Conditions: Common Cold
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 193
Healthy volunteers: no

Brief summary:
This will be a randomized, double-blind, placebo controlled, parallel-group Phase 2 study to evaluate the efficacy of a new formulation of phenylephrine HCl and a currently marketed phenylephrine HCl for relief of nasal congestion in subjects with naturally occurring cold symptoms.

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: None

Interventions: intervention 1: New Formulation Phenylephrine HCl intervention 2: Marketed Phenylephrine HCl intervention 3: Placebo
Intervention descriptions: intervention 1: 2 doses of one tablet 12 hours apart intervention 2: 4 doses of one capsule 4 hours apart intervention 3: 4 doses of placebo capsule and tablet taken 4 hours apart

Protocol document:
Prot_000.pdf: 


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1.
SYNOPSIS
Name of Sponsor/Company:
Johnson & Johnson Consumer Inc., 
Fort Washington, PA 19034
Active Ingredient(s):
Phenylephrine HCl Equivalent, 
 30 mg
Title of Study: 
Randomized, Double-Blind, Placebo-Controlled, Study of the Efficacy of Phenylephrine HCl 
 30 mg and Phenylephrine HCl 
 12 mg Capsules in Subjects 
with Nasal Congestion Due to the Common Cold
Countries: Canada
Investigators: Multicenter study.
Phase of development: 2
Objective: 
To investigate the potential for efficacy of an 
 equivalent to Phenylephrine 
HCl 30 mg twice daily and Phenylephrine HCl 
12 mg Capsules four times 
daily and placebo, administered orally, in subjects with nasal congestion due to the common cold.
Methodology: 
This will be a randomized, double-blind, placebo controlled, parallel-group Phase 2 study to 
evaluate the efficacy of an 
oral tablet equivalent to phenylephrine HCl 30 mg 
taken twice daily and an 
 oral capsule of phenylephrine HCl 12 mg taken four 
times daily for relief of nasal congestion in subjects with naturally occurring cold symptoms.  The 
trial will have a double dummy design so all subjects will take investigational product four times 
a day.  Subjects randomized to the phenylephrine 
 group will take active dose
morning and evening, with a period of 12 hours between the doses, with placebo given in the 
interim doses.  Subjects randomized to the phenylephrine HCl 
 group will take
all four doses of active product. The morning dose will be administered between 7:00AM and 
noon at the site, the next dose will be administered 4 hours (+10 minutes) later at the site and the 
last two doses will be given to the subjects to take 4 hours and 8 hours later.   Approximately 450 
subjects (150 per treatment group), ages 18 years and older, will be enrolled.
Potential subjects will be identified through advertising and unsolicited presentation at the study 
site for complaint of common cold symptoms.  Eligible subjects will have an onset of cold 
symptoms (per subject self-report) within approximately 72 hours (3 days) before study entry, 
consisting of cold symptoms per the following:
•
At Visit 1, at least moderate severity (score ≥ 5, on a scale from 0 = none to 7 = severe) for 


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stuffy/congested nose, and
•
At visit 1, at least mild (score ≥ 3, on a scale from 0 = none to 7 = severe) for sinus 
pressure/tenderness, and
•
Within approximately 72 hours of enrollment, two or more of the following symptoms: runny 
nose, sneezing, sore or scratchy throat, headache, malaise, or cough.
Subjects who qualify per inclusion and exclusion criteria during onsite screening will be 
randomly assigned to one of three blinded treatments: 
 equivalent to 30 mg
phenylephrine HCl, 
 phenylephrine HCl 12 mg, or placebo.  Treatment will be 
for a twelve-hour period (Day 1).
On Day 1, subjects will complete subjective assessments of symptoms at baseline, within
approximately 30 minutes prior to dosing.  Dosing should occur within 72 hours of onset of cold 
symptoms. Study staff will administer the first dose between approximately 7:00 and noon (0 
hour). Subjects will remain at the site for 4 hours following the first dose, and they will complete 
symptom assessments at 2 hours and 4 hours (±10 minutes) post-dose. The 4-hour assessment
will be conducted before administration of the next due dose. At 4 hours (+10 minutes) post first 
dose, subjects will be given the second dose.  Vital signs will be measured at Visit 1 (pre-dose).
Vital signs will also be measured at approximately 2 and 4 hours post initial dose, immediately 
following completion of efficacy assessments.  Subjects will be discharged from the site after the 
4 hour procedures with instructions to complete subjective assessments using a diary at 
approximately 6, 8, 10 and 12 hours after the first dose of medication on Day 1 and to take the 
next two doses at 8 and 12 hours after the first dose was administered at the site. At the 8 and 12 
hour timepoints, the diaries should be completed prior to the medication being taken.
One third of the eligible subjects will be assigned to the pharmacokinetic cohort at a limited 
number of sites. They will have 3-mL blood samples collected by direct venipuncture. Two
samples will be collected; one at approximately 1 (±10 minutes) and another at 4 hrs (±20
minutes) after the initial dose. These subjects will have provided written consent to the collection 
of blood samples. After the pharmacokinetic cohort has been completed, subsequent enrolling 
subjects will not be asked to consent to the collection of blood samples.
Subjects will be instructed to complete the final assessments in their diary the next morning on 
Day 2, 24 hours (+/- 30 mins) after they took the first dose. Subjects will return to the study site 
for a Follow-up Visit on Day 2 (+1 day) for reconciliation of drug and reporting of any adverse 
events or concomitant medications. The 24-hour assessments can also be completed during the 
follow-up visit if it falls within the window.  Vital signs will be obtained and the subject will be 
discharged from the study.
No other cough, cold, allergy, or analgesic/antipyretic medicines (nonprescription or prescription) 
or herbal/dietary supplements will be permitted during the study.  Adverse events will be 
collected during the study to evaluate safety.
Number of subjects (planned): 
Approximately 450 (150 per treatment group)
Diagnosis and main criteria for inclusion: 


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Subjects 18 years or older who meet the inclusion and exclusion criteria, which includes cold 
symptoms due to an acute upper respiratory tract infection, will be eligible for the study.
Eligible subjects will have experienced cold symptoms for no longer than 72 hours (3 days) prior 
to enrollment at Visit 1. These will consist of cold symptoms including a) at Visit 1, at least 
moderate severity (score ≥ 5) for stuffy/congested nose, and b) at Visit 1, at least mild (score ≥ 3) 
for sinus pressure/tenderness, and c) within the past 72 hours, two or more of the following
symptoms: runny nose, sore or scratchy throat, sneezing, headache, malaise, or cough.  
Study product, dosage and mode of administration: 
Phenylephrine HCl
 30 mg; one tablet taken orally twice daily 
(every 12 hours)
Phenylephrine HCl, 
 12 mg; one capsule by mouth four times a day 
(every 4 hours)
Reference therapy (comparator or placebo control), dosage and mode of administration: 
Matching placebo for 
 phenylephrine HCl, 30 mg and
phenylephrine HCl 
capsules, 12 mg.
Duration of treatment: 
Twelve hours of treatment.
Data for evaluation:
Endpoints:
Primary
The primary efficacy endpoint is the change from baseline in the nasal congestion severity score 
(NCSS) averaged over assessments at 2, 4, 6, 8, 10, and 12 hours on Day 1.  The baseline nasal 
congestion score will be measured within approximately 30 minutes before the first dose.
Secondary
The secondary efficacy endpoints include

Change from baseline in the NCSS averaged over assessments at 8, 10, and 12 hours.

Change from baseline in the NCSS at 2, 4, 6, 8, 10, and 12 hours and in the morning of 
Day 2 (24 hours), respectively.

Change from baseline in Sinus Pressure/Tenderness Scores averaged over assessments at 
2, 4, 6, 8, 10, and 12 hours.

Change from baseline in Sinus Pressure/Tenderness Scores at 2, 4, 6, 8, 10, and 12 hours 
and in the morning of Day 2 (24 hours), respectively.
Exploratory
The exploratory efficacy endpoints include

Change from baseline in Head Congestion Scores averaged over assessments at 2, 4, 6, 8, 


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10, and 12 hours.

Change from baseline in Head Congestion Scores at 2, 4, 6, 8, 10, and 12 hours and in the 
morning of Day 2 (24 hours), respectively.

Change from baseline in Reflected Impact of Nasal / Sinus Congestion on Clear Thinking 
(reflected for the previous 12 hours) at 12 hour assessment

Reflected Change in Nasal Congestion Symptoms (reflected over 12 hours after the first 
dose).

Reflected Nasal Functioning (reflected over 12 hours after the first dose).

Change from baseline in Reflected Congestion Severity (reflected for the previous 12 
hours) at 12 hour assessment

Assessment of cold severity using Wisconsin Upper Respiratory Symptom Survey-21 
(reflected over 24 hours) at baseline and in the morning of Day 2 (24 hours).
Efficacy Assessments:
The decongestant effect of the phenylephrine
 formulation will be evaluated with 
the following subjective assessment questions and verbal rating scales (VRS) completed by the 
subject at the designated time points: 

Assessment of Nasal Congestion (stuffy/congested nose), instantaneous, on an 8-point 
scale, at baseline, at 2, 4, 6, 8, 10 and 12 hours after the first dose on Day 1 and in the 
morning of Day 2 (24 hours). 

Assessment of Sinus Pressure/Tenderness, instantaneous, on an 8-point scale, at baseline, 
at 2, 4, 6, 8, 10 and 12 hours after the first dose on Day 1, and in the morning of Day 2 
(24 hours)

Assessment of Head Congestion, instantaneous, on an 8-point scale, at baseline, at 2, 4, 6, 
8, 10 and 12 hours after the first dose on Day 1, and in the morning of Day 2 (24 hours).

Assessment of Reflected Impact of Nasal / Sinus Congestion on Clear Thinking, 
reflective, on a 5-point scale, at baseline and at 12 hours after the first dose on Day 1.

Assessments of Reflected Change in Nasal Congestion Symptoms, reflective, on a 7-
point scale, at 12 hours after the first dose on Day 1.

Assessments of Reflected Nasal Functioning (clear breathing), reflective, on an 8-point 
scale, at 12 hours after the first dose of treatment on Day 1.

Assessment of Reflected Congestion Severity, reflective, on a 5-point scale, at baseline 
and at 12 hours after the first dose on Day 1.

Assessment of cold severity using the Wisconsin Upper Respiratory Symptom Survey 
(WURSS-21) at baseline and in the morning of Day 2 (24 hours).
Pharmacokinetic Assessments: 
Plasma concentration-time data will be subjected to population pharmacokinetic analysis and 
reported separately, however, blood plasma levels will be summarized descriptively by treatment 


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and assessment time points.
Safety Assessments:
Safety assessments will consist of the monitoring of AEs collected throughout the study, and 
review of blood pressure and heart rate measured at baseline (before drug) and at 2 and 4 hours 
after the morning dose on Day 1, and at the End of Study visit that will occur the next day (+ one 
day).
Statistical Methods:
Statistical Analysis of Primary Efficacy Endpoint
For the efficacy analyses, the Full Analysis Set will include all randomized subjects who provide 
a valid baseline assessment of nasal congestion severity.  
This is a Phase II, POC study and therefore the inferential statistical procedures are focused on 
point and interval estimation of pairwise treatment differences in the efficacy endpoints. 
However, to further aid interpretation of findings, p-values from 2-sided tests of the null 
hypotheses of no treatment (mean) difference will be provided in each case.  
The primary analysis of the primary endpoint, which is the change from baseline in the Nasal 
Congestion Score (score for stuffy/congested nose averaged over assessments at 2, 4, 6, 8, 10, and 
12 hours on Day 1), will be based on all randomized subjects who provide at least an assessment 
of nasal congestion at baseline and receive study treatment.  The primary endpoint will be 
analyzed by an ANOVA model with treatment group, study center, and baseline nasal congestion 
score as factors.  For subjects who dropout, their last reported congestion score before the dropout 
will be carried forward to the remaining assessment time points.
Safety Analysis
The safety analysis will be based on all randomized subjects who took at least one dose of 
investigational product.  The safety data will be summarized using standard procedures.






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TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES
1.
SYNOPSIS ...................................................................................................................2
2.
STUDY FLOW CHART AND SCHEDULE OF ACTIVITIES .................................7
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES....................................9
3.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................14
4.
ETHICS ......................................................................................................................15
4.1.
Institutional Review Board (IRB) / Independent Ethics Committee (IEC)................15
4.2.
Ethical Conduct of the Study......................................................................................15
4.3.
Subject Information and Consent ...............................................................................15
5.
STUDY ADMINISTRATIVE STRUCTURE ...........................................................16
6.
INTRODUCTION......................................................................................................17
6.1.
Background.................................................................................................................17
6.2.
Rationale.....................................................................................................................17
7.
STUDY OBJECTIVES AND ENDPOINTS..............................................................18
7.1.
Primary Endpoint........................................................................................................18
7.2.
Secondary Endpoints ..................................................................................................18
7.3.
Exploratory Endpoints................................................................................................18
8.
INVESTIGATIONAL PLAN.....................................................................................19
8.1.
Overall Study Design and Plan...................................................................................19
8.2.
Subject Inclusion Criteria ...........................................................................................20
8.3.
Subject Exclusion Criteria..........................................................................................21
8.4.
Subject Withdrawal Criteria .......................................................................................23
9.
INVESTIGATIONAL PRODUCT MATERIALS AND 
MANAGEMENT .......................................................................................................24
9.1.
Investigational Product ...............................................................................................24
9.2.
Description of Investigational Product.......................................................................24
9.3.
Investigational Product Packaging and Labeling .......................................................24
9.4.
Blinding and Unblinding ............................................................................................25
9.5.
Method of Assigning Subjects to Treatment Groups .................................................25
9.6.
Study Product Storage and Accountability.................................................................26
9.7.
Administration of the Investigational Product............................................................26


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9.8.
Product Quality Complaints .......................................................................................26
10.
STUDY PROCEDURES............................................................................................28
10.1.
Overview.....................................................................................................................28
10.2.
Screening / Day 1 Visit (including up to morning of Day 2) .....................................28
10.3.
End of Study Procedures ............................................................................................30
10.4.
Lifestyle Guidelines....................................................................................................30
10.4.1.
Meals and Dietary Restrictions...................................................................................30
10.4.2.
Alcohol, Caffeine and Tobacco Consumption / Restrictions .....................................31
10.4.3.
Contraception..............................................................................................................31
10.5.
Treatment Compliance................................................................................................32
10.6.
Previous and Concomitant Therapies .........................................................................32
11.
ASSESSMENTS.........................................................................................................33
11.1.
Efficacy Assessments .................................................................................................33
11.1.1.
Nasal Congestion, Sinus Pressure and Head Congestion...........................................33
11.1.2.
Reflected Impact of Nasal / Sinus Congestion on Clear Thinking.............................34
11.1.3.
Reflected Change in Nasal Congestion Symptoms ....................................................34
11.1.4.
Reflected Nasal Functioning.......................................................................................34
11.1.5.
Reflected Congestion Severity ...................................................................................34
11.1.6.
Wisconsin Upper Respiratory Symptom Survey 21...................................................35
11.2.
Pharmacokinetic Assessments....................................................................................36
11.2.1.
Blood collection..........................................................................................................36
11.2.2.
Blood sample processing............................................................................................36
11.2.3.
Shipment of Pharmacokinetic Samples ......................................................................36
11.2.4.
Analytical Procedures.................................................................................................36
11.2.5.
Population Pharmacokinetic Modeling.......................................................................36
11.3.
Safety Assessments.....................................................................................................37
11.3.1.
Vital Signs ..................................................................................................................37
12.
ADVERSE EVENT REPORTING ............................................................................38
12.1.
Introduction.................................................................................................................38
12.2.
Reporting Period.........................................................................................................38
12.3.
Definition of an Adverse Event..................................................................................38
12.4.
Abnormal Test Findings .............................................................................................39


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12.5.
Serious Adverse Events (SAE) for Drugs ..................................................................39
12.6.
Hospitalization............................................................................................................40
12.7.
Resolution...................................................................................................................41
12.8.
Severity Assessment ...................................................................................................41
12.9.
Causality Assessment .................................................................................................42
12.10.
Exposure In Utero.......................................................................................................43
12.11.
Withdrawal Due to Adverse Events ...........................................................................44
12.12.
Eliciting Adverse Event Information..........................................................................44
12.13.
Reporting Requirements.............................................................................................44
12.13.1.
Serious Adverse Event Reporting Requirements .......................................................44
12.14.
Special Situations........................................................................................................45
13.
STATISTICS ..............................................................................................................46
13.1.
Sample Size Determination ........................................................................................46
13.2.
Analysis Sets...............................................................................................................46
13.2.1.
Secondary Endpoints ..................................................................................................46
13.2.2.
Baseline and Demographics .......................................................................................46
13.3.
Efficacy Analysis........................................................................................................47
13.3.1.
Primary Endpoint........................................................................................................47
13.3.2.
Exploratory Endpoints................................................................................................47
13.3.3.
Pharmacokinetics........................................................................................................47
13.3.4.
Psychometric Analyses...............................................................................................47
13.3.5.
Statistical Analyses.....................................................................................................48
13.4.
Safety Analysis ...........................................................................................................49
13.4.1.
Adverse Events ...........................................................................................................49
13.4.2.
Clinical Laboratory Tests ...........................................................................................49
13.4.3.
Vital Signs ..................................................................................................................49
13.5.
Interim Analysis..........................................................................................................49
13.5.1.
Rationale for Interim Analyisis ..................................................................................49
13.5.2.
Communication and Logistics....................................................................................49
13.5.3.
Scope...........................................................................................................................50
13.5.4.
Handling of missing data and assessment time deviations.........................................50
13.5.5.
Statistical methodology ..............................................................................................50


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13.5.6.
Statistical decision rules .............................................................................................53
13.6.
Data Monitoring Committee.......................................................................................53
14.
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................54
14.1.
Study Monitoring........................................................................................................54
14.2.
Audits and Inspections................................................................................................54
14.3.
Institutional Review Board / Independent Ethics Committee (IRB/IEC) ..................55
15.
QUALITY CONTROL AND QUALITY ASSURANCE .........................................56
16.
DATA HANDLING AND RECORDKEEPING.......................................................57
16.1.
Case Report Forms / Electronic Data Capture............................................................57
16.2.
Inspection of Records .................................................................................................57
16.3.
Retention of Records ..................................................................................................58
17.
SPONSOR DISCONTINUATION CRITERIA.........................................................59
18.
PUBLICATION POLICY ..........................................................................................60
19.
LIST OF REFERENCES............................................................................................61
20.
APPENDICES ............................................................................................................62


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LIST OF TABLES
Table 1:
Abbreviations and Specialist Terms...........................................................................14
Table 2:
Investigational Product ...............................................................................................24
Table 3:
Investigational Product ...............................................................................................25
LIST OF FIGURES
No table of figures entries found.




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4.
ETHICS
4.1.
Institutional Review Board (IRB) / Independent Ethics 
Committee (IEC)
It is the responsibility of the Investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent forms, and other relevant documents, e.g., 
advertisements, if applicable, from the IRB/IEC.  All correspondence with the IRB/IEC
should be retained in the Investigator File (Site Master File).  Copies of IRB/IEC approvals 
should be forwarded to the Sponsor.
The only circumstance in which a protocol amendment may be initiated prior to IRB/IEC
approval is where the change is necessary to eliminate apparent immediate hazards to the 
subjects.  In that event, the Investigator must notify the IRB/IEC and the Sponsor in writing 
within 5 working days after implementation.
4.2.
Ethical Conduct of the Study
The study will be performed in accordance with the protocol, International Conference on 
Harmonisation Good Clinical Practice guidelines (ICH E6) and applicable local regulatory 
requirements and laws.
4.3.
Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or subject initials on any forms, reports, publications, or in any other disclosures.  Each 
subject will be assigned a study number that is used in the Case Report Form (CRF) in lieu of 
the subject’s name.  In case of data transfer, the Sponsor will maintain high standards of 
confidentiality and protection of subject personal data.
The informed consent form must be agreed to by the Sponsor and the IRB/IEC and must be 
in compliance with current ICH E6, GCP, local regulatory requirements, and legal 
requirements and be in a language that the subject can read and understand.
The Investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation.  The Investigator, or a 
person designated by the Investigator, will obtain written informed consent from each subject 
before any study-specific activity is performed (except review of Drug Facts Label).  The 
informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB and the Sponsor before use.  The 
Investigator will retain the original of each subject's signed consent form.  A copy of the 
signed and dated consent form will be provided to subjects.
Only subjects who provide informed consent will enter in the study.


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5.
STUDY ADMINISTRATIVE STRUCTURE
Details on the administrative structure of the study (e.g., Principal Investigator (PI)/study site 
personnel, the Sponsor’s study team, and the external service providers/clinical research 
organizations) will be included in the study contact list. The study contact list will also 
include contact information for the Sponsor, Investigator(s), Monitor(s), Clinical and 
Bioanalytical Laboratories, and IRB(s), as well as the names and titles of the person(s) 
authorized to sign the protocol and the protocol amendment(s) for the sponsor. This list will 
be maintained in the trial and site master files throughout the study.








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and 12 hours after the first dose of medication on Day 1 and to take the next two doses at 8 
and 12 hours after the first dose was administered at the site. At the 8 and 12 hour time 
points, the diaries should be completed prior to the medication being taken. 
One third of eligible subjects will be assigned to the pharmacokinetic cohort. They will have 
3-mL blood samples collected by direct venipuncture. Two samples will be collected; one at 
approximately 1 (±10 minutes) and another at 4 hrs (±20 minutes) after the initial dose. 
These subjects will have provided written consent to the collection of blood samples. After 
the pharmacokinetic cohort has been completed, subsequent enrolling subjects will not be 
asked to consent to the collection of blood samples.
Subjects will be instructed to complete the final assessments in their diary the next morning 
on Day 2, 24 hours after the first dose was administered. The 24-hour assessments can also 
be completed during the follow-up visit if it falls within the window. Subjects will return to 
the study site for a Follow-up Visit on Day 2 (+1 day) for reconciliation of drug and 
reporting of any adverse events or concomitant medications. Vital signs will be obtained and 
the subject will be discharged from the study.
No other cough, cold, allergy, or analgesic/antipyretic medicines (nonprescription or 
prescription) or herbal/dietary supplements will be permitted during the study.  Adverse 
events will be collected during the study to evaluate safety.
8.2.
Subject Inclusion Criteria
This clinical study can fulfill its objectives only if appropriate subjects are enrolled. The 
following eligibility criteria are designed to select subjects for whom protocol treatment is 
considered appropriate. All relevant medical and non-medical conditions should be taken 
into consideration when deciding whether this protocol is suitable for a particular subject.  
No waivers to inclusion or exclusion criteria will be permitted.
Subjects must meet all of the following inclusion criteria (and none of the exclusion criteria)
to be eligible for enrollment into the study:
1. Provide a signed and dated informed consent form before any study-related 
procedures.
2. Men or non-pregnant, non-lactating women, aged 18 years or older, who have cold 
symptoms due to an acute upper respiratory tract infection but are otherwise healthy
3. Have experienced onset of common cold symptoms (per subject report) within 72 
hours before study entry consisting of cold symptoms per the following:
a.
At Visit 1, at least moderate severity (score ≥ 5, on a scale from 0 = none to 7 = 
severe) for stuffy/congested nose, and 
b. At Visit 1, at least mild (score ≥ 3, on a scale from 0 = none to 7 = severe) for 
sinus pressure/tenderness, and
c.
Within the past 72 hours, two or more of the following symptoms: runny nose, 
sore or scratchy throat, sneezing, headache, malaise, or cough.


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4. Are normotensive and have no clinically significant abnormalities identified by 
medical history or vital sign measurement (except as consistent with the diagnosis of 
the common cold) as determined by the Investigator at screening.

Blood pressure must be within the following limits after sitting for approximately 
5 minutes: > 90 and <140 mm Hg systolic, and >50 and <90 mm Hg diastolic, at 
screening

Pulse rate >50 and <90 beats/minute at screening;

Body Mass Index (BMI) of 18 to 34 kg/m2 (inclusive);
5. Willing to use only the study treatment for cold symptom relief during the course of 
the study and avoid the use of treatments that may affect nasal / cold 
symptomatology; no other cough, cold, allergy, or analgesic/antipyretic medicines 
(non-prescription or prescription) or herbal/dietary supplements will be permitted 
during the study
6. Females of childbearing potential must have used an effective form of birth control 
for three months before Screening and a negative urine pregnancy test at the 
Screening visit. 
7. Female and male subjects must agree to the contraceptive requirement use during the 
study and for at least 30 days after the last dose (for females) (See Section 10.4.3 ).
8.
Willing and able to comply with the study procedures and visit schedule, which 
includes remaining at the study site for at least 4 hours after the first dose of study 
medicine on Day 1.
9. Able to read and understand English and/or French;
8.3.
Subject Exclusion Criteria
Subjects presenting with any of the following will not be included in the study:
1. Currently experiencing nasal congestion due to allergic rhinitis or chronic respiratory 
disease.
2. Any ear, nose, throat, or respiratory tract disease, other than the common cold,
identified by signs and symptoms reported by the subject, or by medical history or 
medication history 
3. Presence of asthma.
4. History of rhinitis medicamentosa, anatomical nasal obstruction or deformity, nasal 
reconstructive surgery, or chronic sleep apnea.
5. Fever of ≥ 101.0 °F (38.3 °C).
6. Heart disease, controlled or uncontrolled hypertension, thyroid disease, diabetes, 
glaucoma, prostatic hypertrophy, or presence of a disease, which in the opinion of the 
investigator, would preclude the use of phenylephrine.


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7. Are currently taking, or have taken within two weeks of screening, a monoamine 
oxidase inhibitor (MAOI).
8. Have the need to use medications which may impact nasal symptomatology i.e. 
systemic, inhaled (oral or nasal) corticosteroids, and the following drugs with 
significant anticholinergic properties: tricyclic antidepressants, paroxetine, medicines 
used to treat overactive bladder, antipsychotic medication, skeletal muscle relaxants, 
antiparkinsonian medication, the anticonvulsants carbamazepine and oxcarbazepine, 
and dicycloverine (dicyclomine), dimenhydrinate, propantheline, atropine, 
hyoscyamine, belladonna, prochlorperazine and promethazine.
9. Have a bacterial sinus infection within 2 weeks prior to screening.
10. Use of systemic antibiotics within the past 7 days prior to screening.
11. Known or suspected alcohol or substance abuse (e.g., amphetamines, 
benzodiazepines, cocaine, marijuana, opiates).
12. Use of marijuana containing substances within the 10 days prior to screening and 
throughout the study.
13. Positive Urine Drug Screen.
14. Use of alcohol throughout the study.
15. History of smoking tobacco products or use of nicotine-containing substances within 
the previous three months as determined by subject’s medical history or subject’s 
verbal report.
16. Known sensitivity to the investigational product or any excipients of the drug 
product.
17. Before the first dose of study medicine, use of
a.
oral or intranasal cold, cough, allergy, or analgesic/antipyretic medicines within 
approximately 12 hours;
b. menthol products, medicated lozenge, humidifier, nasal saline spray or throat 
spray within approximately 6 hours; 
c.
herbal/dietary supplements within approximately 12 hours.
18. Have difficulty swallowing tablets/capsules or are unable to swallow whole without 
crushing, chewing, splitting, or dissolving.
19. Subjects who were previously randomized and received the IP. 
20. Significant unstable or uncontrolled medical condition that may interfere with a 
subject's participation in the study.
21. Other severe, acute or chronic, medical or psychiatric condition(s) or laboratory 
abnormality that may increase the risk associated with study participation or IP 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.


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22. Currently participating in another clinical trial or has done so in the past 30 days.
23. Subjects who are related to those persons involved directly or indirectly with the 
conduct of this study (i.e., principal investigator, sub-investigators, study 
coordinators, other site personnel, employees of Johnson & Johnson (J&J) 
subsidiaries, contractors of J&J, and the families of each).  
8.4.
Subject Withdrawal Criteria
Subjects have the right to withdraw from the study at any time for any reason without 
compromising their rights to receive further treatment. The Investigator and/or the Sponsor
may terminate a subject from investigational treatment and/or study follow-up in the event of 
any of the following:

Medical reasons considered significant by the subject, Investigator and/or the 
Sponsor, which may include, an AE, intercurrent illness or medical reasons unrelated 
to the study

Non-medical reasons (e.g., subject request or non-compliance with the treatment 
procedure as determined by the investigator, the Sponsor and/or subject)

Pregnancy

Serious eligibility or on-study violation of the protocol

Administrative or other reasons
Should a subject decide to withdraw from the study at any point, all efforts should be made to 
complete all End of Study assessments (if subject cannot come to study site, a telephone call 
to collect information could be performed). In case of questions surrounding the 
circumstances that a subject needs to be withdrawn from the study (e.g., protocol deviation), 
the Sponsor or the Sponsor representative should be consulted. The reason for withdrawal 
should be documented in the subject’s source document and in the Subject Disposition CRF.  




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subject.  The scratch off sticker should not be removed from the label and the integrity of the 
scratch off surface should be preserved.
9.4.
Blinding and Unblinding 
Breaking the blind during the study is restricted to medical emergencies and should only be 
done under circumstances where knowledge of a subject’s treatment is necessary for reasons 
of subject safety. In such cases, the investigator may in an emergency determine the identity 
of the treatment by accessing the Interactive Web Response System (IWRS). The decision 
to unblind a subject can be made by the PI. Where possible, the Sponsor should be informed 
before breaking the blind. However, if an emergency condition exists and there is not 
sufficient time to consult with the Sponsor, the PI alone can request the unblinding of a 
subject. The Sponsor must be informed within 24 hours after the unblinding. Telephone 
contact with the Sponsor or its designee will be available 24 hours per day, 7 days per 
week. The rationale, date, time, and contact attempts for breaking the blind for a subject in a 
trial should be documented in the subject’s file and in the appropriate section of the 
CRF. The reason for un-blinding is not captured through the IWRS.
The study site should take necessary measures to maintain the study treatment blind and 
prevent any unintended or premature unblinding. If unblinding is performed, the occurrence 
will be reported by the PI to the Clinical Research Organization and the Sponsor as soon as 
possible and will be entered into the subject’s record, but the group assignment will not be 
divulged. The subject whose treatment blind has been broken will be immediately 
discontinued from the IP and will be discontinued from the study and followed-up by the 
study staff until the event or its sequelae resolve or stabilize at a level acceptable to the 
Investigator (see Adverse Events section).
The documentation received from the IWRS indicating the code break must be retained with 
the subject’s source documents in a secure manner (e.g., secure e-mail, fax, sealed envelope)
so as not to un-blind the treatment assignment to the study site or Sponsor personnel. The 
investigator is also advised not to reveal the study treatment assignment to the study site 
(except as necessary for the clinical management of the subject) or Sponsor personnel.
9.5.
Method of Assigning Subjects to Treatment Groups
The randomization schedule will be generated by the Sponsor.  Subjects will be randomized 
via an IWRS to receive one of three treatments (phenylephrine
phenylephrine
or placebo, 1:1:1 ratio). 
Table 3:
Investigational Product
 
 
 


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9.6.
Study Product Storage and Accountability
Temperature monitors will be included with the IP that is shipped to the sites. These 
monitors will indicate if the temperature has varied (either too hot or too cold) beyond what 
is appropriate for the product. Sites will store product in accordance with Sponsor’s 
requirements and will report temperature variations as appropriate. The Investigator or a 
designated study staff member will ensure that IP is stored at the correct temperature upon 
arrival at the site.   
The Investigator, or a designated study staff, will ensure that all IP are stored in a secured 
area, under recommended room temperature storage conditions between 68 °F to 77 °F (20 
°C to 25 °C) with excursions allowed as permissible and in accordance with applicable 
regulatory requirements.
The Investigator must maintain adequate records documenting the receipt, use, loss, or other 
disposition of the IP on the IP Accountability Log.  The log must identify the IP and account 
for its disposition on a subject-by-subject basis, including specific dates and quantities 
dispensed and returned.  The log must be signed by the individual who dispensed/retrieved 
the IP, and copies must be provided to the Sponsor for the Trial Master File.
At the end of the study, the Sponsor will provide instructions on the disposition of any 
unused IP.  If the Sponsor authorizes destruction at the study site, the Investigator must 
ensure that the materials are destroyed in compliance with applicable environmental 
regulations, institutional policy, and any special instructions provided by the Sponsor.  
Destruction must be adequately documented.
9.7.
Administration of the Investigational Product 
The first and second dose of the IP will be administered by the investigational study staff at
the site.  Subjects will be given 2 doses to dose the rest of the day.
9.8.
Product Quality Complaints
A Product Quality Complaint (PQC) is any written, electronic, or oral communication that 
alleges deficiencies related to the identity, quality, durability, reliability or safety of a 
product, including its labeling, delivery system or packaging integrity. This does not include 
effectiveness, preference or performance measures, which will be reviewed in aggregate at 
appropriate intervals.
Any PQC discovered during the initial inventory of study supplies should follow the 
instructions provided on the receipt letter; no PQC form should be filed for issues identified 
when opening or unpacking a shipment. Subsequently, any observation of a PQC requires 
immediate notification to the Sponsor or designee via a completed PQC form and telephone 
call. The PI or designee should complete, sign and forward a copy of the PQC form, via an 
agreed upon secure exchange, to the Sponsor or designee.
In addition, PQC information must be included on the IP Dispensing and Accountability Log 
or equivalent in the “Comments” field.  The Sponsor or designee listed can assist the site or 
answer questions related to this process. To aid in the initial conversation and understanding 


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of a PQC, the site staff may be asked to photograph the issue and send it to the Sponsor or 
designee. 
When enrolling subjects into this study it is the site’s responsibility to instruct subjects not to 
use the product if they have a concern related to the product such as an issue with the 
labeling, IP or package integrity and to immediately report it using the instruction on the 
Informed Consent or product label.  


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10.
STUDY PROCEDURES
10.1.
Overview
Collection of AEs and concomitant therapies will start after the study-specific informed 
consent document has been signed and continue until completion of the follow-up 
procedures. The Schedule of Activities/Study Flow Chart (Table 1) summarizes dose 
administration and the timing and frequency of safety and efficacy procedures and 
measurements. In the event of abnormal safety findings during the conduct of the study, the 
attending physician may request additional safety evaluations, either immediately or 
subsequently at a frequency considered appropriate.
10.2.
Screening / Day 1 Visit (including up to morning of Day 2)
Informed consent must be obtained from the subjects before any study related assessments
are conducted.  If subjects did not qualify per Inclusion Criteria 3 they may be re-screened
one other time with a different episode of Upper Respiratory Tract Infection (URTI). For 
subjects who are being re-screened, all inclusion/exclusion criteria must be re-evaluated.
Procedures to be performed at this visit are:

Informed Consent (Informed Consent can be performed the day prior to Visit 1 as 
long as the Day 1 visit is within the 72 hour window of onset of cold symptoms).  

Inclusion and exclusion criteria

Demography

Height, weight and body mass index assessment

Significant medical history (e.g., drug allergy, major medical conditions as noted 
in the Exclusion criteria, previous heavy drinking and/or smoking history)

Collect Adverse Events if subject reports an event beginning after medical history 
has been taken (i.e. if screening and baseline are separate days.)  

Prior and concomitant medication and other therapies (within 14 days)

Vital signs: respiratory rate, oral body temperature

Vital signs: Resting blood pressure and heart rate at baseline (pre-dose) and at 2 
and 4 hours post-dose, immediately following completion of subject assessments
at 2 and 4 hours post dose  (baseline vital signs can be performed either before or 
after baseline assessments.

Urine pregnancy test for all female subjects of childbearing potential

Urine Drug Screen

Allocating treatment assignment via IWRS


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
Administer the first dose of IP between 7:00 and noon and a second dose 4 hours 
(+10 minutes) later.

PK blood draws at 1 hour (±10 minutes) and 4 hours (±20 minutes) post dose for 
those subjects who have consented to the PK portion of the study. The 4 hour PK 
sample should be performed after the 4 hour vital signs have been collected.

Subjects will remain at the site until after the second dose administration.

While subjects are at the site, all lifestyle guidelines outlined in the protocol 
must be followed.

Subject Assessments/Questionnaires

Subject Cold Symptoms Assessment - at baseline

Nasal Congestion Severity Rating - at baseline (within approximately 30 
minutes prior to administration of IP), at 2 and 4 hours (±10 minutes) post-
dose

Sinus Pressure Severity Rating - at baseline (within approximately 30 minutes
prior to administration of IP), at 2 and 4 hours (±10 minutes) post-dose

Head Congestion Severity Rating - at baseline (within approximately 30 
minutes prior to administration of IP), at 2 and 4 hours (±10 minutes) post-
dose

Reflected Impact of Nasal / Sinus Congestion on Clear Thinking – at baseline 
(within approximately 30 minutes prior to administration of IP)

Reflected Congestion Severity Rating – at baseline (within approximately 30 
minutes prior to administration of IP)

Wisconsin Upper Respiratory Symptom Survey (WURSS-21) cold severity 
rating – at baseline (within approximately 30 minutes prior to administration 
of IP)

Dispense IP and instruct subjects on the completion of subject questionnaires 
using diaries.
Subjects will be discharged from the site with instructions to complete the subject 
questionnaires using the Diary as follows:

Nasal Congestion Severity Rating - at 6, 8, 10 and 12 hours post-dose and 
morning of Day 2 (24 hours).

Sinus Pressure Severity Rating - at 6, 8, 10 and 12 hours post-dose and 
morning of Day 2 (24 hours).

Head Congestion Severity Rating - at 6, 8, 10 and 12 hours post-dose and 
morning of Day 2 (24 hours).


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
Reflected Impact of Nasal / Sinus Congestion on Clear Thinking – at Hour 12 
post-dose 

Reflected Congestion Severity Rating – at Hour 12 post-dose 

Reflected Change in Nasal Congestion Symptoms, reflective over the day – at 
Hour 12 post-dose.

Reflected Nasal Functioning (clear breathing) Rating, reflective over the day –
at Hour 12 post-dose.

Wisconsin Upper Respiratory Symptom Survey (WURSS-21) cold severity 
rating – morning of Day 2 (24 hours). 
10.3.
End of Study Procedures 
End of Study Procedures are to be performed at the Follow-up visit on Day 2 (+1 day) when 
the subject returns to the site.
The following information will be collected during this visit: 

Vital signs: blood pressure, heart rate, respiratory rate, oral body temperature

Adverse Events

Concomitant medications/therapies

If the 24 hour assessment window falls during the follow-up visit, this assessment can 
be completed at the site.

Return of diary (if paper)

Return of IP and check compliance.

Subject Disposition
10.4.
Lifestyle Guidelines 
Usual methods for relieving nasal congestion and other cold symptoms, including steam 
humidifier, nasal saline spray, menthol lozenges, menthol gum, menthol shower gels and 
vapor rubs should be strictly avoided until after the final efficacy assessments are completed 
on Day 2.
10.4.1.
Meals and Dietary Restrictions 
While subjects are at the site and offsite on Day 1, all snacks, drinks, and meals during the 
efficacy assessment period should not be consumed within 30 minutes prior to the next 
subjective assessments.  
Warm drinks, including caffeine-containing drinks or hot soup, should not be consumed 
either onsite or offsite until after the efficacy assessments are completed.  A study has shown 
a significant improvement in subjective symptoms scores after consuming these fluids when 
compared with drinks at room temperature [8].


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10.4.2.
Alcohol, Caffeine and Tobacco Consumption / Restrictions 
Subjects will abstain from 

drinking alcohol during the study until all End of Study procedures are completed;

the use of tobacco- or nicotine-containing products until all End of Study 
procedures are completed;

smoking marijuana or the use of marijuana-containing products until all End of 
Study procedures are completed;

drinking caffeine-containing products (e.g., soda, tea, and coffee) during the study 
until the Day 2 assessment is completed.
10.4.3.
Contraception
Female subjects are considered not of childbearing potential if they meet at least one of the
following criteria:

Had a hysterectomy and/or bilateral oophorectomy at least 6 months prior to 
product administration.

Had sterilization surgery (for hysteroscopic sterilization/tubal implants) at least 6 
months prior to screening and has been confirmed effective by medical 
assessment as reported by the subject.

Are post-menopausal (e.g., amenorrhoeic for at least 12 consecutive months, 
without an alternative medical cause, prior to Day 1).
Medically acceptable forms of birth control that may be used by the subject and/or his/her 
partner include: 

Established use of hormonal methods of contraception (oral, injected, implanted, 
patch or vaginal ring).

Barrier methods of contraception with spermicide: condom or occlusive cap 
(diaphragm or cervical/vault caps) with spermicidal foam/gel/ film/ cream/
suppository. 

Intrauterine device or intrauterine system.

Surgical sterilization (e.g., vasectomy that has been confirmed effective by sperm 
count check, tubal occlusion, hysterectomy, bilateral salpingectomy).

Abstinence from heterosexual intercourse, when this is in line with the preferred 
and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception. 
Male and female subjects with reproductive potential must agree to practice a medically 
acceptable form of birth control throughout the study and for at least 30 days after the last 
dose (for females).


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10.5.
Treatment Compliance 
On Day 1, investigational site staff will instruct the subjects on the importance of being 
compliant with the IP and completing the Diary at the specified timepoints.  At the End of
Study visit, subject’s compliance to IP will be checked by the number of doses of IP returned 
compared with the number of doses the subject was supposed to have taken with
consideration of what was entered in the Diary by the subject.  
10.6.
Previous and Concomitant Therapies
Female subjects who are using hormonal contraceptives will continue to take them during the 
study and this concomitant medication will be recorded on the CRF.  Other medications or 
non-drug therapies used 14 days before the Screening visit and during the study will be 
recorded in the source document and CRF.
Any medications taken before the first dose of IP will be considered as prior medications.  
Any medications taken after the first dose of IP until the End of Study will be considered as 
concomitant medications.
Subjects will abstain from using prescription or non-prescription drugs and dietary and herbal 
supplements in accordance with the inclusion/exclusion criteria. All subjects will be 
questioned about concomitant medication at each visit.






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11.1.6.
Wisconsin Upper Respiratory Symptom Survey 21


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11.2.
Pharmacokinetic Assessments
11.2.1.
Blood collection
From a pharmacokinetic cohort of approximately 150 subjects, two blood samples (3 mL) 
will be collected by venipuncture into appropriately labeled K3 EDTA tubes at 1 hour (±10 
minutes) and 4 hours (±20 minutes) after the first dose. The 4 hour PK sample should be 
performed after the 4 hour vital signs have been collected. These samples will be collected at 
the nominal time relative to dosing. The exact time of the sample collection will be noted on 
the source document and CRF. Samples will be assayed for either phenylephrine using 
validated analytical methods.
11.2.2.
Blood sample processing
After collection of pharmacokinetic blood samples into appropriately labeled K3 EDTA 
tubes, the tubes will be gently mixed approximately eight times and immediately placed on 
ice or cryoblocks for transportation to the centrifuge. The tubes will be centrifuged at 
approximately 2700 to 3000 (high-speed) rpm for about 10 minutes within 60 minutes of 
collection. Following centrifugation, the plasma will be immediately returned to an ice bath 
while samples are divided into two identically labeled screw-capped polypropylene tubes. 
They will be frozen at nominally -20ºC or -70ºC within a fluctuation range of ±15ºC at the 
clinic. The time from sample collection to the freeze time should not exceed 60 minutes. 
Frozen samples will be stored at nominally -70ºC at the bioanalytical laboratories. The blood 
and plasma tubes will be labeled with the following information at a minimum: subject 
identification number, sampling time, date of collection, and unique study code (i.e., protocol 
number).
11.2.3.
Shipment of Pharmacokinetic Samples
Pharmacokinetic plasma samples will be shipped at times specified by the Sponsor. Further 
information regarding handling, shipment (e.g., addresses and laboratory contacts), and 
labeling of biological samples will be provided as separate documents to the clinical site.
11.2.4.
Analytical Procedures
Plasma samples will be sorted by assigned staff at the laboratory such that those samples 
having active treatment will be assayed for phenylephrine concentrations. After 
quantification of phenylephrine, remaining plasma will be retained until destruction is 
approved by the Sponsor.
11.2.5.
Population Pharmacokinetic Modeling
Plasma concentration-time data for phenylephrine will be evaluated in a population 
pharmacokinetic analysis with potential simulations to evaluate and optimize future clinical 
study designs. The results will be reported separately from the efficacy and safety results.


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11.3.
Safety Assessments
Safety assessments will consist of the monitoring of AEs collected throughout the study, and 
review of blood pressure and heart rate measured at baseline (before drug) and at 2 and 4 
hours after the morning dose on Day 1, and at the End of Study Visit which will occur on 
Day 2.
11.3.1.
Vital Signs
As shown in the Study Flow Chart and Schedule of Activities, the following vital signs will 
be assessed at Visit 1: respiratory rate, oral body temperature, and resting blood pressure and 
heart rate at baseline (pre-dose).  Resting blood pressure and heart rate will also be assessed 
at 2 and 4 hours post-dose, immediately following completion of subject assessments.  At the 
Follow-up visit on Day 2 (+1 day), resting blood pressure and heart rate, respiratory rate, and 
oral body temperature will be assessed.  Sitting blood pressure will be obtained after the 
subject has been sitting with feet flat for approximately 5 minutes.  At screening, blood 
pressure must be within the following limits after sitting for approximately 5 minutes: > 90
and <140 mm Hg systolic, and >50 and <90 mm Hg diastolic, to be randomized into the 
study.
Blood pressure can be repeated up to three times and recorded in the source document, but 
only the qualifying measurement will be entered in the eCRF.  According to the Joint 
National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood 
Pressure in adults ages 18 and older, hypertension is defined as systolic blood pressure ≥ 140 
mmHg or diastolic blood pressure ≥ 90 mmHg.   This classification is based on the average 
of two or more properly measured seated blood pressure readings on each of two or more 
office visits.


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12.
ADVERSE EVENT REPORTING
12.1.
Introduction
All observed or volunteered AEs regardless of treatment group or suspected causal
relationship to the IP(s) will be reported as described in the following sections. For all AEs, 
the Investigator or medically qualified individual must pursue and obtain adequate 
information both to determine the outcome of the AE and to assess whether it meets the 
criteria for classification as a Serious Adverse Event (SAE) requiring immediate notification 
(within 24 hours) to the Sponsor or its designated representative. For all AEs, sufficient 
information should be obtained by the Investigator or medically qualified individual to try to 
determine causality.  The Investigator is required to assess causality. For AEs with a 
suspected causal relationship to the IP, follow-up by the Investigator or medically qualified 
individual is required until the event or its sequelae resolve or stabilize at a level acceptable 
to the Investigator, and the Sponsor concurs with that assessment.
12.2.
Reporting Period
All AEs for randomized subjects, whether serious or non-serious will be recorded on the 
CRF in the AE section beginning from the time the informed consent is signed and dated. If a 
screen failed subject has an AE, the AE will be recorded in the CRF along with the subject’s 
demographic data. Once, non-serious AE changed to Serious, the subsequent notification and 
completed SAE form should be completed and sent to Sponsor or designated representative 
within the timeline established for SAE reporting.  Informed consent is considered the point 
at which the subject is participating in the clinical study and all events are captured even if it 
is prior to undergoing any study-related procedure and/or receiving IP. Non-serious AEs will 
be reported through the subject’s last study visit (or termination if the subject terminates 
early from the study for any reason). Spontaneous reports of SAEs will be collected through 
and including 30 calendar days after administration of the subject’s last dose or exposure to 
IP.
SAEs require immediate notification to the Sponsor or its designated representative. Any 
SAE occurring any time after the reporting period must be promptly reported if a causal 
relationship to the IP is suspected.
12.3.
Definition of an Adverse Event
An AE is any untoward medical occurrence that occurs in a subject after they have signed an 
informed consent for a trial involving an IP. Any AE that occurs after the informed consent
has been signed, until first usage of IP, will be considered non-treatment emergent and 
cannot (by virtue of time of occurrence) have a causal relationship with the IP.
The event does not need to have a suspected causal relationship with the IP. Therefore, an 
AE can be any unfavorable and unintended sign, symptom, disease or injury temporally 
associated with the use of an IP, whether or not related to the IP. Examples of AEs include,
but are not limited to:


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
Abnormal test findings,

Clinically important signs and symptoms,

Changes in physical examination findings,

Hypersensitivity, and

Progression/worsening of underlying disease.
Additionally, they may include the signs or symptoms resulting from:

Overdose,

Withdrawal,

Abuse,

Drug misuse,

Drug interactions,

Medication errors,

Product dependency,

Exposure in utero, and

Study related procedure.
12.4.
Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as
an AE are as follows:

Test result is associated with accompanying symptoms, and/or

Test result requires additional diagnostic testing or medical/surgical intervention,
and/or

Test result leads to a discontinuation from the study, significant additional 
concomitant treatment, or other therapy, and/or

Test result is considered to be an AE by the Investigator or the Sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
12.5.
Serious Adverse Events (SAE) for Drugs
An AE or suspected adverse reaction is considered “serious” for a drug study if, in the view 
of either the Investigator (physician) or the Sponsor, it results in any of the following 
outcomes:

Results in death,


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
Is life-threatening (immediate risk of death),

Requires inpatient hospitalization or prolongation of existing hospitalization,

Results in persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions,

Results in congenital anomaly/birth defect,

Is considered medically significant (medical and scientific judgment should be
exercised in deciding whether expedited reporting is appropriate in other 
situations, such as important medical events that may not result in death, be 
life-threatening or require hospitalization but may be considered a serious adverse 
drug experience when, based upon appropriate medical judgment, they may 
jeopardize the subject and may require medical or surgical intervention to prevent 
one of the other outcomes listed above). Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an Emergency 
Room or at home, blood dyscrasia, or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse, or 
malignancy), or,

Is a suspected transmission of any infectious agent via a medical product 
(medically significant) and should be reported as an SAE in the category ‘Other 
medically important conditions.’
12.6.
Hospitalization
AEs reported from clinical studies associated with hospitalization or prolonging
hospitalization are considered serious. Any initial admission (even if less than 24 hours) to a
healthcare facility meets these criteria. Admission also includes transfer within the hospital 
to an acute/intensive care unit (e.g., from the psychiatric wing to a medical floor, medical 
floor to a coronary care unit, neurological floor to a tuberculosis unit).  Hospitalization does 
not include the following:

Rehabilitation facilities, 

Hospice facilities, 

Respite care (e.g., caregiver relief), 

Skilled nursing facilities, 

Nursing homes, 

Emergency room visits (unless the reason for the emergency room visit meets one 
of the other outcomes in the definition of serious), and/or 

Same day surgeries (as outpatient/same day/ambulatory procedures) 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 


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
Admission for treatment of a pre-existing condition not associated with the 
development of a new AE or with a worsening of the pre-existing condition (e.g., 
for work-up of persistent pre-treatment lab abnormality), 

Social admission (e.g., subject has no place to sleep), 

Administrative admission (e.g., for yearly physical exam), 

Protocol-specified admission during a clinical study (e.g., for a procedure 
required by the study protocol), 

Optional admission not associated with a precipitating clinical AE (e.g., or 
elective cosmetic surgery), 
Pre-planned treatments or surgical procedures should be noted in the baseline documentation 
for the entire protocol and/or for the individual subject.

Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, 
should not be reported as AEs. However, the medical condition for which the 
procedure was performed should be reported if it meets the definition of an AE. 
For example, an acute appendicitis that begins during the AE reporting period 
should be reported as the AE and the resulting appendectomy should be recorded 
as treatment of the AE.
12.7.
Resolution
The Investigator will be required to assess the outcome of the AE for IP as one of the
following:

Resolved,

Not Resolved,

Fatal,

Resolved with sequelae,

Resolving, or

Unknown.
Any causally-related AEs unresolved upon completion of the last study visit will be followed 
up by the study staff until the event or its sequelae resolve or stabilize at a level acceptable to 
the Investigator and recorded on the CRF.  An event that is assessed as resolved with 
sequelae or resolving indicates that the subject has stabilized to a level acceptable to the 
Investigator and has concurrence by the Sponsor.
12.8.
Severity Assessment
The Investigator or medically qualified individual (physician) will assess the severity of AEs
using the following general categorical descriptors:


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MILD:
Awareness of symptoms that are easily tolerated, causing minimal
discomfort and not interfering with subject's usual function or normal
everyday activities
MODERATE:
Sufficient discomfort is present to cause interference to some extent with
subject's usual function or normal everyday activity
SEVERE: 
Extreme distress, causing significant impairment of functioning or
incapacitation; interferes significantly with subject's usual function; 
prevents normal everyday activities
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily a serious event. For example, a headache may be severe (interferes significantly 
with subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
12.9.
Causality Assessment
The Investigator or medically qualified individual (physician) will assess causality to IP (i.e.,
relationship to IP) for all serious and non-serious AEs. An Investigator’s causality
assessment is the determination of whether there exists a reasonable possibility that the IP
caused or contributed to an AE.

Not Related - An AE that is not related to the use of the drug

Doubtful - An AE for which an alternative explanation is more likely, e.g.,
concomitant drug(s), concomitant disease(s), or the relationship in time suggests 
that a causal relationship to IP is unlikely.

Possible - An AE that might be due to the use of the drug. An alternative
explanation, e.g., concomitant drug(s), concomitant disease(s), is inconclusive. 
The relationship in time is reasonable; therefore, the causal relationship to IP
cannot be excluded.

Probable - An AE that might be due to the use of the drug. The relationship in 
time is suggestive (e.g., confirmed by dechallenge) and an alternative explanation 
is less likely, e.g., concomitant drug(s), concomitant disease(s).

Very Likely - An AE that is listed as a possible adverse reaction and cannot be 
reasonably explained by an alternative explanation, e.g., concomitant drug(s),
concomitant disease(s). The relationship in time is very suggestive (e.g., it is
confirmed by dechallenge and rechallenge) for a causal relationship to the drug.
If the Investigator determines an SAE is associated with study procedures, the Investigator 
must record this suspected causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.


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12.10.
Exposure In Utero
For IPs within clinical studies and for marketed products, an exposure in utero (EIU) occurs 
if:
1. A woman is exposed to the IP at any time between her last menses prior to conception 
through the delivery of the baby.
2. There is a possibility of intrauterine exposure to drug via semen from the male partner 
who is taking the IP at the time of conception, thereby possibly exposing the fetus to 
the product.
If any study subject or study subject’s partner becomes or is found to be pregnant during the
study subject’s participation, the Investigator must report the pregnancy to the Sponsor on a 
Pregnancy Notification Form (to be provided by the Sponsor when applicable). In addition, 
the Investigator must submit information regarding environmental exposure to a Sponsor 
product in a pregnant woman (e.g., a nurse reports that she is pregnant and has been exposed 
to a cytotoxic product by inhalation or spillage) using the Pregnancy Notification Form. This 
must be done irrespective of whether an AE has occurred and notification must occur within 
24 hours of awareness of the pregnancy. Initial notification via telephone to the Sponsor’s 
study team contact must occur immediately upon the investigational site’s awareness of the 
pregnancy. The Pregnancy Notification Form must then be sent to the Sponsor within 24 
hours of the site’s awareness. The information submitted should include the anticipated date 
of delivery (see below for information related to induced termination of pregnancy).
Follow-up is conducted to obtain pregnancy outcome information on all EIU reports. The
Investigator will follow the pregnancy until completion or until pregnancy termination
(i.e., induced abortion) and then notify the Sponsor of the outcome. The Investigator will
provide this information as a follow-up to the initial Drug Exposure During Pregnancy
Collection Form A and/or End of Pregnancy Collection Form B (provided by the Sponsor
when applicable). The reason(s) for an induced abortion should be specified. An EIU report 
is not created when an ectopic pregnancy report is received since this pregnancy is not 
usually viable. Rather, an SAE case is created with the event of ectopic pregnancy.  
The Investigator should follow the procedures for reporting SAEs if the outcome of the 
pregnancy meets the criteria for immediate classification as an SAE (i.e., spontaneous 
abortion, stillbirth, neonatal death, or congenital anomaly [including that in an aborted fetus, 
stillbirth, or neonatal death]). In the case of a live birth, the “normality” of the newborn can 
be assessed at the time of birth (i.e., no minimum follow-up period of a presumably normal 
infant is required before an End of Pregnancy Collection Form B can be completed). The 
“normality” of an aborted fetus can be assessed by gross visual inspection, unless pre-
abortion test findings are suggestive of a congenital anomaly.
Additional pregnancy outcomes that are classified as SAEs and should be reported as such 
include:

“Spontaneous abortion” includes miscarriage and missed abortion.


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
All neonatal deaths that occur within 1 month of birth, without regard to 
causality.

Any infant death after 1 month that the Investigator assesses as possibly related 
to in utero exposure to the IP.
12.11.
Withdrawal Due to Adverse Events
When a subject withdraws due to an SAE, the SAE must be reported in accordance with the 
reporting requirements defined below.
12.12.
Eliciting Adverse Event Information
The Investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs.
12.13.
Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for an SAE. If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
All AEs will be reported on the AE page(s) of the CRF. A Clinical SAE Report Form must 
also be completed if the event is considered to be serious. It should be noted that this 
Clinical SAE Report Form for collection of SAE information is not the same as the AE CRF. 
Where the same data are collected, the forms must be completed in a consistent manner. For 
example, the same AE term should be used on both forms. AEs should be reported using 
concise medical terminology on the CRFs as well as on the form for collection of SAE 
information.
12.13.1.
Serious Adverse Event Reporting Requirements
If an SAE occurs, the Sponsor is to be initially notified by telephone immediately upon 
awareness of the event by the Investigational site. Completed SAE Report form should 
always indicate the causality assessment by Investigator. Follow-up SAE form should re-
state the causality assessment based on new/additional information. Within 24 hours of the
investigational site’s awareness of the event, the study site must send the Sponsor the 
Clinical SAE Report Form. This timeframe also applies to additional new information 
(follow-up) on previously forwarded SAE reports as well as to the initial and follow-up
reporting of EIU cases.  In the rare event that the Investigational site does not become aware 
of the occurrence of an SAE immediately (e.g., if an outpatient study subject initially seeks 
treatment elsewhere), the Investigational site is to report the event immediately after learning 
of it as described and document the time of the investigational site’s first awareness of the 
SAE.
For all SAEs, the Investigator is obligated to pursue and provide information to the Sponsor 
in accordance to the timeframes for reporting as specified above. In addition, an Investigator 
may be requested by the Sponsor to obtain specific additional follow-up information in an 
expedited fashion. This information may be more detailed than that captured on the AE
CRF. In general, this will include a description of the AE in sufficient detail to allow for a 


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complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant 
medications and illnesses must be provided. In the case of a subject’s death, a summary of 
autopsy findings (if available) and death certificate should be collected if permission is 
obtained from the subject’s family. For a hospitalization, a copy of the hospital discharge 
summary should be requested. If obtained, these documents (with subject’s personal 
identifiers redacted) should be forwarded to the Sponsor or its designated representative as 
soon as possible.
Appropriate SAE forms will be provided to the investigational site at the initiation of the 
study. Upon notification of an SAE at the investigational site, the Investigator or designated 
study site staff should call and speak to their Sponsor’s study team contact immediately to 
initially notify them of the SAE.
Within 24 hours of awareness of the event, the Investigator or designated study site staff:

Complete the Clinical SAE Report Form that has been provided by the Sponsor
or designee with as much information as possible, however at a minimum, the 
subject identification number, name of the IP, SAE, and name of the reporter;  

Ensures the Investigator signs the Clinical SAE Report Form prior to sending it 
to the Sponsor;

Scans and send the Clinical SAE Report Form to the Sponsor contacts (See 
Contact List or SAE Pregnancy Flow Diagram provided by the Sponsor 
separately) securely.
12.14.
Special Situations
Special Situations (SS): Safety events that may not meet the definition of an AE; however, 
are required to be collected to meet Health Authority requirements. Examples include:

Overdose of a J&J medicinal product.

Pregnancy exposure (maternal and paternal) to a J&J medicinal product.

Exposure to a J&J product from breastfeeding.

Suspected abuse/misuse of a J&J medicinal product.

Inadvertent or accidental exposure to a J&J medicinal product (including 
occupational exposure).

Unexpected therapeutic or clinical benefit from use of a J&J product.

Medication error involving a J&J medicinal product with or without 
patient/consumer exposure to the J&J product, (e.g., product name confusion) OR 
that caused an unintended effect or could cause an intended effect (e.g. adult 
medicine given to a young child).

Suspected transmission of an infectious agent via a J&J product.


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13.
STATISTICS
The Sponsor will be responsible for the statistical analysis of study data. Detailed 
methodology for the statistical analysis of the data will be documented in a Statistical 
Analysis Plan finalized and approved prior to database lock and release of randomization 
codes.
13.1.
Sample Size Determination 
The study sample size is based on a requirement to achieve appropriate precision of 
estimated treatment mean differences with respect to mean change from baseline in the Nasal 
Congestion Severity Score (NCSS) assessed at 2, 4, 6, 8, 10, and 12 hours on Day 1. From 
available data on the primary endpoint 
 
 it is reasonable to assume a common standard deviation of 1.5 scale units for 
the three study treatments. 
With this assumption, 138 completed study subjects in both compared arms implies a 90% 
probability that the length of a 95% confidence interval for a treatment mean difference with 
respect to the primary endpoint will be at most 0.75 scale units. With an assumed 9% dropout 
rate, 150 subjects will be enrolled in each treatment arm.  
13.2.
Analysis Sets
For the efficacy analyses, the Full Analysis Set will include all randomized subjects who 
provide a valid baseline assessment of nasal congestion severity.  The safety analyses will be 
based on all randomized subjects who take at least one dose of treatment.
13.2.1.
Secondary Endpoints
The secondary efficacy endpoints include

Change from baseline in the NCSS averaged over assessments at 8, 10, and 12 
hours.

Change from baseline in the NCSS at 2, 4, 6, 8, 10, and 12 hours and in the 
morning of Day 2 (24 hours), respectively.

Change from baseline in Sinus Pressure/Tenderness Scores averaged over 
assessments at 2, 4, 6, 8, 10, and 12 hours.

Change from baseline in Sinus Pressure/Tenderness Scores at 2, 4, 6, 8, 10, and 
12 hours and in the morning of Day 2 (24 hours), respectively.
13.2.2.
Baseline and Demographics
Baseline and demographic characteristics will be presented by treatment group.  For 
continuous variables, descriptive summaries will include number of subjects, mean, standard 
deviation, median and range (min, max).  For categorical variables, the number and percent 
of subjects in each response category will be presented.


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13.3.
Efficacy Analysis
13.3.1.
Primary Endpoint 
The primary efficacy endpoint is the change from baseline in the nasal congestion severity 
score (NCSS) averaged over assessments at 2, 4, 6, 8, 10, and 12 hours on Day 1.  The 
baseline nasal congestion score will be measured within approximately 30 minutes before the 
first dose.
13.3.2.
Exploratory Endpoints

Change from baseline in Head Congestion Scores averaged over assessments at 2, 
4, 6, 8, 10, and 12 hours.

Change from baseline in Head Congestion Scores at 2, 4, 6, 8, 10, and 12 hours 
and in the morning of Day 2 (24 hours), respectively.

Change from baseline in Reflected Impact of Nasal / Sinus Congestion on Clear 
Thinking (reflected for the previous 12 hours) at 12 hour assessment

Reflected Change in Nasal Congestion Symptoms (reflected over 12 hours after 
the first dose).

Reflected Nasal Functioning (reflected over 12 hours after the first dose).

Change from baseline in Reflected Congestion Severity (reflected for the previous 
12 hours) at 12 hour assessment

Assessment of cold severity using Wisconsin Upper Respiratory Symptom 
Survey-21 (reflected over 24 hours) at baseline and in the morning of Day 2 (24 
hours).
13.3.3.
Pharmacokinetics
Plasma concentration-time data will be subjected to a population pharmacokinetic analysis 
and reported separately; however, blood plasma levels will be summarized descriptively by 
treatment and assessment time points.
13.3.4.
Psychometric Analyses
In addition to the analyses described here, the data collected in this study will also be used to 
evaluate the psychometric properties of the primary and secondary outcome assessments in 
this context of use and to perform analyses to estimate the level of change in scores that can 
be considered meaningful and important.  Those analyses will be performed using data 
pooled across treatment and placebo groups.   These analyses will be described in a specific 
psychometric analysis plan which will be finalized prior to database lock and will be reported 
separately.


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13.3.5.
Statistical Analyses
This is a Phase II, POC study and therefore the inferential statistical procedures are focused 
on point and interval estimation of pairwise treatment differences in the primary and 
secondary efficacy endpoints. However, to further aid interpretation of findings, p-values 
from 2-sided tests of the null hypotheses of no treatment (mean) difference will be provided 
in each case.  
The primary analysis of the primary endpoint, which is the change from baseline in the Nasal 
Congestion Score (score for stuffy/congested nose averaged over assessments at 2, 4, 6, 8, 
10, and 12 hours on Day 1), will be based on all randomized subjects who provides at least 
an assessment of nasal congestion at baseline and receives study treatment. The primary 
endpoint will be analyzed by an ANOVA model with treatment group, study center, and 
baseline nasal congestion score as factors. For subjects who dropout, their last reported 
congestion score before the dropout will be imputed for the remaining assessment time 
points.
In addition, a secondary analysis of the primary endpoint will be restricted to randomized 
subjects who complete all assessments of congestion for Day 1. The same statistical model 
will be used as in the primary analysis.
Analysis of all other secondary endpoints involving instantaneous nasal congestion scores 
will be performed using an ANOVA model with treatment group, study center, and baseline 
nasal congestion score as factors.
Analysis of secondary endpoints involving Sinus Pressure/Tenderness Scores will be 
performed using an ANCOVA model with treatment group and study center as factors, and 
baseline Sinus Pressure/Tenderness Score as a covariate.
Analysis of endpoints involving Head Congestion Scores will be performed using an 
ANCOVA model with treatment group and study center as factors, and baseline Head 
Congestion Score as a covariate.
Pairwise treatment differences in the distributions of Reflected Change in Nasal Congestion 
Symptoms and Reflected Nasal Functioning scores, both reflected over 12 hours after the 
first dose, will be analyzed using the van Elteren test stratified by center.  
Pairwise treatment differences in the distributions of Change from baseline in Reflected 
Impact of Nasal / Sinus Congestion on Clear Thinking and Change from baseline in 
Reflected Congestion Severity (reflected for the previous 12 hours), will be analyzed using the 
van Elteren test stratified by center.  
All efficacy endpoints, including the assessments of cold severity using the Wisconsin Upper 
Respiratory Symptom Survey (WURSS-21) at baseline and in the morning of Day 2 (24 
hours), will be described by summary statistics.
Presented confidence intervals will be two-sided and have confidence level 95%. To guide 
interpretation p-values from 2-sided tests of the null hypotheses of either no treatment (mean) 
difference or no distributional difference between treatments will be provided in each case.
This is an exploratory Phase 2 POC study. Additional post-hoc analyses may be performed.


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13.4.
Safety Analysis
The safety analyses will be based on all randomized subjects who take at least one dose of 
treatment.
13.4.1.
Adverse Events
The number and percentage of subjects experiencing AEs will be tabulated by treatment 
using the MedDRA coding dictionary.  Subjects experiencing SAEs, treatment-related AEs,
and who discontinued from the study due to an AE will also be presented.  Treatment-related 
AEs will include events marked as being at least possibly related to study treatment. AEs 
will be presented by severity and by relation to treatment.
Subjects will be counted only
once for each system organ class and preferred term by selecting the most severe event.
13.4.2.
Clinical Laboratory Tests
Not applicable.
13.4.3.
Vital Signs
Descriptive statistics of oral body temperature, respiratory rate, heart rate, and blood pressure 
(systolic and diastolic) will be summarized by treatment and assessment time point, as 
applicable.
13.5.
Interim Analysis
13.5.1.
Rationale for Interim Analysis
Planned enrollment was not achieved during the 2017-2018 cold season as previously 
planned, necessitating continued enrollment into subsequent cold season(s) to complete the 
study’s planned enrollment.  In order to avoid exposing patients to unnecessary clinical 
research, an interim futility analysis will occur to assess the likelihood of a study result that 
would lead to an acceptable Phase III sample size estimate.
The potential acceptability of the future Phase III study will be directly proportional to the 
sample size/sponsor resourcing required for the study.   The sponsor has not defined an 
acceptable sample size/resourcing limit.  Therefore, the interim analysis will include three 
sample size thresholds.  
13.5.2.
Communication and Logistics 
The statistical analysis of interim study data will be performed by an independent third party 
statistician and programmer. They will be the only people who will have access to both the 
subject data and the treatment assignments.
Detailed methodology for the interim statistical analysis will be documented in an Interim
Statistical Analysis Plan finalized and approved prior to release of randomization codes to 
the independent third party.


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Study data for the interim analysis will be stored in a version-controlled environment, and 
will not include treatment assignments. Treatment/randomization codes will be provided by 
the JNJ randomization administrator directly to the independent third party statistician and 
independent programmer who will be performing the analysis. Treatment/randomization 
codes will be stored in a secure area only accessible to the independent statistician and 
independent programmer, according to the third party SOPs.
Upon completion of the analysis, the independent third party statistician will communicate 
results directly and restricted (via secure email exchange) to key stakeholders within the 
sponsor organization, that is, the Vice President of Over-the-Counter Research &
Development and the Vice President of Global Medical Affairs.  These individuals may 
provide the results to the Chief Technology Officer of Consumer and the President of Global 
Franchise Organization, Worldwide Over-the-Counter Marketing.  Results will not include 
identification of subject treatment assignments. 
13.5.3.
Scope
The interim statistical analysis will be an analysis of futility based exclusively on interim 
data on the primary endpoint, that is, the change from baseline (score improvement) in the 
nasal congestion severity score (NCSS) averaged over assessments at 2, 4, 6, 8, 10, and 12 
hours on Day 1.
For the interim statistical analysis of the primary study endpoint, the Full Analysis Set (FAS) 
will include all randomized subjects who provide a valid baseline assessment of nasal 
congestion severity.  
13.5.4.
Handling of missing data and assessment time deviations  
In the interim futility analysis of the primary endpoint, subjects who were withdrawn any 
time after the baseline NCSS assessment, will have their last reported NCSS before the 
dropout imputed for the remaining assessment time points during Day 1. For example, any 
subjects without post-baseline assessments will have their baseline values carried forward. 
Any intermittent missing assessments will be imputed using linear interpolation between 
adjacent assessments.
For time deviations in post-baseline assessment time points exceeding 10 minutes in either 
direction relative to target, the corresponding assessment values at the target time points will 
be estimated using linear interpolation. If the actual 12 hour assessment is made more than 10 
minutes before the target time point, the assessment value at 12 hours will be estimated using 
extrapolation based on the last two assessments preceding 12 hours. The interpolated and 
extrapolated assessment values will be used in the statistical interim analysis. 
13.5.5.
Statistical methodology
The interim futility analysis will be based on an adaptation of the methodology described in 
[10] to the current Phase II study and its objective to serve as a basis for the planning of a 
confirmatory Phase III non-inferiority study involving the same three treatment groups. The 
adaptation will be based on the following definition of a successful outcome of a completed 






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δ′* = 
 
 x̅ Placebo)/2 = 
 
Placebo)/2.
13.5.6.
Statistical decision rules
For each choice of N, a recommendation to stop the study for futility will be given, based on 
the outcome of the interim statistical analysis, if at least one of the two conditional 
probabilities of a successful, completed POC study is below 0.2. The only information 
disseminated to sponsor (see Section 0)  will be in the form of a ‘Yes/No’ answer to the 
question
‘Does the interim analysis outcome suggest that the current study should be stopped for 
futility based on the probability of a maximum tolerable Phase III non-inferiority sample size 
of, in total, N subjects?’.
This interim analysis is a futility analysis. To limit the risk of introducing bias in estimates 
based on a potential completion of the Phase II study in 450 subjects, the cut-off probability 
for futility used for evaluation of the conditional probabilities corresponding to the two steps, 
A and B, have been pre-set to a reasonably low value = 0.2.  There will be no other stopping 
rules applied.
13.6.
Data Monitoring Committee
Not applicable. 


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14.
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
14.1.
Study Monitoring
Before an investigational site can enter a subject into the study, a representative of J&J will 
visit the investigational study site to:

Determine the adequacy of the facilities

Discuss with the investigator(s) and other personnel their responsibilities the site's 
responsibility with regard to protocol adherence as well as the study and 
monitoring responsibilities of J&J or its representatives.  These responsibilities 
will be documented in a Clinical Study Agreement between J&J and the 
investigator.
During the study, a monitor from J&J or representative will have regular contacts with the 
investigational site, for the following:

Provide information and support to the investigator(s)

Confirm that facilities remain acceptable

Confirm that the investigational team is adhering to the protocol, that data are 
being accurately recorded in the CRFs, and that IP accountability checks are 
being performed

Perform source data verification.  This includes a comparison of the data in the 
CRFs with the subject’s medical records at the hospital or practice, and other 
records relevant to the study.  This will require direct access to all original records 
for each subject (e.g., clinic charts).

Record and report all protocol deviations not previously sent to J&J.

Confirm AEs and SAEs have been properly documented on CRFs and confirm 
any SAEs have been forwarded to J&J and those SAEs that met criteria for 
reporting have been forwarded to the IRB.
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or study-related direction.
14.2.
Audits and Inspections
Authorized representatives of J&J, a regulatory authority, IRB/IEC may visit the site to 
perform audits or inspections, including source data verification.  The purpose of a J&J audit 
or inspection is to systematically and independently examine all study-related activities and 
documents to determine whether these activities were conducted, and data were recorded, 
analyzed, and accurately reported according to the protocol, Good Clinical Practice (GCP) 
guidelines of the International Conference on Harmonization, and any applicable regulatory 
requirements.  The investigator should contact their study contacts immediately if contacted 
by a regulatory agency about an inspection.


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14.3.
Institutional Review Board / Independent Ethics Committee
(IRB/IEC)
The Principal Investigator must obtain IRB/IEC approval for the investigation.  Initial 
IRB/IEC approval, and all materials approved by the IRB/IEC for this study including the 
subject consent form and recruitment materials must be maintained in the Site Master File by 
the Investigator and made available for inspection.


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15.
QUALITY CONTROL AND QUALITY ASSURANCE
To ensure compliance with GCP and all applicable regulatory requirements, J&J may 
conduct a quality assurance audit.  Please see Section 14.2 for more details regarding the 
audit process.


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16.
DATA HANDLING AND RECORDKEEPING
16.1.
Case Report Forms / Electronic Data Capture
As used in this protocol, the term CRF should be understood to refer to the EDC system.
All data will be collected on source documents by site staff first, and then recorded in an 
EDC system, except for the subject-completed cold symptom questionnaires. The responses 
to these questionnaires will be directly entered into the diary by the subject, then transcribed 
by the site staff into the EDC. 
The EDC system is the database where pertinent study data are collected such as
demography, subject randomization, efficacy assessments, AEs, and subject disposition.
EDC should be completed for each enrolled subject. The completed pages of the EDC system 
are the sole property of the Sponsor and should not be made available in any form to third 
parties, except for authorized representatives of the Sponsor or appropriate regulatory
authorities, without written permission from the Sponsor.
It is the PI’s responsibility to ensure completion and to review and approve all information
captured in the EDC. The subject’s data in the EDC system must be electronically signed by
the PI. These signatures serve to attest that the information contained in the EDC system is
true. At all times, the PI has final personal responsibility for the accuracy and authenticity of
all clinical and laboratory data entered in the EDC. Subject source documents are the
Investigator's/physician's subject records maintained at the study site. In cases where the
source documents are the hospital or the physician's chart, the information collected in the
EDC must match those charts. All final data recorded in EDC system will be copied onto
files and kept by the Sponsor. A copy of these files will also be kept at the clinical site. All
data recorded on source documents will be kept at the clinical site.
It is recommended that the author of an entry in the source documents be identifiable. At a
minimum, the type and level of detail of source data available for a study subject should be
consistent with that commonly recorded at the site. Specific details required as source data
for the study will be reviewed with the PI before the study and will be described in the
monitoring guidelines (or other equivalent document).
16.2.
Inspection of Records
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the 
Investigator agrees to keep records including the identity of all participating subjects 
(sufficient information to link records, e.g., CRFs and hospital records), all original signed 
informed consent forms, copies of all CRFs, SAE forms, source documents, and detailed 
records of treatment disposition.  The records should be retained by the Investigator 
according to ICH guidelines, local regulations, or as specified in the Clinical Study 
Agreement, whichever is longer.


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16.3.
Retention of Records
The Principal Investigator must maintain all documentation relating to the study for a period 
of 25 years.  If it becomes necessary for J&J or the Regulatory Authority to review any 
documentation relating to the study, the Investigator must permit access to such records.
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor 
should be prospectively notified.  The study records must be transferred to an acceptable 
designee, such as another Investigator, another institution, or to the Sponsor.  The 
Investigator must obtain Sponsor's written permission before disposing of any records, even 
if retention requirements have been met.


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17.
SPONSOR DISCONTINUATION CRITERIA
Premature termination of this clinical study may occur because of a regulatory authority 
decision, change in opinion of the IRB/IEC, drug safety problems, or at the discretion of the 
Sponsor.  In addition, the Sponsor retains the right to discontinue development of the study at 
any time.
If a study is prematurely terminated or discontinued, the Sponsor will promptly notify the 
Investigator.  After notification, the Investigator must contact all participating subjects within 
two weeks.  All study materials must be collected and all CRFs completed to the greatest 
extent possible.


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18.
PUBLICATION POLICY
Publication of study results by the Investigator is discussed in the Clinical Study Agreement, 
as appropriate.  Results from this study may be published in the form of oral or written 
presentations at scientific meetings or as one or more peer-reviewed journal articles.  In these 
cases, no information on individual subjects will be revealed.




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20.
APPENDICES
Not applicable

SAP_001.pdf: 


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TABLE OF CONTENTS
1
INTRODUCTION................................................................................................. 4
1.1
STUDY OBJECTIVES ......................................................................................... 5
1.2
STUDY DESIGN.................................................................................................. 5
2
INTERIM ANALYSES ........................................................................................ 7
3
ANALYSIS SETS.................................................................................................. 8
3.1
FULL ANALYSIS SET ............................................................................................ 8
3.2
‘PER PROTOCOL’ ANALYSIS SET..................................................................... 8
3.3
SAFETY ANALYSIS SET ........................................................................................ 8
3.4
OTHER ANALYSIS SETS................................................................................. 8
4
ENDPOINTS AND COVARIATES.................................................................... 8
Reflected Change in Nasal Congestion Symptoms ..................................................... 9
Reflected Congestion Severity................................................................................... 10
Wisconsin Upper Respiratory Symptom Survey 21 .................................................. 10
EFFICACY ENDPOINT(S).............................................................................................. 11
4.1.1
Primary endpoint .......................................................................................... 11
4.1.2
Secondary endpoints..................................................................................... 11
4.1.3
Exploratory endpoints................................................................................... 11
4.2
SAFETY ENDPOINTS ........................................................................................... 12
4.3
OTHER ENDPOINTS .......................................................................................... 12
4.4
COVARIATES...................................................................................................... 12
5
HANDLING OF MISSING VALUES .............................................................. 13
Deviations in Day 1 post-baseline assessment times............................................ 13
6
STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES...... 13
6.1
STATISTICAL HYPOTHESES ................................................................................ 13
6.2
STATISTICAL DECISION RULES .......................................................................... 14
6.3
STATISTICALMETHODS................................................................................... 14
6.4
STATISTICAL ANALYSES .................................................................................... 15
6.4.1
Demographic and Baseline Characteristics................................................. 15
6.4.2
Analysis of primary and secondary efficacy endpoints................................. 16
6.4.3
Analysis of exploratory efficacy endpoints ................................................... 16
6.4.4
Safety Analyses.............................................................................................. 16
APPENDIX 1: SUMMARY TABLES ....................................................................... 18
APPENDIX 2: SUBJECT DATA LISTINGS ........................................................... 19
APPENDIX 3: FIGURES............................................................................................ 20


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APPENDIX 4: INTERIM STATISTICAL ANALYSIS PLAN............................... 21










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3
ANALYSIS SETS
3.1
FULL ANALYSIS SET
For the efficacy analyses, the Full Analysis Set (FAS) will include all randomized 
subjects who provide a valid baseline assessment of nasal congestion severity.  
3.2
‘PER PROTOCOL’ ANALYSIS SET 
No Per Protocol Analysis will be performed.
3.3
SAFETY ANALYSIS SET
Safety Analysis Set: The safety analyses will be based on all randomized subjects who 
take at least one dose of treatment.
3.4
OTHER ANALYSIS SETS
None. 
4
ENDPOINTS AND COVARIATES
Efficacy Assessments (As stated in the protocol)
‘The decongestant effect of phenylephrine 
will be evaluated with the 
following subjective assessment questions and Verbal Rating Scales (VRS) at the 
designated time points using the Diary:

Assessment of Nasal Congestion (stuffy/congested nose), instantaneous, on an 
8-point scale, at baseline, at 2, 4, 6, 8, 10 and 12 hours after the first dose on 
Day 1, and on the morning of Day 2 (24 hours)

Assessment of Sinus Pressure/Tenderness, instantaneous, on an 8-point scale, 
at baseline, at 2, 4, 6, 8, 10 and 12 hours after the first dose on Day 1, and on 
the morning of Day 2 (24 hours)

Assessment of Head Congestion, instantaneous, on an 8-point scale, at 
baseline, at 2, 4, 6, 8, 10 and 12 hours after the first dose on Day 1, and on 
the morning of Day 2 (24 hours)

Assessment of Reflected Impact of Nasal / Sinus Congestion on Clear 
Thinking, on a 5-point scale, at baseline and at 12 hours after the first dose on 
Day 1.

Assessments of Reflected Change in Nasal Congestion Symptoms reflective, on 
a 7-point scale, at 12 hours after the morning dose on Day 1.






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EFFICACY ENDPOINT(S)
4.1.1
Primary endpoint
The primary efficacy endpoint is the change from baseline (score improvement) in the 
nasal congestion severity score (NCSS) averaged over assessments at 2, 4, 6, 8, 10, and 
12 hours on Day 1.  The baseline nasal congestion score will be measured within 
approximately 30 minutes before the first dose.
4.1.2
Secondary endpoints

Change from baseline (score improvement) in the NCSS averaged over 
assessments at 8, 10, and 12 hours.

Change from baseline (score improvement) in the NCSS at 2, 4, 6, 8, 10, and 12 
hours and in the morning of Day 2 (24 hours), respectively.

Change from baseline (score improvement) in Sinus Pressure/Tenderness Scores 
averaged over assessments at 2, 4, 6, 8, 10, and 12 hours.

Change from baseline (score improvement) in Sinus Pressure/Tenderness Scores 
at 2, 4, 6, 8, 10, and 12 hours and in the morning of Day 2 (24 hours), 
respectively.
4.1.3
Exploratory endpoints

Change from baseline (score improvement) in Head Congestion Scores averaged 
over assessments at 2, 4, 6, 8, 10, and 12 hours.

Change from baseline (score improvement) in Head Congestion Scores at 2, 4, 6, 
8, 10, and 12 hours and in the morning of Day 2 (24 hours), respectively.

Change from baseline (score improvement) in Reflected Impact of Nasal / Sinus 
Congestion on Clear Thinking (reflected for the previous 12 hours) at 12 hour 
assessment 

Reflected Change in Nasal Congestion Symptoms (reflected over 12 hours after 
the first dose).

Reflected Nasal Functioning (reflected over 12 hours after the first dose).

Change from baseline (score improvement) in Reflected Congestion Severity 
(reflected for the previous 12 hours) at 12 hour assessment.

Assessment of cold severity using Wisconsin Upper Respiratory Symptom 
Survey-21 (reflected over 24 hours) at baseline and in the morning of Day 2 (24 
hours).


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4.2
SAFETY ENDPOINTS

Occurrence of self-reported and observed adverse events.

Occurrence of serious adverse events.

Occurrence of adverse events leading to subject discontinuation from the study.

The number and percentage of subjects experiencing treatment-emergent adverse 
events.

The number and percentage of subjects experiencing treatment related adverse 
events, i.e. adverse events with a possible, probable, or very likely relation to the 
investigational product. 

Heart rate (pulse) and systolic and diastolic blood pressure data at baseline (pre-
dose) and at 2 and 4 hours post-dose, immediately following completion of 
subject assessments, as well as at end of study (Day 2).

Respiratory rate and oral body temperature measured at baseline (pre-dose) and 
end of study (Day 2).
4.3
OTHER ENDPOINTS 
Data collected in this study will also be used to evaluate the psychometric properties of 
the primary and secondary outcome assessments in this context of use and to perform 
analyses to estimate the level of change in scores that can be considered meaningful and 
important. These analyses will be described in a specific and separate psychometric 
analysis plan which will be finalized prior to database lock and the analysis will be 
reported separately. The details of the psychometric data analyses are not described in 
this document.
No pharmacokinetic analysis will be performed for the current study because the clinical 
program associated with the study has been discontinued and therefore no additional 
pharmacokinetic data is required to support future clinical study designs.  
4.4
COVARIATES 
ANOVA models for analyses of change from baseline in the NCSS scores will be 
adjusted for the baseline NCSS score categorized as either ‘equal to 5’ or ‘greater than 5’. 
(A blind data review found only 14 (7.25%) enrolled subjects with a baseline NCSS score 
equal to 7, hence the merger between the two highest score categories, ‘6’ and ‘7’.)


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ANCOVA models for analyses of change from baseline in Sinus Pressure/Tenderness 
Scores and Head Congestion scores, respectively, will be adjusted for the corresponding 
baseline score. 
5
HANDLING OF MISSING VALUES
In the analyses of change from baseline in the NCSS, Sinus Pressure/Tenderness Scores, 
and Head Congestion scores, respectively, subjects who dropout, will have their last 
reported corresponding score before the dropout imputed for the remaining assessment 
time points. Any intermittent missing assessments will be imputed using linear 
interpolation between adjacent assessments.
The analyses of score changes from baseline in Reflected Impact of Nasal / Sinus 
Congestion on Clear Thinking, Reflected Change in Nasal Congestion Symptoms scores, 
Reflected Nasal Functioning scores, and score changes from baseline in Reflected 
Congestion Severity will be restricted to complete cases, that is, subjects with non-
missing data for the corresponding endpoint.
Deviations in Day 1 post-baseline assessment times 
For time deviations in Day 1 post-baseline assessment time points exceeding 10 minutes 
in either direction relative to target, the corresponding assessment values will be adjusted 
using linear interpolation and the interpolated value at the target assessment time point 
will be used in the statistical analyses. Any 12 hour assessments performed more than 10 
minutes before target, will be adjusted by linear extrapolation to 12 hours using the 10 
and 12 hour assessments. 
6
STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
6.1
STATISTICAL HYPOTHESES
This is a Phase II, Proof-Of-Concept (POC) study and the inferential statistical 
procedures are focused on point and interval estimation of the mean treatment differences 
in efficacy endpoints based on changes from baseline in the NCSS, Sinus 
Pressure/Tenderness Scores, and Head Congestion scores, respectively. However, to 
further aid interpretation of results, p-values from 2-sided tests of the null hypotheses of 
no treatment mean differences will be provided. Specifically, for each of the endpoints 
derived from these scores and each pair of treatments the following null hypothesis will 
be tested,
H0: µ1 = µ2


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versus the alternative hypothesis, 
Ha:
µ1 ≠ µ2
where µ1 and  µ2 are the underlying mean endpoint values of the two compared 
treatments.
The analyses of score changes from baseline in Reflected Impact of Nasal / Sinus 
Congestion on Clear Thinking, Reflected Change in Nasal Congestion Symptoms scores, 
Reflected Nasal Functioning scores, and score changes from baseline in Reflected 
Congestion Severity, respectively, will for each separate endpoint and pair of treatments 
test the null hypothesis of no treatment difference in the endpoint distributions. That is,
H0: The endpoint distributions are the same for both compared treatments
versus the alternative hypothesis, 
H1: The endpoint distributions differ for the two compared treatments
6.2
STATISTICAL DECISION RULES
This is a Phase II, POC study and the inferential statistical procedures are focused on 
point and interval estimation of the mean treatment differences in efficacy endpoints 
based on changes from baseline in the NCSS, Sinus Pressure/Tenderness Scores, and 
Head Congestion scores, respectively. All interval estimates will be two-sided and have 
nominal confidence level 95%.
6.3
STATISTICALMETHODS 
In the analyses of change from baseline in the NCSS, Sinus Pressure/Tenderness Scores, 
and Head Congestion scores, respectively, subjects who dropout, will have their last 
reported corresponding score before the dropout imputed for the remaining assessment 
time points. The analyses will be based on all randomized subjects who provides at least 
a baseline assessment and receives study treatment.
The primary endpoint, which is the overall Day 1 change from baseline in the Nasal 
Congestion Score (score for stuffy/congested nose averaged over assessments at 2, 4, 6, 


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8, 10, and 12 hours on Day 1), will be analyzed in an ANOVA model with treatment 
group, and baseline nasal congestion score (5, ≥ 6) as factors. 
Analysis of all secondary endpoints involving instantaneous nasal congestion scores will 
be performed using an ANOVA model with treatment group, and baseline nasal 
congestion score (5, ≥ 6) as factors.
Analysis of secondary endpoints involving Sinus Pressure/Tenderness Scores will be 
performed using an ANCOVA model with treatment group as factor, and baseline Sinus 
Pressure/Tenderness Score as a covariate.
Analysis of endpoints involving Head Congestion Scores will be performed using an 
ANCOVA model with treatment group as factor, and baseline Head Congestion Score as 
a covariate.
Pairwise treatment differences in the distributions of Reflected Change in Nasal 
Congestion Symptoms and Reflected Nasal Functioning scores, both reflected over 12 
hours after the first dose, will be analyzed using the Mann-Whitney test.  
Pairwise treatment differences in the distributions of Change from baseline in Reflected 
Impact of Nasal / Sinus Congestion on Clear Thinking and Change from baseline in 
Reflected Congestion Severity (reflected for the previous 12 hours), will be analyzed using 
the Mann-Whitney test.  
All efficacy endpoints will be described by summary statistics. This includes summaries 
of the first and last questions (‘How sick do you feel today’ and ‘Compared to yesterday, 
my cold is …’) in the assessments of cold severity using the Wisconsin Upper 
Respiratory Symptom Survey (WURSS-21) at baseline and in the morning of Day 2 (24 
hours), as well as descriptive statistics for a summary score derived from the remaining 
19 questionnaire items.
All presented confidence intervals will be two-sided and have confidence level 95%. To 
further guide data interpretation, p-values from 2-sided tests of the null hypotheses 
specified in Section 6.1 will be presented.
6.4
STATISTICAL ANALYSES
The Department of Quantitative Science at McNeil AB will be responsible for the 
statistical data analyses. SAS version 9.4 will be used for the statistical analyses.
6.4.1
Demographic and Baseline Characteristics
Descriptive statistics (e.g. mean, standard deviation, median, minimum and maximum for 
continuous variables; frequency and percentage for categorical variables) will be 
presented for demographic and baseline characteristics.


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6.4.2
Analysis of primary and secondary efficacy endpoints
Descriptive statistics of primary and secondary efficacy endpoints will be presented based 
on all subjects included in the analyses, see 6.3.
The comparative statistical analyses will be performed as described in Section 6.3 and 
will be based on imputations of any missing scores or out-of-window data, see Section 5.
This is an exploratory Phase 2 POC study. Additional post-hoc analyses may be 
performed.
6.4.3
Analysis of exploratory efficacy endpoints
Descriptive statistics of exploratory endpoints will be presented based on all subjects in 
the Full Analysis Set with non-missing endpoint values (no imputation performed). The
comparative statistical analyses will be performed as described in Section 6.3. The only 
exception concerns endpoints based on Head Congestion scores which will be 
summarized and analyzed according to the description in 6.4.2.
This is an exploratory Phase 2 POC study. Additional post-hoc analyses may be 
performed.
6.4.4
Safety Analyses
Safety analyses will be based on the Safety Analysis Set.  
All adverse events reported during the Adverse Event reporting period will be listed by 
subject ID. Any serious adverse events will be listed separately. 
The number and percentage of subjects experiencing adverse events will be tabulated by 
treatment, system organ class, and preferred term. Separate tables will be provided for 
treatment-emergent and treatment-related adverse events, the latter being restricted to 
adverse events having a possible, probable, or very likely relation to the investigational 
product. Any adverse events occurring before the first treatment administration will be 
listed only. (Any adverse events with onset date coinciding with the date of the first 
treatment administration but missing time of onset will be considered as treatment-
emergent in tables and listings of adverse events.)
In addition, the number and percentage of subjects experiencing adverse events will also 
be tabulated by treatment, system organ class, preferred term, and worst recorded 
severity. Separate tables will be provided for treatment-emergent and treatment-related 
adverse events. 
Any subjects who discontinued the study due to a treatment-emergent adverse event(s) 
will also be separately listed by treatment including descriptions of the adverse events 
leading to withdrawal. 


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The latest version of the Medical Dictionary for Regulatory Activities (MedDRA) will be 
used as Adverse Event classification system.
Heart rate (pulse) and systolic and diastolic blood pressure data summaries will be
presented by treatment and assessment time point for assessments at baseline (pre-dose) 
and at 2 and 4 hours post-dose, immediately following completion of subject
assessments.
Respiratory rate, oral body temperature, heart rate (pulse) and systolic and diastolic blood 
pressure data measured at baseline (pre-dose) and end of study (Day 2) will be presented 
by treatment and visit.
Previous and Concomitant medications will be listed only.
      


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APPENDIX 1: SUMMARY TABLES 

14.1.1 Disposition of Subjects. All randomized subjects.

14.1.2 Demography and Baseline Characteristics. All randomized subjects.

14.1.3 Vital signs at Screening. All randomized subjects.

14.2.1.1 Change from baseline in the nasal congestion severity score (NCSS) by 
assessment time point. Subjects in Full Analysis Set.

14.2.1.2 Mean Change from baseline in the nasal congestion severity score (NCSS).
Subjects in Full Analysis Set.

14.2.2.1 Change from baseline in Sinus Pressure/Tenderness Scores by assessment 
time point. Subjects in Full Analysis Set.

14.2.2.2 Mean Change from baseline in Sinus Pressure/Tenderness Scores. Subjects 
in Full Analysis Set.

14.2.3.1 Change from baseline in Head Congestion Scores by assessment time point. 
Subjects in Full Analysis Set.

14.2.3.2 Primary analysis of Mean Change from baseline in Head Congestion Scores. 
Subjects in Full Analysis Set.

14.2.4 Change from baseline in Reflected Impact of Nasal / Sinus Congestion on 
Clear Thinking (reflected for the previous 12 hours). Subjects in Full Analysis Set.  

14.2.5 Reflected Change in Nasal Congestion Symptoms (reflected over 12 hours 
after the first dose). Subjects in Full Analysis Set.  

14.2.6 Reflected Nasal Functioning (reflected over 12 hours after the first dose). 
Subjects in Full Analysis Set.  

14.2.7 Change from baseline (score improvement) in Reflected Congestion Severity 
(reflected for the previous 12 hours). Subjects in Full Analysis Set.  

14.2.8 Assessment of cold severity using Wisconsin Upper Respiratory Symptom 
Survey-21 (reflected over 24 hours). Subjects in Full Analysis Set.  

14.2.9 Compliance with investigational product. All randomized subjects.

14.3.1.1 Subjects with Treatment Emergent Adverse Events By System Organ Class 
and Preferred Term. Subjects in Safety Analysis Set.


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
14.3.1.2 Subjects with Commonly Reported (≥ 5%) Treatment Emergent Adverse 
Events By System Organ Class and Preferred Term. Subjects in Safety Analysis Set.

14.3.1.3 Subjects with Treatment Emergent Adverse Events By System Organ Class, 
Preferred Term and Severity. Subjects in Safety Analysis Set.

14.3.1.4 Subjects with Treatment Related Adverse Events By System Organ Class 
and Preferred Term. Subjects in Safety Analysis Set.

14.3.1.5 Subjects with Treatment Related Adverse Events By System Organ Class, 
Preferred Term and Severity. Subjects in Safety Analysis Set.

14.3.1.6 Vital Signs at Baseline and End-of-Study. Subjects in Safety Analysis Set.

14.3.1.7 Vital Signs Pre and Post Treatment. Subjects in Safety Analysis Set.

14.3.2 Listing of Deaths, Other Serious and Significant Adverse Events. All 
randomized subjects.
APPENDIX 2: SUBJECT DATA LISTINGS

Randomization code listing. (16.1.7)

Study disposition including status at termination. (16.2.1)

Protocol deviations. (16.2.2)

Subjects excluded from the efficacy analysis. (16.2.3)

Demographic and baseline characteristics. (16.2.4.1)

Vital signs at Screening. (16.2.4.2)

Subjects with Medical History. (16.2.4.3)

Compliance. (16.2.5)

Nasal congestion severity scores (NCSS) by assessment time points. (16.2.6.1.1)

Nasal congestion severity scores (NCSS). Mean change from baseline. (16.2.6.1.2)

Sinus Pressure/Tenderness Scores by assessment time points. (16.2.6.2.1)

Sinus Pressure/Tenderness Scores. Mean change from baseline. (16.2.6.2.2)


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
Head Congestion Scores by assessment time points. (16.2.6.3.1)

Head Congestion Scores. Mean change from baseline. (16.2.6.3.2)

Reflected Impact of Nasal / Sinus Congestion on Clear Thinking, and Reflected 
Congestion Severity. (16.2.6.4)

Reflected Change in Nasal Congestion Symptoms, and Reflected Nasal Functioning. 
(16.2.6.5)

Wisconsin Upper Respiratory Symptom Survey-21. (16.2.6.5)  

Adverse events. (16.2.7.1)

Vital Signs. (16.2.7.2)

Previous and Concomitant medication. (16.2.9)
APPENDIX 3: FIGURES
1. Nasal Congestion Severity Scores Day 1 (Mean ± 2SE).
2. Sinus Pressure/Tenderness Scores Day 1 (Mean ± 2SE).
3. Head Congestion Scores Day 1 (Mean ± 2SE).




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1
RATIONALE
The background and rationale of the interim analysis as stated in the amended protocol:
‘Planned enrollment was not achieved during the 2017-2018 cold season as previously
planned, necessitating continued enrollment into subsequent cold season(s) to complete 
the study’s planned enrollment. In order to avoid exposing patients to unnecessary 
clinical research, an interim futility analysis will occur to assess the likelihood of a study 
result that would lead to an acceptable Phase III sample size estimate. 
The potential acceptability of the future Phase III study will be directly proportional to 
the sample size/sponsor resourcing required for the study. The sponsor has not defined 
an acceptable sample size/resourcing limit. Therefore, the interim analysis will include 
three sample size thresholds.’
2
INTERIM ANALYSIS COMMUNICATIONS AND LOGISTICS
As stated in the amended protocol:
‘The statistical analysis of interim study data will be performed by an independent third 
party statistician and programmer. They will be the only people who will have access to 
both the subject data and the treatment assignments. 
Detailed methodology for the interim statistical analysis will be documented in an
Interim Statistical Analysis Plan finalized and approved prior to release of randomization 
codes to the independent third party. 
Study data for the interim analysis will be stored in a version-controlled environment, 
and will not include treatment assignments. Treatment/randomization codes will be 
provided by the JNJ randomization administrator directly to the independent third party
statistician and independent programmer who will be performing the analysis. 
Treatment/randomization codes will be stored in a secure area only accessible to the 
independent statistician and independent programmer, according to the third party
SOPs.
Upon completion of the analysis, the independent third party statistician will 
communicate results directly and restricted (via secure email exchange) to key
stakeholders within the sponsor organization, that is, the Vice President of Over-the-
Counter Research & Development and the Vice President of Global Medical Affairs.  
These individuals may provide the results to the Chief Technology Officer of Consumer
and the President of Global Franchise Organization, Worldwide Over-the-Counter
Marketing.  Results will not include identification of subject treatment assignments.’






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The randomization schedule was generated by the Sponsor.  Subjects were randomized 
via an IWRS to receive one of three treatments 
or placebo, 1:1:1 ratio). 
 
 
 
 
4
SCOPE OF INTERIM ANALYSIS
The interim statistical analysis will be an analysis of futility based exclusively on interim 
data on the study primary endpoint, that is, the change from baseline (score 
improvement) in the nasal congestion severity score (NCSS) averaged over assessments 
at 2, 4, 6, 8, 10, and 12 hours on Day 1.
5
ANALYSIS SETS
5.1
FULL ANALYSIS SET
For the interim statistical analysis of the primary study endpoint, the Full Analysis Set 
(FAS) will include all randomized subjects who provided a valid baseline assessment of 
nasal congestion severity.  
5.2
‘PER PROTOCOL’ ANALYSIS SET 
No Per Protocol Interim Analysis will be performed.
5.3
SAFETY ANALYSIS SET
No Safety Interim Analysis will be performed.
5.4
OTHER ANALYSIS SETS
Not applicable.  
6
ENDPOINTS AND COVARIATES




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using linear interpolation using adjacent assessment values at target time points.  If the 
actual 12 hour assessment is made more than 10 minutes before the target time point, the 
assessment value at 12 hours will be estimated using extrapolation based on the last two 
assessments preceding 12 hours. The interpolated and extrapolated assessment values 
will be used in the statistical interim analysis. 
8
STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
8.1
STATISTICAL METHODS 
The interim futility analysis will be based on an adaptation of the methodology described 
in [1] to the current Phase II study and its objective to serve as a basis for the planning 
of a confirmatory Phase III non-inferiority study involving the same three treatment 
groups. The adaptation will be based on the following definition of a successful outcome 
of a completed Phase II study in the originally targeted 450 subjects (with 150 subjects in 
each treatment group): 
Definition of a Successful Outcome of a completed Phase II POC (SPOC) study: 
A completed Phase II study, with 450 randomized subjects enrolled in total from the two 
study phases, will provide estimates of the population mean differences for the primary 
study endpoint, 
 vs. Placebo and 
 vs. 
Placebo, respectively, of magnitudes such that a sample size calculation for a Phase III 
non-inferiority study, based on the data from the completed Phase II study, will suggest a 
confirmatory Phase III study of total sample size at most N, assuming an equal number of 
subjects allocated to the three treatment arms, 
/Placebo 
 
/Placebo 
 and 
Placebo 
/Placebo 
, respectively. 
The interim analysis will evaluate futility for three (3) different suggested maximum 
sample sizes, N, of a confirmatory Phase III non-inferiority study: N= 1800, 2700, and 
3600, respectively.
For each fixed choice of N, two conditional probabilities of a SPOC, defined above, will 
be calculated given interim data, corresponding to two, somewhat different, approaches 
to determine the size of a Phase III non-inferiority study:
a. Based on a pre-set non-inferiority margin derived from an interval estimate of 
half the population difference in means between
 and Placebo (using data 
from the completed POC study), while assuming the effects of 
 to be 
the same and a required statistical power of 90%. This approach assesses the 
reference product effect and the resulting margin.
b. Based on a requirement to show, with 90% statistical power, that the 
population difference in means between 
 is at least as large as 
minus half the population difference in means between
 Placebo (using 
data from the completed POC study). This approach assesses the effect of the 
test product vs. placebo and the reference.    




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interval, based on the completed POC study, as an estimate for the margin in a Phase III 
non-inferiority study sample size calculation according to A.
Similarly for step B, with δ′* denoting the estimate from interim data of 
)/2, the second conditional probability is given by 
1 - Φ( (z0.50 – Z′)/√f ′)
where Z′ = [(δ′* - ∆′)×√450] / [σ*×√(1.5 + (i+j)/k + (j+k)/4i + (i+k)/4j)] with notation 
as above extended to: k the number of evaluable subjects in the 
arm at interim and f ′
= 1 - (i+j+k)/450. The use of z0.50 = 0 in the above formula corresponds to using the 
observed point estimate of 
)/2, based on the completed POC 
study, in a Phase III non-inferiority study sample size calculation according to B.
Based on the interim data, the estimates σ*, δ* and δ′* will, with obvious notation, be 
derived according to
σ* = √( [(i-1) × s2
Placebo + (j-1) × s2
+(k-1) × s2 ] / (i+j+k-3) );
δ* = (x̅
 - x̅ Placebo)/2;
δ′* = (x̅
 - x̅
)  +  (x̅
 - x̅ Placebo)/2 = x̅
- (x̅
 + x̅ Placebo)/2.
8.2
STATISTICAL DECISION RULES
For each choice of N, a recommendation to stop the study for futility will be given, based 
on the outcome of the interim statistical analysis, if at least one of the two conditional 
probabilities of a successful, completed POC study is below 0.2. The only information 
disseminated to sponsor will be in the form of a ‘Yes/No’ answer to the question
‘Does the interim analysis outcome suggest that the current study should be stopped for 
futility based on the probability of a maximum tolerable Phase III non-inferiority sample 
size of, in total, N subjects?’.
This interim analysis is a futility analysis. To limit the risk of introducing bias in 
estimates based on a potential completion of the Phase II study in 450 subjects, the cut-
off probability for futility used for evaluation of the conditional probabilities 
corresponding to the two steps, A and B, have been pre-set to a reasonably low value = 
0.2.  There will be no other stopping rules applied.
8.3
STATISTICAL ANALYSIS
The Department of Quantitative Science at McNeil AB will be responsible for the 
statistical data analyses. However, the analysis will be performed by an independent 
third party statistician and programmer. They will be the only people who will have 


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access to both the subject data and the treatment assignments. SAS version 9.4 will be 
used for the statistical analyses.
8.3.1
Futility interim analysis of the study primary endpoint
The interim statistical analysis will be performed as described in Section 8.1. The 
analysis can, in summary, be described according to the following calculation steps:
1.
σ* = √( [(i-1) × s2
Placebo + (j-1) × s2
+(k-1) × s2 ] / (i+j+k-3) );
For each of N = 1800, 2700, and 3600 then calculate:
2.1 
∆= ∆(N) = √6 × σ* × (z0.025 + z0.10)/√N;
      2.2
δ* = (x̅
 - x̅ Placebo)/2;
      2.3
Z = [2×(δ* - ∆)×√300] / [σ*×√(2 + i/j + j/i)],
                        with i, j = the number of evaluable subjects in the Placebo and
 arms at            
                        interim, respectively; 
      2.4
CP = 1 - Φ( (z0.65 – Z)/√f ), with  f = 1 - (i+j)/300;
      3.1
∆′ = ∆′(N) = 3 × σ* × (z0.025 + z0.10) / √(2N);
      3.2
δ′* = x̅
- (x̅
+ x̅ Placebo)/2;
      3.3
Z′ = [(δ′* - ∆′)×√450] / [σ*×√(1.5 + (i+j)/k + (j+k)/4i + (i+k)/4j)],
                        with i, j, k = the number of evaluable subjects in the Placebo, 
                        arms at interim, respectively;
      3.4
CP′ = 1 - Φ( (z0.50 – Z′)/√f ′), with f ′ = 1 - (i+j+k)/450;
      4.
If  min(CP, CP′) < 0.20 then the answer to the question ‘Does the interim 
                        analysis outcome suggest that the current study should be stopped for
                        futility based on the probability of a maximum tolerable Phase III 
                        non-inferiority sample size of, in total, N subjects?’ is ‘Yes’;
                        Else the answer is ‘No’.


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The analysis results to be communicated (via secure email exchange) exclusively to key 
stakeholders within the sponsor organization, that is, the Vice President of OTC R&D 
and the Vice President of Global Medical Affairs, will be presented in – and restricted to 
- the following table:
Max Tolerable Phase III 
Sample Size
Interim Analysis Suggests 
To Stop Study for Futility?
1800
Yes/No
2700
Yes/No
3600
Yes/No
9
REFERENCES
[1] K.K. Gordon Lan and Janet Wittes: The B-value: A Tool for Monitoring Data. 
Biometrics, Vol. 44, No. 2, 1988 (pp. 579-585).