Clinical trial NCT03761784
Conditions: Acne Vulgaris
Keywords: Acne Vulgaris
Sponsor: Sol-Gel Technologies, Ltd.
Start date: 2018-12-21; Completion date: 2019-12-31
Enrollment: 424 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To assess the efficacy of S6G5T-3 compared to its Vehicle when applied once daily for 12 weeks in participants with acne vulgaris.

Detailed description:
In this Phase 3, multi-center, 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 9 years of age with facial acne vulgaris will be eligible for enrollment for daily treatment with S6G5T-3 or its vehicle S6G5T-8, for 12 weeks.

Arms: arm 1: Participants will topically apply S6G5T-3 cream, once daily to face for 12 weeks. arm 2: Participants will topically apply S6G5T-8 vehicle cream, once daily to face for 12 weeks.
Interventions: intervention 1: S6G5T-3 intervention 2: S6G5T-8
Intervention descriptions: intervention 1: Once a day topical cream intervention 2: Once a day topical cream

Protocol documents:
Prot_000.pdf: 
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agrees that no unpublished information contained herein will be published or disclosed without prior written approval of Sol-Gel 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. 
CLINICAL STUDY PROTOCOL 
Title: 
A Phase 3 Multi-Center, Double-Blind, 
Randomized, Vehicle-Controlled Study of  
S6G5T-3 in the Treatment of Acne Vulgaris 
Protocol No: 
SGT-65-04 
Protocol Version: 
2.0 
Amendment 1.0 version: 
01-Nov-2018
Original Version: 
23-Mar-2018
Sponsor :  
Sol-Gel Technologies Ltd. 
7 Golda Meir St. 
Weizmann Science Park 
Ness Ziona 7403650, Israel 
NCT # NCT03761784




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2 INVESTIGATOR PROTOCOL 
ACKNOWLEDGMENT 
 
Protocol Title: 
A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-
Controlled Study of S6G5T-3 in the Treatment of Acne Vulgaris  
Study products: 
Product S6G5T-3 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 Study 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 
 
 
 
Protocol number: SGT-65-04, Version 2.0  
 
 
 
 


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3 TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ................................................................................. 1 
1 
PROTOCOL APPROVAL – SPONSOR SIGNATURE ..................................... 2 
2 
INVESTIGATOR PROTOCOL ACKNOWLEDGMENT .................................. 3 
4 
PROTOCOL SYNOPSIS ..................................................................................... 9 
5 
LIST OF ABBREVIATIONS AND TERMS .................................................... 18 
6 
INTRODUCTION AND BACKGROUND ....................................................... 20 
7 
OBJECTIVES .................................................................................................... 23 
8 
ETHICS .............................................................................................................. 24 
9 
INSTITUTIONAL REVIEW BOARD (IRB) AND INFORMED CONSENT . 24 
10 
OVERALL STUDY DESIGN ........................................................................... 25 
11 
STUDY POPULATION ..................................................................................... 26 
11.1 
RANDOMIZATION AND BLINDING ................................................. 26 
11.2 
INCLUSION CRITERIA ....................................................................... 27 
11.3 
EXCLUSION CRITERIA ...................................................................... 28 
11.4 
PROHIBITED, PREVIOUS AND CONCOMITANT MEDICATIONS/ THERAPIES
 ........................................................................................................ 30 
11.5 
PRECAUTIONS .................................................................................. 32 
12 
STUDY PROCEDURES .................................................................................... 33 
12.1 
STUDY PATIENT IDENTIFICATION .................................................... 33 
12.2 
SCREEN FAILURE AND DISCONTINUATION CRITERIA ....................... 33 
12.3 
PATIENT SCREENING AND ENROLLMENT ......................................... 33 
12.4 
ASSIGNMENT OF RANDOMIZATION .................................................. 34 
12.5 
DEMOGRAPHICS/MEDICAL HISTORY ............................................... 34 
12.6 
CONCOMITANT MEDICATIONS ......................................................... 34 
12.7 
PHYSICAL EXAMINATION ................................................................. 34 
12.8 
VITAL SIGNS .................................................................................... 34 
12.9 
URINE PREGNANCY TEST ................................................................. 35 
12.10 
STUDY FLOW CHART ...................................................................... 36 
12.11 
SCREENING VISIT (VISIT 1) .............................................................. 37 
12.12 
BASELINE VISIT (VISIT 2, DAY 1) .................................................... 37 
12.13 
ON-TREATMENT (VISIT 3) – WEEK 2, DAY 15 (± 3 DAYS) .............. 38 
12.14 
ON-TREATMENT VISITS (VISITS 4 AND 5) – WEEKS 4 AND 8, DAYS 29 
AND DAY 57 (± 3 DAYS) .................................................................. 39 
12.15 
END OF STUDY (VISIT 6) – WEEK 12, DAY 85 (± 4 DAYS) OR EARLY 
TERMINATION ................................................................................. 40 
12.16 
UNSCHEDULED VISIT ..................................................................... 40 
12.17 
CLINICAL OUTCOME ASSESSMENTS............................................... 40 
12.18 
INVESTIGATOR GLOBAL ASSESSMENT (IGA)................................. 41 


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12.19 
INFLAMMATORY AND NON-INFLAMMATORY LESION COUNTS ........ 42 
12.19.1 INFLAMMATORY LESION DEFINITIONS: ........................................... 42 
12.19.2 NON-INFLAMMATORY LESION DEFINITIONS: ................................... 42 
12.20 
PATIENT-REPORTED OUTCOMES (PRO) .......................................... 42 
12.21 
ACNE-SPECIFIC QUALITY OF LIFE QUESTIONNAIRE (ACNE-QOL)44 
13 
PHOTOGRAPHY .............................................................................................. 45 
14 
SAFETY EVALUATIONS ................................................................................ 45 
14.1 
CUTANEOUS REACTIONS ASSESSMENTS .......................................... 45 
14.2 
LOCAL TOLERABILITY ASSESSMENTS .............................................. 46 
15 
ADVERSE EVENTS ......................................................................................... 47 
15.1 
DEFINITIONS .................................................................................... 47 
15.2 
ELICITING AND REPORTING OF ADVERSE EVENTS ........................... 49 
15.3 
EXPEDITED REPORTING RESPONSIBILITIES OF THE STUDY CENTER . 50 
15.4 
SUBMITTING AN EXPEDITED SAFETY REPORT TO THE IRB .............. 50 
15.5 
SAE & AES REQUIRING DISCONTINUATION OF STUDY DRUG, 
INCLUDING PREGNANCIES ................................................................ 51 
15.6 
PREGNANCY ..................................................................................... 51 
15.7 
POST STUDY ADVERSE EVENTS ...................................................... 52 
15.7.1 NON-SERIOUS ADVERSE EVENTS ..................................................... 52 
15.7.2 SERIOUS ADVERSE EVENTS ............................................................. 52 
16 
STUDY PRODUCTS / CLINICAL SUPPLIES ................................................ 52 
16.1 
METHOD OF TREATMENT ASSIGNMENT ........................................... 52 
16.2 
FORMULATIONS ............................................................................... 53 
16.3 
STUDY PRODUCTS PACKAGING AND LABELING ............................... 53 
16.4 
PREPARATION, DISPENSING AND STORAGE INSTRUCTIONS .............. 54 
16.5 
DOSING INSTRUCTIONS .................................................................... 55 
16.6 
STUDY PRODUCT ACCOUNTABILITY AND STUDY RECORDS AT SITES55 
16.7 
RETURN AND DESTRUCTION OF STUDY PRODUCT SUPPLIES ............ 56 
16.8 
ADDITIONAL SUPPLIES PROVIDED BY SPONSOR ............................... 56 
17 
STATISTICAL CONSIDERATIONS ............................................................... 56 
17.1 
GENERAL STATISTICAL METHODS ................................................... 56 
17.1.1 PATIENT DISPOSITION ...................................................................... 57 
17.1.2 DEMOGRAPHICS AND BASELINE CHARACTERISTICS ........................ 57 
17.1.3 PROTOCOL DEVIATIONS ................................................................... 57 
17.1.4 ANALYSIS POPULATIONS ................................................................. 57 
17.2 
STUDY PRODUCT EVALUATIONS AND ANALYSES............................. 58 
17.3 
ASSESSMENT OF EFFICACY .............................................................. 58 
17.3.1 PRIMARY EFFICACY ......................................................................... 58 
17.3.2 SECONDARY EFFICACY .................................................................... 58 
17.3.3 SUPPORTIVE EFFICACY .................................................................... 59 
17.3.4 EXPLORATORY ENDPOINT ............................................................... 59 


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17.4 
STATISTICAL HYPOTHESIS TESTING ................................................. 59 
17.4.1 TEST OF SUPERIORITY FOR LESION COUNT VARIABLES ................... 59 
17.4.2 TEST OF SUPERIORITY FOR IGA ....................................................... 60 
17.4.3 TEST OF SUPERIORITY FOR SECONDARY EFFICACY AND CONTROL OF 
MULTIPLICITY ................................................................................. 60 
17.4.4 SUPPORTIVE EFFICACY ANALYSES .................................................. 61 
17.4.5 POOLING ANALYSIS ......................................................................... 61 
17.4.6 MISSING EFFICACY DATA IMPUTATIONS ......................................... 62 
17.4.6.1 LESION COUNT AND PRE-FACE VARIABLE MISSING DATA 
IMPUTATION .................................................................................... 62 
17.4.6.2 IGA MISSING DATA IMPUTATION .................................................... 63 
17.4.7 SENSITIVITY EFFICACY ANALYSES .................................................. 64 
17.4.7.1 SENSITIVITY ANALYSES FOR ABSOLUTE CHANGE IN LESION COUNT . 64 
17.4.7.2 SENSITIVITY ANALYSES FOR IGA .................................................... 64 
17.4.8 SUBGROUP ANALYSES ..................................................................... 65 
17.5 
ASSESSMENT OF SAFETY ................................................................. 65 
17.6 
ADVERSE EVENTS ............................................................................ 65 
17.6.1 VITAL SIGN MEASUREMENTS .......................................................... 66 
17.6.2 CONCOMITANT MEDICATIONS ......................................................... 66 
17.7 
SAMPLE SIZE DETERMINATION ........................................................ 66 
18 
ADMINISTRATIVE CONSIDERATIONS ...................................................... 67 
18.1 
PROTOCOL COMPLIANCE ................................................................. 67 
18.2 
PROTOCOL REVISIONS ..................................................................... 67 
18.3 
PROTOCOL MONITORING ................................................................. 67 
18.4 
REQUIRED STUDY DOCUMENTS ....................................................... 67 
18.5 
ELECTRONIC CASE REPORT FORMS (ECRF)/SOURCE DOCUMENTS . 67 
18.6 
REPORTS TO THE IRB ...................................................................... 68 
18.7 
QUALITY ASSURANCE AUDITS ........................................................ 68 
18.8 
RECORDS RETENTION ...................................................................... 68 


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19 
REFERENCES ................................................................................................... 69 
20 
APPENDIXES .................................................................................................... 70 
APPENDIX 1: PATIENT INSTRUCTIONS SHEET .................................................. 70 
APPENDIX 2:  PRO – PRE-FACE - SIGNS/SYMPTOMS ........................................ 72 
APPENDIX 3:  PRO – PRE-FACE - IMPACTS ......................................................... 73 
APPENDIX 4:  PRO – PGI-S ....................................................................................... 74 
APPENDIX 5:  PRO – PGI-C ...................................................................................... 75 
APPENDIX 6:  PRO – PGI-TS .................................................................................... 76 
APPENDIX 7:  PRO – PGI-SE .................................................................................... 77 
APPENDIX 8: ADMINISTRATION OF ACNE-QOL ............................................... 78 
APPENDIX 9: ACNE-SPECIFIC QOL QUESTIONNAIRE ...................................... 80 
 


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LIST OF TABLES 
TABLE 1: PROHIBITED MEDICATION AND WASHOUT PERIODS ...................... 28 
TABLE 2: INVESTIGATOR GLOBAL ASSESSMENT (IGA) SCALE ....................... 41 
TABLE 3: ASSESSMENTS OF ERYTHEMA, SCALING, DRYNESS AND 
PIGMENTATION .......................................................................................... 46 
TABLE 4: ASSESSMENTS OF ITCHING, BURNING AND STINGING ................... 46 
 
 
 
 


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4 PROTOCOL SYNOPSIS 
 
Title: 
A Phase 3 Multi-Center, Double-Blind, Randomized, Vehicle-Controlled 
Study of S6G5T-3 in the Treatment of Acne Vulgaris  
Study 
Number: 
SGT-65-04 
Study Phase: 
3 
Indication: 
Acne vulgaris 
Study Period: 
12 weeks (84 Days) 
Study 
Products: 
1.  S6G5T-3: 
E-BPO/E-ATRA 
3%/0.1% 
developed 
by 
Sol-Gel 
Technologies and manufactured by 
 New-
Zealand. 
2.  S6G5T-8: Vehicle Cream, developed by Sol-Gel Technologies and 
manufactured by 
 New Zealand. 
Study 
Objectives: 
To assess the efficacy and safety of S6G5T-3 compared to its Vehicle when 
applied once daily for 12 weeks in Patients with acne vulgaris. 
Study Design: 
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 9 years of age with 
moderate or severe facial acne vulgaris. Investigator Global Assessment 
(IGA) grade 3 or 4 will be eligible for enrollment for daily treatment with 
S6G5T-3 or its vehicle, S6G5T-8, for 12 weeks. 
Study 
Population: 
Approximately 420 male and female Patients, at least 9 years of age, who 
meet the inclusion/exclusion criteria will be enrolled in this study.  
Investigational 
sites: 
Approximately 25 study centers in the US will participate in this study. 
Dosing: 
Patients will be randomized in a 2:1 ratio to the study product or vehicle 
treatment groups, 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). 
Study product will be spread as a thin layer, avoiding the eyes, lips, inside 
the nose, mouth and all mucous membranes. Patients will receive detailed 
instructions on the method of application and quantity of use in order to 
assure that treatment is consistent among all Patients to best extent possible. 
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) 


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6. Visit 6/Week 12, Day 85 (± 4 Days)/ End of Study or Early 
Termination. 
Patients will be admitted into the study after written informed consent has 
been obtained, and all inclusion/exclusion criteria have been met, including 
a clinical diagnosis of acne vulgaris. Patients with severe acne vulgaris who 
are appropriate for systemic treatment need to be counseled regarding their 
treatment options by the Principal Investigator. 
Prior to any treatment related assessments, questionnaires are to be 
completed by all patients, starting the age of 9 years old: 
1. Patient reported outcomes (PRO) will be assessed with the Patient-
Reported Evaluation of Facial Acne (PRE-FACE) and the Patient 
Global Impression of Symptom Severity (PGI-S) at: Screening, 
Baseline, Weeks 2, 4, 8, and 12/ Early Termination. The Patient 
Global Impression of Change (PGI-C), Patient Global Impression of 
treatment Side Effects (PGI-SE), and Patient Global Impression of 
Treatment Satisfaction (PGI-TS) will be assessed at: Weeks 2, 4, 8, 
and 12/ End of Study or Early Termination.  
2. Acne Quality of Life (QoL) questionnaire at Baseline and week 12/ 
End of Study or Early Termination 
At each visit, a 5-point scale Investigator Global Assessment (IGA) ranging 
from 0 (Clear) to 4 (Severe) of acne assessment and facial lesion counts 
(inflammatory and non-inflammatory) will be performed. Investigators will 
be provided with instructions for IGA assessments and lesion counts to 
ensure consistency of procedures.  
Safety will be assessed at all visits and will include monitoring of adverse 
experiences; the Investigator Cutaneous Safety Assessment rating of 
pigmentation, erythema, dryness and scaling on a scale ranging from 0 
(None) to 3 (Severe); and the Patient assessment of Local Tolerability rating 
itching burning and stinging on a scale ranging from 0 (None) to 3 (Severe). 
Urine pregnancy tests will be performed for all females of child-bearing 
potential and premenarchal females, at every visit: Screening, Baseline, 
Weeks 2, 4, 8 and 12/ End of Study or Early Termination.  
Standardized optional photography of the face at Baseline and all study visits 
will be performed at select sites. 
Regardless of the duration of the study, all patients that exhibit serious 
adverse event (SAE), will be followed up until the SAE stabilizes or resolves, 
based on Investigator’s medical judgment. 
Clinical Trial 
Duration: 
Planned enrollment duration: about 9 months  
The maximal duration for each participating patient is up to 119 days as 
follows:  


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Screening Period: up to 35 days prior to baseline (Screening evaluations 
should be repeated if Baseline is >35 days after screening)  
Treatment Period: 12 weeks/84 days 
In addition, patients that experience an adverse event (AE) will be followed 
up until the AE stabilizes or resolves, based on the Investigator’s medical 
judgment. 
Study 
Products: 
Encapsulated Benzoyl Peroxide 3%/Encapsulated All-Trans-Retinoic Acids 
0.1% Cream or Vehicle Cream 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 52-gram pumps. 
Patient 
Inclusion 
Criteria: 
Patients may participate in the study if they meet all the following criteria: 
1. Patient must consent to participate, verified by signing an approved 
written Informed Consent Form (ICF). For Patients under the age of 
consent, both a signed assent form and a signed ICF from the 
parent/guardian are required in accordance with local and federal 
regulations. 
2. Male and female 9 years of age and older. 
3. Willingness and capacity for protocol compliance (for Patients under 
the age of consent, the parent/guardian must be willing and able to 
comply with study requirements). 
4. Have a diagnosis of facial acne with ≥30 and ≤150 non-inflammatory 
lesions and ≥20 and ≤100 inflammatory lesions including the nose. 
5. Have a score of “3” or “4” (Moderate or Severe) on the IGA scale. 
6. Have two (2) or fewer cysts or nodules (defined as an inflammatory 
lesion greater than or equal to 5 mm in diameter).  
7. All females of child-bearing potential and premenarchal, excluding 
women who are surgically sterile (including Essure procedure, tubal 
ligation, bilateral oophorectomy or hysterectomy) or post-menopausal:  
[defined as amenorrhea >12 consecutive months; or women on hormone 
replacement therapy (HRT) with documented plasma follicle-
stimulating hormone (FSH) level >35mLU/mL]  for at least 1 year, 
must use one of the following birth control methods throughout the 
duration of the study: 
a) One of these highly effective contraception methods: 
• Intrauterine device (IUD); 
• Hormonal, for at least 3 months. (Pills, injections, implants, 
transdermal patch, vaginal ring); 
• Abstinence 
OR 
b) Double-barrier methods (male and female) of contraception listed 
below: 
• Combined use of male and female condom; 
• Male condom and female occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/ 


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cream/suppository; or 
• Male condom and female contraceptive sponge 
with spermicide 
In addition, Patients entering the trial that are on hormonal 
contraceptives must have been on this method for at least 3 consecutive 
months (90 days) prior to Baseline and agree to continue the same 
hormonal contraceptive or pill for the duration of the trial. Patients who 
have 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 Baseline and have undergone an Essure confirmation test to 
ensure its efficacy. A sterile/vasectomized sexual partner alone is not 
considered an adequate form of birth control.  In this case an additional 
contraceptive method is required. 
8. Male Patients must be clean-shaven or have a cut beard/facial hair that 
does not interfere with study assessment, and they should also agree to 
remain so during the study visits. 
9. Use of multivitamins at recommended daily doses is acceptable and the 
patient agrees not to change dose during study participation. 
10. Premenarchal females and FOCBP must have a negative urine 
pregnancy test at the screening and baseline visits. 
Patient 
Exclusion 
Criteria: 
The presence of any of the following will exclude the potential Patients from 
entry into the study: 
1. More than two acne nodules or cysts (defined as an inflammatory lesion 
greater than or equal to 5 mm in diameter). 
2. Acne conglobata, acne fulminans, secondary acne (chloracne, drug-
induced acne, etc.)  
3. History of blood dyscrasia (e.g., leukemia, haemophilia, sickle cell 
anemia, multiple myeloma, etc.) 
4. Underlying disease that requires the use of interfering topical or 
systemic therapy. 
5. Other dermatological conditions that require the use of interfering 
topical or systemic therapy or that might interfere with study 
assessments such as, but not limited to, atopic dermatitis, perioral 
dermatitis, or rosacea. 
6. Beard, facial hair, or tattoo that may interfere with study assessments. 
7. Use of tanning booths or tanning lamps within one week prior to 
Baseline and an unwillingness to refrain from use during the study. 
8. Use of hormonal contraceptives, unless Patient is on a stable dose for at 
least three consecutive months prior to enrollment and agrees not to 
change or discontinue type of hormonal contraceptive use during study 
participation. 
9. Use of hormonal contraceptives solely for the control of acne. 
10. Use of systemic Isotretinoin and/or Anti- androgens in the past 6 
months. 


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11. Use of prohibited medications prior to the study and unwillingness to 
refrain from use during the study. 
12. Does not meet one or more specified washout period prior to Baseline 
for TOPICAL treatments on the face as follows: 
Topical Medication/Therapy 
Washout Period 
Hyaluronic Acid and Retinol 
1 day 
Antimicrobial Soaps 
1 week 
Phototherapy devices for acne (e.g., ClearLight™), 
adhesive cleansing strips (e.g., Ponds, Biore) as well 
as, use of tanning booths or tanning lamps. 
1 week 
 
 
OTC topical products containing salicylic acid and BPO (e.g. 
Clearasil, Clean & Clear) 
 1 week 
 
Astringents (e.g., Witch hazel, Noxzema), abrasives (e.g., 
Clarisonic brushes, facial scrub products), and preparations 
that contain spices or lime or lemon 
1 week 
Topical medicated cleansers with sulfur or triclosan 
1 week 
Potentially irritating OTC acne products: Alpha-hydroxy-
Acid, and Glycolic Acid 
1 week 
Essential Oils (used specifically for acne, e.g., tree tea oil, 
oregano, lavender, etc.) 
1 week 
Azelaic Acid 
2 weeks 
Topical Corticosteroids in treatment area (inhaled and 
intranasal are allowed), topical vasoconstrictors and 
topical non-steroidal anti-inflammatory drugs, topical 
antibiotics (including antimicrobials like benzoyl 
peroxide containing products, [e.g., benzamycin], zinc 
and sulfur)  
2 weeks 
 
Other topical acne procedures (including photodynamic 
therapy or laser, microdermabrasion) as well cosmetic 
procedures (i.e., facials, peels, comedo extraction, facial 
threading, use of Nair on the face 
2 weeks 
Topical retinoids (e.g., tretinoin, Differin, Adapalene) 
4 weeks 
13. Does not meet one or more specified washout period prior to Baseline for 
SYSTEMIC medications as follows: 
Systemic Medications 
Washout Period 
Corticosteroids (includes intramuscular) 
4 weeks 


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14. Known sensitivities to the study drug ingredients. Allergy to benzoyl  
peroxide, tretinoin, parabens and glycerin or other ingredients listed in  
the Investigator Brochure. 
15. Use of testosterone and Ostarine within four (4) weeks prior to Baseline 
and an unwillingness to refrain from use during the study. 
16. Use of Lithium supplements or prescription (e.g., Lithium Orotate and 
Lithium Carbonate) within four (4) weeks prior to Baseline and an 
unwillingness to refrain from use during the study. 
17. Clinically significant abnormal findings or conditions (other than acne), 
which might, in the opinion of the Investigator, interfere with study 
evaluations or pose a risk to Patient safety during the study. 
18. Female Patients who are pregnant and/or nursing or planning to become 
pregnant during the course of the trial.  Patients who test positive for 
pregnancy after start of test treatment will be discontinued from test 
treatment but will be followed for safety purposes. 
19. Participation in another investigational drug or device research study 
within 30 days of enrollment or five half-lives of the drug, whichever is 
longer. 
20. Previous enrollment in this study or current enrollment in this study at 
another participating site. 
21. Current or history of facial skin cancer. 
22. Patient is an employee or family member of the study Investigator or 
other study staff having direct involvement in the study. 
23. Patients living (e.g., siblings, spouses, relatives) in the same household 
cannot be enrolled in the study at the same time. 
24. Female Patients with a history of polycystic ovarian disease 
25. Topical and oral treatment for acne other than the face (e.g., chest or 
back) is not allowed during the study. 
1Antibiotics  
4 weeks 
Testosterone (All forms includes injections) 
4 weeks 
Ostarine (All forms, includes oral) 
4 weeks 
Lithium (e.g., Lithium Orotate, Lithium Carbonate) 
4 weeks 
Hormonal contraceptives used for less than three consecutive 
months prior to enrollment or used solely for acne control. 
3 months2 
Isotretinoin and Anti-androgens 
6 months 
                                                          
1 Upon randomization one course of penicillin and its derivatives (e.g. amoxicillin) and cephalosporins are 
allowed for a duration of 10 days or less, however not during the two (2) week period just prior to week 12 
visit. 
2 If a Patient is on hormonal contraceptives for less than 3 months, she should continue using the same 
hormonal contraceptives and she can be considered to enter the study after completing 3 months of use. 


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Primary 
Efficacy 
Endpoints:  
• 
Proportion of Patients with an assessment of clear or almost clear and 
with at least a 2-grade improvement in IGA from baseline at Week 12. 
• Absolute change from Baseline in lesion count on the face at Week 12 
(separately for inflammatory and non-inflammatory lesions). 
Secondary 
Efficacy 
Endpoints:  
The secondary efficacy endpoints will be the following: 
• Percent change from Baseline, in non-inflammatory lesion count at 
Week 12. 
• Percent change from Baseline, in inflammatory lesion count at Week 
12. 
• Proportion of Patients in the E-BPO/E-ATRA cream arm compared 
to vehicle control achieving at least a 4-point reduction on Item 1 
(pimples) of the PRE-FACE from Baseline to Week 12. 
• Proportion of Patients in the E-BPO/E-ATRA Cream arm compared 
to vehicle control achieving at least a 4-point reduction on Item 5 
(embarrassment) of the PRE-FACE from Baseline to Week 12. 
• Absolute change from Baseline, in non-inflammatory lesion count at 
Week 8 
• Absolute change from Baseline, in inflammatory lesion count at 
Week 8. 
• Absolute change from Baseline, in non-inflammatory lesion count at 
Week 4. 
• Absolute change from Baseline, in inflammatory lesion count at 
Week 4. 
Supportive 
Efficacy 
Endpoints:  
• Proportion of Patients with an assessment of clear or almost clear and 
with at least a 2-grade improvement from Baseline in IGA, at Weeks 2, 
4 and 8. 
• Absolute change from Baseline in inflammatory and non-inflammatory 
lesion counts from Baseline to weeks 2, 4 and 8. 
• PRE-FACE ASD:  Mean absolute change in PRE-FACE ASD scores 
from Baseline to Weeks 2, 4, and 8. 
• PRE-FACE AID: Mean absolute change in PRE-FACE AID scores from 
Baseline to Weeks 2, 4, and 8. 
• Proportion of Patients in treatment relative to control who report at least 
“minimally improved” as measured by the PGI-C at Week 12. 
• Patient Global Impress of Symptom Severity (PGI-S) at Week 12. 
• Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 
12. 


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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. 
Exploratory 
Endpoint: 
• The mean change in Acne-specific Quality of Life questionnaire (Acne-
QoL) domain scores from Baseline to Week 12. 
Safety: 
 
 
The incidence of all AEs reported during the study will be summarized by 
treatment group. Safety of the study product with will be evaluated by 
comparing the nature, severity and frequency of their AE profiles. Safety 
variables include Investigator Cutaneous Safety Assessment score, 
treatment-emergent AEs (TEAEs), SAEs, treatment related AEs, AEs 
leading to study discontinuation, concomitant medications. 
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 AE related to study product 
or documented lack of treatment effect will be included in the PP population. 
Data for these Patients 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 
The co-primary efficacy analyses will be to compare Product S6G5T-3 with 
vehicle for (1) success rate at Week 12 (defined as ‘clear’ or ‘almost clear’ 
[at least a 2-grade improvement in the IGA]) and (2) absolute change from 
baseline in lesion counts at Week 12 based on the intent-to-treat [ITT] 
population (separately for inflammatory and non-inflammatory lesions). 
Statistical Hypothesis Testing  
Tests of superiority for the absolute change from Baseline in inflammatory 
lesions or non-inflammatory will be based on either parametric or non-


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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. 
Following imputation of missing values, a skewness test, based on the 
methods presented by J.H. 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-ranked 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 IGA 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. Imputation will be conducted independently for each treatment 
group. 
Sensitivity Efficacy Analyses 
Sensitivity analyses for the primary efficacy endpoints will use 3 methods. 
The first method will use a repeated measures ANCOVA, with treatment, 
analysis center, and visit (i.e., Week 2, Week 4 and Week 8) as independent 
factors and a covariate of baseline. In this analysis, data from all post-
Baseline visits will be included with no imputation for missing data. 
The second sensitivity analyses will use the model based multiple imputation 
method to impute missing data for the absolute change at Week 12.  
The third sensitivity analysis will involve a tipping point analysis. 
Statistical analysis plan (SAP), describing all statistical analyses will be 
provided as a separate document.  


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5 LIST OF ABBREVIATIONS AND TERMS 
AE(s) 
Adverse Event(s) 
ANCOVA 
Analysis of Covariance 
ATRA 
All Trans Retinoic Acids: Tretinoin 
BPO 
Benzoyl Peroxide 
°C / °F 
Degrees Centigrade / Degrees Fahrenheit 
CFR 
Code of Federal Regulations 
ClinRo 
Clinician Reported Outcome 
CRA 
Clinical Research Associate 
CRO 
E-ATRA 
Contract Research Organization 
Encapsulated All Trans Retinoic Acid: Encapsulated tretinoin 
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) 
hCG 
Human Chorionic Gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
HRQoL 
Health related Quality of Life 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IND 
Investigational New Drug 
IRAE 
Immediately Reportable Adverse Event 
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 
NRS 
Milligram 
Numeric Rating Scale 
OTC 
Over The Counter 
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 
PRE-FACE 
Patient-Reported Evaluation of Facial Acne 
PRO 
Patient Reported Outcome 
PP 
Per Protocol 
Qd 
Once a Day 
QoL 
Quality of Life 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
Sub-I 
Sub-Investigator 
TEAE 
Treatment-Emergent Adverse Event 


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VRS 
Verbal rating scale 


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6 INTRODUCTION AND BACKGROUND 
Acne vulgaris is a common condition of the pilosebaceous units of the skin (hair 
follicles and oil glands). Acne is the most common skin disorder in the United States, 
affecting 40-50 million Americans. Acne usually begins in puberty, but the condition 
is not restricted to any age group.  
Approximately 85% of people between the ages of 12 and 24 experience at least 
minor, most often on the face, chest, and back (Bhate, 2013). Acne is caused by four 
major factors: 
1. Production of oil by enlarged oil glands in the skin. 
2. Blockage of the hair follicles that release oil. 
3. Growth of bacteria, called Propionibacterium acnes, within the hair follicles. 
4. Inflammatory/immune response to P. acnes  
The pathophysiologic features of acne suggest that combination therapy should be 
utilized as early as possible to simultaneously attack the multiple pathogenic factors 
of the condition (Gollnick 2003). Antimicrobials have been a mainstay of acne 
treatment for many years, having multiple mechanisms of action. The most important 
may be the ability of antibiotics to decrease the number of P. acnes in and around the 
follicle. They have a bacteriostatic effect on P. acnes, which prevents the bacteria from 
producing pro-inflammatory molecules (Leyden 2001). 
In clinical practice, it is common for physicians to prescribe multiple topical products 
for acne. Topical products are applied one or two times a day by the Patient.  However, 
many of these compounds are irritating with resultant development of facial erythema 
and discontinuation of the products or noncompliance with therapy. Benzoyl peroxide 
(BPO) and tretinoin (ATRA) are two active ingredients with different 
pharmacological actions that are commonly used for the treatment of acne. 
Topical retinoids are keratinization inhibitors. They work by decreasing the 
cohesiveness of follicular epithelial cells.  This, results in an inhibition in the 
formation of microcomedones, preventing the formation of mature comedones and 
inflammatory lesions (Gollnick 2003). Use of retinoids promotes the normal 
desquamation of follicular epithelium. The action of the retinoid may enhance the 
penetration of other topical compounds used to treat acne. 
Benzoyl peroxide (BPO) is a commonly used topical antibacterial agent for acne 
available either by prescription or over the counter (OTC).  BPO has been found to be 
lethal to P. acnes as well as other bacteria that may reside on the skin.  So far there 
has been no indication of any bacteria developing a resistance to BPO.  It has also 
been demonstrated that BPO has keratolytic activity contributing to its efficacy in 
treating comedonal acne (Tanghetti 2008). BPO reduces the cohesiveness of the cells 
of the stratum corneum, thus improving topical drug delivery through the epidermal 
barrier. 
Silica microcapsule systems have been developed to overcome many of the limitations 


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(such as degradation and irritation) of standard pharmaceutical formulations involving 
multiple active ingredients. The encapsulation of active ingredients in silica 
microcapsules serves to protect components in the formulation from interacting with 
one another and, as a consequence, increases overall formulation stability. Silica is 
chemically inert, photochemically and physically stable, and safe for topical use. Sol-
Gel’s silica encapsulated products meet the criteria for categorical exclusion defined 
in 21 CFR 25.31(e), and that to the knowledge of Sol-Gel, no extraordinary 
circumstances exist as defined in 21 CFR 25.21. Thus, no environmental assessment 
is required according to 21 CFR 25.20(l). For the case of E-BPO/E-ATRA, 
microencapsulation of both BPO and tretinoin protects the tretinoin from oxidative 
decomposition by BPO, thereby enhancing the stability for this novel combination 
product and ensuring a suitable clinical and commercial shelf life. The encapsulation 
may also contribute to decreased skin irritation as evidenced in the 14-day minipig 
irritation study referenced in the nonclinical section of the Investigator’s Brochure. 
Combination topical therapy is the recommended standard of care for the management 
of Patients with acne (Gollnick 2003). Combination therapy targets multiple 
pathogenic factors: abnormal follicular keratinization, P. acnes proliferation and 
inflammation. Combining the separate product applications into a single delivery 
system would provide the Patient with the convenience of a single product, thus 
improving Patient adherence and improving treatment outcomes. 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 


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7 OBJECTIVES  
The primary objectives of this pivotal study are: 
1. To assess the efficacy of S6G5T-3 compared to its Vehicle when applied once 
daily for 12 weeks in Patients with acne vulgaris. 
2. To assess the safety of S6G5T-3 when applied once daily for 12 weeks in 
Patients with acne vulgaris. 
The co-primary efficacy endpoints are to be evaluated using the following parameters: 
• Proportion of Patients with an assessment of clear or almost clear and with at 
least a 2-grade improvement in IGA from baseline at Week 12. 
• Absolute change from Baseline in lesion count on the face at Week 12 
(separately for inflammatory and non-inflammatory lesions). 
The secondary objective of this pivotal study is: 
To demonstrate statistical superiority in efficacy of Products S6G5T-3 as compared to 
the vehicle regarding percent change from baseline. 
The secondary efficacy endpoints will be the following: 
• Percent change from Baseline, in non-inflammatory lesion count at Week 12. 
• Percent change from Baseline, in inflammatory lesion count at Week 12. 
• Proportion of Patients in the E-BPO/E-ATRA cream arm compared to vehicle 
control achieving at least a 4-point reduction on Item 1 (pimples) of the PRE-FACE 
from Baseline to Week 12. 
• Proportion of Patients in the E-BPO/E-ATRA Cream arm compared to vehicle 
control achieving at least a 4-point reduction on Item 5 (embarrassment) of the 
PRE-FACE from Baseline to Week 12. 
• Absolute change from Baseline, in non-inflammatory lesion count at Week 8 
• Absolute change from Baseline, in inflammatory lesion count at Week 8. 
• Absolute change from Baseline, in non-inflammatory lesion count at Week 4. 
• Absolute change from Baseline, in inflammatory lesion count 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 acne for Products S6G5T-3 compared to vehicle. 
Supportive efficacy endpoints include the following: 
• Proportion of Patients with an assessment of clear or almost clear and with at 
least a 2-grade improvement in IGA from Baseline, at Weeks 2, 4 and 8. 
• Absolute change from Baseline in inflammatory and non-inflammatory lesion 
counts from Baseline to weeks 2, 4 and 8. 
• PRE-FACE ASD:  Mean absolute change in PRE-FACE ASD scores from 
Baseline to Weeks 2, 4, and 8. 
• PRE-FACE AID: Mean absolute change in PRE-FACE AID scores from 
Baseline to Weeks 2, 4, and 8. 
• Proportion of Patients in treatment relative to control who report at least 
“minimally improved” as measured by the PGI-C at Week 12. 
• Patient Global Impress of Symptom Severity (PGI-S) at Week 12. 


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• Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 12. 
The safety objectives of this pivotal study are: 
To determine the nature, severity and frequency of the AEs rate and the local 
cutaneous reaction and tolerability of Products S6G5T-3 compared to the vehicle. 
The safety endpoints to be assessed include the following: 
• The frequency of both local and systemic AEs 
• Investigator Cutaneous Reaction (erythema, dryness, pigmentation and scaling) 
and Local Tolerability Assessment (itching burning and stinging) at Baseline 
and at all study visits. 
 
8 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 study 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. 
9 INSTITUTIONAL REVIEW BOARD (IRB) AND 
INFORMED CONSENT 
Before study initiation, this protocol, the investigational brochure for Encapsulated 
Benzoyl Peroxide 3%/Encapsulated All-Trans-Retinoic Acids 0.1% Cream (E-BPO/E-
ATRA 3%/0.1%) in the treatment of acne vulgaris, the ICF, 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 Contract Research Organization (CRO) 
designee. 
The IRB-approved ICF must include all elements required by the Food and Drug 
Administration (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 ICF. 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 ICF, 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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10  OVERALL STUDY DESIGN 
This study will be a randomized, double-blind, multicenter, parallel group, active- and 
vehicle-controlled pivotal study to asses efficacy, and safety of Products S6G5T-3 
and its vehicle for the treatment of acne vulgaris for 12 weeks. Approximately 420 
Patients with moderate to severe acne vulgaris (rated 3 or 4 on the 5-point IGA) will 
be enrolled at up to 25 sites. Patients in this randomized, double-blind, vehicle-
controlled, parallel-group multi-center study will be randomly assigned in a 2:1 ratio 
to Encapsulated Benzoyl Peroxide 3%/Encapsulated All-Trans-Retinoic Acids 0.1% 
(E-BPO/E-ATRA) Cream or Vehicle Cream respectively. Patients with severe acne 
vulgaris who are appropriate for systemic treatment need to be counseled regarding 
their treatment options by the Principal Investigator (PI). 
 
The overall schedule of study visits includes:   
• 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 Study or Early Termination 
 
Treatment efficacy will be evaluated using both clinician reported outcome (ClinRO) 
and Patient-reported outcome (PRO) questionnaires. Clinician reported efficacy 
assessments will include facial inflammatory and non-inflammatory lesion counts and 
an IGA which asks assessors to rate Patient’s acne from 0 (Clear) to 4 (Severe). Patient 
reported efficacy assessments include the Patient-Reported Evaluation of Facial Acne 
(PRE-FACE), the Patient Global Impression of Symptom Severity (PGI-S), the Patient 
Global Impression of Change (PGI-C), and the Patient Global Impression of Treatments 
Satisfaction (PGI-TS).   
Safety will be assessed at all visits and will include monitoring local and systemic AEs; 
the Investigator Cutaneous Safety Assessment rating of pigmentation, erythema, 
dryness and scaling on a scale ranging from 0 (None) to 3 (Severe) and the Patient 
assessment of Local Tolerability Assessment rating itching, burning and stinging on a 
scale ranging from 0 (None) to 3 (Severe). A Patient Global Impression of Treatment 
Side Effects (PGI-SE) will also be administered as part of the study design. 
Clinician reported outcomes will be collected at study Visit 1, 2, 3, 4, 5 and 6. Patient-
reported outcomes will be collected at study visit 2, 3, 4, 5, and 6 (with the exception 
of the PGI-C, PGI-TS and PGI-SE) which are not collected at Visit 1 or Visit 2).  AEs 
and concomitant medications will be assessed throughout the treatment period. A urine 
pregnancy test is required at Visit 1, 2, 3, 4, 5 and 6 for all females of child-bearing 
potential and premenarchal. 
 


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11  STUDY POPULATION  
11.1 Randomization and Blinding  
It is planned that approximately 420 Patients, who meet the inclusion/exclusion criteria, 
will be enrolled in this study at up to 25 U.S. study sites. Patients will be at least 9 years 
of age and older, of either gender.  
The study products will be administered in a double-blinded fashion (i.e., the treatment 
assignment will not be known to the Patient or to study personnel including 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/E-ATRA 3%/0.1% Cream (Product S6G5T-3) (280 Patients) 
• Vehicle Cream (Product S6G5T-8) (140 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 Product S6G5T-3 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 Product S6G5T-3 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 the 
database is locked. 
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 PI in the case of an emergency unblinding. 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 of one or all Patients may be necessary in the case that the safety of study 
Patient(s) 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 un-
blind 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 
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11.2 Inclusion Criteria 
To be included in the study, Patients must meet the following eligibility /inclusion 
criteria: 
1. Patient must consent to participate, verified by signing an approved written 
Informed Consent Form (ICF). For Patients under the age of consent, both a 
signed assent form and a signed ICF from the parent/guardian are required in 
accordance with local and federal regulations. 
2. Male and female 9 years of age and older. 
3. Willingness and capacity for protocol compliance (for Patients under the age of 
consent, the parent/guardian must be willing and able to comply with study 
requirements). 
4. Have a diagnosis of facial acne with ≥30 and ≤150 non-inflammatory lesions and 
≥20 and ≤100 inflammatory lesions including the nose. 
5. Have a score of “3” or “4” (Moderate or Severe) on the IGA scale. 
6. Have two (2) or fewer cysts or nodules (defined as an inflammatory lesion greater 
than or equal to 5 mm in diameter).  
7. All females of child-bearing potential and premenarchal, excluding women who 
are surgically sterile (including Essure procedure, tubal ligation, bilateral 
oophorectomy or hysterectomy) or post-menopausal:  [defined as amenorrhea >12 
consecutive months; or women on hormone replacement therapy (HRT) with 
documented plasma follicle-stimulating hormone (FSH) level >35mLU/mL]  for 
at least 1 year, must use one of the following birth control methods throughout the 
duration of the study: 
c) One of these highly effective contraception methods: 
• Intrauterine device (IUD); 
• Hormonal, for at least 3 months. (Pills, injections, implants, transdermal 
patch, vaginal ring); 
• Abstinence 
OR 
d) Double-barrier methods (male and female) of contraception listed below: 
• Combined use of male and female condom; 
• Male condom and female occlusive cap (diaphragm or cervical/vault caps) 
with spermicidal foam/gel/film/ cream/suppository; or 
• Male condom and female contraceptive sponge with spermicide 
In addition, Patients entering the trial that are on hormonal contraceptives must 
have been on this method for at least 3 consecutive months (90 days) prior to 
Baseline and agree to continue the same hormonal contraceptive for the duration 
of the trial. Patients who have 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 Baseline and have undergone an Essure confirmation test to ensure its efficacy. 
A sterile/vasectomized sexual partner alone is not considered an adequate form of 
birth control.  In this case an additional contraceptive method is required. 
8. Male Patients must be clean-shaven or have a cut beard/facial hair that does not 
interfere with study assessment, and they should also agree to remain so during the 
study visits. 
9. Use of multivitamins at recommended daily doses is acceptable and the patient 
agrees not to change dose during study participation. 


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10. Premenarchal females and FOCBP must have a negative urine pregnancy test at 
the screening and baseline visits. 
11.3 Exclusion Criteria 
Patients are excluded from the study if any of the following criteria are met: 
1. More than two acne nodules or cysts (defined as an inflammatory lesion greater 
than or equal to 5 mm in diameter). 
2. Acne conglobata, acne fulminans, secondary acne (chloracne, drug-induced acne, 
etc.)  
3. History of blood dyscrasia (e.g., leukemia, haemophilia, sickle cell anemia, 
multiple myeloma, etc.) 
4. Underlying disease that requires the use of interfering topical or systemic therapy. 
5. Other dermatological conditions that require the use of interfering topical or 
systemic therapy or that might interfere with study assessments such as, but not 
limited to, atopic dermatitis, perioral dermatitis, or rosacea. 
6. Beard, facial hair, or tattoo that may interfere with study assessments. 
7. Use of tanning booths or tanning lamps within one week prior to Baseline and an 
unwillingness to refrain from use during the study. 
8. Use of hormonal contraceptives, unless Patient is on a stable dose for at least three 
consecutive months prior to enrollment and agrees not to change or discontinue 
type of hormonal contraceptive use during study participation. 
9. Use of hormonal contraceptives solely for the control of acne. 
10. Use of Isotretinoin and/or Anti- androgens in the past 6 months. 
11. Use of prohibited medications prior to the study and unwillingness to refrain from 
use during the study. 
12. Does not meet one or more specified washout period prior to Baseline for 
TOPICAL treatments on the face as follows: 
Table 1: prohibited medication and washout periods 
 
Topical Medication/Therapy 
Washout Period 
Hyaluronic Acid and Retinol 
1 day 
Antimicrobial Soaps 
1 week 
Phototherapy devices for acne (e.g., ClearLight™), adhesive 
cleansing strips (e.g., Ponds, Biore) as well as, use of tanning 
booths or tanning lamps. 
1 week 
 
 
OTC topical products containing salicylic acid and BPO (e.g. 
Clearasil, Clean & Clear) 
 1 week 
 
Astringents (e.g., Witch hazel, Noxzema), abrasives (e.g., Clarisonic 
brushes, facial scrub products), and preparations that contain spices or 
lime or lemon 
1 week 
Topical medicated cleansers with sulfur or triclosan 
1 week 
Potentially irritating OTC acne products: Alpha-hydroxy-Acid, and 
Glycolic Acid 
1 week 


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14. Known sensitivities to the study drug ingredients. Allergy to benzoyl  
peroxide, tretinoin, parabens and glycerin or other ingredients listed in  
the Investigator Brochure. 
15. Use of testosterone and Ostarine within four (4) weeks prior to Baseline and an 
unwillingness to refrain from use during the study. 
16. Use of Lithium supplements or prescription (e.g., Lithium Orotate and Lithium 
Carbonate) within four (4) weeks prior to Baseline and an unwillingness to refrain 
from use during the study. 
17. Clinically significant abnormal findings or conditions (other than acne), which 
might, in the opinion of the Investigator, interfere with study evaluations or pose a 
risk to Patient safety during the study. 
18. Female Patients who are pregnant and/or nursing or planning to become pregnant 
during the course of the trial.  Patients who test positive for pregnancy after start 
of test treatment will be discontinued from test treatment but will be followed for 
safety purposes. 
19. Participation in another investigational drug or device research study within 30 
days of enrollment or five half-lives of the drug, whichever is longer. 
                                                          
1 Upon randomization one course of penicillin and its derivatives (e.g. amoxicillin) and cephalosporins 
are allowed for a duration of 10 days or less, however not during the two (2) week period just prior to 
week 12 visit. 
2 If a Patient is on hormonal contraceptives for less than 3 months, she should continue using the same 
hormonal contraceptives and she can be considered to enter the study after completing 3 months of use. 
Essential Oils (used specifically for acne, e.g., tree tea oil, oregano, 
lavender, etc.) 
1 week 
Azelaic Acid 
2 weeks 
Topical Corticosteroids in treatment area (inhaled and intranasal 
are allowed), topical vasoconstrictors and topical non-steroidal 
anti-inflammatory drugs, topical antibiotics (including 
antimicrobials like benzoyl peroxide containing products, [e.g., 
benzamycin], zinc and sulfur)  
2 weeks 
 
Other topical acne procedures (including photodynamic therapy 
or laser, microdermabrasion) as well cosmetic procedures (i.e., 
facials, peels, comedo extraction, facial threading, use of Nair on 
the face 
2 weeks 
Topical retinoids (e.g., tretinoin, Differin, Adapalene) 
4 weeks 
13. Does not meet one or more specified washout period prior to Baseline for SYSTEMIC 
medications as follows: 
Systemic Medications 
Washout Period 
Corticosteroids (includes intramuscular) 
4 weeks 
1Antibiotics  
4 weeks 
Testosterone (All forms includes injections) 
4 weeks 
Ostarine (All forms, includes oral) 
4 weeks 
Lithium (e.g., Lithium Orotate, Lithium Carbonate) 
4 weeks 
Hormonal contraceptives used for less than three consecutive months 
prior to enrollment or used solely for acne control. 
3 months2 
Isotretinoin and Anti-androgens 
6 months 


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20. Previous enrollment in this study or current enrollment in this study at another 
participating site. 
21. Current or history of facial skin cancer. 
22. Patient is an employee or family member of the study Investigator or other study 
staff having direct involvement in the study. 
23. Patients living (e.g., siblings, spouses, relatives) in the same household cannot be 
enrolled in the study at the same time. 
24. Female Patients with a history of polycystic ovarian disease 
25. Topical and oral treatment for acne other than the face (e.g., chest or back) is not 
allowed during the study. 
11.4 Prohibited, 
Previous 
and 
Concomitant 
Medications/ 
Therapies 
Any previous acne therapies must be stopped for the appropriate washout period as 
specified below and as noted in the exclusion criteria, and are excluded as concomitant 
medications / therapies throughout the trial unless otherwise specified below: 
• Topical Hyaluronic Acid and Retinol within 1 day of Baseline. 
• Antimicrobial Soaps within 1 week of Baseline. 
• Phototherapy devices for acne (e.g., ClearLight™), adhesive cleansing strips 
(e.g., Ponds, Biore) as well as use of Nair on the face, use of tanning booths or 
tanning lamps), within 1 week of Baseline. 
• OTC topical products containing salicylic acid and BPO (e.g., Clearasil, Clean 
& Clear) within 1 week of Baseline. 
• Astringents (e.g., witch hazel, Noxzema), abrasives (e.g., Clarisonic brushes, 
facial scrub products), and preparations that contain spices or lime or lemon 
within 1 week of Baseline. 
• Use of medicated cleansers on the face (e.g., sulfur or triclosan) within 1 week 
of Baseline. 
• Topical alpha-hydroxy-Acid and glycolic acid within 1 week of Baseline. 
• Topical essential oils (used specifically for acne, e.g., tree tea oil, oregano, 
lavender, etc.) within 1 week of Baseline. 
• Topical azelaic Acid within 2 weeks of Baseline. 
• Topical corticosteroids (inhaled and intranasal are allowed), topical 
vasoconstrictors and topical non-steroidal anti-inflammatory drugs; topical 
antibiotics (including   antibacterial like benzoyl peroxide containing products, 
[e.g., benzamycin], zinc and sulfur) – within 2 weeks of Baseline. 
• Other topical acne procedures (including photodynamic therapy or laser, 
microdermabrasion) as well as cosmetic procedures (i.e., facials, peels, comedo 
extraction, facial threading, within 2 weeks of Baseline 
• Topical retinoids (e.g., Differin, Adapalene)– 4 weeks prior to Baseline. 
• Systemic corticosteroids (includes intramuscular) within 4 weeks of Baseline. 
• Systemic antibiotics 4 weeks prior to baseline.  Upon randomization one course 
of penicillin and its derivatives (e.g. amoxicillin) and cephalosporins are 
allowed for a duration of 10 days or less, however not during the two (2) week 
period just prior to week 12 visit.  
• Systemic testosterone (all forms includes injections) within 4 weeks of Baseline 
• Systemic Ostarine (all forms, includes oral) within 4 weeks of Baseline. 
• Systemic Lithium (e.g., Lithium Orotate, Lithium Carbonate) within 4 weeks of 


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Baseline. 
• Systemic hormonal contraceptives used for less than three consecutive months 
prior to Baseline or used solely for acne control within 3 months of Baseline. 
• Systemic Isotretinoin and Anti-androgens) within 6 months of Baseline. 
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 Baseline) is allowed.  
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 (2) hours after study product application. Approved moisturizer/sunscreen 
may be applied after at least 30 minutes following 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 Baseline 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 medications and therapies used during the study must be recorded on 
the Concomitant Medications 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 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 Medications form at each visit. The reason for any change in concomitant 
medications/therapies should be reported as, or in conjunction with, an AE except as 
noted below:  
• Prophylactic therapies, such as vaccines, must be recorded on the Concomitant 
Medications form, but the reasons for these therapies should not be reported as 
AEs.  
• Changes in therapy for pre-existing conditions that are not related to a worsening 
of the condition must be reported on the Concomitant Medications form, but the 
reasons for these changes should not be reported as AEs. The condition must be 
reported in the Medical History form. 
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. 


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Patients should avoid UV exposure by sun bathing or tanning parlors.  
11.5 Precautions 
The following precautions are to be taken during this study: 
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 (suggest before going to bed) to avoid spreading it on 
other areas of the face (e.g., eyes, ears, neck, etc.) and bedding.  
5. The study product should be spread smoothly and 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. 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.  Make-up 
should not be changed during the study. 
8. Patients should not apply moisturizers, make-up, creams, lotions, powders or any 
topical product they do not routinely use on their face. 
9. Patients should not cover the treated area with a bandage (occlusive dressing) or 
other types of dressing after applying the study product.  
10. Patients should limit sun exposure, including sunlamps (non-prescription UV light 
sources); avoid tanning beds/booths/parlors and sauna while on the study. 
11. Patients should use moisturizer with SPF supplied by the Sponsor or from study-
approved products and protective apparel (e.g. wide- brimmed hat) when outdoors. 
Patients should wait at least 30 minutes after study product is applied on the face 
before applying an approved sunscreen. Weather extremes, such as wind or cold, 
may be irritating to Patient. 
12. UVA/UVB treatments to the face are also prohibited.  
13. 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 Investigator or 
Sub-Investigator (Sub-I). 
14. Patients should consult the Investigator with any questions regarding concomitant 
medications/therapies. 
15. Abrasive cleansers or washes, alcoholic toners, astringents are prohibited 
throughout the study.  
16. “Waxing” as a depilatory method should be avoided on skin treated with study 
product. 
17. Patients should be informed that local skin reactions [dryness, burning, stinging, 
pruritus (itching), scaling/peeling] may occur. 


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12 STUDY PROCEDURES 
12.1 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. 
12.2 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 ICF, and would not have received study product. The ICF 
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 or designee’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. 
• AE – 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. Best efforts should be performed 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. 
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 or Early Termination assessments.  
In the case of Patients who discontinue due to an AE, 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. 
12.3 Patient Screening and Enrollment 
The study personnel will review the IRB-approved ICF, and assent as applicable, with 
each Patient and give the Patient an opportunity to have all questions answered before 
proceeding. The ICF must be signed by each Patient before the Patient is enrolled into 


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the study. A copy of the signed ICF 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 35 days from their initial informed 
consent/assent signing must be screen-failed, then re-consented as a “new” Patient 
before any further study procedures can begin. 
12.4 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 
assigning treatment group. The study product supplies will be packed in kits containing 
4-pumps and will be numbered in a scrambled randomized method.  The kits will be 
dispensed by the IWRS according to the baseline assigned randomized treatment group.  
The first supplied pump in each kit is marked A (e.g. number of pump within a kit is 
1234A).  At Week 4 the Patient will return the pump and will be dispensed with the 
next pump which is marked with same number followed by B. At Week 8, the Patient 
will return the pump and will be dispensed with a pump marked with same number 
followed by C. Pump marked as D may be dispensed to Patients who lost/damage/ran-
out of study product. 
12.5 Demographics/Medical History 
A demographic profile and complete medical history will be recorded prior to 
randomizing and starting study product. Medical histories having resolved 2 or more 
years before Baseline need not be collected unless considered relevant by the 
Investigator. 
12.6 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 prior to commencing the use 
of the study products.  
12.7 Physical Examination 
The Investigator, Sub-I or appropriately delegated and qualified designee will perform 
a brief physical examination, prior to the Patient starting study product as well as at the 
End of Study (Visit 6) Week 12/Early Termination Visit. The exam will include heart, 
lung, abdomen evaluation as well as recording height and weight.  
12.8 Vital Signs 
Vital signs are performed at the time of the physical examination and include sitting 
blood pressure, temperature, heart rate and respiratory rate. 


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12.9 Urine Pregnancy Test 
All Females of child-bearing potential and premenarchal (excluding women who are 
surgically sterile or post-menopausal [defined as amenorrhea >12 consecutive months; 
or women on hormone replacement therapy (HRT) with documented plasma follicle-
stimulating hormone (FSH) level >35mLU/mL] for at least 1 year), 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 may 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 be conducted at every visit, starting from Screening and until 
Week 12/ End of Study or Early Termination Visit. If more than 2 weeks washout 
period is needed between Screening to Baseline visit, urine pregnancy test should be 
repeated at the Baseline visit.  For this study, the following are considered acceptable 
methods of birth control: Intrauterine device (IUD); Hormonal, for at least 3 months. 
(Pills, injections, implants, transdermal patch, vaginal ring); Abstinence. Double-
barrier methods (male and female) of the following contraception: Combined use of 
male and female condom; Male condom and female occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/ cream/suppository; Male condom 
and female contraceptive sponge with spermicide. 
 
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/vasectomized sexual partner alone is not considered an adequate form of birth 
control.  In this case an additional contraceptive method is required. 
 
 


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12.10 
Study Flow Chart  
 
Procedures 
Visit 11 
Visit 22 
Visit 32 
Visit 42 
Visit 52 
Visit 63 
(EOS4/ ET5) 
Name of Visit 
Screening 
 
Baseline 
Day 1 
Week 2 
Day 15 
Week 4 
Day 29 
Week 8 
Day 57 
Week 12  
Day 85 
Visit Window 
Day -35 to 
Day 0 
 
±3 days 
±3 days 
±3 days 
±4 days 
Informed Consent/Assent  
X 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
Medical History/ Previous Therapies 
X 
X 
 
 
 
 
Brief Physical Examination & Vital signs 
 
X 
 
 
 
X 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
Urine Pregnancy Test6  
X 
X7 
X 
X 
X 
X 
Complete PRE-FACE and PGI-S8, 
X 
X 
X 
X 
X 
X 
Complete PGI-C, PGI-TS and PGI-SE9  
 
 
X 
X 
X 
X 
Complete Acne-QoL questionnaire10 
 
X 
 
 
 
X 
IGA 
X 
X 
X 
X 
X 
X 
Lesion Counts 
X 
X 
X 
X 
X 
X 
Assessment of Eligibility 
 
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 
Dispense Study Product  
 
X11 
 
X 
X 
 
Dispense Cleanser & Moisturizer 
 
X12 
 
 
 
 
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 
Prior and Concomitant Therapy and 
Medication Reviewed 
X 
X 
X 
X 
X 
X 
Assessment of Adverse Events 
X13 
X 
X 
X 
X 
X 
Photography (select site(s)) 
 
X 
X 
X 
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 Week 12/ End of Study procedures should be completed for Patients who terminate early. 
4 EOS – End of Study 
5 ET – Early Termination 
6 All females of child-bearing potential and premenarchal must undergo Urine Pregnancy Tests, at every visit. 
7 Urine Pregnancy test should be repeated if more than 2 weeks washout is needed. 
8 Questionnaires are to be completed by all patients prior to any treatment related assessments. In case Screening Visit and 
Baseline occur at the same day, the PRO questionnaires should be completed prior to screening procedures. 
9 Questionnaires are to be completed by all patients prior to any treatment related assessments. 
10 Questionnaires are to be completed by all patients prior to any treatment related assessments. In case Screening Visit and 
Baseline occur at the same day, the QoL questionnaires should be completed prior to screening procedures. 
11 Dispense one pump of study product at the Baseline Visit and dispense additional pump at Visit 4 and 5. 
12 The Patients will use only products which were supplied by the Sponsor or approved by the Investigator. 
13 Adverse events after ICF is signed will be collected. 


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12.11 
Screening Visit (Visit 1)  
If no washout is needed, Visit 1 (Screening) and Visit 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 ICF for all Patients prior to any study related 
procedures. 
• Confirm the Patient meets the inclusion/exclusion criteria as outlined in sections 
11.211.2 and  11.3 
• Record any AEs. 
• Perform a Urine Pregnancy Test for all females of child-bearing potential and 
premenarchal (see section 12.9); 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 the 
Concomitant Medications form as outlined in section 11.4. 
• Ask the Patient to complete PRE-FACE questionnaires (see APPENDIX 2:  PRO – 
PRE-FACE - Signs/Symptoms and APPENDIX 3:  PRO – PRE-FACE - Impacts). Patient 
will also complete the PGI-S questionnaire (see APPENDIX 4:  PRO – PGI-S). 
PRE-FACE and PGI-S questionnaires are to be completed prior to 
Investigator’s assessment of signs of acne as described in section 12.20. In case 
Screening Visit and Baseline are on the same day, the PRO questionnaires 
should be completed prior to screening procedures. 
• Ask the Patient to complete the QoL Questionnaire (see APPENDIX 9: ACNE-
SPECIFIC Qol QUESTIONNAIRE) only if the Screening and Baseline visits are 
expected to occur on the same day (no washout is required), in which case the 
QOL should be completed prior to Investigator’s assessment of signs of acne as 
described in section 12.18  other screening procedures. 
• Perform IGA to determine eligibility (See section 12.18) 
• Perform facial inflammatory and non-inflammatory lesion counts to determine 
eligibility (Section 12.19).  
• Determine if Patient requires washout and schedule Baseline Visit. 
12.12 
Baseline Visit (Visit 2, Day 1) 
The following procedures will be conducted at this visit: 
• Confirm the Patient meets the inclusion/exclusion criteria.  
• Assess eligibility. 
• Update since Screening Visit the medical history for the Patient. 
• Perform brief physical examination and vital signs measurement as described 
in section 12.7and 12.812.8. 
• Perform a Urine Pregnancy Test for all females of child-bearing potential and 
premenarchal (see section 12.912.9); the results must be negative for the Patient 
to be enrolled. 
• Update since Screening the Patient’s concomitant medications and/or therapies 
on Concomitant Medications form as outlined in section 11.4. 
• Ask the Patient to complete PRE-FACE questionnaires (see APPENDIX 2:  PRO – 
PRE-FACE - Signs/Symptoms and APPENDIX 3:  PRO – PRE-FACE - Impacts). Patient 


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will also complete the PGI-S questionnaire (see APPENDIX 4:  PRO – PGI-S). 
PRE-FACE and PGI-S questionnaires are to be completed prior to 
Investigator’s assessment of signs of acne as described in section 12.20. 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 Acne-QoL questionnaire (see APPENDIX 9: ACNE-
SPECIFIC Qol QUESTIONNAIRE).  
• Perform the efficacy evaluations including the Investigator’s Global 
Assessment, inflammatory and non-inflammatory lesion counts described in 
sections 12.18 & 12.19. Every effort shall be made to have the same Investigator 
perform the Baseline and Visit 6/Week 12/ End of Study or Early Termination 
evaluations for the same Patient. 
• Perform Cutaneous Reaction Assessment and Local Tolerability Assessment as 
described in section 14.1 & 14.2. 
• Take standardized photography of the face (at selected sites, see separate 
photographic manual for instructions) as described in section 13. 
• Instruct the Patient on the study product application as described in section 16.5.  
• Dispense the Patient Instruction Sheet and Diary Card to the Patient (see 
APPENDIX 1: PATIENT INSTRUCTIONS SHEET). 
• Record any AEs. 
• Instruct the Patient that throughout the study overexposure of the face to 
sunlight should be avoided. Instruct the Patient to use the sponsor-provided or 
study-approved cleanser and moisturizer/sunscreen; any exposure to tanning 
beds must be avoided during the study. 
• Perform randomization via IWRS after inclusion/exclusion criteria are 
confirmed as met. 
• Weigh and dispense study drug in a cool pack bag if needed. 
• Instruct the Patient on the study product application as described in APPENDIX 
1: PATIENT INSTRUCTIONS SHEET.  Pump usage will be demonstrated by the site 
personnel at the clinic, using a demonstration (dummy) pump, to help assure the 
Patient understands the procedure. 
• Dispensing Cleanser and Moisturizer with Sunscreen 
• Remind Patient to not wear make-up to all subsequent visits. 
• Schedule the next study visit. 
12.13 
On-treatment (Visit 3) – Week 2, Day 15 (± 3 days) 
The following procedures will be conducted at this visit: 
• Ask the Patient to complete the following questionnaires: PRE-FACE (see 
APPENDIX 2:  PRO – PRE-FACE - Signs/Symptoms and APPENDIX 3:  PRO – PRE-
FACE - Impacts), PGI-S (see APPENDIX 4:  PRO – PGI-S), PGI-C (see APPENDIX 5:  
PRO – PGI-C), PGI-TS (see APPENDIX 6:  PRO – PGI-TS) and PGI-SE (see 
APPENDIX 7:  PRO – PGI-SE). All of the questionnaires should be completed 
prior to Investigator’s assessment of signs of acne as described in section 
12.20. 
• Observe and query the Patient in a non-directive fashion about any AEs since 
the previous study visit.  
• Query the Patient about any changes in concomitant therapies and medication 
since the previous study visit. 


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• Perform a Urine Pregnancy Test for all females of child-bearing potential and 
premenarchal (see section 12.9). 
• Perform the efficacy evaluations including the Investigator’s Global 
Assessment, inflammatory and non-inflammatory lesion counts described in 
sections 12.18 - 12.19. 
• Perform Cutaneous Reaction Assessment and Local Tolerability Assessment as 
described in section 14.1 & 14.2. 
• Take standardized photography of face (at selected sites, see separate 
photographic manual for instructions) as described in section 13. 
• Review the Patient’s compliance with the study requirements (review Patient 
diary). The Patient Diary Card will Not be collected at this visit.  
• 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. 
12.14 On-treatment Visits (Visits 4 and 5) – Weeks 4 and 8, 
Days 29 and Day 57 (± 3 days) 
The following procedures will be conducted at these visits: 
• Ask the Patient to complete the following questionnaires: PRE-FACE (see 
APPENDIX 2:  PRO – PRE-FACE - Signs/Symptoms and APPENDIX 3:  PRO – PRE-
FACE - Impacts), PGI-S (see APPENDIX 4:  PRO – PGI-S), PGI-C (see APPENDIX 5:  
PRO – PGI-C), PGI-TS (see APPENDIX 6:  PRO – PGI-TS) and PGI-SE (see 
APPENDIX 7:  PRO – PGI-SE). All the questionnaires should be completed prior 
to Investigator’s assessment of acne as described in section 12.20. 
• Observe and query the Patient in a non-directive fashion about any AEs since 
the previous study visit.  
• Query the Patient about any changes in concomitant therapies and medication 
since the previous study visit. 
• Perform a Urine Pregnancy Test for all females of child-bearing potential and 
premenarchal (see section 12.9). 
• Perform efficacy evaluations: IGA, inflammatory and non-inflammatory lesion 
counts described in sections 12.18 & 12.19.  
• Perform Cutaneous Reaction Assessment and Local Tolerability Assessment as 
described in section 14.1 - 14.2. 
• Take standardized photography of face (at selected sites, see separate 
photographic manual for instructions) as described in section 13. 
• 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. 


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12.15 
End of Study (Visit 6) – Week 12, Day 85 (± 4 days) or 
Early Termination 
The following procedures will be conducted at this visit: 
• Ask the Patient to complete the following questionnaires: PRE-FACE (see 
APPENDIX 2:  PRO – PRE-FACE - Signs/Symptoms and APPENDIX 3:  PRO – PRE-FACE 
- Impacts), PGI-S (see APPENDIX 4:  PRO – PGI-S), PGI-C (see APPENDIX 5:  PRO – 
PGI-C), PGI-TS (see APPENDIX 6:  PRO – PGI-TS) and PGI-SE (see APPENDIX 7:  
PRO – PGI-SE). All the questionnaires should be completed prior to Investigator’s 
assessment of signs of acne, as described in section 12.18. 
• Ask the Patient to complete Acne-QoL questionnaire (see APPENDIX 9: ACNE-
SPECIFIC Qol QUESTIONNAIRE) 
• Observe and query the Patient in a non-directive fashion about any AEs since 
the previous study visit.  
• Query the Patient about any changes in concomitant therapies and medication 
since the previous study visit. 
• Perform physical examination as described in section 12.7. 
• Assess vital signs as described in section 12.8. 
• Perform efficacy evaluations: IGA, inflammatory and non-inflammatory lesion 
counts described in sections 12.18 - 12.19. 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 Reaction Assessment and Local Tolerability Assessment as 
described in section 14.1- 14.2. 
• Take standardized photography of face (at selected sites, see separate 
photographic manual for instructions) as described in section 13. 
• 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 child-bearing potential and 
premenarchal (see section 12.9). 
• Collect and weigh the study product. 
 
12.16 
Unscheduled Visit 
An unscheduled visit may occur at any time during the study at the Patient’s request or 
as deemed necessary by the Investigator for any reason. For example: dispensing new 
pump/kit or in order to report any discomfort following the usage of the study drug.  At 
a minimum, concomitant medications, AEs and the date and reason for the unscheduled 
visit will be recorded. Other procedures to be performed during an unscheduled visit, 
will be according to the discretion of the Investigator. 
 
12.17 
Clinical Outcome Assessments  
Consistent with recommendations from the FDA “Guidance for Industry, Acne 
Vulgaris: Establishing Effectiveness of Drugs Intended for Treatment Guidance for 


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Industry.” (May2018), the determination of efficacy will be based on evaluations of the 
IGA and inflammatory and non-inflammatory absolute lesion counts, on the face at 
Week 12/ End of Study or Early Termination. Additionally, Patient reports of 
symptoms and disease impacts will be collected as secondary efficacy assessments.  
The Cutaneous Safety Assessment or Erythema and Scaling, evaluated by the 
Investigators, provides a reliable assessment of local effects, while the local tolerance 
measures of itching, burning and stinging sensation are designed to provide Patient-
reported outcomes that will support recommendations for use and expected reactions. 
The additional safety measures, including AEs reporting, Urine Pregnancy Tests for 
females, and Concomitant Medications are standard, accepted measures in clinical 
research. 
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 Acne Vulgaris. 
For consistency of evaluations, the same designated evaluator who performs the 
Baseline assessments shall perform the assessments at Week 12/ End of Study or Early 
Termination. When this becomes impossible, another delegated evaluator may perform 
the assessments. 
12.18 
Investigator Global Assessment (IGA) 
The Investigator Global Assessment (IGA) will be performed at visits: Screening, 
Baseline, Weeks 2, 4, 8 and 12/ End of Study or Early Termination. 
Patients are eligible for enrollment if they have facial acne with a global severity grade 
of a 3 (moderate) or a 4 (severe) on the IGA scale at Baseline.  
The IGA scale provided in the following Table will be used to describe the global 
severity grade and subsequent score: 
Table 2: Investigator Global Assessment (IGA) Scale 
Grade 
Description 
0 – Clear 
Normal, clear skin with no evidence of acne vulgaris 
1 – Almost 
Clear 
Rare non-inflammatory lesions present, with rare non-inflamed papules 
(papules must be resolving and may be hyperpigmented, though not pink-
red) 
2 – Mild 
Some non-inflammatory lesions are present, with few inflammatory 
lesions (papules/pustules only; no nodulo-cystic lesions) 
3 – Moderate 
Multiple Non-inflammatory lesions and, inflammatory 
lesions are evident: several to many comedones and papules/pustules, and 
there may or may not be one small nodulo-cystic lesion 
4 – Severe 
Inflammatory lesions are more apparent, many comedones and 
papules/pustules, there may or may not be a few nodulo-cystic lesions 


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12.19 
Inflammatory and Non-Inflammatory Lesion Counts 
Lesions count will be performed at visits: Screening, Baseline, Weeks 2, 4, 8 and 12/ 
End of Study or Early Termination.   
At Screening/Baseline, Patients must have at least 20 and no more than 100 
inflammatory lesions (papules, pustules) and at least 30 and no more than 150 non-
inflammatory (open and closed comedones) lesions on the face, including the nose. 
Patients must have two (2) or fewer cysts or nodules. 
12.19.1 
 Inflammatory Lesion Definitions: 
Papule – A small, solid elevation less than 5 mm in diameter.  Most of the lesion is 
above the surface of the skin. 
Pustule – A small circumscribed elevation less than 5 mm in diameter that contains 
yellow-white exudate. 
Nodule - An inflammatory lesion greater than or equal to 5 mm in diameter. 
Cyst – An inflammatory lesion that contains yellow-white exudate that is greater than 
or equal to 5mm in diameter. 
12.19.2 
 Non-Inflammatory Lesion Definitions: 
Open Comedone - (Black head) A lesion in which the follicle opening is widely 
dilated with the contents protruding out onto the surface of the skin, with 
compacted melanin cells giving the plug a black appearance. 
Closed Comedone - (White head) A lesion in which the follicle opening is closed, but 
the sebaceous gland is enlarged by the pressure of the sebum buildup, which in 
turn cause the skin around the follicle to thin and become elevated with a white 
appearance. 
12.20 
Patient-Reported Outcomes (PRO) 
There are five PRO questionnaires to be administered in the study and each is 
summarized below. Each will be administered to all Patients, from the age of 9 years 
old, during the designated study visits with instructions 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 item(s); the Study Staff will ask the 
Patient to complete the form. The PRO questionnaire data will be entered into the 
eCRF, and a copy will be placed with the Patient source at the site according to the 
ICH-GCP guideline. 
 
The Patient-Reported Evaluation of Facial Acne (PRE-FACE): The PRE-FACE, 
which can be completed in less than 2 minutes, is a seven item PRO questionnaire that 
assesses acne vulgaris-related signs, symptoms and impacts.  The four-item acne sign 
and symptom domain (ASD) assesses the severity of acne vulgaris-related pimples, 
whiteheads, blackheads, and redness, at their worst, in the 24 hours prior to 


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administration on an 11-point numeric rating scale (NRS) ranging from 0 (“no 
[Concept] at all”) to 10 (“[Concept] as bad as you can imagine”).  The three-item acne 
impact domain (AID) assesses acne vulgaris-related embarrassment, self-
consciousness, and sadness in the seven days prior to administration on an 11-point 
NRS ranging from 0 (“not [Concept] at all) to 10 (“extremely [Concept]”). The PRE-
FACE will be administered at study visits 2-6, including Screening, Baseline, and at 
Weeks 2, 4, 8, and 12/ End of Study or Early Termination.   
 
Patient Global Impression of symptom Severity (PGI-S): The PGI-S (presented in 
appendix 4) is a single-item global self-assessment of the current severity of Patients’ 
acne vulgaris symptoms rated on a five-point verbal response scale ranging from 0 
(None: No pimples, clear skin) to 4 (Very severe: Large amount of pimples, no clear 
skin), where higher scores indicate greater severity of acne vulgaris symptoms.  The 
PGI-S will be administered at study visits 2-6, including Screening, Baseline, and at 
Weeks 2, 4, 8, and 12/ End of Study or Early Termination.  While PGI-S results can 
inform treatment efficacy, a main use for the tool in this study is to support 
supplementary anchor-based analysis.  Anchor-based analysis use an external criterion 
(in this case, the PGI-S) to categorize Patients into groups each reflecting an a priori 
determined change grouping (e.g., no change, large positive change, or large negative 
change) to inform conclusions about the meaning of observed within person change on 
other measures.      
 
Patient Global Impression of Change (PGI-C): The PGI-C is a single item 
questionnaire that asks respondents to describe the change they have noticed in their 
acne symptoms since the start of the study on 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 Week 2, Week 4, Week 
8 and Week 12/ End of Study or Early Termination.  Similar to the PGI-S described 
above, the PGI-C data collected in this study to support supplementary anchor-based 
analysis.  
Patient Global Impression of Treatment Satisfaction (PGI-TS): The PGI-TS is a 
single item questionnaire that asks respondents to describe how satisfied they are 
“right now” with the acne 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 Week 2, Week 4, Week 8 and Week 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. 
 
Patient Global Impression of treatment Side Effects (PGI-SE): The PGI-SE is a 
single item questionnaire that asks respondents to describe how bothered they are 
“right now” with the acne treatment administered as part of the study on a 5-point 
VRS ranging from “I am not bothered” to “I am very bothered”.  The questionnaire 
can be completed in less than 30 seconds and is administered via pen-and-paper at the 
site visits at Week 2, Week 4, Week 8 and Week 12/ End of Study or Early 


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Termination. Though data generated from the PGI-SE 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. 
 
12.21 
Acne-Specific Quality of Life Questionnaire (Acne-QoL) 
The Acne-specific Quality of Life questionnaire (Acne-QoL) is a health-related quality 
of life instrument developed by MERCK & CO., INC. for use in clinical trials to assess 
the impact of therapy on quality of life among patients with facial acne. 
The Acne-QoL questionnaire consists of 19 questions. Each will be administered to all 
Patients, aged 9 and older, during the designated study visits. Study Staff will instruct 
the patients to complete the questionnaire:  
• 
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.  
The Acne-QoL is self-administrated (i.e. the patient is able to complete the 
questionnaire without assistance) and should take approximately 10 minutes or less to 
complete. The questionnaire is administered via pen-and-paper (using a black ballpoint 
pen) during the site visits at Baseline visit and Week 12/ End of Study or Early 
Termination.  
In the event the Patient skips any questionnaire item(s); the Study Staff will ask the 
Patient to complete all of the questions. The Acne-QoL questionnaire data will be 
entered into the eCRF, and a copy will be placed with the remaining Patient’s source 
documents at the site according to the ICH-GCP guideline. 
The questions in the Acne-QoL questionnaire are organized in four domains which 
address the impact of facial acne on health-related quality of life (HRQoL): Self 
Perception, Role-Social, Role-Emotional and Acne Symptoms. The items included 
within each domain are those which facial acne sufferers consider important, which can 
distinguish between acne severity groups and were responsive to changes in acne 
severity over time following treatment in an uncontrolled study. For all domain scores, 
the responses to items comprising the domain are summed, and no weighting scheme 
is used. 
Self-Perception: The Self Perceptions domain of the Acne-QoL is comprised of 5 
questions. In each question, the respondent is asked for the extent to which their facial 
acne has affected a particular area of their self-perception over the past week. Items 
such as feeling self-conscious, feeling unattractive, dissatisfaction with self-appearance 
are included in the domain. The response options are on a 0-6 scale (extremely, very 
much, quite a bit, a good bit, somewhat, a little bit, not at all). The range of possible 
scores is 0 to 30. 
Role-social: The Role-social domain of the Acne-QoL is comprised of 4 questions 
which attempt to assess the impact of facial acne on a respondent’s intersocial 
relationships. For example, questions related to going out in public, meeting new 


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people, and socializing are included. The response options are on 0-6 scale (extremely, 
very much, quite a bit, a good bit, somewhat, a little bit, not at all). The range of possible 
scores is 0 to 24. 
Role-emotional: The Role-emotional domain is focused on the emotional effect or 
impact of facial acne. The domain includes questions about the respondent’s annoyance 
at having to spend time cleaning and treating their face, their worry or concern that 
medications were working fast enough, the bothersomeness of needing to always have 
cover-up available, etc. The response options are on a 0-6 scale exactly as the same as 
that for the Self-Perceptions and Role-Social domains, ranging from “extremely” to 
“not at all”. The range of possible scores is 0-30. 
Acne Symptoms: The final domain of the Acne-QoL is aimed at assessing the physical 
symptoms experienced by facial acne sufferers, which acne patients rated as frequent 
and important. The response options for this domain are on a 0-6 scale (extensive, a 
whole lot, a lot, a moderate amount, some, very few, none) and differs from the above 
domains for several of the questions. Five questions comprise the Acne Symptoms 
domain covering symptoms such as the number of bumps on the face, the extent of 
scabbing from the acne, and the level of worry associated with scarring from the acne. 
Possible domain scores range from 0 to 30. 
Within each domain, a minimum number of responses is required in order to score the 
domain. Overall domain scores will be calculated so long as at least 3 items are 
answered for each domain. If the minimum number of items have been answered but 
1-2 questions have missing responses the mean value of the answered questions will be 
used to replace the missing values.  If fewer than the minimum number of items have 
been answered, the domain score will not be calculated.  Further details on calculation 
of the domain scores will be detailed in the Statistical Analysis Plan (SAP). 
13 PHOTOGRAPHY 
Standardized photography of facial acne at Baseline, and at the Weeks 2, 4, 8 and 
12/End of Treatment Visit 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. 
14 SAFETY EVALUATIONS 
Safety will be assessed by monitoring incidence of Cutaneous Reactions Assessments, 
Local Tolerability Assessments, and AEs reporting; at Baseline, at all treatment visits 
and end-of-treatment visit. 
14.1 Cutaneous Reactions Assessments 
The evaluator will assess local application site cutaneous reactions by rating the 
erythema, dryness, pigmentation and scaling at each study visits except Screening visit. 
The evaluator will determine the score for each of these variables by direct evaluation. 
The following definitions of terms will be applied to these evaluations. 
Cutaneous Signs Evaluation will include assessments of erythema, scaling, dryness 
and pigmentation based on the following 4-point scale shown in table 3 below. 


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Table 3: Assessments of erythema, scaling, dryness and pigmentation 
Erythema 
Score 
Rating 
Definition 
0 
None 
No erythema 
1 
Mild 
Slight pinkness present 
2 
Moderate 
Definite redness, easily recognized 
3 
Severe 
Intense redness 
 
Scaling 
0 
None 
No scaling 
1 
Mild 
Barely perceptible shedding, noticeable only on light 
scratching or rubbing 
2 
Moderate 
Obvious but not profuse shedding 
3 
Severe 
Heavy scale production 
 
 
 
 
Pigmentation 
0 
None 
No disturbance of pigmentation 
1 
Mild 
Barely perceptible pigment change 
2 
Moderate 
Markedly darker or lighter 
3 
Severe 
Complete de-pigmentation or severe hyperpigmentation 
 
 
 
 
Dryness 
0 
None 
No dryness 
1 
Mild 
Slight but define roughness 
2 
Moderate 
Moderate roughness 
3 
Severe 
Marked roughness 
Application site reactions (erythema, scaling, dryness and pigmentation) are not to be 
recorded as AEs 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. 
14.2 Local Tolerability Assessments 
The evaluator will assess local application site tolerability by rating the itching, burning 
and stinging at each study visits except Screening visit. 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 following definitions of terms will be applied to these 
evaluations:  
Local Tolerability Assessment: The evaluations of itching, burning and stinging will be 
made by the Investigator at the time of the visit. 
Table 4: Assessments of Itching, Burning and Stinging 
Itching 
Score 
Rating 
Definition 
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 
0 
None 
No burning 
1 
Mild 
Slight burning sensation; not really bothersome 
2 
Moderate 
Definite warm, burning sensation that is 
somewhat bothersome 
3 
Severe 
Hot burning sensation that causes definite 


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discomfort and may interrupt daily activities or 
sleep 
 
 
 
 
Stinging 
0 
None 
No stinging 
1 
Mild 
Slight stinging sensation; not really bothersome 
2 
Moderate 
Definite stinging sensation that is somewhat 
bothersome 
3 
Severe 
Severe stinging sensation that causes definite 
discomfort and may interrupt daily activities or 
sleep 
Application site reactions (itching, burning and stinging) are not to be recorded as AEs 
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 AEs in the 
source document and eCRFs. 
15 ADVERSE EVENTS 
When an AE occurs requiring an early termination from the study for a Patient, the 
Investigator or medical professional 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. 
15.1  Definitions 
An 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 AE 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 SAE is an AE 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 AEs 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 AEs (IRAE) is any SAE or any AE that necessitates 
discontinuation of study product, including pregnancy. 
Unexpected AE 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 


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product, the Investigator’s Brochure, or as described in the clinical protocol and consent 
materials.  
 
 
Intensity  
Intensity of AEs is 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. 
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: 
• Does not follow a reasonable temporal sequence from the time of study drug 
administration; and 
• Was likely produced by other factors such as the subject’s clinical state, 
therapeutic intervention, or concomitant therapy but for which relationship 
cannot be definitely ruled out. 
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. 


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Action Taken with Study Treatment 
 
The Investigator will describe the action taken with the study treatment in the 
appropriate section of the eCRF, as follows: 
• Dose Increased 
• Dose Not Changed 
• Dose Reduced 
• Drug Interrupted 
• Drug Withdrawn 
• Not Applicable 
• Unknown 
Action Taken to Treat Event 
 
The Investigator will describe other action(s) taken in the appropriate section of the 
eCRF, as follows: 
• None 
• Concomitant Medication 
• Procedure/Therapy 
• Hospitalization/Prolonged Hospitalization 
• Withdrawal from Study 
• Other 
 
15.2  Eliciting and Reporting of Adverse Events 
The Investigator will periodically assess Patients for the occurrence of AEs. In order to 
avoid bias in eliciting AE, 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 AEs (as 
defined in Section 18.6), 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 AE, 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 AEs must be reported to the CRO within 24 hours of 
when the Investigator first learns of the occurrence of the event.  
AEs will be documented in the source document and recorded in a timely manner on 
eCRFs. AEs 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.  
AEs reporting begins from the signing of informed consent/assent. Study product-
related AEs should be followed until resolved or 30 days after the final study treatment. 
Regardless the duration of the study, all patients that exhibit 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. 
The following data should be documented for each AE: 
• Description of the symptom event 


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• Classification of “serious” or “not serious” 
• Severity 
• Date of first occurrence and date of resolution (if applicable) 
• Action(s) taken 
• Causal relationship 
• Outcome of event (Recovered/Resolved, Recovered/Resolved with Sequelae, 
Not Recovered/Not Resolved, Unknown, Fatal [with date and cause reported]) 
15.3 Expedited Reporting Responsibilities of the Study Center 
For any SAE, 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 SAEs are described below. Adequate information must be collected 
with supporting documentation to complete a standard report for submission to Sol-
Gel. The AE 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 study product-related AE(s) or SAE(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 AE. The Investigator should continue to report any significant 
follow-up information to the sponsor up to the point that the event has resolved. Any 
SAE 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 SAE, the Investigator (or the Study Coordinator) will promptly report 
any SAE 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. 
15.4 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. 
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 


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authorities. All Investigators participating in ongoing clinical studies will receive 
copies of the SAE reports submitted on an expedited basis to regulatory authorities  
15.5 SAE & AEs Requiring Discontinuation of Study Drug, 
including Pregnancies 
Any SAE, should be collected following signing the ICF including any protocol 
required run-in period, 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 should be reported to 
the Sponsor or its designee immediately and within 1 working day. 
Patients who discontinue study product due to experiencing Study product-related AEs 
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. 
 
15.6 Pregnancy 
At the time, Investigator or site personnel becomes aware that a study Patient became 
pregnant following study participation, the 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) 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 no more than 30 days within 
completion of the pregnancy. 
Upon delivery, miscarriage or abortion, the 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 study identifier(s); 
• Gestational age at delivery, miscarriage or abortion; 


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• 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. 
15.7  Post Study Adverse Events 
15.7.1 Non-serious Adverse Events 
AEs 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. 
15.7.2 Serious Adverse Events 
SAEs 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 SAEs, or any 
new SAEs 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 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 SAE 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 and captured in the eCRF. 
16 STUDY PRODUCTS / CLINICAL SUPPLIES 
16.1 Method of Treatment Assignment 
Patients who satisfy all of 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 3%/Encapsulated All-Trans-Retinoic 
Acids 0.1% Cream or Vehicle Cream, once daily on a 2:1 basis for twelve (12) weeks. 


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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). 
16.2 Formulations 
Study Product name: Encapsulated Benzoyl Peroxide (E-BPO) and Encapsulated 
Tretinoin (E-ATRA) Cream, 3%/0.1% (E-BPO/E-ATRA 
3%/0.1%) Encapsulated  
Sponsor name: 
S6G5T-3 
 
Active ingredients: 
Benzoyl peroxide & all trans retinoic acid 
Inactive ingredients:   See list below 
Placebo Product: 
Vehicle Cream (for study product) 
Sponsor name: 
S6G5T-8 
Active ingredients: 
None 
Inactive ingredients: See list below 
The inactive ingredients include: Polyquarternium-7, Hydrochloric Acid, (S)-Lactic 
Acid, silicon Dioxide, Sodium Hydroxide, Cetrimonium Chloride, Squalane, Butylated 
Hydroxytoluene, Beeswax, Macrogol Stearate Type I, Cetyl Alcohol, Cyclomethicone 
5, Mono– and di– Glycerides, Anhydrous Citric Acid, Edetate Disodium, Glycerin, 
Imidurea, Carbomer 980, Methylparaben (only in vehicle), Tartrazine (only in vehicle) 
& Purified Water. 
16.3 Study Products Packaging and Labeling 
The study product (Encapsulated Benzoyl Peroxide 3%/Encapsulated All-Trans-
Retinoic Acids 0.1% Cream), S6G5T-3, and placebo for the study product (vehicle 
cream), S6G5T-8, will be packaged and labeled in 52 gr. pump. During the 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 under refrigerating conditions in the rage of 
2-8°C (36-46°F) in blocks of three (3) products to keep ratio 2:1 between study product 
and vehicle. The study products will be labelled as follows: 
• Protocol number 
• Patient number  
• Patient initials 
• Dispenser initials 
• Dispense date 


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• Contains: Study Product (Encapsulated Benzoyl Peroxide 3%/Encapsulated 
All-Trans-Retinoic Acid 0.1% Cream or its Vehicle Cream  (  
• Directions for use: Apply as directed, for topical use only 
• Patient: store at room temperature at or below 25°C (77°F). Do not freeze. 
• Keep container tightly closed 
• Keep out of reach of children 
• Sponsor information 
• Investigational drug warning. “Caution: New Drug - Limited by Federal Law to 
Investigational Use 
Each Study Product Kit Box label, will contain four (4) 52 gr. each, pumps that will 
carry a one-part tear-off label that must remain attached to the box. Both label parts will 
show an identical information label and have spaces to enter the Patient’s initials, date 
dispensed, dispenser’s initials and each label shows: 
• Protocol number 
• Patient number  
• Patient initials  
• Dispenser initials 
• Dispense date 
• Contains: 4 pumps, 52 gr. each, of Study Product (Encapsulated Benzoyl 
Peroxide 3%/Encapsulated All-Trans-Retinoic Acids 0.1% Cream or its Vehicle 
Cream) 
• Directions for use: Apply as directed, for topical use only  
• Pharmacist of site staff: Prior to dispensing: Store in a refrigerator 2°C to 8°C 
(36°F to 46°F). Excursions permitted down to 0°C (32°F) and up to 25°C 
(77°F). Do not freeze. 
• Keep out of reach of children 
• Investigational drug warning. “Caution: New Drug - Limited by Federal Law to 
Investigational Use only”  
• Sponsor information 
 
16.4 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 assigned by IWRS at Baseline. IP will be dispensed at Baseline, 
Week 4 and Week 8 from the assigned kit. IP will be returned at Week 4, Week 8 and 
Week 12/ End of Study or Early Termination. IP weight will be documented in eCRF 
prior to dispensing and after return of each pump per flow chart (section 12.10). 
Each Patient will be instructed on the importance of returning his or her study product 
at every designated visit (excluding on Visit3/ Week 2). 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. 


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Study product should be stored refrigerated (2°C to 8°C, 36°F to 46°F) at the site, 
excursions permitted down to 0°C (32°F) and up to 25°C (77°F) until it is dispensed to 
the Patient. After dispensing to the Patient, the pump should be stored at room 
temperature at or below 25°C (77°F) with. Do not freeze the product. 
16.5 Dosing Instructions 
Topical application of study product will be made to the face once daily, at home and 
prior to bedtime, after cleansing, for a period of twelve (12) weeks. Study product will 
be applied as a thin coating that is gently rubbed into 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 cleanse their face with the given cleanser or Sponsor’s approved cleanser 
using only the hands and pat dry with a soft clean towel. After the face has dried 
completely, the Patient shall apply one "pea sized" amount on each area of the face 
(chin, left cheek, right cheek, nose and forehead). The Patient will need to spread the 
investigational product smoothly and evenly.  The investigational product will not be 
used on the mouth, eyes, inside the nose and lips or any body part other than the face. 
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.  
No time interval between dosing and meals or any other activity is specified. During 
the trial, Investigators should remind Patients to avoid exposure to sunlight and 
sunlamps and to wear sunscreen when sun exposure cannot be avoided. 
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 bottle. 
If necessary and in the case where a sunscreen with a higher SPF is required, Patient 
can be instructed to use another moisturizer with sunscreen that includes a higher SPF 
(Sun Protection Factor). Such case will require Sponsor approval. 
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. 
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 every visit, 
excluding to Visit3/ Week 2. 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 like clothing and bed sheets. 
16.6 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 


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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, pump only- without the cover (~ 80g) before dispensing 
and upon return and weights will be recorded on the appropriate source document and 
eCRF.  
16.7 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. 
16.8 Additional Supplies Provided by Sponsor 
• Regulatory study file system (Investigator Binder) 
• Urine pregnancy test kits  
• Cleanser 
• Moisturizer/sunscreen 
17 STATISTICAL CONSIDERATIONS 
17.1 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.  
The primary method of handling missing efficacy data will be based on estimation using 
the method of Markov Chain Monte Carlo (MCMC) imputation. 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. 
Sensitivity analyses for the primary efficacy endpoints will use 3 methods. For the 
lesion count endpoint, the first method will use a repeated measures ANCOVA, with 
treatment, analysis center, and visit (i.e., Week 2, Week 4 and Week 8) as independent 
factors and a covariate of baseline. In this analysis, data from all post-baseline visits 
will be included with no imputation for missing data. 
The second sensitivity analyses will use the model based multiple imputation method 
to impute missing data for the absolute change at Week 12.  
The third sensitivity analysis will involve a tipping point analysis. 


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Similar methods for the dichotomized IGA will involve a repeated measures logistic 
regression model and a model based multiple imputation and tipping point analysis. 
A SAP, describing all statistical analyses will be provided as a separate document. The 
SAP will be finalized prior to unblinding of the study treatments. 
17.1.1 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. 
17.1.2 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 17.4.5 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. 
17.1.3 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. 
17.1.4 Analysis Populations 
Approximately 420 male and female Patients at least 9 years of age with moderate or 
severe acne vulgaris 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: 
• 280 Patients will be randomized to receive S6G5T-3, Encapsulated Benzoyl 
Peroxide 3%/Encapsulated All-Trans-Retinoic Acid 0.1% Cream 
• 
140 Patients will be randomized to receive S6G5T-8, 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. 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; 


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• Have not been compliant with the dosing regimen (i.e., Patients may not miss 
more than five consecutive days of dosing and must take 80-120% 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 AE related to study treatment or 
documented lack of treatment effect will be included in the PP population. Data for 
these Patients 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.  
17.2 Study product Evaluations and Analyses 
Inflammatory and non-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. 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.  
Patients will be asked to complete PRO questionnaires at appropriate time points.  
All statistical analysis will be conducted for both PP and ITT population. 
17.3 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. 
17.3.1 Primary Efficacy 
There are two co-primary efficacy endpoints: 
• Proportion of Patients with an assessment of clear or almost clear and with at 
least a 2-grade improvement in IGA from baseline at Week 12. 
• Absolute change from Baseline in lesion count on the face at Week 12 
(separately for inflammatory and non-inflammatory lesions). 
17.3.2 Secondary Efficacy 
The secondary efficacy endpoints will be the following: 
• Percent change from Baseline, in non-inflammatory lesion count at Week 12. 
• Percent change from Baseline, in inflammatory lesion count at Week 12. 
• Proportion of patients in the E-BPO/E-ATRA cream arm compared to vehicle 
control achieving at least a 4-point reduction on Item 1 (pimples) of the PRE-FACE 
from Baseline to Week 12. 


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• Proportion of patients in the E-BPO/E-ATRA Cream arm compared to vehicle 
control achieving at least a 4-point reduction on Item 5 (embarrassment) of the 
PRE-FACE from Baseline to Week 12. 
• Absolute change from Baseline, in non-inflammatory lesion count at Week 8. 
• Absolute change from Baseline, in inflammatory lesion count at Week 8. 
• Absolute change from Baseline, in non-inflammatory lesion count at Week 4. 
• Absolute change from Baseline, in inflammatory lesion count at Week 4. 
 
17.3.3 Supportive Efficacy 
 Supportive efficacy endpoints include the following: 
• Proportion of Patients with an assessment of clear or almost clear and with at 
least a 2-grade improvement in IGA at Weeks 2, 4 and 8. 
• Absolute change from Baseline in inflammatory and non-inflammatory lesion 
counts from Baseline to weeks 2, 4 and 8. 
• PRE-FACE ASD:  Mean absolute change in PRE-FACE ASD scores from 
Baseline to Weeks 2, 4, and 8. 
• PRE-FACE AID: Mean absolute change in PRE-FACE AID scores from 
Baseline to Weeks 2, 4, and 8. 
• Proportion of Patients in treatment relative to control who report at least 
“minimally improved” as measured by the PGI-C at Week 12. 
• Patient Global Impress of Symptom Severity (PGI-S) at Week 12. 
• Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 12. 
17.3.4 Exploratory Endpoint 
The mean change in Acne-QoL domain scores from Baseline to Week 12. 
17.4 Statistical Hypothesis Testing  
17.4.1 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 18.4.6. 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 (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 


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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. 
17.4.2 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. 
17.4.3 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 of percent change in lesions will follow 
the methods for the primary lesion count analyses.  Methods corresponding to the 
analysis of IGA will be used to compare the proportion of patients in the E-BPO/E-
ATRA Cream arm versus vehicle control achieving at least a 4-point reduction in 
pimples or in embarrassment scores from Baseline to Week 12. 
The overall Type I error will be controlled by requiring the three 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. 
Evaluation of the secondary efficacy variables will use a gated sequential procedure 
starting with the comparisons of the first step and proceeding onto the next step and etc. 
This 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: 
Step 
Number Secondary Endpoint 
1 
Percent change from Baseline, in non-inflammatory lesion count at Week 12. 
2 
Percent change from Baseline, in inflammatory lesion count at Week 12. 
3 
Proportion of patients in the E-BPO/E-ATRA cream arm compared to vehicle 
control achieving at least a 4-point reduction on Item 1 (pimples) of the PRE-
FACE from Baseline to Week 12. 
4 
Proportion of patients in the E-BPO/E-ATRA Cream arm compared to 
vehicle control achieving at least a 4-point reduction on Item 5 
(embarrassment) of the PRE-FACE from Baseline to Week 12. 
5 
Absolute change from Baseline, in non-inflammatory lesion count at Week 8 
6 
Absolute change from Baseline, in inflammatory lesion count at Week 8. 
7 
Absolute change from Baseline, in non-inflammatory lesion count at Week 
4. 


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8 
Absolute change from Baseline, in inflammatory lesion count at Week 4. 
 
17.4.4 Supportive Efficacy Analyses  
Appropriate descriptive statistics will be computed for all Supportive Efficacy 
parameters. Additionally, all inferential testing will follow the methods for the co-
primary variables wherein the continuous variables will parallel the lesion count 
analyses and the discrete variables will follow the analysis of the IGA.  
17.4.5 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 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 and non-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 
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. 
If any of the analyses are not computationally feasible due to some investigational sites 
having very few Patients enrolled, the low-enrolling investigational sites will be 
excluded from the analysis. 
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 


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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. 
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. 
17.4.6 Missing Efficacy Data Imputations 
17.4.6.1 Lesion Count and PRE-FACE 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. Imputation will be 
conducted independently for each treatment group. 
Multiple imputation and subsequent analysis will involve 3 distinct phases with these 
principal tasks: 


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1. Create a dataset of Patients, one for each treatment group, with observed values 
and those needing estimation by MCMC. The missing lesion count values in 
each dataset will be filled in using the MCMC method 5 times to generate 5 
datasets. The resulting datasets for each treatment arm will be combined into 
one complete dataset 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 dataset, the variable of interest for baseline minus the Week 
12 value will be computed. Each complete dataset 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. 
The following 4 random seeds have been pre-specified by using a random number 
generator: 
• Inflammatory Lesion Counts; S6G5T-3: Seed = 813883085       
• Inflammatory Lesion Counts; S6G5T-8 Vehicle: Seed = 2010726808         
• Non-inflammatory Lesion Counts; S6G5T-3: Seed = 1326750493           
• Non-inflammatory Lesion Counts; S6G5T-8 Vehicle: Seed = 1498908882        
17.4.6.2 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 Week 12 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 Week 12 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 dataset, one for each treatment group, of Patients with observed values 
and those needing estimation by MCMC. The missing IGA values in each 
dataset will be filled in using the MCMC method 5 times to generate 5 datasets. 
The resulting datasets for each treatment arm will be combined into one 
complete dataset 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 dataset, the dichotomous success rate (clear or almost clear 
with a 2-point change from baseline) will be computed. The Week 12 estimated 
global values will be rounded to the nearest integer value prior to evaluating the 
success rate. Each complete dataset will be analyzed with a logistic regression 
with factors of treatment group and analysis center. 


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3. The results from these analyses will be combined into a single inference using 
SAS PROC MIANALYZE. 
The following 4 random seeds have been pre-specified by using a random number 
generator: 
• PRO Pimples Scores; S6G5T-3: Seed = 1597410322     
• PRO Pimples Scores; S6G5T-3 Vehicle: Seed = 466920922     
• PRO Embarrassment Scores; S6G5T-3: Seed = 288784276     
• PRO Embarrassment Scores; S6G5T-3 Vehicle: Seed = 1746263137     
17.4.7 Sensitivity Efficacy Analyses 
17.4.7.1 Sensitivity analyses for absolute change in lesion count 
The first sensitivity analyses for absolute change in lesion count (both inflammatory 
and non-inflammatory) will use a repeated measures ANCOVA, with treatment, 
analysis center, and visit (i.e., Week 2, Week 4 and Week 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 analyses 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 datasets. 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 dataset 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. 
The third sensitivity analysis will involve a tipping point analysis. Full details will be 
presented in the SAP. 
17.4.7.2 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., Week 2, Week 4 and Week 8) 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. 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 datasets. 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). 


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2. Each complete dataset 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. 
 
The third sensitivity analysis will involve a tipping point analysis. Full details will be 
presented in the SAP. 
17.4.8 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. An additional analysis will include age with categories of less 
than 18 and 18 to less than the median age and greater than or equal to the median age. 
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. 
17.5 Assessment of Safety 
Safety will be evaluated by tabulations of AEs, the Investigator Cutaneous Safety 
Assessment rating of pigmentation, erythema, dryness and scaling; and the Patient 
assessment of Local Tolerability rating itching, burning and stinging 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. 
17.6 Adverse Events 
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 (if applicable), 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 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. 
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. 
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 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. 


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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 study product relatedness. The AE onset 
will also be shown relative (in number of days) to the day of initial dose of the 
randomized study product. 
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. 
17.6.1 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. 
17.6.2 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. 
17.7 Sample Size Determination 
The following power calculations are based on the observed Week 12 results of the 
Phase 2 study, SGT-65-02. This study was a six-arm trial including S6G5T-3 and 
Vehicle Cream in the treatment of acne vulgaris. Estimates from the S6G5T-3 arm were 
used in the power assessments. The anticipated randomization ratio is 2:1 for S6G5T-
3 and S6G5T-8 Vehicle Cream, 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 274 in the S6G5T-3 and 137 in the Vehicle Cream group (total of 411) 
has 99% power to detect a statistically significant difference in inflammatory lesions.  
The estimated absolute change from baseline in treatment means were -16.7 and -12.2 
for S6G5T-3 and Vehicle Cream, respectively, with a common standard deviation of 
10.0.  
A sample size of 146 in the S6G5T-3 and 73 in the Vehicle Cream group (total of 219) 
has 99% power to detect a statistically significant difference in non-inflammatory 
lesions.  The estimated absolute change from baseline in treatment means were -23.7 
and -13.7 for S6G5T-3 and Vehicle Cream, respectively, with a common standard 
deviation of 19.0. 
A sample size of 231 in the S6G5T-3 and 116 in the Vehicle Cream has group (total of 
346) has 99% power to detect a statistically significant difference 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 33.3% and 12.6% for S6G5T-
3 and Vehicle Cream, respectively. 
Therefore, a total of 420 Patients has adequate power to demonstrate statistical 
significance of S6GT5-3 over S6GT5-8 Vehicle Cream for the lesion count endpoints 
as well as dichotomized IGA. 


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18 ADMINISTRATIVE CONSIDERATIONS 
18.1 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. 
18.2 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. 
18.3 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. 
18.4 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 Acknowledgment’ page from the Sponsor and 
IRB approved protocol. 
• Documentation of IRB approval of the protocol, ICF, any other written 
information provided to Patients and any recruitment advertisements. 
• A copy of the IRB approved ICF. 
• 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. 
18.5 Electronic Case Report Forms (eCRF)/Source Documents 
Electronic case report forms (eCRFs) called also electronic data capture (EDC) system, 


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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 ICF.  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. 
18.6 Reports to the IRB 
Before study initiation, the Investigator must have written and dated approval from the 
IRB for the protocol, ICF, 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. 
18.7 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. 
18.8 Records Retention 
The Investigator must maintain records of the study product disposition, copies of the 
CRFs 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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19 REFERENCES  
1. Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 
2013Mar;168(3):474-485. 
 
2. Gollnick H, Cunliffe W Berson D, et al; Global Alliance to Improve Outcomes in Acne. 
Management of acne: a report form a Global Alliance to Improve Outcomes in Acne.  
J Am Acad Dermatol.  2003;49(suppl 1):S1-S37. 
 
3. Leyden J, Kaidbey K, Levy SF. The combination formulation of clindamycin 1% plus 
benzoyl peroxide 5% versus 3 different formulations of topical clindamycin alone in 
the reduction of Propionibacterium acnes. Am J Clin Dermatol 2001;2 (4):63-266. 
4. Tanghetti E. The evolution of benzoyl peroxide therapy. Cutis. 2008 Nov;82 (5 
Suppl):5-11. 
5. FDA Guidance for Industry - Patient-Reported Outcome Measures: Use in Medical 
Product Development to Support Labeling Claims; accessed March 23, 2016 at 
https://www.fda.gov/downloads/drugs/guidances/ucm193282.pdf 
6. Zar, JH.  Bio-statistical analysis, 1984 2nd ed. Englewood Cliffs (NJ)Prentice-Hall. 
7. Acne QoL questionnaire:  
• Girman CJ, Hartmaier S, Thiboutot D, JOHNSON J, Barber B, DeMuro-Mercon 
C, Waldstreicher J Evaluating health-related quality of life in acne patients: 
Development of a self-administered questionnaire for clinical trials. Quality of 
Life 1996:5:481-490. 
• Martin AR, Lookingbill DP, Botek A, Light J, Thiboutot D, Girman CJ. Health-
Related quality of life among patients with facial acne – assessment of a new 
acne-specific questionnaire. Clin Exp Dermatol 2001: 26(5):380-385. 
• SE Fehnel, LD Mclead, J Brandman, DI Arbit, CJ McLaughlin-Miley, JH 
Coombs, AR Martin, CJ Girman. Responsiveness of Acne-Specific Quality of 
Life Questionnaire (Acne-QoL) to treatment for acne vulgaris in placebo-
controlled clinical trials. Qual life Res 2003:11:809-816. 
 
 
 
 


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20 APPENDIXES 
APPENDIX 1: PATIENT INSTRUCTIONS 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: 
• Apply the cream, once a day, every day, at home and prior to bedtime, for twelve 
(12) weeks.  
• Wash your face gently with the mild cleanser provided by the doctor or with 
study approved cleanser and water. Rinse thoroughly and gently pat dry.   
• After the face has dried completely, apply a pea sized amount of study product 
for each area of the face (chin, left cheek, right cheek, nose and forehead) as a 
thin layer, 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. (excessive rubbing 
should be avoided).   
• Do not apply the cream on the mouth, eyes, inside the nose and lips or any body 
part other than the face.   
• Do NOT treat specific lesions but rather the whole area. 
• Be sure to wash your hands before and after you apply the product.  But do not 
wash your face for at least two (2) hours after you apply the 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 test product at room temperature (at or below 25°C/77°F).  Do not freeze 
or expose to extreme temperature.  Keep test product in an upright position.  
• Avoid contact with the eyes, inside the nose, lips, mouth and all mucous 
membranes. 
• Caution: This test product contains ingredient which may cause bleaching of 
colored fabric. 
• 
The test product should be used only by the person for whom it was provided 
• The test product should be kept out of the reach of children or others of limited 
capacity to read or understand these instructions. 
• Containers of test product must be returned to the study staff, even if they are 
empty. 
• 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 Calendar provided 
to you; indicate reason for any missed dose on the diary calendar. 


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• Throughout the study, continue to use on your face only the same cleanser 
provided by the Investigator for this study. 
• If you use a moisturizer and/or sunscreen, you must use the one provided by the 
doctor for this study. If necessary, after consultation with your site staff you 
might be permitted to use another moisturizer with sunscreen that includes a 
higher SPF (Sun Protection Factor) which will require the sponsor to 
preapprove its use.  
• The pump you received has enough cream for full four (4) weeks of treatment. 
If you are running out of cream in the pump before your next visit, contact the 
study staff immediately. A new pump will be supplied, and you will be 
reinstructed on how to use it.   
• On the day of your study visit, do not apply study product, the moisturizer 
with sunscreen, or make-up and do not shave your face.  
• You must not use any other treatment for your acne while you are participating 
in this study. 
• Avoid unnecessary sun exposure and tanning booths. When sun exposure 
cannot be avoided, use the provided moisturizer with sunscreen and wear a 
wide-brimmed hat. 
• It is important to 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. On Visit3/ Week 2 ONLY, Do Not bring the study product pump. 
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/ End of 
Study or Early Termination, 
Day 85 
Date:                        Time:       
 
Thank you for following these instructions


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APPENDIX 2:  PRO – PRE-FACE - SIGNS/SYMPTOMS 
 
  
 
 


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APPENDIX 3:  PRO – PRE-FACE - IMPACTS 
 
 


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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: ADMINISTRATION OF ACNE-QOL 
 
 
 
 


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APPENDIX 9: ACNE-SPECIFIC QOL 
QUESTIONNAIRE 
 
 
 


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SAP_001.pdf: 
Statistical Analysis Plan 
Sol-Gel Technologies Ltd. SGT-65-04 
Version: 2 
Date: 26 NOV 2019 
TOOL.AN.10-01.01 Statistical Analysis Plan Template          
 Page 1 of 210 
CONFIDENTIAL 
STATISTICAL ANALYSIS PLAN 
Protocol Number: 
SGT-65-04 
Study Title: 
A Phase 3 Multi-Center, Double-Blind, 
Randomized, Vehicle-Controlled Study 
of S6G5T-3 in the Treatment of Acne 
Vulgaris 
Development Phase of Study: 
3 
Sponsor: 
Sol-Gel Technologies Ltd. 
Sponsor Contact: 
 
Statistical Analysis Plan based on Protocol Version: 
2.0 
Statistical Analysis Plan Date: 
26NOV2019 
Statistical Analysis Plan Version: 
V2 
NCT # NCT03761784




 
 
Statistical Analysis Plan 
Sol-Gel Technologies Ltd. SGT-65-04 
Version: 2 
Date: 26 NOV 2019 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
    Page 3 of 210 
CONFIDENTIAL 
SAP Change History 
Version Date 
Summary of Changes  
Author 
1 
30APR2019 Original document 
 
2 26NOV2019 In Section 8.1.11 an age grouping (9-11, 12-17 and 18-
30, 31 and up) was added. 
In Section 8.7 the text was revised so that the secondary 
efficacy analysis is also being performed on the Per-
Protocol population.  
In the table mocks the treatment header was updated to 
E-BPO/E-ATRA 3%/0.1% Cream for the active arm. 
In Section 8.4.4 the text ws updated to properly reflect 
the intended Week 12 window of +/- 4 days. 
 
 
 


 
 
Statistical Analysis Plan 
Sol-Gel Technologies Ltd. SGT-65-04 
Version: 2 
Date: 26 NOV 2019 
 
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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 Primary Objectives .......................................................................................................10 
5.2 Secondary Objective .....................................................................................................11 
5.3 Supportive Objective ....................................................................................................11 
5.4 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 .......................................................................14 
7.1 Efficacy Endpoints ........................................................................................................14 
7.1.1 
Primary Efficacy Endpoints ............................................................................14 
7.1.2 
Secondary Efficacy Endpoints ........................................................................14 
7.1.3 
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 .....................................................19 


 
 
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8.1.5.3 
PRE-FACE Missing Data Imputation ..........................................20 
8.1.5.4 
Medication Date Imputation ........................................................21 
8.1.6 
Interim Analyses and Data Monitoring ...........................................................21 
8.1.7 
Multicenter Studies ..........................................................................................21 
8.1.8 
Multiple Comparisons/Multiplicity .................................................................24 
8.1.9 
Use of an Efficacy Subset of Subjects .............................................................24 
8.1.10 Active-Control Studies Intended to Show Equivalence ..................................25 
8.1.11 Examination of Subgroups ..............................................................................25 
8.2 Disposition of Subjects .................................................................................................26 
8.3 Protocol Deviations .......................................................................................................26 
8.4 Data Sets Analyzed .......................................................................................................26 
8.4.1 
Randomized Population ..................................................................................26 
8.4.2 
Intent-to-Treat (ITT) Population .....................................................................27 
8.4.3 
Safety Population ............................................................................................27 
8.4.4 
Per-Protocol (PP) Population ..........................................................................27 
8.5 Demographic and Other Baseline Characteristics ........................................................28 
8.6 Prior and Concomitant Medications .............................................................................28 
8.7 Analysis of Efficacy ......................................................................................................29 
8.7.1 
Primary Efficacy Analysis ...............................................................................29 
8.7.1.1 
Lesion Counts ..............................................................................29 
8.7.1.2 
Investigator Global Assessment (IGA) ........................................31 
8.7.2 
Sensitivity Efficacy Analysis ..........................................................................31 
8.7.2.1 
Sensitivity Analyses for Absolute Change in Lesion Count ........31 
8.7.2.1.1 
Repeated Measures ...............................................31 
8.7.2.1.2 
Model Based Multiple Imputation ........................31 
8.7.2.1.3 
Tipping Point ........................................................32 
8.7.2.2 
Sensitivity Analyses for IGA .......................................................32 
8.7.2.2.1 
Repeated Measures ...............................................32 
8.7.2.2.2 
Model Based Multiple Imputation ........................33 
8.7.2.2.3 
Tipping Point ........................................................33 
8.7.3 
Secondary Efficacy Analysis ...........................................................................34 
8.7.4 
Supportive Efficacy Analysis ..........................................................................34 
8.7.5 
Exploratory Endpoint Analysis .......................................................................34 
8.8 Safety Evaluation ..........................................................................................................35 
8.8.1 
Extent of Exposure ..........................................................................................35 


 
 
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8.8.2 
Adverse Events (AEs) .....................................................................................36 
8.8.1 
Clinical Laboratory Evaluation .......................................................................37 
8.8.1 
Other Observations Related to Safety .............................................................37 
8.8.1.1 
Cutaneous Safety Assessments ....................................................37 
8.8.1.2 
Local Tolerability Assessments ...................................................37 
8.8.1.3 
Vital Signs ....................................................................................37 
8.8.1.4 
Physical Examination...................................................................38 
9. 
DETERMINATION OF SAMPLE SIZE .........................................................................38 
10. CHANGES IN THE PLANNED ANALYSES..................................................................39 
11. REFERENCES ....................................................................................................................40 
12. INDEX OF PLANNED TABLES ......................................................................................41 
13. INDEX OF PLANNED FIGURES ..................................................................................171 
14. INDEX OF PLANNED LISTINGS .................................................................................173 
 
 


 
 
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1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Acne-QoL 
Acne Quality-of-Life Questionnaire 
AE(s) 
adverse event(s) 
AID 
Acne impact domain 
ANCOVA 
analysis of covariance 
ANOVA 
analysis of variance 
ATC 
Anatomical Therapeutic Chemical 
ASD 
acne sign and symptom domain 
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) 
PRO 
Patient Reported Outcome 
PRE-FACE 
Patient-Reported Evaluation of Facial Acne 
PGI-C 
Patient Global Impression of Change 


 
 
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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 
PT 
preferred term 
QST 
QST Consultations, Ltd. 
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-65-04 
o Version 1.0 issued on 23MAR2018,  
o Version 2.0 issued on 01NOV2018, 
• Case report form (CRF) for SGT-65-04. 
• 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 
Acne vulgaris is a common condition of the pilosebaceous units of the skin (hair follicles and oil 
glands). Acne is the most common skin disorder in the United States, affecting 40-50 million 
Americans. Acne usually begins in puberty, but the condition is not restricted to any age group. 
Approximately 85% of people between the ages of 12 and 24 experience at least minor, most 
often on the face, chest, and back [1]. Acne is caused by four major factors: 
1. Production of oil by enlarged oil glands in the skin. 
2. Blockage of the hair follicles that release oil. 
3. Growth of bacteria, called Propionibacterium acnes, within the hair follicles. 
4. Inflammatory/immune response to P. acnes. 
The pathophysiologic features of acne suggest that combination therapy should be utilized as 
early as possible to simultaneously attack the multiple pathogenic factors of the condition [2]. 
Antimicrobials have been a mainstay of acne treatment for many years, having multiple 
mechanisms of action. The most important may be the ability of antibiotics to decrease the 
number of P. acnes in and around the follicle. They have a bacteriostatic effect on P. acnes, 
which prevents the bacteria from producing pro-inflammatory molecules [3]. 
In June 2017, Sol Gel completed a double blind, randomized, dose ranging Phase 2 trial for 
S6G5T-3 involving 726 adult Patients at thirty-six centers in the United States (SGT-65-02: A 
Phase 2, Randomized, Double Blind, Active and Vehicle Controlled, 12-Week Study Evaluating 
the Efficacy, Safety, and Tolerability of S6G5T-3 and S6G5T-1 for the Treatment of Acne 
Vulgaris). 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 and non-inflammatory lesion count at Week 12 (end of trial). All 
Patients were 9 years of age or older with IGA of 3 or 4, 20 or more inflammatory lesions and 25 
non-inflammatory lesions at enrollment. Patients were randomly divided into six groups of 119 
to 122 Patients each and received a once daily dose, with one group receiving S6G5T-3 
encapsulated benzoyl peroxide/encapsulated ATRA (E-BPO/E-ATRA 3%/0.1%), S6G5T-1 


 
 
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(E-BPO/E-ATRA (3%/0.05%), E-ATRA 0.1%, E-ATRA 0.05%, E-BPO 3% and Vehicle Cream 
alone. S6G5T-3 demonstrated numerical superiority to the active component E-BPO 3% and 
vehicle for the co-primary endpoints (treatment success and lesion counts inflammatory) at the 
Week 12 visit but only matched efficacy for non-inflammatory lesions for E-ATRA 0.1%. The 
success rate for at Least 2-Grade Improvement and Clear or Almost Clear was 12.27%, 22.10%, 
31.72% and 39.68% for Vehicle Cream, E-BPO 3%, E-ATRA 0.1% and S6G5T-3, respectively. 
The mean inflammatory change from Baseline was -11.5, -13.8, -14.9 and -16.9. for Vehicle 
Cream, E-BPO 3%, E-ATRA 0.1% and S6G5T-3, respectively. The mean non-inflammatory 
change from Baseline was –13.7, -16.2, -23.8 and -23.6 for Vehicle Cream, E-BPO 3%, E-
ATRA 0.1% and S6G5T-3, respectively. S6G5T-3 each demonstrated statistical superiority (p= 
0.006 or less) to vehicle for the co-primary endpoints (treatment success, lesion counts both 
inflammatory and non-inflammatory) at the Week 12 visit. 
In addition, S6G5T-3 were safe and well tolerated. The most common treatment-emergent 
adverse events (TEAEs) (≥5% incidence in any treatment group) were application site dryness, 
exfoliation and pain as well as upper respiratory infection. Cutaneous safety and tolerability 
assessment (erythema, scaling, pigmentation, itching, burning and stinging) by the Investigator 
showed that the proportion of Patients with these complaints tended to remain unchanged from 
Baseline over 12 weeks. On the other hand, based on self-assessments, a slightly greater 
proportion of Patients in the S6G5T-3 treatment groups had at least one higher post-baseline 
assessment of scaling, burning and stinging (mild) compared to vehicle. There were no apparent 
differences in mean changes from Baseline in any of the hematological and clinical chemistry 
test results in all treatment groups at Weeks 8 and 12. Most urinalysis test results were normal at 
Baseline and at Weeks 8 and 12. There were no clinically significant abnormalities in ECGs in 
the study. 
In conclusion, both S6G5T-1 and S6G5T-3 demonstrate efficacy and safety in the treatment of 
acne vulgaris, however, S6G5T-3 showed additional benefit in achieving a greater proportion of 
treatment IGA success. Therefore, S6G5T-3 was selected as the “to be marketed formulation” 
and the active arm in this study. 
5. STUDY OBJECTIVES 
5.1 
Primary Objectives 
The primary objectives of this pivotal study are: 
• To assess the efficacy of S6G5T-3 compared to its Vehicle when applied once daily for 
12 weeks in Patients with acne vulgaris. 


 
 
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• To assess the safety of S6G5T-3 when applied once daily for 12 weeks in Patients with 
acne vulgaris. 
5.2 
Secondary Objective 
The secondary objective of this pivotal study is: 
• To demonstrate statistical superiority in efficacy of Products S6G5T-3 as compared to the 
vehicle regarding percent change from Baseline. 
5.3 
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 acne for Products S6G5T-3 compared to vehicle. 
5.4 
Safety Objective 
The safety objectives of this pivotal study are: 
• To determine the nature, severity and frequency of the adverse event (AE) rate and the 
localcutaneous reaction and tolerability of Products S6G5T-3 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 to assess efficacy, and safety of Products S6G5T-3 and its 
vehicle for the treatment of acne vulgaris for 12 weeks. Approximately 420 Patients with 
moderate to severe acne vulgaris (rated 3 or 4 on the 5-point IGA) will be enrolled at up to 31 
sites. Patients in this randomized, double-blind, vehicle-controlled, parallel-group multi-center 
study will be randomly assigned in a 2:1 ratio to Encapsulated Benzoyl Peroxide 
3%/Encapsulated All-Trans-Retinoic Acids 0.1% (E-BPO/E-ATRA) Cream or Vehicle Cream 
respectively. Patients with severe acne vulgaris who are appropriate for systemic treatment need 
to be counseled regarding their treatment options by the Principal Investigator (PI). 
The overall schedule of study visits includes: 
• Visit 1/Screening 
• Visit 2/Baseline, Day 1 


 
 
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• 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 Study or Early Termination 
Treatment efficacy will be evaluated using both clinician reported outcome (ClinRO) and 
Patient-reported outcome (PRO) questionnaires. Clinician reported efficacy assessments will 
include facial inflammatory and non-inflammatory lesion counts and an IGA which asks 
assessors to rate Patient’s acne from 0 (Clear) to 4 (Severe). Patient reported efficacy 
assessments include the Patient-Reported Evaluation of Facial Acne (PRE-FACE), the Patient 
Global Impression of Symptom Severity (PGI-S), the Patient Global Impression of Change 
(PGI-C), and the Patient Global Impression of Treatments Satisfaction (PGI-TS). 
Safety will be assessed at all visits and will include monitoring local and systemic AEs; the 
Investigator Cutaneous Safety Assessment rating of pigmentation, erythema, dryness and scaling 
on a scale ranging from 0 (None) to 3 (Severe) and the Patient assessment of Local Tolerability 
Assessment rating itching, burning and stinging on a scale ranging from 0 (None) to 3 (Severe). 
A Patient Global Impression of Treatment Side Effects (PGI-SE) will also be administered as 
part of the study design. 
Clinician reported outcomes will be collected at study Visit 1, 2, 3, 4, 5 and 6. Patient-reported 
outcomes will be collected at study visit 2, 3, 4, 5, and 6 (with the exception of the PGI-C, 
PGI-TS and PGI-SE) which are not collected at Visit 1 or Visit 2). AEs and concomitant 
medications will be assessed throughout the treatment period. A urine pregnancy test is required 
at Visit 1, 2, 3, 4, 5 and 6 for all females of child-bearing potential and premenarchal.  
6.1.1 
Schedule of Visits and Assessments 
The schedule of assessments can be found in Section 12.10 of the protocol.  
6.1.2 
Method of Assigning Subjects to Treatment Groups 
It is planned that approximately 420 Patients, who meet the inclusion/exclusion criteria, will be 
enrolled in this study at up to 31 U.S. study sites. Patients will be at least 9 years of age and 
older, of either gender. 
The study products will be administered in a double-blinded fashion (i.e., the treatment 
assignment will not be known to the Patient or to study personnel including 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: 


 
 
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• E-BPO/E-ATRA 3%/0.1% Cream (Product S6G5T-3) (280 Patients) 
• Vehicle Cream (Product S6G5T-8) (140 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. Patients will be randomized through the IWRS and assigned a unique 
randomization ID assigning treatment group. The study product supplies will be packed in kits 
containing 4-pumps and will be numbered in a scrambled randomized method. The kits will be 
dispensed by the IWRS according to the Baseline assigned randomized treatment group. 
6.1.3 
Blinding 
The staff involved in data management and statistical evaluation will remain blinded until 
identification of the analysis populations is completed and the database is locked. 
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 PI in the case of an emergency unblinding. 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 of one or all Patients may be necessary in 
the case that the safety of study Patient(s) 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 


 
 
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above-designated individuals; and any unblinding will be documented in the source records 
accordingly. 
7. EFFICACY AND SAFETY ENDPOINTS 
7.1 
Efficacy Endpoints 
7.1.1 
Primary Efficacy Endpoints 
The co-primary efficacy endpoints are as follows: 
• Proportion of Patients with an assessment of clear or almost clear and with at least a 
2-grade improvement in IGA from Baseline at Week 12. 
• Absolute change from Baseline in lesion count on the face at Week 12 (separately for 
inflammatory and non-inflammatory lesions). 
7.1.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are as follows: 
• Percent change from Baseline, in non-inflammatory lesion count at Week 12. 
• Percent change from Baseline, in inflammatory lesion count at Week 12. 
• Proportion of Patients in the E-BPO/E-ATRA cream arm compared to vehicle control 
achieving at least a 4-point reduction on Item 1 (pimples) of the PRE-FACE from 
Baseline to Week 12. 
• Proportion of Patients in the E-BPO/E-ATRA Cream arm compared to vehicle control 
achieving at least a 4-point reduction on Item 5 (embarrassment) of the PRE-FACE from 
Baseline to Week 12. 
• Absolute change from Baseline, in non-inflammatory lesion count at Week 8 
• Absolute change from Baseline, in inflammatory lesion count at Week 8. 
• Absolute change from Baseline, in non-inflammatory lesion count at Week 4. 
• Absolute change from Baseline, in inflammatory lesion count at Week 4. 
7.1.3 
Supportive Efficacy Endpoints 
The supportive efficacy endpoints are as follows: 


 
 
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• Proportion of Patients with an assessment of clear or almost clear and with at least a 
2-grade improvement in IGA from Baseline, at Weeks 2, 4 and 8. 
• Absolute change from Baseline in inflammatory and non-inflammatory lesion counts 
from Baseline to Week 2. 
• PRE-FACE ASD: Mean absolute change in PRE-FACE ASD scores from Baseline to 
Weeks 2, 4, and 8. 
• PRE-FACE AID: Mean absolute change in PRE-FACE AID scores from Baseline to 
Weeks 2, 4, and 8. 
• Proportion of Patients in treatment relative to control who report at least “minimally 
improved” as measured by the PGI-C at Week 12. 
• Patient Global Impress of Symptom Severity (PGI-S) at Week 12. 
• Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 12. 
7.1.4 
Exploratory Endpoints 
The exploratory endpoint is the mean change in Acne-QoL domain 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, and vital signs. 
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. 
The primary method of handling missing efficacy data will be based on estimation using the 
method of Markov Chain Monte Carlo (MCMC) imputation. 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 


 
 
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analyses and subsequent imputation result inference with SAS PROC MIANALYZE. 
Descriptive statistics will also be derived from the multiply imputed datasets. 
Sensitivity analyses for the primary efficacy endpoints will use 3 methods. For the lesion count 
endpoint, the first method will use a repeated measures analysis of covariance (ANCOVA), with 
treatment, analysis center, visit (i.e., Week 2, Week 4 and Week 8), and treatment group by visit 
interaction as independent factors and a covariate of Baseline. In this analysis, data from all post-
baseline visits will be included with no imputation for missing data. 
The second sensitivity analyses will use the model based multiple imputation method to impute 
missing data for the absolute change at Week 12. 
The third sensitivity analysis will involve a tipping point analysis. 
Similar methods for the dichotomized IGA will involve a repeated measures logistic regression 
model and a model based multiple imputation and tipping point analysis. 
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.  


 
 
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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 
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 acne 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 


 
 
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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 Per Protocol (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. 
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 Week 12 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. 


 
 
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A total of 4 random seeds are needed to impute lesion counts. The following 4 random seeds 
have been pre-specified by using a random number generator: 
• Inflammatory Lesion Counts; S6G5T-3: Seed = 813883085 
• Inflammatory Lesion Counts; S6G5T-8 Vehicle: Seed = 2010726808 
• Non-inflammatory Lesion Counts; S6G5T-3: Seed = 1326750493 
• Non-inflammatory Lesion Counts; S6G5T-8 Vehicle: Seed = 1498908882 
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.  
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 with a 
2-point change from Baseline) 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. 
The following 2 random seeds have been pre-specified by using a random number generator: 


 
 
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• IGA; S6G5T-3: Seed = 377388888 
• IGA; S6G5T-3 Vehicle: Seed = 1174190226 
8.1.5.3 
PRE-FACE Missing Data Imputation 
The same procedure will be used for the analyses based on proportion of PRE-FACE item 1 
(pimples) and item 5 (embarrassment) successes as the IGA success. Specifically, missing PRE-
FACE items 1 and 5 values from which the dichotomized versions are 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 PRE-FACE items 1 and 5 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 PRE-FACE items 1 and 5 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 (at least a 4-point reduction 
from Baseline) 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. 
The following 4 random seeds have been pre-specified by using a random number generator: 
• PRE-FACE Pimples Scores; S6G5T-3: Seed = 1597410322 
• PRE-FACE Pimples Scores; S6G5T-3 Vehicle: Seed = 466920922 


 
 
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• PRE-FACE Embarrassment Scores; S6G5T-3: Seed = 288784276 
• PRE-FACE Embarrassment Scores; S6G5T-3 Vehicle: Seed = 1746263137 
8.1.5.4 
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.  
• 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 


 
 
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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. 
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 and non-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 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 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. 


 
 
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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. 
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 and non-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 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. 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. 


 
 
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8.1.8 
Multiple Comparisons/Multiplicity 
The overall Type I error will be controlled by requiring the three 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. 
Evaluation of the secondary efficacy variables will use a gated sequential procedure starting with 
the comparisons of the first step and proceeding onto the next step and etc. 
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. 
Step 
Number 
Secondary Endpoint 
1 
Percent change from Baseline, in non-inflammatory lesion count at Week 12. 
2 
Percent change from Baseline, in inflammatory lesion count at Week 12. 
3 
Proportion of patients in the E-BPO/E-ATRA cream arm compared to vehicle 
control achieving at least a 4-point reduction on Item 1 (pimples) of the 
PREFACE from Baseline to Week 12. 
4 
Proportion of patients in the E-BPO/E-ATRA Cream arm compared to vehicle 
control achieving at least a 4-point reduction on Item 5 (embarrassment) of the 
PRE-FACE from Baseline to Week 12. 
5 
Absolute change from Baseline, in non-inflammatory lesion count at Week 8 
6 
Absolute change from Baseline, in inflammatory lesion count at Week 8. 
7 
Absolute change from Baseline, in non-inflammatory lesion count at Week 4.. 
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 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 S6G5T-3. 


 
 
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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;  
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 
o Categories of less than 18,18 to less than the median age of ITT subjects and 
greater than or equal to the median age of ITT subjects; if the median age of ITT 
subjects is 18 or less, the subgroup will be less than 18 and greater than or equal 
to 18 
o Categories of 9-11 years, 12-17 years, 18-30 years, and 31 years and older 
• 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 
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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. 
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. 


 
 
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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 any significant 
protocol violations 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: 
• 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 applications and must take 80-120% 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.  


 
 
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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, race, ethnicity, and Baseline IGA will be summarized by counts and percentages. Age, 
height (cm), weight (kg), body mass index (BMI), and Baseline lesion counts will be 
summarized with descriptive statistics.  
Age, height, weight, BMI, and Baseline lesion counts will be compared among the two treatment 
groups using a two-way analysis of variance (ANOVA) with factors of treatment group and 
analysis center. Ethnicity, race, sex, and Baseline IGA will be analyzed with a Cochran-Mantel-
Haenszel test stratified by analysis center. 
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. 
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 


 
 
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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 8.1.5.4 
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 and non-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. 
Primary, secondary, and supportive efficacy analyses will be conducted on the ITT (primary) 
population. Primary and secondary efficacy analyses will be conducted on the PP (supportive) 
population. 
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. 
8.7.1.1 
Lesion Counts 
Tests of superiority for the absolute change from Baseline in inflammatory and non-
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 


 
 
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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 lesion counts 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 
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 


 
 
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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 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. 
8.7.2 
Sensitivity Efficacy Analysis 
8.7.2.1 
Sensitivity Analyses for Absolute Change in Lesion Count 
8.7.2.1.1 
Repeated Measures 
The first sensitivity analyses for absolute change in lesion count (both inflammatory and non-
inflammatory) will use a repeated measures ANCOVA, with treatment, analysis center, visit (i.e., 
Week 2, Week 4 and Week 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. 
8.7.2.1.2 
Model Based Multiple Imputation 
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: 
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; 


 
 
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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. 
Two random seeds will be needed to impute the inflammatory and non-inflammatory lesion 
counts. The following random seed has been pre-specified by using a random number generator: 
 
Inflammatory Lesion Count Seed= 1098696156 
 
Non-inflammatory Lesion Count Seed= 1003722056     
8.7.2.1.3 
Tipping Point 
A tipping point analysis of the primary endpoints will be performed as a sensitivity analysis for 
the handling of missing data. The multiple imputation datasets used for the primary analyses will 
be used for the tipping point analyses for lesion counts. To perform the tipping point analysis, the 
imputed values from the multiple imputation datasets for only the E-BPO/E-ATRA cream arm 
will be adjusted, by adding a constant (shift value) to the lesion counts. Change from Baseline 
will then be recalculated with the changed imputed values. The shifted multiple imputed datasets 
will then be analyzed as described in the primary endpoint section. This will then be repeated by 
adding the constant again to create another new shifted multiple imputed dataset and that dataset 
will be analyzed. The resulting point estimates and p-values associated with each shift value will 
be presented in order to assess the magnitude of the shift value required to “tip” the p-value 
greater than 0.05.  
8.7.2.2 
Sensitivity Analyses for IGA 
8.7.2.2.1 
Repeated Measures 
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., Week 2, Week 4 and Week 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. 


 
 
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8.7.2.2.2 
Model Based Multiple Imputation 
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; 
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= 1857263794 
8.7.2.2.3 
Tipping Point 
A tipping point analysis of the primary endpoint will be performed as a sensitivity analysis for 
the handling of missing data. To perform the tipping point analysis for the dichotomized IGA, all 
combinations for the number of imputed successes for the nonrespondents in the E-BPO/E-
ATRA cream group and the vehicle group will be analyzed to identify the points that would 
indicate a treatment failure using a p-value greater than 0.05. The resulting points of treatment 
failure will be plotted with the average number of successes in each treatment group from the 
primary multiple imputation analysis overlayed. The tipping points of the study will be identified 
by the points where the particular combinations of imputed successes that change the treatment 
success to a treatment failure. 


 
 
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8.7.3 
Secondary Efficacy Analysis 
Appropriate descriptive statistics will be computed for all secondary efficacy parameters. 
Additionally, all inferential testing of percent change in lesions will follow the methods for the 
primary lesion count analyses. Methods corresponding to the analysis of IGA will be used to 
compare the proportion of patients in the E-BPO/EATRA Cream arm versus vehicle control 
achieving at least a 4-point reduction in pimples (item1 of the PRE-FACE) or in embarrassment 
(item5 of the PRE-FACE) scores from Baseline to Week 12. 
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 the ITT and PP populations. 
8.7.4 
Supportive Efficacy Analysis 
Appropriate descriptive statistics will be computed for all supportive efficacy parameters.  
Additionally, all inferential testing will follow the methods for the co-primary variables wherein 
the continuous variables will parallel the lesion count analyses and the discrete dichotomized 
variables will follow the analysis of the IGA. Inferential testing for PGI-S and PGI-TS at Week 
12 will use a cumulative logistic regression with factors of treatment group and analysis center. 
Missing values will not be imputed. 
8.7.5 
Exploratory Endpoint Analysis 
The mean change in Acne-Qol domain scores from Baseline to Week 12 will be summarized 
using descriptive statistics. 
Domain scores will be calculated as follows:  
1. Code each response. Responses are numbered starting with 0 in ascending order.  
• For questions 1-14 and 18-19: 
o Extremely=0, Very Much=1, Quite A Bit=2, A Good Bit=3, Somewhat=4, A 
Little Bit=5, Not At All=6 
• For questions 15-17: 
o 0=Extensive, 1=A Whole Lot, 2=A Lot, 3=A Moderate Amount, 4=Some, 
5=Very Few, 6=None 


 
 
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2. Check for missing values and impute as follows:  
• Within each domain, a minimum number of responses is required in order to score the 
domain. At least 3 items must be answered within each domain in order to calculate 
the domain scores. If the minimum number of items have been answered but 1-2 
questions have missing responses, calculate the mean value within the domain for the 
answered items and replace missing values with the mean value. 
3. Calculate overall domain scores for each domain by summing the coded responses to 
each question in the domain.  
• Domains will be calculated as follows: 
o Self-Perception domain calculated from questions 1, 2, 3, 6, and 10. 
o Role-Emotional domain calculated from questions 4, 5, 7, 8, and 9. 
o Role-Social domain calculated from questions 11, 12, 13, and 14. 
o Acne Symptoms domain calculated from questions 15, 16, 17, 18, and 19. 
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 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 


 
 
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be used to compare the proportion of patients in each treatment group who report any AE 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 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. 
8.8.1 
Clinical Laboratory Evaluation 
Urine pregnancy test results will be presented in a by-subject listing.  
8.8.1 
Other Observations Related to Safety 
8.8.1.1 
Cutaneous Safety Assessments 
Descriptive statistics by treatment group and visit will be provided for pigmentation, erythema, 
dryness, and scaling.  
8.8.1.2 
Local Tolerability Assessments 
Descriptive statistics by treatment group and visit will be provided for itching, burning and 
stinging.  
8.8.1.3 
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) 


 
 
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• Diastolic Blood Pressure: <90 mm Hg (low), 90-100 mmHg (normal), >100 mmHg 
(high) 
Heart Rate: <60 beats per minute (low), 60-100 beats per minute (normal), >100 beats per 
minute (high). 
8.8.1.4 
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.  
9. DETERMINATION OF SAMPLE SIZE 
The following power calculations are based on the observed Week 12 results of the Phase 2 
study, SGT-65-02. This study was a six-arm trial including S6G5T-3 and Vehicle Cream in the 
treatment of acne vulgaris. Estimates from the S6G5T-3 arm were used in the power 
assessments. The anticipated randomization ratio is 2:1 for S6G5T-3 and S6G5T-8 Vehicle 
Cream, 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 274 in the S6G5T-3 and 137 in the Vehicle Cream group (total of 411) has 99% 
power to detect a statistically significant difference in inflammatory lesions. The estimated 
absolute change from Baseline in treatment means were -16.7 and -12.2 for S6G5T-3 and 
Vehicle Cream, respectively, with a common standard deviation of 10.0. 
A sample size of 146 in the S6G5T-3 and 73 in the Vehicle Cream group (total of 219) has 99% 
power to detect a statistically significant difference in non-inflammatory lesions. The estimated 
absolute change from Baseline in treatment means were -23.7 and -13.7 for S6G5T-3 and 
Vehicle Cream, respectively, with a common standard deviation of 19.0. 
A sample size of 231 in the S6G5T-3 and 116 in the Vehicle Cream has group (total of 346) has 
99% power to detect a statistically significant difference 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 33.3% and 12.6% for S6G5T-3 and Vehicle Cream, respectively. 
Therefore, a total of 420 Patients has adequate power to demonstrate statistical significance of 
S6GT5-3 over S6GT5-8 Vehicle Cream for the lesion count endpoints as well as dichotomized 
IGA. 


 
 
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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. 
Absolute change from Baseline in inflammatory and non-inflammatory lesion counts from 
Baseline to weeks 4 and 8 were removed from the supportive efficacy endpoints, as they were 
also included in the secondary efficacy endpoints.  
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. The protocol provided did not provide seeds for the IGA 
MCMC imputation or for the model based multiple imputation, so those were added in the SAP. 
Geographic region was removed from the examination of subgroups as all sites in the study are 
in the United States.  
An additional age grouping of 9-11 years, 12-17 years, 18-30 years, and 31 years and older was 
added to the subgroup summaries.  


 
 
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The secondary efficacy analysis wil be presented on the PP population in addition to the ITT 
population as specified in the protocol.  
11. REFERENCES 
1. Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 
2013Mar;168(3):474-485. 
2. Gollnick H, Cunliffe W Berson D, et al; Global Alliance to Improve Outcomes in Acne. 
Management of acne: a report form a Global Alliance to Improve Outcomes in Acne. J 
Am Acad Dermatol. 2003;49(suppl 1):S1-S37. 
3. Leyden J, Kaidbey K, Levy SF. The combination formulation of clindamycin 1% plus 
benzoyl peroxide 5% versus 3 different formulations of topical clindamycin alone in the 
reduction of Propionibacterium acnes. Am J Clin Dermatol 2001;2 (4):63-266. 
4. Zar, JH. Bio-statistical analysis, 1984 2nd ed. Englewood Cliffs (NJ)Prentice-Hall. 
 
 


 
 
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12. INDEX OF PLANNED TABLES 
Table 14.0.1: Summary of Subject Completion/Discontinuation  (All Randomized Subjects) ....44 
Table 14.0.2.1: Summary of Subject Enrollment and Evaluability  (All Randomized Subjects)..45 
Table 14.0.2.2: Summary of Subject Evaluability by Analysis Center and Investigational Site      
(All Randomized Subjects) ...................................................................46 
Table 14.1.1.1: Summary of Subject Demographic Characteristics  (Intent-to-
Treat Population) ...................................................................................47 
Table 14.1.1.2: Summary of Subject Demographics (Per-Protocol Population) ...........................48 
Table 14.1.1.3: Summary of Subject Demographics (Safety Population) .....................................48 
Table 14.1.2.1: Subject Baseline Characteristics  (Intent-to-Treat Population) ............................49 
Table 14.1.2.2: Subject Baseline Characteristics (Per-Protocol Population).................................50 
Table 14.1.2.3: Subject Baseline Characteristics (Safety Population)...........................................50 
Table 14.1.3.1: Summary of Medical History by System Organ Class and Preferred 
Term  (Intent-to-Treat Population)........................................................51 
Table 14.1.3.2: Summary of Medical History by System Organ Class and Preferred Term (Per-
Protocol Population) .............................................................................51 
Table 14.1.3.3: Summary of Medical History by System Organ Class and Preferred Term (Safety 
Population) ............................................................................................51 
Table 14.1.4.1: Summary of Prior Medications by ATC Level 2 and Preferred 
Name  (Safety Population) ....................................................................52 
Table 14.1.4.2: Summary of Concomitant Medications by ATC Level 2 and Preferred 
Name  (Safety Population) ....................................................................53 
Table 14.2.1.1: Pooling Analysis for Primacy Efficacy Endpoints   (Intent-to-Treat Population)54 
Table 14.2.1.2: Primary Efficacy Analysis: Absolute Change from Baseline in Lesion Counts 
and Dichotomized IGA Success at Week 12  (Intent-to-
Treat Population) ...................................................................................55 
Table 14.2.1.3: Primary Efficacy Analysis: Absolute Change from Baseline in Lesion Counts 
and Dichotomized IGA Success at Week 12 (Per-
Protocol Population) .............................................................................56 
Table 14.2.2.1.1: Summary of Inflammatory Lesion Counts at Each Evaluation  (Intent-to-
Treat Population) ...................................................................................57 
Table 14.2.2.1.2: Summary of Inflammatory Lesion Counts at Each Evaluation (Per-Protocol 
Population) ............................................................................................61 


 
 
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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).......................................62 
Table 14.2.3.1.1: Summary of Non-Inflammatory Lesion Counts at Each Evaluation  (Intent-to-
Treat Population) ...................................................................................63 
Table 14.2.3.1.2: Summary of Non-Inflammatory Lesion Counts at Each Evaluation (Per-
Protocol Population) .............................................................................67 
Table 14.2.3.2: Summary of Absolute Change in Non-Inflammatory Lesion Counts at Week 12 
by Analysis Center  (Intent-to-Treat Population)..................................68 
Table 14.2.4.1.1: Summary of Investigator Global Assessment at Each Evaluation  (Intent-to-
Treat Population) ...................................................................................69 
Table 14.2.4.1.2: Summary of Investigator Global Assessment at Each Evaluation (Per-Protocol 
Population) ............................................................................................73 
Table 14.2.4.2: Summary of Investigator Global Assessment (Two Grade Reduction from 
Baseline and Clear or Almost Clear) at Week 12 by Analysis Center 
(Intent-to-Treat Population) ..................................................................74 
Table 14.2.5.1: Subgroup Summaries of Primary Endpoints  (Intent-to-Treat Population) ..........75 
Table 14.2.6.1: Sensitivity Analysis of Primary Endpoints: Absolute Change from Baseline in 
Lesion Counts and Dichotomized IGA Success at Week 12  (Intent-to-
Treat Population) ...................................................................................83 
Table 14.2.7.1: Sensitivity Tipping-Point Analysis of the Primary Endpoint: Lesion Counts at 
Week 12  (Intent-to-Treat Population) ..................................................85 
Table 14.2.8.1: Secondary Efficacy Analyses  (Intent-to-Treat Population) .................................86 
Table 14.2.8.2: Secondary Efficacy Analyses (Per-Protocol Population) .....................................88 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each 
Evaluation  (Intent-to-Treat Population) ...............................................89 
Table 14.2.9.2: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each 
Evaluation (Per-Protocol Population) .................................................116 
Table 14.2.10.1: Supportive Efficacy Analyses: PGI-TS, PGI-S, and PGI-C at Week 12  (Intent-
to-Treat Population) ............................................................................117 
Table 14.2.11.1: Supportive Efficacy Analyses: Lesion Count and IGA ....................................118 
Table 14.2.12.1: Supportive Efficacy Analyses: PRE-FACE ASD Scores .................................121 
Table 14.2.13.1: Supportive Efficacy Analyses: PRE-FACE AID Scores ..................................124 
Table 14.2.14.1: Summary of Patient Global Impression of Change (PGI-C) at Each 
Evaluation   (Intent-to-Treat Population) ............................................127 


 
 
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Table 14.2.15.1: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each 
Evaluation   (Intent-to-Treat Population) ............................................129 
Table 14.2.16.1: Summary of Patient Global Impression of Treatments Satisfaction (PGI-TS) at 
Each Evaluation   (Intent-to-Treat Population) ...................................131 
Table 14.2.17.1: Summary of Acne-QoL Questionnaire Responses at Baseline and Week 
12  (Intent-to-Treat Population) ..........................................................133 
Table 14.3.0.1: Summary of Extent of Exposure  (Safety Population) .......................................137 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each 
Evaluation  (Safety Population) ..........................................................138 
Table 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event 
Characteristics  (Safety Population) ....................................................152 
Table 14.3.1.2.2: Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term (Safety Population)....................................154 
Table 14.3.1.2.3: Summary of Treatment-Emergent 
Adverse Events by Severity  (Safety Population) ...............................155 
Table 14.3.1.2.4: Summary of Treatment-Emergent Adverse Events by Relationship to Study 
Drug (Safety Population) ....................................................................156 
Table 14.3.1.3.1: Summary of Treatment-Emergent Serious Adverse Event 
Characteristics  (Safety Population) ....................................................157 
Table 14.3.1.3.2: Summary of Treatment-Emergent Serious Adverse Events by MedDRA 
System Organ Class and Preferred Term (Safety Population) ............159 
Table 14.3.1.3.3: Summary of Serious Treatment-Emergent 
Adverse Events by Severity  (Safety Population) ...............................160 
Table 14.3.1.3.4: Summary of Treatment-Emergent Serious Adverse Events by Relationship to 
Study Drug (Safety Population) ..........................................................161 
Table 14.3.1.4: Summary of Vital Signs  (Safety Population) ....................................................162 
Table 14.3.1.4.2: Shift Table of Vital Signs  (Safety Population) ...............................................167 
Table 14.3.1.5: Summary of Abnormal Physical Examination Findings by Visit  (Safety 
Population) ..........................................................................................168 
Table 14.3.1.6: Summary of Patient Global Impression of Treatment Side-Effects (PGI-SE) at 
Each Evaluation   (Safety Population) ................................................169 
 


 
 
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Table 14.0.1: Summary of Subject Completion/Discontinuation 
 (All Randomized Subjects) 
 
  
E-BPO/E-ATRA 3%/0.1% 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 Parent/Guardian 
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/E-ATRA  
 
3%/0.1% 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/E-ATRA 3%/0.1% 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/E-ATRA  
 
3%/0.1% Cream 
 
(N=xxx)  
 
  
Vehicle Cream 
 
(N=xxx)  
 
  
Total 
 
(N=xxx)  
 
 
 
P-Value  
 
Age (years) 
n 
xx 
xx 
xx 
x.xxxa 
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%) 
< 18  years 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
≥ 18 years and < Median (xx years) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
≥ Median (xx years) 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
9-11  years 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
12-17 years 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
18-30 years 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
≥ 31 years 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a P-value from a two-way analysis of variance with factors of treatment group and analysis center. 
b P-value from a Cochran-Mantel-Haenszel general association test, stratified by analysis center. 
c 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/E-ATRA  
 
3%/0.1% Cream 
 
(N=xxx)  
 
  
Vehicle Cream 
 
(N=xxx)  
 
  
Total 
 
(N=xxx)  
 
 
 
P-Value  
 
Sex 
n 
xx 
xx 
xx 
x.xxxb 
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 
x.xxxb 
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%) 
Race 
n 
xx 
xx 
xx 
x.xxxb 
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/Otherc 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a P-value from a two-way analysis of variance with factors of treatment group and analysis center. 
b P-value from a Cochran-Mantel-Haenszel general association test, stratified by analysis center. 
c 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/E-ATRA  
 
3%/0.1% Cream 
 
(N=xxx)  
 
  
Vehicle Cream 
 
(N=xxx)  
 
  
Total 
 
(N=xxx)  
 
 
 
P-Value  
 
Height (cm) 
n 
xx 
xx 
xx 
x.xxxa 
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 
x.xxxa 
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 
x.xxxa 
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 
 
 
a P-value from a two-way analysis of variance with factors of treatment group and analysis center. 
b P-value from a Cochran-Mantel-Haenszel general association test, stratified by analysis center. 
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/E-ATRA  
 
3%/0.1% Cream 
 
(N=xxx)  
 
  
Vehicle Cream 
 
(N=xxx)  
 
  
Total 
 
(N=xxx)  
 
 
 
P-Value  
 
Inflammatory Lesion Count 
n 
xx 
xx 
xx 
x.xxxa 
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 
Non-Inflammatory Lesion Count 
n 
xx 
xx 
xx 
x.xxxa 
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 
x.xxxb 
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%) 
 
 
a P-value from a two-way analysis of variance with factors of treatment group and analysis center. 
b P-value from a Cochran-Mantel-Haenszel general association test, stratified by analysis center. 
 
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/E-ATRA  
 
3%/0.1% 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/E-ATRA 3%/0.1% 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/E-ATRA 3%/0.1% 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 Treatment 
 Group P-Value  
 
Skewness 
 
P-Value 
 
 Analysis Center   
 
Treatment 
 
 Group P-Value  
Absolute Change from Baseline in Inflammatory Lesion Counts at Week 12 
x.xxxc 
x.xxxc 
Ranked Analysis 
x.xxxa 
x.xxxe 
Unranked Analysis 
x.xxxb 
x.xxxf 
Absolute Change from Baseline in Non-Inflammatory Lesion Counts at Week 12 
x.xxxc 
x.xxxc 
Ranked Analysis 
x.xxxa 
x.xxxe 
Unranked Analysis 
x.xxxb 
x.xxxf 
Two Grade Reduction from Baseline in IGA and 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 the respective 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 the respective 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 
the respective Baseline lesion count as a covariate.  
f P-value for the interaction term from an unranked analysis of covariance with factors of treatment, analysis center, treatment by analysis center interaction and 
the respective 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 Lesion Counts and Dichotomized IGA Success at Week 12 
 (Intent-to-Treat Population) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-Inflammatory Lesion Count – Absolute Change 
from Baseline 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
At Least Two Grade Reduction from Baseline and 
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  
the respective 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 the respective 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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Repeat Table 14.2.1.2 for the following table: 
 
Table 14.2.1.3: Primary Efficacy Analysis: Absolute Change from Baseline in Lesion Counts 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/E-ATRA 3%/0.1% 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/E-ATRA 3%/0.1% 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 3 of 4) 
 
Inflammatory Lesion Counts 
  
E-BPO/E-ATRA 3%/0.1% 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/E-ATRA 3%/0.1% 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) 
 
 


 
 
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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/E-ATRA 3%/0.1% 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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.3.1.1: Summary of Non-Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 1 of 4) 
 
Non-Inflammatory Lesion Counts 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.3.1.1: Summary of Non-Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 2 of 4) 
 
Non-Inflammatory Lesion Counts 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.3.1.1: Summary of Non-Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 3 of 4) 
 
Non-Inflammatory Lesion Counts 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.3.1.1: Summary of Non-Inflammatory Lesion Counts at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 4 of 4) 
 
Non-Inflammatory Lesion Counts 
  
E-BPO/E-ATRA 3%/0.1% 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 
Page 67 of 210  
CONFIDENTIAL 
Repeat Table 14.2.3.1.1 for the following table: 
 
Table 14.2.3.1.2: Summary of Non-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.” 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.3.2: Summary of Absolute Change in Non-Inflammatory Lesion Counts at Week 12 by Analysis Center 
 (Intent-to-Treat Population) 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.4.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 1 of 4) 
 
Investigator Global Assessment 
  
E-BPO/E-ATRA 3%/0.1% Cream 
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
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% 
 
 
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 
Table 14.2.4.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 2 of 4) 
 
Investigator Global Assessment 
  
E-BPO/E-ATRA 3%/0.1% 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% 
Two Grade Reduction from Baseline 
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
Two Grade Reduction from Baseline and 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 
Table 14.2.4.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 3 of 4) 
 
Investigator Global Assessment 
  
E-BPO/E-ATRA 3%/0.1% 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% 
Two Grade Reduction from Baseline 
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
Two Grade Reduction from Baseline and 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 
Table 14.2.4.1.1: Summary of Investigator Global Assessment at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 4 of 4) 
 
Investigator Global Assessment 
  
E-BPO/E-ATRA 3%/0.1% 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% 
Two Grade Reduction from Baseline 
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
Two Grade Reduction from Baseline and 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 
Page 73 of 210  
CONFIDENTIAL 
Repeat Table 14.2.4.1.1 for the following table: 
 
Table 14.2.4.1.2: Summary of Investigator Global Assessment at Each Evaluation (Per-Protocol Population) 
 
Change footnote to “Note: Missing values imputed using last observation carried forward.” 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 74 of 210  
CONFIDENTIAL 
Table 14.2.4.2: Summary of Investigator Global Assessment (Two Grade Reduction from Baseline and Clear or Almost Clear) 
at Week 12 by Analysis Center 
(Intent-to-Treat Population) 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.5.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 1 of 8) 
  
Age 
 
Age < Median Age (xx) 
 
 
Age >= Median Age (xx) 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.5.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 2 of 8) 
  
Age 
 
Age < 18 
 
 
18 <= Age < Median Age (xx) 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.5.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 3 of 8) 
  
Age 
 
9-11 years 
 
 
12-17 years 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.5.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 4 of 8) 
  
Age 
 
18-30 years 
 
 
>= 31 years 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.5.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 5 of 8) 
  
Sex 
 
Male 
 
 
Female 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.5.1: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 6 of 8) 
  
Ethnicitya 
 
Hispanic or Latino 
 
 
Not Hispanic or Latino 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 7 of 8) 
  
Race 
 
White 
 
 
Non-White 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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: Subgroup Summaries of Primary Endpoints 
 (Intent-to-Treat Population) 
(Page 8 of 8) 
  
Baseline IGA 
 
Moderate 
 
 
Severe 
 
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
Two Grade Reduction from Baseline in IGA and 
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 14.2.6.1: Sensitivity Analysis of Primary Endpoints: Absolute Change from Baseline in Lesion Counts and Dichotomized IGA Success at Week 12 
 (Intent-to-Treat Population) 
(Page 1 of 2) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-Inflammatory Lesion Count – Absolute Change 
from Baseline 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
At Least Two Grade Reduction from Baseline and 
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 the respective 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 the respective 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 14.2.6.1: Sensitivity Analysis of Primary Endpoints: Absolute Change from Baseline in Lesion Counts and Dichotomized IGA Success at Week 12 
 (Intent-to-Treat Population) 
(Page 2 of 2) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-Inflammatory Lesion Count – Absolute Change 
from Baseline 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
At Least Two Grade Reduction from Baseline and 
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  
the respective 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 the respective 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 14.2.7.1: Sensitivity Tipping-Point Analysis of the Primary Endpoint: Lesion Counts at Week 12 
 (Intent-to-Treat Population) 
 
 
Inflammatory Lesion Count 
 
 
Non-Inflammatory Lesion Count 
 
  
  
 
Shift Value 
 
  
  
 
P-Valuea 
 
  
  
 
Shift Value 
 
  
  
 
P-Valuea 
 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
x.xx 
 
x.xxx 
 
 
a  P-value from an analysis of covariance with factors of treatment group and analysis center and the respective Baseline lesion count as a covariate.  
  
Note: Multiple imputation (MCMC) used to impute missing values, with shift values applied to the imputed lesion count values from E-BPO/E-ATRA  
        3%/0.1% Cream group. Values have been adjusted for multiple imputation.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
{NOTE TO PROGRAMMER: ADJUST FOOTNOTE “a” TO THE FOLLOWING IF THE NON-PARAMETRIC ANLYSIS WAS CONSIDERED TO 
BE THE CORRECT ANALYSIS FOR THE PRIMARY EFFICACY ANLYSIS: “P-value from a ranked analysis of covariance with factors of treatment 
group and analysis center and the respective Baseline lesion count as a covariate.”} 
 
 


 
 
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Table 14.2.8.1: Secondary Efficacy Analyses 
 (Intent-to-Treat Population) 
(Page 1 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
At Least 4-Point Reduction on Item 1 (Pimples) of the 
PRE-FACE from Baseline to Week 12 
Success 
xx.x% 
xx.x% 
N/A 
x.xxxd 
Failure 
xx.x% 
xx.x% 
At Least 4-Point Reduction on Item 5 (Embarrassment) 
of the PRE-FACE from Baseline to Week 12 
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  
respective 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 respective 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 14.2.8.1: Secondary Efficacy Analyses 
 (Intent-to-Treat Population) 
(Page 2 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
 
a Least squares means, standard deviations and treatment p-value from an analysis of covariance with factors of treatment and analysis center and the  
respective 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 respective 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 14.2.8.1: Secondary Efficacy Analyses 
 (Intent-to-Treat Population) 
(Page 3 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% 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 
Non-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 
 
a Least squares means, standard deviations and treatment p-value from an analysis of covariance with factors of treatment and analysis center and the  
respective 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 respective 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) 
 
Repeat Table 14.2.8.1 for the following table: 
 
Table 14.2.8.2: Secondary Efficacy Analyses (Per-Protocol Population) 
 
Change footnote to “Note: Missing values imputed using last observation carried forward.” 
 
 


 
 
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Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
 (Intent-to-Treat Population) 
(Page 1 of 28) 
 
Rate the pimples on your face todaya 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
  
xx.x% 
  
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No pimples, 10 = Pimples as bad as you can imagine  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 28) 
 
Rate the pimples on your face todaya 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
  
xx.x% 
  
xx.x% 
 
Failure 
  
xx.x% 
  
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No pimples, 10 = Pimples as bad as you can imagine  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 3 of 28) 
 
Rate the pimples on your face todaya 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
  
xx.x% 
  
xx.x% 
 
Failure 
  
xx.x% 
  
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No pimples, 10 = Pimples as bad as you can imagine  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 4 of 28) 
 
Rate the pimples on your face todaya 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
  
xx.x% 
  
xx.x% 
 
Failure 
  
xx.x% 
  
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No pimples, 10 = Pimples as bad as you can imagine  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.9.1 Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 5 of 28) 
 
Rate the blackheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No blackheads, 10 = Blackheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 6 of 28) 
 
Rate the blackheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No blackheads, 10 = Blackheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 7 of 28) 
 
Rate the blackheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No blackheads, 10 = Blackheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 8 of 28) 
 
Rate the blackheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No blackheads, 10 = Blackheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.9.1 Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 9 of 28) 
 
Rate the whiteheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No whiteheads, 10 = Whiteheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 10 of 28) 
 
Rate the whiteheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No whiteheads, 10 = Whiteheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 11 of 28) 
 
Rate the whiteheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No whiteheads, 10 = Whiteheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 12 of 28) 
 
Rate the whiteheads on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No whiteheads, 10 = Whiteheads as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1 Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 13 of 28) 
 
Rate the redness on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No redness, 10 = Redness as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 14 of 28) 
 
Rate the redness on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No redness, 10 = Redness as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 15 of 28) 
 
Rate the redness on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No redness, 10 = Redness as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 16 of 28) 
 
Rate the redness on your face today 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = No redness, 10 = Redness as bad as you can imagine 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1 Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 17 of 28) 
 
Over the past seven days, rate how embarrassed you felt 
because of the acne on your facea 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 Success 
  
xx.x% 
  
xx.x% 
 Failure 
xx.x% 
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not embarrassed at all, 10 = Extremely embarrassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 18 of 28) 
 
Over the past seven days, rate how embarrassed you felt 
because of the acne on your facea 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
  
xx.x% 
  
xx.x% 
 
Failure 
  
xx.x% 
  
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not embarrassed at all, 10 = Extremely embarrassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 19 of 28) 
 
Over the past seven days, rate how embarrassed you felt 
because of the acne on your facea 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
  
xx.x% 
  
xx.x% 
 
Failure 
  
xx.x% 
  
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not embarrassed at all, 10 = Extremely embarrassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 20 of 28) 
 
Over the past seven days, rate how embarrassed you felt 
because of the acne on your facea 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
  
xx.x% 
  
xx.x% 
 
Failure 
  
xx.x% 
  
xx.x% 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not embarrassed at all, 10 = Extremely embarrassed 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1 Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 21 of 28) 
 
Over the past seven days, rate how self-conscious you felt 
because of the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 22 of 28) 
 
Over the past seven days, rate how self-conscious you felt 
because of the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 23 of 28) 
 
Over the past seven days, rate how self-conscious you felt 
because of the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 112 of 210  
CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 24 of 28) 
 
Over the past seven days, rate how self-conscious you felt 
because of the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not self-conscious at all, 10 = Extremely self-conscious 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 113 of 210  
CONFIDENTIAL 
Table 14.2.9.1 Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 25 of 28) 
 
Over the past seven days, rate how sad you felt because of 
the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not sad at all, 10 = Extremely sad 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 26 of 28) 
 
Over the past seven days, rate how sad you felt because of 
the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not sad at all, 10 = Extremely sad 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 27 of 28) 
 
Over the past seven days, rate how sad you felt because of 
the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not sad at all, 10 = Extremely sad 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.9.1: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 28 of 28) 
 
Over the past seven days, rate how sad you felt because of 
the acne on your face. 
  
E-BPO/E-ATRA 3%/0.1% 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 
At Least 4-Point Reduction from Baseline  
 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Multiple imputation used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
Note: 0 = Not sad at all, 10 = Extremely sad 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Repeat Table 14.2.9.1 for the following table: 
 
Table 14.2.9.2: Summary of Patient-Reported Evaluation of Facial Acne (PRE-FACE) at Each Evaluation (Per-Protocol Population) 
 
Change footnote to “Last observation carried forward used to impute missing values for only item 1 (pimples) and item 5 (embarrassment). 
 
 


 
 
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Table 14.2.10.1: Supportive Efficacy Analyses: PGI-TS, PGI-S, and PGI-C at Week 12 
 (Intent-to-Treat Population) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Treatment 
 
P-Value  
 
Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 12 
0 - I am very satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
x.xxxb 
1 - I am satisfied 
xx ( xx.x%) 
xx ( xx.x%) 
2 - I am neither satisfied nor 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%) 
Patient Global Impression of Symptom Severity (PGI-S) at Week 12 
0 - None: no pimples, clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
x.xxxb 
1 - Mild: very few pimples, almost clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Moderate: some pimples 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Severe: many pimples, almost no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Very severe: Large amount of pimples, no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
At Least “Minimally Improved” in PGI-C from Baseline to Week 12 
Success 
  
xx.x% 
  
xx.x% 
x.xxxa 
Failure 
  
xx.x% 
  
xx.x% 
 
a P-value from a logistic regression with factors of treatment group and analysis center. 
b P-value from a cumulative logistic regression with factors of treatment group and analysis center. 
Note:  No imputation of 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 14.2.11.1: Supportive Efficacy Analyses: Lesion Count and IGA 
 (Intent-to-Treat Population) 
(Page 1 of 3) 
  
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
At Least Two Grade Reduction from Baseline and 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective 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 14.2.11.1: Supportive Efficacy Analyses: Lesion Count and IGA 
 (Intent-to-Treat Population) 
(Page 2 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
At Least Two Grade Reduction from Baseline and 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective 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 14.2.11.1: Supportive Efficacy Analyses: Lesion Count and IGA 
 (Intent-to-Treat Population) 
(Page 3 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
Inflammatory Lesion Count –Absolute Change 
from Baseline to Week 2 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
Non-Inflammatory Lesion Count –Absolute Change 
from Baseline to Week 2 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
At Least Two Grade Reduction from Baseline and 
Achieving Clear or Almost Clear at Week 2 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective 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 14.2.12.1: Supportive Efficacy Analyses: PRE-FACE ASD Scores 
 (Intent-to-Treat Population) 
(Page 1 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
PRE-FACE Item 1 (Pimples) –Absolute Change 
from Baseline to Week 8d 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 2 (Blackheads) –Absolute Change 
from Baseline to Week 8 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 3 (Whiteheads) –Absolute Change 
from Baseline to Week 8 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 4 (Redness) –Absolute Change 
from Baseline to Week 8 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective Baseline lesion count as a covariate.   
d  Multiple imputation used to impute missing values for only item 1 (pimples).  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.12.1: Supportive Efficacy Analyses: PRE-FACE ASD Scores 
 (Intent-to-Treat Population) 
(Page 2 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
PRE-FACE Item 1 (Pimples) –Absolute Change 
from Baseline to Week 4d 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 2 (Blackheads) –Absolute Change 
from Baseline to Week 4 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 3 (Whiteheads) –Absolute Change 
from Baseline to Week 4 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 4 (Redness) –Absolute Change 
from Baseline to Week 4 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective Baseline lesion count as a covariate.   
d  Multiple imputation used to impute missing values for only item 1 (pimples).  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.12.1: Supportive Efficacy Analyses: PRE-FACE ASD Scores 
 (Intent-to-Treat Population) 
(Page 3 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
PRE-FACE Item 1 (Pimples) –Absolute Change 
from Baseline to Week 2d 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 2 (Blackheads) –Absolute Change 
from Baseline to Week 2 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 3 (Whiteheads) –Absolute Change 
from Baseline to Week 2 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 4 (Redness) –Absolute Change 
from Baseline to Week 2 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective Baseline lesion count as a covariate.   
d  Multiple imputation used to impute missing values for only item 1 (pimples).  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.13.1: Supportive Efficacy Analyses: PRE-FACE AID Scores 
 (Intent-to-Treat Population) 
(Page 1 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
PRE-FACE Item 5 (Embarrassed) –Absolute Change 
from Baseline to Week 8d 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 6 (Self-Conscious) –Absolute 
Change from Baseline to Week 8 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 7 (Sad) –Absolute Change 
from Baseline to Week 8 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective Baseline lesion count as a covariate.   
d  Multiple imputation used to impute missing values for only item 5 (embarrassed).  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.13.1: Supportive Efficacy Analyses: PRE-FACE AID Scores 
 (Intent-to-Treat Population) 
(Page 2 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
PRE-FACE Item 5 (Embarrassed) –Absolute Change 
from Baseline to Week 4d 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 6 (Self-Conscious) –Absolute 
Change from Baseline to Week 4 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 7 (Sad) –Absolute Change 
from Baseline to Week 4 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective Baseline lesion count as a covariate.   
d  Multiple imputation used to impute missing values for only item 5 (embarrassed).  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
 
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Table 14.2.13.1: Supportive Efficacy Analyses: PRE-FACE AID Scores 
 (Intent-to-Treat Population) 
(Page 3 of 3) 
  
 
E-BPO/E-ATRA 
 
3%/0.1% Cream  
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
 
Skewness 
 
P-Value 
  
 
Treatment 
 
P-Value  
 
PRE-FACE Item 5 (Embarrassed) –Absolute Change 
from Baseline to Week 2d 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 6 (Self-Conscious) –Absolute 
Change 
LSMeana 
xx.x 
xx.x 
x.xxxb 
x.xxxa 
LSSDa 
xx.xx 
xx.xx 
x.xxxc 
PRE-FACE Item 7 (Sad) –Absolute Change 
from Baseline to Week 2 
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  
respective 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.  
c P-value from a ranked analysis of covariance with factors of treatment and analysis center and the respective Baseline lesion count as a covariate.   
d  Multiple imputation used to impute missing values for only item 5 (embarrassed).  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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Table 14.2.14.1: 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 acne symptoms 
changed? 
  
E-BPO/E-ATRA 3%/0.1% 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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Table 14.2.14.1: 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 acne symptoms 
changed? 
  
E-BPO/E-ATRA 3%/0.1% 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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Table 14.2.15.1: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 1 of 2) 
 
Right now, my acne symptoms are: 
  
E-BPO/E-ATRA 3%/0.1% Cream 
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Baseline 
n 
xx  
xx 
0 - None: no pimples, clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild: very few pimples, almost clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate: some pimples 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe: many pimples, almost no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Very severe: Large amount of pimples, no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
Week 2 
n 
xx  
xx 
0 - None: no pimples, clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild: very few pimples, almost clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate: some pimples 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe: many pimples, almost no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Very severe: Large amount of pimples, no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
Week 4 
n 
xx  
xx 
0 - None: no pimples, clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild: very few pimples, almost clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate: some pimples 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe: many pimples, almost no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Very severe: Large amount of pimples, no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
 
  
Note:  No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.2.15.1: Summary of Patient Global Impression of Symptom Severity (PGI-S) at Each Evaluation 
  (Intent-to-Treat Population) 
(Page 2 of 2) 
 
Right now, my acne symptoms are: 
  
E-BPO/E-ATRA 3%/0.1% Cream 
 
(N=xxx)  
 
  
Vehicle Cream  
 
(N=xxx)  
 
Week 8 
n 
xx  
xx 
0 - None: no pimples, clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild: very few pimples, almost clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate: some pimples 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe: many pimples, almost no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Very severe: Large amount of pimples, no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
Week 12 
n 
xx  
xx 
0 - None: no pimples, clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
1 – Mild: very few pimples, almost clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
2 – Moderate: some pimples 
xx ( xx.x%) 
xx ( xx.x%) 
3 – Severe: many pimples, almost no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
4 – Very severe: Large amount of pimples, no clear skin 
xx ( xx.x%) 
xx ( xx.x%) 
 
  
Note:  No imputation of missing values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
 
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Table 14.2.16.1: 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 acne 
treatment: 
  
E-BPO/E-ATRA 3%/0.1% 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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CONFIDENTIAL 
Table 14.2.16.1: 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 acne 
treatment: 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.17.1: Summary of Acne-QoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 1 of 4) 
 
Self-Perception Domain 
  
E-BPO/E-ATRA 3%/0.1% 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. 
 
Self-Perception domain calculated from the questions 1, 2, 3, 6, and 10. 
 
Role-Emotional domain calculated from questions 4, 5, 7, 8, and 9.  
 
Role-Social domain calculated from questions 11, 12, 13, and 14.  
 
Acne Symptoms domain calculated from questions 15, 16, 17, 18, and 19. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.17.1: Summary of Acne-QoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 2 of 4) 
 
Role-Emotional Domain 
  
E-BPO/E-ATRA 3%/0.1% 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. 
 
Self-Perception domain calculated from the questions 1, 2, 3, 6, and 10. 
 
Role-Emotional domain calculated from questions 4, 5, 7, 8, and 9.  
 
Role-Social domain calculated from questions 11, 12, 13, and 14.  
 
Acne Symptoms domain calculated from questions 15, 16, 17, 18, and 19. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.17.1: Summary of Acne-QoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 3 of 4) 
 
Role-Social Domain 
  
E-BPO/E-ATRA 3%/0.1% 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. 
 
Self-Perception domain calculated from the questions 1, 2, 3, 6, and 10. 
 
Role-Emotional domain calculated from questions 4, 5, 7, 8, and 9.  
 
Role-Social domain calculated from questions 11, 12, 13, and 14.  
 
Acne Symptoms domain calculated from questions 15, 16, 17, 18, and 19. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.2.17.1: Summary of Acne-QoL Questionnaire Responses at Baseline and Week 12 
 (Intent-to-Treat Population) 
(Page 4 of 4) 
 
Acne Symptoms Domain 
  
E-BPO/E-ATRA 3%/0.1% 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. 
 
Self-Perception domain calculated from the questions 1, 2, 3, 6, and 10. 
 
Role-Emotional domain calculated from questions 4, 5, 7, 8, and 9.  
 
Role-Social domain calculated from questions 11, 12, 13, and 14.  
 
Acne Symptoms domain calculated from questions 15, 16, 17, 18, and 19. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
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Table 14.3.0.1: Summary of Extent of Exposure 
 (Safety Population) 
 
  
E-BPO/E-ATRA 3%/0.1% 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%) 
No 
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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 1 of 14) 
 
Erythema 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 2 of 14) 
 
Erythema 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 3 of 14) 
 
Scaling 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 4 of 14) 
 
Scaling 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 5 of 14) 
 
Pigmentation 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 6 of 14) 
 
Pigmentation 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 7 of 14) 
 
Dryness 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 8 of 14) 
 
Dryness 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 9 of 14) 
 
Itching 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 10 of 14) 
 
Itching 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 11 of 14) 
 
Burning 
  
E-BPO/E-ATRA 3%/0.1% 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) 
 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 12 of 14) 
 
Burning 
  
E-BPO/E-ATRA 3%/0.1% 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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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 13 of 14) 
 
Stinging 
  
E-BPO/E-ATRA 3%/0.1% 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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CONFIDENTIAL 
Table 14.3.1.1: Summary of  Cutaneous Signs and Local Tolerability at Each Evaluation 
 (Safety Population) 
 (Page 14 of 14) 
 
Stinging 
  
E-BPO/E-ATRA 3%/0.1% 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/E-ATRA  
 
3%/0.1% 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 occurring 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 14.3.1.2.1: Summary of Treatment-Emergent Adverse Event Characteristics 
 (Safety Population) 
(Page 2 of 2) 
  
 
E-BPO/E-ATRA  
 
3%/0.1% 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 occurring 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/E-ATRA  
 
3%/0.1% 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 occurring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
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/E-ATRA 3%/0.1% 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 occurring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
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/E-ATRA 3%/0.1% 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 occurring 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 14.3.1.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
 (Safety Population) 
(Page 1 of 2) 
  
 
E-BPO/E-ATRA  
 
3%/0.1% 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 occurring 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 14.3.1.3.1: Summary of Treatment-Emergent Serious Adverse Event Characteristics 
 (Safety Population) 
(Page 2 of 2) 
  
 
E-BPO/E-ATRA  
 
3%/0.1% 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 occurring 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 14.3.1.3.2: 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/E-ATRA  
 
3%/0.1% 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 occurring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
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/E-ATRA 3%/0.1% 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 occurring prior to first application. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
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/E-ATRA 3%/0.1% 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 occurring 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: Summary of Vital Signs 
 (Safety Population) 
(Page 1 of 5) 
  
Temperature (°C) 
 
E-BPO/E-ATRA 3%/0.1% 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: Summary of Vital Signs 
 (Safety Population) 
(Page 2 of 5) 
  
Respiratory Rate (breaths/min) 
 
E-BPO/E-ATRA 3%/0.1% 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: Summary of Vital Signs 
 (Safety Population) 
(Page 3 of 5) 
  
Systolic Blood Pressure (mmHg) 
 
E-BPO/E-ATRA 3%/0.1% 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: Summary of Vital Signs 
 (Safety Population) 
(Page 4 of 5) 
  
Diastolic Blood Pressure (mmHg) 
 
E-BPO/E-ATRA 3%/0.1% 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: Summary of Vital Signs 
 (Safety Population) 
(Page 5 of 5) 
  
Heart Rate (beats/min) 
 
E-BPO/E-ATRA 3%/0.1% 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/E-ATRA 3%/0.1% 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 3% 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 acne treatment: 
 
E-BPO/E-ATRA 3%/0.1% 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%) 
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%) 
 
 
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 2 of 2) 
 
Right now, how bothered are you by the side effects of 
your acne treatment: 
 
E-BPO/E-ATRA 3%/0.1% Cream 
 
(N=xxx)  
 
 
Vehicle Cream 
 
(N=xxx)  
 
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 14.2.7.2: Sensitivity Tipping-Point Analysis of the Primary Endpoint: Treatment Success 
in IGA at Week 12 (Intent-to-Treat Population) .................................172 


 
 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 172 of 210  
CONFIDENTIAL 
Figure 14.2.7.2: Sensitivity Tipping-Point Analysis of the Primary Endpoint: Treatment Success in IGA at Week 12 
(Intent-to-Treat Population) 
 
 
  
 
  
 
 
Note:  The horizontal and vertical axes indicate the number of successes that can potentially be observed among nonrespondents in the each treatment group. 
  
Each plotted point indicates the number of imputed successes in each treatment group that would alter the study’s conclusion with the staircase region  
  
indicating the tipping points of the study. 
  
The red lines represent average number of imputed successes from the primary analysis using multiple imputation (MCMC) to impute missing  
  
values. 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
 
 
TOOL.AN.10-01.01 Statistical Analysis Plan 
Template 
Page 173 of 210 
 
CONFIDENTIAL 
14. INDEX OF PLANNED LISTINGS 
Listing 16.1.7: Randomization Scheme .......................................................................................175 
Listing 16.2.1.1: End of Study Information .................................................................................176 
Listing 16.2.2.1: Inclusion/Exclusion Criteria .............................................................................177 
Listing 16.2.2.2: Screen Failure ...................................................................................................178 
Listing 16.2.2.3: Protocol Deviations ..........................................................................................179 
Listing 16.2.3: Analysis Populations ...........................................................................................180 
Listing 16.2.4.1: Subject Demographic Information ...................................................................181 
Listing 16.2.4.2.1: Unique Medical/Surgical History Coded to MedDRA System Organ Classes 
and Preferred Terms ............................................................................182 
Listing 16.2.4.2.2: Medical/Surgical History...............................................................................183 
Listing 16.2.4.3.1: Unique Medication Names Coded to WHO Drug Global Dictionary ATC 
Level 2 Terms and Preferred Names ...................................................184 
Listing 16.2.4.3.2: Prior and Concomitant Medications ..............................................................185 
Listing 16.2.4.4.1: Unique Procedure/Therapy Names Coded to MedDRA System Organ Classes 
and Preferred Terms ............................................................................186 
Listing 16.2.4.4.2: Prior and Concomitant Procedures/Therapies ...............................................187 
Listing 16.2.5.1: Study Visit Compliance ....................................................................................188 
Listing 16.2.5.2: Subject Dosing Compliance .............................................................................189 
Listing 16.2.5.3: Subject Dosing Deviations ...............................................................................190 
Listing 16.2.5.4: Study Medication Accountability Log .............................................................191 
Listing 16.2.5.5: Photography ......................................................................................................192 
Listing 16.2.6.1: Investigator Global Assessment .......................................................................193 
Listing 16.2.6.2: Lesion Counts ...................................................................................................194 
Listing 16.2.6.3.1: Acne-QoL Descriptions .................................................................................195 
Listing 16.2.6.3.2: Acne-QoL ......................................................................................................197 
Listing 16.2.6.3.3: Acne-QoL Domain Scores ............................................................................198 
Listing 16.2.6.4: PRO - Patient Reported Evaluation of Facial Acne (PRE-FACE) ...................199 
Listing 16.2.6.5: PRO - Patient Reported Impression of Symptom Severity (PGI-S) ................200 
Listing 16.2.6.6: PRO – Patient Global Impression of Change (PGI-C), Patient Global 
Impression of Treatment Satisfaction (PGI-TS), Patient Global 
Impression of Treatment Side-Effects (PGI-SE) ................................201 


 
 
 
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CONFIDENTIAL 
Listing 16.2.7.1: Cutaneous Signs and Local Tolerability...........................................................202 
Listing 16.2.7.2.1: Unique Adverse Events Coded to MedDRA System Organ Classes and 
Preferred Terms ...................................................................................203 
Listing 16.2.7.2.2: Pre-Treatment Adverse Events ......................................................................204 
Listing 16.2.7.2.3: Treatment-Emergent Adverse Events ............................................................205 
Listing 16.2.7.2.4: Serious Adverse Events .................................................................................206 
Listing 16.2.7.2.5: Subjects Who Prematurely Discontinued Study and/or Discontinued Study 
Drug Due to Adverse Events...............................................................207 
Listing 16.2.8.1: Urine Pregnancy Tests ......................................................................................208 
Listing 16.2.8.2: Physical Examination .......................................................................................209 
Listing 16.2.8.3: Vital Signs ........................................................................................................210 


 
 
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CONFIDENTIAL 
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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CONFIDENTIAL 
Listing 16.2.1.1: End of Study Information 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                       Date of Study 
                                                       Completion/       Did Subject                              Continue to the 
                           Date of First Date of 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 xxxxxxx xxxx 
                                                                                                                xxxxxxxx 
 
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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Page 177 of 210  
CONFIDENTIAL 
 
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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CONFIDENTIAL 
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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CONFIDENTIAL 
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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CONFIDENTIAL 
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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CONFIDENTIAL 
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. 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
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. 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
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, Acne Diagnosis (all Acne MH will appear first), Onset Date, End Date, Verbatim Term  
 
 


 
 
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CONFIDENTIAL 
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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Page 185 of 210  
CONFIDENTIAL 
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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CONFIDENTIAL 
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. 
 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
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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CONFIDENTIAL 
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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CONFIDENTIAL 
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. 
 


 
 
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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. 
 


 
 
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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 
 
 


 
 
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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 194 of 210  
CONFIDENTIAL 
Listing 16.2.6.2: Lesion Counts 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                                                  Total                                   Total 
                                                  Date of        Evaluator     Inflammatory                          Non-Inflammatory 
Subject  Age/Sex  Eval       Visit                Assessment     Initials      Lesion Count      Nodules/Cysts         Lesion Count 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx xxxxx           xxxxxxxxxx      xxx              xx                  xx                   xx 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx xxxxx           xxxxxxxxxx      xxx              xx                  xx                   xx 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx xxxxx           xxxxxxxxxx      xxx              xx                  xx                   xx 
 
xxxxxx     xxxx   xxxxxxxx   xxxxxxxxx            xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx x               xxxxxxxxxx      xxx              xx                  xx                   xx 
                             xxxx xxxxx           xxxxxxxxxx      xxx              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 195 of 210  
CONFIDENTIAL 
 
Listing 16.2.6.3.1: Acne-QoL Descriptions 
                                                            (Page 1 of 2) 
 
______________________________________________________________________________________________________________________________________ 
 
Number  Acne-QoL Question 
______________________________________________________________________________________________________________________________________ 
 
1       In the past WEEK, how unattractive did you feel because of your facial acne? 
 
2       In the past WEEK, how embarrassed did you feel because of your facial acne? 
 
3       In the past WEEK, how self-conscious (uneasy about oneself) did you feel about your facial acne? 
 
4       In the past WEEK, how upset were you about having facial acne? 
 
5       In the past WEEK, how annoyed did you feel at having to spend time every day cleaning and treating your face because of your  
        facial acne? 
 
6       In the past WEEK, how dissatisfied with your self-appearance did you feel because of your facial acne? 
 
7       In the past WEEK, how concerned or worried were you about not looking your best because of your facial acne? 
 
8       In the past WEEK, how concerned or worried were you that your acne medication/products were working fast enough in clearing up  
        the acne on your face? 
 
9       In the past WEEK, how bothered did you feel about the need to always have medication or cover-up available for the acne on  
        your face? 
 
10      In the past WEEK, how much was your self-confidence (sure of yourself) negatively affected because of your facial acne? 
 
11      In the past WEEK, how concerned or worried were you about meeting new people because of your facial acne? 
 
12      In the past WEEK, how concerned or worried were you about going out in public because of your facial acne? 
 
13      In the past WEEK, how much was socializing with people a problem for you because of your facial acne? 
 
14      In the past WEEK, how much was interacting with the opposite sex (or same sex if gay or lesbian) a problem for you because of  
        your facial acne? 
 
15      In the past WEEK, how many bumps did you have on your face?      
         
16      In the past WEEK, how many bumps full of pus did you have on your face?                                  
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
 
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CONFIDENTIAL 
Listing 16.2.6.3.1: Acne-QoL Descriptions 
                                                            (Page 1 of 2) 
 
______________________________________________________________________________________________________________________________________ 
 
Number  Acne-QoL Question 
______________________________________________________________________________________________________________________________________ 
 
17      In the past WEEK, how much scabbing from your facial acne did you have? 
 
18      In the past WEEK, how concerned or worried were you about scarring from your facial acne? 
 
19      In the past WEEK, how oily was your facial skin? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
Page 197 of 210  
CONFIDENTIAL 
Listing 16.2.6.3.2: Acne-QoL 
                                                             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   
______________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxxx     xxxxxxxx   xxxxxxxxxx   xxxxxxxxxx   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    
 
xxxxxx    xxxxx     xxxxxxxx   xxxxxxxxxx   xxxxxxxxxx   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    
 
xxxxxx    xxxxx     xxxxxxxx   xxxxxxxxxx   xxxxxxxxxx   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    
 
xxxxxx    xxxxx     xxxxxxxx   xxxxxxxxxx   xxxxxxxxxx   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    
 
xxxxxx    xxxxx     xxxxxxxx   xxxxxxxxxx   xxxxxxxxxx   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    
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: Questions 1-14, 18-19: 0=Extremely, 1=Very Much, 2=Quite A Bit, 3=A Good Bit, 4=Somewhat, 5=A Little Bit, 6=Not At All. 
      Questions 15-17: 0=Extensive, 1=A Whole Lot, 2=A Lot, 3=A Moderate Amount, 4=Some, 5=Very Few, 6=None. 
      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 198 of 210  
CONFIDENTIAL 
Listing 16.2.6.3.3: Acne-QoL Domain Scores 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                        Date of      
Subject  Age/Sex  Eval      Visit      Assessment      Self Perception      Role-social        Role-emotional           Acne Symptoms    
______________________________________________________________________________________________________________________________________ 
 
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 
 
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 199 of 210  
CONFIDENTIAL 
 
 
Listing 16.2.6.4: PRO - Patient Reported Evaluation of Facial Acne (PRE-FACE) 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                      Date of                                                          
Subject Age/Sex  Eval      Visit      Assessment  Category       Assessment                                              Result             
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx    xxxxxxxx  xxxxxxxxx  xxxxxxxxxx  Signs/Symptoms  Rate the pimples on your face today                       x 
 
                                                                  Rate the blackheads on your face today                    x 
 
                                                                  Rate the whiteheads on your face today                    x 
 
                                                                  Rate the redness on your face today                       x 
 
                                                  Impacts         Over the past seven days, rate how embarrassed            x 
                                                                  you felt because of the acne on your face 
 
                                                                  Over the past seven days, rate how sad you felt           x 
                                                                  because of the acne on your face. 
 
                           xxxx x     xxxxxxxxxx  Signs/Symptoms  Rate the pimples on your face today                       x 
 
                                                                  Rate the blackheads on your face today                    x 
 
                                                                  Rate the whiteheads on your face today                    x 
 
                                                                  Rate the redness on your face today                       x 
 
                                                  Impacts         Over the past seven days, rate how embarrassed            x 
                                                                  you felt because of the acne on your face 
 
                                                                  Over the past seven days, rate how sad you felt           x 
                                                                  because of the acne on your face. 
 
 
 
 
 
  
 
 
 
                                                
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number, Category (in order presented on eCRF), and Assessment (in order presented on eCRF). 


 
 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
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CONFIDENTIAL 
Listing 16.2.6.5: PRO - Patient Reported Impression of Symptom Severity (PGI-S) 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                       Date of                                                          
Subject Age/Sex  Eval      Visit       Assessment    Assessment                                          Result             
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx    xxxxxxxx  xxxxxxxxx   xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
  
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
                                                                   
                           xxxx xx     xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
xxxxxx   xxxx    xxxxxxxx  xxxxxxxxx   xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
  
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
                                                                   
                           xxxx xx     xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
 
 
 
  
 
 
 
xxxxxx   xxxx    xxxxxxxx  xxxxxxxxx   xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
  
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
 
                           xxxx x      xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
                                                                   
                           xxxx xx     xxxxxxxxxx    Right now, my acne symptoms are                     xxxxxxx xx xxxxxxx xxxx xxx 
                                                
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Visit Number. 
 
 


 
 
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CONFIDENTIAL 
Listing 16.2.6.6: PRO – Patient Global Impression of Change (PGI-C), Patient Global Impression of Treatment Satisfaction (PGI-TS), 
Patient Global Impression of Treatment Side-Effects (PGI-SE) 
                                                             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    PGI-C           CHANGE           xxxxxxxxxxxxxx             
                                                              PGI-TS          SATISFACTION     xxxxxx xxx xxxx    
                                                              PGI-SE          SIDE-EFFECTS     xxxxxxxxxxxxxx       
                                                                              
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           CHANGE           xxxxxxxxxxxxxx             
                                                              PGI-TS          SATISFACTION     xxxxxx xxx xxxx    
                                                              PGI-SE          SIDE-EFFECTS     xxxxxxxxxxxxxx       
                                                                              
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           CHANGE           xxxxxxxxxxxxxx             
                                                              PGI-TS          SATISFACTION     xxxxxx xxx xxxx    
                                                              PGI-SE          SIDE-EFFECTS     xxxxxxxxxxxxxx       
                                                                              
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           CHANGE           xxxxxxxxxxxxxx             
                                                              PGI-TS          SATISFACTION     xxxxxx xxx xxxx    
                                                              PGI-SE          SIDE-EFFECTS     xxxxxxxxxxxxxx       
                                  
xxxxxx        xxxx       xxxxxxx    xxxxxxxxx   xxxxxxxxxx    PGI-C           CHANGE           xxxxxxxxxxxxxx             
                                                              PGI-TS          SATISFACTION     xxxxxx xxx xxxx    
                                                              PGI-SE          SIDE-EFFECTS     xxxxxxxxxxxxxx       
 
                                    xxxxxxxxx   xxxxxxxxxx    PGI-C           CHANGE           xxxxxxxxxxxxxx             
                                                              PGI-TS          SATISFACTION     xxxxxx xxx xxxx    
                                                              PGI-SE          SIDE-EFFECTS     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 202 of 210  
CONFIDENTIAL 
Listing 16.2.7.1: Cutaneous Signs and Local Tolerability 
                                                             Treatment Arm 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                         
                                                                       Evaluator                                            
Subject  Age/Sex  Eval          Visit           Date of Assessment     Initials      Test                           Result      
______________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxx    xxxxxxxx      xxxxxxxxx       xxxxxxxxxx             xxx           Erythema                       xxxxxxxx          
                                                                                     Scaling                        xxx xxxx                  
                                                                                     Pigmentation                   xxxxxxxxxxxx    
                                                                                     Dryness                        xxxxxxxxxxx 
                                                                                     Itching                        xxxxxxxxxxx 
                                                                                     Burning                        xxxxxxxxxxx 
                                                                                     Stinging                       xxxxxxxxxxx 
                                                                           
                                                                          
                                xxxx x          xxxxxxxxxx     xxx                   Erythema                       xxxxxxxx          
                                                                                     Scaling                        xxx xxxx                  
                                                                                     Pigmentation                   xxxxxxxxxxxx    
                                                                                     Dryness                        xxxxxxxxxxx 
                                                                                     Itching                        xxxxxxxxxxx 
                                                                                     Burning                        xxxxxxxxxxx 
                                                                                     Stinging                       xxxxxxxxxxx 
                                      
                                xxxx x          xxxxxxxxxx     xxx                   Erythema                       xxxxxxxx          
                                                                                     Scaling                        xxx xxxx                  
                                                                                     Pigmentation                   xxxxxxxxxxxx    
                                                                                     Dryness                        xxxxxxxxxxx 
                                                                                     Itching                        xxxxxxxxxxx 
                                                                                     Burning                        xxxxxxxxxxx 
                                                                                     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 203 of 210  
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 
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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. 


 
 
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Page 205 of 210  
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 206 of 210  
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 207 of 210  
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 208 of 210  
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 209 of 210  
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 210 of 210  
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).