• runny nose 
• blocked nose 
• sneezing 
 
Other symptoms 
• headache 
• muscle ache 
• chills 
• sore throat 
• cough 
 
Subject baseline disease characteristics will be presented in a listing. 
 
6.3. Medical History 
 
Medical history will be listed. 
 
6.4. Inclusion and Exclusion Criteria 
 
The subjects who fail to meet the inclusion/exclusion criteria will be listed. Please refer to 
Protocol Sections 4.1 and 4.2 for details of with inclusion/exclusion. 
 
7. Treatments and Medications 
 
7.1. Prior and Concomitant Medications 
Details of any relevant medical or surgical history, including allergies or drug sensitivity, 
will be recorded in the CRF. Wherever possible, diagnoses and not symptoms will be 
recorded. Any medication and non-drug therapies/procedures therapy taken in the 90 days 


 
prior to the Screening Visit will also be recorded. Relevant history will be recorded in the 
CRF. 
 
For purposes of analysis, prior medications are defined as any medication with a stop date 
that is prior to the initial study drug dosing date and concomitant medications are defined 
as any medications with a start date on or after the initial study drug dosing date, but prior 
to the last study drug dosing or any medications with a start date prior to the initial study 
drug dosing date and a stop date after the initial study dosing date. 
 
For medications with partial start or stop dates, the partial dates will be imputed according 
to Table 1 and then will be categorized as prior medication or concomitant medication 
according to the definitions, Medications with completely missing dates will be included in 
the concomitant medication summary. 
 
Imputation rules for the start or stop date of missing or incomplete medications are 
presented in Table 1. 
Any changes in concomitant medication or non-drug treatments/procedures will be 
recorded in subject’s e-diary and will also be captured in the CRF. There will be a specific 
question in the e-diary asking about acetaminophen/paracetamol and all other concomitant 
medication usage prior to each dose of study treatment. 
The number and percentage of subjects receiving prior and concomitant medications will 
be displayed by medication classes (levels 1 and 2) of the Anatomical Therapeutic 
Chemical (ATC) classification system and by treatment group using Safety set. A listing 
of all medications taken by subjects, including those are only prior, will be produced. 


 
Table 1. Imputation rules for the start or stop date of missing or incomplete 
medications 
 
 
Missing 
Imputation 
Exception 
Start date 
(concomitant 
medication) 
Day 
01 
Default to Study Day 1 if 
an event starts the same 
year and month as Day 1 
and the stop date contains a 
full date and the stop date 
is later than Day 1; 
Otherwise If the stop date 
is prior to Day 1, default to 
1 day prior to the stop date 
Day/Month 
01Jan 
Default to Study Day 1 if 
an event started the same 
year as Day1 and the stop 
date contains a full date 
and the stop date is later 
than Day 1; Otherwise If 
the stop date is prior to 
Day 1, default to 1 day 
prior to the stop date 
Day/Month/Year No imputation 
Assume start prior to study 
entry. 
Stop date 
(concomitant 
medication) 
Day 
Last day of the 
month 
Default to the End of Study 
Date if the concomitant 
medication stopped the 
same year and month as 
the End of Study Date. 
Day/Month 
31DEC 
Default to the End of Study 
Date if the concomitant 
medication stopped the 
same year as the End of 
Study Date. 
Day/Month/Year No imputation 
Assume stops after study 
end. 
7.2. Study Treatments 
Subjects will receive either 1146A formulation ( 
 carbomer 980 gel) or placebo. Study 
medication will be administered via a nasal spray device (1 dose =3 actuations per nostril, 
each actuation is 140L). Dosing administration is 3 actuations per nostril per dose, four 
times a day for 7 days.  Subjects will be instructed to alternate nostrils after each actuation.
CCI
 


 
First administration of study medication will occur at the study site by independent site 
personnel supervision; first dosing can occur any time prior to 13:00. On Days 2-7, all 
subjects will administer their initial morning dose immediately following recording of their 
common cold symptom assessment at 07:00 ±2 hours and the remaining 3 doses every 4 
hours ± 30 minutes. 
 
7.2.1. Extent of Exposure 
 
Study medication exposure will be summarized descriptively by treatment group for the 
Safety population, including the following summaries: 
 
• Number and percentages of subjects who took study medication by study day 
• Total number of and percentages of administrations 
o Days 1 to 4 
▪ For subjects dosing between 8:00-11:00 on Day 1, the target number 
of medication administration is 96 actuations. 
▪ For subjects dosing between 11:01-13:00 on Day 1, the target 
number of medication administration is 90 actuations. 
o Days 1 to 7 
▪ For subjects dosing between 8:00-11:00 on Day 1, the target number 
of medication administration is 168 actuations. 
▪ For subjects dosing between 11:01-13:00 on Day 1, the target 
number of medication administration is 162 actuations. 
• Total dose and average daily dose received 
o Days 1 to 4 
▪ For subjects dosing between 8:00-11:00 on Day 1, the target number 
of doses is 13,440 mg and the target average daily dose is 3,360 mg. 
▪ For subjects dosing between 11:01-13:00 on Day 1, the target 
number of doses is 12,560 mg and the target average daily dose is 
2,520 mg for Day 1 and 3,360 mg for Days 2-4. 
o Days 1 to 7 
▪ For subjects dosing between 8:00-11:00 on Day 1, the target number 
of doses is 23,520 mg and the target average daily dose is 3,360 mg. 
▪ For subjects dosing between 11:01-13:00 on Day 1, the target 
number of doses is 22,680 mg and the target average daily dose is 
2,520 mg for Day 1 and 3,360 mg for Days 2-7. 
 
7.2.2. Treatment Compliance 
Treatment compliance is assessed by the recording of dosing times and number of 
actuations in the subject e-diary.  Treatment compliance for Days 1-4 and Days 1-7 will be 


 
summarized descriptively (number of subjects and percentage) for <80% Compliance, 80- 
120% Compliance, >120% Compliance and by treatment group for the Safety population. 
 
8. Efficacy Analysis 
Efficacy analyses will be performed on both the mITT population and PP population. The 
primary endpoint average nasal symptom score Days 1-4 (ANSS1-4) and secondary  
efficacy endpoint total symptom score Days 1-4 (ATSS 1-4) will be analyzed using the 
mITT population and PP population, all the other secondary and exploratory efficacy 
endpoints will be analyzed using the mITT population. The mITT analyses will be 
considered primary; the PP analyses will be considered supportive of the primary analyses 
on the mITT population. 
 
8.1. Primary Efficacy Endpoint 
 
The primary efficacy endpoint is average nasal symptom score on Days 1 to 4 (ANSS1-4). 
At each assessment, the individual nasal symptom scores will be summed to provide the 
NSS. On each day, the NSS scores at each assessment (excluding the baseline NSS on Day 
1) will be averaged (mean) to provide a daily NSS. A subject’s ANSS1-4  is calculated as  
the mean of these daily NSS across study Days 1 to 4. 
 
8.1.1. Primary Analysis 
 
The primary efficacy analysis of the ANSS1-4 in each treatment group will be performed on 
the mITT population. An analysis of covariance (ANCOVA) at a significance level of 
0.05, with factors for treatment, center and Day 1 dosing time stratification, and Baseline 
NSS (Day 1 prior to the first dose) as a covariate, will be used to test the following 
hypothesis: 
 
H0: ANSS1-4 active group = ANSS1-4 control group 
vs. 
H1: ANSS1-4 active group ≠ ANSS1-4 control group 
 
When assumption of normality in ANCOVA model is violated, nonparametric methods, 
e.g., Wilcoxon rank sum test stratified by center and dosing time strata (i.e., van Elteren 
test ) can be used. 
 
The ANSS1-4 values for each treatment group will be descriptively summarized. For the 
difference  of  the  ANSS1-4  between  the  two  treatment  groups,  the  mean  and  the 95% 


 
confidence interval for the mean based on the Wald statistic will also be presented. The 
two-sided p-value based on the Wald statistic Chi-Square will be calculated. 
The descriptive statistics will also be broken down by center, gender, and Day 1 dosing 
time stratification. 
 
If there are more than 10% of subjects, who are enrolled after Protocol Amendment 3 and 
in the mITT population, with onset of symptoms of common cold between >48 and <72 
hours from onset date and time and randomization date and time, time of onset of 
symptoms of common cold will be factored in the analysis of covariance described above 
for this subset of subjects. The descriptive statistics will also be provided for this subset of 
subjects. 
 
8.1.2. Data Imputation 
 
Dropouts will not be replaced and for the primary analysis, missing data after dropout will 
not be imputed. 
 
For data that is missing at intermediate assessments from subjects who still continue in the 
study, the fact that these subjects remain in the study and provide data at subsequent 
assessments supports the assumption that the mechanism for the missing data at these 
intermediate assessments is unlikely to be related to either their randomized treatment or 
the condition under study. Therefore, missing common cold symptom scores between two 
non-missing symptom scores will be imputed by the mean of the last available and the next 
available symptom score with the imputed mean rounded up to the next whole number.. 
Assessment date and time of the imputed common cold symptom scores will not imputed. 
 
Subjects will be instructed not to take any additional cough/cold medications, including but 
not limited to, prescription, OTC, non-drug/nutritional supplement, or procedures 
throughout the study. Subjects will be instructed to use acetaminophen/paracetamol over 
other OTC medications, but should try to avoid use if possible. In the event that a subject 
uses any additional cough/cold medication (including acetaminophen/paracetamol), its 
usage (time and reason for use) will be recorded in the e-diary. The primary analysis 
(modified ITT) will use the recorded cold symptom scores, irrespective of other  
cough/cold medication usage. The number of subjects using other cough/cold medications 
and frequency of use will be summarized by treatment group. 
 
8.1.3. Sensitivity Analysis for Primary Endpoint 


 
In the event that more than 10% of subjects do not complete the first 4 days of treatment 
(i.e. the period over which the primary endpoint is evaluated) or if there is a differential 
drop-out rate between the treatment groups, sensitivity analyses for primary endpoint will 
be performed using the following methods: 
a. Last observation carried forward (LOCF). If a subject has no further cold 
assessments after taking an alternative cough/cold medication (including 
acetaminophen/paracetamol), for subjects in the active group, subsequent 
symptom scores will be imputed with LOCF+1 (as per the additional 
sensitivity analysis described below). 
b. Control-based pattern imputation (Ratitch and O’Kelly 2011). The control- 
based pattern imputation will impute missing scores using available data 
from placebo subjects for each study day. 
 
Additional sensitivity analyses will be performed whereby cold symptom assessments 
made within 4 hours after the use of any other cough/cold medication (including 
acetaminophen/paracetamol) are set to missing and the following imputation algorithm 
applied: 
 
For subjects in the placebo group, individual symptom scores will be replaced using 
LOCF; for subjects in the active group, individual symptom scores will be replaced with 
LOCF+1. If the previous score for an individual symptom is 3 (maximum possible score), 
then LOCF will be used, as LOCF+1 would result in a value of 4, which is not possible. 
This imputation algorithm reflects the fact that the true cold symptom score, had 
alternative medication not been used, would have been at least as severe as the cold 
symptom score prior to the use of the alternative medication, and it is designed to ensure 
the imputed values do not introduce a bias in favor of the test product. 
 
The sensitivity analyses will be performed based on the mITT population. Details of 
sensitivity analyses are provided in Appendix D. 
 
8.1.4. Secondary Analysis for Primary Endpoint 
 
If more than 20% of the symptom scores in the calculation of the ANSS1-4 for an analysis 
population are missing, the summaries and analyses described for the ANSS1-4 in Section 
8.1.1 will be repeated for that analysis population on the ANSS1-4 calculated without 
imputation of missing symptom scores (i.e. observed case analysis). The secondary 
analyses will be performed based on the mITT population. 
 
In addition, the analysis described in Section 8.1.1 will be repeated for the PP population. 
 
8.1.5. Adjustment of Covariates 


 
All efficacy models will be adjusted by center and Day 1 dosing time stratification, and 
Baseline values. 
 
8.2. Secondary Efficacy Endpoint 
 
The secondary efficacy endpoints are (1) average nasal symptom score over Days 1 to 7 
(ANSS1-7), (2) average total symptom scores over Days 1 to 4 (ATSS1-4), and (3) average 
total symptom scores over Days 1 to 7 (ATSS1-7). 
 
The ANSS1-7, ATSS1-4, and ATSS1-7 will be summarized and analyzed in the same manner 
as ANSS1-4.  The ATSS1-4, and ATSS1-7, will also be analyzed using ANCOVA  with a  
term included for treatment, treatment by Day 1 dosing time interaction, center and Day 1 
dosing time stratification, and Baseline TSS (Day 1 prior to the first dose) as covariates. 
From this model, estimates of ATSS1-4, and ATSS1-7 for each dosing time strata will be 
obtained. 
 
8.3. Other Efficacy Endpoints 
 
8.3.1. Exploratory Analysis 
 
The mean daily NSS (MDNSS) per study day will be derived as the mean of a subject’s 
NSS scores per study day. The MDNSS and its change from baseline will be summarized 
by descriptive statistics by treatment group and day. NSS and MDNSS will be displayed 
graphically as line graphs showing the mean +/- SE within each treatment group over time. 
 
Likewise, the mean daily total symptom score (MDTSS) per day will be calculated. The 
MDTSS and its change from baseline will be summarized by descriptive statistics by 
treatment group and day. TSS and MDTSS will be displayed graphically as line graphs 
showing the mean +/- SE within each treatment group over time. 
 
Finally, for each symptom, the mean daily individual symptom scores (MDISS) per day 
will be calculated. The MDISS and change from baseline will be summarized by 
descriptive statistics by treatment group and day. Individual symptom scores and MDISS 
will be displayed graphically as line graphs showing the mean +/- SE within each  
treatment group over time. 
 
The course of each of the 8 common cold symptoms across the treatment period will be 
summarized using frequency tables by treatment group and day. 
 
9. Safety Analysis 


 
Safety analyses will be summarized for the Safety population. All tables will be presented 
by treatment group. 
 
9.1. Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence in a subject enrolled 
into this study regardless of its causal relationship to study treatment. Subjects will be 
instructed to contact the investigator at any time after randomization if any symptoms 
develop. 
AE analysis tables, namely overall AE tables and summary of all AE events tables, will be 
summarized. One listing of AE information will be presented, including treatment 
emergent and non-treatment emergent AEs. 
 
For AEs with missing date, please refer to Table 1 for imputation rules. 
 
9.1.1. Incidence of Adverse Events 
Treatment-emergent adverse events (TEAE) , i.e. AEs that start or worsen during the 
treatment period (on or after first study medication administration), will be summarized by 
presenting the number and percentage of subjects having any AE, any AE in each 
MedDRA System Organ Class (SOC) and having each individual AE (using MedDRA 
preferred term (PT)). At each level of subject summarization, a subject is counted once if 
the subject reported one or more events. Percentages will be calculated out of the number  
of subjects in the Safety population. The number of events will also be presented in the 
table. 
 
The summary of TEAEs will be presented in descending order from the SOC with the 
highest total incidence (that is, summed across all treatment groups) to the SOC with the 
lowest total incidence. If the total incidence for any two or more SOC is equal, the SOC 
will be presented in alphabetical order. Within each SOC, the PTs will be presented in 
descending order, in the same manner as SOC. 
 
The incidence of TEAE between treatment groups is compared using a frequency table for 
Safety population. 
 
9.1.2. Relationship of Adverse Events to Study Treatment 
Summaries of TEAEs which are related to study treatment will be presented by number of 
subjects. The investigator will provide an assessment of the relationship of the event to the 
study treatment. A treatment related AE is an event that is related to study medication 
assessed “Possible” or “Probable” or “Definite” to the question of “Relationship to the 
study treatment” as reported on an AE CRF page for any subject who had taken one dose 
of the study medication. TEAEs that are missing a relationship will be presented in the 


 
summary table as “Related” but will be presented in the data listing with a missing 
relationship. Percentages will be calculated based on the number of subjects in the Safety 
population. 
 
The TEAE data will be categorized and presented by SOC and PT in a manner similar to 
that described in Section 9.1.1. 
 
 
9.1.3. Severity of Adverse Event 
 
A summary of AEs by treatment and severity will be presented in a table. In the AE 
severity table, if a subject reported multiple occurrences of the same AE, only the most 
severe AE will be presented. AEs with missing severity will be included in the summary 
table as severe, but will be presented in the data listing with a missing severity. 
Percentages will be calculated out of the number of subjects in the Safety population. 
 
9.1.4. Serious Adverse Events 
 
A SAE is defined as any untoward medical occurrence that at any dose results in death, is 
life-threatening, requires inpatient hospitalization or prolongation, results in significant 
disability/incapacity, is a congenital anomaly/birth defect, is an important medical events 
that may jeopardize the subject or may require medical intervention to prevent one of the 
outcomes listed above. SAEs will be collected through the end of the study. 
 
All SAEs, regardless of their treatment-emergent status will be summarized by system 
organ class (SOC) and PT. Percentages will be calculated out of the number of subjects in 
the Safety population. 
 
All SAEs will be presented in a listing. 
 
9.1.5. Adverse Events Leading to Study Discontinuation 
All subjects who have an AE where the answer to “Did the subject withdraw from study as 
a result of AE?” is “Yes” will be presented in a listing. 
 
9.1.6. Death 
 
All deaths will be presented in a listing. 
 
 
9.2. Clinical Laboratory Evaluations 


 
9.2.1. Urine Drug Screen and Pregnancy Test 
Urine will be collected at screening to perform urine drug test (urine dipstick). Urine will 
be tested for the following drugs or illicit substances: barbiturates, benzodiazepines, 
amphetamines, cocaine, opiates, and cannabis. In case of a positive finding at the screening 
visits or any substance class, the subject must be excluded from participation in the study. 
Results will be recorded in the CRF. 
 
All women of childbearing potential will have a urine pregnancy test. It will be conducted 
at the site using a urine dipstick. A positive urine pregnancy test disqualifies a subject from 
the study. Results from the pregnancy test will be recorded in the CRF. 
 
Number of subjects in each substance will be summarized and all laboratory data will be 
presented in a listing. Urine drug and pregnancy test for women will also be presented in 
listings. 
 
9.3. Vital Sign Measurements 
Vital sign data will be collected, including 
• sitting systolic blood pressure (mmHg) which is the average of 3 measurements, 
• sitting diastolic blood pressure (mmHg) which is the average of 3 measurements, 
• pulse rate (beats per minute), 
• respiration rate (breath per min), 
• oral body temperature (ºC) 
• height (cm) 
• weight (kg) 
 
Summary table for change from baseline will be presented for the collected data by 
treatment group for subjects in the Safety population. Baseline height and weight will be 
summarized with other demographic parameters. 
 
All vital sign data by subject will also be presented in a listing. 
 
9.4. Physical Examination 
 
A complete physical examination will be performed at Screening (Visit 1, Day 1) for 
eligibility. It will include examination of general appearance, skin, neck (including 
thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, and 
extremities, vascular and neurological. 
 
All physical examination by subject in the Safety population will be presented in a listing. 


 
 
9.5. Nasal Examination 
Nasal examination will be performed for eligibility at Screening (Visit 1, Day 1) 
All nasal examination by subject will be presented in a listing. 
10. References 
 
American College of Toxicology (ACT). Final report on the safety assessment of carbomers 
-934, -910, -934P, -940, -941 and -962. Elder RL, editor. Int. J. Toxicology. 1982;1:109- 
141, DOI: 10.3109/10915818209013151. 
Eccles R., Et Al. Efficacy And Safety Of Iota-Carrageenan Nasa Spray Versus Placebo In 
Early Treatment Of The Common Cold In Adults: The ICC Trial. Respiratory Research. 
2015; 16:121 
Fazekas T., Et Al. Lessons Learned From A Double-Blind Randomized Placebo-Controlled 
Study With A Iota-Carrageenan Nasal Spray As Medical Device In Children With Acute 
Symptoms Of Common Cold. Bmc Complementary and Alstrenative Medicine. 2012; 
12:147 
Fitzmaurice , Garrett; Laird, Nan; Ware, James. (2011). Applied Longitudinal Analysis, 
2nd Edition 
Gwaltney JM Jr., and Druce HM. (1997). Efficacy of brompheniramine maleate for the 
treatment of rhinovirus colds. Clinical Infectious Diseases. 25:1188-1194. 
Hayden FG, Diamond L, Wood PB, Korts DC, Wecker MT. Effectiveness and safety of 
intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo- 
controlled trial. Ann Intern Med. 1996 Jul 15;125:89-97. 
Kennedy JL, Turner RB, Braciale T, Heymann PW, Borish L. Pathogenesis of rhinovirus 
infection. Curr Opin Virol. 2012;2(3):287-293. 
Ludwig M, Enzenhofer E, Schneider S, Rauch M, Bodenteich A, Neuman K, Prieschl- 
Grassauer E, Grassauer A, Lion T, Mueller Ca. Efficacy Of A Carrageenan Nasal Spray In 
Patients With Common Cold: A Randomized Controlled Trial. Respiratory Research. 
2013; 14:124 
Lubrizol. Formulating Toothpaste Using Carbopol® Polymer [Internet]. 2010 [cited 2014 
Oct 30]. Available from:http://www.lubrizol.com/Life- 
Science/Documents/Pharmaceutical/Bulletins/Bulletin-24---Formulating-Toothpaste- 
Using-Carbopol-Polymer.pdf. 
Rubin, D. B. (1987). Multiple Imputation for Nonresponse in Surveys, New York: John 
Wiley & Sons. 
Sperber SJ, Sorrentino JV, Riker DK, Hayden FG. Evaluation of an alpha agonist alone 
and in combination with a nonsteroidal antiinflammatory agent in the treatment of 
experimental rhinovirus colds. Bull N Y Acad Med. 1989 Jan;65(1):145-60. 


 
Sperber SJ, Hendley JO, Hayden FG, Riker DK, Sorrentino JV, Gwaltney JM Jr. Effects of 
naproxen on experimental rhinovirus colds. A randomized, double-blind, controlled trial. 
Ann Intern Med. 1992 Jul 1;117(1):37-41. 
Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013 Jun 18; 
6:CD001364. DOI: 10.1002/14651858.CD001364.pub4. 
Turner RB, Hendley JO, Gwaltney JM Jr. Shedding of infected ciliated epithelial cells in 
rhinovirus colds. J Infect Dis. 1982;145(6):940-953. 
Turner RB. Efficacy of Tremacamara, a soluble intercellular adhesion molecule 1, for 
experimental rhinovirus infection. JAMA. 1999;281(19):1797-1804. 


 
11. Appendices 
 
Appendix A. Schedule of Events 
 
 


 
 
 


 
Appendix B - Medications and Treatments 
 


 
Appendix C. Protocol Deviations 
 
DESCRIPTION OF RULE 
SIGNIFICANCE 
Subjects are not within the age of 18 to 75 years old. 
Significant 
Patient is not in good general and mental health with, in the opinion of 
the Investigator or medically qualified designee clinically significant 
or relevant abnormalities in medical history or upon physical and 
Investigator-led nasal examination. 
Significant 
Females of childbearing potential (refer to Section 4.4. of protocol) 
who are not practicing a reliable method of contraception. 
Significant 
Investigator has not confirmed diagnosis of symptomatic common 
cold with an onset of < 72 hours prior to randomization. 
Significant 
The total symptom score (TSS) is not > 9 AND there is not a score >1 
for at least one of the following symptoms: sore throat, runny nose, or 
blocked nose. 
Significant 
PREGNANCY: Women who have a positive urine pregnancy test. 
Significant 
BREAST-FEEDING: Women who are breast-feeding. 
Significant 
CONCURRENT MEDICATION/MEDICAL HISTORY: Defined in 
protocol Exclusion criteria 3. 
Significant 
ALLERGY/INTOLERANCE: Defined in protocol Exclusion criteria 
5. 
Significant 
CLINICAL STUDY/ EXPERIMENTAL PRODUCT: Defined in 
protocol Exclusion criteria 5. 
Significant 
SUBSTANCE ABUSE: Defined in protocol Exclusion criteria 6. 
Significant 
PERSONNEL: Defined in protocol Exclusion criteria 7. 
Significant 
DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA: Defined 
in protocol Exclusion criteria 8. 
Significant 
Wrong dosing time (2 or more times on any day during Days 1-7) 
Not Significant 
Missed doses (<80% of target number of actuations over Days 1-7) 
Not Significant 
Additional doses (>120% of target number of actuations over Days 1- 
7) 
Not Significant 
Subjects who miss 2 or more doses on any day during Days 1-7 
Not Significant 
Subject who miss a total of 6 or more of their doses during Days 1-7 
Not Significant 
Wrong dosing time (2 or more times on any day during Days 1-4) 
Significant 
Missed doses (<80% of target number of actuations over Days 1-4) 
Significant 
Additional doses (>120% of target number of actuations over Days 1- 
4) 
Significant 
Subjects who miss 2 or more doses on any day during Days 1-4 
Significant 
Subject who miss a total of 4 or more of their doses during Days 1-4 
Significant 
Use of prohibited medications as listed in protocol 
Significant 
Nasal swab sample not collected at screening 
Not Significant 
Urine drug screen not completed at screening 
Significant 


 
 
DESCRIPTION OF RULE 
SIGNIFICANCE 
Urine pregnancy testing not completed 
Significant 
Subject who misses 2 or more of their nasal symptom assessments on 
any day during Days 1-7 
Not Significant 
Any subject who misses a total of 6 or more of their nasal symptom 
assessments during Days 1-7 
Not Significant 
Subject who misses 2 or more of their nasal symptom assessments on 
any day during Days 1-4 
Significant 
Any subject who misses a total of 4 or more of their nasal symptom 
assessments during Days 1-4 
Significant 
Screening procedures not completed 
Significant 
Subject not enrolled within 72 hours of symptom onset 
Significant 
Subject randomized out of sequence (IWRS problem) 
Significant 
Received incorrect treatment, not according to randomization 
schedule 
Significant 
Subject randomized prior to the completion of ICF 
Significant 
SAE not reported by site to PPD at all or not within 24 hours of 
awareness 
Significant 
SAE not reported by PPD to GSKCH at all or not within 1 business 
day of awareness 
Significant 
Pregnancy not reported by site to PPD within 2 weeks of learning of 
subject becoming pregnant 
Significant 
Site did not follow up to obtain required information for SAE 
reporting 
Significant 
AE not included on AE section of the eCRF 
Not Significant 
Failure to discontinue subjects that meet defined discontinuation 
criteria 
Significant 
Subject did not sign ICF 
Significant 
ICF signed by subject prior to IRB approval 
Significant 
ICF signed by subject but not approved by IRB 
Significant 
Original ICF signed and dated after screen/enroll date 
Significant 
ICF was lost, no copy available 
Significant 
ICF was lost, copy available 
Significant 
Subject signed consent but did not date it, but there is other sufficient 
information to confirm the date 
Significant 
Subject forgot to sign the ICF but gave verbal consent 
Significant 
Investigator and/or witness did not sign or date the ICF and there isn’t 
any supporting documentation to confirm that the consent process was 
performed appropriately 
Significant 
Version date not recorded on ICF 
Significant 
Subject signed a superseded/outdated version of the ICF (and never 
signed correct version) 
Significant 


 
 
DESCRIPTION OF RULE 
SIGNIFICANCE 
Revised ICF not signed; subject visit has occurred & not remediated at 
a subsequent visit 
Significant 
Blood Pressure Repeat Assessments not completed in 1-2 minute 
intervals per protocol. 
Significant 
Early Termination procedures not completed 
Significant 
ICF Section "AGREEMENT TO BE IN THE STUDY" was not 
completed by the subject 
Significant 
Incorrect actuations according to StudyWorks Smart Reports 
Significant 
Out of Window Visit 
Not Significant 
Site personnel did not enter Dose time into eDiary 
Not Significant 
Subject dosed IP on Day 8 
Significant 
Subject's first dose after 13:00 on Day 1 
Significant 
Subject missed 1 nasal assessment on any day between Days 1-8 
Not Significant 
Subject who miss a total of 5 or less of their doses during Days 1-7 
Not Significant 
Subject who missed 1 IP dose on any one day during Days 1-7 
Not Significant 
IP not returned 
Significant 
Subject who missed completing self-assessments in the eDiary 
Significant 
Self-assessment of common cold symptoms using a 4-point scale was 
not recorded in the subject e-diary immediately prior to the first dose 
at Baseline 
Significant 
Any subject who misses a total of 5 or less of their nasal symptom 
assessments during Days 1-7 
Not Significant 
Temperature Excursions for -70 Freezer: Nasal Swab Sample 
Not Significant 
Subject initialed and dated every page of the ICF and added the 
printed name on the signature page but did not add signature on the 
signature page 
Significant 
IP Storage Temperature Excursion 
Not Significant 
Subject discontinued at Day 2. No doses or self-assessments 
completed after Day 1. 
Not Significant 
ICH/GCP Deviation: Delegation of Authority Log Tasks Not 
Delegated or Not Delegated Correctly 
Not Significant 
Urine Drug Screen Test not read at 5 mins but was read at 3 mins. 
Not Significant 
Subject did not add initials and date on page 16 of ICF 
Not Significant 
Urine Temperature Not Captured on urine Drug Screen Requisition 
Not Significant 


 
Appendix D – Details of Sensitivity Analyses 
 
A. Sensitivity analysis whereby cold symptom assessments made within 4 hours after 
the use of any other cough/cold medication (including acetaminophen/paracetamol) 
will be performed for the primary endpoint ANSS1-4 using last observation carried 
forward LOCF as follows: 
a. The nasal symptom scores (blocked nose, runny nose, and sneezing) 
recorded within 4 hours after the use of any other cough/cold medication 
(including acetaminophen/paracetamol) are set to missing. 
b. The missing scores from step a. are imputed, 
i. for subjects in the Placebo group, using the score from the latest 
non-missing score before the medication was taken, or 
ii. for subjects in the Active group, using the score from the latest non- 
missing score + 1 before the medication was taken if the score is less 
than or equal 2, or using the score from the latest non-missing score 
before the medication was taken if the score is equal to 3. 
c. Missing nasal symptom scores between two non-missing nasal symptom 
scores are not imputed for this sensitivity analysis. 
 
B. In the event that more than 10% of subjects do not complete the first 4 days of 
treatment (i.e. the period over which the primary endpoint is evaluated) or if there 
is a differential drop-out rate between the treatment groups, sensitivity analyses for 
the primary endpoint ANSS1-4   will be performed using the following methods: 
1. last observation carried forward (LOCF) 
a. The missing scores will be imputed using the score of the latest non-missing 
score before the drop-out. 
b. If the latest non-missing score before drop-out was made within 4 hours 
after the use of any other cough/cold medication (including 
acetaminophen/paracetamol), the score will be set to missing and imputed 
as described in Section A. 


 
2. Controlled-
CCI
based pattern imputation. 


CCI


CCI


CCI


CCI


CCI


CCI