Clinical trial NCT03564119
Conditions: Papulopustular Rosacea
Keywords: papulopustular rosacea
Sponsor: Sol-Gel Technologies, Ltd.
Start date: 2018-06-21; Completion date: 2019-06-10
Enrollment: 372 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To assess the efficacy and safety of S5G4T-1 compared to S5G4T-1 vehicle when applied once daily for 12 weeks in participants with papulopustular rosacea.

Detailed description:
In this Phase 3, double-blind, randomized, vehicle-controlled, parallel-group pivotal study, participants will be admitted only after a written informed consent has been obtained and after all inclusion/exclusion criteria have been met. Male and female participants at least 18 years of age with moderate or severe papulopustular rosacea will be eligible for enrollment for daily treatment with S5G4T-1 or its vehicle for 12 weeks.

Arms: arm 1: Participants will topically apply S5G4T-1 cream, once daily to face for 12 weeks. arm 2: Participants will topically apply S5G4T-2 vehicle cream, once daily to face for 12 weeks.
Interventions: intervention 1: S5G4T-1 intervention 2: S5G4T-2
Intervention descriptions: intervention 1: Once a day topical cream intervention 2: Once a day topical cream

Protocol documents:
Prot_002.pdf: 
CLINICAL STUDY PROTOCOL 
Title: 
A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled 
Study of S5G4T-1 in the Treatment of Papulopustular Rosacea 
Protocol No: 
SGT-54-02: October 24, 2018 
Protocol Version: 
4 
Original Version: 
3.0 
Sponsor: 
Sol-Gel Technologies Ltd. 
7 Golda Meir St. 
Weizmann Science Park 
Ness Ziona 7403650, Israel 
Confidential 
The information contained in this document is confidential and proprietary property of Sol-Gel Technologies, Inc. The recipient agrees that no 
unpublished information contained herein will be published or disclosed without prior written approval of Sol-Gel except as may be disclosed 
to independent ethics committees/institutional review boards or duly authorized representatives of the US Food and Drug Administration 
under the condition that they maintain confidentiality. 
NCT #NCT03564119


 
 
 
 
 
SGT-54-02, Ver 4.0 
 
 
2. 
PROTOCOL APPROVAL-SPONSOR SIGNATURE PAGE 
 
Protocol Title: 
 
Study Products: 
A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled 
Study ofS5G4T-1 in the Treatment of Papulopustular Rosacea 
S5G4T-I compared to Vehicle 
Sol-Gel Technologies Ltd. commits to conduct the study as described herein in accordance with 
the current International Conference on Harmonization (ICH) - Good Clinical Practices (cGCPs) 
and the World Medical Association Declaration of Helsinki and in compliance with the obligations 
and requirements of the Sponsor as listed in 21 CFR Part 312. The following individuals approve 
the October 24, 2018 vel'Sion of the SGT-54-02 protocol. All chang s to this version of the 
protocol must have prior written approval and require an amendment or administrative letter. 
 
Sponsor Representative: 
 
 
Sol-Gel Technologies Ltd. 
7 Golda  Meir  St. 
Weizmann Science Park 
Ness Z.iona 7403650. Israel 
Medical Monitor: 
 
Symbio. LLC 
21 Perry St.. 
Port Jellerson. NY  I 1777 
 
Signature: 
Date: 
Signature: 
Date: 
Biostatistics and Data Management: 
 
 
QST Consultations. Ltd. 
11275 Edgewatc:r Dr. 
Allendale. Ml  49401 
 
Signature: 
 
Date: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
Page 2 of85 
November 13, 2018 


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3. 
INVESTIGATOR PROTOCOL ACKNOWLEDGMENT 
Protocol Title: A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled 
Study of S5G4T-1 in the Treatment of Papulopustular Rosacea 
Study Products:     S5G4T-1 compared to Vehicle 
I have read this protocol and commit to conduct the study as outlined herein, in accordance with 
the current International Conference on Harmonization (ICH) current Good Clinical Practices 
(cGCPs) and the World Medical Association Declaration of Helsinki and complying with the 
obligations and requirements of clinical investigator(s) and all other requirements as listed in 
21 CFR Part 312 and all other applicable regulations. Any deviations will be agreed to by prior 
discussion between the Sponsor/Contract Research Organization (CRO) and me. 
I am thoroughly familiar with the appropriate use of the investigational products(s), as described 
in this protocol, and any other information provided by the sponsor or designee, including, but not 
limited to, the current Investigator Brochure (or equivalent document). I agree to provide sufficient 
time, and adequate numbers of qualified staff and facilities for the foreseen duration of the clinical 
study to conduct the study properly, ethically and safely. 
I agree to completely inform all Patients in this study concerning the pertinent details and purpose 
of the study prior to their agreement to participate in the study in accordance with cGCPs and 
regulatory authority requirements. I will be responsible for maintaining each Patient’s consent 
form in the study file and providing each Patient with a copy of the signed consent form. 
 
 
 
Investigator’s Signature 
Date 
Investigator’s Printed Name 


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4. 
TABLE OF CONTENTS 
2. PROTOCOL APPROVAL – SPONSOR SIGNATURE PAGE .............................................. 2 
3. INVESTIGATOR PROTOCOL ACKNOWLEDGMENT ...................................................... 3 
4. TABLE OF CONTENTS ......................................................................................................... 4 
5. PROTOCOL SYNOPSIS ......................................................................................................... 9 
5.1. 
Synopsis ........................................................................................................................ 9 
5.2. 
Study Flow Chart ........................................................................................................21 
6. LIST OF ABBREVIATIONS AND TERMS .........................................................................22 
7. INTRODUCTION AND BACKGROUND ...........................................................................24 
8. OBJECTIVE ...........................................................................................................................26 
9. ETHICS ..................................................................................................................................28 
10. INSTITUTIONAL REVIEW BOARD (IRB) AND INFORMED CONSENT .....................29 
11. OVERALL STUDY DESIGN ................................................................................................30 
12. STUDY POPULATION .........................................................................................................31 
12.1. Randomization and Blinding ......................................................................................31 
12.2. Inclusion Criteria ........................................................................................................32 
12.3. Exclusion Criteria .......................................................................................................33 
12.4. Prohibited, Previous and Concomitant Therapies ......................................................35 
12.5. Precautions ..................................................................................................................36 
13. STUDY PROCEDURES ........................................................................................................38 
13.1. Study Patient Identification ........................................................................................38 
13.2. Screen Failure and Discontinuation Criteria...............................................................38 
13.3. Patient Screening and Enrollment...............................................................................39 
13.4. Assignment of Randomization ...................................................................................39 
13.5. Demographics/Medical History ..................................................................................39 
13.6. Concomitant Medications ...........................................................................................39 
13.7. Physical Examination .................................................................................................39 
13.8. Urine Pregnancy Test ..................................................................................................40 
13.9. Study Flow Chart ........................................................................................................41 
13.10. Screening Visit (Visit 1) .............................................................................................42 
13.11. Baseline Visit (Visit 2, Day 1) ....................................................................................42 
13.12. On treatment (Visit 3) – Week 2, Day 15 (± 3 days) ..................................................43 
13.13. On-treatment Visits (Visits 4 and 5) – Weeks 4 and 8, Days 29 and 57 
(± 3 days) ....................................................................................................................44 
13.14. On-treatment (Visit 6) – Week 12, Day 85 (± 4 days) or End of Treatment or 
Early Termination .......................................................................................................44 
14. CLINICAL OUTCOME ASSESSMENTS ............................................................................46 
14.1. Investigator Global Assessment (IGA) .......................................................................46 
14.2. Inflammatory Lesion Counts ......................................................................................47 
14.3. Erythema Severity Assessments .................................................................................47 


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14.4. Telangiectasia Assessment .........................................................................................47 
14.5. Patient Reported Outcomes (PRO) .............................................................................48 
14.6. Rosacea Quality of Life (RosaQoL) ...........................................................................49 
15. PHOTOGRAPHY...................................................................................................................51 
16. SAFETY EVALUATIONS ....................................................................................................52 
16.1. Cutaneous Safety Assessments ...................................................................................52 
16.2. Local Tolerability Assessments ..................................................................................53 
17. ADVERSE EVENTS ..............................................................................................................54 
17.1. Departure from the Protocol for Individual Patients ..................................................54 
17.2. Definitions ..................................................................................................................54 
17.3. Causal Relationship to Study product .........................................................................55 
17.4. Eliciting and Reporting of Adverse Events ................................................................55 
17.5. Expedited Reporting Responsibilities of the Study Center.........................................56 
17.6. Submitting an Expedited Safety Report to the IRB ....................................................56 
17.7. SAE & AEs Requiring Discontinuation of Study Drug, including Pregnancies ........57 
17.8. Pregnancy ...................................................................................................................57 
17.9. Post Study Adverse Events .........................................................................................58 
17.9.1. Non-serious Adverse Events ...........................................................................58 
17.9.2. Serious Adverse Events ..................................................................................58 
18. STUDY PRODUCTS / CLINICAL SUPPLIES ....................................................................59 
18.1. Method of Treatment Assignment ..............................................................................59 
18.2. Formulations ...............................................................................................................59 
18.3. Study Products Packaging and Labeling.....................................................................59 
18.4. Preparation, Dispensing and Storage Instructions ......................................................61 
18.5. Dosing Instructions .....................................................................................................61 
18.6. Study Product Accountability and Study Records at Sites .........................................62 
18.7. Return and Destruction of Study Product Supplies ....................................................62 
18.8. Additional Supplies Provided by Sponsor ..................................................................62 
19. STATISTICAL CONSIDERATIONS ...................................................................................63 
19.1. General Statistical Methods ........................................................................................63 
19.1.1. Patient Disposition ..........................................................................................63 
19.1.2. Demographics and Baseline Characteristics ...................................................63 
19.1.3. Protocol Deviations ........................................................................................63 
19.1.4. Analysis Populations ......................................................................................63 
19.2. Study Product Evaluations and Analyses ...................................................................64 
19.3. Assessment of Efficacy ...............................................................................................65 
19.3.1. Primary Efficacy .............................................................................................65 
19.3.2. Secondary Efficacy .........................................................................................65 
19.3.3. Supportive Efficacy ........................................................................................65 
19.4. Statistical Hypothesis Testing .....................................................................................66 
19.4.1. Test of Superiority for Lesion Count Variables .............................................66 
19.4.2. Test of Superiority for IGA ............................................................................66 
19.4.3. Test of Superiority for Secondary Efficacy and Control of Multiplicity ........66 
19.4.4. Supportive Efficacy Analyses .........................................................................67 


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19.4.5. Exploratory Endpoint ......................................................................................67 
19.4.6. Pooling Analysis .............................................................................................68 
19.4.7. Missing Efficacy Data Imputations ................................................................69 
19.4.7.1. Lesion Count Variable Missing Data Imputation ..........................69 
19.4.7.2. IGA Missing Data Imputation .......................................................70 
19.4.8. Sensitivity Efficacy Analyses .........................................................................71 
19.4.8.1. Sensitivity Analyses for Absolute Change in Lesion Count ..........71 
19.4.8.2. Sensitivity Analyses for IGA .........................................................71 
19.4.9. Subgroup Analyses .........................................................................................72 
19.5. Assessment of Safety ..................................................................................................72 
19.6. Adverse Events ...........................................................................................................72 
19.6.1. Vital Sign Measurements ................................................................................73 
19.6.2. Concomitant Medications ...............................................................................73 
19.7. Sample Size Determination ........................................................................................73 
20. ADMINISTRATIVE CONSIDERATIONS ..........................................................................74 
20.1. Protocol Compliance ..................................................................................................74 
20.2. Protocol Revisions ......................................................................................................74 
20.3. Protocol Monitoring ....................................................................................................74 
20.4. Required Study Documents ........................................................................................74 
20.5. Electronic Case Report Forms (eCRF)/Source Documents ........................................75 
20.6. Reports to the IRB/Ethics Committee (EC) ................................................................75 
20.7. Quality Assurance Audits ...........................................................................................75 
20.8. Records Retention .......................................................................................................75 
21. REFERENCES .......................................................................................................................76 


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LIST OF TABLES 
Table 1: 
Investigator Global Assessment (IGA) Scale ..................................................46 
Table 2: 
Rosacea Erythemaa Assessment Scale .............................................................47 
Table 3: 
Telangiectasia Assessment Scale .....................................................................47 
Table 4: 
Cutaneous Safety Assessment Scale ................................................................52 
Table 5: 
Local Tolerability Assessment Scale ...............................................................53 
Table 6: 
Process for Testing the Secondary Efficacy Endpoints ...................................67 


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LIST OF APPENDICES 
Appendix 1: 
Patient Instruction Sheet ..................................................................................77 
Appendix 2: 
PRO – PAPSS ..................................................................................................79 
Appendix 3: 
PRO – PAPI .....................................................................................................80 
Appendix 4: 
PRO – PGI-S ....................................................................................................81 
Appendix 5: 
PRO – PGI-C ...................................................................................................82 
Appendix 6: 
PRO – PGI-TS .................................................................................................83 
Appendix 7: 
PRO – PGI-SE .................................................................................................84 
Appendix 8: 
ROSACEA QUALITY OF LIFE QUESTIONNAIRE (ROSAQOL) .............85 


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5. 
PROTOCOL SYNOPSIS 
5.1. 
Synopsis 
 
Title: 
A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled 
Study of S5G4T-1 in the Treatment of Papulopustular Rosacea 
Study Number: 
SGT-54-02 
Study Phase: 
3 
Indication: 
Papulopustular rosacea 
Study Period: 
12 weeks (84 Days) 
Study Products: 
1. S5G4T-1: Encapsulated Benzoyl Peroxide (E-BPO) Cream, 5%, 
developed by Sol-Gel Technologies and manufactured by 
 
 Montreal, Canada. 
2. S5G4T-2: Vehicle Cream, developed by Sol-Gel Technologies and 
manufactured by 
, Montreal, Canada. 
Study Objectives: To assess the efficacy and safety of S5G4T-1 compared to S5G4T-1 
Vehicle when applied once daily for 12 weeks in patients with 
papulopustular rosacea 
Study Design: 
In this Phase 3, double-blind, vehicle-controlled study, patients will be 
admitted into this multi-center, double-blind, randomized, vehicle-
controlled, parallel-group pivotal study only after a written informed 
consent has been obtained and after all inclusion/exclusion criteria have 
been met. Male and female patients at least 18 years of age with 
moderate or severe papulopustular rosacea [Investigator Global 
Assessment (IGA) grade 3 or 4] will be eligible for enrollment for daily 
treatment with S5G4T-1 or its vehicle for 12 weeks. 
Study 
Population: 
Approximately 350 male and female patients, at least 18 years of age, who 
meet the inclusion/exclusion criteria will be enrolled in the study. 
Investigational 
Sites 
It is estimated that up to 28 study centers in US will participate in this 
study. 
Dosing: 
Patients will be randomized in a 2:1 ratio to the study product or vehicle 
treatment group, respectively. Patients will apply the study product once 
daily for 12 weeks. Patients will use a “pea-size” amount for each area of 
the face (chin, left cheek, right cheek, nose, left forehead and right 
forehead). The study product will be spread as a thin layer in such a way 
as to provide an even distribution, avoiding the eyes, lips, inside the nose, 
mouth and all mucous membranes. Patients will receive detailed 
instructions on the method of application and quantity to use in order to 
assure that treatment is harmonized among all patients to best extent 
possible. 


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5.1. 
Synopsis 
 
Methodology: 
Clinical and Safety Evaluations will be performed at: 
1. Visit 1/Screening 
2. Visit 2/Baseline, Day 1 
3. Visit 3/Week 2, Day 15 (± 3 Days) 
4. Visit 4/Week 4, Day 29 (± 3 Days) 
5. Visit 5/Week 8, Day 57 (± 3 Days) 
6. Visit 6/Week 12, Day 85 (± 4 Days)/End of Treatment/End of 
Study) 
Patients will be admitted into the study after all inclusion/exclusion 
criteria have been met, including a clinical diagnosis of rosacea and after 
written informed consent has been obtained. Subjects with severe rosacea 
who are appropriate for systemic treatment need to be counseled regarding 
their treatment options by the Principal Investigator. 
At each visit, a 5-point IGA scale of rosacea; rosacea erythema, and 
telangiectasia; and inflammatory (papules, pustules) lesion counts will be 
performed and recorded. 
Safety will be assessed at all visits, and will include monitoring of local 
adverse experiences, Investigator Cutaneous Safety Assessment rating of 
dryness and scaling and Local Tolerability Assessment rating of itching 
and burning/stinging on a scale ranging from 0 (None) to 3 (Severe); 
patients will complete a Patient Reported Outcomes (PRO) questionnaire 
at Visit 2, 3, 4, 5 and 6 and Rosacea Quality of Life Questionnaire 
(RosaQoL) at Baseline and Visit 6 or at early termination.. 
Standardized photography of facial rosacea at Visit 2, 3, 4, 5 and 6 will be 
performed at select site(s). 
In addition to IGA, at each visit, the following safety measures will be 
recorded: monitoring for any AE including local and systemic; 
investigator Cutaneous Safety Assessment rating of erythema, dryness 
and scaling and Local Tolerability Assessments rating of itching and 
burning/stinging on a scale ranging from 0 (None) to 3 (Severe). 
Urine pregnancy tests will be performed on females of child-bearing 
potential at Screening, Baseline and every 4 weeks during study or at early 
termination. 
Regardless of the duration of the study, patients that exhibit serious 
adverse event (SAE), will be followed up until the SAE resolves, based 
on investigator’s medical judgment. 
Clinical Trial 
Duration 
Screening: -35 to 0 days prior to Baseline 
Duration of treatment: 12 weeks/84 days 
Patients have the right to stop the study for any reason at any given time. 


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5.1. 
Synopsis 
 
Study product 
dosage and 
Reference 
therapy 
Encapsulated Benzoyl Peroxide Cream, 5% or vehicle will be dispensed 
every 4 weeks (Baseline, Week 4 and Week 8) to patients and used daily 
during the study. 
The study product and vehicle will be supplied in 55-gram pumps (total 
weight including pump is 85 grams). 
Patient Inclusion 
Criteria: 
Patients may participate in the study if they meet all of the following 
criteria: 
1. Patient must sign an Institutional Review Board (IRB) approved 
written informed consent for this study. 
2. Male and female 18 years of age and older. 
3. Patients must have clinical diagnosis of moderate to severe 
rosacea with a Baseline Investigator’s Global Assessment (IGA) 
Score of 3 (moderate severity) or 4 (severe) on a severity scale of 
0 to 4. 
4. Have a minimum total of 15 and a maximum total of 70 
inflammatory lesions (papules and/or pustules) including those 
present on the nose. 
5. Have two nodules or less (nodule defined as a papule or pustule 
greater than 5 mm in diameter) at Baseline. 
6. Patients must be willing and able to understand and comply with 
the requirements of the study, apply the medication as instructed, 
refrain from use of the following medications (during the study, 
return for the required treatment period visits, comply with 
therapy prohibitions, and are able to complete the study): 
− topical rosacea medication including: Metronizadole 0.75% 
to 1%, Azelaic acid, Brimonidine, Oxymetazoline, Sodium 
Sulfacetamide 10%, Sulfur 5%, Benzoyl Peroxide, 
Clindamycin, Erythromycin, Benzoyl Peroxide and 
Clindamycin, Sulfur lotions, retinoids, Ivermectin Cream 1%, 
Ivermectin lotion 0.5%; or 
− topical and systemic (oral and injectable) antibiotics known 
to impact rosacea e.g., tetracycline and its derivatives, 
erythromycin and its derivatives, doxycycline and its 
derivatives, minocycline and its derivatives, azithromycin and 
its derivatives, clarithromycin and its derivatives, 
metronidazole and its derivatives, sulfamethoxazole, or 
trimethoprim and retinoids (e.g., isotretinoin) 


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5.1. 
Synopsis 
 
Patient Inclusion 
Criteria 
(continued): 
7. Patients must be willing to minimize or not significantly alter 
controllable external factors that might trigger rosacea flare-ups 
(such as spicy food, thermally hot foods, soups and drinks, hot 
environments, prolonged sun exposure, strong winds, alcoholic 
beverages, etc.) throughout their participation in the study. 
8. Patients must be generally healthy and free from any clinically 
significant disease, other than rosacea, that might interfere with 
the study evaluations. 
9. Sexually active females of child-bearing potential, excluding 
women who are sterilized (including Essure procedure, tubal 
ligation, bilateral oophorectomy or hysterectomy) or 
post- menopausal for at least 2 years, must use one of the 
following birth control options*: 
− Intrauterine device (IUD) 
− Hormonal (injections, implants, transdermal patch, vaginal 
ring) 
− Abstinence 
− Oral contraceptives 
− Female condom 
− Diaphragm with spermicides 
− Cervical cap with spermicides 
− Contraceptive sponge 
* In addition, patients entering the trial that are on hormonal 
contraceptives must have been on this method for at least 
3 months (90 days) prior to the trial and continue the method for 
the duration of the trial. Patients who had used hormonal 
contraception and stopped must have stopped no less than 
3 months prior to Baseline. Patients entering the study who had 
an Essure procedure must have had this procedure at least 
3 months prior to the study and have undergone an Essure 
confirmation test to ensure its efficacy. A sterile sexual partner 
is not considered an adequate form of birth control. 


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5.1. 
Synopsis 
 
Patient Exclusion 
Criteria: 
The presence of any of the following will exclude the potential patients 
from entry into the study: 
1. Females, who are pregnant, breastfeeding, or planning a 
pregnancy within the period of their study participation or were 
found to have positive pregnancy test at baseline or screening 
visits. 
2. Presence of more than 2 facial nodules or any nodule greater than 
1 cm. 
3. Current or past ocular rosacea (e.g., conjunctivitis, blepharitis, or 
keratitis) of sufficient severity to require topical or systemic 
antibiotics. 
4. Presence of any other facial skin condition that might interfere 
with rosacea diagnosis and/or assessment including but not 
limited to (e.g., on the face: rosacea conglobata, rosacea 
fulminans, acne vulgaris, acne conglobata, acne fulminans, or 
secondary acne (chloracne, drug-induced acne, etc.), facial 
pustulosis of the chin, dermatitis (including peri-orbital and 
seborrheic dermatitis), demodicidosis, facial keratosis pilaris, 
acute lupus erythematous, psoriasis, eczema, acneiform eruptions 
caused by medications, steroid acne, steroid folliculitis, sunburn, 
rhinophyma, or bacterial folliculitis). 
5. Any uncontrolled, chronic or serious disease or medical 
condition that would prevent participation in a clinical trial or, in 
judgment of the Investigator, would put the patient at undue risk 
or might confound the study assessments. 
6. Excessive facial hair (e.g., beards, sideburns, moustaches, etc.) 
that would interfere with diagnosis or assessment of rosacea. 
7. History of unresponsiveness to topical benzoyl peroxide. 
8. Concurrent use of drugs causing acneiform eruptions (e.g., 
azathioprine, haloperidol, halogens, lithium, systemic 
corticosteroids, phenytoin, phenobarbital, testosterone, anabolic 
steroids, isoniazid). 
9. Known sensitivities to the study product ingredients. Allergy to 
benzoyl peroxide, parabens and glycerin or other ingredients 
listed in the investigator brochure. 


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5.1. 
Synopsis 
 
Patient Exclusion 
Criteria 
(continued): 
10. Use: 
− within 180 days prior to Baseline or during the study of oral 
retinoids (e.g., Accutane®) or therapeutic vitamin A 
supplements of greater than 10,000 units/day (multivitamins 
are allowed). 
− within 90 days prior to Baseline or during the study radiation 
therapy and/or anti-neoplastic agents. 
− start or change of dose within 90 days prior to Baseline or 
during the study of vasodilators, vasoconstrictors, 
anticoagulation or beta-blockers therapy and use throughout 
the study. Use of such therapy must remain constant 
throughout the study. 
− start or change of dose within 90 days prior to Baseline of 
hormonal treatment (oral, implanted, topical contraceptives 
and androgens). Use of such therapy must remain constant 
during the study. 
− within 30 days prior to Baseline or during the study of 
therapeutic Vitamin D supplements of greater than 2,000 
units/day (daily multivitamins with Vitamin D not exceeding 
more than 2000 IU/day are allowed). If a patient on a 
constant stable prescribed weekly dose, they should remain 
on this dose during the study. 
− within 30 days prior to Baseline or during the study of (1) 
systemic steroids, (2) topical retinoids to the face (e.g., 
tretinoin) (3) systemic (e.g., oral or injectable) antibiotics 
known to impact rosacea (e.g., tetracycline and its 
derivatives, erythromycin and its derivatives, doxycycline 
and its derivatives, minocycline and its derivatives, 
macrolides and its derivatives, azithromycin and its 
derivatives, clarithromycin and its derivatives, metronidazole 
and its derivatives, sulfamethoxazole, bactrim or 
trimethoprim); short term treatment of all other antibiotics 
(not affecting rosacea for) ≤ 14 days for non-rosacea related 
conditions is acceptable, (4) immunosuppressive agents, or 
immunomodulators (e.g. cyclosporine, tacrolimus, 
pimecrolimus). 
− of medicated make-up (including anti-aging make-up) 
throughout the study and significant change in the use of 
consumer products within 14 days of study entry and 
throughout the study. 


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5.1. 
Synopsis 
Patient Exclusion 
Criteria 
(continued): 
− of niacin and niacinamide (Vitamin B3) within 24 hours of 
study entry and throughout the study. 
− of intranasal and inhaled corticosteroids do not require a 
washout and may be used throughout the study if at a stable 
and standard dose. 
11. Facial use within 14 days prior to Baseline or during the study of 
(1) topical steroids, (2) topical anti-inflammatory agents or 
topical non-steroidal anti-inflammatory drugs (NSAID), (3) 
topical antimycotics, (4) any topical rosacea treatments (e.g., 
Metronizadole 0.75% to 1%, Azelaic acid, Brimonidine, 
Oxymetazoline, Sodium Sulfacetamide 10%, Sulfur 5%, Benzoyl 
Peroxide, Clindamycin, Erythromycin, Benzoyl Peroxide and 
Clindamycin, Sulfur lotions, Retinoids, Ivermectin) or (5) topical 
antibiotics. 
12. Use on the face within 30 days prior to Baseline or during the 
study of (1) cryodestruction or chemodestruction, (2) 
dermabrasion, (3) photodynamic therapy, (4) acne surgery, (5) 
intralesional steroids, (6) laser resurfacing or electrodessication, 
(7) x-ray therapy, (8) pulse dye laser, (9) long-pulsed Nd-YAG 
laser, (10) Intense pulse light or pulse light laser, (11) 
electrocautery or electrocoagulation, (12) CO2 laser, Fractioned 
lasers, or loop electrosurgery, (13) facial peels or other facial 
cosmetic surgery (e.g., Thermage®, etc.). 
13. Use of medicated cleansers on the face (e.g., benzoyl peroxide, 
salicylic acid, sulfur or triclosan) within 7 days of Baseline and 
throughout the study. 
14. Patient consumes excessive alcohol, abuses drugs, or has a 
condition that could compromise the patient’s ability to comply 
with study requirements and/or have drug or alcohol addiction 
requiring treatment in the past 12 months. 
15. Use of topical astringents or abrasives (e.g., rubs, exfoliating 
cleansers and products containing salicylic acid and/or alcohol), 
topical preparations that contain spices or lime, medicated topical 
preparations (prescription and OTC products) within 7 days prior 
to Visit 2 (Baseline) and throughout the study. 
16. Use of antipruritics (including antihistamines), spa or sauna 
treatments or chlorine exposure (swimming pool etc.) within 24 
hours (1 day) of all study visits (Visit 2, Baseline, through End of 
Study). 


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5.1. 
Synopsis 
 
Patient Exclusion 
Criteria 
(continued): 
17. Participation in any clinical study involving an investigational 
product, agent or device that might influence the intended effects 
or mask the side effects of study product, within 30 days prior to 
Visit 2 (Baseline) and throughout the study. 
18. Previous enrollment in this study or current enrollment in this 
study at another participating site. 
19. Employee (or employee’s family member) of the research center 
or private practice, or patients who have a conflict of interest. 
20. Patients living (e.g., siblings, spouses, relatives) in the same 
household cannot be enrolled in the study at the same time. 
21. Use of tanning booths, sun lamps or excessive UV radiation (e.g., 
phototherapy, daily extended exposure or occupational exposure 
to the sun), sunbathing or excessive exposure to the sun 1 week 
(7 days) prior to Baseline and throughout the study. 
22. Patients who in the opinion of the investigator, are unlikely to be 
able to follow the restrictions of the protocol and complete the 
study. 
Primary Efficacy 
Endpoints: 
• Proportion of patients with the primary measure of success “Clear” (0) 
or “Almost clear” (1) in the IGA relative to Baseline at Week 12 
• Absolute change in inflammatory lesion counts from baseline to 
Week 12 
Secondary 
Efficacy 
Endpoints: 
• Percent change in inflammatory lesion count from baseline to 
Week 12 
• Absolute change in inflammatory lesion count from baseline to 
Week 8 
• Proportion of patients with the primary measure of success “Clear” 
(0) or “Almost clear” (1) in the IGA relative to Baseline at Week 8 
• Absolute change in inflammatory lesion count from baseline to 
Week 4 
• Proportion of patients with the primary measure of success “Clear” 
(0) or “Almost clear” (1) in the IGA relative to Baseline at Week 4 


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5.1. 
Synopsis 
 
Supportive 
efficacy 
endpoints: 
• Percent change in inflammatory lesion count at Week 8 
• Percent change in inflammatory lesion count at Week 4 
• Mean change comparison in PAPSS item 1 (burning) between 
groups from Baseline to Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 2 (itching) between 
groups from Baseline to Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 3 (redness) between 
groups from Baseline to Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 4 (bumps) between 
groups from Baseline to Weeks 4, 8 and 12 Rosacea erythema 
assessment at Week 12 
• Telangiectasia assessment at Week 12 
• The proportion of patients in treatment relative to control who 
report at least “minimally improved” as measured by the PGI-C at 
Week 12 
• Mean change in the components of the PAPI score between groups 
from Baseline to Week 12 
• Proportion of patients in the treatment relative to control achieving 
a three-point improvement in the components of the PAPI score 
from Baseline to Week 12 
• Patient Global Impression of Symptom Severity (PGI-S) at 
Week 12 
• Patient Global Impression of Treatment Satisfaction (PGI-TS) at 
Week 12 
• A set of cumulative distribution function (CDF) curves will be 
generated to allow for the evaluation of within-person change by 
treatment group. Specifically, 5 plots will be generated showing 
the change from baseline to Week 12 [and/or other, earlier time 
points if so desired] by the cumulative percent of subjects for each 
of the treatment arms (change on the x-axis will be expressed as 
absolute change) on: 
o PAPSS total scale scores; 
o PAPSS item 1 (burning) scores; 
o PAPSS item 2 (itching) scores; 
o PAPSS item 3 (redness) scores; and 
o PAPSS item 4 (bumps) scores 


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5.1. 
Synopsis 
 
Safety Endpoints: • Adverse events (AEs), including serious adverse events (SAEs) 
occurring at any time during the trial. 
• Investigator Cutaneous Safety Assessment and Local Tolerability 
Assessments score at any time during the trial. 
Safety: 
The incidence of all adverse events reported during the study will be 
summarized by treatment group. Safety will be evaluated by comparing 
the nature, severity and frequency of their adverse event profiles. Safety 
variables include Investigator Cutaneous Safety Assessment score, 
treatment-emergent adverse events (AEs), SAEs, treatment related AEs, 
AEs leading to study discontinuation and concomitant medications 


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5.1. 
Synopsis 
 
Statistical 
Method: 
General Statistical Methods 
All statistical processing will be performed using SAS® version 9.3 or 
later unless otherwise stated. Statistical significance will be based on 
two-tailed tests of the null hypothesis resulting in p-values of 0.05 or less. 
Analysis Populations 
The intent-to-treat (ITT) population will consist of all randomized patients 
who were dispensed study product. The safety population will be 
comprised of all randomized patients who are presumed to have used the 
study product at least once and who provide at least one post-baseline 
safety evaluation. Patients will be considered per protocol (PP) if they 
complete the 12-week evaluation without noteworthy study protocol 
violations (i.e., any patient or investigator activity that could have possibly 
interfered with the therapeutic administration of the treatment or the 
precise evaluation of treatment efficacy). 
Patients that discontinue from the study due to an adverse event related to 
study treatment or documented lack of treatment effect will be included in 
the PP population. Data for these subjects will not be imputed by multiple 
imputation but rather their data will be imputed with values consistent 
with their status as treatment failures. Prior to breaking the blind, other 
additional criteria may be added to the list to accommodate for unforeseen 
events that occurred during the conduct of the trial that result in 
noteworthy study protocol violations 
Evaluations and Analyses 
Inflammatory lesion count will be recorded for each patient at Baseline 
and at Weeks 2, 4, 8 and 12. The absolute and percent change from 
baseline of inflammatory lesions will be derived for each patient at 
Weeks 2, 4, 8 and 12. 
The IGA will be recorded for each patient at Baseline, Weeks 2, 4, 8 and 
12. The IGA will be dichotomized into “success” and “failure” at 
Weeks 2, 4, 8 and 12 with a patient considered a success for those visits if 
the IGA is at least 2 grades less than baseline and are Clear or Almost 
Clear. 
The Rosacea erythema assessment, and telangiectasia assessment will be 
recorded at Baseline, Weeks 2, 4, 8 and 12. 
Patients will be asked to complete a Patient Reported Outcome, PRO 
questionnaire at Baseline, Weeks 2, 4, 8 and 12 and a Rosacea Quality of 
Life, RosaQoL questionnaire at Baseline and Week 12(or at the early 
termination visit). 
All assessments will be conducted for both ITT and PP. 


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5.1. 
Synopsis 
 
Statistical 
Method 
(continued): 
Statistical Hypothesis Testing 
Tests of superiority for the absolute change from Baseline in inflammatory 
lesions will be based on either parametric or non-parametric methods 
consistent with the statistical assumptions required to support the 
analyses. Specifically, the tests of superiority will be based on an 
ANCOVA with factors of treatment and analysis center and the respective 
Baseline lesion count as a covariate or on ranked data submitted to an 
ANCOVA with factors of treatment and analysis center and the respective 
Baseline lesion count as a covariate. If the treatment-by-analysis center 
interaction effect is significant at an alpha less than 0.10, then the effect 
will be included in the model; otherwise it will be removed. 
A skewness test, based on the methods presented by Zar 1984, will be 
applied to the residuals resulting from an ANCOVA. A two-sided p-value 
for the skewness test significant at 0.01 will imply the use of the non- 
parametric method. If a parametric analysis is indicated, the results of the 
parametric analysis will be considered the primary analysis. Should a 
non-parametric analysis be indicated, the absolute or percent changes in 
inflammatory lesions will be rank-transformed prior to submitting them to 
the ANCOVA. Results of the rank-transformed analyses then will be 
considered the primary analysis; however, results of the non- rank-
transformed analyses will also be presented. 
The IGA will be dichotomized into “success” and “failure” with a patient 
considered a success for those visits if the Investigator’s Global 
Assessment is at least 2 grades less than Baseline and “Clear” or “Almost 
Clear”. The analysis of the dichotomized IGA will be based on a logistic 
regression test with factors of treatment group and analysis center. 
Missing Efficacy Data Imputations 
Missing Week 12 data will be estimated by multiple imputation and 
subsequently analyzed. Missing lesion count data will be derived for the 
analysis using the method of Markov Chain Monte Carlo (MCMC) 
multiple imputation. The pattern of missing observations in each 
treatment group cannot influence the missing value estimation in the other 
because the imputation will be conducted independently for each 
treatment group. 
Safety 
Evaluation: 
Safety will be evaluated by tabulations of adverse events (AEs), 
Cutaneous Safety Assessments for dryness and scaling, assessments for 
scores (erythema and telangiectasia) and Patient Global Impression of 
Treatment Side-Effects (PGI-SE) will be presented with descriptive 
statistics at Baseline and at the scheduled study visits. Frequencies and 
percentages for each outcome category will be included in these statistics. 


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5.2. 
Study Flow Chart 
 
Procedures 
Visit 11 
Visit 22 
Visit 32 
Visit 42 
Visit 52 
Visit 62,3 
(EOT4/ 
EOS5) 
Name of Visit 
Screening 
-35 – 0 
Baseline 
Day 1 
Week 2 
Day 15 
Week 4 
Day 29 
Week 8 
Day 57 
Week 12 
Day 85 
Visit window 
± 3 days 
± 3 days 
± 3 days 
± 4 days 
Informed Consent 
X 
Demographics 
X 
Medical History/Previous Therapies 
X 
X 
Brief Physical Examination 
X 
X 
Inclusion/Exclusion Criteria 
X 
X 
Urine Pregnancy Test6 
X 
X 
X 
X 
X 
IGA 
X 
X 
X 
X 
X 
X 
Inflammatory Lesion Counts 
X 
X 
X 
X 
X 
X 
Assessment of Eligibility 
X 
Rosacea Erythema Assessment 
X 
X 
X 
X 
X 
Telangiectasia Assessment 
X 
X 
X 
X 
X 
Randomization 
X 
Cutaneous Safety Assessment and 
Local Tolerability Assessments 
X 
X 
X 
X 
X 
Administer/ Review Patient 
Instructions 
X 
X 
X 
X 
Weigh Study Product 
X 
X 
X 
X 
Study Product Dispensed 
X7 
X 
X 
Provide Cleanser and 
Moisturizer/Sunscreen8 
X 
Diary Card dispensed 
X 
X 
X 
Study Product Collected 
X 
X 
X 
Diary Card collected 
X 
X 
X 
Patient Compliance Reviewed (Diary) 
X 
X 
X 
X 
Concomitant Therapy and Medication 
History Reviewed 
X 
X 
X 
X 
X 
X 
Adverse Events 
X9 
X 
X 
X 
X 
X 
Photography (select site(s)) 
X 
X 
X 
X 
X 
Complete PAPSS, PAPI and PGI-S10,11 
X 
X 
X 
X 
X 
Complete PGI-C, PGI-TS and 
PGI-SE12 
X 
X 
X 
X 
Complete RosaQoL13 
X 
X 
 
 
1 If no washout is needed, Visits 1 and 2 may occur on the same day. If a washout is needed, Visit 2 must occur within one month 35 days of 
Visit 1. 
2 All visit dates are in reference to Baseline, e.g., Visit 5 occurs 8 weeks ± 3 days after Baseline Visit. 
3 All Week 12 procedures should be completed for Patients who terminate early. 
4 EOT – end of treatment 
5 EOS – end of study 
6 All women of childbearing potential 
7 Dispense one pump of test material at the Baseline Visit and dispense additional pump at Visit 4 and 5. 
8 Or study approved cleanser and moisturizer 
9 Adverse events after ICF is signed will be collected. 
10 PAPSS is Patient Assessment of Papulopustular rosacea Signs and Symptoms; PAPI is Patient Assessment of Papulopustular rosacea Impacts; 
PGI-S is Patient Global Impression of Symptom Severity. Questionnaires will be completed prior to PI assessment. 
11 In case Screening Visit and Baseline are on the same day, the PRO questionnaires should be completed prior to screening procedures. 
12 PGI-C is Patient Global Impression of Change; PGI-TS is Patient Global Impression of Treatment Satisfaction; PGI-SE is Patient Global 
Impression of Treatment Side-Effects. Questionnaires will be completed prior to PI assessment. 
13 RosaQoL is a Rosacea Quality of Life questionnaire. 


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6. 
LIST OF ABBREVIATIONS AND TERMS 
 
AE(s) 
Adverse Event(s) 
ANCOVA 
Analysis of Covariance 
BPO 
Benzoyl Peroxide 
°C 
Degrees Centigrade 
CFR 
Code of Federal Regulations 
CRO 
Contract Research Organization 
E-BPO 
Encapsulated Benzoyl Peroxide 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
g 
Grams 
cGCP 
current Good Clinical Practice 
h 
hour(s) 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IGA 
Investigator’s Global Assessment 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IWRS 
Interactive Web Response System 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
min 
Minutes 
mg 
Milligram 
NRS 
Numerical Rating Scale 
OTC 
Over-the-Counter 
PAPI 
Patient Assessment of Papulopustular Rosacea Impacts 
PAPSS 
Patient Assessment of Papulopustular Rosacea Signs and Symptoms 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Symptom Severity 
PGI-SE 
Patient Global Impression of Treatment Side-Effects 
PGI-TS 
Patient Global Impression of Treatment Satisfaction 
PI 
Principal Investigator 
PRO 
Patient Reported Outcome 


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PP 
Per Protocol 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
VRS 
Verbal Rating Scale 


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7. 
INTRODUCTION AND BACKGROUND 
S5G4T-1 is an innovative topical formulation containing 5% encapsulated benzoyl peroxide (E-
BPO) that Sol-Gel is developing for the treatment of rosacea. If approved, S5G4T-1 will be the 
first product containing E-BPO for the treatment of rosacea. Sol-Gel believes S5G4T-1 has the 
potential to be as tolerable as, and more effective than, currently marketed rosacea drugs. 
Rosacea is a chronic and recurrent inflammatory dermatological disorder of unknown etiology. 
The disease is common, especially in fair-skinned people of Celtic and northern European heritage. 
The onset of the disorder is usually between the ages of 30 and 50. Early stages of the disease 
affect women more often than men at a ratio of 3 to 1 (Jansen and Plewig 1997 and 
McDonnell and Tomecki 2000). Rosacea usually starts as flushing and subtle redness on the 
cheeks, nose, chin or forehead. Alcohol, hot drinks, spicy foods, stress, sunlight and extreme heat 
or cold can trigger the onset of this disease. If left untreated, rosacea can slowly worsen over time. 
As the condition progresses, patients experience inflammatory lesions (papules and pustules), 
vivid erythema and telangiectasia. Patients may develop furuncles, cystic nodules, granulomas 
and tissue hypertrophy, sometimes leading to rhinophyma. 
The first report on the treatment of rosacea with benzoyl peroxide as a single agent was described 
by in Montes et al. in 1983. In this limited study, 5% benzoyl peroxide, after 5 to 8 weeks of 
treatment, demonstrated superiority compared to control with respect to papules, pustules and 
erythema but not telangiectasia. The formulation was a basic formulation with benzoyl peroxide 
dissolved and delivered in acetone. Irritation and burning was reported in both groups, most likely 
due to the well-known effects of benzoyl peroxide. 
More recently, Breneman et al. 2004 published the results of a study in collaboration with 
J. Leyden. This study was a double-blind, vehicle-controlled study, using a combination gel 
product of 5% benzoyl peroxide and 1% clindamycin to treat patients having moderate to severe 
rosacea. The most dramatic effect of the benzoyl peroxide/clindamycin treatment was on the 
reduction of papules and pustules. Side effects included the well-known effects of benzoyl 
peroxide, burning and itching. 
Yamasaki et al. published a paper in 2007 which may explain why benzoyl peroxide potentially 
has a therapeutic benefit in the treatment of rosacea. The team reported that a protease that splits 
the antimicrobial peptide, cathelicidin, from its protein precursor is elevated in inflammatory 
rosacea. Cathelicidin subsequently induces the formation of the pro-inflammatory cytokine IL-8. 
It has also been previously reported that Propionibacterium acnes induces elevated levels of 
cathelicidin in the skin. These observations support the hypothesis that P. acnes has a major role 
in the etiology of rosacea, and provide a mechanistic understanding of why benzoyl peroxide may 
have a therapeutic benefit in the treatment of rosacea. 
Rosacea is treated with both systemic and topical therapies. However, topical therapies are 
preferable because of side effects caused by the use of systemic therapies. 
According to the U.S. National Rosacea Society, approximately 16 million people in the United 
States are affected by rosacea. According to a study commissioned by the Sponsor, approximately 
4.8 million people in the United States experience subtype II symptoms and physicians estimate 
that only 20% of the U.S. rosacea population is treated. The topical drugs approved by the FDA 
to treat subtype II rosacea generated aggregate revenues of approximately $392 million in the 
United States for the 12 months period ending June 30, 2017. 


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8. 
OBJECTIVE 
• The primary objective of this pivotal study is: 
1. To assess the efficacy and safety of S5G4T-1 compared to S5G4T-1 Vehicle when applied 
once daily for 12 weeks in patients with papulopustular rosacea. 
The co-primary efficacy endpoints are to be evaluated using the following parameters: 
• Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” 
(1) in the IGA relative to Baseline at Week 12. 
• Absolute change in inflammatory lesion counts from baseline to Week 12. 
• The secondary objective of this pivotal study is: 
To demonstrate statistical superiority in efficacy of S5G4T-1 compared to the vehicle with regard 
to percent change from baseline. 
The co-secondary efficacy endpoints are: 
• Percent change in inflammatory lesion count from baseline to Week 12 
• Absolute change in inflammatory lesion count from baseline to Week 8 
• Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” 
(1) in the IGA relative to Baseline at Week 8 
• Absolute change in inflammatory lesion count from baseline to Week 4 
• Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” 
(1) in the IGA relative to Baseline at Week 4 
 
• The supportive objective of this pivotal study is: 
To determine the time required to observe improvement in the efficacy parameters associated with 
clearance of rosacea for S5G4T-1 compared to vehicle. 
Supportive efficacy endpoints include the following: 
• Percent change in inflammatory lesion count at Week 8 
• Percent change in inflammatory lesion count at Week 4 
• Mean change comparison in PAPSS item 1 (burning) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 2 (itching) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 3 (redness) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 4 (bumps) between groups from Baseline to 
Weeks 4, 8 and 12 Rosacea erythema assessment at Week 12 
• Telangiectasia assessment at Week 12 
• The proportion of patients in treatment relative to control who report at least “minimally 
improved” as measured by the PGI-C at Week 12 


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• Mean change in the components of the PAPI score between groups from Baseline to 
Week 12 
• Proportion of patients in the treatment relative to control achieving a three-point 
improvement in the components of the PAPI score from Baseline to Week 12 
• Patient Global Impression of Symptom Severity (PGI-S) at Week 12 
• Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 12. 
• A set of cumulative distribution function (CDF) curves will be generated to allow for the 
evaluation of within-person change by treatment group. Specifically, 5 plots will be 
generated showing the change from baseline to Week 12 [and/or other, earlier time points 
if so desired] by the cumulative percent of subjects for each of the treatment arms (change 
on the x-axis will be expressed as absolute change) on: 
PAPSS total scale scores; 
PAPSS item 1 (burning) scores; 
PAPSS item 2 (itching) scores; 
PAPSS item 3 (redness) scores; and 
PAPSS item 4 (bumps) scores 
 
 
• The safety objective of this pivotal study is: 
The safety objectives of this study are to determine the nature, severity and frequency of the 
adverse event rate, the Cutaneous Safety Assessment and the Local Tolerability Assessment of 
S5G4T-1 compared to the vehicle. 
The safety endpoints to be assessed include the following: 
• Adverse events (AEs), including serious adverse events (SAEs) occurring at any time 
during the trial. 
• Investigator Cutaneous Safety Assessment and Local Tolerability Assessments score at any 
time during the trial. 


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9. 
ETHICS 
This study will be conducted in compliance with FDA regulations, the ethical principles of the 
Declaration of Helsinki, and the current ICH- Good Clinical Practice (cGCP) guidelines. The 
investigator and all study staff will conduct the study in compliance with this protocol. 
The protocol, informed consent documents, any information provided to patients, recruitment 
advertisements and any amendments to these items will have Institutional Review Board (IRB) 
approval prior to their use in the study. Voluntary informed consent will be given by every patient 
prior to the initiation of any study related procedures. The rights, safety and well-being of the 
study patients are the most important considerations and prevail over the interests of science and 
society. 
All personnel involved in the conduct of this study must be qualified by education, training and 
experience to perform their assigned responsibilities. 


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10. 
INSTITUTIONAL REVIEW BOARD (IRB) AND INFORMED 
CONSENT 
Before study initiation, this protocol, the investigational brochure for encapsulated benzoyl 
peroxide cream (E-BPO) in the treatment of rosacea, the informed consent form, and any other 
written information given to patients, and any advertisement for patient recruitment must have IRB 
approval. The investigator will submit documentation of the IRB approval to the Sponsor, Sol-Gel 
Technologies Ltd., or their CRO designee. 
The IRB-approved consent form must include all elements required by FDA, state, and local 
regulations, and may include appropriate additional elements. 
The investigator/designee will explain the study to each potential patient and the patient must 
indicate voluntary consent by signing and dating the approved informed consent form. The 
consent process will be conducted prior to the start of any study-related procedures including a 
washout period. The investigator must provide the patient with a copy of the consent form, in a 
language the patient understands. 
The investigator will maintain documentation that informed consent was obtained prior to the 
initiation of any study-related procedures. 


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11. 
OVERALL STUDY DESIGN 
This study will be a randomized, double-blind, multicenter, parallel group, active- and vehicle-
controlled pivotal study of the efficacy, and safety of S5G4T-1 and its vehicle for the treatment 
of papulopustular rosacea for 12 weeks. Approximately 350 patients with moderate to severe 
rosacea (rated 3 or 4 on the 5-point IGA scale) will be enrolled at up to 28 sites. Patients in this 
randomized, double-blind, vehicle-controlled, parallel-group multi-center study will be randomly 
assigned in a 2:1 ratio to S5G4T-1 or vehicle, respectively. Subjects with severe rosacea who are 
appropriate for systemic treatment need to be counseled regarding their treatment options by the 
Principal Investigator. 
Patients will receive once daily treatment with S5G4T-1 or vehicle cream for 12 weeks. After the 
screening period, qualified patients will be randomly assigned at the Baseline visit and treated for 
12 weeks. Efficacy assessments will include facial inflammatory lesion counts and IGA 
assessment ranging from 0 (Clear) to 4 (Severe). Investigators will be provided with instructions 
for lesion counts to ensure consistency of procedure. Patient reported outcomes (PRO) will be 
assessed with the PAPSS (Patient Assessment of Papulopustular rosacea Signs and Symptoms), 
PAPI (Patient Assessment of Papulopustular rosacea Impacts) and PGI-S (Patient Global 
Impression of Symptom Severity) that will be administered at Baseline, Weeks 2, 4, 8 and 12, or 
at early termination. In addition, the PGI-C (Patient Global Impression of Change), PGI-TS 
(Patient Global Impression of Treatments Satisfaction) and PGI-SE (Patient Global Impression of 
Treatments Side Effects) will be administered at Weeks 2, 4, 8 and 12, or at early termination 
[FDA Guidance 2009]. Rosacea Quality of Life (RosaQoL) questionnaire will be administered at 
Baseline, and Week 12, or at early termination. Safety will be assessed at all visits and will include 
monitoring local and systemic adverse events (AEs); the investigator Cutaneous Safety 
Assessment rating of erythema, dryness and scaling and Local Tolerability Assessments rating of 
itching and burning/stinging on a scale ranging from 0 (None) to 3 (Severe). 
Patients will return to centers for IGA, lesion counts, PRO questionnaire, , Investigator Cutaneous 
Safety Assessment and Local Tolerability Assessments at Weeks 2, 4, 8 and 12. At Week 12 (or 
at the early termination visit) patients will be asked to complete RosaQoL questionnaire. Adverse 
events and concomitant medications will be assessed throughout the treatment period. A urine 
pregnancy test is required at Visit 1, 2, 4, 5 and 6 for all females of child-bearing potential. 
Clinical Evaluations will be performed at: 
• Visit 1/Screening 
• Visit 2/Baseline, Day 1 
• Visit 3/Week 2, Day 15 (± 3 Days) 
• Visit 4/Week 4, Day 29 (± 3 Days) 
• Visit 5/Week 8, Day 57 (± 3 Days) 
• Visit 6/Week 12, Day 85 (± 4 Days)/End of Treatment) 


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12. 
STUDY POPULATION 
12.1. 
Randomization and Blinding 
It is planned that approximately 350 patients who meet the inclusion/exclusion criteria will be 
enrolled in this study at up to 28 U.S. study sites. Patients will be at least 18 years of age and 
older, of either gender. Efforts will be made to enroll patients ages matching the target study 
population. 
The study product will be administered in a double-blinded fashion, i.e., the treatment assignment 
will not be known to the patient, to study personnel, or Sol-Gel and its representatives. Patients 
will be instructed not to discuss the study product with the study personnel. Patients will be 
randomly assigned in a 2:1 ratio as follows: 
• E-BPO Cream, 5% (S5G4T-1) (234 patients) 
• Vehicle Cream (S5G4T-2) (117 patients) 
Each patient who signs an informed consent, meets inclusion/exclusion criteria, and successfully 
completes the screening procedures, will be enrolled in the study. The patient randomization 
schedule will be a permuted block design stratified by investigational site. Blocks will be 
composed of 3 treatment assignments in a ratio of 2:1 study product and vehicle, respectively. 
Complete blocks from the randomization schedule will be allocated to investigational sites as they 
randomize patients to maintain the randomization ratio of 2:1 study product and vehicle, 
respectively. 
Additionally, the staff involved in data management and statistical evaluation will remain blinded 
until identification of the per protocol population is finished and a database lock memo is issued. 
The randomization schedule and treatment code will not be revealed to the patients, study 
personnel, Sol-Gel or its representatives until after the database lock, except to the Medical 
Monitor or Principal Investigator for an emergency. Access to the randomization list will be 
maintained by and limited to the unblinded Biostatistician and the designated personnel directly 
responsible for labeling of study materials. The Medical Monitor will not have access to the 
randomization list, but may determine that unblinding one or all patients may be necessary in the 
case that the safety of study patients is at risk. In an emergency, the study blind may be broken 
only if: 
• In the opinion of the Medical Monitor and/or the PI, it is in the patient's best interest to do 
so 
• Knowledge of the treatment will alter the clinical management of the patient 
In the case of an emergency that requires unblinding, the Investigator can request to unblind the 
patient without prior contact with the Medical Monitor although follow-up between the 
Investigator and Medical Monitor must occur so that all parties are aware of the unblinding. 
Although it is recommended that the Investigator contact the Medical Monitor prior to unblinding 
any patient, in instances where this is not feasible or advisable the PI may directly access the 
patient's treatment assignment. In all situations, the Interactive Web Response System (IWRS) 
will be used to obtain treatment assignment information with limited access to only the above-
designated individuals, and any unblinding will be documented as a protocol deviation. 


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12.2. 
Inclusion Criteria 
To be included in the study, patients must meet the following eligibility /inclusion criteria: 
1. Patient must sign an Institutional Review Board (IRB) approved written informed consent for 
this study. 
2. Male and female 18 years of age and older. 
3. Patients must have clinical diagnosis of moderate to severe rosacea with a Baseline (IGA Score 
of 3 (moderate severity) or 4 (severe) on a severity scale of 0 to 4. 
4. Have a minimum total of 15 and a maximum total of 70 inflammatory lesions (papules and/or 
pustules) including those present on the nose. 
5. Have two nodules or less (nodule defined as a papule or pustule greater than 5 mm in diameter) 
at Baseline. 
6. Patients must be willing and able to understand and comply with the requirements of the study, 
apply the medication as instructed, refrain from use of the following medications (during the 
study, return for the required treatment period visits, comply with therapy prohibitions, and are 
able to complete the study): 
• topical rosacea medication including: Metronizadole 0.75% to 1%, Azelaic acid, 
Brimonidine, Oxymetazoline, Sodium Sulfacetamide 10%, Sulfur 5%, Benzoyl Peroxide, 
Clindamycin, Erythromycin, Benzoyl Peroxide and Clindamycin, Sulfur lotions, retinoids, 
Ivermectin Cream 1%, Ivermectin lotion 0.5%, or 
• topical and systemic (oral and injectable) antibiotics known to impact rosacea e.g., 
tetracycline and its derivatives, erythromycin and its derivatives, doxycycline and its 
derivatives, minocycline and its derivatives, azithromycin and its derivatives, 
clarithromycin and its derivatives, metronidazole and its derivatives, sulfamethoxazole, or 
trimethoprim and retinoids (e.g., isotretinoin) 
7. Patients must be willing to minimize or not significantly alter controllable external factors that 
might trigger rosacea flare-ups (such as spicy food, thermally hot foods, soups and drinks, hot 
environments, prolonged sun exposure, strong winds, alcoholic beverages, etc.) throughout 
their participation in the study. 
8. Patients must be generally healthy and free from any clinically significant disease, other than 
rosacea, that might interfere with the study evaluations. 
9. Sexually active females of child-bearing potential, excluding women who are sterilized 
(including Essure procedure, tubal ligation, bilateral oophorectomy or hysterectomy) or 
post- menopausal for at least 2 years, must use one of the following birth control options*: 
• Intrauterine device (IUD) 
• Hormonal (injections, implants, transdermal patch, vaginal ring) 
• Abstinence 
• Oral contraceptives, 
• Female condom 
• Diaphragm with spermicides 


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• Cervical cap with spermicides 
• Contraceptive sponge 
* In addition, patients entering the trial that are on hormonal contraceptives must have been on 
this method for at least 3 months (90 days) prior to the trial and continue the method for the 
duration of the trial. Patients who had used hormonal contraception and stopped must have 
stopped no less than 3 months prior to Baseline. Patients entering the study who had an 
Essure procedure must have had this procedure at least 3 months prior to the study and have 
undergone an Essure confirmation test to ensure its efficacy. A sterile sexual partner is not 
considered an adequate form of birth control. 
12.3. 
Exclusion Criteria 
Patients are excluded from the study if any of the following criteria are met: 
1. Females, who are pregnant, breastfeeding, or planning a pregnancy within the period of their 
study participation or were found to have positive pregnancy test at baseline or screening visits. 
2. Presence of more than 2 facial nodules or any nodule greater than 1 cm. 
3. Current or past ocular rosacea (e.g., conjunctivitis, blepharitis, or keratitis) of sufficient 
severity to require topical or systemic antibiotics. 
4. Presence of any other facial skin condition that might interfere with rosacea diagnosis and/or 
assessment including but not limited to (e.g., on the face: rosacea conglobata, rosacea 
fulminans, acne vulgaris, acne conglobata, acne fulminans, or secondary acne (chloracne, 
drug-induced acne, etc.), facial pustulosis of the chin, dermatitis (including peri-orbital and 
seborrheic dermatitis), demodicidosis, facial keratosis pilaris, acute lupus erythematous, 
psoriasis, eczema, acneiform eruptions caused by medications, steroid acne, steroid folliculitis, 
sunburn, rhinophyma, or bacterial folliculitis). 
5. Any uncontrolled, chronic or serious disease or medical condition that would prevent 
participation in a clinical trial or, in judgment of the Investigator, would put the patient at undue 
risk or might confound the study assessments. 
6. Excessive facial hair (e.g., beards, sideburns, moustaches, etc.) that would interfere with 
diagnosis or assessment of rosacea. 
7. History of unresponsiveness to topical benzoyl peroxide. 
8. Concurrent use of drugs causing acneiform eruptions (e.g., azathioprine, haloperidol, halogens, 
lithium, systemic corticosteroids, phenytoin, phenobarbital, testosterone, anabolic steroids, 
isoniazid). 
9. Known sensitivities to the study product ingredients. Allergy to benzoyl peroxide, parabens 
and glycerin or other ingredients listed in the investigator brochure. 
10. Use: 
• within 180 days prior to Baseline or during the study of oral retinoids (e.g., Accutane®) or 
therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are 
allowed). 
• within 90 days prior to Baseline radiation therapy and/or anti-neoplastic agents. 


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• start or change of dose within 90 days prior to Baseline or during the study of vasodilators, 
vasoconstrictors, anticoagulation or beta-blockers therapy and use throughout the study. 
Use of such therapy must remain constant throughout the study. 
• start or change of dose within 90 days prior to Baseline of hormonal treatment (oral, 
implanted, topical contraceptives and androgens). Use of such therapy must remain 
constant during the study. 
• within 30 days prior to Baseline or during the study of therapeutic Vitamin D supplements 
of greater than 2,000 units/day (daily multivitamins with Vitamin D not exceeding more 
than 2000 IU/day are allowed). If a patient on a constant stable prescribed weekly dose, 
they should remain on this dose during the study. 
• within 30 days prior to Baseline or during the study of (1) systemic steroids, (2) topical 
retinoids to the face (e.g., tretinoin) (3) systemic (e.g., oral or injectable) antibiotics known 
to impact rosacea (e.g., tetracycline and its derivatives, erythromycin and its derivatives, 
doxycycline and its derivatives, minocycline and its derivatives, macrolides and its 
derivatives, azithromycin and its derivatives, clarithromycin and its derivatives, 
metronidazole and its derivatives, sulfamethoxazole, bactrim or trimethoprim); short term 
treatment of all other antibiotics (not affecting rosacea for) ≤ 14 days for non-rosacea 
related conditions is acceptable, (4) immunosuppressive agents, or immunomodulators 
(e.g. cyclosporine, tacrolimus, pimecrolimus). 
• of medicated make-up (including anti-aging make-up) throughout the study and significant 
change in the use of consumer products within 14 days of study entry and throughout the 
study. 
• of niacin and niacinamide (Vitamin B3) within 24 hours of study entry and throughout the 
study. 
• of intranasal and inhaled corticosteroids do not require a washout and may be used 
throughout the study if at a stable and standard dose. 
11. Facial use within 14 days prior to Baseline or during the study of (1) topical steroids, (2) topical 
anti-inflammatory agents or topical non-steroidal anti-inflammatory drugs (NSAID), (3) 
topical antimycotics, (4) any topical rosacea treatments (e.g., Metronizadole 0.75% to 1%, 
Azelaic acid, Brimonidine, Oxymetazoline, Sodium Sulfacetamide 10%, Sulfur 5%, Benzoyl 
Peroxide, Clindamycin, Erythromycin, Benzoyl Peroxide and Clindamycin, Sulfur lotions, 
Retinoids, Ivermectin) or (5) topical antibiotics. 
12. Use on the face within 30 days prior to Baseline or during the study of (1) cryodestruction or 
chemodestruction, (2) dermabrasion, (3) photodynamic therapy, (4) acne surgery, (5) 
intralesional steroids, (6) laser resurfacing or electrodessication, (7) x-ray therapy, (8) pulse 
dye laser, (9) long-pulsed Nd-YAG laser, (10) Intense pulse light or pulse light laser, (11) 
electrocautery or electrocoagulation, (12) CO2 laser, Fractioned lasers, or loop electrosurgery, 
(13) facial peels or other facial cosmetic surgery (e.g., Thermage®, etc.). 
13. Use of medicated cleansers on the face (e.g., benzoyl peroxide, salicylic acid, sulfur or 
triclosan) within 7 days of Baseline and throughout the study. 
14. Patient consumes excessive alcohol, abuses drugs, or has a condition that could compromise 
the patient’s ability to comply with study requirements and/or have drug or alcohol addiction 
requiring treatment in the past 12 months. 


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15. Use of topical astringents or abrasives (e.g., rubs, exfoliating cleansers and products containing 
salicylic acid and/or alcohol), topical preparations that contain spices or lime, medicated 
topical preparations (prescription and OTC products) within 7 days prior to Visit 2 (Baseline) 
and throughout the study. 
16. Use of antipruritics (including antihistamines), spa or sauna treatments or chlorine exposure 
(swimming pool etc.) within 24 hours (1 day) of all study visits (Visit 2, Baseline, through End 
of Study). 
17. Participation in any clinical study involving an investigational product, agent or device that 
might influence the intended effects or mask the side effects of study product, within 30 days 
prior to Visit 2 (Baseline) and throughout the study. 
18. Previous enrollment in this study or current enrollment in this study at another participating 
site. 
19. Employee (or employee’s family member) of the research center or private practice, or patients 
who have a conflict of interest. 
20. Patients living (e.g., siblings, spouses, relatives) in the same household cannot be enrolled in 
the study at the same time. 
21. Use of tanning booths, sun lamps or excessive UV radiation (e.g., phototherapy, daily extended 
exposure or occupational exposure to the sun), sunbathing or excessive exposure to the sun 
1 week (7 days) prior to Baseline and throughout the study. 
22. Patients who in the opinion of the investigator, are unlikely to be able to follow the restrictions 
of the protocol and complete the study. 
12.4. 
Prohibited, Previous and Concomitant Therapies 
Any previous rosacea therapies must be stopped for the appropriate washout period as specified 
below and as noted in the exclusion criteria: 
• Topical astringents or abrasives or preparations that contain spices or lime, medicated 
topical preparations applied to the face (prescription and OTC products) within 7 days prior 
to Baseline. 
• Use of medicated cleansers on the face (e.g., benzoyl peroxide, salicylic acid, sulfur or 
triclosan) within 7 days of Baseline. 
• Topical anti-rosacea treatments – 2 weeks prior to Baseline. 
• Topical antibiotics, antimicrobials – 2 weeks prior to Baseline. 
• Topical anti-inflammatories on the face such as corticosteroids, vasoconstrictors and 
non-steroidal anti-inflammatory drugs (NSAID) – 2 weeks prior to Baseline. 
• Topical retinoids – 30 days prior to Baseline. 
• Systemic rosacea treatments, corticosteroids, antibiotics – 4 weeks prior to Baseline. 
• Systemic retinoids – 6 months prior to Baseline. 


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Other than the study products, no other topical medications are permitted to be used on the face. 
All topical or systemic medications listed above and under exclusion criteria are prohibited. Other 
prohibited treatments include but are not limited to astringents, toners, clarifying lotions, 
medicated shaving products, cosmetic procedures and chemical peeling products used on the face. 
A stable regimen of inhaled corticosteroids for stable medical conditions (in the 2 months 
preceding enrollment) and antibiotic treatment of an infection of less than 14 days are allowed 
during the study. 
No medicated cleansers or moisturizers are allowed on the face. Only the sponsor-provided 
cleanser and moisturizer/sunscreen (or a study-approved cleanser or moisturizer/sunscreen) will 
be allowed to be used on the face during the study. Study product shall be applied to clean skin 
and no cleanser should be applied to the face within two hours of study product application. 
Approved moisturizer/sunscreen may be applied after 30 minutes or more of study product 
application. Patients who use make-up must have used the same brands/types of make-up for a 
minimum period of 1 month (30 days) prior to study entry and must agree to not change make-up 
brand/type or frequency of use throughout the study. Patients should not apply the moisturizer or 
sunscreen or combination of them or wear make-up during study visits as it may interfere with the 
evaluator’s assessments. 
All concomitant therapies used during the study must be recorded on the Concomitant Therapy 
electronic case report form (eCRF). 
Therapies (medication and non-medication therapies) not restricted by the protocol may be used 
during the study for the treatment or prevention of disease or to maintain good health. Vitamins 
and mineral supplements are permitted at dosages considered by the investigator as reasonable for 
maintaining good health. Non-prohibited chronic therapies being used at Baseline (Visit 2) may 
be continued. Patients may use systemic anti-inflammatory agents [i.e., NSAIDs (ibuprofen or 
aspirin) for pain relief] as needed (with no more than 7 days of consecutive use) throughout the 
study. Prophylactic use of low dose aspirin (81 mg) is allowed. Patients may use acetaminophen 
for pain relief, as needed throughout the study. 
Any changes in concomitant therapies during the study must be recorded on the Concomitant 
Therapy form at each visit. The reason for any change in concomitant therapies should be reported 
as, or in conjunction with, an adverse event except as noted below: 
• Prophylactic therapies, such as vaccines, must be recorded on the Concomitant Therapy 
form, but the reasons for these therapies should not be reported as adverse events. 
• Changes in therapy for pre-existing conditions that are not related to a worsening of the 
condition must be reported on the Concomitant Therapy form, but the reasons for these 
changes should not be reported as adverse events. The condition must be reported in the 
Medical History. 
If a patient receives prohibited treatment during the study, the patient may be allowed to continue 
in the study at the discretion of the investigator and Sponsor / Medical Monitor. 
Patients should avoid UV exposure by sun bathing or tanning parlors. 
12.5. 
Precautions 
The following precautions are to be taken during this study: 


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1. Patients should avoid contact of the study product with the eyes, mouth, and lips or on any cuts 
or broken skin. In case of accidental exposure, the eyes should be rinsed with plenty of water. 
2. The study product should not be applied to cuts, abrasions, eczematous or sunburned skin. 
3. Patients should wash hands before and after applying study product. 
4. Patients should allow the treated area to completely dry for at least 30 minutes after applying 
the study product to avoid spreading it on other areas of the face (e.g., eyes, ears, neck, etc.) 
and pillow cases. 
5. The study product should be spread evenly in a thin layer on each area of the face (chin, left 
cheek, right cheek, nose, left forehead and right forehead); excessive rubbing must be avoided. 
6. The study product should not be applied more than once daily and patients should not use more 
than the recommended amount. 
7. Patients should not wash their face more than 2 or 3 times a day. 
8. Facial makeup (non-medicated) may be applied according to the patient’s normal daily routine 
(but not prior to 30 minutes after study product application). 
9. Patients should not apply moisturizers, make-up, creams, lotions, powders or any topical 
product they do not routinely use on their face 
10. Patients should not cover the treated area with a bandage (occlusive dressing) or other types of 
dressing after applying the study product. 
11. Patients should limit sun exposure, including sunlamps (non-prescription UV light sources); 
avoid tanning beds/booths/parlors and sauna while using the study product. 
12. Patient should use moisturizer with SPF supplied by the Sponsor or from study-approved list 
product and protective apparel (e.g. wide- brimmed hat) when outdoors. Patients should wait 
approximately 30 minutes after study product is applied on the face before applying a 
sunscreen. Weather extremes, such as wind or cold, may be irritating to patients receiving 
treatment. 
13. UVA/UVB treatments are also prohibited. 
14. Patients must not wear make-up to any study visits, so as not to interfere with the evaluations. 
If a patient comes to his/her visits with make-up on his/her face, the patient will be allowed to 
wash his/her face with a non-medicated cleanser and must wait at least 30 minutes before any 
study evaluation is made by the Principal Investigator (PI) or Sub-Investigator (Sub-I). 
15. Patients should consult the investigator with any questions regarding concomitant medications. 
16. Abrasive cleansers or washes, alcoholic toners, astringents are prohibited throughout the study. 
17. “Waxing” as a depilatory method should be avoided on skin treated with study product. 
18. Patients should be informed that local skin reactions [dryness, burning/stinging, pruritus 
(itching), scaling/peeling] may occur. 
19. Patients should minimize or not significantly alter consumption of any foods and beverages 
that might provoke erythema, flushing, and blushing (including spicy food, alcoholic 
beverages, and thermally hot drinks, including hot coffee and tea) throughout the study. 


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13. 
STUDY PROCEDURES 
13.1. 
Study Patient Identification 
When the patient signs the informed consent, he/she will be assigned a three (3)-digit patient 
number. The complete patient ID will consist of the 3-digit site number followed by the 3-digit 
patient number: e.g., 
(first patient screened at site 
. This number will remain with the 
patient for the duration of the study and will not be reassigned to another patient should the patient 
screen fail. 
13.2. 
Screen Failure and Discontinuation Criteria 
A screen failure is a patient who is not randomized/enrolled in the study due to ineligibility, after 
signing an Informed Consent Form, and would not have received study product. The Informed 
Consent Form signed by the patient should be kept with the source document for patients who do 
not pass the screening procedures. The documentation should include identification of the 
eligibility criterion or criteria that were and were not met. The patient should not be re-screened 
for this study without Sol-Gel’s approval. 
Although encouraged to complete the study whenever possible, patients are free to discontinue 
their participation in this study at any time and for any reason without prejudice. A patient may 
be withdrawn from the study prior to study completion for any of the following reasons: 
• Investigator opinion that it is not in the patient’s best interest to continue. 
• Patient Request /Withdraw Consent – Whenever the patient decides it is in his/her best 
interest to withdraw. 
• Lack of Efficacy/ Worsening of Condition. 
• Adverse Event – when the investigator thinks it’s in the patient’s best interest 
• Lost to Follow-up – Documentation confirmed at minimum by two phone calls and 
certified letter. Every effort should be made to capture an explanation for the lost-to follow- 
up event. 
• Protocol Violation – When requirements of the protocol are not respected, especially when 
patient safety is concerned. 
• Pregnancy. 
• Unblinding of study product. 
Study staff should make efforts to encourage patients to complete the study on time. If a patient 
prematurely withdraws during the study, every effort should be made to complete at least the 
Week 12/End of Study assessments. 
In the case of patients who discontinue due to an Adverse Event, the Investigator will conduct 
follow-up contacts with the patient until the Investigator, Sponsor and Medical Monitor agree the 
event is satisfactorily resolved and/or stabilized. 
Patients discontinued early from the study shall not be replaced. 


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13.3. 
Patient Screening and Enrollment 
The study personnel will review the IRB approved informed consent form with each patient and 
give the patient an opportunity to have all questions answered before proceeding. The consent 
form must be signed by each patient before the patient is enrolled into the study. A copy of the 
signed consent will be given to every patient (or legally authorized representative) and the original 
will be maintained with the patients’ records. 
Patients that require a wash-out of more than 30 days from their initial informed consent/assent 
signing must be re-consented before any further study procedures can begin. 
13.4. 
Assignment of Randomization 
The patient randomization schedule will be a permuted block design stratified by investigational 
site. Blocks will be composed of 3 treatment assignments in a ratio of 2:1 study product and 
vehicle, respectively. Complete blocks from the randomization schedule will be allocated to 
investigational sites as they randomize patients. Patients will be randomized through the IWRS 
and assigned a unique randomization ID indicating treatment group. The study product supplies 
will be packed in 4 pumps per kit and will be numbered in a scrambled randomized method. The 
kits will be dispensed by the IWRS according to the randomized treatment group. 
The first supplied pump in each kit is marked A (e.g. number of pump within a kit is XXXXA), at 
Visit 4/ Week 4 the patient will return the pump and will be dispensed with the next pump which 
is marked B. At Visit 5/ Week 8, the patient will return the pump and will be dispensed with a 
pump marked C. Pump marked as D may be dispensed to patients who lost/damaged/ran-out of 
study product. 
13.5. 
Demographics/Medical   History 
A demographic profile and complete medical history will be recorded prior to starting study 
product. The medical history will include a complete review of all current diseases and their 
respective treatments. 
13.6. 
Concomitant   Medications 
Concomitant medications and any medications taken in the 30 days prior to signing informed 
consent will be recorded as prior/concomitant medications (using their generic name, if known) 
with the corresponding indication. The medications to be recorded will include prescription and 
over-the-counter (OTC) medications and dietary supplements. All medications taken on either a 
regular or “prn” basis, including vitamins, aspirin and acetaminophen, should be recorded on this 
page prior to commencing the use of the study product. 
13.7. 
Physical Examination 
The investigator, sub-investigator or appropriately delegated and qualified designee will perform 
a brief physical examination, prior to the patient starting study product. The exam will include 
heart, lung, abdomen evaluation as well as recording height, weight and vital signs. Vital signs 
are to include sitting blood pressure, oral temperature, heart rate and respiratory rate. 


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13.8. 
Urine Pregnancy Test 
Females of childbearing potential (excluding women who are surgically sterilized or post-
menopausal for at least 2 years), in addition to having a negative urine pregnancy test, must be 
willing to use an acceptable form of birth control during the study. An investigator could repeat the 
pregnancy test at any time during the study if there is any suspicion or possibility that the patient 
is pregnant. Urine pregnancy test will also be conducted starting at Visit 1/Screening and at each 
visit [Baseline, Weeks 2, 4, 8 and 12 (End of Study)]. For the purpose of this study, the 
following are considered acceptable methods of birth control: intrauterine device (IUD); 
hormonal (injections, implants, transdermal patch, vaginal ring); abstinence; oral contraceptives; 
female condom; diaphragm with spermicides; cervical cap with spermicides; contraceptive 
sponge. 
Patients entering the trial that are on hormonal contraceptives must have been on this method for 
at least 3 months (90 days) prior to the trial and continue the method for the duration of the trial. 
Patients who had used hormonal contraception and stopped must have stopped no less than 3 
months prior to Baseline. Patients entering the study who had an Essure procedure must have had 
this procedure at least 3 months prior to the study and have undergone an Essure confirmation test 
to ensure its efficacy. A sterile sexual partner is not considered an adequate form of birth control. 


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13.9. 
Study Flow Chart 
 
Procedures 
Visit 11 
Visit 22 
Visit 32 
Visit 42 
Visit 52 
Visit 62,3 
(EOT4/ 
EOS5) 
Name of Visit 
Screening 
-35 – 0 
Baseline 
Day 1 
Week 2 
Day 15 
Week 4 
Day 29 
Week 8 
Day 57 
Week 12 
Day 85 
Visit window 
± 3 days 
± 3 days 
± 3 days 
± 4 days 
Informed Consent 
X 
Demographics 
X 
Medical History/Previous Therapies 
X 
X 
Brief Physical Examination 
X 
X 
Inclusion/Exclusion Criteria 
X 
X 
Urine Pregnancy Test6 
X 
X 
X 
X 
X 
IGA 
X 
X 
X 
X 
X 
X 
Inflammatory Lesion Counts 
X 
X 
X 
X 
X 
X 
Assessment of Eligibility 
X 
Rosacea Erythema Assessment 
X 
X 
X 
X 
X 
Telangiectasia Assessment 
X 
X 
X 
X 
X 
Randomization 
X 
Cutaneous Safety Assessment and 
Local Tolerability Assessments 
X 
X 
X 
X 
X 
Administer/ Review Patient 
Instructions 
X 
X 
X 
X 
Weigh Study Product 
X 
X 
X 
X 
Study Product Dispensed 
X7 
X 
X 
Provide Cleanser and 
Moisturizer/Sunscreen8 
X 
Diary Card dispensed 
X 
X 
X 
Study Product Collected 
X 
X 
X 
Diary Card collected 
X 
X 
X 
Patient Compliance Reviewed (Diary) 
X 
X 
X 
X 
Concomitant Therapy and Medication 
History Reviewed 
X 
X 
X 
X 
X 
X 
Adverse Events 
X9 
X 
X 
X 
X 
X 
Photography (select site(s)) 
X 
X 
X 
X 
X 
Complete PAPSS, PAPI and PGI-S10,11 
X 
X 
X 
X 
X 
Complete PGI-C, PGI-TS and 
PGI-SE12 
X 
X 
X 
X 
Complete RosaQoL13 
X 
X 
 
 
1 If no washout is needed, Visits 1 and 2 may occur on the same day. If a washout is needed, Visit 2 must occur within 35 days of Visit 1. 
2 All visit dates are in reference to Baseline, e.g., Visit 5 occurs 8 weeks ± 3 days after Baseline Visit. 
3 All Week 12 procedures should be completed for Patients who terminate early. 
4 EOT – end of treatment 
5 EOS – end of study 
6 All women of childbearing potential 
7 Dispense one pump of test material at the Baseline Visit and dispense additional pump at Visit 4 and 5. 
8  Or study approved cleanser and moisturizer 
9 Adverse events after ICF is signed will be collected. 
10 PAPSS is Patient Assessment of Papulopustular rosacea Signs and Symptoms; PAPI is Patient Assessment of Papulopustular rosacea Impacts; 
PGI-S is Patient Global Impression of Symptom Severity. Questionnaires will be completed prior to PI assessment. 
11 In case Screening Visit and Baseline are at the same day, the PRO questionnaires should be completed prior to screening procedures. 
12 PGI-C is Patient Global Impression of Change; PGI-TS is Patient Global Impression of Treatment Satisfaction; PGI-SE is Patient Global 
Impression of Treatment Side-Effects. Questionnaires will be completed prior to PI assessment. 
13 RosaQoL is a Rosacea Quality of Life questionnaire 


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13.10. Screening Visit (Visit 1) 
If no washout is needed, Visits 1 (Screening) and 2 (Baseline) may occur on the same day. If a 
washout is needed, Visit 2 (Baseline) must occur within 35 days of Visit 1 (Screening). The 
following procedures will be conducted at this visit: 
• Obtain a signed and dated, written informed consent for all patients prior to any study 
related procedures. 
• Confirm the patient meets the inclusion/exclusion criteria as outlined in Section 12.2 and 
Section 12.3. 
• Record any adverse events. 
• Perform a urine pregnancy test for all females of childbearing potential (see Section 12.2); 
the results must be negative for the patient to be enrolled. 
• Report the medical history and demographics for the patient. 
• Record the patient’s concomitant medications and/or therapies on Concomitant Therapy 
form as outlined in Section 13.8. 
• Perform investigator’s global assessment (IGA) to determine eligibility (See Section 14.1) 
• Perform facial inflammatory lesion counts to determine eligibility: (Section 14.2). 
• Determine if patient requires washout and schedule Baseline Visit. 
13.11. 
Baseline Visit (Visit 2, Day 1) 
The following procedures will be conducted at this visit: 
• Confirm the patient continues to meet the inclusion/exclusion criteria. 
• Update since Screening Visit the medical history for the patient. 
• Ask the patient to complete PAPSS, PAPI questionnaire (see Appendix 2 and Appendix 3). 
Patient will also complete the PGI-S questionnaire (see Appendix 4). The PAPSS, PAPI 
and PGI-S questionnaires are to be completed prior to any other assessments or procedures 
as described in Section 14.5. In case Screening Visit and Baseline are at the same day, the 
PRO questionnaires should be completed prior to screening procedures. 
• Ask the patient to complete Rosacea Quality of Life (RosaQoL) questionnaire (see 
Appendix 8). 
• Perform brief physical examination as described in Section 13.7. 
• Perform a urine pregnancy test for all females of childbearing potential (see Section 13.8); 
the results must be negative for the patient to be enrolled. 
• Update since screening the patient’s concomitant therapies on Concomitant Therapy form 
as outlined in Section 13.6. 
• Perform the efficacy evaluations including the Investigator’s Global Assessment, 
inflammatory lesion counts, rosacea erythema assessment, and telangiectasia assessment 
described in Sections 14.1 to 14.4. Every effort shall be made to have the same investigator 
perform the Baseline and Visit 6/Week 12 evaluations for the same patient. 
• Perform Cutaneous Safety Assessment and Local Tolerability Assessment as described in 
Sections 16.1 to 16.2. 


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• Take standardized photography of face (at selected sites, see separate photographic manual 
for instructions) as described in Section 15. 
• Weigh the study product before dispensing. 
• Instruct the patient on the study product application as described in Appendix 1. Pump 
usage will be demonstrated by the site personnel on a sample pump at the clinic to help 
assure the patient understands the procedure. 
• Dispense the Patient Instruction Sheet and Diary Card to the patient (see Appendix 1 for 
appropriate instructions for study patients). 
• Record any adverse events. 
• Instruct the patient that throughout the study overexposure of the face to sunlight should 
be avoided. Instruct the patient to use the sponsor-provided cleanser and 
moisturizer/sunscreen; any exposure to tanning beds must be avoided during the study. 
• Perform randomization for study product by using IWRS. 
• Dispense study product pump to patient. 
• Remind patient to not wear make-up to all subsequent visits 
• Schedule the next study visit. 
13.12. 
On treatment (Visit 3) – Week 2, Day 15 (± 3 days) 
The following procedures will be conducted at this visit: 
• Ask the patient to complete PAPSS, PAPI questionnaire (see Appendix 2 and Appendix 3). 
Patient will also complete the PGI-S questionnaire (see Appendix 4), PGI-C (see 
Appendix 5), PGI-TS (see Appendix 6) and PGI-SE (see Appendix 7). The PAPSS, PAPI, 
PGI-S, PGI-C PGI-TS and PGI-SE questionnaires are to be completed prior to any other 
assessments or procedures as described in Section 14.5. 
• Observe and query the patient in a non-directive fashion about any adverse events since 
the previous study visit. Initiate or update the appropriate adverse event form as required. 
• Query the patient about any changes in concomitant therapies since the previous study visit 
and update the Concomitant Therapy eCRF as required. 
• Perform the efficacy evaluations including the Investigator’s Global Assessment, 
inflammatory lesion counts, rosacea erythema assessment, and telangiectasia assessment 
described in Sections 14.1 to 14.4. 
• Perform Cutaneous Safety Assessment and Local Tolerability Assessment as described in 
Sections 16.1 to 16.2. 
• Take standardized photography of face (at selected sites, see separate photographic manual 
for instructions) as described in Section 15. 
• Review the patient’s compliance with the study requirements (review patient diary). 
• Record number of missed doses on the appropriate eCRF page. 
• Review the study product application instructions with the patient. 
• Schedule/confirm the next study visit. 


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13.13. 
On-treatment Visits (Visits 4 and 5) – Weeks 4 and 8, Days 29 and 57 (± 3 days) 
The following procedures will be conducted at these visits: 
• Ask the patient to complete PAPSS, PAPI questionnaire (see Appendix 2 and Appendix 3). 
Patient will also complete the PGI-S questionnaire (see Appendix 4), PGI-C (see 
Appendix 5), PGI-TS (see Appendix 6) and PGI-SE (see Appendix 7). The PAPSS, PAPI, 
PGI-S, PGI-C PGI-TS and PGI-SE questionnaires are to be completed prior to any other 
assessments or procedures as described in Section 14.5. 
• Observe and query the patient in a non-directive fashion about any adverse events since 
the previous study visit. Initiate or update the appropriate adverse event form as required. 
• Query the patient about any changes in concomitant therapies since the previous study visit 
and update the Concomitant Therapy eCRF as required. 
• Perform a urine pregnancy test for all females of childbearing potential (see Section 12.2). 
• Perform efficacy evaluations: IGA, inflammatory lesion counts, rosacea erythema 
assessment, and telangiectasia assessment described in Sections 14.1 to 14.4. 
• Perform Cutaneous Safety Assessment and Local Tolerability Assessment as described in 
Sections 16.1 to 16.2. Take standardized photography of face (at selected sites, see 
separate photographic manual for instructions) as described in Section 15. 
• Review the patient’s compliance with the study requirements; collect and review the 
Patient Diary Card. 
• Dispense a Diary Card to the patient 
• Record number of missed doses on the appropriate eCRF page. 
• Review the study product application instructions with the patient. 
• Collect and weigh returned study product pump. 
• Weigh and dispense the next pump of study product. 
• Schedule/confirm the next study visit. 
13.14. 
On-treatment (Visit 6) – Week 12, Day 85 (± 4 days) or End of Treatment or Early 
Termination 
The following procedures will be conducted at this visit: 
• Ask the patient to complete PAPSS, PAPI questionnaire (see Appendix 2 and Appendix 3). 
Patient will also complete the PGI-S questionnaire (see Appendix 4), PGI-C (see 
Appendix 5), PGI-TS (see Appendix 6) and PGI-SE (see Appendix 7). The PAPSS, PAPI, 
PGI-S, PGI-C PGI-TS and PGI-SE questionnaires are to be completed prior to any other 
assessments or procedures as described in Section 14.5. 
• Ask the patient to complete Rosacea Quality of Life (RosaQoL) questionnaire (see 
Appendix 8). 
• Observe and query the patient in a non-directive fashion about any adverse events since 
the previous study visit. 
• Query the patient about any changes in concomitant therapies since the previous study visit 
and update the Concomitant Therapy eCRF. 
• Perform physical examination as described in Section 13.7. 


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• Perform efficacy evaluations: IGA, inflammatory lesion counts, rosacea erythema 
assessment, and telangiectasia assessment described in Sections 14.1 to 14.4. The 
evaluator who performed the Baseline evaluations should perform all subsequent 
evaluations for a patient. when this is not possible, it is recommended that another 
delegated evaluator with overlapping experience with the patient may perform the 
evaluations. 
• Perform Cutaneous Safety Assessment and Local Tolerability Assessment as described in 
Sections 16.1 to 16.2. 
• Take standardized photography of face (at selected sites, see separate photographic manual 
for instructions) as described in Section 15. 
• Review the patient’s compliance with the study requirements; collect and review the 
Patient Diary Card. 
• Record number of missed doses and report the last date the patient applied the study 
product. 
• Perform a urine pregnancy test for all females of childbearing potential (see Section 12.2). 
• Collect and weigh the study product. 
• Complete the End of Study/Study Termination eCRF. 
• Discharge the patient from the study. 


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14. 
CLINICAL OUTCOME ASSESSMENTS 
The determination of efficacy will be based on investigator evaluations of the signs and symptoms 
of rosacea. Evaluators must be a physician or have appropriate documented experience and 
training. Every effort will be made to ensure appropriate training is provided to the investigators 
for consistent diagnosis and evaluation of rosacea. 
For consistency of evaluations, the same designated evaluator who performs the Baseline 
assessments shall perform the assessments at Visit 6/Week 12; when this becomes impossible, 
another delegated evaluator may perform the assessments. 
14.1. 
Investigator Global Assessment (IGA) 
The Investigator Global Assessment (IGA) will be performed at Screening/Baseline, Weeks 2, 4, 
8 and 12 (End of Study) visits. 
Patients are eligible for enrollment if they have facial rosacea with a global severity of a 3 
(moderate) or a 4 (severe) on the IGA scale. 
The IGA scale provided in Table 1 will be used to describe the severity grade and subsequent 
score: 
 
Table 1: Investigator Global Assessment (IGA) Scale 
 
Grade 
Description 
0 – Clear 
Skin clear of inflammatory papules or pustules 
1 – Almost Clear 
Very few small papules or pustules and very mild dull erythema is present 
2 – Mild 
Few small papules or pustules and mild dull or light pink erythema is present 
3 – Moderate 
Several to many small or larger papules or pustules and moderate light to bright red 
erythema is present 
4 – Severe 
Numerous small and/or larger papules or pustules and severe erythema that is bright red to 
deep red is present 


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14.2. 
Inflammatory Lesion Counts 
Inflammatory lesions (papules and pustules) counts will be performed at Screening, Baseline, 
Weeks 2, 4, 8 and 12 (End of Study) visits. At Screening/Baseline patients must have at least 15 
and not more than 70 inflammatory lesions (papules, pustules) on the face. 
Papules and pustules are defined as follows: 
• Papule – A solid, elevated inflammatory lesion equal to or less than 5 mm in diameter 
• Pustule – An elevated inflammatory lesion equal to or less than 5 mm in diameter, contains 
pus (yellow-white exudate) 
Nodules will not be included in the inflammatory lesion count and are defined as: 
• Nodule/Cyst – Palpable solid inflammatory lesion, greater than 5 mm in diameter, has 
depth, not necessarily elevated 
14.3. 
Erythema Severity Assessments 
Erythema is defined as redness of the skin. It will be scored on a scale of 0 (none) to 3 (severe) at 
Baseline, Weeks 2, 4, 8, and 12 (End of Study) visits. The Rosacea Erythema Assessment Scale is 
provided in Table 2. 
 
 
Table 2: Rosacea Erythemaa Assessment Scale 
 
Grade 
Description 
0 – None 
No visible erythema 
1 – Mild 
Slight erythema (dull or light pink), centro-facial 
2 – Moderate 
Definite erythema (light to bright red), either centro-facial or generalized to whole face 
3 – Severe 
Severe erythema (bright red to deep red), either centro-facial or generalized to whole face 
a Generalized erythema associated with rosacea 
 
 
14.4. 
Telangiectasia Assessment 
Facial telangiectasia will be evaluated on a scale of 0 to 3 at Baseline and Weeks 2, 4, 8 and 12 
(End of Study) visits; the Telangiectasia is provided in Table 3 
 
Table 3: Telangiectasia Assessment Scale 
 
Grade 
Description 
0 – None 
No Telangiectasia 
1 – Mild 
Only a few fine vessels discernible, involves approximately 10% or less of facial area 
2 – Moderate 
Multiple and more prominent fine vessels, involves approximately 10 – 30% of the facial 
area 
3 – Severe 
Numerous and prominent fine and/or courser vessels, involves more than 30% of the facial 
area 


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14.5. 
Patient Reported Outcomes (PRO) 
There are six PRO questionnaires to be administered in the study and each is summarized below. 
Each will be administered to all patients during the designated study visits with instruction from 
the Study Staff that they be completed: 
• Only by the patient without amendment or interpretation of the patient’s response by a 
clinician or anyone else. 
• Prior to any other assessments or procedures. 
In the event the patient skips any questionnaire items; the Study Staff will ask the patient to 
complete the form. The PRO questionnaire data will be entered into EDC, and a copy will be 
placed with the patient source at the site according to the ICH-GCP guideline (4.9.5). 
The PAPSS (Appendix 2): The PAPSS is a 4-item questionnaire that asks patients to assess the 
severity of their rosacea symptoms (burning, itching, redness, and bumps) in the 24 hours prior to 
assessment on an 11-point numeric rating scale (NRS) ranging from “0=none” to “10=worst 
possible symptom”. The questionnaire can be completed in less than one minute and is 
administered via pen-and-paper at the Baseline visit and site visits at Weeks 2, 4, 8 and 12 (End 
of Study) or early termination. Items can be scored individually as well as together to form a total 
score. In the present context, within visit scores from Items 1 (burning), 2 (itching), and 4 (bumps) 
are summed and averaged to create a total score that will be used to evaluate efficacy hypotheses. 
The PAPI (Appendix 3): The PAPI is a 3-item questionnaire that asks patients to assess the 
papulopustular rosacea related embarrassment, self-consciousness, and frustration in the 7 days 
prior to assessment on an 11-point NRS ranging from 0 [“not (concept) at all”] to 10 [“extremely 
(concept)”]. The questionnaire can be completed in less than one minute and is administered via 
pen-and-paper at the Baseline visit and site visits at Weeks 2, 4, 8 and 12 (End of Study) or early 
termination. Items can be scored individually as well as together to form a total score. 
PGI-S (Appendix 4): The PGI-S is a single item questionnaire that asks respondents to describe 
the severity of their rosacea symptoms “right now” (i.e., at the present moment) on a five-point 
verbal response scale ranging from “Clear” (face is clear, no redness) to “Severe” (face has 
numerous small and/or large bumps, severe redness). Patients are encouraged to look in a mirror 
to help with their response and the questionnaire can be completed in less than 30 seconds. The 
PGI-S is administered via pen-and-paper at the Baseline visit and site visits at Weeks 2, 4, 8 and 
12 (End of Study) or early termination. Though data generated from the PGI-C can be supportive 
of efficacy hypotheses, the primary purpose of the tool is to support anchor-based analyses that 
will inform how researchers may interpret the meaning of change in the primary and secondary 
assessments. 


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PGI-C (Appendix 5): The PGI-C is a single item questionnaire that asks respondents to describe 
the change they have noticed in their rosacea symptoms since the start of the study a 7-point VRS 
ranging from “Very much improved” to “Very much worse”. Patients are encouraged to look in a 
mirror to help with their response and the questionnaire can be completed in less than 30 seconds. 
The PGI-C is administered via pen-and-paper at the site visits at Weeks 2, 4, 8 and 12 (End of 
Study) or early termination. Though data generated from the PGI-C can be supportive of efficacy 
hypotheses, its primary purpose is to support anchor-based analyses that will inform how 
researchers may interpret the meaning of change in the primary and secondary assessments. 
PGI-TS (Appendix 6): The PGI-TS is a single item questionnaire that asks respondents to describe 
how satisfied they are “right now” with the rosacea treatment administered as part of the study on 
a 5-point VRS ranging from “I am very satisfied” to “I am very dissatisfied”. The questionnaire 
can be completed in less than 30 seconds and is administered via pen-and-paper at the site visits 
at Weeks 2, 4, 8 and 12 (End of Study) or early termination. Though data generated from the 
PGI-TS can be used for other purposes, its primary purpose is to support anchor-based analyses 
that will inform how researchers may interpret the meaning of change in the primary and secondary 
assessments. 
PGI-SE (Appendix 7): The PGI-SE is a single item questionnaire that asks respondents to describe 
how bothered they are “right now” with the rosacea treatment administered as part of the study on 
a 5-point VRS ranging from “I am not bothered” to “I am extremely bothered”. The questionnaire 
can be completed in less than 30 seconds and is administered via pen-and-paper at the site visits 
at Weeks 2, 4, 8 and 12 (End of Study) or early termination. Though data generated from the 
PGI-TSE can be used for other purposes, its primary purpose is to support anchor-based analyses 
that will inform how researchers may interpret the meaning of change in the primary and secondary 
assessments. 
14.6. 
Rosacea Quality of Life (RosaQoL) 
There is a symptom subscale with seven questions (items 2, 6, 9, 16, 17, 18 and 19 in Appendix 
8) , a functional subscale with 3 questions (items 13, 15 and 21 in Appendix 8) and an emotion 
subscale with 11 questions (items 1, 3, 4, 5, 7, 8, 10, 11 12, 14 and 20 in Appendix 8) to be 
administered in the study. The questionnaire will be administered to all patients during the 
designated study visits with the appropriate instructions from the Study Staff. The questionnaire 
should be completed: 
• Only by the patient without amendment or interpretation of the patient’s response by a 
clinician or anyone else. 
• After completion of the Patient Reported Outcomes (PRO) questionnaires 
In the event the patient skips any questionnaire items; the Study Staff will ask the patient to 
complete the form. The QoL questionnaire data will be entered into the EDC system by the Study 
Staff, and a copy will be placed with the patient source documents at the site according to the 
ICH-GCP guideline (4.9.5). 
All items should be scored for the following answers: 
• Never: 1 
• Rarely: 2 
• Sometimes: 3 


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• Often: 4 
• All the time: 5 
 
The Site Staff and anyone else provided with a copy of the RosaQoL instrument for the purpose 
of the study will be instructed that the RosaQoL instrument is protected by Common Law 
copyright. No part of this may be reproduced or transmitted in any form or by any means, now 
known or to be invented or adapted, for purpose of financial gain or profit. 
An overall total score will be calculated; this score will be the unweighted mean of all RosaQoL 
questions. In addition to the total score, each subscale (symptom, functional and emotion) will 
also have a score calculated; these scores will the unweighted mean of the group of questions that 
comprise the subscale. Further details on the handling of missing responses and calculation of the 
subscale scores will be detailed in the Statistical Analysis Plan (SAP). 


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15. 
PHOTOGRAPHY 
Standardized photography of facial rosacea at Baseline, and at the site visits at Weeks 2, 4, 8 and 
12 (End of Study) will be performed at select sites. These photographs will be optional for patients 
at the selected sites and will not be used for efficacy assessment purposes. Participating 
investigators shall refer to separate photographic manual for instructions. 


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16. 
SAFETY EVALUATIONS 
Safety will be assessed by monitoring incidence of Cutaneous Safety Assessment, Local 
Tolerability Assessment and adverse events reporting; at Baseline, at all treatment and end-of-
treatment visits. 
16.1. 
Cutaneous Safety Assessments 
The evaluator will assess local application site cutaneous reactions by rating the dryness and 
scaling at the Baseline visit and site visits at Weeks 2, 4, 8 and 12 (End of Study) or unscheduled 
visits. The evaluator will determine the score for each of these variables by direct evaluation. The 
definitions of grades provided in Table 4 will be applied to these evaluations. The Cutaneous 
Safety Assessment of dryness and scaling will be made by the investigator at the time of the visit. 
 
Table 4: Cutaneous Safety Assessment Scale 
 
Grade 
Description 
Dryness 
0 – None 
No dryness 
1 – Mild 
Slight but definite dryness 
2 – Moderate 
Moderate dryness 
3 – Severe 
Marked dryness and/or cracking 
Scaling 
0 – None 
No scaling 
1 – Mild 
Barely perceptible scaling 
2 – Moderate 
Obvious but not profuse scaling 
3 – Severe 
Heavy scale production and/or peeling 
 
 
Application site reactions (dryness and scaling) are not to be recorded as adverse events unless 
they result in either: 
• The temporary discontinuation of the study product. 
• The discontinuation of the patient from the study. 
• The use of a new concomitant medication in order to treat this event. 
Any other application site reaction not listed above (such as pain) should be recorded as adverse 
events in the source document and eCRFs. 


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16.2. 
Local Tolerability Assessments 
The evaluator will assess local application site tolerability by rating the itching and 
burning/stinging at the Baseline visit and site visits at Weeks 2, 4, 8 and 12 (End of Study) or 
unscheduled visits. The evaluator will determine the score for each of these variables by asking 
the patient to grade their experience over the past 24 hours. The definitions of grades provided 
in Table 5 will be applied to these evaluations. The Local Tolerability Assessment evaluations of 
itching and burning/stinging will be made by the investigator at the time of the visit. 
 
Table 5: Local Tolerability Assessment Scale 
 
Grade 
Description 
Itching 
0 – None 
No itching 
1 – Mild 
Slight itching, not really bothersome 
2 – Moderate 
Definite itching that is somewhat bothersome 
3 – Severe 
Intense itching that may interrupt daily activities and/or sleep 
Burning/Stinging 
0 – None 
No burning/stinging 
1 – Mild 
Slight burning/stinging sensation; not really bothersome 
2 – Moderate 
Definite warm, burning/stinging sensation that is somewhat bothersome 
3 – Severe 
Hot burning sensation that causes definite discomfort and may interrupt daily activities or 
sleep 
 
 
Application site reactions (itching and burning/stinging) are not to be recorded as adverse events 
unless they result in either: 
• The temporary discontinuation of the study product. 
• The discontinuation of the patient from the study. 
• The use of a new concomitant medication in order to treat this event. 
Any other application site reaction not listed above should be recorded as adverse events in the 
source document and eCRFs. 


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17. 
ADVERSE EVENTS 
17.1. 
Departure from the Protocol for  Individual Patients 
When an emergency occurs requiring a departure from the protocol for a patient, departure will be 
only for that patient. In such circumstances, the investigator or other physician in attendance will 
contact the Medical Monitor or the Sponsor by telephone and follow up with a written description 
as soon as possible.  The overseeing IRB should also be notified. 
17.2. 
Definitions 
An adverse event (AE) is defined as any untoward medical occurrence in a patient administered a 
medicinal product and which does not necessarily have to have a causal relationship with this 
treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or 
disease temporally associated with the use of a medicinal product, whether or not considered 
related to this medicinal product. 
A serious adverse event (SAE) is an adverse event that results in any of the following outcomes: 
• Death 
• Life-threatening event (i.e., the patient was, in the opinion of the investigator, at immediate 
risk of death from the event as it occurred. It does not include an event that, had it occurred 
in a more severe form, might have caused death) 
• Requires in-patient hospitalization or prolongs hospitalization 
• A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions 
• Congenital anomaly/birth defect 
• Other adverse events that may be considered serious based upon appropriate medical 
judgment, may jeopardize the patient and may require medical or surgical intervention to 
prevent one of the outcomes listed above. 
Immediately Reportable Adverse Events (IRAE) is any serious AE or any AE that necessitates 
discontinuation of study product, including pregnancy. 
Unexpected Adverse Event is any adverse drug experience, the specificity or severity of which is 
not consistent with the current approved product labeling (package insert) for the study product, 
the Investigator’s Brochure, or as described in the clinical protocol and consent materials. 
Intensity of Adverse Events are the maximum intensity of an AE during a day should be recorded 
on the eCRF. If the intensity of an AE changes over a number of days, then separate entries should 
be made having distinct onset dates for the changes in severity. 
• Mild - AEs are usually transient, requiring no special treatment, and do not interfere with 
patient’s daily activities. 
• Moderate - AEs typically introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities, but are usually ameliorated by simple therapeutic 
measures. 
• Severe - AEs interrupt a patient’s usual daily activity and traditionally require systemic 
drug therapy or other treatment. 


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17.3. 
Causal Relationship to Study product 
The following criteria should be used in assessing the apparent causal relationship of an AE to 
study product: 
Definitely - The AE: 
• follows a reasonable temporal sequence from study product administration 
• abates upon discontinuation of the study product (de-challenge) 
• is confirmed by reappearance of the reaction on repeat exposure 
Probably - The AE: 
• follows a reasonable temporal sequence from study product administration 
• abates upon discontinuation of the study product (de-challenge). 
• cannot be reasonably explained by the known characteristics of the patient’s state. 
Possible - The AE: 
• follows a reasonable temporal sequence from study product administration 
• but that could readily be produced by a number of other factors. 
Unlikely - The AE: 
• follows a reasonable temporal sequence from study product administration. 
• could have been produced by either the patient’s clinical state or by study product 
administration. 
Not related - The AE: 
• does not have a reasonable temporal association with the administration of study product 
• has some other obvious explanation for the event. 
17.4. 
Eliciting and Reporting of Adverse Events 
The investigator will periodically assess patients for the occurrence of adverse events. In order to 
avoid bias in eliciting adverse events, the patient or parent/legally authorized representative should 
be asked a non-specific question (e.g., “How have you been feeling since your last visit?”) to assess 
whether any AE has been experienced since the last visit. All adverse events (as defined in 
Section 17.2), either observed by the Investigator or one of his/her medical collaborators, or 
reported by the patient spontaneously, or in response to direct questioning, will be reported and 
documented in the source and the study reporting forms. When reporting an adverse event, the 
Investigator must assign a severity grade to each event and declare an opinion on the relatedness 
of the event to the study product or procedure. Serious or unexpected adverse events must be 
reported to the CRO within 24 hours of when the Investigator first learns of the occurrence of the 
event. 
Adverse events will be documented in the source document and recorded in a timely manner on 
case report forms. Adverse events that are identified at the last assessment visit (or the Early 
Termination Visit) must be recorded on the AE eCRF with the status of the AE noted. 


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Adverse event reporting begins from the signing of informed consent/assent. Study product-
related adverse events should be followed until resolved or 30 days after the final study 
treatment. Regardless the duration of the study, patients that exhibit serious adverse event (SAE), 
will be followed up until the SAE resolves, based on investigator’s medical judgment or are 
considered to be chronic (stabilized for at least 30 days). All events that are ongoing at this time 
will be recorded as ongoing on the eCRF. 
17.5. 
Expedited Reporting Responsibilities of the Study Center 
For any serious or unexpected adverse event, the Sponsor or its designee must be notified within 
24 hours of when the Investigator first learns of the occurrence of the event. Expedited reporting 
requirements for serious adverse events are described below. Adequate information must be 
collected with supporting documentation to complete a standard report for submission to Sol-Gel. 
The adverse event term on the AE eCRF and the SAE report should agree exactly. Special 
attention should be given to recording hospitalizations and concomitant medications. 
Patients with unresolved study or product-related adverse event(s) or serious adverse event(s) 
should be followed by the investigator until the events are resolved, events determined to be 
chronic or the patient is lost to follow-up. Resolution means the patient has returned to the Baseline 
state of health, or the investigator does not expect any further improvement or worsening of the 
adverse event. The investigator should continue to report any significant follow-up information 
to the sponsor up to the point that the event has resolved. Any serious adverse event reported by 
the patient to the investigator that occurs within 30 days after the last assessment, and are 
determined by the investigator to be reasonably associated with the use of the study product, should 
be reported to the sponsor within 24 hours of when the Investigator first learns of the occurrence 
of the event. 
When reporting a serious adverse event (SAE) the Investigator (or the Study Coordinator) will 
promptly report any serious adverse event or pregnancy to the Sponsor or its designee by telephone 
email, immediately after the investigator becomes aware of the event. An SAE form should be 
completed and sent by fax, email, or overnight courier to the Sponsor or its designee within 24 
hours of knowledge of the event by the site. In many cases, only preliminary information will be 
available. Appropriate follow up information should be sought (hospital discharge summaries, 
operative reports etc.) and a follow up SAE report form submitted. A designation of causality 
from the study product should always be included with a follow up report. Assess and report the 
causality of the event. 
17.6. 
Submitting an Expedited Safety Report to the IRB 
Once all supporting documentation is received for the reported event, the Medical Monitor, in 
conjunction with Sol-Gel, will determine if the safety report is eligible for expedited review. When 
expedited safety reporting to regulatory authorities is indeed required, the Investigator should 
review and update any newly available materials at once. Follow-up queries may be sent to the 
study center to further clarify the event. 


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The Sponsor, or its designee, is responsible for submitting reports of serious, unexpected related 
AEs to regulatory authorities on an expedited basis, according to the ICH E2A Guideline and to 
other regulatory authorities according to national and local regulations as required. The Sponsor, 
or its designee, is responsible for prompt submission to the IRB or EC of any expedited SAE 
reports submitted to regulatory authorities. All investigators participating in ongoing clinical 
studies will receive copies of the SAE reports submitted on an expedited basis to regulatory 
authorities 
17.7. 
SAE & AEs Requiring Discontinuation of Study Drug, including Pregnancies 
ANY SAE, WHICH OCCURS AFTER A PATIENT HAS ENTERED THE STUDY, WHETHER 
OR NOT RELATED TO STUDY PRODUCT, MUST BE REPORTED TO THE SPONSOR OR 
ITS DESIGNEE IMMEDIATELY (WITHIN 24 HOURS) VIA TELEPHONE, EMAIL OR 
FACSIMILE. IF INITIALLY REPORTED VIA TELEPHONE, THIS MUST BE FOLLOWED-
UP BY A FACSIMILE OR EMAIL OF THE WRITTEN SAE REPORT WITHIN 24 HOURS 
OF THE CALL TO THE SPONSOR OR ITS DESIGNEE. 
Non-serious events that require discontinuation of study product (including laboratory 
abnormalities) should be reported to the Sponsor or its designee immediately and within 1 working 
day. 
Patients who discontinue due to experiencing study product-related adverse events should be 
followed clinically until their health has returned to baseline status, or until all parameters have 
returned to normal. It is expected that the investigator will provide or arrange appropriate 
supportive care for the patient. 
A patient who experiences a severe adverse event related to study product will be discontinued 
from the study, but, regardless of the duration of the study, patients that exhibit serious adverse 
event (SAE), will be followed up until the SAE resolves, based on investigator’s medical judgment 
or are considered to be chronic (stabilized for at least 30 days). For safety reporting instructions 
see SAE and Pregnancy Form Report Instructions. 
17.8. 
Pregnancy 
At the time, Principal Investigator or site personnel becomes aware that a study patient became 
pregnant following study participation, the Principal Investigator or designee will report the 
pregnancy immediately by phone and/or by faxing a completed Pregnancy Report to the Sponsor 
or its designee within one working day of being notified of the pregnancy report. 
The report will include the following elements: 
• Patient (mother’s) coded study identifier; 
• Date of patient’s last menstrual period; 
• Total accumulated dose of study treatment administered to date; 
• Date of study product administration. 
The investigator will follow the patient until completion of the pregnancy and must assess the 
outcome in the shortest possible time but not more than 30 days within completion of the 
pregnancy. 


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Upon delivery, miscarriage or abortion, the Principal Investigator or designee must forward a 
follow-up Pregnancy Report with any relevant information on the present condition of the fetus to 
the Sponsor or its designee, including: 
• Mother’s coded study identifier(s); 
• Gestational age at delivery, miscarriage or abortion; 
• Birth weight, gender, length and head circumference, if available; 
• Apgar scores recorded after birth, if available; 
• Any abnormalities. 
If the outcome of the pregnancy meets the criteria for immediate classification of an SAE (e.g., 
spontaneous or therapeutic abortion [any congenital anomaly detected in an aborted fetus is to be 
documented], stillbirth, neonatal death, or congenital anomaly), the investigator will report the 
event by phone and by faxing a completed SAE report form to the Sponsor or its designee within 
one working day of being notified of the pregnancy report. 
If the trial is completed before the outcome of the pregnancy is known, the Sponsor or its designee 
will assume the responsibility for following up on the pregnancy. The Sponsor or its designee will 
contact the Investigator or Study coordinator on or around the potential expected date of delivery 
to follow-up on the outcome of pregnancy and will also check on the status of the infant 8 weeks 
post-delivery. Upon awareness of the pregnancy outcome and known status of the infant following 
8 weeks of delivery, the investigator will complete the applicable pregnancy report forms and fax 
to the Sponsor or its designee within 1 day of being notified. 
17.9. 
Post Study Adverse Events 
17.9.1. 
Non-serious Adverse Events 
Adverse events that are identified at the last assessment visit (or the Early Termination Visit) must 
be recorded on the AE eCRF with the status of the AE noted. 
17.9.2. 
Serious Adverse Events 
Serious adverse events that are identified on the last assessment visit (or the Early Termination 
Visit) must be recorded on the AE eCRF page and reported to Sol-Gel according to the procedures 
outlined above. Patients with unresolved previously reported serious adverse events, or any new 
serious adverse events identified on the last assessment visit, should be followed by the 
investigator until the events are resolved, or the patient is lost to follow-up. Resolution means the 
patient has returned to the baseline state of health, or the investigator does not expect any further 
improvement or worsening of the adverse event. The investigator should continue to report any 
significant follow-up information to Sol-Gel up to the point that the event has resolved. Any 
serious adverse event reported by the patient to the investigator that occurs after the last 
assessment, and are determined by the investigator to be reasonably associated with the use of the 
study product, should be reported to Sol-Gel. 


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18. 
STUDY PRODUCTS / CLINICAL SUPPLIES 
18.1. 
Method of Treatment Assignment 
Patients who satisfy all the inclusion and none of the exclusion criteria will be randomized to one 
of two treatment arms. Randomization will be performed in the IWRS according to a computer-
generated randomization schedule. The randomization schedule will be generated by the 
unblinded statistician and uploaded to the IWRS. The randomization schedule will be maintained 
securely within the IWRS. Patients will be randomized to Encapsulated Benzoyl Peroxide 
Cream, 5%, or Vehicle Cream, once daily on a 2:1 basis for twelve (12) weeks. 
Once a patient is determined eligible for the study at the Baseline visit, the patient will be 
randomized to study product assignment by the IWRS. Each study product carton will contain 
four pumps of the same product; The first supplied pump in each kit is marked A (e.g. number of 
pump within a kit is XXXXA), at Visit 4/ Week 4 the patient will return the pump and will be 
dispensed with the next pump which is marked B. At Visit 5/ Week 8, the patient will be dispensed 
with a pump marked C. The pump marked as D is a backup pump. The patient number will be 
added to both parts of the kit label (open part and tear-off label and to the pump label). 
18.2. 
Formulations 
Study Product name: 
Encapsulated Benzoyl Peroxide Cream, 5% 
Sponsor name: 
S5G4T-1 
Active ingredients: 
benzoyl peroxide 
Inactive ingredients: 
see list below 
Placebo Product: 
Vehicle Cream (for study product) 
Sponsor name: 
S5G4T-2 
Active ingredients: 
none 
Inactive ingredients: 
see list below 
The inactive ingredients include: silicon dioxide, cetrimonium chloride, polyquaternium-7, lactic 
acid, hydrochloric acid, polyoxyl 100 stearate, cetyl alcohol, cyclomethicone 5, glyceryl 
monostearate, citric acid anhydrous, sodium hydroxide, edetate disodium, glycerin, phenoxy 
ethanol, methylparaben (only in vehicle) and water. 
18.3. 
Study Products Packaging and Labeling 
The study product (Encapsulated Benzoyl Peroxide Cream, 5%), S5G4T-1, and placebo for the 
study product (Vehicle Cream), S5G4T-2, will be packaged and labeled in 55-g airless pump. At 
the first 12 weeks of treatment, a double-blind technique will be used. In order to maintain the 
blind, the study product and vehicle will be supplied in identically-appearing labeled pump cartons. 
Neither the patient nor the investigational staff (sponsor, investigator, and evaluators) will know 
which treatment a patient is receiving. 
The study products will be shipped to sites in blocks of three (3) products to keep ratio 2:1 between 
study product and vehicle. The study products will be labeled with the following: 
• Protocol Number 


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• Patient Number 
• Kit Number 
• Pump Number 
• Patient Initials 
• Dispense Date 
• Dispenser Initials 
• Contains: one (1) pump of S5G4T-1 (Encapsulated Benzoyl Peroxide) Cream, 5% or its 
Vehicle Cream, 55 g 
• Directions for use: Apply as directed, for topical use only. 
• Storage conditions “Store at Room Temperature 20 to 25°C (68 to 77°F). Excursions 
permitted between 15 to 30°C (59 to 86°F).” 
• Keep container tightly closed. 
• Do not freeze and do not refrigerate. 
• Keep out of reach of children. 
• Study product warning. “Caution: New Drug - Limited by Federal Law to Investigational 
Use” 
• Sponsor Information 
Each Study Product Kit Box will contain four (4) pumps and will carry a two-part label with a 
perforation. The tear-off section of the label will be attached to the study product dispensing log 
at the time the study product is dispensed. The other label part must remain attached to the box. 
Both label parts will have spaces to enter the patient’s initials, date dispensed, dispenser’s initials. 
The constant label part shows: 
• Protocol Number 
• Patient Number 
• Patient Initials 
• Kit Number 
• Randomization Date 
• Contains: four (4) pumps of Encapsulated Benzoyl Peroxide (E-BPO) Cream, 5% or its 
Vehicle Cream, 55 g. 
• Directions for use: Apply as directed, for topical use only. 
• Storage conditions “Store at Room Temperature 20 to 25°C (68 to 77°F). Excursions 
permitted between 15 to 30°C (59 to 86°F).” 
• Keep container tightly closed. 
• Do not freeze and do not refrigerate. 
• Keep out of reach of children. 
• Study product warning. “Caution: New Drug - Limited by Federal Law to Investigational 
Use” 
• Sponsor Information 


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18.4. 
Preparation, Dispensing and Storage Instructions 
The study product must be dispensed only to study patients and only at study sites specified on the 
form FDA 1572 by authorized personnel as required by applicable regulations and guidelines. 
Study product will be dispensed at: Baseline, Weeks 4 and 8. Study product will be returned at: 
Weeks 4, 8 and 12. Study product weight will be documented in EDC prior to dispensing and after 
return of each pump per flow chart (Section 13.9 and Section 5.2). 
Each Patient will be instructed on the importance of returning his or her study product at each 
designated visit. If a Patient does not return his or her study product, he or she will be instructed 
to return it at the next visit. 
The study coordinator will question the patient on history of study product use since the last visit 
and will record any missed doses (as recorded on the patient diary) in both the source documents 
and the appropriate eCRF. A patient who deviates significantly from the prescribed dosage will 
be counseled. 
Study product should be stored at room temperature 20 to 25°C (68 to 77°F). Excursions permitted 
between 15 to 30°C (59 to 86°F). Do not freeze or refrigerate the product. 
18.5. 
Dosing Instructions 
Topical application of study product will be made to the face once daily at approximately the same 
time of the day, for a period of twelve (12) weeks. Study product will be applied as a thin coating 
that is gently rubbed in to the skin. 
Each patient will receive both verbal and written instructions (see Appendix 1) as to the proper 
dosing and study product application techniques. 
Patients will be instructed to apply the study product for 12 weeks, once a day after cleansing. No 
time interval between dosing and meals or any other activity is specified. 
Patients will cleanse their face with the given cleanser or sponsor approved cleanser using only 
the hands and pat dry with a soft clean towel. Patients will use a “pea-size” amount for each area 
of the face (chin, left cheek, right cheek, nose, left forehead and right forehead). The Patient should 
gently rub the cream into the skin. This amount of cream should be sufficient to cover the area on 
the face excluding the mouth, eyes, inside the nose, and lips. The Patient should wash his/her 
hands after application but should not wash face at least 2 hours after study product application. 
Patients should wait at least 30 minutes before applying moisturizer/sunscreen after application of 
study product to the face. During the trial that investigators remind patients to avoid exposure to 
sunlight and sunlamps and to wear sunscreen when sun exposure cannot be avoided. 
The Patients will be instructed to continue using the same supplied/approved facial cleanser and 
not to change products during the study. At each visit, Patients are to be asked if they have changed 
their cleansing routine. The supplied/approved cleanser and moisturizer/sunscreen should be 
applied according to the directions on the pump. Facial makeup (non-medicated) may be applied 
according to the patient’s normal daily routine (but not prior to 30 minutes after study product 
application); however, patients should be instructed not to apply the moisturizer or sunscreen or 
combination of them or wear make-up during study visits as it may interfere with the evaluator’s 
assessments. No other products should be used on the face. 


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Pump usage will be demonstrated by the site personnel on a sample pump at the clinic to help 
assure the patient understands the procedure. The patient will be provided a set of instructions 
(Appendix 1) that includes study reminders and restrictions as described in this protocol. Patients 
will be instructed to bring the study product to each visit and to not apply study product one hour 
prior to the study visit. Patients should be instructed to store the study product at room 
temperature, not in the refrigerator or freezer and informed that the test article may bleach colored 
fabric. 
18.6. 
Study Product Accountability and Study Records at Sites 
Upon receipt of the clinical supplies, the study staff will conduct a complete inventory of study 
products and assume responsibility for their storage and dispensing. In accordance with federal 
regulations, the Investigators must agree to keep all study products in a secure, temperature-
controlled location with restricted access. 
All supplies sent to the Investigators will be accounted for and in no case used in any unauthorized 
manner. All used and unused study product will be appropriately inventoried by the clinical site, 
and verified by the clinical monitor. 
Study product will be weighed before dispensing and upon return and weights will be recorded on 
the appropriate source document and eCRF. 
18.7. 
Return and Destruction of Study Product Supplies 
Upon completion or termination of the study, all remaining pumps (in kits) must be appropriately 
inventoried and returned to Sponsor or designee by a traceable method. All missing pumps of 
study products must be explained on the completed Clinical Supplies Return Form. The study site 
must keep a copy of the Clinical Supplies Return Form in the study file. 
18.8. 
Additional Supplies Provided by Sponsor 
• Regulatory study file system (Investigator Binder) 
• Urine pregnancy test kits 
• Cleanser 
• Moisturizer/sunscreen 


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19. 
STATISTICAL CONSIDERATIONS 
19.1. 
General Statistical Methods 
All statistical processing will be performed using SAS® version 9.3 or later unless otherwise 
stated. Statistical significance will be based on two-tailed tests of the null hypothesis resulting in 
p-values of 0.05 or less.  These methods are intended to analyze the results of the study. 
The primary method of handling missing efficacy data will be based on estimation using the 
method of Markov Chain Monte Carlo (MCMC) imputation. This method provides robust 
estimation when the pattern of missingness is arbitrary. Additionally, the estimation will be done 
for each treatment group separately so that the pattern of missingness for one group does not 
influence the estimation of missing data for another group. Groups of complete datasets following 
the estimation will be concatenated to form analysis datasets for the comparative analyses and 
subsequent imputation result inference with SAS PROC MIANALYZE. Descriptive statistics will 
also be derived from the multiply imputed datasets. 
Additionally, a model-based multiple imputation process will be used as a sensitivity analysis to 
the MCMC imputation. Finally, the absolute change in lesion count will be analyzed using a 
repeated measures ANCOVA for lesion count data or a repeated measures logistic regression 
model (generalized estimating equations) for the dichotomized Investigator’s Global Assessment, 
IGA. 
A statistical analysis plan (SAP), describing all statistical analyses will be provided as a separate 
document. The SAP will be finalized prior to unblinding of the study treatments. 
19.1.1. 
Patient Disposition 
A tabulation of patient disposition will be provided. The tabulation will include the numbers of 
patients who enter the study, complete the study, and discontinue the study. The reasons for 
discontinuation will be included. 
19.1.2. 
Demographics and Baseline Characteristics 
Patient demographic and baseline characteristics will be summarized by treatment group for the 
ITT, PP, and safety populations. For continuous variables (e.g. age) comparisons among the two 
treatment groups will be conducted using a two-way analysis of variance (ANOVA) with factors 
of treatment group and analysis center (see Section 19.4.6 for definition of “analysis center”). 
Ethnicity and race will be analyzed with a Cochran-Mantel-Haenszel test stratified by analysis 
center. Past and current medical conditions, as well as history of disease will be presented in a 
data listing. 
19.1.3. 
Protocol Deviations 
All protocol deviations will be reported to the sponsor and recorded throughout the study. A 
tabulation of protocol deviations will be presented in a data listing. 
19.1.4. 
Analysis Populations 
Approximately 350 male and female patients at least 18 years of age with moderate or severe 
papulopustular rosacea with 3 or 4 [moderate to severe] on the IGA scale will be enrolled and 
randomized in the study with a 2:1 randomization ratio, it is anticipated that: 


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• 234 patients will be randomized to receive S5G4T-1, Encapsulated Benzoyl Peroxide (E-
BPO) Cream, 5% 
• 117 patients will be randomized to receive S5G4T-2, Vehicle Cream 
The ITT population will consist of all randomized patients who were dispensed study product. 
The safety population will be comprised of all randomized patients who are presumed to have used 
the study product at least once and who provide at least one post-baseline safety evaluation. 
An intent-to-treat (ITT) analysis will be conducted on all study patients. A per-protocol (PP) 
analysis will also be conducted. Patients will be eligible for the PP analysis if they complete the 
12-week evaluation without noteworthy study protocol violations (i.e., any patient or investigator 
activity that could have possibly interfered with the therapeutic administration of the treatment or 
the precise evaluation of treatment efficacy). The PP population will include patients in the ITT 
population who do not meet any of the following criteria: 
• Failed any of the inclusion/exclusion criteria; 
• Have taken any interfering concomitant medications; 
• Did not attend the Week 12 Visit; 
• Missed more than 1 post baseline study visit prior to Week 12 
• Have not been compliant with the dosing regimen (i.e., Patients may not miss more than 
five consecutive days of dosing and must take 80 to 120% of expected doses. The number 
of expected doses will be determined for each patient based on the length of their 
participation in the study); 
• Out of visit window (± 4 days) at the 12-week Visit. 
Patients that discontinue from the study due to an adverse event related to study treatment or 
documented lack of treatment effect will be included in the PP population. Data for these subjects 
will not be imputed by multiple imputation but rather their data will be imputed with values 
consistent with their status as treatment failures. Prior to breaking the blind, other additional 
criteria may be added to the list to accommodate for unforeseen events that occurred during the 
conduct of the trial that result in noteworthy study protocol violations. 
19.2. 
Study Product Evaluations  and  Analyses 
Inflammatory lesion count will be recorded for each patient at the Baseline and at Weeks 2, 4, 8 
and 12. The absolute and percent change from baseline of inflammatory lesions will be derived 
for each patient at Weeks 2, 4, 8 and 12. 
The IGA will be recorded for each patient at the Baseline visit and site visits at Weeks 2, 4, 8 and 
12 (End of Study). The IGA will be dichotomized into “success” and “failure” at Weeks 2, 4, 8 
and 12 with a patient considered a success for those visits if the IGA is at least 2 grades less than 
baseline and are Clear or Almost Clear. 
The Rosacea Erythema assessment, and Telangiectasia assessment will be recorded at Baseline 
and at Weeks 2, 4, 8 and 12. 
Patients will be asked to complete Patient Reported Outcome, PRO, questionnaires at appropriate 
time points. 
All statistical analysis will be conducted for both PP and ITT population. 


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19.3. 
Assessment of Efficacy 
Primary, secondary, and supportive efficacy analyses will be conducted on the ITT (primary) 
population. Primary efficacy analyses will be conducted on the PP (supportive) population. 
19.3.1. 
Primary Efficacy 
There are two co-primary efficacy endpoints: 
• Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” 
(1) in the IGA relative to Baseline at Week 12. 
• Absolute change in inflammatory lesion counts from baseline to Week 12. 
19.3.2. 
Secondary Efficacy 
The secondary efficacy endpoints will be the following: 
• Percent change in inflammatory lesion count from baseline to Week 12 
• Absolute change in inflammatory lesion count from baseline to Week 8 
• Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” 
(1) in the IGA relative to Baseline at Week 8 
• Absolute change in inflammatory lesion count from baseline to Week 4 
• Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” 
(1) in the IGA relative to Baseline at Week 4 
• . 
19.3.3. 
Supportive Efficacy 
Supportive efficacy endpoints include the following: 
• Percent change in inflammatory lesion count at Week 8 
• Percent change in inflammatory lesion count at Week 4 
• Mean change comparison in PAPSS item 1 (burning) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 2 (itching) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 3 (redness) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 4 (bumps) between groups from Baseline to 
Weeks 4, 8 and 12 Rosacea erythema assessment at Week 12 
• Telangiectasia assessment at Week 12 
• The proportion of patients in treatment relative to control who report at least “minimally 
improved” as measured by the PGI-C at Week 12 
• Mean change in the components of the PAPI score between groups from Baseline to 
Week 12 
• Proportion of patients in the treatment relative to control achieving a three-point 
improvement in the components of the PAPI score from Baseline to Week 12 


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• Patient Global Impression of Symptom Severity (PGI-S) at Week 12 
• Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 12 
• A set of cumulative distribution function (CDF) curves will be generated to allow for the 
evaluation of within-person change by treatment group. Specifically, 5 plots will be 
generated showing the change from baseline to Week 12 [and/or other, earlier time points 
if so desired] by the cumulative percent of subjects for each of the treatment arms (change 
on the x-axis will be expressed as absolute change) on: 
o PAPSS total scale scores; 
o PAPSS item 1 (burning) scores; 
o PAPSS item 2 (itching) scores; 
o PAPSS item 3 (redness) scores; and 
o PAPSS item 4 (bumps) scores 
19.4. 
Statistical Hypothesis Testing 
19.4.1. 
Test of Superiority for Lesion Count Variables 
This section provides the basic model and statistical approach which is used in combination with 
the multiple imputation procedures described in Section 19.4.6. Tests of superiority for the 
absolute change from Baseline in inflammatory lesions will be based on non-parametric methods 
consistent with the statistical assumptions required to support the analyses. Specifically, the tests 
of superiority will be based on ranked data submitted to an ANCOVA with factors of treatment 
and analysis center and the respective Baseline lesion count as a covariate. 
For informational purposes, a skewness test, based on the methods presented by Zar 1984, will be 
applied to the residuals resulting from an ANCOVA using the untransformed lesion count data. A 
two-sided p-value for the skewness test significant at 0.05 would validate the use of the non-
parametric method. The results of a non-ranked ANCOVA with factors of treatment and analysis 
center and the respective Baseline lesion count as a covariate will also be presented for 
informational purposes. 
19.4.2. 
Test of Superiority for IGA 
The IGA will be dichotomized into “success” and “failure” with a patient considered a success for 
those visits if the Investigator’s Global Assessment is at least 2 grades less than Baseline and 
“Clear” or “Almost Clear”. The analysis of the dichotomized IGA will be based on a logistic 
regression test with factors of treatment group and analysis center. 
19.4.3. 
Test of Superiority for Secondary Efficacy and Control of Multiplicity 
Appropriate descriptive statistics will be computed for all Secondary Efficacy parameters. 
Additionally, all inferential testing will follow the methods for the primary lesion count analyses 
as well as those for the dichotomized IGA success rates (as appropriate). 
The overall Type I error will be controlled by requiring the two co-primary efficacy endpoints to 
be statistically significant. Specifically, failure of either one of the primary efficacy endpoints will 
invalidate the statistical significance of the secondary efficacy endpoints. 


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A stepwise process will be conducted for testing the secondary efficacy endpoints in order to 
control for multiplicity. These tests will be performed for only the ITT population. The testing 
process will terminate whenever a statistical test for a step is not significant. All subsequent tests 
for the remaining steps will be considered not significant. The order of testing is provided in 
Table 6. 
 
Table 6: Process for Testing the Secondary Efficacy Endpoints 
 
Step 
Number 
Secondary Endpoint 
1 
Percent change in inflammatory lesion count from baseline to Week 12 
2 
Absolute change in inflammatory lesion count from baseline to Week 8 
3 
Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” (1) in 
the IGA relative to Baseline at Week 8 
4 
Absolute change in inflammatory lesion count from baseline to Week 4 
5 
Proportion of patients with the primary measure of success “Clear” (0) or “Almost clear” (1) in 
the IGA relative to Baseline at Week 4 
 
19.4.4. 
Supportive Efficacy Analyses 
Appropriate descriptive statistics will be computed for all Supportive Efficacy parameters. 
Additionally, inferential testing for the following endpoints will use an ANOVA with factors of 
treatment, analysis center and the respective Baseline score. The overall Type I error will be 
controlled by the Benjamini-Hochberg method. Missing values will not be imputed. 
• Mean change comparison in PAPSS item 1 (burning) between groups from Baseline to 
Week 12 
• Mean change comparison in PAPSS item 2 (itching) between groups from Baseline to 
Week 12 
• Mean change comparison in PAPSS item 3 (redness) between groups from Baseline to 
Week 12 
• Mean change comparison in PAPSS item 4 (bumps) between groups from Baseline to 
Week 12 
19.4.5. 
Exploratory Endpoint 
The mean change in RosaQoL subscale scores from Baseline to Week 12. 


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19.4.6. 
Pooling Analysis 
The clinical study will be conducted under a common protocol for each investigational site with 
the intention of pooling the data for analysis. Every effort will be made to promote consistency in 
study execution at each investigational site. The study is intended to be conducted in a manner 
such that a minimum of 5 patients will be enrolled in each treatment arm for any investigator. In 
the event that there are too few patients in a treatment arm for an investigator, then this 
investigator's data will be combined to achieve the desired sample size minimum per arm. The 
combining of investigator's data will be accomplished by taking the investigator with the smallest 
enrollment and combining it with the investigator with the largest enrollment. If there is a further 
need to combine data, then the data of the investigator with the second smallest enrollment will be 
combined with the investigator's data which had the second largest enrollment and so on. This 
process will continue for all investigators who did not have a minimum of 5 patients per treatment 
arm. The process of combining investigator data that have insufficient patients per treatment arm 
will result in redefining the groups of investigators for the purposes of statistical analyses. These 
combined groups will be referred to as "analysis centers" in the statistical analyses based on 
ANCOVA and stratified logistic testing. 
Prior to investigating the treatment effect within the analysis centers, the magnitude of the site 
mail effect will be investigated to determine if the main site-to-site variability is such that it could 
mask the analysis center effects. Thus, if computationally possible, a one-way ANCOVA (for 
lesion count variables) or a logistic regression analysis (for IGA) with a factor of site will be 
conducted prior to pooling. If the data structure interferes with the logistic regression, a descriptive 
analysis of the site effect will be undertaken. Conclusions appropriate to the findings of this step 
will be presented. 
The consistency of treatment response will be investigated across the analysis centers subsequent 
to combining the data as described above. Statistical tests will be conducted to identify if there 
are extreme analysis centers that could affect the interpretation of common statistical and clinical 
conclusions. An analysis center by treatment interaction will be included in the primary variable 
analyses to test for parallel treatment effect at an alpha level of 0.10. Change from baseline in 
inflammatory lesions will be analyzed with an ANCOVA (unranked or ranked) with factors of 
treatment, analysis center, and treatment by analysis center interaction and the respective baseline 
lesion count variable as a covariate. For the purpose of testing consistency of treatment response, 
the dichotomized IGA will be analyzed with a logistic regression procedure with factors of 
treatment, analysis center, and treatment by analysis center interaction. Further examination will 
follow for any variables that have a significant ANCOVA or logistic regression interaction term. 
In the event that the ANCOVA or logistic regression interaction (referred to henceforth as the 
"appropriate test") p-value is less than or equal to 0.10, a sensitivity analysis that excludes analysis 
centers with the extreme efficacy result will be performed to determine the robustness of the 
treatment effect. On the other hand, if the outcome of the appropriate test has a p-value greater 
than 0.10, then the conclusions from the pooled data will be considered to be free of the impact of 
extreme analysis centers. 
The first step in conducting a sensitivity analysis is to identify the extreme analysis center or 
centers that contribute to the statistical significance of the appropriate test. The process involves 
submitting subsets of analysis centers to the appropriate test and observing the appropriate test p-
value for the subset. Subsets with p-values greater than 0.10 for the appropriate test are 
considered homogeneous. 


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The search for an extreme analysis center begins by analyzing all subsets that can be created by 
excluding one analysis center. If one or more of the subsets result in an appropriate test p-value 
greater than or equal to 0.10, then the analysis center excluded from the subset with the largest p-
value for the appropriate test is deemed to be the extreme analysis center. 
If all appropriate test subset p-values are less than or equal to 0.10, then the process will analyze 
the appropriate test for all subsets that can be created by excluding two analysis centers.  If one or 
more of these subsets generate appropriate test p-values larger than 0.10, then the analysis centers 
excluded from the subset with the largest appropriate test p-value are deemed the extreme analysis 
centers. 
Thus, the process of identifying the extreme analysis centers will continue in a stepwise manner 
by first excluding one, then two, then three, etc., analysis centers until the appropriate test p-value 
exceeds 0.10. 
Once the extreme analysis center or centers have been identified, then the treatment p-values of 
the remaining analysis centers will be computed. Inferences will be drawn from the treatment p-
value, as well as any pertinent observations regarding the extreme analysis center or centers. 
Additionally, it is noted that this process excludes patients from the analysis in a non-random 
manner and has an unpredictable impact on the power of the treatment effect test. In the event that 
the treatment effect of the remaining subset is not statistically significant, due consideration of the 
post-hoc aspects of the process will be given when the results are interpreted. Conclusions will be 
presented by the sponsor as appropriate to the findings of the sensitivity analysis. 
19.4.7. 
Missing Efficacy Data Imputations 
19.4.7.1. Lesion Count Variable Missing Data Imputation 
Missing Week 12 data will be estimated by multiple imputation and subsequently analyzed. 
Missing lesion count data will be derived for the analysis using the method of Markov Chain Monte 
Carlo (MCMC) multiple imputation. The pattern of missing observations in each treatment group 
cannot influence the missing value estimation in the other because the imputation will be 
conducted independently for each treatment group. 
Multiple imputation and subsequent analysis will involve 3 distinct phases with these principal 
tasks: 
1. Create a data set of patients, one for each treatment group, with observed values and those 
needing estimation by MCMC. The missing lesion count values in each data set will be 
filled in using the MCMC method 5 times to generate 5 data sets. The resulting data sets 
for each treatment arm will be combined into one complete data set for each imputation. 
Syntax: 
proc mi data=datain out=dataout seed=&seed. nimpute=5 
<options>; 
where trtpn=(1, or 2); 
mcmc chain=multiple; 
var baseline week2 week4 week8 week12; 
run; 


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2. For each complete data set, the variable of interest for baseline minus the Week 12 value 
will be computed. Each complete data set will be analyzed as specified for the particular 
analysis. 
3. The results from these analyses will be combined into a single inference using SAS PROC 
MIANALYZE. 
A total of 6 random seeds are needed to impute inflammatory lesion counts. These random seeds 
have been pre-specified by using a random number generator: 
• Inflammatory Lesion Counts Week 12 S5G4T-1: Seed = 2046620966 
• Inflammatory Lesion Counts Week 12 Vehicle: Seed = 693843173 
• Inflammatory Lesion Counts Week 8 S5G4T-1: Seed = 385596352 
• Inflammatory Lesion Counts Week 8 Vehicle: Seed = 386411964 
• Inflammatory Lesion Counts Week 4 S5G4T-1: Seed = 796550211 
• Inflammatory Lesion Counts Week 4 Vehicle: Seed = 40534656 
 
19.4.7.2. IGA Missing Data Imputation 
A similar procedure will be used for the analyses based on proportion of IGA successes wherein 
the ANCOVA analysis is replaced with a logistic regression analysis. Specifically, missing 12 
week IGA values from which the dichotomized IGA is derived will be estimated by (MCMC). 
The pattern of missing observations in each treatment group cannot influence the missing value 
estimation in the other because the imputation is being conducted independently for each treatment 
group. 
The missing 12-week IGA values will be derived for the analysis using the method of Markov 
Chain Monte Carlo (MCMC) multiple imputation. Multiple imputation and subsequent analysis 
will involve 4 principal tasks: 
1. Create a data set, one for each treatment group, of patients with observed values and those 
needing estimation by MCMC. The missing IGA values in each data set will be filled in 
using the MCMC method 5 times to generate 5 data sets. The resulting data sets for each 
treatment arm will be combined into one complete data   set   by   imputation. 
Syntax: 
proc mi data=datain out=dataout seed=&seed. nimpute=5 
<options>; 
where trtpn=(1, or 2); 
mcmc chain=multiple; 
var baseline week2 week4 week8 week12; 
run; 


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2. For each complete data set, the dichotomous success rate (clear or almost clear with a 2-
point change from baseline) will be computed. The 12-week estimated global values will 
be rounded to the nearest integer value prior to evaluating the success rate. Each 
complete data set will be analyzed with a logistic regression with factors of treatment group 
and analysis center. 
3. The results from these analyses will be combined into a single inference using SAS PROC 
MIANALYZE. 
A total of 2 random seeds will be needed to impute IGA for the two treatment groups. Those 2 
random seeds have been pre-specified by using a random number generator: 
• IGA Week 12 S5G4T-1: Seed = 712066910 
• IGA Week 12 Vehicle: Seed = 1200150465 
• IGA Week 8 S5G4T-1: Seed = 1871392013 
• IGA Week 8 Vehicle: Seed = 1866129897 
• IGA Week 4 S5G4T-1: Seed = 301965746 
• IGA Week 4 Vehicle: Seed = 812607204 
19.4.8. 
Sensitivity Efficacy Analyses 
19.4.8.1. Sensitivity Analyses for Absolute Change in Lesion Count 
The first sensitivity analysis for absolute change in lesion count will use a repeated measures 
ANCOVA, with treatment, analysis center, and visit (i.e., Weeks 2, 4 and 8) as independent factors 
and a covariate of baseline lesion count. In this analysis, data from all post-baseline visits will be 
included with no imputation for missing data. 
The second sensitivity analysis will use the model based multiple imputation method to impute 
missing data for the absolute change in lesion counts at Week 12. Although the full details will be 
presented in the Statistical Analysis Plan (SAP), the multiple imputation will involve 4 principal 
tasks: 
1. Missing values will be filled in 5 times to generate 5 complete data sets. The imputation 
model used will be an ANCOVA with factors of treatment group and analysis center, and 
a covariate of baseline lesion count (i.e., the imputation model will be the same as the 
analysis model). Appropriate modifications will be made should the analysis be based on 
a non-parametric method. 
2. Each complete data set will be analyzed with an ANCOVA with factors of treatment group, 
and analysis center, and a covariate of baseline lesion count. 
3. Results from these analyses will be combined into a single inference. 
19.4.8.2. Sensitivity Analyses for IGA 
The first sensitivity analysis for the dichotomized IGA success will use a repeated measures 
logistic regression model (generalized estimating equations), with dichotomized IGA success as 
the dependent variable and treatment, analysis center, and visit (i.e., Weeks 2, 4 and 8) as 
independent factors. In this analysis, data from all post-baseline visits will be included with no 
imputation for missing data. 


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The second sensitivity analysis will use the model based multiple imputation method to impute 
missing data for the dichotomized IGA data. Although the full details will be presented in the 
SAP, the multiple imputation will involve 4 principal tasks: 
1. Missing values will be filled in 5 times to generate 5 complete data sets. The imputation 
model used logistic regression with factors of treatment group and analysis center (i.e., the 
imputation model will be the same as the analysis model). 
2. Each complete data set will be analyzed with a logistic regression a factors of treatment 
group and analysis center. 
3. Results from these analyses will be combined into a single inference. 
19.4.9. 
Subgroup Analyses 
Subset analyses will be conducted for the ITT populations for the subgroups baseline global 
severity, gender, age, ethnicity, race, and geographic region. Age will be dichotomized to less 
than the median age of patients and greater than or equal to the median age of patients. Subset 
analyses will be conducted on the variables absolute change from baseline in inflammatory lesions 
at Week 12 as well as the dichotomized global severity score at Week 12. These analyses will 
contain only descriptive statistics. 
19.5. 
Assessment of Safety 
Safety will be evaluated by tabulations of adverse events (AEs), Cutaneous Safety Assessments 
for dryness and scaling, assessments for scores (erythema and telangiectasia) and Patient Global 
Impression of Treatment Side-Effects (PGI-SE) will be presented with descriptive statistics at 
Baseline and at Weeks 2, 4, 8 and 12 for each treatment group. Frequencies and percentages for 
each outcome category will be included in these statistics. Mean values will be presented 
graphically by week and treatment group. 
19.6. 
Adverse Events 
All adverse events occurring during the study will be recorded and classified on the basis of 
MedDRA terminology. Descriptions of AEs will include the date of onset, the date the AE ended, 
the severity of the AE, the relationship to study product, the action taken regarding study product 
usage, the action taken to treat the AE, and the outcome. All reported treatment-emergent AEs 
(TEAEs) will be summarized by the number of Patients reporting AEs, system organ class, 
severity, seriousness, and relationship to study product. TEAEs are those AEs with an onset on or 
after the date of the first study product application. 
Adverse events will be summarized by treatment group and severity. Each patient will be counted 
only once within a system organ class or a preferred term by using the adverse events with the 
highest severity within each category. 
Adverse events will be summarized by treatment group and relationship to study product. Each 
patient will be counted only once within a system organ class or a preferred term by using the 
adverse events with the greatest relationship within each category. 


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Comparisons among treatment groups will be made by tabulating the frequency of patients with 
one or more AEs (classified into MedDRA terms) during the study. The Fisher’s Exact test will 
be used to compare the proportion of patients in each treatment group who report any adverse 
event at a significance level of 0.05. The specific system organ classes and preferred terms 
analyzed will be those that are reported by at least one percent of the patients in any treatment 
group. 
All information pertaining to AEs noted during the study will be listed by patient, detailing 
verbatim given by the investigator, preferred term, system organ class, start date, stop date, 
severity, actions taken, and drug relatedness. The AE onset will also be shown relative (in number 
of days) to the day of initial dose of the randomized study product. 
Serious adverse events (SAEs) will be tabulated by patient within treatment groups. 
In addition, a list of patients who discontinued from the study and a list of patients who experienced 
SAEs will also be provided. 
19.6.1. 
Vital Sign Measurements 
Vital signs as well as changes from Baseline in vital sign measurements will be summarized with 
descriptive statistics for each treatment group at all applicable study visits. 
19.6.2. 
Concomitant Medications 
All previous therapies and concomitant medications will be classified based on terminology from 
the WHO Drug Dictionary. Previous therapies and concomitant medications data will be presented 
in data listings. 
19.7. 
Sample Size Determination 
The following power calculations are based on the observed Week 12 results of the Phase 2 study, 
SGT-EBP01-09. This study was a three-arm trial including E-BPO Cream, 1% and 5%, and 
Vehicle in the Treatment of Rosacea. Estimates from the E-BPO Cream, 5% arm were used in the 
power assessments. The anticipated randomization ratio is 2:1 for E-BPO Cream, 5% and Vehicle, 
respectively. The computations were performed with nQuery Advisor Version 7.0 using a two-
sided test with a statistical significance value of 0.05. 
A sample size of 86 in the E-BPO Cream, 5% and 43 in the Vehicle has group has 95% power to 
detect a statistically significant difference in the proportion of patients who have at least a 2-grade 
reduction at Week 12 from baseline in IGA and are Clear or Almost Clear. The estimated 
percentages with a 2-grade reduction at Week 12 from baseline in the IGA and Clear or Almost 
Clear are 53.3% and 20.0% for the E-BPO Cream and Vehicle, respectively. 
A sample size of 200 in the E-BPO Cream, 5% and 100 in the Vehicle group has 95% power to 
detect a statistically significant difference in inflammatory lesions. The estimated absolute change 
from baseline in treatment means were -14.1 and -7.4 for the E-BPO Cream and Vehicle, 
respectively, with a standard deviation of 6.70 and 17.24, respectively. 
The sample sizes above will be increased to give a planned enrollment of 234 in the E-BPO Cream, 
5% group and 117 in the Vehicle group since the Phase 3 trial is expected to enroll patients who 
are as a group more severe than those of the Phase 2 trial. This is a consequence of some changes 
in the inclusion criteria. 


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20. 
ADMINISTRATIVE CONSIDERATIONS 
20.1. 
Protocol Compliance 
The IRB-approved protocol must be followed except in the case of a change that is intended to 
eliminate an immediate risk to patients. All protocol deviations must be documented in the source 
documents and in the comment CRFs. 
20.2. 
Protocol Revisions 
Sponsor or designee must prepare all protocol revisions. All protocol amendments must receive 
IRB approval prior to implementation. All administrative letters must be submitted to the IRB for 
their information. Copies of all correspondence with the IRB regarding this study must be sent to 
Sponsor or CRO designee. New or altered consent forms required by the IRB due to a protocol 
revision must be signed by all patients currently enrolled in the study and must be used for any 
subsequent patient enrollment. 
20.3. 
Protocol Monitoring 
Representatives of Sponsor must be allowed to visit all study sites, to review study records and to 
directly compare them with source documents (including, but not limited to patient and hospital 
records), to discuss the study conduct with the investigator and study staff; and to verify that the 
investigator, study staff and facilities remain acceptable for the conduct of the study. 
Representatives of government regulatory authorities (i.e., FDA) may also evaluate the study 
records, source documents, investigator, study staff, and facilities. 
The investigator must immediately notify Sponsor of any audits by any regulatory agency, and 
must promptly provide copies of any audit reports. 
20.4. 
Required Study Documents 
The investigator must provide the following documents to Sponsor or CRO designee before any 
patients are enrolled and/or study product may be shipped to the study site: 
• The signed INVESTIGATOR PROTOCOL ACKNOWLEDGEMENT page from the 
Sponsor and IRB approved protocol. 
• Documentation of IRB approval of the protocol, informed consent form, any other written 
information provided to patients and any recruitment advertisements. 
• A copy of the IRB approved informed consent form 
• A current IRB assurance number and/or a membership roster. 
• A completed, signed and dated Form FDA 1572. 
• The appropriate financial disclosure documentation. 
• A current signed and dated curriculum vitae and a copy of the current medical license for 
the investigator and sub-investigators listed on the Form FDA 1572. 
• The signed agreement between the investigator and Sponsor, or designee, and related 
financial information for the study (this file is confidential and currently FDA has no 
authority to review this information. Keep this information in a separate file). 


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20.5. 
Electronic Case Report Forms (eCRF)/Source Documents 
Electronic case report forms (eCRFs) called also electronic data capture (EDC) system, will be 
used for recording all data from source documents for each patient. Source documents are the 
point of first entry for all data collected. Whenever possible, an original recording of an 
observation should be retained as source document. 
The investigator will ensure that the eCRFs are properly and completely filled in. The eCRFs must 
be completed for all patients who have signed an informed consent form. The eCRFs will be 
monitored against source documents. If data in the eCRF is not duplicated in a source document, 
a source document should be created and maintained by the site to capture that information. Source 
documentation for patients includes but is not limited to the physician’s patient records, diaries, 
photographs. All source documents will be maintained at the study site. 
The Investigator or delegate may enter corrections in the eCRFs, which will create an auditable 
history of all changes and by whom they were made. The final eCRF will be approved by the 
Investigator by electronic signature. 
20.6. 
Reports to the IRB/Ethics Committee (EC) 
Before study initiation, the investigator must have written and dated approval from the IRB for the 
protocol, consent form, patient recruitment materials /process (e.g., advertisements), and any other 
written information to be provided to patient. The investigator should also provide the IRB with 
a copy of the Investigator’s Brochure and/or package insert. The investigator should provide the 
IRB with reports, updates, and other information (e.g., safety updates, protocol amendments, and 
administrative letters) according to regulatory requirements or Institution procedures. 
20.7. 
Quality Assurance Audits 
Representatives from Sponsor and/or a third party selected by Sponsor may conduct a quality 
assurance audit of this study. During the audit, the Investigator must provide the auditor with 
direct access to all relevant documents and discuss any findings with the auditor. 
In the event of an inspection by the Food and Drug Administration or other regulatory authorities, 
the Investigator will notify the Sponsor /CRO as soon as possible of such notice and must give the 
inspector direct access to relevant documents and discuss any findings with the inspector. 
20.8. 
Records Retention 
The investigator must maintain records of the study product disposition, copies of the case report 
forms and all source documents for the maximum period of five years after NDA approval as 
required by Sponsor. The investigator must contact Sponsor prior to destroying any records 
associated with this study. 
If the location of the study files changes from the address noted on the FDA Form 1572, written 
notification of the new location must be given to Sponsor. If the investigator withdraws from 
participation in the study the records shall be transferred to a mutually agreed-to designee. Written 
notification of such a transfer must be given to Sponsor. 


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21. 
REFERENCES 
Breneman D., Savin R., VandePol C., Vamvakias G., Levy S., Leyden J. Double-blind, 
randomized, vehicle-controlled clinical trial of once-daily benzoyl peroxide/clindamycin topical 
gel in the treatment of patients with moderate to severe rosacea. Int. J of Derm. 2004; 43(5):381-
387. 
Jansen T. and Plewig G. Rosacea: classification and treatment. JR Soc Med. 1997; 90(3):144-150. 
McDonnell JK and Tomecki KJ. Rosacea: an update. Clev Clinic J Med. 2000; 67(8):587-590. 
Montes LF., Cordero AA., Kriner J., Loder J., Flanagan AD. Topical treatment of acne rosacea 
with benzoyl peroxide acetone gel.  Cutis 1983; 32(2):185-190. 
Yamasaki K., Di Nardo A., Bardan A., Murakami M., Ohtake T. Coda A., Dorschner RA., 
Bonnart C., Descargues P., Hovnanian A., Morhenn VB. and Gallo RL. Increased serine protease 
activity and cathelicidin promotes skin inflammation in rosacea. Nat. Med. 2007; 13:975-980. 
Zar, JH. Bio-statistical analysis, 1984 2nd ed. Englewood Cliffs (NJ) Prentice-Hall. (Available 
upon request). 


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APPENDIX 1: 
PATIENT INSTRUCTION SHEET 
Please follow these instructions carefully. Contact the study staff at the telephone number noted 
below if you have any questions about the study: 
 
 
Contact: 
At: 
 
 
STUDY PRODUCT APPLICATION: 
• At first application, priming is required. 
• Apply the cream once a day every day during the study period [twelve (12) weeks]. 
• Wash your face gently with the mild cleanser provided by the doctor or by study approved 
cleanser for this study from the sponsor and water. Rinse thoroughly and gently pat dry. 
• A thin coating of study product should be applied once daily (preferably at the same time 
each day) to the entire face during the study period [twelve (12) weeks]. 
• Apply one gentle pump application of test material from pump onto the tip of your finger 
the size of a pea for each area of the face (chin, left cheek, right cheek, nose, left forehead 
and right forehead), as instructed at your first study visit. 
• Apply the cream on each area of the face as evenly as possible and gently rub into the skin. 
Each pea-size amount should be used to evenly cover the following parts on your face: 
chin, left cheek, right cheek, nose, left forehead and right forehead excluding the mouth, 
eyes and lips. 
• Do NOT treat specific lesions but rather the entire face. 
• Be sure to wash your hands after you apply the study product. But do not wash your face 
for at least two hours after you apply study product. 
• Wait for at least 30 minutes before applying the moisturizer/sunscreen provided by the 
doctor for this study. 
• If applicable, wait at least 30 minutes before applying only non-medicated make-up. 
 
ADDITIONAL REMINDERS: 
• Store study product at Room Temperature 20 to 25°C (68 to 77°F). Excursions permitted 
between 15 to 30°C (59 to 86°F). Do not freeze, refrigerate or expose to extreme 
temperature.” 
• Avoid contact with the eyes, inside the nose, mouth and all mucous membranes. 
• Caution: This product contains benzoyl peroxide which can bleach hair or colored fabric. 
• THE PRODUCT SHOULD BE USED ONLY BY THE PERSON FOR WHOM IT WAS 
PRESCRIBED and it should be kept out of the reach of children or others of limited 
capacity to read or understand. 
• Pumps of study product must be returned to the study facility, even if they are empty. 


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• If you miss any doses, at your next visit inform the study doctor of the date(s) of the missed 
dose(s). Please record all doses on the Diary Card provided to you; indicate reason for any 
missed dose on the Diary Card. 
• Throughout the study, continue to use on your face only the same cleanser provided by the 
doctor for this study. 
• If you use a moisturizer and/or sunscreen, you must use the one provided by the doctor for 
this study. 
• On the day of your study visit, do not apply moisturizer/sunscreen, or make-up. 
• You must not use any other treatment for your rosacea while you are participating in this 
study. 
• Avoid unnecessary sun exposure and tanning booths. When sun exposure cannot be 
avoided, use the approved moisturizer/sunscreen and wear a wide-brimmed hat. 
It is important that you inform the study site about any medications (i.e., prescriptions, over-the-
counter medications, street drugs, or herbal medications) that you have taken during the study. 
Bring this sheet, your updated Diary Card, and your study product pump with you to every study 
visit. 
 
STUDY VISIT SCHEDULE: 
 
VISIT 2: Baseline Day 1 
Date: 
Time: 
VISIT 3: Week 2, Day 15 
Date: 
Time: 
VISIT 4: Week 4, Day 29 
Date: 
Time: 
VISIT 5: 
Week 8, Day 57 
Date: 
Time: 
VISIT 6: Week 12, Day 85 
Date: 
Time: 
 
 
Thank you for following these instructions. 


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APPENDIX 2: 
PRO – PAPSS 
 


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APPENDIX 3: 
PRO – PAPI 
 


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APPENDIX 4: 
PRO – PGI-S 
 
 
 


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APPENDIX 5: 
PRO – PGI-C 
 
 
 


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APPENDIX 6: 
PRO – PGI-TS 
 
 
 
 


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APPENDIX 7: 
PRO – PGI-SE 
 
 
 


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APPENDIX 8: 
ROSACEA QUALITY OF LIFE QUESTIONNAIRE 
(ROSAQOL) 
 

SAP_001.pdf: 
Statistical Analysis Plan 
Sol-Gel Technologies Ltd. SGT-54-02 
Version: 1.0 
Date: 02 MAY 2019 
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 Page 1 of 194 
CONFIDENTIAL 
STATISTICAL ANALYSIS PLAN 
Protocol Number: 
SGT-54-02 
Study Title: 
A Phase 3 Multi-Center, Double-Blind, 
Randomized, Vehicle-Controlled Study 
of S5G4T-1 in the Treatment of 
Papulopustular Rosacea 
Development Phase of Study: 
3 
Sponsor: 
Sol-Gel Technologies Ltd. 
Sponsor Contact: 
 
Statistical Analysis Plan based on Protocol Version: 
4 
Statistical Analysis Plan Date: 
02MAY2019 
Statistical Analysis Plan Version: 
V1.0 
NCT #NCT03564119




 
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SAP Change History 
Version Date 
Summary of Changes  
Author 
1 02MAY2019 Original document 
 
 
 
 


 
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TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................7 
2. 
PREFACE ..............................................................................................................................8 
3. 
RESPONSIBILITIES ...........................................................................................................9 
4. 
INTRODUCTION .................................................................................................................9 
5. 
STUDY OBJECTIVES .......................................................................................................10 
5.1 Secondary Objective .....................................................................................................10 
5.2 Supportive Objective ....................................................................................................11 
5.3 Safety Objective ............................................................................................................11 
6. 
STUDY DESIGN .................................................................................................................11 
6.1 Overall Study Design ....................................................................................................11 
6.1.1 
Schedule of Visits and Assessments ...............................................................12 
6.1.2 
Method of Assigning Subjects to Treatment Groups ......................................12 
6.1.3 
Blinding ...........................................................................................................13 
7. 
EFFICACY AND SAFETY ENDPOINTS .......................................................................13 
7.1 Efficacy Endpoints ........................................................................................................13 
7.1.1 
Primary Efficacy Endpoints ............................................................................13 
7.1.2 
Secondary Efficacy Endpoints ........................................................................14 
7.1.3 
Additional Supportive Efficacy Endpoints ......................................................14 
7.1.4 
Exploratory Endpoints .....................................................................................15 
7.2 Safety Endpoints ...........................................................................................................15 
8. 
STATISTICAL AND ANALYTICAL PLANS ................................................................15 
8.1 General Methodology ...................................................................................................15 
8.1.1 
Statistical Analysis ..........................................................................................16 
8.1.2 
Baseline Definition ..........................................................................................16 
8.1.3 
Visit Windowing .............................................................................................16 
8.1.4 
Adjustments for Covariates .............................................................................17 
8.1.5 
Handling of Dropouts or Missing Data ...........................................................17 
8.1.5.1 
Lesion Count Variable Missing Data Imputation ........................18 
8.1.5.2 
IGA Missing Data Imputation .....................................................18 
8.1.5.3 
Medication Date Imputation ........................................................19 


 
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8.1.6 
Interim Analyses and Data Monitoring ...........................................................20 
8.1.7 
Multicenter Studies ..........................................................................................20 
8.1.8 
Multiple Comparisons/Multiplicity .................................................................22 
8.1.9 
Use of an Efficacy Subset of Subjects .............................................................23 
8.1.10 Active-Control Studies Intended to Show Equivalence ..................................23 
8.1.11 Examination of Subgroups ..............................................................................23 
8.2 Disposition of Subjects .................................................................................................24 
8.4 Data Sets Analyzed .......................................................................................................25 
8.4.1 
Randomized Population ..................................................................................25 
8.4.2 
Intent-to-Treat (ITT) Population .....................................................................25 
8.4.3 
Safety Population ............................................................................................25 
8.4.4 
Per-Protocol (PP) Population ..........................................................................25 
8.5 Demographic and Other Baseline Characteristics ........................................................26 
8.6 Prior and Concomitant Medications .............................................................................27 
8.7 Analysis of Efficacy ......................................................................................................27 
8.7.1 
Primary Efficacy Analysis ...............................................................................27 
8.7.1.1 
Lesion Counts ..............................................................................28 
8.7.1.2 
Investigator Global Assessment (IGA) ........................................29 
8.7.2 
Sensitivity Efficacy Analysis ..........................................................................29 
8.7.2.1 
Sensitivity Analyses for Absolute Change in Lesion Count ........29 
8.7.2.2 
Sensitivity Analyses for IGA .......................................................30 
8.7.3 
Secondary Efficacy Analysis ...........................................................................31 
8.7.4 
Supportive Efficacy Analysis ..........................................................................31 
8.7.5 
Exploratory Endpoint Analysis .......................................................................32 
8.8 Safety Evaluation ..........................................................................................................33 
8.8.1 
Extent of Exposure ..........................................................................................33 
8.8.2 
Adverse Events (AEs) .....................................................................................34 
8.8.3 
Clinical Laboratory Evaluation .......................................................................35 
8.8.4 
Other Observations Related to Safety .............................................................35 
8.8.4.1 
Cutaneous Safety Assessments ....................................................35 
8.8.4.2 
Local Tolerability Assessments ...................................................35 
8.8.4.3 
Vital Signs ....................................................................................35 
8.8.4.4 
Physical Examination...................................................................36 
8.8.4.5 
Patient Global Impression of Treatment Side-Effects     
(PGI-SE)  .....................................................................................36 


 
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9. 
DETERMINATION OF SAMPLE SIZE .........................................................................36 
10. CHANGES IN THE PLANNED ANALYSES..................................................................36 
11. REFERENCES ....................................................................................................................38 
12. INDEX OF PLANNED TABLES ......................................................................................39 
13. INDEX OF PLANNED FIGURES ..................................................................................150 
14. INDEX OF PLANNED LISTINGS .................................................................................157 
 
 


 
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1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE(s) 
adverse event(s) 
ANCOVA 
analysis of covariance 
ANOVA 
analysis of variance 
ATC 
Anatomical Therapeutic Chemical 
BMI 
body mass index 
C 
Celsius 
cm 
centimeters 
CRF(s) 
case report form(s) 
eCRF(s) 
electronic case report form(s) 
E-BPO 
encapsulated benzoyl peroxide 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
IGA 
Investigator Global Assessment 
ITT 
Intent-to-Treat 
IWRS 
Interactive Web Response System 
kg 
kilograms 
LOCF 
last observation carried forward 
LSMean or LSM 
least square mean 
max 
maximum 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
min 
minimum 
n 
number of observations 
N 
number of subjects (sample size) 
PAPI 
Patient Assessment of Papulopustular rosacea Impacts 
PAPSS 
Patient Assessment of Papulopustular Rosacea Signs and Symptoms 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Symptom Severity 
PGI-SE  
Patient Global Impression of Treatments Side Effects 
PGI-TS 
Patient Global Impression of Treatments Satisfaction 
PP 
per-protocol 


 
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PT 
preferred term 
QST 
QST Consultations, Ltd. 
RosQoL 
Rosacea Quality-of-Life 
SAE(s) 
serious adverse event(s) 
SAS® 
Statistical Analysis System (SAS® Institute Inc., Cary, NC) 
SD 
standard deviation 
SOC 
system organ class 
TEAE(s) 
treatment-emergent adverse event(s) 
WHO 
World Health Organization 
2. PREFACE  
This Statistical Analysis Plan (SAP) describes the statistical analyses as it is foreseen before 
breaking the blind. The SAP will serve as a compliment to the study protocol and supersedes it in 
case of differences. In case of major differences between the study protocol and SAP, e.g. 
changes in the analysis related to the primary endpoint, a protocol amendment will be 
considered. The SAP may be updated during the study conduct and will be finalized before 
breaking the blind. 
The following documents were reviewed in preparation of this SAP: 
• Clinical Study Protocol SGT-54-02 
o Version 1.0 issued on 15MAR2018,  
o Version 2.0 issued on 30APR2018, 
o Version 3.0 issued on 07JUN2018, 
o Version 4.0 issued on 13NOV2018 
• Case report form (CRF) for SGT-54-02. 
• ICH E9 Guidance on Statistical Principles for Clinical Trials. 
• ICH E3 Structure and Content of Clinical Study Reports (CSRs) 
The reader of this SAP is encouraged to also read the clinical protocol for details on the conduct 
of this study, and the operational aspects of clinical assessments and timing for completing a 
patient in this study. 


 
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3. RESPONSIBILITIES 
The study statistician will be responsible for the statistical analysis planning. QST Consultations, 
Ltd. (QST), a Contract Research Organization (CRO) selected by Sol-Gel, will be responsible for 
the execution of all statistical programming deliverables. The statistical programming work will 
be supervised by the study statistician.   
4. INTRODUCTION 
S5G4T-1 is an innovative topical formulation containing 5% encapsulated benzoyl peroxide 
(E-BPO) that Sol-Gel is developing for the treatment of papulpustular rosacea. If approved, 
S5G4T-1 will be the first product containing E-BPO for the treatment of papulpustular rosacea. 
Sol-Gel believes S5G4T-1 has the potential to be as tolerable as, and more effective than, 
currently marketed rosacea drugs. 
Rosacea is a chronic and recurrent inflammatory dermatological disorder of unknown etiology. 
The disease is common, especially in fair-skinned people of Celtic and northern European 
heritage. The onset of the disorder is usually between the ages of 30 and 50. Early stages of the 
disease affect women more often than men at a ratio of 3 to 1 [1, 2]. Rosacea usually starts as 
flushing and subtle redness on the cheeks, nose, chin or forehead. Alcohol, hot drinks, spicy 
foods, stress, sunlight and extreme heat or cold can trigger the onset of this disease. If left 
untreated, rosacea can slowly worsen over time. As the condition progresses, patients experience 
inflammatory lesions (papules and pustules), vivid erythema and telangiectasia. Patients may 
develop furuncles, cystic nodules, granulomas and tissue hypertrophy, sometimes leading to 
rhinophyma. 
Rosacea is treated with both systemic and topical therapies. However, topical therapies are 
preferable because of side effects caused by the use of systemic therapies. 
According to the U.S. National Rosacea Society, approximately 16 million people in the United 
States are affected by rosacea. According to a study commissioned by the Sponsor, 
approximately 4.8 million people in the United States experience subtype II symptoms and 
physicians estimate that only 20% of the U.S. rosacea population is treated. The topical drugs 
approved by the Food and Drug Administration (FDA) to treat subtype II rosacea generated 
aggregate revenues of approximately $392 million in the United States for the 12 months period 
ending June 30, 2017. 
In August 2012, Sol-Gel completed a double blind, randomized, dose-ranging Phase 2 trial for 
S5G4T-1 involving 92 adult patients at ten centers in the United States (SGT-EBPO1-09: A 
Multi-Center, Double-Blind, Randomized, Vehicle-Controlled, Dose-Range Study of 


 
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Encapsulated Benzoyl Peroxide Gel, 1% and 5%, and Vehicle Gel in the Treatment of Rosacea). 
The Phase 2 trial had two co-primary endpoints: success in Investigator Global Assessment 
(IGA) namely, a two-grade reduction in IGA on a scale of 0 to 4 ("clear", "almost clear", "mild", 
"moderate", "severe") with clear or almost clear at Week 12; and a reduction in the mean 
inflammatory lesion count at Week 12 (end of trial). The second co-primary endpoint was the 
change from Baseline in the inflammatory lesions (papules and pustules) count at end of trial. All 
patients were 18 years of age or older with 12 or more inflammatory lesions at enrollment. 
Patients were randomly divided into three groups of 30 to 32 patients each and received a once 
daily dose, with one group receiving S5G4T-1 (E-BPO 5%), a second group receiving a 1% 
concentration of E-BPO and a third control group receiving the vehicle (placebo) alone. The 
evaluator rated the following signs of local skin irritation on a scale of 0 to 3 ("none", "mild", 
"moderate", "severe") for dryness and scaling. Information on adverse events (AEs) was also 
collected. 
Both E-BPO 1% and S5G4T-1 demonstrated statistically significant improvement in comparison 
to the vehicle in reducing papulopustular lesions based on the percentage change in the 
inflammatory lesion count from Baseline at Week 12, p = 0.014 and p = 0.02, respectively, and 
S5G4T-1 also demonstrated statistically significant improvement in comparison to the vehicle in 
achieving the IGA success co-primary endpoint (p = 0.0013). All three formulations were well 
tolerated. A few patients had moderate local application site irritation (dryness, scaling, pruritus, 
stinging and burning) during treatment.  
A clear trend of dose response with IGA success of 20.0% for the vehicle, 37.5% for the E-
BPO 1% and 53.3% for S5G4T-1 was observed. Both S5G4T-1 and E-BPO 1% significantly 
reduced the number of inflammatory lesions with a trend towards dose response indicated by 
median reduction of 10 lesions in the vehicle group compared to 12.5 and 15 in the E-BPO 1% 
and S5G4T-1 groups, respectively. 
5. STUDY OBJECTIVES 
The primary objectives of this pivotal study are: 
• To assess the efficacy and safety of S5G4T-1 compared to S5G4T-1 Vehicle when 
applied once daily for 12 weeks in patients with papulopustular rosacea. 
5.1 
Secondary Objective 
The secondary objective of this pivotal study is: 
• To demonstrate statistical superiority in efficacy of S5G4T-1 compared to the vehicle 
with regard to percent change from baseline. 


 
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5.2 
Supportive Objective 
The supportive objective of this pivotal study is: 
• To determine the time required to observe improvement in the efficacy parameters 
associated with clearance of rosacea for S5G4T-1 compared to vehicle. 
5.3 
Safety Objective 
The safety objectives of this pivotal study are: 
• To determine the nature, severity and frequency of the adverse event rate, the Cutaneous 
Safety Assessment and the Local Tolerability Assessment of S5G4T-1 compared to the 
vehicle. 
6. STUDY DESIGN 
6.1 
Overall Study Design 
This study will be a randomized, double-blind, multicenter, parallel group, active- and vehicle-
controlled pivotal study of the efficacy and safety of S5G4T-1 and its vehicle for the treatment of 
papulopustular rosacea for 12 weeks. Approximately 350 patients with moderate to severe 
rosacea (rated 3 or 4 on the 5-point IGA scale) will be enrolled at up to 28 sites. Patients in this 
randomized, double-blind, vehicle-controlled, parallel-group multi-center study will be randomly 
assigned in a 2:1 ratio to S5G4T-1 or vehicle, respectively. Subjects with severe rosacea who are 
appropriate for systemic treatment need to be counseled regarding their treatment options by the 
Principal Investigator. 
Patients will receive once daily treatment with S5G4T-1 or vehicle cream for 12 weeks. After the 
screening period, qualified patients will be randomly assigned at the Baseline visit and treated or 
12 weeks. Efficacy assessments will include facial inflammatory lesion counts and IGA 
assessment ranging from 0 (clear) to 4 (severe). Investigators will be provided with instructions 
for lesion counts to ensure consistency of procedure. Patient reported outcomes (PRO) will be 
assessed with the PAPSS (Patient Assessment of Papulopustular Rosacea Signs and Symptoms), 
PAPI (Patient Assessment of Papulopustular rosacea Impacts), and PGI-S (Patient Global 
Impression of Symptom Severity) that will be administered at Baseline, Weeks 2, 4, 8, and 12, or 
at early termination. In addition, the PGI-C (Patient Global Impression of Change), PGI-TS 
(Patient Global Impression of Treatments Satisfaction), and PGI-SE (Patient Global Impression 
of Treatments Side Effects) will be administered at Weeks 2, 4, 8, and 12, or at early termination 
[FDA Guidance 2009]. Safety will be assessed at all visits and will include monitoring local and 
systemic adverse events (AEs); the Investigator Cutaneous Safety Assessment rating of 


 
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erythema, dryness and scaling, and the Local Tolerability Assessments rating of itching and 
burning/stinging on a scale ranging from 0 (none) to 3 (severe). 
Patients will return to centers for IGA, lesion counts, PRO questionnaire, Investigator Cutaneous 
Safety Assessment, and Local Tolerability Assessments at Weeks 2, 4, 8 and 12. AEs and 
concomitant medications will be assessed throughout the treatment period. A urine pregnancy 
test is required at Visit 1, 2, 4, 5, and 6 for all females of child-bearing potential. 
Clinical Evaluations will be performed at: 
• Visit 1/Screening 
• Visit 2/Baseline, Day 1 
• Visit 3/Week 2, Day 15 (± 3 Days) 
• Visit 4/Week 4, Day 29 (± 3 Days) 
• Visit 5/Week 8, Day 57 (± 3 Days) 
• Visit 6/Week 12, Day 85 (± 4 Days)/End of Treatment) 
6.1.1 
Schedule of Visits and Assessments 
The schedule of assessments can be found in Section 13.9 of the protocol. 
6.1.2 
Method of Assigning Subjects to Treatment Groups 
Patients who satisfy all the inclusion and none of the exclusion criteria will be randomized to one 
of two treatment arms. Randomization will be performed in the Interactive Web Response 
System (IWRS) according to a computer-generated randomization schedule. The randomization 
schedule will be generated by the unblinded statistician and uploaded to the IWRS. The 
randomization schedule will be maintained securely within the IWRS. Patients will be 
randomized to E-BPO 5% or vehicle cream, once daily on a 2:1 basis for twelve (12) weeks.  
Once a patient is determined eligible for the study at the Baseline visit, the patient will be 
randomized to study product assignment by the IWRS. Each study product carton will contain 
four pumps of the same product; The first supplied pump in each kit is marked A (e.g. number of 
pump within a kit is XXXXA), at Visit 4/ Week 4 the patient will return the pump and will be 
dispensed with the next pump which is marked B. At Visit 5/ Week 8, the patient will be 
dispensed with a pump marked C. The pump marked as D is a backup pump. The patient number 
will be added to both parts of the kit label (open part and tear-off label and to the pump label). 


 
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6.1.3 
Blinding 
The staff involved in data management and statistical evaluation will remain blinded until 
identification of the analysis population is completed and a database lock memo is issued.  
The randomization schedule and treatment code will not be revealed to the patients, study 
personnel, Sol-Gel or its representatives until after the database lock, except to the Medical 
Monitor or Principal Investigator for an emergency. Access to the randomization list will be 
maintained by and limited to the unblinded Biostatistician and the designated personnel directly 
responsible for labeling of study materials. The Medical Monitor will not have access to the 
randomization list, but may determine that unblinding one or all patients may be necessary in the 
case that the safety of study patients is at risk. In an emergency, the study blind may be broken 
only if: 
• In the opinion of the Medical Monitor and/or the Principal Investigator, it is in the 
patient's best interest to do so 
• Knowledge of the treatment will alter the clinical management of the patient 
In the case of an emergency that requires unblinding, the Investigator can request to unblind the 
patient without prior contact with the Medical Monitor although follow-up between the 
Investigator and Medical Monitor must occur so that all parties are aware of the unblinding. 
Although it is recommended that the Investigator contact the Medical Monitor prior to 
unblinding any patient, in instances where this is not feasible or advisable the Principal 
Investigator may directly access the patient's treatment assignment. In all situations, the IWRS 
will be used to obtain treatment assignment information with limited access to only the above-
designated individuals, and any unblinding will be documented as a protocol deviation. 
7. EFFICACY AND SAFETY ENDPOINTS 
7.1 
Efficacy Endpoints 
7.1.1 
Primary Efficacy Endpoints 
There are two co-primary efficacy endpoints: 
• Proportion of patients with the primary measure of success (clear or almost clear) in IGA 
relative to Baseline at Week 12 
• Absolute change in inflammatory lesion counts from Baseline to Week 12 


 
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7.1.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are as follows: 
• Percent change in inflammatory lesion count from Baseline to Week 12 
• Absolute change in inflammatory lesion count from Baseline to Week 8 
• Proportion of patients with the primary measure of success (clear or almost clear) in the 
IGA relative to Baseline at Week 8 
• Absolute change in inflammatory lesion count from Baseline to Week 4 
• Proportion of patients with the primary measure of success (clear or almost clear) in the 
IGA relative to Baseline at Week 4 
7.1.3 
Additional Supportive Efficacy Endpoints 
The supportive efficacy endpoints include the following: 
• Percent change in inflammatory lesion count at Week 8 
• Percent change in inflammatory lesion count at Week 4 
• Mean change comparison in PAPSS item 1 (burning) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 2 (itching) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 3 (redness) between groups from Baseline to 
Weeks 4, 8 and 12 
• Mean change comparison in PAPSS item 4 (bumps) between groups from Baseline to 
Weeks 4, 8 and 12  
• Rosacea erythema assessment at Week 12 
• Telangiectasia assessment at Week 12 
• The proportion of patients in treatment relative to control who report at least “minimally 
improved” (defined as “very much improved”, “much improved” or “minimally 
improved”) as measured by the PGI-C at Week 12 
• Mean change in the components of the PAPI score between groups from Baseline to 
Week 12 


 
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• Proportion of patients in the treatment relative to control achieving a three-point 
improvement in the components of the PAPI score from Baseline to Week 12 
• PGI-S at Week 12 
• PGI-TS at Week 12 
• PAPSS within-person absolute change from Baseline to Week 12 (and/or other, earlier 
time points if so desired) 
Other supportive endpoints not outlined in the SAP will be explored by Sol-Gel as appropriate.  
7.1.4 
Exploratory Endpoints 
The exploratory endpoint is the mean change in Rosacea Quality-of-Life (RosaQoL) subscale 
scores from Baseline to Week 12.  
7.2 
Safety Endpoints 
Safety will be assessed through Cutaneous Safety Assessment, Local Tolerability Assessment, 
AE reporting, physical examination, vital signs, and PGI-SE. 
8. STATISTICAL AND ANALYTICAL PLANS 
8.1 
General Methodology 
All statistical processing will be performed using SAS® version 9.3 or later unless otherwise 
stated. Statistical significance will be based on two-tailed tests of the null hypothesis resulting in 
p-values of 0.05 or less. These methods are intended to analyze the results of the study. 
The primary method of handling missing efficacy data will be based on estimation using the 
method of Markov Chain Monte Carlo (MCMC) imputation. This method provides robust 
estimation when the pattern of missingness is arbitrary. Additionally, the estimation will be done 
for each treatment group separately so that the pattern of missingness for one group does not 
influence the estimation of missing data for another group. Groups of complete datasets 
following the estimation will be concatenated to form analysis datasets for the comparative 
analyses and subsequent imputation result inference with SAS PROC MIANALYZE. 
Descriptive statistics will also be derived from the multiply imputed datasets. 
Additionally, a model-based multiple imputation process will be used as a sensitivity analysis to 
the MCMC imputation. Finally, the absolute change in lesion count will be analyzed using a 
repeated measures analysis of covariance (ANCOVA) for lesion count data and a repeated 
measures logistic regression model (generalized estimating equations) for the dichotomized IGA. 


 
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8.1.1 
Statistical Analysis 
All analyses will be performed by QST using SAS® Version 9.3 or later. All summary tables 
and data listings will be prepared utilizing SAS® software. 
The standard operating procedures (SOPs) of QST will be followed in the creation and quality 
control of all data displays and analyses. 
All data listings will be by subject.  Additionally, all listings except the screen failure and 
randomization listings will be by treatment.  
8.1.2 
Baseline Definition 
Baseline is defined as the last non-missing assessment prior to first application of study drug. If 
the date of first application is unknown due to the subject being lost to follow-up, the Baseline 
visit record will be used as Baseline if it is non-missing. Missing results will not be flagged as 
Baseline. 
8.1.3 
Visit Windowing 
Data will be summarized based on nominal visit indications with the exception of data captured 
at early termination and unscheduled visits. Data from early termination and unscheduled visits 
will be summarized based on mapped visit values. The analysis windows for early termination 
and unscheduled visits are presented in the following table.  
Analysis Windows for Efficacy and Safety Assessments 
Scheduled Visit 
Target Study Day 
Window (Days) 
Week 2 
15 
8 to 21 
Week 4 
29 
22 to 42 
Week 8 
57 
43 to 70 
Week 12 
85 
71 to 98 
 
Data collected at early termination and unscheduled visits prior to study day 8 will not be 
analyzed, with the exception of those identified as Baseline values. Data collected at early 
termination and unscheduled visits after study day 98 will not be included in analyses.  
The definition for the study day included in each study window is defined as below: 
 
Study Day prior to Day 1 = Visit Date – Day 1 Date 
 
Study Day on or after Day 1 = Visit Date – Day 1 Date + 1 


 
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If an assessment’s mapped visit is a visit at which the subject has data from a scheduled visit 
present, or if no analyses are planned for the assessment at the mapped visit, the data collected at 
the early termination or unscheduled visit will not be included in analyses.  
In the event of multiple values from unscheduled or early termination assessments within an 
analysis window, the value closest to the scheduled visit target study day will be used for 
analyses. If two values tie as closest to the time point (for example, one value is before and the 
other value is after the time point), then the later value will be selected.  
Data collected at all visits will be included in the data listings with visit presented as reported by 
the site. 
8.1.4 
Adjustments for Covariates 
Baseline lesion count will be a covariate for the primary efficacy endpoint for lesion counts. No 
other covariates are planned to be used in the analyses for this study.  
8.1.5 
Handling of Dropouts or Missing Data 
Missing data for the ITT population will be estimated by multiple imputation and subsequently 
analyzed. Missing lesion count and IGA data will be derived for the analysis using the method of 
Markov Chain Monte Carlo (MCMC) multiple imputation. The pattern of missing observations 
in each treatment group cannot influence the missing value estimation in the other group because 
the imputation will be conducted independently for each treatment group. 
Last observation carried forward (LOCF) will be used to impute missing data for the efficacy 
analyses using the PP population. 
Patients that discontinue from the study due to an AE related to study treatment or documented 
lack of treatment effect will be included in the PP population. Data for these subjects will not be 
imputed by multiple imputation or LOCF but rather their data will be imputed with values 
consistent with their status as treatment failures. For these subjects, values for lesion count and 
IGA will be imputed such that change from Baseline is zero, meaning the values will be set to 
the Baseline value. This imputation will be done after the data for all subjects has been through 
the MI process. 
Incomplete start and end dates for medications will be imputed. Other safety data will not be 
imputed and will be summarized on an observed case basis. 


 
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8.1.5.1 
Lesion Count Variable Missing Data Imputation 
Multiple imputation and subsequent analysis will involve 3 distinct phases with these principal 
tasks: 
1. Create a data set of patients, one for each treatment group, with observed values and 
those needing estimation by MCMC. The missing lesion count values in each data set 
will be filled in using the MCMC method 5 times to generate 5 data sets. The resulting 
data sets for each treatment arm will be combined into one complete data set for each 
imputation. 
Syntax: 
proc mi data=datain out=dataout seed=&seed. nimpute=5 <options>; 
  where trtpn=(1, or 2); 
  mcmc chain=multiple; 
  var baseline week2 week4 week8 week12; 
run; 
2. For each complete data set, the variable of interest for Baseline minus the value for the 
week imputed will be computed. Each complete data set will be analyzed as specified for 
the particular analysis. 
3. The results from these analyses will be combined into a single inference using SAS 
PROC MIANALYZE. 
A total of 2 random seeds are needed to impute inflammatory lesion counts. These random seeds 
have been pre-specified by using a random number generator: 
• Inflammatory Lesion Counts S5G4T-1: Seed = 1787019983 
• Inflammatory Lesion Counts Vehicle: Seed = 814066626 
8.1.5.2 
IGA Missing Data Imputation 
A similar procedure will be used for the analyses based on proportion of IGA successes wherein 
the ANCOVA analysis is replaced with a logistic regression analysis. Specifically, missing IGA 
values from which the dichotomized IGA is derived will be estimated by MCMC. 
The pattern of missing observations in each treatment group cannot influence the missing value 
estimation in the other because the imputation is being conducted independently for each 
treatment group. 


 
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The missing IGA values will be derived for the analysis using the method of MCMC multiple 
imputation. Multiple imputation and subsequent analysis will involve 3 principal tasks: 
1. Create a data set, one for each treatment group, of patients with observed values and 
those needing estimation by MCMC. The missing IGA values in each data set will be 
filled in using the MCMC method 5 times to generate 5 data sets. The resulting data sets 
for each treatment arm will be combined into one complete data set by imputation. 
Syntax: 
proc mi data=datain out=dataout seed=&seed. nimpute=5 <options>; 
  where trtpn=(1, or 2); 
  mcmc chain=multiple; 
  var baseline week2 week4 week8 week12; 
run; 
2. For each complete data set, the dichotomous success rate (clear or almost clear) will be 
computed. The estimated global values will be rounded to the nearest integer value prior 
to evaluating the success rate. Each complete data set will be analyzed with a logistic 
regression with factors of treatment group and analysis center. 
3. The results from these analyses will be combined into a single inference using SAS 
PROC MIANALYZE. 
A total of 2 random seeds will be needed to impute IGA for the two treatment groups. Those 2 
random seeds have been pre-specified by using a random number generator: 
• IGA Week S5G4T-1: Seed = 325011659 
• IGA Week Vehicle: Seed = 1440479769 
8.1.5.3 
Medication Date Imputation 
If the medication start date is incomplete, then it will be imputed as follows for the purpose of 
determining concomitant use:  
• If the start date is completely missing, the start date will be equal to the first dose date. 
However, if the stop date is not missing and is before the first dose date, then the stop 
date will be used instead. 
• If the start day is missing, the first day of the month will be used.  


 
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• If the start day and month are missing, then the first day of the first month (January) will 
be used. 
If the medication stop date is incomplete, then it will be imputed as follows for the purpose of 
determining concomitant use:  
• If the stop date is completely missing and the medication is not ongoing, the stop date 
will be equal to the last dose date or date of completion/withdrawal, whichever is the 
latest.  
• If the stop day is missing, the last day of the month will be used.  
If the stop day and month are missing, then the last day of the last month (December) will be 
used. 
8.1.6 
Interim Analyses and Data Monitoring 
No interim analysis or data monitoring is planned for this study. 
8.1.7 
Multicenter Studies 
The clinical study will be conducted under a common protocol for each investigational site with 
the intention of pooling the data for analysis. Every effort will be made to promote consistency 
in study execution at each investigational site. The study is intended to be conducted in a manner 
such that a minimum of 15 subjects will be randomized and included in the ITT population (i.e., 
at least ten subjects in the active treatment arm and five subjects in the vehicle treatment arm) for 
any investigator. In the event that there are too few subjects in a treatment arm for an 
investigational site, then the site’s data will be combined with other site’s data to achieve the 
desired sample size minimum per treatment arm. The combining of investigator data will be 
accomplished by taking the data of the investigator with the smallest enrollment and combining 
them with the data of the investigator with the largest enrollment, restricted to investigational 
sites which did not meet minimum enrollment. If there is a further need to combine data, then the 
data of the investigator with the second smallest enrollment will be combined with the site’s data 
which had the second largest enrollment (restricted to investigational sites which did not meet 
minimum enrollment), and so on. This process will continue for all investigators who did not 
have a minimum of 15 subjects enrolled. The process of combining investigator data that have 
insufficient subjects per treatment arm will result in redefining the groups of investigators for the 
purposes of statistical analyses. These combined groups will be referred to as “analysis centers” 
in the statistical analyses. 


 
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The consistency of treatment response will be investigated across the analysis centers subsequent 
to combining the data as described above. Statistical tests will be conducted to identify if there 
are extreme analysis centers that could affect the interpretation of common statistical and clinical 
conclusions. An analysis center by treatment interaction will be included in the primary analyses 
to test for parallel treatment effect at an alpha level of 0.10. Change from Baseline in 
inflammatory lesions will be analyzed with an ANCOVA (unranked or ranked) with factors of 
treatment group, analysis center, and treatment group by analysis center interaction, and the 
Baseline lesion count variable as a covariate. For the purpose of testing consistency of treatment 
response, the dichotomized IGA will be analyzed with a logistic regression with factors of 
treatment group, analysis center, and the interaction term of treatment group by analysis center. 
Further examination will follow for any variables that have a significant ANCOVA or logistic 
regression interaction term. 
In the event that the ANCOVA or logistic regression interaction (referred to henceforth as the 
“appropriate test”) p-value is less than or equal to 0.10, a sensitivity analysis that excludes 
analysis centers with the extreme efficacy result will be performed to determine the robustness of 
the treatment effect. On the other hand, if all three analyses result in interaction terms with 
p-values greater than 0.10, then the conclusions from the pooled data will be considered to be 
free of the impact of extreme analysis centers. 
The first step in conducting a sensitivity analysis is to identify the extreme analysis center or 
centers that contribute to the statistical significance of the appropriate test. The process involves 
submitting subsets of analysis centers to the appropriate test and observing the appropriate test 
p-value for the subset. Subsets with p-values greater than 0.10 for the appropriate test are 
considered homogeneous. 
The search for an extreme analysis center begins by analyzing all subsets that can be created by 
excluding one analysis center. If one or more of the subsets result in an appropriate test p-value 
greater than or equal to 0.10, then the analysis center excluded from the subset with the largest 
p-values for the appropriate test is deemed to be the extreme analysis center. 
If all appropriate test subset p-values are less than or equal to 0.10, then the process will analyze 
the appropriate test for all subsets that can be created by excluding two analysis centers. If one or 
more of these subsets generate appropriate test p-values larger than 0.10, then the analysis 
centers excluded from the subset with the largest appropriate test p-value are deemed the extreme 
analysis centers. 
Thus, the process of identifying the extreme analysis centers will continue in a stepwise manner 
by first excluding one, then two, then three, etc., analysis centers until the appropriate test p-
value exceeds 0.10. 


 
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Once the extreme analysis center or centers have been identified, then the treatment p-values of 
the remaining analysis centers will be computed. Inferences will be drawn from the p-values as 
well as any pertinent observations regarding the extreme analysis center or centers. Additionally, 
it is noted that this process excludes patients from the analysis in a non-random manner and has 
an unpredictable impact on the power of the treatment effect test. In the event that the treatment 
effect of the remaining subset is not statistically significant, due consideration of the post-hoc 
aspects of the process will be given when the results are interpreted. Conclusions will be 
presented by the Sponsor as appropriate to the findings of the sensitivity analysis. 
Prior to investigating the treatment effect within the analysis centers, the treatment effect within 
investigational site will be investigated to determine if the site-to-site variability is such that it 
could mask the analysis center effects. Thus, prior to pooling, change from Baseline in 
inflammatory lesions will be analyzed with an ANCOVA (unranked or ranked) with factors of 
treatment group, investigational site, and treatment group by investigational site interaction, and 
the Baseline lesion count variable as a covariate. The dichotomized primary endpoint will be 
analyzed with a logistic regression with factors of treatment group, investigational site, and the 
interaction term of treatment group by investigational site. If any of the analyses are not 
computationally feasible due to some investigational sites having very few subjects enrolled, the 
low-enrolling investigational sites will be excluded from the analysis. 
8.1.8 
Multiple Comparisons/Multiplicity 
In testing the secondary efficacy endpoints the overall Type I error will be controlled by 
requiring the two co-primary efficacy endpoints to be statistically significant. Specifically, 
failure of either one of the primary efficacy endpoints will invalidate the statistical significance 
of the secondary efficacy endpoints. 
A stepwise process will be conducted for testing the secondary efficacy endpoints in order to 
control for multiplicity. These tests will be performed for only the ITT population. The testing 
process will terminate whenever a statistical test for a step is not significant. All subsequent tests 
for the remaining steps will be considered not significant. The order of testing is provided below. 
 
 


 
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Step 
Number 
Secondary Endpoint 
1 
Percent change in inflammatory lesion count from Baseline to Week 12 
2 
Absolute change in inflammatory lesion count from Baseline to Week 8 
3 
Proportion of patients with the primary measure of success “Clear” (0) or 
“Almost clear” (1) in the IGA relative to Baseline at Week 8 
4 
Absolute change in inflammatory lesion count from Baseline to Week 4 
5 
Proportion of patients with the primary measure of success “Clear” (0) or 
“Almost clear” (1) in the IGA relative to Baseline at Week 4 
 
In testing the supportive efficacy endpoints, the overall Type I error will be controlled by the 
Benjamini-Hochberg method. The Hochberg and Bejamini adaptive step-down Bonferoni 
method will be used within PROC MULTTEST in SAS (AHOLM option in PROC 
MULTTEST).  
8.1.9 
Use of an Efficacy Subset of Subjects 
Subjects randomized to study drug who were dispensed study product and do not have major 
protocol deviations will form the Per Protocol (PP) Population. The requirements for the PP 
Population are outlined in Section 8.4.4. Any additional major protocol deviations will be 
defined at the time of evaluability evaluation, the time between the database soft lock and hard 
lock before unblinding. 
Excluding subjects who have major protocol deviations will decrease the variability in treatment 
response and will allow for a better determination of dose-response relationship of S5G4T-1, 
E-BPO Cream, 5%. 
8.1.10 
Active-Control Studies Intended to Show Equivalence 
Not applicable to this study. 
8.1.11 
Examination of Subgroups 
Subset analyses will be conducted for the ITT populations for the subgroups based on at least the 
following:  
• Baseline Global Severity; 


 
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o Categorized as Baseline IGA = 3 (moderate) and Baseline IGA = 4 (severe); due 
to the inclusion criteria requiring subjects to have either a 3 or 4 IGA score at 
study entry other IGA response categories will not be presented 
• Sex; 
o Male versus female subjects 
• Age; 
o Dichotomized to less than the median age of ITT subjects and greater than or 
equal to the median age of ITT subjects 
• Ethnicity; 
o Categorized as Hispanic or Latino and Not Hispanic or Latino; ethnicities of Not 
Reported and Unknown will not be included 
• Race 
o Categorized as White and Non-White; subjects indicating more than one race 
category which includes both white and a non-white race will be summarized 
under the Non-White subgroup. 
Subset analyses will be conducted on the variables absolute change from Baseline in 
inflammatory lesions at Week 12 as well as the dichotomized global severity score at Week 12. 
These analyses will contain only descriptive statistics. 
8.2 
Disposition of Subjects 
The number of subjects included in each analysis population (randomized, ITT, Safety, and PP) 
will be summarized by treatment group and overall. The number of subjects completed and 
discontinued (including the reasons for discontinuation) will be summarized for each treatment 
group as well as by overall. The percentages will be calculated based on the number of 
randomized patients, unless otherwise specified. 
8.3 
Protocol Deviations 
In order to define the PP Population, protocol deviations potentially influencing the evaluation of 
the primary efficacy endpoint will be defined as major deviations. The protocol deviations that 
will exclude a subject from PP are given in Section 8.4.4. 


 
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In case other deviations detected during the study conduct are considered to potentially influence 
the evaluation of the primary efficacy endpoint, these deviations will be documented prior to the 
database lock and the patients having these deviations will be excluded from the PP Population. 
All protocol deviations will be reported to the sponsor and recorded throughout the study. 
Protocol deviations will not be entered into the database. SolGel will provide a list of protocol 
deviations to QST. A tabulation of protocol deviations will be presented in a data listing. 
8.4 
Data Sets Analyzed 
Subjects will be presented/summarized based on the primary reason for exclusion. Below is the 
order to be used in summaries:  
8.4.1 
Randomized Population 
All subjects who are randomized to study treatment will be included in the randomized 
population and will be analyzed according to the treatment group they were randomized. Listings 
will be provided for all randomized subjects. 
8.4.2 
Intent-to-Treat (ITT) Population 
All subjects in the randomized population who are dispensed study product will be included in 
the ITT population and will be analyzed according to the treatment group they were randomized. 
All efficacy analyses will be presented using the ITT population. 
8.4.3 
Safety Population 
All subjects in the randomized population who are presumed to have used the study product at 
least once and who provide at least one post-baseline safety evaluation will be included in the 
Safety population and will be analyzed according to the treatment they received. Presumed to 
have used study product will be defined as having at least one confirmed application of study 
medication. All safety analyses will be performed using the Safety population. 
8.4.4 
Per-Protocol (PP) Population 
All subjects in the ITT population who complete the Week 12 evaluation without noteworthy 
study protocol violations (i.e., any patient or investigator activity that could have possibly 
interfered with the therapeutic administration of the treatment or the precise evaluation of 
treatment efficacy) will be included in the PP population and analyzed according to the treatment 
group they received. The PP population will include subjects in the ITT population who do not 
meet any of the following criteria: 


 
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• Failed any of the inclusion/exclusion criteria; 
• Have taken any interfering concomitant medications; 
• Did not attend the Week 12 Visit; 
• Missed more than 1 post-baseline study visit prior to Week 12; 
• Have not been compliant with the dosing regimen (i.e., Patients may not miss more than 
five consecutive days of dosing and must take 80 to 120% of expected applications. The 
number of expected applications will be determined for each patient based on the length 
of their participation in the study); 
• Out of visit window (± 4 days) at the 12-week Visit. 
Subjects that discontinue from the study due to an AE related to study treatment or documented 
lack of treatment effect will be included in the PP population. Data for these subjects will not be 
imputed by multiple imputation but rather their data will be imputed with values consistent with 
their status as treatment failures. See Section 8.1.5 for additional detail. Prior to breaking the 
blind, other additional criteria may be added to the list to accommodate for unforeseen events 
that may occur during the conduct of the trial and result in noteworthy study protocol violations. 
All efficacy analyses performed on the PP population will be according to the treatment they 
received. 
8.5 
Demographic and Other Baseline Characteristics 
All Baseline summaries will be done on the ITT, PP, and Safety populations by treatment group 
and overall. 
Sex (categorical), race (categorical), and ethnicity (categorical) will be summarized by counts 
and percentages. Age (continuous), height (cm) (continuous), and weight (kg) (continuous), and 
body mass index (BMI) (continuous) will be summarized with descriptive statistics.  
Age will be calculated as the difference in days between the date of birth and the date of 
informed consent and converted to years by dividing the number of days by 365.25 and using a 
floor function to drop the decimal portion. In case the exact birth day is missing, day 15 will be 
used. The BMI will be calculated as weight (kg) divided by squared height (m2). 
Medical histories will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) dictionary and presented in a by-subject listing. 


 
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The medical history data will be summarized with frequencies and percentages of patients with 
at least one medical history term reported, and patient frequencies and percentages on the System 
Organ Class (SOC) and Preferred Term (PT) levels. The number of events will also be 
summarized. The table will be sorted by overall descending frequency of SOC and then, within a 
SOC, by overall descending frequency of PT. 
8.6 
Prior and Concomitant Medications 
Concomitant medications will be coded to preferred name and Anatomical Therapeutic Chemical 
(ATC) classification of ingredients using the World Health Organization (WHO) Drug Global 
Dictionary, Format B3, Version March 1, 2018. 
Medications which start prior to first application will be considered prior medications. Ongoing 
medications and medications ending after the date of first application will be considered 
concomitant medications. If the date of first application is unknown and the medication is not 
listed as ongoing the interval will be considered “unknown”. If the date of first application is 
unknown and the medication is listed as ongoing the interval will be considered concomitant.  
Incomplete medication start and end dates will be imputed as described in Section 8.1.5.3 
A summary of prior and concomitant medications will be provided. 
A by-subject listing of all prior and concomitant medications will be presented for the Safety 
population.  
8.7 
Analysis of Efficacy 
Inflammatory lesion counts will be summarized at each evaluation from Baseline through 
Week 12. Absolute and percent change in lesion counts will be summarized at Weeks 2, 4, 8, and 
12. IGA scores will be summarized from Baseline through Week 12 using descriptive statistics. 
The dichotomized IGA scores will be summarized at Weeks 2, 4, 8, and 12 using descriptive 
statistics. 
All efficacy results will be presented in by-subject listings. 
8.7.1 
Primary Efficacy Analysis 
The primary efficacy analysis will be presented on both the ITT and PP populations. 


 
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8.7.1.1 
Lesion Counts 
Tests of superiority for the absolute change from Baseline in inflammatory lesions will be based 
on either parametric or non-parametric methods consistent with the statistical assumptions 
required to support the analyses. Specifically, the tests of superiority will be based on an 
ANCOVA with factors of treatment and analysis center and the respective Baseline lesion count 
as a covariate or on ranked data submitted to an ANCOVA with factors of treatment and analysis 
center and the respective Baseline lesion count as a covariate. If the treatment-by-analysis center 
interaction effect is significant at an alpha less than 0.10, then the effect will be included in the 
model; otherwise it will be removed. 
A skewness test, based on the methods presented by J.H. Zar [4], will be applied to the residuals 
resulting from an ANCOVA. A two-sided p-value for the skewness test significant at 0.01 will 
imply the use of the non-parametric method. If a parametric analysis is indicated, the results of 
the parametric analysis will be considered the primary analysis. Should a non-parametric 
analysis be indicated, the absolute or percent changes in inflammatory lesions will be rank 
transformed prior to submitting them to the ANCOVA. Results of the rank-transformed analyses 
then will be considered the primary analysis; however, results of the non-ranked transformed 
analyses will also be presented. 
The following steps provide a brief synopsis of the process that will be followed.  
1. Missing data will be imputed using multiple imputation. Refer to Section 8.1.5.1.  
2. The pooling analysis will be conducted. Refer to Section 8.1.7.  
a. The treatment-by-analysis center interaction p-values from both parametric and 
non-parametric (unranked and ranked) analyses will be presented, along with the 
skewness p-value calculated from the residuals from the unranked ANCOVA. 
The skewness p-value will determine which analysis results to report:  
i. Skewness p-value > 0.01: Report results based on the parametric 
(unranked) approach.    
ii. Skewness p-value ≤ 0.01: Report results based on the non-parametric 
(ranked) approach. 
3. For the primary efficacy analysis 
a. Results of both parametric and non-parametric (unranked and ranked) analyses 
will be presented. For each, data will be submitted to an ANCOVA with factors of 
treatment and analysis center and Baseline lesion count as a covariate (if the 


 
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treatment-by-analysis center interaction p-value is ≤ 0.10, the interaction will also 
be included in the model). The residuals from the unranked analysis will be used 
to calculate the skewness p-value. The skewness p-value will determine which 
analysis results to report:  
i. Skewness p-value > 0.01: Report results from the parametric (unranked) 
ANCOVA.  
ii. Skewness p-value ≤ 0.01: Report results from the non-parametric (ranked) 
ANCOVA.  
4. If there was a significant treatment by analysis center interaction (as determined in step 1 
– the pooling analysis), a sensitivity analysis will be performed as described in 
Section 8.1.7 to find the extreme analysis center(s). Then step 3 above will be repeated 
the extreme analysis center(s) removed, to confirm the treatment response.  
8.7.1.2 
Investigator Global Assessment (IGA) 
The IGA will be dichotomized into “success” and “failure” with a patient considered a success 
for those visits if the IGA is “clear” or “almost clear”. The analysis of the dichotomized IGA will 
be based on a logistic regression test with factors of treatment group and analysis center. 
8.7.2 
Sensitivity Efficacy Analysis 
8.7.2.1 
Sensitivity Analyses for Absolute Change in Lesion Count 
The first sensitivity analysis for absolute change in lesion count will use a repeated measures 
ANCOVA, with treatment, analysis center, visit (i.e., Weeks 2, 4 and 8), and treatment group by 
visit interaction as independent factors and a covariate of Baseline lesion count. In this analysis, 
data from all post-baseline visits will be included with no imputation for missing data. 
The second sensitivity analysis will use the model based multiple imputation method to impute 
missing data for the absolute change in lesion counts at Week 12. The multiple imputation will 
involve 3 principal tasks: 
1. Missing values will be filled in 5 times to generate 5 complete data sets. The imputation 
model used will be an ANCOVA with factors of treatment group and analysis center, and 
a covariate of Baseline lesion count (i.e., the imputation model will be the same as the 
analysis model).  
Syntax: 


 
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proc mi data=datain out=dataout seed=&seed. nimpute=5 <options>; 
  class trtpn sitegr1; 
  var trtpn baseline sitegr1 week12; 
  monotone logistic (sitegr1=trtpn baseline); 
  monotone reg (week12=trtpn baseline sitegr1); 
run; 
2. Each complete data set will be analyzed with an ANCOVA with factors of treatment 
group, and analysis center, and a covariate of Baseline lesion count. Appropriate 
modifications will be made should the analysis be based on a non-parametric method. 
3. Results from these analyses will be combined into a single inference. 
One random seed will be needed to impute the inflammatory lesion counts. The following 
random seed has been pre-specified by using a random number generator: 
 
Inflammatory Lesion Count Seed=1827396453 
8.7.2.2 
Sensitivity Analyses for IGA 
The first sensitivity analysis for the dichotomized IGA success will use a repeated measures 
logistic regression model (generalized estimating equations), with dichotomized IGA success as 
the dependent variable and treatment, analysis center, visit (i.e., Weeks 2, 4 and 8), and treatment 
group by visit interaction as independent factors. In this analysis, data from all post-baseline 
visits will be included with no imputation for missing data. 
The second sensitivity analysis will use the model based multiple imputation method to impute 
missing data for the dichotomized IGA data. The multiple imputation will involve 3 principal 
tasks: 
1. Missing values will be filled in 5 times to generate 5 complete data sets. The imputation 
model used logistic regression with factors of treatment group and analysis center (i.e., 
the imputation model will be the same as the analysis model). 
Syntax:  
proc mi data=datain out=dataout seed=&seed. nimpute=5 <options>; 
  class trtpn sitegr1 diiga; 
  var trtpn sitegr1 diiga; 
  monotone logistic (sitegr1=trtpn); 
  monotone logistic (diiga=trtpn sitegr1); 
run; 


 
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2. Each complete data set will be analyzed with a logistic regression a factors of treatment 
group and analysis center. 
3. Results from these analyses will be combined into a single inference. 
One random seed will be needed to impute IGA. The following random seed has been 
pre-specified by using a random number generator: 
IGA Seed= 65762814 
8.7.3 
Secondary Efficacy Analysis 
Appropriate descriptive statistics will be computed for all secondary efficacy parameters. 
The percent change from Baseline to Week 12 in inflammatory lesion counts and the absolute 
change from Baseline in inflammatory lesion counts at Week 8 and Week 4 will be analyzed 
using the same ANCOVA method described for the primary endpoint. 
The proportion of subjects who are dichotomized to success (“clear” or “almost clear”) at Week 
8 and Week 4 will be analyzed using the same logistic analysis method described for the 
co-primary endpoint. 
A stepwise process will be conducted for testing the secondary efficacy endpoints in order to 
control for multiplicity, refer to Section 8.1.8.  
The secondary efficacy analysis will be presented on only the ITT population. 
8.7.4 
Supportive Efficacy Analysis 
Appropriate descriptive statistics will be computed for all supportive efficacy parameters. 
In addition, the mean change comparison in PAPSS item 1 (burning), item 2 (itching), item 3 
(redness) and item 4 (bumps) from Baseline to Week 12 will be analyzed  using an analysis of 
variance (ANOVA) with factors of treatment, analysis center, and the respective Baseline score. 
Missing values will not be imputed. 
A set of cumulative distribution function curves will be generated to allow for the evaluation of 
within-person change by treatment group. Specifically, 5 plots will be generated showing the 
change from Baseline to Week 12 (and/or other, earlier time points if so desired) by the 
cumulative percent of subjects for each of the treatment arms (change on the x-axis will be 
expressed as absolute change) on: 
• PAPSS total scale scores 


 
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o The total scale score is the sum of PAPSS items 1 through 4.  
• PAPSS item 1 (burning) scores 
• PAPSS item 2 (itching) scores 
• PAPSS item 3 (redness) scores 
• PAPSS item 4 (bumps) scores 
8.7.5 
Exploratory Endpoint Analysis 
The mean change in RosaQoL subscale scores from Baseline to Week 12 will be summarized 
using descriptive statistics. 
The subscores for the RosaQoL are computed as follows:  
Total Score: the unweighted mean of all RosaQoL questions 
Symptom subscale score: the unweighted mean of the following symptom questions 
My rosacea burns or stings (item #2) 
My rosacea is irritated (item #6) 
My rosacea makes my skin sensitive (item #9) 
My skin feels bumpy (uneven, not smooth, irregular) (item #16) 
My skin flushes (item #17) 
My skin gets irritated easily (cosmetics, aftershaves, cleansers) (item #18) 
My eyes bother me (feels dry or gritty) (item #19) 
Functional subscale score: the unweighted mean of the following functional questions 
I try to cover up my rosacea (with make-up) (item #13) 
I avoid certain foods or drinks because of my rosacea (item #15) 
I avoid certain environments (heat, humidity, cold) because of my rosacea (item #21) 
Emotion subscale score: the unweighted mean of the following emotion questions 
I worry that my rosacea may be serious (item #1) 
I worry about getting scars from my rosacea (item #3) 


 
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I worry that my rosacea may get worse (item #4) 
I worry about side effects from rosacea medications (item #5) 
I am embarrassed by my rosacea (item #7) 
I am frustrated by my rosacea (item #8) 
I am annoyed by my rosacea (item #10) 
I am bothered by the appearance of my skin (redness, blotchiness) (item #11) 
My rosacea makes me feel self-conscious (item #12) 
I am bothered by persistence/reoccurrence of my rosacea (item #14) 
I think about my rosacea (item #20) 
Each individual item should be scored as follows: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 
and 5=All the time. Missing data values will not be used. If a subscale has items with missing 
results, the subscore and the total will not be calculated.  
8.8 
Safety Evaluation 
8.8.1 
Extent of Exposure 
The extent of exposure to study drug in each treatment group will be summarized by total 
number of days of exposure, total number of applications, number of missed applications and 
number and percentage of subjects who are compliant. A subject will be considered compliant 
with the dosing regimen if the subject applied 80% to 120% of the expected number of 
applications and did not miss more than 5 consecutive applications while enrolled in the study. 
Days of exposure = Date of last study application – Date of first study application + 1 
The total number of applications taken is as follows: 
(Date of Last Application – Date of First Application + 1) – (Number of Days marked as missed 
applications on the CRF) + (Number of extra applications marked on the CRF) 
If a subject did apply medication on the last day, the total number of applications expected is as 
follows: 
Date Subject End Participation – Date of Baseline +1.  
If the total number of applications exceeds 89 then it will be set to 89. 


 
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If a subject did not apply medication on the last day, the total number of applications expected is 
as follows: 
Date Subject End Participation - Date of Baseline 
If the total number of applications exceeds 88 then it will be set to 88. 
Compliance will be calculated as a percentage as 100 times the total number of applications 
taken from the first application until Week 12 divided by the total number of applications 
expected from first application until Week 12. Subjects who discontinue study medication before 
Week 12 will be considered to be 0% compliant for the number of days from discontinuing study 
medication until Week 12.  
Compliance will not be calculated for subjects who are lost to follow-up or subjects who have 
unknown first or last application dates.  
8.8.2 
Adverse Events (AEs) 
All AEs occurring during the study will be recorded and classified on the basis of MedDRA 
terminology. Descriptions of AEs will include the date of onset, the date the AE ended, the 
severity of the AE, the relationship to study product, the action taken regarding study product 
usage, the action taken to treat the AE, and the outcome. All reported treatment-emergent AEs 
(TEAEs) will be summarized by the number of patients reporting AEs, system organ class, 
severity, seriousness, and relationship to study product. TEAEs are those AEs with an onset on 
or after the date of the first study product application; if the AE is not indicated as prior to first 
application on the CRF then it will be considered a TEAE.  
AEs will be summarized by treatment group and severity. Each patient will be counted only once 
within a system organ class or a preferred term by using the AEs with the highest severity within 
each category. 
AEs will be summarized by treatment group and relationship to study product. Each patient will 
be counted only once within a system organ class or a preferred term by using the AEs with the 
greatest relationship within each category. 
If relationship to study drug is reported as definitely, probably, or possible, then this is defined as 
related. If relationship to study drug is reported as unlikely or not related, then this is defined as 
unrelated. 
Comparisons among treatment groups will be made by tabulating the frequency of patients with 
one or more AEs (classified into MedDRA terms) during the study. The Fisher’s Exact test will 
be used to compare the proportion of patients in each treatment group who report any AE at a 


 
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significance level of 0.05. The specific system organ classes and preferred terms analyzed will be 
those that are reported by at least one percent of the patients in any treatment group. 
All information pertaining to AEs noted during the study will be listed by patient, detailing 
verbatim given by the investigator, preferred term, system organ class, start date, stop date, 
severity, actions taken, and drug relatedness. The AE onset will also be shown relative (in 
number of days) to the day of initial application of the randomized study product. 
Serious adverse events (SAEs) will be tabulated by patient within treatment groups. 
In addition, a list of patients who discontinued from the study and a list of patients who 
experienced SAEs will also be provided. 
8.8.3 
Clinical Laboratory Evaluation 
Urine pregnancy test results will be presented in a by-subject listing.  
8.8.4 
Other Observations Related to Safety 
8.8.4.1 
Cutaneous Safety Assessments 
Descriptive statistics by treatment group and visit will be provided for dryness and scaling.  
8.8.4.2 
Local Tolerability Assessments 
Descriptive statistics by treatment group and visit will be provided for itching and 
burning/stinging.  
8.8.4.3 
Vital Signs 
Vital sign measurements include heart rate (HR), sitting blood pressure (BP) (both systolic and 
diastolic), body temperature, and weight. The data will be summarized with descriptive statistics 
by visit and treatment group. In addition, the changes from baseline will be summarized with 
descriptive statistics. 
Furthermore, to identify potentially clinically significant vital signs, the following criteria will be 
used and tabulated as a shift table by visit: 
• Systolic Blood Pressure: <90 mmHg (low), 90-140 mmHg (normal), >140 mmHg (high) 
• Diastolic Blood Pressure: <90 mm Hg (low), 90-100 mmHg (normal), >100 mmHg 
(high) 


 
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• Heart Rate: <60 beats per minute (low), 60-100 beats per minute (normal), >100 beats 
per minute (high). 
8.8.4.4 
Physical Examination 
Abnormal physical examination findings will be summarized by body system, visit, and 
treatment group. In addition to the summary, all physical examination findings will be listed.  
8.8.4.5 
Patient Global Impression of Treatment Side-Effects (PGI-SE) 
Descriptive statistics by treatment group and visit will be provided for PGI-SE.  
9. DETERMINATION OF SAMPLE SIZE 
The following power calculations are based on the observed Week 12 results of the Phase 2 
study, SGT-EBP01-09. This study was a three-arm trial including E-BPO cream, 1% and 5%, 
and vehicle in the treatment of rosacea. Estimates from the E-BPO cream, 5% arm were used in 
the power assessments. The anticipated randomization ratio is 2:1 for E-BPO cream, 5% and 
vehicle, respectively. The computations were performed with nQuery Advisor Version 7.0 using 
a two-sided test with a statistical significance value of 0.05. 
A sample size of 86 in the E-BPO cream, 5% and 43 in the vehicle group has 95% power to 
detect a statistically significant difference in the proportion of patients who have at least a 
2-grade reduction at Week 12 from Baseline in IGA and are clear or almost clear. The estimated 
percentages with a 2-grade reduction at Week 12 from Baseline in the IGA and clear or almost 
clear are 53.3% and 20.0% for the E-BPO cream and vehicle, respectively. 
A sample size of 200 in the E-BPO cream, 5% and 100 in the vehicle group has 95% power to 
detect a statistically significant difference in inflammatory lesions. The estimated absolute 
change from Baseline in treatment means were -14.1 and -7.4 for E-BPO cream and vehicle, 
respectively, with a standard deviation (SD) of 6.70 and 17.24, respectively. 
The sample sizes above will be increased to give a planned enrollment of 234 in the E-BPO 
cream, 5% group and 117 in the vehicle group since the Phase 3 trial is expected to enroll 
patients who are as a group more severe than those of the Phase 2 trial. This is a consequence of 
some changes in the inclusion criteria. 
10. CHANGES IN THE PLANNED ANALYSES 
There are no changes in the conduct of the study, but there are minor changes to the planned 
analyses. 


 
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Due to feedback received, the primary efficacy analysis was adjusted back to the original 
analysis. The modification to only use the non-parametric version as described in v4 of the 
protocol was not accepted by the agency. The original approach uses an ANCOVA analysis with 
the terms for treatment, analysis center, and Baseline count (and treatment-by-center interaction 
if the term is significant at 0.10). If the two-sided p-value for the skewness test is significant at 
0.01, then the rank-transformed data will be used instead of nominal values. The original 
approach was accepted by the agency.  
The pooling analysis described in the protocol is updated in the statistical analysis plan (SAP) to 
reflect the intended analysis. The protocol discusses pooling sites with five or fewer subjects 
enrolled in each treatment arm. Taking into consideration the randomization ratio, the SAP 
requires ten subjects in the active treatment arm and five subjects in the vehicle group.  
As part of the pooling analysis, the treatment effect within investigational site must be 
investigated. The protocol states the site main effect will be examined by using a one-way 
analysis of variance (for lesion count variables) or a logistic regression analysis (for 
dichotomized IGA) with a factor of site. The SAP instead explains site will be incorporated into 
the primary analysis models. Change from Baseline in lesion counts will be analyzed with an 
ANCOVA (unranked or ranked) with factors of treatment group, investigational site and 
treatment group by investigational site interaction, and the respective Baseline lesion count 
variable as a covariate. The dichotomized primary endpoint will be analyzed with a logistic 
regression with factors of treatment group, investigational site and the interaction term of 
treatment group by investigational site. 
The protocol describes repeated measures sensitivity analyses for the primary efficacy endpoints. 
Treatment group, analysis center and visit are listed as factors for the repeated measures 
analyses. In addition to these factors, the SAP includes a factor of treatment group by visit 
interaction. 
The protocol describes imputing only Week 12 data with MCMC imputation, but all missing 
post-baseline data will be imputed. Only 2 seeds are needed for the MCMC imputation for 
inflammatory lesions (one seed for S5G4T-1 and one seed for vehicle) instead of the 6 seeds that 
are given in the proctol. Only 2 seeds are needed for the MCMC imputation for IGA (one seed 
for S5G4T-1 and one seed for vehicle) so only one seed was given in the SAP. Using only the 
Week 12 seed addresses concern from the FDA with regard to imputing data at each visit as the 
multiple seeds in the protocol suggests. Only one seed is needed for treatment group as PROC 
MI will impute data across the visits.    
All seeds given the in SAP were produced in SAS as seeds given in the 54-02 protocol were 
identical to the 54-01 study protocol.  


 
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Geographic region was removed from the examination of subgroups as all sites in the study are 
in the United States.  
11. REFERENCES 
1. Jansen T. and Plewig G. Rosacea: classification and treatment. JR Soc Med. 1997; 
90(3):144-150. 
2. McDonnell JK and Tomecki KJ. Rosacea: an update. Clev Clinic J Med. 2000; 
67(8):587-590. 
3. Zar, JH. Bio-statistical analysis, 1984 2nd ed. Englewood Cliffs (NJ) Prentice-Hall. 
(Available upon request). 
 


 
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12. INDEX OF PLANNED TABLES 
Table 14.0.1: Summary of Subject Completion/Discontinuation  (All Randomized Subjects) ....43 
Table 14.0.2.1: Summary of Subject Enrollment and Evaluability  (All Randomized Subjects)..44 
Table 14.0.2.2: Summary of Subject Evaluability by Analysis Center and Investigational Site  (A
ll Randomized Subjects) .......................................................................45 
Table 14.1.1.1: Summary of Subject Demographic Characteristics  (Intent-to-
Treat Population) ...................................................................................46 
Table 14.1.1.2: Summary of Subject Demographics (Per-Protocol Population) ...........................47 
Table 14.1.1.3: Summary of Subject Demographics (Safety Population) .....................................47 
Table 14.1.2.1: Subject Baseline Characteristics  (Intent-to-Treat Population) ............................48 
Table 14.1.2.2: Subject Baseline Characteristics (Per-Protocol Population).................................49 
Table 14.1.2.3: Subject Baseline Characteristics (Safety Population)...........................................49 
Table 14.1.3.1: Summary of Medical History by System Organ Class and Preferred 
Term  (Intent-to-Treat Population)........................................................50 
Table 14.1.3.2: Summary of Medical History by System Organ Class and Preferred Term (Per-
Protocol Population) .............................................................................50 
Table 14.1.3.3: Summary of Medical History by System Organ Class and Preferred Term (Safety 
Population) ............................................................................................50 
Table 14.1.4.1: Summary of Prior Medications by ATC Level 2 and Preferred 
Name  (Safety Population) ....................................................................51 
Table 14.1.4.2: Summary of Concomitant Medications by ATC Level 2 and Preferred 
Name  (Safety Population) ....................................................................52 
Table 14.2.1.1: Pooling Analysis for Primacy Efficacy Endpoints   (Intent-to-Treat Population)53 
Table 14.2.1.2: Primary Efficacy Analysis: Absolute Change from Baseline in Inflammatory 
Lesion Count and Dichotomized IGA Success at Week 12  (Intent-to-
Treat Population) ...................................................................................54 
Table 14.2.1.3: Primary Efficacy Analysis: Absolute Change from Baseline in Inflammatory 
Lesion Count and Dichotomized IGA Success at Week 12 (Per-
Protocol Population) .............................................................................55 
Table 14.2.2.1.1: Summary of Inflammatory Lesion Counts at Each Evaluation  (Intent-to-
Treat Population) ...................................................................................56 
Table 14.2.2.1.2: Summary of Inflammatory Lesion Counts at Each Evaluation (Per-Protocol 
Population) ............................................................................................60 


 
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Table 14.2.2.2: Summary of Absolute Change in Inflammatory Lesion Counts at Week 12 by 
Analysis Center  (Intent-to-Treat Population).......................................61 
Table 14.2.3.1.1: Summary of Investigator Global Assessment at Each Evaluation  (Intent-to-
Treat Population) ...................................................................................62 
Table 14.2.3.1.2: Summary of Investigator Global Assessment at Each Evaluation (Per-Protocol 
Population) ............................................................................................66 
Table 14.2.3.2: Summary of Investigator Global Assessment (Achieving Clear or Almost Clear) 
at Week 12 by Analysis Center (Intent-to-Treat Population) ...............67 
Table 14.2.4.1: Subgroup Summaries of Primary Endpoints  (Intent-to-Treat Population) ..........68 
Table 14.2.5.1: Sensitivity Analysis of Primary Endpoints: Absolute Change from Baseline in 
Inflammatory Lesion Count and Dichotomized IGA Success at Week 
12  (Intent-to-Treat Population) ............................................................73 
Table 14.2.6.1: Secondary Efficacy Analyses  (Intent-to-Treat Population) .................................75 
Table 14.2.7.1: Patient Assessment of Papulopustular rosacea Signs and Symptoms (PAPSS) 
Analyses at Week 12  (Intent-to-Treat Population) ..............................78 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms 
(PAPSS) at Each Evaluation   (Intent-to-Treat Population)..................79 
Table 14.2.8.2: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms 
(PAPSS) at Each Evaluation (Per-Protocol Population) .......................93 
Table 14.2.9.1: Summary of Erythema Assessment at Each Evaluation   (Intent-to-Treat 
Population) ............................................................................................94 
Table 14.2.9.2: Summary of Erythema Assessment at Each Evaluation (Per-
Protocol Population) .............................................................................95 
Table 14.2.10.1: Summary of Telangiectasia Assessment at Each Evaluation   (Intent-to-Treat 
Population) ............................................................................................96 
Table 14.2.10.2: Summary of Telangiectasia Assessment at Each Evaluation (Per-
Protocol Population) .............................................................................97 
Table 14.2.11.1: Summary of Patient Global Impression of Change (PGI-C) at Each 
Evaluation   (Intent-to-Treat Population) ..............................................98 
Table 14.2.11.2: Summary of Patient Global Impression of Change (PGI-C) at Each Evaluation 
(Per-Protocol Population)....................................................................100 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at 
Each Evaluation   (Intent-to-Treat Population) ...................................101 
Table 14.2.12.2: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at 
Each Evaluation (Per-Protocol Population) ........................................112 


 
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Table 14.2.13.1: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each 
Evaluation   (Intent-to-Treat Population) ............................................113 
Table 14.2.13.2: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each 
Evaluation (Per-Protocol Population) .................................................114 
Table 14.2.14.1: Summary of Patient Global Impression of Treatments Satisfaction (PGI-TS) at 
Each Evaluation   (Intent-to-Treat Population) ...................................115 
Table 14.2.14.2: Summary of Patient Global Impression of Treatments Satisfaction (PGI-TS) at 
Each Evaluation (Per-Protocol Population) ........................................116 
Table 14.2.15.1: Summary of RosaQoL Questionnaire Responses at Baseline and Week 
12  (Intent-to-Treat Population) ..........................................................117 
Table 14.2.15.2: Summary of RosaQoL Questionnaire Responses at Baseline and Week 12 (Per-
Protocol Population) ...........................................................................121 
Table 14.3.0.1: Summary of Extent of Exposure  (Safety Population) .......................................122 
Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability 
Evaluations  (Safety Population) .........................................................123 
Table 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event 
Characteristics  (Safety Population) ....................................................131 
Table 14.3.1.2.2: Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term (Safety Population)....................................133 
Table 14.3.1.2.3: Summary of Treatment-Emergent 
Adverse Events by Severity  (Safety Population) ...............................134 
Table 14.3.1.2.4: Summary of Treatment-Emergent Adverse Events by Relationship to Study 
Drug (Safety Population) ....................................................................135 
Table 14.3.1.3.1: Summary of Treatment-Emergent Serious Adverse Event 
Characteristics  (Safety Population) ....................................................136 
Table 14.3.1.3.2: Summary of Treatment-Emergent Serious Adverse Events by MedDRA 
System Organ Class and Preferred Term (Safety Population) ............138 
Table 14.3.1.3.3: Summary of Serious Treatment-Emergent 
Adverse Events by Severity  (Safety Population) ...............................139 
Table 14.3.1.3.4: Summary of Treatment-Emergent Serious Adverse Events by Relationship to 
Study Drug (Safety Population) ..........................................................140 
Table 14.3.1.4.1: Summary of Vital Signs  (Safety Population) .................................................141 
Table 14.3.1.4.2: Shift Table of Vital Signs  (Safety Population) ...............................................146 
 


 
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Table 14.3.1.5: Summary of Abnormal Physical Examination Findings by Visit  (Safety 
Population) ..........................................................................................147 
Table 14.3.1.6: Summary of Patient Global Impression of Treatment Side-Effects (PGI-SE) at 
Each Evaluation   (Safety Population) ................................................148 
 


 
 
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Table 14.0.1: Summary of Subject Completion/Discontinuation 
 (All Randomized Subjects) 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
    (N=xxx)  
 
  
  Total  
 
(N=xxx)  
 
Completed Study 
Yes 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
No 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Discontinuation 
Adverse Event 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Lost to Follow-Up 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Lack of Efficacy 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Pregnancy 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Protocol Violation 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Withdrawal by Subject 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Study Terminated by Sponsor 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Physician Decision 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Worsening of Condition 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Other 
xx 
( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.0.2.1: Summary of Subject Enrollment and Evaluability 
 (All Randomized Subjects) 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
  
Total  
 
(N=xxx)  
 
Number of Randomized Subjects 
xx 
xx 
xx 
Number of Subjects Included in the ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reason Excluded from the ITT Population 
Not Dispensed Study Drug 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the Safety Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the Safety Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reasons Excluded from the Safety Populationa 
No Documented use of Study Drug 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
No Post Baseline Safety Assessment 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the PP Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the PP Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Reasons Excluded from the PP Populationa 
Not Included in ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Violated Inclusion/Exclusion Criteria 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Used Interfering Concomitant Medication 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Did not Attend Week 12/ET Visit 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Missed More Than 1 Post-Baseline Visit Prior to Week 12 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Compliant with Dosing Regimenb 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12/ET Visit Out of Window (+/-4 days) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
   Other 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a  Table includes primary reason (assigned in order presented in table) for reason subject was excluded. 
b Subjects lost to follow-up not included. A subject was considered compliant with the dosing regimen if the subject applied 80-120% of the expected number of 
applications and did not miss more than 5 consecutive applications while enrolled in the study. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 


 
 
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Table 14.0.2.2: Summary of Subject Evaluability by Analysis Center and Investigational Site 
 (All Randomized Subjects) 
(Page 1 of xx) 
 
E-BPO 5% Cream  
  
Vehicle Cream  
 
 
Analysis 
 
Center  
 
 Investigational 
 
Site  
 
 
Number 
 
Randomized 
  
ITT  
  
PP  
  
Safety  
  
ITT  
  
PP  
  
Safety  
 
xx 
xx 
 
xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
xx 
xx 
 
xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
xx 
 
xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
xx 
xx 
 
xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
xx 
xx 
 
xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
xx 
 
xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
xx 
 
xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 xx 
 
 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.1.1: Summary of Subject Demographic Characteristics 
 (Intent-to-Treat Population) 
(Page 1 of 2) 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
  
Total  
 
(N=xxx)  
 
Age (years) 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
< Median (xx years) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
≥ Median (xx years) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Sex 
n 
xx 
xx 
xx 
Male 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Ethnicity 
n 
xx 
xx 
xx 
Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Not Reported/Unknown 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a See Listing 16.2.4.1 for a complete list of other races. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.1.1: Summary of Subject Demographics 
 (Intent-to-Treat Population) 
(Page 2 of 2) 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
  
Total  
 
(N=xxx)  
 
Race 
n 
xx 
xx 
xx 
American Indian or Alaska Native 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
White 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Multiple/Othera 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a See Listing 16.2.4.1 for a complete list of other races. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
Repeat Table 14.1.1.1 for the following tables: 
 
Table 14.1.1.2: Summary of Subject Demographics (Per-Protocol Population) 
Table 14.1.1.3: Summary of Subject Demographics (Safety Population) 
 
 


 
 
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Table 14.1.2.1: Subject Baseline Characteristics 
 (Intent-to-Treat Population) 
(Page 1 of 2) 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
  
Total  
 
(N=xxx)  
 
Height (cm) 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
Weight (kg) 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
BMI (kg/m2) 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.1.2.1: Subject Baseline Characteristics 
 (Intent-to-Treat Population) 
(Page 2 of 2) 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
  
Total  
 
(N=xxx)  
 
Inflammatory Lesion Count 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
Investigator Global Assessment 
n 
xx 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.1.2.1 for the following table: 
 
Table 14.1.2.2: Subject Baseline Characteristics (Per-Protocol Population) 
Table 14.1.2.3: Subject Baseline Characteristics (Safety Population) 
 
 


 
 
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Table 14.1.3.1: Summary of Medical History by System Organ Class and Preferred Term 
 (Intent-to-Treat Population) 
(Page 1 of xx) 
 
System Organ Class 
Preferred Term 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
  
Vehicle Cream  
 
(N=xxx)  
 
  
Total  
 
(N=xxx)  
 
By Subjecta  By Eventb   By Subjecta   By Eventb   By Subjecta   By Eventb  
Number (%) of Subjects Reporting at Least One Medical History Term 
xx ( xx.x%)
xx ( xx.x%) 
xx ( xx.x%) 
System Organ Class 
xx ( xx.x%) xx 
xx ( xx.x%) xx 
xx ( xx.x%) xx 
Preferred Term 
xx ( xx.x%) xx 
xx ( xx.x%) xx 
xx ( xx.x%) xx 
 
 
a Counts reflect number of subjects reporting one or more medical history terms that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once. Percentages are based on the number of subjects in the safety population.  
b Counts reflect number of medical history terms that map to MedDRA.  
Note:  MedDRA Version 21.0 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
{NOTE TO PROGRAMMER: The table will be sorted by overall descending frequency of SOC and then, within a SOC, by overall descending 
frequency of PT} 
 
Repeat Table 14.1.3.1 for the following table: 
Table 14.1.3.2: Summary of Medical History by System Organ Class and Preferred Term (Per-Protocol Population) 
Table 14.1.3.3: Summary of Medical History by System Organ Class and Preferred Term (Safety Population) 
 
 


 
 
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Table 14.1.4.1: Summary of Prior Medications by ATC Level 2 and Preferred Name 
 (Safety Population) 
(Page 1 of xx) 
 
ATC Level 2 Terma 
Preferred Name 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Number (%) of Subjects Reporting at Least One Prior Medication 
xx ( xx.x%) 
xx ( xx.x%) 
ATC Level 2 Term 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Name 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Counts reflect number of subjects reporting one or more medications that map to the WHO term. At each level of summarization (ATC Level 2 Term or  
Preferred Name) subjects are counted once. Percentages are based on the number of subjects in the safety population.  
Note: WHO Drug Global Dictionary, Format B3, Version March 1, 2018 
Prior medications are those used before the date of first study drug application.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.1.4.2: Summary of Concomitant Medications by ATC Level 2 and Preferred Name 
 (Safety Population) 
(Page 1 of xx) 
 
ATC Level 2 Terma 
Preferred Name 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Number (%) of Subjects Reporting at Least One Concomitant Medication 
xx ( xx.x%) 
xx ( xx.x%) 
ATC Level 2 Term 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Name 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Counts reflect number of subjects reporting one or more medications that map to the WHO term. At each level of summarization (ATC Level 2 Term or  
Preferred Name) subjects are counted once. Percentages are based on the number of subjects in the safety population.  
Note: WHO Drug Global Dictionary, Format B3, Version March 1, 2018 
Concomitant medications are those used on/after the date of first study drug application.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.1.1: Pooling Analysis for Primacy Efficacy Endpoints  
 (Intent-to-Treat Population) 
 
Investigational Site Pooling Analysis   Analysis Center Pooling Analysis  
Endpoint 
 
 
Skewness 
 
P-Value 
 
 Investigational   
 Site by Tretment  
 Group P-Value  
 
Skewness 
 
P-Value 
 
 Analysis Center   
 
Tretment 
 
 Group P-Value  
Absolute Change from Baseline in Inflammatory Lesion Counts at Week 12 
x.xxxc 
Ranked Analysis 
x.xxxa 
x.xxxe 
Unranked Analysis 
x.xxxb 
x.xxxf 
Achieving Clear or Almost Clear at Week 12 
NA 
x.xxxd 
NA 
x.xxxg 
 
 
a P-value for the interaction term from a ranked analysis of covariance with factors of treatment, investigational site, treatment by investigational site interaction 
and Baseline lesion count as a covariate.  
b P-value for the interaction term from an unranked analysis of covariance with factors of treatment, investigational site, treatment by investigational site  
interaction and Baseline lesion count as a covariate.  
c Skewness test, based on methods presented by J.H. Zar (1984), assessed for each imputed dataset. The average p-value is presented. 
d P-value for the interaction term from a logistic regression with factors of treatment, investigational site, treatment by investigational site interaction.  
e P-value for the interaction term from a ranked analysis of covariance with factors of treatment, analysis center, treatment by analysis center interaction and 
Baseline lesion count as a covariate.  
g P-value for the interaction term from an unranked analysis of covariance with factors of treatment, analysis center, treatment by analysis center interaction and 
Baseline lesion count as a covariate.  
g P-value for the interaction term from a logistic regression with factors of treatment, analysis center, treatment by analysis center interaction.  
Note:  Multiple imputation (MCMC) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
{NOTE TO PROGRAMMER: ADJUST FOOTNOTE “d” AND/OR “g” IF FIRTH’S PENALIZED LIKELIHOOD IS NEEDED} 
 
 


 
 
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Table 14.2.1.2: Primary Efficacy Analysis: Absolute Change from Baseline in Inflammatory Lesion Count and Dichotomized IGA Success at Week 12 
 (Intent-to-Treat Population) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
N/A 
x.xxxd 
Failure 
xx.x% 
xx.x% 
 
a Least squares means, standard deviations and treatment p-value from an analysis of covariance with factors of treatment group and analysis center and  
Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. 
b Skewness test, based on methods presented by J.H. Zar (1984), assessed for each imputed dataset.  The average p-value is presented.  
c P-value from a ranked analysis of covariance with factors of treatment group and analysis center and Baseline lesion count as a covariate.   
d P-value from a logistic regression with factors of treatment group and analysis center.   
Note:  Multiple imputation (MCMC) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
{NOTE TO PROGRAMMER: ADJUST FOOTNOTE “d” IF FIRTH’S PENALIZED LIKELIHOOD IS NEEDED} 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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Repeat Table 14.2.1.2 for the following table: 
 
Table 14.2.1.3: Primary Efficacy Analysis: Absolute Change from Baseline in Inflammatory Lesion Count and Dichotomized IGA Success at Week 12 (Per-
Protocol Population) 
 
Update footnote to “Note: Missing values imputed using last observation carried forward.” 
 
 


 
 
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Table 14.2.2.1.1: Summary of Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 1 of 4) 
 
Inflammatory Lesion Counts 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Percent Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics for Weeks 2, 4, 8, and 12 represent average values, obtained from  
 
averaging the summary statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.2.1.1: Summary of Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 2 of 4) 
 
Inflammatory Lesion Counts 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Percent Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics for Weeks 2, 4, 8, and 12 represent average values, obtained from  
 
averaging the summary statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.2.1.1: Summary of Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 2 of 4) 
 
Inflammatory Lesion Counts 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Percent Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics for Weeks 2, 4, 8, and 12 represent average values, obtained from  
 
averaging the summary statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.2.1.1: Summary of Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 4 of 4) 
 
Inflammatory Lesion Counts 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Percent Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics for Weeks 2, 4, 8, and 12 represent average values, obtained from  
 
averaging the summary statistics generated from each imputed dataset. Negative values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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Repeat Table 14.2.2.1.1 for the following table: 
 
Table 14.2.2.1.2: Summary of Inflammatory Lesion Counts at Each Evaluation (Per-Protocol Population) 
 
Change footnote to “Note: Missing values imputed using last observation carried forward. Negative values represent decrease from Baseline.” 
 
 


 
 
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Table 14.2.2.2: Summary of Absolute Change in Inflammatory Lesion Counts at Week 12 by Analysis Center 
 (Intent-to-Treat Population) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Analysis Center (Investigational Sites) 
 
n 
 
 
Mean 
  SD   
n 
 
 
Mean 
  SD  
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
xx (y, z) 
xx 
xx.x 
xx.xx 
xx 
xx.x 
xx.xx 
 
 
.
Note:  Multiple imputation (MCMC) used to impute missing values. Summary statistics represent average values, obtained from averaging the summary  
 
statistics generated from each imputed dataset. Negative values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
 
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Table 14.2.3.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 1 of 4) 
 
Investigator Global Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 2 
0 - Clear 
  
xx.x% 
  
xx.x% 
1 - Almost Clear 
  
xx.x% 
  
xx.x% 
2 - Mild 
  
xx.x% 
  
xx.x% 
3 - Moderate 
  
xx.x% 
  
xx.x% 
4 - Severe 
  
xx.x% 
  
xx.x% 
Achieving Clear or Almost Clear 
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Percentages for Weeks 2, 4, 8, and 12 represent average values, obtained from averaging  
 
the summary statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.3.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 2 of 4) 
 
Investigator Global Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
0 - Clear 
  
xx.x% 
  
xx.x% 
1 - Almost Clear 
  
xx.x% 
  
xx.x% 
2 - Mild 
  
xx.x% 
  
xx.x% 
3 - Moderate 
  
xx.x% 
  
xx.x% 
4 - Severe 
  
xx.x% 
  
xx.x% 
Achieving Clear or Almost Clear 
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Percentages for Weeks 2, 4, 8, and 12 represent average values, obtained from averaging  
 
the summary statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.3.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 3 of 4) 
 
Investigator Global Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
0 - Clear 
  
xx.x% 
  
xx.x% 
1 - Almost Clear 
  
xx.x% 
  
xx.x% 
2 - Mild 
  
xx.x% 
  
xx.x% 
3 - Moderate 
  
xx.x% 
  
xx.x% 
4 - Severe 
  
xx.x% 
  
xx.x% 
Achieving Clear or Almost Clear 
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Percentages for Weeks 2, 4, 8, and 12 represent average values, obtained from averaging  
 
the summary statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.3.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 4 of 4) 
 
Investigator Global Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
0 - Clear 
  
xx.x% 
  
xx.x% 
1 - Almost Clear 
  
xx.x% 
  
xx.x% 
2 - Mild 
  
xx.x% 
  
xx.x% 
3 - Moderate 
  
xx.x% 
  
xx.x% 
4 - Severe 
  
xx.x% 
  
xx.x% 
Achieving Clear or Almost Clear 
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Percentages for Weeks 2, 4, 8, and 12 represent average values, obtained from averaging  
 
the summary statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Repeat Table 14.2.3.1.1 for the following table: 
 
Table 14.2.3.1.2: Summary of Investigator Global Assessment at Each Evaluation (Per-Protocol Population) 
 
Change footnote to “Note: Missing values imputed using last observation carried forward.” 
 
 


 
 
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Table 14.2.3.2: Summary of Investigator Global Assessment (Achieving Clear or Almost Clear) at Week 12 by Analysis Center 
(Intent-to-Treat Population) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Analysis Center (Investigational Sites) 
xx.x% 
xx.x% 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
xx (y, z) 
xx.x% 
xx.x% 
 
 
 
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics represent average values, obtained from averaging the summary  
 
statistics generated from each imputed dataset. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.4.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 1 of 5) 
  
Age 
 
Age < Median Age (xx) 
 
 
Age >= Median Age (xx) 
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
xx.x% 
xx.x% 
Failure 
xx.x% 
xx.x% 
xx.x% 
xx.x% 
 
a Ethnicities of Not Reported and Unknown are not included.  
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics represent average values, obtained from averaging the summary statistics 
        generated from each imputed dataset. Negative absolute change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
 
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Table 14.2.4.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 2 of 5) 
  
Sex 
 
Male 
 
 
Female 
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
xx.x% 
xx.x% 
Failure 
xx.x% 
xx.x% 
xx.x% 
xx.x% 
 
a Ethnicities of Not Reported and Unknown are not included.  
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics represent average values, obtained from averaging the summary statistics 
        generated from each imputed dataset. Negative absolute change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.4.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 3 of 5) 
  
Ethnicitya 
 
Hispanic or Latino 
 
 
Not Hispanic or Latino 
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
xx.x% 
xx.x% 
Failure 
xx.x% 
xx.x% 
xx.x% 
xx.x% 
 
a Ethnicities of Not Reported and Unknown are not included.  
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics represent average values, obtained from averaging the summary statistics 
        generated from each imputed dataset. Negative absolute change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.4.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 4 of 5) 
  
Race 
 
White 
 
 
Non-White 
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
xx.x% 
xx.x% 
Failure 
xx.x% 
xx.x% 
xx.x% 
xx.x% 
 
a Ethnicities of Not Reported and Unknown are not included.  
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics represent average values, obtained from averaging the summary statistics 
        generated from each imputed dataset. Negative absolute change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.4.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 5 of 5) 
  
Baseline IGA 
 
Moderate 
 
 
Severe 
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
xx to xx 
xx to xx 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
xx.x% 
xx.x% 
Failure 
xx.x% 
xx.x% 
xx.x% 
xx.x% 
 
a Ethnicities of Not Reported and Unknown are not included.  
Note: Multiple imputation (MCMC) used to impute missing values. Summary statistics represent average values, obtained from averaging the summary statistics 
        generated from each imputed dataset. Negative absolute change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
 
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Table 14.2.5.1: Sensitivity Analysis of Primary Endpoints: Absolute Change from Baseline in Inflammatory Lesion Count and Dichotomized IGA Success at 
Week 12 
 (Intent-to-Treat Population) 
(Page 1 of 2) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
N/A 
x.xxxd 
Failure 
xx.x% 
xx.x% 
 
a Least squares means, standard deviations and treatment p-value from a repeated measures analysis of covariance with factors of treatment group,  
analysis center, visit and treatment group by visit interaction, and Baseline lesion count as a covariate. Negative least squares means values represent 
  decrease from Baseline. 
b Skewness test based on methods presented by J.H. Zar (1984).  
c P-value from a ranked repeated measures analysis of covariance with factors of treatment group, analysis center, visit and treatment group by visit interaction, 
and Baseline lesion count as a covariate. 
d P-value from a repeated measures logistic regression with factors of treatment group, analysis center, visit and treatment group by visit interaction. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.5.1: Sensitivity Analysis of Primary Endpoints: Absolute Change from Baseline in Inflammatory Lesion Count and Dichotomized IGA Success at 
Week 12 
 (Intent-to-Treat Population) 
(Page 2 of 2) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
Achieving Clear or Almost Clear 
Success  
xx.x% 
xx.x% 
N/A 
x.xxxd 
Failure 
xx.x% 
xx.x% 
 
a Least squares means, standard deviations and treatment p-value from an analysis of covariance with factors of treatment group and analysis center and  
Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. 
b Skewness test, based on methods presented by J.H. Zar (1984), assessed for each imputed dataset. The average p-value is presented. 
c P-value from a ranked analysis of covariance with factors of treatment group and analysis center and Baseline lesion count as a covariate.   
d P-value from a logistic regression with factors of treatment group and analysis center.   
Note:  Multiple imputation (regression model) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.6.1: Secondary Efficacy Analyses 
 (Intent-to-Treat Population) 
(Page 1 of 3) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
Inflammatory Lesion Count – Percent Change 
from Baseline to Week 12 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
 
a Least squares means, standard deviations and treatment p-value from an analysis of covariance with factors of treatment and analysis center and the  
Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. 
b Skewness test, based on methods presented by J.H. Zar (1984), assessed for each imputed dataset. The average p-value is presented. 
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the Baseline lesion count as a covariate.   
d P-value from a logistic regression with factors of treatment group and analysis center. 
Note:  Multiple imputation (MCMC) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
{NOTE TO PROGRAMMER: ADJUST FOOTNOTE “d” IF FIRTH’S PENALIZED LIKELIHOOD IS NEEDED} 
 
 


 
 
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Table 14.2.6.1: Secondary Efficacy Analyses 
 (Intent-to-Treat Population) 
(Page 2 of 3) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
Inflammatory Lesion Count –Absolute Change 
from Baseline to Week 8 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
Achieving Clear or Almost Clear at Week 8 
Success 
xx.x% 
xx.x% 
N/A 
x.xxxd 
Failure 
xx.x% 
xx.x% 
 
a Least squares means, standard deviations and treatment p-value from an analysis of covariance with factors of treatment and analysis center and the  
Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. 
b Skewness test, based on methods presented by J.H. Zar (1984), assessed for each imputed dataset. The average p-value is presented. 
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the Baseline lesion count as a covariate.   
d P-value from a logistic regression with factors of treatment group and analysis center. 
Note:  Multiple imputation (MCMC) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.6.1: Secondary Efficacy Analyses 
 (Intent-to-Treat Population) 
(Page 3 of 3) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
Inflammatory Lesion Count – Absolute Change 
from Baseline to Week 4 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
Achieving Clear or Almost Clear at Week 4 
Success 
xx.x% 
xx.x% 
N/A 
x.xxxd 
Failure 
xx.x% 
xx.x% 
 
a Least squares means, standard deviations and treatment p-value from an analysis of covariance with factors of treatment and analysis center and the  
Baseline lesion count as a covariate. Negative least squares means values represent decrease from Baseline. 
b Skewness test, based on methods presented by J.H. Zar (1984), assessed for each imputed dataset. The average p-value is presented. 
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the Baseline lesion count as a covariate.   
d P-value from a logistic regression with factors of treatment group and analysis center. 
Note:  Multiple imputation (MCMC) used to impute missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
 
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Table 14.2.7.1: Patient Assessment of Papulopustular rosacea Signs and Symptoms (PAPSS) Analyses at Week 12 
 (Intent-to-Treat Population) 
  
 E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Treatment 
 
   P-Value  
 
PAPSS Total Scale Score – Absolute Change from Baseline to Week 12 
LSMeana 
xx.x 
xx.x 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
 
PAPSS Burning – Absolute Change from Baseline to Week 12 
LSMeana 
xx.x 
xx.x 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
 
PAPSS Itching – Absolute Change from Baseline to Week 12 
LSMeana 
xx.x 
xx.x 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
 
PAPSS Redness – Absolute Change from Baseline to Week 12 
LSMeana 
xx.x 
xx.x 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
 
PAPSS Bumps – Absolute Change from Baseline to Week 12 
LSMeana 
xx.x 
xx.x 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
 
 
a Least squares means, standard deviations and treatment p-value from an analysis of variance with factors of treatment, analysis center, and the respective 
Baseline score. Negative least squares means values represent decrease from Baseline. 
Note: No imputation of missing values. To control family-wise type I error rate at 5%, the Benjamini-Hochberg procedure (Hochberg and Bejamini adaptive  
step-down Bonferroni method) was utilized, and each p-value with an (*) is to be considered statistically significant. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 15) 
 
Total Scale Scores 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
Total scale score is the sum of all PAPSS items.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 15) 
 
Total Scale Scores 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
Total scale score is the sum of all PAPSS items.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 3 of 15) 
 
Total Scale Scores 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
Total scale score is the sum of all PAPSS items.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 4 of 15) 
 
Over the past 24 hours, what was the worst burning you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No burning at all, 10 = Worst possible burning 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 5 of 15) 
 
Over the past 24 hours, what was the worst burning you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No burning at all, 10 = Worst possible burning 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 6 of 15) 
 
Over the past 24 hours, what was the worst burning you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No burning at all, 10 = Worst possible burning 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 7 of 15) 
 
Over the past 24 hours, what was the worst itching you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No itching at all, 10 = Worst possible itching 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 8 of 15) 
 
Over the past 24 hours, what was the worst itching you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No itching at all, 10 = Worst possible itching 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 9 of 15) 
 
Over the past 24 hours, what was the worst itching you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No itching at all, 10 = Worst possible itching 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 10 of 15) 
 
Over the past 24 hours, what was the worst redness you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No redness at all, 10 = Worst possible redness 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 11 of 15) 
 
Over the past 24 hours, what was the worst redness you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No redness at all, 10 = Worst possible redness 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 12 of 15) 
 
Over the past 24 hours, what was the worst redness you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No redness at all, 10 = Worst possible redness 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 13 of 15) 
 
Over the past 24 hours, what were the worst bumps you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No bumps at all, 10 = Worst possible bumps 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 14 of 15) 
 
Over the past 24 hours, what were the worst bumps you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No bumps at all, 10 = Worst possible bumps 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.8.1: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 15 of 15) 
 
Over the past 24 hours, what were the worst bumps you 
experienced because of your rosacea? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
 
Note: No imputation of missing values. 
 
0 = No bumps at all, 10 = Worst possible bumps 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.2.8.1 for the following table: 
 
Table 14.2.8.2: Summary of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Each Evaluation (Per-Protocol Population) 
 
 
 


 
 
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Table 14.2.9.1: Summary of Erythema Assessment at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 2) 
 
Rosacea Erythema Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx  
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 2 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.9.1: Summary of Erythema Assessment at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 2) 
 
Rosacea Erythema Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.2.9.1 for the following table: 
 
Table 14.2.9.2: Summary of Erythema Assessment at Each Evaluation (Per-Protocol Population) 
 
 


 
 
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Table 14.2.10.1: Summary of Telangiectasia Assessment at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 2) 
 
Telangiectasia Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx  
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 2 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.10.1: Summary of Telangiectasia Assessment at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 2) 
 
Telangiectasia Assessment 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx 
xx 
0 - None 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.2.10.1 for the following table: 
 
Table 14.2.10.2: Summary of Telangiectasia Assessment at Each Evaluation (Per-Protocol Population) 
 
 


 
 
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Table 14.2.11.1: Summary of Patient Global Impression of Change (PGI-C) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 2) 
 
Since the start of the study, how have your rosacea 
symptoms changed? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 2 
n 
xx  
xx 
0 - Very much improved 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Much improved 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
3 - No Change 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Minimally worse 
xx ( xx.x%) 
xx ( xx.x%) 
5 - Much worse 
xx ( xx.x%) 
xx ( xx.x%) 
6 - Very much worse 
xx ( xx.x%) 
xx ( xx.x%) 
At least minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx  
xx 
0 - Very much improved 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Much improved 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
3 - No Change 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Minimally worse 
xx ( xx.x%) 
xx ( xx.x%) 
5 - Much worse 
xx ( xx.x%) 
xx ( xx.x%) 
6 - Very much worse 
xx ( xx.x%) 
xx ( xx.x%) 
At least minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values. At least minimally improved defined as “very much improved”, “much improved”, or “minimally improved”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.11.1: Summary of Patient Global Impression of Change (PGI-C) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 2) 
 
Since the start of the study, how have your rosacea 
symptoms changed? 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx  
xx 
0 - Very much improved 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Much improved 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
3 - No Change 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Minimally worse 
xx ( xx.x%) 
xx ( xx.x%) 
5 - Much worse 
xx ( xx.x%) 
xx ( xx.x%) 
6 - Very much worse 
xx ( xx.x%) 
xx ( xx.x%) 
At least minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx  
xx 
0 - Very much improved 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Much improved 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
3 - No Change 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Minimally worse 
xx ( xx.x%) 
xx ( xx.x%) 
5 - Much worse 
xx ( xx.x%) 
xx ( xx.x%) 
6 - Very much worse 
xx ( xx.x%) 
xx ( xx.x%) 
At least minimally improved 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values. At least minimally improved defined as “very much improved”, “much improved”, or “minimally improved”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Repeat Table 14.2.11.1 for the following table: 
 
Table 14.2.11.2: Summary of Patient Global Impression of Change (PGI-C) at Each Evaluation (Per-Protocol Population) 
 
 


 
 
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Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 12) 
 
Over the past seven days, rate how embarrassed you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not embarrassed at all, 10 = Extremely embarassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 12) 
 
Over the past seven days, rate how embarrassed you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not embarrassed at all, 10 = Extremely embarassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 3 of 12) 
 
Over the past seven days, rate how embarrassed you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not embarrassed at all, 10 = Extremely embarassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 4 of 12) 
 
Over the past seven days, rate how embarrassed you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not embarrassed at all, 10 = Extremely embarassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 5 of 12) 
 
Over the past seven days, rate how self-conscious you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 6 of 12) 
 
Over the past seven days, rate how self-conscious you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 7 of 12) 
 
Over the past seven days, rate how self-conscious you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 8 of 12) 
 
Over the past seven days, rate how self-conscious you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 9 of 12) 
 
Over the past seven days, rate how frustrated you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 2 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not frustrated at all, 10 = Extremely frustrated 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 10 of 12) 
 
Over the past seven days, rate how frustrated you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 4 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not frustrated at all, 10 = Extremely frustrated 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 11 of 12) 
 
Over the past seven days, rate how frustrated you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. 
 
 0 = Not frustrated at all, 10 = Extremely frustrated 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.12.1: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 12 of 12) 
 
Over the past seven days, rate how frustrated you felt 
because of your rosacea. 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 12 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
Three-Point Improvement from Baseline 
xx ( xx.xx%) 
xx ( xx.xx%) 
 
  
Note:  No imputation of missing values. Absolute Change calculated as Post-Baseline Visit – Baseline. Negative values represent decrease from Baseline. 
 
 0 = Not frustrated at all, 10 = Extremely frustrated 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.2.12.1 for the following table: 
 
Table 14.2.12.2: Summary of Patient Assessment of Papulopustular rosacea Impacts (PAPI) at Each Evaluation (Per-Protocol Population) 
 
 
 


 
 
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Table 14.2.13.1: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 2) 
 
Right now, my rosacea symptoms are: 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx  
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 2 
n 
xx  
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx  
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
  
Note:  No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.13.1: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 2) 
 
Right now, my rosacea symptoms are: 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx  
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx  
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
  
Note:  No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.2.13.1 for the following table: 
 
Table 14.2.13.2: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each Evaluation (Per-Protocol Population) 
 
 


 
 
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Table 14.2.14.1: Summary of Patient Global Impression of Treatments Satisfaction (PGI-TS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 2) 
 
Right now, how satisfied are you with your rosacea 
treatment: 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 2 
n 
xx  
xx 
0 – I am very satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
1 – I am satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
2 – I am neither satisfied not dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
3 – I am dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
4 – I am very dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx  
xx 
0 – I am very satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
1 – I am satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
2 – I am neither satisfied not dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
3 – I am dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
4 – I am very dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
 
  
Note:  No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.14.1: Summary of Patient Global Impression of Treatments Satisfaction (PGI-TS) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 2) 
 
Right now, how satisfied are you with your rosacea 
treatment: 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx  
xx 
0 – I am very satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
1 – I am satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
2 – I am neither satisfied not dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
3 – I am dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
4 – I am very dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx  
xx 
0 – I am very satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
1 – I am satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
2 – I am neither satisfied not dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
3 – I am dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
4 – I am very dissatisfied 
xx ( xx.x%) 
xx ( xx.x%) 
 
  
Note:  No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.2.14.1 for the following table: 
 
Table 14.2.14.2: Summary of Patient Global Impression of Treatments Satisfaction (PGI-TS) at Each Evaluation (Per-Protocol Population) 
 
 


 
 
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Table 14.2.15.1: Summary of RosaQoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 1 of 4) 
 
Total Score 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Week 12 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
Absolute Change from Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Note: No imputation of missing values. Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
Total Score calculated from the unweighted mean of all RosaQoL questions. 
 
Symptom Subscale Score calculated from items 2, 6, 9, 16, 17, 18, and 19. 
 
Functional Subscale Score calculated from items 13, 15, and 21. 
 
Emotional Subscale Score calculated from items 1, 3, 4, 5, 7, 8, 10, 11, 12, 14, and 20. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.15.1: Summary of RosaQoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 2 of 4) 
 
Symptom Subscale Score 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Week 12 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
Absolute Change from Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Note: No imputation of missing values. Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
Total Score calculated from the unweighted mean of all RosaQoL questions. 
 
Symptom Subscale Score calculated from items 2, 6, 9, 16, 17, 18, and 19. 
 
Functional Subscale Score calculated from items 13, 15, and 21. 
 
Emotional Subscale Score calculated from items 1, 3, 4, 5, 7, 8, 10, 11, 12, 14, and 20. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.15.1: Summary of RosaQoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 3 of 4) 
 
Functional Subscale Score 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Week 12 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
Absolute Change from Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Note: No imputation of missing values. Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
Total Score calculated from the unweighted mean of all RosaQoL questions. 
 
Symptom Subscale Score calculated from items 2, 6, 9, 16, 17, 18, and 19. 
 
Functional Subscale Score calculated from items 13, 15, and 21. 
 
Emotional Subscale Score calculated from items 1, 3, 4, 5, 7, 8, 10, 11, 12, 14, and 20. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.15.1: Summary of RosaQoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 4 of 4) 
 
Emotional Subscale Score 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Week 12 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
Absolute Change from Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Note: No imputation of missing values. Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
Total Score calculated from the unweighted mean of all RosaQoL questions. 
 
Symptom Subscale Score calculated from items 2, 6, 9, 16, 17, 18, and 19. 
 
Functional Subscale Score calculated from items 13, 15, and 21. 
 
Emotional Subscale Score calculated from items 1, 3, 4, 5, 7, 8, 10, 11, 12, 14, and 20. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Repeat Table 14.2.15.1 for the following table: 
 
Table 14.2.15.2: Summary of RosaQoL Questionnaire Responses at Baseline and Week 12 (Per-Protocol Population) 
 
 


 
 
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Table 14.3.0.1: Summary of Extent of Exposure 
 (Safety Population) 
 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Total Number of Days of Exposure 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
 
 
Total Number of Applications 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
Total Number of Missed Applications 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min. to Max. 
  xx to xx 
  xx to xx 
Complianta 
n 
xx 
xx 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
Noe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a A subject was considered compliant with the dosing regimen if the subject applied 80-120% of the expected number of applications and did not miss more  
than 5 consecutive applications while enrolled in the study. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 1 of 8) 
 
Dryness 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Week 2 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 2 of 8) 
 
Dryness 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 3 of 8) 
 
Scaling 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Week 2 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 4 of 8) 
 
Scaling 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 5 of 8) 
 
Itching 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Week 2 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 6 of 8) 
 
Itching 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 7 of 8) 
 
Burning/Stinging 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Week 2 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.1: Summary of  Cutaneous Safety and Tolerability Evaluations 
 (Safety Population) 
 (Page 8 of 8) 
 
Burning/Stinging 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx 
xx 
0 – None 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event Characteristics 
 (Safety Population) 
(Page 1 of 2) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Subjects Reporting Any Treatment-Emergent Adverse Event 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Treatment-Emergent Adverse Events 
xx 
xx 
Subjects Reporting Any Serious Treatment-Emergent Adverse Event 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Serious Treatment-Emergent Adverse Events 
xx 
xx 
Subjects Reporting Treatment-Emergent Adverse Event with Outcome of Fatal 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Treatment-Emergent Adverse Events with Outcome of Fatal 
xx 
xx 
Subjects Who Discontinued Study Drug Due to a Treatment-Emergent Adverse Event 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Treatment-Emergent Adverse Events Leading to Discontinuation of Study Drug 
xx 
xx 
Subjects Who Discontinued from the Study Due to a Treatment-Emergent Adverse Event 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Treatment-Emergent Adverse Events Leading to Discontinuation of Study 
xx 
xx 
 
Note: Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
Related defined as “Definitely”, “Probably”, or “Possible”. Not Related defined as “Unlikely” or “Not related”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event Characteristics 
 (Safety Population) 
(Page 2 of 2) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
By Maximum Severity 
Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
By Strongest Relationship to Study Drug 
Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Maximum Severity within Relationship to Study Drug 
Related 
 Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related  
 Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
 
Note: Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
Related defined as “Definitely”, “Probably”, or “Possible”. Not Related defined as “Unlikely” or “Not related”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.2.2: Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term 
(Safety Population) 
(Page 1 of x) 
  
System Organ Classa  
Preferred Term  
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
 
 
P-Valueb 
 
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xx  ( xx.x%) 
xx  ( xx.x%) 
x.xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xx  ( xx.x%) 
xx  ( xx.x%) 
x.xxx 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once. 
b P-value for the difference between treatment groups from a Fisher’s Exact test. The specific system organ classes and preferred terms analyzed will be those  
that are reported by at least one percent of the patients in any treatment group. 
Note:  MedDRA Version 21.0 
Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.2.3: Summary of Treatment-Emergent Adverse Events by Severity 
 (Safety Population) 
(Page 1 of x) 
  
System Organ Classa  
Preferred Term  
 
Severity 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once under the greatest reported reported severity. 
Note:  MedDRA Version 21.0. 
 
Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.2.4: Summary of Treatment-Emergent Adverse Events by Relationship to Study Drug 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa  
Preferred Term  
 
Relationship 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once under the greatest reported relationship. 
Note:  MedDRA Version 21.0. 
 
Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
 
Related defined as “Definitely”, “Probably”, or “Possible”. Not Related defined as “Unlikely” or “Not related”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
 (Safety Population) 
(Page 1 of 2) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Subjects Reporting Any Serious Treatment-Emergent Adverse Event 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Serious Treatment-Emergent Adverse Events 
xx 
xx 
Subjects Reporting Serious Treatment-Emergent Adverse Event with Outcome of Fatal 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Serious Treatment-Emergent Adverse Events with Outcome of Fatal 
xx 
xx 
Subjects Who Discontinued Study Drug Due to a Serious Treatment-Emergent Adverse Event 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Serious Treatment-Emergent Adverse Events Leading to Discontinuation of Study Drug 
xx 
xx 
Subjects Who Discontinued from the Study Due to a Serious Treatment-Emergent Adverse Event 
xx  ( xx.x%) 
xx  ( xx.x%) 
Number of Serious Treatment-Emergent Adverse Events Leading to Discontinuation of Study 
xx 
xx 
 
Note: Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
Related defined as “Definitely”, “Probably”, or “Possible”. Not Related defined as “Unlikely” or “Not related”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
 (Safety Population) 
(Page 2 of 2) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
By Maximum Severity 
Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
By Strongest Relationship to Study Drug 
Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Maximum Severity within Relationship to Study Drug 
Related 
 Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related  
 Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
 Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
 
Note: Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
Related defined as “Definitely”, “Probably”, or “Possible”. Not Related defined as “Unlikely” or “Not related”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 
 


 
 
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Table 14.3.1.3.2: Summary of Treatment-Emergent Serious Adverse Events by MedDRA System Organ Class and Preferred Term 
(Safety Population) 
(Page 1 of x) 
  
System Organ Classa  
Preferred Term  
 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
 
 
P-Valueb 
 
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xx  ( xx.x%) 
xx  ( xx.x%) 
x.xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xx  ( xx.x%) 
xx  ( xx.x%) 
x.xxx 
 
a Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA. At each level of summarization (System Organ Class or  
Preferred Term) subjects are counted once. 
b P-value for the difference between treatment groups from a Fisher’s Exact test. The specific system organ classes and preferred terms analyzed will be those 
that are reported by at least one percent of the patients in any treatment group. 
Note:  MedDRA Version 21.0 
Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.3.3: Summary of Serious Treatment-Emergent Adverse Events by Severity 
 (Safety Population) 
(Page 1 of x) 
  
System Organ Classa  
Preferred Term  
 
Severity 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Severe 
xx  ( xx.x%) 
xx  ( xx.x%) 
Moderate 
xx  ( xx.x%) 
xx  ( xx.x%) 
Mild 
xx  ( xx.x%) 
xx  ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more serious adverse events that map to MedDRA. At each level of summarization (System Organ Class  
or Preferred Term) subjects are counted once under the greatest reported severity. 
Note:  MedDRA Version 21.0. 
 
Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.3.1.3.4: Summary of Treatment-Emergent Serious Adverse Events by Relationship to Study Drug 
(Safety Population) 
(Page 1 of xx) 
  
System Organ Classa  
Preferred Term  
 
Relationship 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
Not Related 
xx  ( xx.x%) 
xx  ( xx.x%) 
 
a Counts reflect numbers of subjects reporting one or more serious adverse events that map to MedDRA. At each level of summarization (System Organ Class  
or Preferred Term) subjects are counted once under the greatest reported relationship. 
Note:  MedDRA Version 21.0. 
 
Treatment-emergent adverse events are those events that were not indicated as occuring prior to first application. 
 
Related defined as “Definitely”, “Probably”, or “Possible”. Not Related defined as “Unlikely” or “Not related”. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.4.1: Summary of Vital Signs 
 (Safety Population) 
(Page 1 of 5) 
  
Temperature (°C) 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Baseline 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 12 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xxx 
xxx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
Note: No imputation of missing values. Negative change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.4.1: Summary of Vital Signs 
 (Safety Population) 
(Page 2 of 5) 
  
Respiratory Rate (breaths/min) 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Baseline 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 12 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xxx 
xxx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
Note: No imputation of missing values. Negative change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.4.1: Summary of Vital Signs 
 (Safety Population) 
(Page 3 of 5) 
  
Systolic Blood Pressure (mmHg) 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Baseline 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 12 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xxx 
xxx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
Note: No imputation of missing values. Negative change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.4.1: Summary of Vital Signs 
 (Safety Population) 
(Page 4 of 5) 
  
Diastolic Blood Pressure (mmHg) 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Baseline 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 12 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xxx 
xxx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
Note: No imputation of missing values. Negative change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.4.1: Summary of Vital Signs 
 (Safety Population) 
(Page 5 of 5) 
  
Heart Rate (beats/min) 
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Baseline 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Week 12 
 
 
n 
xxx 
xxx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min. to Max. 
xx to xx 
xx to xx 
Change from Baseline 
 n 
xxx 
xxx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min. to Max. 
xx to xx 
xx to xx 
 
Note: No imputation of missing values. Negative change values represent decrease from Baseline. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.4.2: Shift Table of Vital Signs 
 (Safety Population) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Systolic Blood Pressure (mmHg)  
Week 12 
  
Week 12 
 
Baseline 
 
<90 mmHg 
  90-140 mmHg   
>140 mmHg 
 
 
<90 mmHg 
 
 90-140 mmHg  
 
>140 mmHg 
 
<90 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
90-140 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
>140 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Diastolic Blood Pressure (mmHg)  
Week 12 
  
Week 12 
 
Baseline 
 
<90 mmHg 
  90-100 mmHg   
>100 mmHg 
 
 
<90 mmHg 
 
 90-100 mmHg  
 
>100 mmHg 
 
<90 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
90-100 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
>100 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Heart Rate (beats/min) 
 
Week 12 
  
Week 12 
 
Baseline 
 
<60 bpm 
  
60-100 bpm 
  
>100 bpm 
 
 
<60 bpm 
 
 
60-100 bpm 
 
 
>100 bpm 
 
<60 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
60-100 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
>100 mmHg 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
Note: No imputation of missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.5: Summary of Abnormal Physical Examination Findings by Visit 
 (Safety Population) 
  
 
E-BPO 5% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
Heart 
Baseline 
 
 
 n 
xx  
xx 
 Abnormal 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
 n 
xx  
xx 
 Abnormal 
xx ( xx.x%) 
xx ( xx.x%) 
Lung 
Baseline 
 
 
 n 
xx  
xx 
 Abnormal 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
 n 
xx  
xx 
 Abnormal 
xx ( xx.x%) 
xx ( xx.x%) 
Abdomen 
Baseline 
 
 
 n 
xx  
xx 
 Abnormal 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
 n 
xx  
xx 
 Abnormal 
xx ( xx.x%) 
xx ( xx.x%) 
 
Note: No imputation of missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.3.1.6: Summary of Patient Global Impression of Treatment Side-Effects (PGI-SE) at Each Evaluation 
  (Safety Population) 
(Page 1 of 2) 
 
Right now, how bothered are you by the side effects of 
your rosacea treatment: 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 2 
n 
xx  
xx 
0 - I am not bothered 
xx ( xx.x%) 
xx ( xx.x%) 
1 - I am somewhat bothered 
xx ( xx.x%) 
xx ( xx.x%) 
2 - I am moderately bothered 
xx ( xx.x%) 
xx ( xx.x%) 
3 - I am very bothered 
xx ( xx.x%) 
xx ( xx.x%) 
4 - I am extremely bothered 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx  
xx 
0 - I am not bothered 
xx ( xx.x%) 
xx ( xx.x%) 
1 - I am somewhat bothered 
xx ( xx.x%) 
xx ( xx.x%) 
2 - I am moderately bothered 
xx ( xx.x%) 
xx ( xx.x%) 
3 - I am very bothered 
xx ( xx.x%) 
xx ( xx.x%) 
4 - I am extremely bothered 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.6: Summary of Patient Global Impression of Treatment Side-Effects (PGI-SE) at Each Evaluation 
  (Safety Population) 
(Page 2 of 2) 
 
Right now, how bothered are you by the side effects of 
your rosacea treatment: 
  
E-BPO 5% Cream  
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx  
xx 
0 - I am not bothered 
xx ( xx.x%) 
xx ( xx.x%) 
1 - I am somewhat bothered 
xx ( xx.x%) 
xx ( xx.x%) 
2 - I am moderately bothered 
xx ( xx.x%) 
xx ( xx.x%) 
3 - I am very bothered 
xx ( xx.x%) 
xx ( xx.x%) 
4 - I am extremely bothered 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx  
xx 
0 - I am not bothered 
xx ( xx.x%) 
xx ( xx.x%) 
1 - I am somewhat bothered 
xx ( xx.x%) 
xx ( xx.x%) 
2 - I am moderately bothered 
xx ( xx.x%) 
xx ( xx.x%) 
3 - I am very bothered 
xx ( xx.x%) 
xx ( xx.x%) 
4 - I am extremely bothered 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: No imputation of missing values.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
13. INDEX OF PLANNED FIGURES 
Figure 14.2.3.1: Cumulative Distribution Function of Patient Assessment of Papulopustular 
Rosacea Signs and Symptoms (PAPSS) at Week 12 (Intent-to-Treat 
Population) ..........................................................................................151 
Figure 14.2.3.2: Cumulative Distribution Function of Patient Assessment of Papulopustular 
Rosacea Signs and Symptoms (PAPSS) at Week 12 (Per-
Protocol Population) ...........................................................................156 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
             
    Page 151 of 194  
CONFIDENTIAL 
Figure 14.2.3.1: Cumulative Distribution Function of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Week 12 
(Intent-to-Treat Population) 
(Page 1 of 5) 
 
 
 
Total Scale Score 
 
 
 
 
 
 
Note: No imputation of missing values. Absolute Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
             
    Page 152 of 194  
CONFIDENTIAL 
 
Figure 14.2.3.1: Cumulative Distribution Function of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Week 12 
(Intent-to-Treat Population) 
(Page 2 of 5) 
 
 
 
Burning 
 
 
 
 
 
 
Note: No imputation of missing values. Absolute Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
             
    Page 153 of 194  
CONFIDENTIAL 
 
Figure 14.2.3.1: Cumulative Distribution Function of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Week 12 
(Intent-to-Treat Population) 
(Page 3 of 5) 
 
 
 
Itching 
 
 
 
 
 
 
Note: No imputation of missing values. Absolute Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
             
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Figure 14.2.3.1: Cumulative Distribution Function of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Week 12 
(Intent-to-Treat Population) 
(Page 4 of 5) 
 
 
 
Redness 
 
 
 
 
 
 
Note: No imputation of missing values. Absolute Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Figure 14.2.3.1: Cumulative Distribution Function of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Week 12 
(Intent-to-Treat Population) 
(Page 5 of 5) 
 
 
 
Bumps 
 
 
 
 
 
 
Note: No imputation of missing values. Absolute Change calculated as Week 12 – Baseline. Negative values represent decrease from Baseline. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Repeat Figure 14.2.3.1 for the following tables: 
 
Figure 14.2.3.2: Cumulative Distribution Function of Patient Assessment of Papulopustular Rosacea Signs and Symptoms (PAPSS) at Week 12 (Per-
Protocol Population) 
 
 
 


 
 
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14. INDEX OF PLANNED LISTINGS 
Listing 16.1.7: Randomization Scheme .......................................................................................159 
Listing 16.2.1.1: End of Study Information .................................................................................160 
Listing 16.2.2.1: Inclusion/Exclusion Criteria .............................................................................161 
Listing 16.2.2.2: Screen Failure ...................................................................................................162 
Listing 16.2.2.3: Protocol Deviations ..........................................................................................163 
Listing 16.2.3: Analysis Populations ...........................................................................................164 
Listing 16.2.4.1: Subject Demographic Information ...................................................................165 
Listing 16.2.4.2.1: Unique Medical/Surgical History Coded to MedDRA System Organ Classes 
and Preferred Terms ............................................................................166 
Listing 16.2.4.2.2: Medical/Surgical History...............................................................................167 
Listing 16.2.4.3.1: Unique Medication Names Coded to WHO Drug Global Dictionary ATC 
Level 2 Terms and Preferred Names ...................................................168 
Listing 16.2.4.3.2: Prior and Concomitant Medications ..............................................................169 
Listing 16.2.4.4.1: Unique Procedure/Therapy Names Coded to MedDRA System Organ Classes 
and Preferred Terms ............................................................................170 
Listing 16.2.4.4.2: Prior and Concomitant Procedures/Therapies ...............................................171 
Listing 16.2.5.1: Study Visit Compliance ....................................................................................172 
Listing 16.2.5.2: Subject Dosing Compliance .............................................................................173 
Listing 16.2.5.3: Subject Dosing Deviations ...............................................................................174 
Listing 16.2.5.4: Study Medication Accountability Log .............................................................175 
Listing 16.2.5.5: Photography ......................................................................................................176 
Listing 16.2.6.1: Investigator Global Assessment .......................................................................177 
Listing 16.2.6.2: Inflammatory Lesion Counts ............................................................................178 
Listing 16.2.6.3.1: RosaQoL Descriptions...................................................................................179 
Listing 16.2.6.3.2: RosaQoL ........................................................................................................181 
Listing 16.2.6.3.3: RosaQoL Subscales Scores ...........................................................................182 
Listing 16.2.6.4: Erythema Severity/Telangiectasia Assessments...............................................183 
Listing 16.2.6.5: PRO – PAPSS, PAPI, PGI-S ............................................................................184 
Listing 16.2.6.6: PRO – PGI-C, PGI-TS, PGI-SE .......................................................................185 
Listing 16.2.7.1: Cutaneous Safety and Tolerability Assessments ..............................................186 


 
 
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Listing 16.2.7.2.1: Unique Adverse Events Coded to MedDRA System Organ Classes and 
Preferred Terms ...................................................................................187 
Listing 16.2.7.2.2: Pre-Treatment Adverse Events ......................................................................188 
Listing 16.2.7.2.3: Treatment-Emergent Adverse Events ............................................................189 
Listing 16.2.7.2.4: Serious Adverse Events .................................................................................190 
Listing 16.2.7.2.5: Subjects Who Prematurely Discontinued Study and/or Discontinued Study 
Drug Due to Adverse Events...............................................................191 
Listing 16.2.8.1: Urine Pregnancy Tests ......................................................................................192 
Listing 16.2.8.2: Physical Examination .......................................................................................193 
Listing 16.2.8.3: Vital Signs ........................................................................................................194 


 
 
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Listing 16.1.7: Randomization Scheme 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                  
Subject    Age/Sex   Eval         Randomization Date     Kit Number   Assigned Arm        
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxx xx xxxxx 
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxxxx xxxxx  
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxx xx xxxxx 
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxx xx xxxxx 
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxx xx xxxxx 
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxxxx xxxxx  
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxx xx xxxxx 
 
xxxxxx     xxxx      xxxxxxxxx    xxxxxxxxxxxxxxxx       xxxx         xxxxxxx xxxxx  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
 
 


 
 
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Listing 16.2.1.1: End of Study Information 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                      Date of Study 
                            Date of      Date of      Completion/      Did Subject                              Continue to the 
                            First        Last         Discontinuation  Complete     Primary Reason              the Long Term  
Subject  Age/Sex  Eval      Application  Application  (Day)1              the Study    for Study Discontinuation   Safety Study  
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx     xxxxxxxx  xxxxxxxxxx   xxxxxxxxxx   xxxxxxxxxxxxxx   xxx                                       xxx x xxx xxxxxx xxxx 
                                                                                                                 xxxxxxxx xxxxxxxxxxx 
 
xxxxxx   xxxx     xxxxxxxx  xxxxxxxxxx   xxxxxxxxxx   xxxxxxxxxxxxxx   xx           xxxxxxx xxxxx                xx x xxx xxxxxxx xxxx 
                                                                                                                 xxx xxxxxxxx 
 
xxxxxx   xxxx     xxxxxxxx  xxxxxxxxxx   xxxxxxxxxx   xxxxxxxxxxxxxx   xx           xxxx xx xxxxxxxxxx xxxxxxx   xx x xxx xxxxxxx xxxx 
                                                                                    xx xxxx xx xxxxxxxxxxx       xxx xxxxxxxx 
                                                                                    xxxxx xxxxx xxxxx xxx xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –    
  date of first application + 1 for dates on or after first application. 
   
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
If Primary Reason for Study Discontinuation is Lost to Follow-Up, Protocol Violation, Withdrawal by Subject, or Other, the reason 
specification will be included following a colon (for example, WITHDRAWAL BY SUBJECT: xxxxx) 
If subject will not continue to the LTS, the reason specification will be included in the final column following a colon. 
 
 


 
 
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Listing 16.2.2.1: Inclusion/Exclusion Criteria  
                                                             Treatment Group   
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject     Age/Sex     Eval          Criterion Failed    Description 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxx              xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
xxxxxx      xxxx        xxxxxxxxx     xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
xxxxxx      xxxx        xxxxxxxxx     xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
                                      xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
                                      xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
                                                          xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxxxxxxxxx xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Criterion Failed. 
 
 


 
 
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Listing 16.2.2.2: Screen Failure 
                                                             (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                         Date of    
Subject     Age/Sex     Eval          Screen Failure       Reason for Screen Failure 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxxxxxx           xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxxxxxx           xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxxxxxx           xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
                                      xxxxxxxxxx           xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
                                      xxxxxxxxxx           xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
                                                           xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxxxxxxxxx xxx 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
 
 


 
 
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Listing 16.2.2.3: Protocol Deviations 
                                                             Treatment Group   
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject     Age/Sex     Eval          Deviation                                                                           Date (Day1)                  
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxx x xxxxxxxx xxx xx xxxxxx xxxxxx xxx xxx xx xxxxxxxxxxxxx                  xxxxxxxxxxxxxxx 
 
                                      xxxxxx xxx xx xxxxxx xxxxxx xxx xxx xx                                           xxxxxxxxxxxxxxx 
 
                                      xxxxxx x xxxxxxxx  
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxx xxx xx xxxxxx xxxxxx xxx xxx xx                                           xxxxxxxxxxxxxxx 
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxx xxx xx xxxxxx xxxxxx xxx xxx xx                                           xxxxxxxxxxxxxxx 
 
 
 
                                       
 
                                       
                                       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date - Baseline date for dates prior to Baseline visit.  Otherwise, day is calculated as date - Baseline date                  
  + 1 for dates on or after Baseline visit.   
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Date. 
 
 


 
 
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Listing 16.2.3: Analysis Populations 
                                                             Treatment Group 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject    Age/Sex     Population           Included Reason(s) Excluded                      Exception(s) 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx        Intent-to-Treat      xxx 
                       Safety               xxx 
                       Per-Protocol         xx       xxxxxxxxxxx xxxxxxx xxxxxxxxx 
                                                     xxxxxxxxxxx xxxxxxx xxxxxxxxx 
 
xxxxxx     xxxx        Intent-to-Treat      xxx 
                       Safety               xxx 
                       Per-Protocol         xxx      xxxxxxxxxxx xxxxxxx xxxxxxxxx           xxxxxxxxxxx xxxxxxx xxxxxxxxx 
 
xxxxxx     xxxx        Intent-to-Treat      xxx 
                       Safety               xx       xxxxxxxxxxx xxxxxxx xxxxxxxxx 
                       Per-Protocol         xx       xxxxxxxxxxx xxxxxxx xxxxxxxxx 
                                                     xxxxxxxxxxx xxxxxxx xxxxxxxxx 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Population (as ordered above). 
 
 


 
 
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Listing 16.2.4.1: Subject Demographic Information 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                      B: Date of Birth                                                                                     
                      A: Age            R: Race                  C: Childbearing Potential             I: Informed Consent Date     
Subject  Eval         S: Sex            E: Ethnicity             M: Method of Birth Control            P: Photography Consent Signed 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxxxxxxx    B: xxxx-xx-xx     R: xxxxxx xxxxxxxx       C: xxx                                I: xxxx-xx-xx 
                      A: xx                xx xxxxx xxxxxxx      M: xxxxxxxxx xxxxxxxxxx               P: xxx 
                      S: xxxxxx            xxxxxxxx xxxxxxxxxx      xxxxxxxxxxxxx xxxxxxxxxxx 
                                        E: xxx xxxxxxxx xx          xxxx x xxxxxxxxxx xx  
                                           xxxxxx                   xxxxxxxxx xxxxxxxxxx 
                                                                    xxxx xxxxxxx 
 
 
xxxxxx   xxxxxxxxx    B: xxxx-xx-xx      R: xxxxx                C: xx                                 I: xxxx-xx-xx 
                      A: xx              E: xxxxxxxx xx xxxxxx   M:                                    P: xx 
                      S: xxxx            
 
xxxxxx   xxxxxxxxx    B: xxxx-xx-xx      R: xxxxx                C: xxx                                I: xxxx-xx-xx 
                      A: xx              E: xxxxxxxx xx xxxxxx   M: xxxxxxxx xxxxxxxxxxxxx             P: xx xxxx x xxxxxxxxxxx xxxxx 
                      S: xxxxxx            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
 


 
 
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Listing 16.2.4.2.1: Unique Medical/Surgical History Coded to MedDRA System Organ Classes and Preferred Terms 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                
MedDRA System Organ Class                     MedDRA Preferred Term                       Medical/Surgical History Verbatim Term 
______________________________________________________________________________________________________________________________________ 
 
xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx           xxxxxxx                                     xxxxxx 
 
                                              xxxx xxxxxxxxx xxxxxxxx                     xxxx xxxxxxxxxx xxxxxx 
 
xxxxxxxxxx xxx xxxxxxxxxxxx                   xxxxxxxxxxx                                 xxxxxxxxxxx 
 
                                              xxxxxxxxxxxxx                               xxxxxxxxxxxxx x xxxx xxx xxx 
                                                                    
                                                                                          xxxxxxxxxxxxx xx xxxxx xx xxxx xxxxx xxx 
                       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by System Organ Class, Preferred Term, and Verbatim Term. 
 


 
 
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Listing 16.2.4.2.2: Medical/Surgical History 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                               
                               Medical/Surgical History           S: MedDRA System Organ Class                     S: Onset Date 
Subject    Age/Sex   Eval      Verbatim Term                      P: MedDRA Preferred Term                         E: End Date 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx      xxxxxxxx  xxxxxxx                            S: xxxx xxx xxxxxxxxxxxx xxxxxx xxxxxxxxx        S: xxxx 
                                                                  P: xxxxxxx                                       E: 
 
                               xxxxxxx xx xxxxxxxxxxx xxxxxxxxx   S: xxxxxx xxxxxx xxxxxxxxx                       S: xxxx 
                                                                  P: xxxxxxxx xxxxx xxxxxxx                        E: xxxxxxx 
 
xxxxxx     xxxx      xxxxxxxx  xxxxxxx                            S: xxxx xxx xxxxxxxxxxxx xxxxxx xxxxxxxxx        S: xxxx 
                                                                  P: xxxxxxx                                       E: 
 
xxxxxx     xxxx      xxxxxxxx  xxxxxxx                            S: xxxx xxx xxxxxxxxxxxx xxxxxx xxxxxxxxx        S: xxxx 
                                                                  P: xxxxxxx                                       E: 
 
xxxxxx     xxxx      xxxxxxxx  xxxxxxx                            S: xxxx xxx xxxxxxxxxxxx xxxxxx xxxxxxxxx        S: xxxx 
                                                                  P: xxxxxxx                                       E: 
 
                               xxxxxxxxxxxxxxxx                   S: xxxxxx xxxxxx xxxx                            S: xxxxxxxxxx 
                                                                  P: xxxx xxxxxxxxxxx                              E: xxxxxxxx                         
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Rosacea Diagnosis (all Rosacea MH will appear first), Onset Date, End Date, Verbatim Term  
 
 


 
 
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Listing 16.2.4.3.1: Unique Medication Names Coded to WHO Drug Global Dictionary ATC Level 2 Terms and Preferred Names 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                               
                                                                                                  I: Indication 
WHO ATC Level 2 Term     WHO Preferred Name             Medication Verbatim Term                  T: Route 
_____________________________________________________________________________________________________________________________________ 
 
xxxxxxxxxxxxxx               xxxxxxxxxxxxxx                     xxxxxxxx                          I: xxxxxxxxxxx 
                                                                                                  R: xxxxxxxxxxx 
 
                                                                xxxxxxxxx                         I: xxxxxxxxxxx 
                                                                                                  R: xxxxxxxxxxx                                       
 
xxxxxxxxxxxxxx               xxxxxxxxxxxxxx                     xxxxxxxx                          I: xxxxxxxxxxx 
                                                                                                  R: xxxxxxxxxxx 
 
                                                                xxxxxxxxx                         I: xxxxxxxxxxx 
                                                                                                  R: xxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: ATC Level 2 Term and Preferred Name map to WHO Drug Global Dictionary, Format B3, Version March 1, 2018. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by ATC Level 2 Term, Preferred Name, Medication Verbatim Term, Indication, and Route. 
 


 
 
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Listing 16.2.4.3.2: Prior and Concomitant Medications 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                                                           
S: Subject   A: ATC Level 2 Term                                     S: Start Date (Day)¹   I: Indication 
A: Age/Sex   P: Preferred Name                                       E: End Date (Day)¹     D: Dose                 F: Frequency 
E: Eval      M: Medication Name                                      P: Prior/Concomitant   U: Units                T: Route    
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    A: xxxxxxxxxx xxx xxxxxxxxxxx                           S: xxxxxxxxxxxxxxx     I: xxxxxxx              F: xxx 
A: xxxx      P: xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxx xxxxxxx xxx     E: xxxxxxxxxxxxxxx     D: xx                   T: xxxxxxxxxxxxxx 
E: xxxxxxxxx M: xxxxxx xxxxx xxxxxxxxx                               P: xxxxxxxxxxxxxxxxxxx U: xxxxxxxxxxx                                             
 
             A: xxxxxxxx xx xxxxxxxx                                 S: xxxxxxxxxxxxxxx     I: xxxxxxx              F: xx 
             P: xxxxxxxxxxx xxxxxxx xxx                              E: xxxxxxxxxxxxxxx     D: xx                   T: xxxxx 
             M: xxxxxx xxxxxxxxx                                     P: xxxxx 
         U: xxxxxxxx 
 
 
 
      
 
S: xxxxxx    A: xxxxxxxxxx xxx xxxxxxxxxxx                           S: xxxxxxxxxxxxxxx     I: xxxxxxx              F: xxx 
A: xxxx      P: xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxx xxxxxxx xxx     E: xxxxxxxxxxxxxxx     D: xx                   T: xxxxxxxxxxxxxx 
E: xxxxxxxxx M: xxxxxx xxxxx xxxxxxxxx                               P: xxxxxxxxxxxxxxxxxxx U: xxxxxxxxxxx                                             
 
             A: xxxxxxxx xx xxxxxxxx                                 S: xxxxxxxxxxxxxxx     I: xxxxxxx              F: xx 
             P: xxxxxxxxxxx xxxxxxx xxx                              E: xxxxxxxxxxxxxxx     D: xx                   T: xxxxx 
             M: xxxxxx xxxxxxxxx                                     P: xxxxx 
         U: xxxxxxxx 
 
 
 
      
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –  
  date of first application + 1 for dates on or after first application. 
 
Note: ATC Level 2 Term and Preferred Name map to WHO Drug Global Dictionary, Format B3, Version March 1, 2018. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Medication Name, Indication, Route, Frequency. If the Route is Topical, then the area 
treated is presented within parenthesis (T: Topical (specify area)). 
 


 
 
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Listing 16.2.4.4.1: Unique Procedure/Therapy Names Coded to MedDRA System Organ Classes and Preferred Terms 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
MedDRA System Organ Class         MedDRA Preferred Term             Procedure/Therapy Verbatim Term   Indication                       
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxxxxxxxx                    xxxxxxxxxxxxxx                    xxxxxxxx  xx xxxxx                xxxxxxxxxxx 
                                                                                                   
                                                                    xxxxxxxxx                         xxxxx xx xxxx 
                                                                                                                                       
 
xxxxxxxxxxxxxx                    xxxxxxxxxxxxxx                    xxxxxxxx                          xxxxxxxx 
                                                                                                   
                                                                                                      xxxxxxxxxxx 
 
                                                                    xxxxxxxxx                         xxxxxxxxxxx 
                                                                                                       
xxxxx xxx xx xxxxxxx              xxxxxxx xxxxxxx xxxx              xxxxxxxx xxxxxx                   xxxxxxxx xxxxxxxx xx xx xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by System Organ Class, Preferred Term, Verbatim Term, and Indication. 
 


 
 
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Listing 16.2.4.4.2: Prior and Concomitant Procedures/Therapies 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                 S: MedDRA System Organ Class                  S: Start Date (Day)¹ 
                                 P: MedDRA Preferred Term                      E: End Date (Day)¹        I: Indication 
Subject    Age/Sex    Eval       M: Procedure/Therapy Name                     P: Prior/Concomitant      A: Anatomical Area Treated                    
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx       xxxxxxxx   S: xxxxxxx xxx xxxxxxxx xxxxxxxxx             S: xxxxxxxxxxxxxxxxx      I: xxxxx xxxxxxx 
                                 P: xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx           E: xxxxxxxxxxxxxxxxx      A: 
                                 M: xxxxxxx xxxxx xxxxxxx xxxxxxx              P: xxxxxxxxxxxxxxxxx 
 
xxxxxx     xxxx       xxxxxxxx   S: xxxxxxx xxx xxxxxxxx xxxxxxxxx             S: xxxxxxxxxxxxxxxxx      I: xxxxx xxxxxxx 
                                 P: xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx           E: xxxxxxxxxxxxxxxxx      A: 
                                 M: xxxxxxx xxxxx xxxxxxx xxxxxxx              P: xxxxxxxxxxxxxxxxx 
 
xxxxxx     xxxx       xxxxxxxx   S: xxxxxxx xxx xxxxxxxx xxxxxxxxx             S: xxxxxxxxxxxxxxxxx      I: xxxxx xxxxxxx 
                                 P: xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx           E: xxxxxxxxxxxxxxxxx      A: 
                                 M: xxxxxxx xxxxx xxxxxxx xxxxxxx              P: xxxxxxxxxxxxxxxxx      
 
                                 S: xxxxxxx xxxxxxxx xxxx                      S: xxxxxxxxxxxxxxxxx      I: xxxxxxxxx xxxxx xx xx  
                                 P: xxx xxxxxxxxxx xxxxxxxx                    E: xxxxxxxxxxxxxxxxx      A: xxxxxxxxxx 
                                 M: xxxxxxx xxxxxxx                            P: xxxxxxxxxxxxxxxxx 
                                                                                
                                 S: xxxxxxx xxxxxxxx xxxx                      S: xxxxxxxxxxxxxxxxx      I: xxxxxxxxx xxxxx xx xx  
                                 P: xxx xxxxxxxxxx xxxxxxxx                    E: xxxxxxxxxxxxxxxxx      A: xxxxxxxxxx 
                                 M: xxxxxxx xxxxxxx                            P: xxxxxxxxxxxxxxxxx 
                                                                                
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –  
  date of first application + 1 for dates on or after first application. 
 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Procedure/Therapy Name, and Indication. 
 


 
 
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Listing 16.2.5.1: Study Visit Compliance 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
             
                                                                                          Reason Screening                                             
                                                                                  Within  And Baseline         
                                                                         Study    Visit   Occurred on         Reason for   
Subject  Age/Sex  Eval       Visit                      Visit Date       Day1     Window2 Different Days      Unscheduled Visit                        
______________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxx    xxxxxxxx   xxxxxxxxx                  xxxxxxxxxx       xx        xxx            
                             xxxxxxxx                   xxxxxxxxxx       xx        xxx    xxxxxxx xxx xx 
                                                                                          xxxxxxxxxx 
                             xxxx x                     xxxxxxxxxx       xx        xxx 
                             xxxx x                     xxxxxxxxxx       xx        xxx 
                             xxxx x                     xxxxxxxxxx       xx        xxx  
                             xxxx xxxxx                 xxxxxxxxxx       xx        xxx  
 
 
 
 
    
xxxxxx    xxxx    xxxxxxxx   xxxxxxxxx                  xxxxxxxxxx       xx        xxx            
                             xxxxxxxx                   xxxxxxxxxx       xx        xxx     
                             xxxx x                     xxxxxxxxxx       xx        xxx 
                             xxxx x                     xxxxxxxxxx       xx        xxx 
                             xxxxxxxxxxx xxxxx xxx      xxxxxxxxxx       xx                                    xxxxxxxxxxxxxx      
                             xxxx x                     xxxxxxxxxx       xx        xxx  
                             xxxx xxxxx                 xxxxxxxxxx       xx        xxx  
                                                          
xxxxxx    xxxx    xxxxxxxx   xxxxxxxxx                  xxxxxxxxxx       xx        xxx            
                             xxxxxxxx                   xxxxxxxxxx       xx        xxx     
                             xxxx x                     xxx xxxx         xx        xxx                         xxx xxxx 
                             xxxx x                     xxx xxxx         xx        xxx                         xxx xxxx 
                             xxxx x                     xxxxxxxxxx       xx        xxx  
                             xxxx xxxxx                 xxxxxxxxxx       xx        xxx  
                                 
                                  
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – Baseline date for dates prior to Baseline visit. Otherwise, day is calculated as date – Baseline date 
  + 1 for dates on or after Baseline visit. 
2 Determined by protocol-specified visit window for scheduled visits after Baseline.  
     
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number. 
 


 
 
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Listing 16.2.5.2: Subject Dosing Compliance 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                              
 
 
 
 
 
 
 
 
 
 
 
 
      Maximum Number 
                                                          Number of  Calculated1    Amount of    of Consecutive      
                             Date of First  Date of Last  Days of    Number of     Study Drug      Missed         Percent   
Subject  Age/Sex   Eval      Application    Application   Exposure    Applications   Used (g)    Applications     Compliant   Compliant2                
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx      xxxxxxxx  xxxxxxxxxx     xxxxxxxxxx       xx          xx        xxxx            xx             xxxxx       xxx 
  
xxxxxx   xxxx      xxxxxxxx  xxxxxxxxxx     xxxxxxxxxx       xx          xx        xxxx            xx             xxxxx       xxx 
 
xxxxxx   xxxx      xxxxxxxx  xxxxxxxxxx     xxxxxxxxxx       xx          xx        xxxx            xx             xxxxx       xxx 
 
xxxxxx   xxxx      xxxxxxxx  xxxxxxxxxx     xxxxxxxxxx       xx          xx        xxxx            xx             xxxxx       xxx 
 
xxxxxx   xxxx      xxxxxxxx  xxxxxxxxxx     xxxxxxxxxx       xx          xx        xxxx            xx             xxxxx       xxx 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
              
                                  
______________________________________________________________________________________________________________________________________ 
1 The total number of applicationss was calculated using the date of first application, date of last application, and number of applied  
  applications at a deviation. 
2 A subject was considered compliant with the dosing regimen if the subject did not miss more than 5 consecutive days applying and  
  applied 80-120% of expected applications based on the length of their participation in the study. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
 


 
 
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Listing 16.2.5.3: Subject Dosing Deviations 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                                           
Subject     Age/Sex     Eval               Date of Dosing Deviation (Day)¹                    Number of Applications Applied                           
______________________________________________________________________________________________________________________________________ 
 
xxxxxx       xxxx       xxxxxxxx           xxxxxxxxxxxxx                                                  x 
                                           xxxxxxxxxxxxx                                                  x 
 
xxxxxx       xxxx       xxxxxxxx           xxxxxxxxxxxxx                                                  x 
 
xxxxxx       xxxx       xxxxxxxx           xxxxxxxxxxxxx                                                  x   
                                           xxxxxxxxxxxxx                                                  x   
                                           xxxxxxxxxxxxx                                                  x  
                                           xxxxxxxxxxxxx                                                  x 
                                           xxxxxxxxxxxxx                                                  x  
                                           xxxxxxxxxxxxx                                                  x 
 
xxxxxx       xxxx       xxxxxxxx           xxxxxxxxxxxxx                                                  x 
                                           xxxxxxxxxxxxx                                                  x 
  
xxxxxx       xxxx       xxxxxxxx           xxxxxxxxxxxxx                                                  x 
 
 
 
 
 
 
 
 
               
                                  
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –    
  date of first application + 1 for dates on or after first application. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Date of Dosing Deviation. 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 175 of 194  
CONFIDENTIAL 
Listing 16.2.5.4: Study Medication Accountability Log 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                               Kit       Kit       Pump             ______Dispensing______     ________Return________    Amount    
Subject   Age/Sex    Eval      Number    Contents  Identifier       Date        Weight (g)     Date        Weight (g)    Used (g)     
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx      xxxxxxxx  xxxx      xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
 
                               xxxx      xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxx xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
  
xxxxxx     xxxx      xxxxxxxx  xxxx      xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxx xxxx                    
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxx xxxx       xxxxxxxxxx  xxxx           
 
xxxxxx     xxxx      xxxxxxxx  xxxx      xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxx xxxx 
                                         xxxx       x                xxxxxxxxxx  xxxx           xxxxxxxxxx  xxxx          xxxx 
 
 
 
 
 
 
 
 
 
 
 
               
                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Note to progammers: Kit Contents is the treatment the kit contained. 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 176 of 194  
CONFIDENTIAL 
Listing 16.2.5.5: Photography 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                                                     
Subject      Age/Sex     Eval          Visit                     Were Photographs Taken                       Date Taken                               
______________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx                          xxx                                 xxxxxxxxxx                          
                                       xxxx x                             xxx                                 xxxxxxxxxx                         
                                       xxxx x                             xx                                                          
                                       xxxx x                             xxx                                 xxxxxxxxxx                         
                                       xxxx xxxxx                         xxx                                 xxxxxxxxxx                         
 
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx                          xxx                                 xxxxxxxxxx                         
                                       xxxx x                             xxx                                 xxxxxxxxxx                         
                                       xxxx x                             xxx                                 xxxxxxxxxx                         
                                       xxxx x                             xxx                                 xxxxxxxxxx       
                                       xxxxxxxxxxx xxxxx xxx              xxx                                 xxxxxxxxxx                         
                                       xxxx xxxxx                         xx                                                        
 
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx                          xxx                                 xxxxxxxxxx                         
                                       xxxx x                             xxx                                 xxxxxxxxxx                         
                                       xxxx x                             xxx                                 xxxxxxxxxx                         
                                       xxxx x                             xxx                                 xxxxxxxxxx                         
                                       xxxx xxxxx                         xxx                                 xxxxxxxxxx                         
 
 
 
 
 
 
 
 
 
 
 
 
               
                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 177 of 194  
CONFIDENTIAL 
Listing 16.2.6.1: Investigator Global Assessment 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                                 Date of      Evaluator 
Subject      Age/Sex     Eval          Visit                     Assessment   Initials        Result                           
______________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx                 xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx xxxxx                xxxxxxxxxx    xxx             xxxxxxxxxx                          
 
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx                 xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx xxxxx                xxxxxxxxxx    xxx             xxxxxxxxxx                          
 
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx                 xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx x                    xxxxxxxxxx    xxx             xxxxxxxxxx                         
                                       xxxx xxxxx                xxxxxxxxxx    xxx             xxxxxxxxxx                          
 
 
 
 
 
 
 
 
               
                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 178 of 194  
CONFIDENTIAL 
Listing 16.2.6.2: Inflammatory Lesion Counts 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                                                                        Total 
                                                  Date of      Evaluator                           Inflammatory              
Subject  Age/Sex  Eval       Visit                Assessment   Initials     Papules     Pustules    Lesion Count     Nodules/Cysts  
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx xxxxx           xxxxxxxxxx      xxx           xx          xx           xx               x 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx xxxxx           xxxxxxxxxx      xxx           xx          xx           xx               x 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx xxxxx           xxxxxxxxxx      xxx           xx          xx           xx               x 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx x               xxxxxxxxxx      xxx           xx          xx           xx               x 
                             xxxx xxxxx           xxxxxxxxxx      xxx           xx          xx           xx               x 
 
 
 
 
               
                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 179 of 194  
CONFIDENTIAL 
Listing 16.2.6.3.1: RosaQoL Descriptions 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Number     RosaQoL Question 
______________________________________________________________________________________________________________________________________ 
 
1          I worry that my rosacea may be serious 
 
2          My rosacea burns or stings 
 
3          I worry about getting scars from my rosacea 
 
4          I worry that my rosacea may get worse 
 
5          I worry about side effects from rosacea medications 
 
6          My rosacea is irritated 
 
7          I am embarrassed by my rosacea 
 
8          I am frustrated by my rosacea 
 
9          My rosacea makes my skin sensitive 
 
10         I am annoyed by my rosacea 
 
11         I am bothered by the appearance of my skin (redness, blotchiness) 
 
12         My rosacea makes me feel self-conscious 
 
13         I try to cover up my rosacea (with make-up) 
 
14         I am bothered by persistence/reoccurrence of my rosacea 
 
15         I avoid certain foods or drinks because of my rosacea 
              
16         My skin feels bumpy (uneven, not smooth, irregular)                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 180 of 194  
CONFIDENTIAL 
Listing 16.2.6.3.1: RosaQoL Descriptions 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Number     RosaQoL Question 
______________________________________________________________________________________________________________________________________ 
 
17         My skin flushes 
 
18         My skin gets irritated easily (cosmetics, aftershaves, cleansers) 
 
19         My eyes bother me (feels dry or gritty) 
 
20         I think about my rosacea 
 
21         I avoid certain environments (heat, humidity, cold) because of my rosacea 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 181 of 194  
CONFIDENTIAL 
Listing 16.2.6.3.2: RosaQoL 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                        Date of 
Subject  Age/Sex  Eval      Visit      Assessment   1   2   3   4   5   6   7   8   9  10  11  12  13  14  15  16  17  18  19  20  21 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
                            xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
                            xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
                            xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
                            xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
                            xxxxxxxxxx  xxxxxxxxxx  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x   x   x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
1 = Never; 2 = Rarely; 3 = Sometimes; 4 = Often; 5 = All the time; ND = Not Done 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 182 of 194  
CONFIDENTIAL 
 
Listing 16.2.6.3.3: RosaQoL Subscales Scores 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                        Date of      
Subject  Age/Sex  Eval      Visit      Assessment   Total Score           Symptom               Functional              Emotion 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
                            xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
                            xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
                            xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
                            xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
                            xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
                            xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
 
xxxxxx   xxxxx    xxxxxxxx  xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
                            xxxxxxxxxx  xxxxxxxxxx     xx                    xx                      xx                    xx 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 183 of 194  
CONFIDENTIAL 
 
 
Listing 16.2.6.4: Erythema Severity/Telangiectasia Assessments 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                               Date of         Evaluator                                
Subject      Age/Sex     Eval          Visit                   Assessment      Initials              Assessment            Result  
______________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx               xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx  
    
                                       xxxx x                  xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx 
 
                                       xxxx x                  xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx 
 
                                       xxxx x                  xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx    
     
                                       xxxx xxxxx              xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx  
    
xxxxxx        xxxx       xxxxxxxx      xxxxxxxxx               xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx 
     
                                       xxxx x                  xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx 
 
                                       xxxx x                  xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx 
 
                                       xxxx x                  xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx 
     
                                       xxxx xxxxx              xxxxxxxxxx      xxx                   Rosacea Erythema      xxxxxxxxxx             
                                                                                                     Telangiectasia        xxxxxxxxxx 
                                                                        
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number, and Assessment (in order presented on eCRF). 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 184 of 194  
CONFIDENTIAL 
Listing 16.2.6.5: PRO – PAPSS, PAPI, PGI-S 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                   Date of                               Object of                            
Subject Age/Sex  Eval      Visit                   Assessment  PRO Category              Assessment           Result             
______________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxx   xxxxxxxx  xxxxxxxxx               xxxxxxxxxx  PAPSS                     BURNING               xxxxxxxxxxx 
                                                                                         ITCHING               xxxxxxxxxxx 
                                                                                         REDNESS               xxxxxxxxxxx 
                                                                                         BUMPS                 xxxxxxxxxxx 
                                                               PAPI                      EMBARRASSED           xxxxxxxxxxx 
                                                                                         SELF-CONSCIOUS        xxxxxxxxxxx 
                                                                                         FRUSTRATED            xxxxxxxxxxx 
 
 
 
 
 
 
 
 
   PGI-S                     ROSACEA               xxxxxxxxxxx  
          
 
 
 
 
                      
 
                           xxxx x                  xxxxxxxxxx  PAPSS                     BURNING               xxxxxxxxxxx 
                                                                                         ITCHING               xxxxxxxxxxx 
                                                                                         REDNESS               xxxxxxxxxxx 
                                                                                         BUMPS                 xxxxxxxxxxx 
                                                               PAPI                      EMBARRASSED           xxxxxxxxxxx 
                                                                                         SELF-CONSCIOUS        xxxxxxxxxxx 
                                                                                         FRUSTRATED            xxxxxxxxxxx 
 
 
 
 
 
 
 
 
   PGI-S                     ROSACEA               xxxxxxxxxxx  
          
 
 
 
 
                                                
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number, PRO Category, and Assessment (in order presented on eCRF). 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 185 of 194  
CONFIDENTIAL 
Listing 16.2.6.6: PRO – PGI-C, PGI-TS, PGI-SE 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                Date of                        
Subject      Age/Sex     Eval       Visit       Assessment    PRO Category    Result            
______________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxx       xxxxxxxx   xxxxxxxxx   xxxxxxxxxx    PGI-C           xxxxxxxxxxxxxx             
                                                              PGI-TS          xxxxxx xxx xxxx    
                                                              PGI-SE          xxxxxxxxxxxxxx       
                                                                              
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           xxxxxxxxxxxxxx             
                                                              PGI-TS          xxxxxx xxx xxxx    
                                                              PGI-SE          xxxxxxxxxxxxxx       
                                                                              
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           xxxxxxxxxxxxxx             
                                                              PGI-TS          xxxxxx xxx xxxx    
                                                              PGI-SE          xxxxxxxxxxxxxx       
                                                                              
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           xxxxxxxxxxxxxx             
                                                              PGI-TS          xxxxxx xxx xxxx    
                                                              PGI-SE          xxxxxxxxxxxxxx       
                                  
xxxxxx        xxxx       xxxxxxx    xxxxxxxxx   xxxxxxxxxx    PGI-C           xxxxxxxxxxxxxx             
                                                              PGI-TS          xxxxxx xxx xxxx    
                                                              PGI-SE          xxxxxxxxxxxxxx       
 
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           xxxxxxxxxxxxxx             
                                                              PGI-TS          xxxxxx xxx xxxx    
                                                              PGI-SE          xxxxxxxxxxxxxx       
                                                
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit Number, and PRO Assessment (in order presented on eCRF). 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 186 of 194  
CONFIDENTIAL 
Listing 16.2.7.1: Cutaneous Safety and Tolerability Assessments 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                        Date of       Evaluator                                            
Subject  Age/Sex  Eval          Visit                   Assessment    Initials      Test                           Result      
______________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxx    xxxxxxxx      xxxxxxxxx               xxxxxxxxxx     xxx           Dryness                       xxxxxxxx          
                                                                                     Scaling                       xxx xxxx                  
                                                                                     Itching                       xxxxxxxxxxxx    
                                                                                     Burning/Stinging              xxxxxxxxxxx 
                                                                           
                                xxxx x                  xxxxxxxxxx     xxx           Dryness                       xxxxxxxx          
                                                                                     Scaling                       xxx xxxx                  
                                                                                     Itching                       xxxxxxxxxxxx    
                                                                                     Burning/Stinging              xxxxxxxxxxx 
                                      
                                xxxx x                  xxxxxxxxxx     xxx           Dryness                       xxxxxxxx          
                                                                                     Scaling                       xxx xxxx                  
                                                                                     Itching                       xxxxxxxxxxxx    
                                                                                     Burning/Stinging              xxxxxxxxxxx 
 
                                xxxxxxxx                xxxxxxxxxx     xxx           Dryness                       xxxxxxxx          
                                                                                     Scaling                       xxx xxxx                  
                                                                                     Itching                       xxxxxxxxxxxx    
                                                                                     Burning/Stinging              xxxxxxxxxxx 
  
xxxxxx    xxxx    xxxxxxxx      xxxxxxxxx               xxxxxxxxxx     xxx           Dryness                       xxxxxxxx          
                                                                                     Scaling                       xxx xxxx                  
                                                                                     Itching                       xxxxxxxxxxxx    
                                                                                     Burning/Stinging              xxxxxxxxxxx 
                                                                           
                                xxxx x                  xxxxxxxxxx     xxx           Dryness                       xxxxxxxx          
                                                                                     Scaling                       xxx xxxx                  
                                                                                     Itching                       xxxxxxxxxxxx    
                                                                                     Burning/Stinging              xxxxxxxxxxx 
                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit Number, and Test (in order presented on eCRF). 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 187 of 194  
CONFIDENTIAL 
Listing 16.2.7.2.1: Unique Adverse Events Coded to MedDRA System Organ Classes and Preferred Terms 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                                              Application 
MedDRA System Organ Class                 MedDRA Preferred Term                  Area        Adverse Event   
______________________________________________________________________________________________________________________________________ 
 
xxxxxxx xxxxxxxxx xxx xxxxxxxxxxxxxxx     xxxxxxxxxx xxx xxxxxxxxxxxxxxxx     xxx            xxxxxxxxxxxx xxxxxxxx xx xx xxxxxx 
                                                                               
                                                                              xx             xxxxxxxx 
                                                                             
                                                                              xx             xxxxx xxxxxxxx 
 
                                          xxxxxxxxx                           xx             xxxxxxxx 
 
xxxxxx xxxxxx xxxxxxxxx                   xxxxxxxx                            xx             xxxxxxx 
 
xxxx xxx xxxxxxxxxxxx xxxxxx xxxxxxxxx    xxxxxxx                             xxx            xxxxxxxxx xx xxxxxxx     
     
                                          xxxx xxxxxxxxxxx                    xx             xxxxxxx xxxx xxxxxxxxx xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
 
 
                                  
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by System Organ Class, Preferred Term, Adverse Event. 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 188 of 194  
CONFIDENTIAL 
Listing 16.2.7.2.2: Pre-Treatment Adverse Events 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                   A: In the Application Area 
S: Subject   S: MedDRA System Organ Class          G: Severity                   A: Action Taken with Study Drug  
A: Age/Sex   P: MedDRA Preferred Term              R: Relationship to Study Drug T: Action Taken to Treat Event  S: Start Date (Day)¹ 
E: Eval      A: Adverse Event                      S: Serious Event              O: Outcome                      E: End Date (Day)¹ 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    S: xxxx xxx xxxxxxxxxxxx xxxxxx       A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx  
A: xxxx      P: xxx xxxxxxxxxxx                    G: xxxx                       T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxx xxxx xxxxxxxxx xxxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xx                         
 
             S: xxxxxxx xxxxxxxxx xxx xxxxxxxxx    A: xxx                        A: xxx xxxxxxxxxx               S: xxxxxxxxxxxxxxx 
             P: xxxxxxxxxx                         G: xxxx                       T: xxxxxxxxxxxx xxxxxxxxxx      E: xxxxxxxxxxxxxxx 
             A: xxxxxxxx xxxxx xxxxxxxx xxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xx                         
 
S: xxxxxx    S: xxxx xxxxxxxxx xxxxxx              A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxxxxxxxx                          G: xxxxxxxx                   T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxxxx xxxxx                    R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xx                         
 
S: xxxxxx    S: xxxx xxxxxxxxx xxxxxx              A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxxxxxxxx                          G: xxxxxxxx                   T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxxxx xxxxx                    R: xxxxxxx                    O: xxxxxxxxxxxxxxxxxx            
                                                   S: xxx                         
 
             S: xxxxxxx xxxxxxxxx xxx xxxxxxxxx    A: xxx                        A: xxx xxxxxxxxxx               S: xxxxxxxxxxxxxxx 
             P: xxxxxxxxxx                         G: xxxx                       T: xxxxxxxxxxxx xxxxxxxxxx      E: xxxxxxxxxxxxxxx 
             A: xxxxxxxx xxxxx xxxxxxxx xxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xx                                                 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –    
  date of first application + 1 for dates on or after first application. 
 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Adverse Event. 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 189 of 194  
CONFIDENTIAL 
Listing 16.2.7.2.3: Treatment-Emergent Adverse Events 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                   A: In the Application Area 
S: Subject   S: MedDRA System Organ Class          G: Severity                   A: Action Taken with Study Drug  
A: Age/Sex   P: MedDRA Preferred Term              R: Relationship to Study Drug T: Action Taken to Treat Event  S: Start Date (Day)¹ 
E: Eval      A: Adverse Event                      S: Serious Event              O: Outcome                      E: End Date (Day)¹ 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    S: xxxx xxx xxxxxxxxxxxx xxxxxx       A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx  
A: xxxx      P: xxx xxxxxxxxxxx                    G: xxxx                       T: xxxx                         E: xxxxxxxxxxxxxxx  
E: xxxxxxxx  A: xxxxxxx xxxx xxxxxxxxx xxxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xx                         
 
             S: xxxxxxx xxxxxxxxx xxx xxxxxxxxx    A: xxx                        A: xxx xxxxxxxxxx               S: xxxxxxxxxxxxxxx 
             P: xxxxxxxxxx                         G: xxxx                       T: xxxxxxxxxxxx xxxxxxxxxx      E: xxxxxxxxxxxxxxx 
             A: xxxxxxxx xxxxx xxxxxxxx xxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xx                         
 
S: xxxxxx    S: xxxx xxxxxxxxx xxxxxx              A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxxxxxxxx                          G: xxxxxxxx                   T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxxxx xxxxx                    R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xxx                         
 
S: xxxxxx    S: xxxx xxxxxxxxx xxxxxx              A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxxxxxxxx                          G: xxxxxxxx                   T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxxxx xxxxx                    R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
                                                   S: xxx                         
 
             S: xxxxxxx xxxxxxxxx xxx xxxxxxxxx    A: xxx                        A: xxx xxxxxxxxxx               S: xxxxxxxxxxxxxxx 
             P: xxxxxxxxxx                         G: xxxx                       T: xxxxxxxxxxxx xxxxxxxxxx      E: xxxxxxxxxxxxxxx 
             A: xxxxxxxx xxxxx xxxxxxxx xxxx       R: xxxxxxx                    O: xxxxxxxxxxxxxxxxxx            
                                                   S: xx                                     
                                      
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –    
  date of first application + 1 for dates on or after first application. 
 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Adverse Event. 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 190 of 194  
CONFIDENTIAL 
Listing 16.2.7.2.4: Serious Adverse Events 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
             S: MedDRA System Organ Class                       
             P: MedDRA Preferred Term              A: In the Application Area 
S: Subject   A: Adverse Event                      G: Severity                   A: Action Taken with Study Drug  
A: Age/Sex   O: Occurred Prior to First            R: Relationship to Study Drug T: Action Taken to Treat Event  S: Start Date (Day)¹ 
E: Eval         Application                        S: Serious Event              O: Outcome                      E: End Date (Day)¹ 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    S: xxxx xxx xxxxxxxxxxxx xxxxxx       A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxx xxxxxxxxxxx                    G: xxxx                       T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxx xxxx xxxxxxxxx xxxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
             O: xx                                 S: xxx                         
 
             S: xxxxxxx xxxxxxxxx xxx xxxxxxxxx    A: xxx                        A: xxx xxxxxxxxxx               S: xxxxxxxxxxxxxxx 
             P: xxxxxxxxxx                         G: xxxx                       T: xxxxxxxxxxxx xxxxxxxxxx      E: xxxxxxxxxxxxxxx 
             A: xxxxxxxx xxxxx xxxxxxxx xxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
             O: xx                                 S: xxx                         
 
 
S: xxxxxx    S: xxxx xxxxxxxxx xxxxxx              A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxxxxxxxx                          G: xxxxxxxx                   T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxxxx xxxxx                    R: xxxxxxx                    O: xxxxxxxxxxxxxxxxxx            
             O: xx                                 S: xxx                         
 
 
 
 
 
 
 
 
 
                                      
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –    
  date of first application + 1 for dates on or after first application. 
 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Adverse Event. 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 191 of 194  
CONFIDENTIAL 
Listing 16.2.7.2.5: Subjects Who Prematurely Discontinued Study and/or Discontinued Study Drug Due to Adverse Events 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                                                                                       
             S: MedDRA System Organ Class                       
             P: MedDRA Preferred Term              A: In the Application Area 
S: Subject   A: Adverse Event                      G: Severity                   A: Action Taken with Study Drug  
A: Age/Sex   O: Occurred Prior to First            R: Relationship to Study Drug T: Action Taken to Treat Event  S: Start Date (Day)¹ 
E: Eval         Application                        S: Serious Event              O: Outcome                      E: End Date (Day)¹ 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    S: xxxx xxx xxxxxxxxxxxx xxxxxx       A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxx xxxxxxxxxxx                    G: xxxx                       T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxx xxxx xxxxxxxxx xxxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
             O: xx                                 S: xxx                         
 
             S: xxxxxxx xxxxxxxxx xxx xxxxxxxxx    A: xxx                        A: xxx xxxxxxxxxx               S: xxxxxxxxxxxxxxx 
             P: xxxxxxxxxx                         G: xxxx                       T: xxxxxxxxxxxx xxxxxxxxxx      E: xxxxxxxxxxxxxxx 
             A: xxxxxxxx xxxxx xxxxxxxx xxxx       R: xxx xxxxxxx                O: xxxxxxxxxxxxxxxxxx            
             O: xx                                 S: xxx                         
 
 
S: xxxxxx    S: xxxx xxxxxxxxx xxxxxx              A: xx                         A: xxx xx xxxxxxx               S: xxxxxxxxxxxxxxx 
A: xxxx      P: xxxxxxxxx                          G: xxxxxxxx                   T: xxxx                         E: xxxxxxxxxxxxxxx 
E: xxxxxxxx  A: xxxxxxxxx xxxxx                    R: xxxxxxx                    O: xxxxxxxxxxxxxxxxxx            
             O: xx                                 S: xxx                         
 
 
 
 
 
 
 
 
 
                                      
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first application for dates prior to first application. Otherwise, day is calculated as date –    
  date of first application + 1 for dates on or after first application. 
 
Note: System Organ Class and Preferred Term map to MedDRA (Version 21.0). 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, Adverse Event. 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 192 of 194  
CONFIDENTIAL 
Listing 16.2.8.1: Urine Pregnancy Tests  
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
Subject  Age/Sex  Eval          Visit                   Date of Assessment          Results        Reason Test Not Done                       
______________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxx    xxxxxxxx      xxxxxxxxx               xxxxxxxxxx                 xxxxxxxx   
                                xxxxxxxx                xxxxxxxxxx                 xxxxxxxx           
                                xxxx x                                                              xxx xxxx  
                                xxxx x                  xxxxxxxxxx                 xxxxxxxx 
                                xxxx x                  xxxxxxxxxx                 xxxxxxxx 
                                                                                                                                                       
xxx        xxxx    xxxxxxxx     xxxxxxxxx               xxxxxxxxxx                 xxxxxxxx 
                                xxxxxxxx                xxxxxxxxxx                 xxxxxxxx           
                                xxxx x                  xxxxxxxxxx                 xxxxxxxx 
                                xxxx x                  xxxxxxxxxx                 xxxxxxxx 
                                xxxx x                  xxxxxxxxxx                 xxxxxxxx                                             
                                                                       
xxx        xxxx    xxxxxxxx     xxxxxxxxx                                                          xxx xxxxxxxxxx  
                                xxxxxxxxx                                                          xxx xxxxxxxxxx 
                                xxxx x                                                             xxx xxxxxxxxxx 
                                xxxx x                                                             xxx xxxxxxxxxx 
                                xxxx x                                                             xxx xxxxxxxxxx 
 
 
 
 
                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number. 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 193 of 194  
CONFIDENTIAL 
Listing 16.2.8.2: Physical Examination 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                    Date of                                                              Reason Exam 
Subject Age/Sex  Eval       Visit                   Assessment  Body System                  Exam Finding                Not Done                      
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx    xxxxxxxx   xxxxxxxx                xxxxxxxxxx  xxxxx                        xxxxxx 
                                                                xxxx                         xxxxxx 
                                                                xxxxxxx                      xxxxxx 
                                                                xxxxxxxxxxxxxx               xxxxxxxxx xxxxxxxxx xxxx  
                                                                xxxxxxxxxxxxxxxxxxxxxxxxx    xxxxxx xxxxx xxxx xxx 
                                                                xxxxxxxxx                    xxxxxxxxx xx xxxx xxxxxx  
  
                            xxxx xxxxx              xxxxxxxxxx  xxxxx  
                                                                xxxx             
                                                                xxxxxxxx 
                                                                xxxxxxxxxxxxxx                xxx xxxx                  xxx xxxxxxxxxx 
                                                                xxxxxxxxxxxxxx                xxx xxxx                  xxx xxxxxxxxxx 
                                                                xxxxxxxxxxxxxx                xxx xxxx                  xxx xxxxxxxxxx                 
 
xxxxxx   xxxx    xxxxxxxx   xxxxxxxx                xxxxxxxxxx  xxxxx                        xxxxxx 
                                                                xxxx                         xxxxxx 
                                                                xxxxxxx                      xxxxxx 
                                                                xxxxxxxxxxxxxx               xxxxxxxxx xxxxxxxxx xxxx  
                                                                xxxxxxxxxxxxxxxxxxxxxxxxx    xxxxxx xxxxx xxxx xxx 
                                                                xxxxxxxxx                    xxxxxxxxx xx xxxx xxxxxx  
  
                            xxxx xxxxx              xxxxxxxxxx  xxxxx  
                                                                xxxx             
                                                                xxxxxxxx 
                                                                xxxxxxxxxxxxxx                xxx xxxx                  xxx xxxxxxxxxx 
                                                                xxxxxxxxxxxxxx                xxx xxxx                  xxx xxxxxxxxxx 
                                                                xxxxxxxxxxxxxx                xxx xxxx                  xxx xxxxxxxxxx                 
 
 
 
                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit Number, and Body System (in order presented on eCRF). 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 194 of 194  
CONFIDENTIAL 
Listing 16.2.8.3: Vital Signs 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                    Date of                                                                                  
Subject Age/Sex  Eval       Visit                   Assessment  Vital Sign                  Result                       Units 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx    xxxxxxxx   xxxxxxxx                xxxxxxxxxx  xxxxxxxxx xxxxx xxxxxxxx    xx                           xxxx  
                                                                xxxxx xxxx                  xx                           xxxxxxxxx  
                                                                xxxxxx                      xxxxx                        xx   
                                                                xxxxxxxxxxx xxxx            xx                           xxxxxxxxxxx 
                                                                xxxxxxxx xxxxx xxxxxxxx     xxx                          xxxx 
                                                                xxxxxxxxxxx                 xxxx                         x    
                                                                xxxxxx                      xxx                          xx 
  
                            xxxx xxxxx              xxxxxxxxxx  xxxxxxxxx xxxxx xxxxxxxx    xx                           xxxx 
                                                                xxxxx xxxx                  xxx xxxx    
                                                                xxxxxxxxxxx xxxx            xxx                          xxxxxxxxxxx   
                                                                xxxxxxxx xxxxx xxxxxxxx     xxx                          xxxx 
                                                                xxxxxxxxxxx                 xx                           x 
                                                              
xxxxxx   xxxx    xxxxxxxx   xxxxxxxx                xxxxxxxxxx  xxxxxxxxx xxxxx xxxxxxxx    xx                           xxxx 
                                                                xxxxx xxxx                  xx                           xxxxxxxxx  
                                                                xxxxxx                      xxx                          xx 
                                                                xxxxxxxxxxx xxxx            xx                           xxxxxxxxxxx 
                                                                xxxxxxxx xxxxx xxxxxxxx     xx                           xxxx 
                                                                xxxxxxxxxxx                 xx                           x 
                                                                xxxxxx                      xxx                          xx                
 
                            xxxx xxxxx              xxxxxxxxxx  xxxxxxxxx xxxxx xxxxxxxx    xxx xxxx 
                                                                xxxxx xxxx                  xxx xxxx    
                                                                xxxxxxxxxxx xxxx            xxx xxxx 
                                                                xxxxxxxx xxxxx xxxxxxxx     xxx xxxx  
                                                                xxxxxxxxxxx                 xxx xxxx                                                   
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit Number, and Vital Sign (in alphabetical order).