Human Comedogenicity Test
Phase: NA
Conditions: Comedogenicity
Sponsor: Johnson & Johnson Consumer Inc. (J&JCI)

PROTOCOL # GATT CO-161115154122-SACT 
 
 
 
PROTOCOL TITLE 
Human Comedogenicity Test 
PROTOCOL 
IDENTIFICATION : 
CO-161115154122-SACT 
DATE & VERSION : 
10 February 2017, Final Version (1.0) 
SPONSOR : 
 
 
 
STUDY SITE : 
 
 
 
 
PRINCIPAL 
INVESTIGATOR (PI): 
Michael J. Babcock, MD, FAAD 
STUDY MANAGER: 
 
STUDY DIRECTOR: 
 
DEPARTMENT HEAD: 
 
DESIGNATED 
PHYSICIAN 
REPRESENTATIVE 
(DPR): 
 
 
 
 
 
 
 
This study will be performed in compliance with International Conference on Harmonization Guidelines 
for Good Clinical Practice (E6). 
 
 
 
 
 
 
 
 
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CONFIDENTIAL: The information in this document contains trade secrets and commercial information that are privileged 
or confidential and may not be disclosed unless such disclosure is required by Federal or State law or regulations. Subject 
to the foregoing, this information may be disclosed only to those persons involved in the study who have a need to know, 
but all such persons must be instructed not to further disseminate this information to others. These restrictions on 
disclosure will apply equally to all future information supplied to you, which is indicated as privileged or confidential. 

Protocol Title: Human Comedogenicity Test 
Protocol identification: CO-161115154122-SACT- date: 10FEB2017 Final Version (1) 
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VERSION TRACKING 
 
VERSION 
DATE 
STATE 
REASON FOR CHANGE 
DESCRIPTION OF CHANGE 
1.0 
10FEB2017 
FINAL 
New 
N/A 

Protocol Title: Human Comedogenicity Test 
Protocol identification: CO-161115154122-SACT- date: 10FEB2017 Final Version (1) 
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SYNOPSIS 
 
PROTOCOL IDENTIFICATION 
CO-161115154122-SACT 
PROTOCOL TITLE 
Human Comedogenicity Test 
PRINCIPAL INVESTIGATOR 
Michael J. Babcock, MD, FAAD 
STUDY SITE 
 
 
 
 
OBJECTIVE 
To determine the potential of a test material to 
induce comedones. 
STUDY DESIGN 
A single center, evaluator blinded, randomized 
study to test the potential of comedogenicity of 
test products. 
The backs of volunteers with a propensity to 
comedone formation are patched with the test 
material three times a week for a four-week 
period. At the last visit, a follicular biopsy is 
performed on each site of each subject, 
Microcomedones on the slides are counted and 
the product categorized as to comedogenic 
potential.” 
STUDY POPULATION 
Males and Females aged 18-45 years old who 
meet the eligibility criteria of the study. 
SAMPLE SIZE 
Enroll up to 18 volunteers satisfying the 
inclusion and exclusion criteria. 15 subjects 
completing the study is sufficient. 
INVESTIGATIONAL STUDY MATERIALS 
Test Material (TM) information will be provided 
in protocol addendum for each test panel. 
DOSE AND MODE OF APPLICATION 
Test materials and Negative Control will be 
applied with occlusive or semi-occlusive  
patches. The patch type may be changed if 
irritation develops. Occlusive patches consist of 
a non-woven cotton pad (e.g., Webril®) covered 
by Blenderm tape and held securely to skin on 
all sides with a porous, hypoallergenic tape (e.g., 
Micropore®). Semi-occlusive patches consist of a 
non-woven cotton pad (e.g., Webril®) covered 
and held securely to skin on all sides with a 
porous, hypoallergenic tape (e.g., Micropore®). 
Patches are placed on the back no closer than 2 
cm apart. The cotton pads used for the patches 

Protocol Title: Human Comedogenicity Test 
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are approximately 4 cm2 in area, and are dosed 
with a quantity of test material as follows 
(unless otherwise instructed by the Sponsor): 
Liquids and fragrances approximately 100 μl; 
Creams, lotions, petroleum, etc. approximately 
100 μl; Paper or other solid materials will cover 
the pad area. 
STUDY DURATION 
The study will consist of approximately 13 visits: 
Visit 1 (Screening/Baseline), Visit 2 through 12: 
Patching and Grading, Make-up visit, and Visit 
13 (Grading and Follicular Biopsy collection visit) 
METHODOLOGY 
Skin sites on the back in the interscapular region 
will be utilized as application sites. The test 
material(s) and negative control will be assigned 
to specific sites for each subject be assigned to 
specific site for each subject according to a 
randomization scheme and will be applied 
repetitively under occlusive/semi-occlusive 
patches for a period of 28 days. 
SAFETY AND ADVERSE EVENTS 
Any Adverse Event (AE) (including Serious 
Adverse Events (SAE) related or unrelated to the 
test material(s) or study participation must be 
documented as required (occurrence date, site, 
outcome, and assessment of causality, severity, 
and relatedness). 
SAEs must be reported immediately and relevant 
supportive documentation must be                 
sent to the Study Manager or designee within 24 
hours of the site becoming aware of the event. 
See section 10.3.3. for reporting timelines. 

Protocol Title: Human Comedogenicity Test 
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LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
AE 
Adverse Event 
CRF 
Case Report Form 
EDC 
Electronic Data Capture 
ICH GCP 
International Conference on Harmonisation Good Clinical Practice 
ICD 
Informed Consent Document 
IEC 
Independent Ethics Committee 
IP 
Investigational Product 
IRB 
Institutional Review Board 
PI 
Principal Investigator 
PP 
Per-Protocol 
PQC 
Product Quality Complaint 
SI 
Sub-Investigator 
SAE 
Serious Adverse Event 
TEAE 
Treatment Emergent Adverse Event 

Protocol Title: Human Comedogenicity Test 
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TABLE OF CONTENTS 
1 
BACKGROUND .................................................................................................................................... 8 
2 
RATIONALE ......................................................................................................................................... 8 
3 
OBJECTIVE(S) ...................................................................................................................................... 8 
4 
OVERALL STUDY DESIGN AND PLAN DESCRIPTION ................................................................................. 8 
5 
STUDY DURATION ............................................................................................................................ 10 
6 
SUBJECT SELECTION AND ENROLLMENT .......................................................................................... 10 
6.1 
INFORMED CONSENT ............................................................................................................... 10 
6.2 
STUDY POPULATION ................................................................................................................. 11 
6.2.1 
Inclusion Criteria............................................................................................................... 11 
6.2.2 
Exclusion Criteria .............................................................................................................. 12 
6.3 
CONCURRENT PRODUCTS ........................................................................................................ 13 
6.4 
CONCURRENT MEDICATION ..........................................................................................................13 
6.5 
SCREENING FAILURE ................................................................................................................. 13 
7 
SAMPLE SIZE DETERMINATION ..............................................................................................................13 
8 
INVESTIGATIONAL STUDY MATERIALS ............................................................................................. 13 
8.1 
IDENTITY OF INVESTIGATIONAL STUDY MATERIALS ................................................................. 13 
8.2 
RANDOMIZATION ..................................................................................................................... 14 
8.3 
BLINDING PROCEDURE ............................................................................................................. 14 
8.4 
STUDY MATERIAL STORAGE AND ACCOUNTABILITY ....................................................................14 
8.5 
PRODUCT QUALITY COMPLAINTS .................................................................................................15 
8.6 
APPLICATION OF THE INVESTIGATIONAL PRODUCT ................................................................. 15 
9 
INVESTIGATIONAL PLAN ................................................................................................................... 15 
9.1 
STUDY PROCEDURES AND EVALUATION SCHEDULE ....................................................................15 
9.2 
STUDY INSTRUMENT(S) ............................................................................................................ 18 
9.3 
SUBJECT COMPLETION/WITHDRAWAL .........................................................................................18 
9.3.1 
Subject Completion .......................................................................................................... 19 
9.3.2 
Subject Withdrawal .......................................................................................................... 19 
10 
STATISTICAL ANALYSIS PLAN ........................................................................................................ 19 
11 
MANAGEMENT OF INTERCURRENT EVENTS ................................................................................ 20 
11.1 
AMENDMENTS TO THE PROTOCOL ...............................................................................................20 
11.2 
PROTOCOL DEVIATIONS ........................................................................................................... 20 
11.3 
ADVERSE EVENT REPORTING ................................................................................................... 20 
11.3.1 
Introduction ..................................................................................................................... 20 
11.3.2 
Definitions ........................................................................................................................ 21 

Protocol Title: Human Comedogenicity Test 
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11.3.2.1 
Adverse Event (AE) ........................................................................................................21 
11.3.2.2 
Serious Adverse Event (SAE) .........................................................................................22 
11.3.2.3 
Severity ..................................................................................................................... 22 
11.3.2.4 
Causality Assessment ............................................................................................... 23 
11.3.3 
Procedures for Reporting Adverse Events ........................................................................ 23 
11.3.4 
Monitoring and Resolution of Adverse Events ................................................................. 25 
11.3.4.1 
Non-Serious AEs ............................................................................................................25 
11.3.4.2 
Serious AEs (SAEs) .................................................................................................... 25 
11.3.4.3 
Resolution ................................................................................................................ 25 
11.3.5 
Exposure In Utero ............................................................................................................. 25 
12 
ETHICAL CONSIDERATIONS ................................................................................................................26 
12.1 
STUDY SUBMISSION TO INSTITUTIONAL REVIEW BOARD/ INDEPENDENT ETHICS COMMITTEE 
OR HEALTH AUTHORITIES..................................................................................................................... 26 
13 
DATA HANDLING AND RECORD KEEPING ..................................................................................... 27 
14 
STUDY MONITORING, QUALITY CONTROL AND QUALITY ASSURANCE ........................................ 27 
15 
SPONSOR DISCONTINUATION CRITERIA ....................................................................................... 28 
16 
FINAL REPORT .............................................................................................................................. 28 
17 
CONFIDENTIALITY ...............................................................................................................................28 
18 
PUBLICATION ................................................................................................................................ 28 
19 
BIBLIOGRAPHIC REFERENCES .............................................................................................................29 
20 
PROTOCOL SIGNATURES PAGE ..................................................................................................... 30 
21 
PRINCIPAL INVESTIGATOR RESPONSIBILITY STATEMENT ................................................................31 
Appendix I. Protocol Amendment ........................................................................................................ 32 
Appendix II. Contact Information ......................................................................................................... 33 

Protocol Title: Human Comedogenicity Test 
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1 
BACKGROUND 
The  human  comedogenicity  test  has  been  shown  to  be  a  predictive  method  for  assessing  the 
comedogenic potential of products intended for use on skin. 
2 
RATIONALE 
This human comedogenicity test panel(s) is being conducted on product(s) making the claim of “non- 
comedogenic”. 
3 
OBJECTIVE(S) 
The objective of this protocol is to evaluate the comedogenic potential of the test material(s) using the 
back of human volunteers. 
4 
OVERALL STUDY DESIGN AND PLAN DESCRIPTION 
A single center, evaluator blinded, randomized, four-week clinical test panel(s). This human 
comedogenicity test panel(s) is being conducted in order to assess the comedogenic potential of the 
test material(s) and determine if the test material(s) induce microcomedones under repetitive patch 
test conditions. The target population for each test panel is adult men and women (age 18 through 45 
years), who are acne-prone and have large pores on the back and/or a history of acne vulgaris on the 
face or back. Subjects will be patched on the upper back with test material dosed patches and an 
undosed occlusive patch (negative control) every Monday, Wednesday, and Friday for 4 consecutive 
weeks. Each test site will be graded for irritation after each patch removal. After 12 full patching 
sessions, a follicular biopsy will be collected from the test material and control sites, and graded for 
microcomedones. 

Protocol Title: Human Comedogenicity Test 
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5 
STUDY DURATION 
Each test panel will consist of 13 subject visits: Screening/Baseline (Visit 1) will be completed on either 
a Monday, Wednesday or Friday, and Visit 2 will be completed 48-72 hours post Visit 1. Visits 3-13 will 
occur 48-72 hours post each subsequent visit, i.e., Monday, Wednesday, and Friday for four consecutive 
weeks. 
As necessary, a subject may complete a make-up patching visit. Make-up visit will be conducted 48-72 
hours post Visit 12. Subject will return to site for Visit 13 for the collection of Follicular Biopsies. 
Visit 13 will be conducted 48-72 hours post Visit 12 or post make-up visit if applicable. 
Note: 72-hour exposure time is only applicable for visits conducted on Friday and/or to allow for site 
closed days. 
 
 
6 
SUBJECT SELECTION AND ENROLLMENT 
Each study panel can fulfill its objective only if appropriate and required number of subjects is enrolled. 
The following eligibility criteria are designed to select subjects for whom protocol procedures are 
considered appropriate. All relevant medical and non-medical conditions should be taken into 
consideration, in addition to the inclusion/exclusion criteria  below, when deciding if a particular 
individual is suitable for this protocol. The inclusion and exclusion criteria will be reviewed for each 
subject and confirmed by the Principal Investigator (PI) or a medically qualified individual (MD/DO) at 
Visit 1 in order to determine subject eligibility for the relevant test panel. 
Prior to any review of personal data, Informed Consent documents should be signed. 
 
 
6.1 
INFORMED CONSENT 
The Informed Consent Document (ICD), will be read by the subject or explained to the subject by the PI 
or designee. The PI or designee must ensure that each study subject is fully informed about the nature 
and objectives of the study and possible risks associated with participation. After understanding and 
agreeing, the subject will express his/her consent to the subject’s participation in the study by signing 
the ICD. 
No subject will be evaluated without a signed ICD, which should be kept by the PI as part of the Site 
Master File. The ICDs of subjects who are not enrolled in the study will also be part of the Site Master 
File. 
One copy of the signed ICD must be given to the subject; the subject will remain free to withdraw this 
consent at any moment without any negative consequence to the subject. 
The ICD must be approved by the Sponsor and the IRB must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements. 
In addition to the ICD, an IRB approved Supplemental Consent form may be completed if the subject 
has indicated that they have previously had eczema and would like to participate in the study. See 
exclusion criterion VIII. 

Protocol Title: Human Comedogenicity Test 
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6.2 
STUDY POPULATION 
Individuals must meet all of the following eligibility criteria for enrollment into the study. 
 
 
6.2.1 
Inclusion Criteria 
Individuals must meet all of the following inclusion criteria for enrollment into the study: 
I. 
Male or female. 
II. 
18 to 45 years old. 
III. 
Individuals that are willing to provide written informed consent and are able to read, 
speak, write, and understand English. 
IV. 
Individuals who are acne-prone with large pores on the back, or individuals who have a 
history of acne vulgaris on the face or back. 
V. Individuals who have had at least a 2-week rest period since participation in any previous 
clinical studies involving patch applications on the back. 
VI. 
Individuals who are willing to avoid direct sun exposure on the back and use of tanning 
beds for the duration of the study. 
VII. 
Generally, in good health based on medical history reported by the subject. 
VIII. 
Have generally healthy skin condition appropriate for study assessments 
IX. 
Available for the entire study duration. 
X. 
Individuals who are willing to keep patch sites as dry as possible and refrain from 
swimming  or  soaking  in  a  hot  tub  for  the  duration  of  the  study  (no  showering/bathing 
restrictions). 
XI. 
Willing to cooperate and follow instructions. 
XII. 
Female subjects, not of child-bearing potential, must meet at least one of the following criteria: 
• 
Had a hysterectomy and/or bilateral oophorectomy, 
• 
Be post-menopausal (amenorrhea for at least 1 year), 
• 
Had a Tubal Ligation, 
• 
Surgical sterilization (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); 
XIII. 
Female subjects, of child-bearing potential, must agree to practice a medically acceptable form 
of birth control during the study and 30 days after study completion. Females must have used 
such birth control for at least 3 months prior to study start; 
XIV. 
Medically acceptable forms of birth control that may be used by the subject and/or his/her 
partner include: 
• 
Established use of hormonal methods of contraception (oral, injected, implanted, patch 
or vaginal ring). 
• 
Barrier methods of contraception with or without spermicide: condom or occlusive cap 
(diaphragm or cervical/vault caps), 
• 
Intrauterine device (IUD) or intrauterine system (IUS), 
• 
Surgical sterilization (e.g., in a monogamous relationship with male partner with 
vasectomy that has been confirmed effective by sperm count check, tubal occlusion, 
hysterectomy, bilateral salpingectomy). 
• 
Abstinence from heterosexual intercourse: When this is in line with the preferred and 
usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of 
contraception; 

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6.2.2 
Exclusion Criteria 
Subjects with any of the hereafter criteria must be excluded from the study: 
I. Individuals with known allergies or sensitivities to common topical skincare products, including 
adhesives and/or cyanoacrylate (super glue) or ingredients to the test materials for a specific test 
panel. 
II. Deprived from liberty by a judiciary or administrative decision. 
III. Having undergone organ excision (kidney, lung, spleen, and liver), an organ transplant, or a skull 
concussion with extended loss of consciousness within the last 5 years or with present symptoms 
and/or side effects. 
IV. Individuals with self-reported UNCONTROLLED metabolic conditions, such as diabetes, hypertension, 
hyper/hypothyroidism, hypercholesterolemia, etc. 
V. Individuals with CONTROLLED health conditions may be excluded from the study at the discretion of 
the PI or designee: 
• Subjects with conditions that do not affect the skin, such as hypertension and 
hypercholesterolemia, could be enrolled when their health condition is managed through diet, 
medication, etc. 
• Subjects with conditions, which might affect the skin, such as hyper/hypothyroidism, diabetes 
must be excluded, regardless whether their health condition is controlled or not. 
VI. Subjects who are taking medication for chronic conditions (e.g., insulin, antihistamines, steroidal and 
non-steroidal anti-inflammatory drugs, antibiotics, etc...) – exception could be made for 
hypercholesterolemia as per point IV. 
VII. Individuals with adult asthma and/or epilepsy. 
VIII. Skin diseases on tested sites (e.g., psoriasis, eczema, erythema, edema, scars, wounds, melanomas, 
etc.), which may influence the outcome of the study; 
a.    Supplemental Consent 
During the eligibility screening, individuals who indicate that they have previously had eczema 
will be advised of the Koebner phenomenon, which refers to the appearance of these conditions 
either at the patch site or unrelated sites. If the individual chooses to participate in the study, 2 
copies of a supplemental consent form will be signed by the subject (1 for the study files and 1 
will be given to the subject). 
 
IX. Subjects who are self-reported to be pregnant, lactating or planning to become pregnant; females of 
child-bearing potential who are unwilling or unable to use an acceptable method of contraception 
during the study. 
X. Male subjects who have a pregnant partner. 
XI. Male subjects whose partner is planning to become pregnant during the study period or is unwilling 
or unable to use an acceptable method of contraception. 
XII. Simultaneous participation in any other type of clinical study. 
XIII. An individual who has any condition which in the PI’s judgment makes the candidate an inappropriate 
subject for study participation. 
XIV. Subjects who are related to those persons involved directly or indirectly with the conduct of this study 
(i.e., PI, sub-investigators, study coordinators, other  site personnel, employees of the Sponsor 
subsidiaries, contractors of the Sponsor, and the families of each). 
XV. Individuals with a condition or situation which, in the PI’s opinion, may put the subject at significant 
risk, may confound the study results, or may interfere significantly with the subject’s participation in 
the study. 
XVI. Individual viewed by the PI as not being able to complete the study. 

Protocol Title: Human Comedogenicity Test 
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XVII. Subjects who are planning to use any new personal care products (e.g. makeup) or are planning to 
change existing brands during the study 
 
6.3 
CONCURRENT PRODUCTS 
During the study, subjects will be permitted to follow their normal bathing routine. They will not be 
permitted to apply any topical product to the patch sites during the span of this study. Subjects should 
not start using any new personal care products (e.g. makeup, cleanser) or change their currently used 
brands during the study. 
6.4 
CONCURRENT MEDICATION 
If a subject is taking any medication during the course of the study or within 2 weeks prior to the study, 
it must be recorded on the Concomitant Medication Form or equivalent. The minimum information 
required is the name of the medication. If this medication is linked to the treatment of an IP-related AE, 
dose and duration of the treatment should be specified. Medications excluded are indicated in the 
Subject Exclusion criteria; the use of any excluded medications during the study will result in 
discontinuation of the subject. 
 
 
6.5 
SCREENING FAILURE 
All individuals who signed ICD and withdraw their participation or fail to meet all of the screening criteria 
during the initial evaluation will be considered a “screening failure.” These subjects will be replaced 
(note: screening numbers will not be reused) and their data will not be considered in the final report. 
 
 
7 
SAMPLE SIZE DETERMINATION 
A sufficient number of subjects will be screened to enroll as many as 18 qualified subjects to ensure 
completion of 15 subjects per test panel. 
8 
INVESTIGATIONAL STUDY MATERIALS 
8.1 
IDENTITY OF INVESTIGATIONAL STUDY MATERIALS 
The test material(s) will be manufactured and packaged by the Sponsor. The ingredient list and Safety 
Attestation letter for each product will be provided to the PI for review and submission to the IRB. The 
ingredient list and Safety Attestation letters will be filed in the Site Master File for the test panels. 
Formula numbers of the test material(s) will be provided via the protocol addendum form prior to the 
conduct of each study. 
A label will be affixed to each test material. The label may contain (but is not limited to) fields for the 
following information: 
• 
Reference Number 
• 
Type of test material 
• 
Directions 
• 
Net Contents or Net Weight 
• 
Formula number 
• 
Storage Information 
• 
“For Investigational Use Only” 

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8.2 
RANDOMIZATION 
Upon qualification and enrollment, each subject will be sequentially issued a subject number starting 
with “001”. Once a subject number has been assigned to a subject, it cannot be reassigned to another 
subject. The subject numbers will be used to randomly assign the test material(s) and control to the 
specific test sites for each subject according to a randomization scheme created by the site. 
The site will create the randomization scheme for each test panel prior to the initiation of the test panel. 
8.3 
BLINDING PROCEDURE 
This study will be evaluator-blinded, so the PI or delegated evaluator conducting the NACDG grading 
evaluations will not know the placement of the TM and control patched test sites. The PI or delegated 
evaluator should not participate in product(s)/patch application and should not have access to the 
randomization. 
 
In the event that the PI/evaluator believes an un-blinding is necessary and circumstances allow, the 
PI/designee will contact the Study Manager who will consult with the DPR to determine whether 
unblinding is needed. If it is determined that the blind should be broken, the PI/evaluator will contact 
the designated site representative to obtain information about the individual subject’s randomization. 
The time, date, and reason for the un-blinding should be noted in the subject’s source document and 
documentation should be provided to the Sponsor. 
 
If there is a medical emergency and the PI/evaluator deems it necessary to know the randomization 
urgently for the subject’s proper medical care, then the PI/evaluator may break the blind immediately 
by contacting the designated site representative. The PI/designee should promptly document and 
explain to the Study Manager any premature un-blinding. 
 
The PI/evaluator may assist with data entry/review/analysis after individual subjects complete all test 
procedures. This will not be documented as premature un-blinding. 
 
8.4 
STUDY MATERIAL STORAGE AND ACCOUNTABILITY 
The PI or designee must ensure that deliveries of test material(s) from the Sponsor are correctly received 
by a responsible person and that the test material(s) is stored in a secure area under recommended 
storage conditions. The test material(s) will be secured in a locked room or cabinet that is only accessible 
to authorized site personnel and kept at 59 - 86°F (15 -30°C). Temperature should be recorded at least 
daily. The PI must maintain adequate records documenting the receipt, use, loss, or other disposition of 
the investigational product on the Investigational Product Accountability/Dispensing Log or site 
equivalent 
At the end of the study, investigational test material(s) (used and/or unused) may be destroyed by the 
site following its Standard Operating Procedure (SOP) and in compliance with applicable regulations, 
institutional policy, and any special instructions provided by the Sponsor, or they may be returned to 
the Sponsor depending on the product classification. 
When product is destroyed on-site, the destruction must be properly documented and documentation 
provided to the Study Manager and/or designee. 
In case of return to Sponsor, all containers must be returned to 
 
. 

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8.5 
PRODUCT QUALITY COMPLAINTS 
A Product Quality Complaint (PQC) is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, or safety of a product, including its 
labeling, delivery system or packaging integrity. It also includes device malfunctions. Any PQC discovered 
during the initial inventory should follow the instructions provided on the receipt letter; no PQC form 
should be filed for issues identified when opening or unpacking a shipment. Subsequently, any 
observation of a PQC requires immediate notification to the Study Manager via a completed PQC form 
and telephone call. The PI or designee should complete, sign, and forward a copy of the PQC form to 
the Study Manager. 
In addition, PQC information must be included on the Investigational Product accountability  and 
reconciliation Form or equivalent in the comments field. The Study Manager listed can assist you or 
answer questions related to this process. To aid in the initial conversation and understanding of a PQC, 
the site staff may be asked to photograph the issue and send it to the Study Manager. 
 
 
8.6 
APPLICATION OF THE INVESTIGATIONAL PRODUCT 
Test materials will be applied using occlusive or semi-occlusive patches. The patch type may be 
changed during the study if irritation develops. Occlusive patches consist of a non-woven cotton pad 
(e.g., Webril®) covered by Blenderm tape and held securely to skin on all sides with a porous, 
hypoallergenic tape (e.g., Micropore®). Semi-occlusive patches consist of a non-woven cotton pad 
(e.g., Webril®) covered and held securely to skin on all sides with a porous, hypoallergenic tape (e.g, 
Micropore®). Open patches consist of a non-woven cotton pad (e.g., Webril®) held to the skin on 2 
opposing sides by a strip of hypoallergenic tape (e.g., Micropore®). The pad is open 
on 2 sides like a Band-Aid ®. 
 
Patches will be placed on the upper back, to the right and left of the spine. Patches will not be applied 
closer than 2 centimeters (cm) to each other.  The cotton pads used for the patches are approximately 
4 cm2 in area, and will be dosed with a quantity of test material as follows (unless otherwise instructed 
by the Sponsor): 
• 
Liquids and fragrances approximately 100 microliters (µL) 
• 
Creams, lotions, petroleum, etc. approximately 100 µL 
• 
Paper, powder or other solid materials a sufficient amount to cover the pad area 
 
Patches will be applied starting at the lower edge of the patch and pressing from below to let air 
escape. The patch will be secured by gently rubbing the tape (especially the corners) to ensure good 
adherence. 
 
 
9 
INVESTIGATIONAL PLAN 
 
9.1 
STUDY PROCEDURES AND EVALUATION SCHEDULE 
Pre-Study: 

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Candidate subjects will be recruited using IRB-approved materials. Interested candidates will be 
scheduled for Visit 1. 
 
Screening/Baseline: Visit 1 
 
Interested candidates will report to the site and take part in the following procedures: 
 
1. Prospective candidates will be sequentially assigned a 2-digit screening number preceded by 
“S” (e.g. S01). 
2. Subjects will be given an IRB-approved ICD and IRB-approved Supplemental Consent form 
(when applicable) to read and sign. They will have all of their study related questions 
answered by the Investigator or designated staff, and if they agree, they will sign 2 copies of 
the ICD and Supplemental Consent form (when applicable). They will retain 1 copy, and 1 will 
be kept in the study file. 
3. Subjects will complete a health and eligibility questionnaire and a medical and medication 
history questionnaire. 
4. Potential test sites (upper back) will be examined by the Investigator or designee for 
qualification criteria. 
5. The screened subjects that meet all eligibility requirements will be enrolled into the study and 
assigned a subject number as describe in the “Randomization” section. 
6. A delegated clinician will delineate up to six test sites on the subject’s upper back, to the right 
and left of the spine, using an indelible marker. Each test site will be a 4 cm2 and no closed 
than 2 cm2 from each other. The test sites may be re-delineated at subsequent visits as 
needed 
7. The test sites will be wiped with distilled or deionized water and allowed to air dry prior to 
patching. 
8. The test material dosed patches and an undosed negative control patch will be applied to each 
subject’s upper back according to the predetermined randomization. 
9. Subjects will be provided with a calendar of study visits and study instructions. Subjects will be 
reminded of sun exposure/tanning and swimming/hot tub restrictions. Subjects will also be 
instructed to reinforce the edges of the patch with a bandage tape in the event that the tape 
applied in the clinic does not adhere. 
 
 
Interim Visits: Visit 2 – Visit 12 
 
Visit 2 will be completed 48-72 hours post Visit 1. Visits 3-12 will occur 48-72 hours post each 
subsequent visit, i.e., Monday, Wednesday, and Friday for four consecutive weeks. Subjects will report 
to the site at their scheduled visit time and will participate in the following procedures at each interim 
visit: 
 
1. The PI or designee will interview the subjects to collect and record any AEs or changes to 
health/concomitant medications that may have occurred since the previous visit. Subjects will 
also be interviewed for compliance with study directions. Refer to Adverse Event Reporting 
section. 
2. Patches applied during the prior visit will be removed by clinic personnel. 
3. Each test site will be evaluated for irritation/reactions by the delegated evaluator. 
4. Test sites may be re-delineated as needed, as described in Visit 1. 

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5. New test material dosed patches and an undosed negative control patch will be applied to the 
same test sites as described for Visit 1. 
 
Make-up Visit 
 
As necessary, a subject may complete a make-up patching visit. Make-up will be conducted 48-72 
hours post Visit 12. Subject will return to site for Visit 13 for the collection of Follicular Biopsies. 
Subjects will report to the site at their scheduled visit time and will participate in the following 
procedures: 
 
1. The PI or designee will interview the subjects to collect and record any AEs or changes to 
health/concomitant medications that may have occurred since the previous visit. Subjects will 
also be interviewed for compliance with study directions. Refer to Adverse Event Reporting 
section. 
2. Patches applied during the prior visit will be removed by clinic personnel. 
3. Each test site will be evaluated for irritation/reactions by the delegated evaluator. 
4. Test sites may be re-delineated as needed, as described in Visit 1. 
5. New test material dosed patches and an undosed negative control patch will be applied to the 
same test sites as described for Visit 1. 
 
 
Visit 13: 
 
Visit 13 will be conducted 48-72 hours post Visit 12. Subjects will report to the site at their scheduled 
visit time and will participate in the following procedures 
1. The PI or designee will interview the subjects to collect and record any AEs or changes to 
health/concomitant medications that may have occurred since the previous visit. Subjects will 
also be interviewed for compliance with study directions. Refer to Adverse Event Reporting 
section. 
2. Patches applied during the prior visit will be removed by clinic personnel. 
3. Each test site will be evaluated for irritation/reactions by the delegated evaluator. 
4. A delegated clinician will collect follicular biopsies from each test site as described below in 
the Study Instrument(s) section. 
5. The PI or designee will interview the subjects to collect and assess any AEs or changes to 
health. 
6. After all assessments are completed, subjects will leave site. 
 
Note: 72-hour exposure time is only applicable for visits conducted on Friday and/or to allow for site 
closed days. 
 
Site Irritation / Reaction Grading 
 
At visits 2 through 13 (and makeup visit if applicable), the designated test sites will be graded for 
irritation/reactions using the North American Contact Dermatitis Group (NACDG) grading scale. 
Sites will be adequately illuminated using lighting provided by a 60-watt incandescent blue day light 
bulb. 
 
NACDG Grading Scale 

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0 No reaction 
+0.5 Macular erythema 
+1 Indurated erythema 
+2 Erythema, infiltration and vesicles 
+3 Bullous reaction or ulcer 
If irritation develops as indicated by the NACDG score, the patch type may be changed or patch 
applications may be skipped for specific sites. Skipping a patch application should be documented as a 
protocol deviation. This may also have an impact on the follicular biopsy process at the final study 
visit. Any changes made to the patch type, application schedule, or biopsy procedures will be 
documented in the appropriate source documents. 
 
9.2 
STUDY INSTRUMENT(S) 
Follicular Biopsies: 
Follicular biopsies will be collected from each patch site at Visit 13 or make-up visit for each subject. The 
following procedures will be followed for follicular biopsy collection: 
• 
The test sites will be gently cleansed with warm soapy, water and patted dry. 
• 
A glass slide containing a drop of cyanoacrylate glue will be held against each site until it has 
dried. 
• 
The slide will then be removed slowly, so as to extract follicles and their contents. 
• 
The specimen slides will be stored in labeled slide boxes until graded. 
• 
The specimens collected using the cyanoacrylate follicular biopsy technique will be evaluated 
by a trained  grader using a stereomicroscope (magnification  ratio of 0.8). Hyperkeratotic 
follicles (microcomedones) will appear as cylindrical horny impactions surrounding extracted 
vellus hairs. 
 
Specimens will be graded using a 5-point global assessment scale as follows: 
0 None (0%, No microcomedones) 
0.5 Slight (1-24% Smallish horny masses) 
1 Mild (25-49% Smallish horny masses) 
2 Moderate (50-74% Moderately sized horny masses) 
3 Severe (75-100% Larger globoid microcomedones) 
 
The results from the microcomedone grading of the follicular biopsies will be recorded using the 
Stephens Electronic Data Capture (EDC) system, if available, which documents the identity of the 
evaluator/technician as well as the time and date of all entries, or all corrected entries. Subject data can 
also be provided by Stephens at the Sponsor’s request. Paper grading forms will be completed if EDC is 
unavailable. Any test site with a NACDG grading score of 2 or greater may not receive a follicular biopsy, 
which will be noted in the appropriate source documents. 
 
9.3 
SUBJECT COMPLETION/WITHDRAWAL 

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9.3.1 
Subject Completion 
Subjects are considered to have completed the study when all study procedures have been completed 
as designated by the protocol. Completion should be noted in the source documents and Screening and 
Enrollment log. 
9.3.2 
Subject Withdrawal 
When an individual who has signed the ICD is not enrolled in the study or withdraws/is withdrawn 
prior to completing the study, the reason is to be documented in the source documents, Screening 
and Enrollment log, and in the final study report. Reasons for subject withdrawal may include: 
 
• 
Screen Failure (e.g. fails to meet inclusion/exclusion criteria, chooses not to enroll, etc.) 
• 
Participant is determined to be ineligible after enrollment 
• 
Subject’s choice to withdraw 
• 
Investigator terminated (e.g. noncompliance, etc.) 
• 
Adverse Event / SAE (must be reported in accordance with the reporting requirements 
defined in the Adverse Event Reporting Section. 
• 
Lost to follow-up 
• 
Other 
 
 
Subjects may withdraw from the trial at any time at their request, or they may be withdrawn at any time 
at the discretion of the Sponsor, PI, or designee for safety, behavioral, or administrative reasons. If a 
subject does not return for a scheduled visit, 3 documented attempts will be made to contact the subject 
in order to establish the reason for withdrawal, and the outcome will be documented. The PI or designee 
should inquire about the reason for withdrawal, request that the subject return for a final visit, if 
applicable, and follow-up with the subject regarding any unresolved adverse events. 
Should a subject withdraw from the trial and also withdraw consent for disclosure of future information, 
no further evaluations should be performed and no additional data should be collected. The PI and staff 
may retain and continue to use any data collected before such withdrawal of consent. 
Additional subjects may be enrolled in a test panel to compensate for early subject withdrawal 
10 STATISTICAL ANALYSIS PLAN. 
The per-protocol (PP) population will be the primary population for comedogenicity analyses. The PP 
population will include all subjects who received treatment and completed the study in general 
accordance with the protocol. Only the data of completing subjects will be analyzed. Subjects may be 
removed from the analysis in the case of an AE, SAE, non-compliance, or Investigator discretion. The 
reason for any subjects excluded from the analyses will be documented in a note to file and included 
in the study report. 
 
Demographic data and baseline characteristics will be summarized for all subjects who are enrolled in 
the study. For continuous variables, descriptive statistics including number of subjects (N), mean, 
median, standard deviation (SD), minimum (MIN) and maximum (MAX) values will be presented. For 
categorical variables, the frequency and percentage of each category will be provided. 
 
A descriptive statistical summary will be provided for the global assessments of microcomedone data 
from biopsies for the test material and control sites. The descriptive statistical summary includes the 
number of observations (N), mean, median, standard deviation (SD), minimum (MIN), and maximum 

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(MAX). 
 
In addition, microcomedone scores will be analyzed using a mixed-effects model, where the test 
Material/negative control is a fixed effect and the subject is a random effect. Each test product will be 
compared to the negative control within the model frame. A test material will be considered positive 
for comedogenicity if it has a mean microcomedone value of 1.0 or greater, and is statistically greater 
than the mean microcomedone value for the negative control site. 
 
All statistical tests will be 2-sided at significance level alpha=0.05. P-values will be reported to 3 
decimal places (0.000). No multiple testing corrections will be considered in the study. Statistical 
analyses are performed using SAS software version 9.30 or later series (SAS Statistical Institute). The 
results will be sent to the Sponsor along the raw data in a Microsoft Excel document at the completion 
of the study. 
 
A test material is considered negative for comedogenicity as long as it satisfies 1 of the following 2 
conditions: the microcomedone mean score is less than 1.0 and/or the mean score is not greater than 
the control with p-value < 0.05. 
 
11 
MANAGEMENT OF INTERCURRENT EVENTS 
11.1 
AMENDMENTS TO THE PROTOCOL 
Neither the PI nor Sponsor will modify this protocol without obtaining the concurrence of the other. The 
party initiating a modification will confirm it in writing. Amendments must be approved by the Sponsor 
and IRB prior to implementation. 
Note that submission of administrative change/non-substantial amendments to regulatory authorities 
and/or IRB/IECs for approval prior to study implementation is determined after consultation with the 
local regulatory representative and/or IRB/IEC policy and may vary by country/region. 
The only circumstance in which an amendment may be initiated prior to IRB approval is where the change 
is necessary to eliminate apparent immediate hazards to the subjects. In that event, the PI must notify 
the IRB and the Sponsor in writing within 3 working days after the implementation. 
 
 
11.2 
PROTOCOL DEVIATIONS 
Protocol deviations should be avoided whenever possible. When a protocol deviation occurs, it must be 
captured on a Deviation Log. 
The PI or designee will also contact the Study Manager, Contact with the Study Manager will be made 
as soon as possible in order to discuss the situation and agree on an appropriate action. If it is 
determined that the subject safety/well-being was affected, the IRB/IEC, if any, will also be notified. 
The final report will describe the deviation from the protocol and the circumstances requiring it. 
 
 
11.3 
ADVERSE EVENT REPORTING 
11.3.1 Introduction 
Timely, accurate, and complete reporting and analysis of safety information from clinical studies are 
crucial for the protection of subjects, investigators, and the Sponsor, and are mandated by regulatory 

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agencies worldwide. The Sponsor has established procedures in conformity with regulatory 
requirements to ensure appropriate reporting of safety information. 
 
11.3.2 Definitions 
11.3.2.1 
Adverse Event (AE) 
An AE is any untoward medical occurrence in a clinical study subject temporally associated with the 
clinical investigation, whether or not the event has a causal relationship to the subject’s participation 
in the trial. It is therefore any unfavorable and unintended sign (including an abnormal finding), 
symptom, or disease that occurs during the trial. This can include any occurrence that is new in onset, 
an aggravation of severity/frequency of a baseline condition, or abnormal results of diagnostic 
procedures, including laboratory test abnormalities. 
 
Examples of AEs include but are not limited to: 
Abnormal test findings, 
Clinically important symptoms and signs, 
Changes in physical examination findings, 
Hypersensitivity, and 
Progression/worsening of underlying disease. 
Any change in existing medical condition (Medical History) would be considered an AE and recorded 
appropriately. 
 
Additionally, they may include the signs or symptoms resulting from: 
Investigational product overdose, 
Investigational product withdrawal, 
Investigational product abuse, 
Investigational product misuse, 
Investigational product interactions, 
Medication errors, 
Investigational product dependency, 
Exposure in utero, and 
Study related procedure. 
 
The criteria for determining whether an abnormal objective test finding should be reported as an AE 
are as follows: 
Test result is associated with accompanying symptoms, and/or 
Test result requires additional diagnostic testing or medical/surgical intervention, and/or 
Test result leads to a discontinuation from the study, significant additional concomitant 
treatment, or other therapy, and/or 
Test result is considered to be an adverse event by the PI or the Sponsor. 
 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not constitute 
an AE. Any abnormal test result that is determined to be an error does not require reporting as an AE. 
 
Expected AE 
All investigational products have the potential to cause some uncomfortable effects or other reactions. 
Signs and symptoms of erythema, edema, scaling/dryness, itching, burning, stinging, and tingling are 

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considered clinical endpoints if they are mild in nature and should not be reported as AE. These 
conditions may or may not resolve over time. Symptoms that are persistent and moderate to severe in 
nature, or that involve elevation (e.g. edema, papules, vesicles, spreading) will be considered adverse 
events (AEs). The Investigator or designee will have the final authorization to determine if a reaction will 
be considered an AE. 
If a subject is discontinued due to worsening of a sign or symptom (including worsening of the signs 
and or symptoms recorded as part of the evaluations), then it should be recorded as an AE. 
 
Treatment Emergent AE (TEAE) 
TEAE is defined as any event not present prior to the initiation of the IPs. Note that AEs will be 
summarized for all subjects who signed the ICD, differentiating TEAEs. 
AEs are considered serious and require expedited reporting if they meet the definition of a Serious 
Adverse Event (see part below). 
 
11.3.2.2 
Serious Adverse Event (SAE) 
An SAE is an AE (untoward medical occurrence) that fulfills at least one of the following criteria: 
 
• 
results in death; 
• 
is life-threatening (immediate risk of death); 
• 
requires inpatient hospitalization or prolongation of existing hospitalization; 
• 
results in a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions; 
• 
is a suspected transmission of any infectious agent via a medicinal product (medically 
significant) and should be reported as an SAE in the category “Other medically important 
conditions”; 
• 
results in a congenital anomaly/birth defect; 
• 
is another medically significant event (i.e. a medically significant condition that may jeopardize 
the subject or require medical or surgical intervention to prevent any of the previously listed 
outcomes). Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in situations other than those listed above. Examples of                    
such medical events include allergic bronchospasm requiring intensive treatment in an 
Emergency Room or at home, blood dyscrasia, or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse, or malignancy). 
 
11.3.2.3 
Severity 
The severity of all AEs must be evaluated by the PI or, if the PI does not have a medical background, by a 
medically qualified individual (MD/DO). The severity classifications are: 
• 
Severe – Extreme distress, causing significant impairment of functioning or incapacitation; 
interferes significantly with subject's usual function; prevents normal everyday activities. 
• 
Moderate – Sufficient discomfort is present to cause interference to some extent with 
subject's usual function or normal everyday activity. 
• 
Mild – Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with subject's usual function or normal everyday activities. 

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Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily a serious event. For example, a headache may be severe (interferes significantly with 
subject's usual function) but would not be classified as serious unless it met one of the criteria for 
SAEs, listed above. 
 
11.3.2.4 
Causality Assessment 
An AE (serious or non-serious) is considered “study-related” if the causality assessment is possible, 
probable, or very likely. The PI or, if the PI does not have a medical background, a medically qualified 
individual (MD/DO) determines the causality by using the following definitions: 
 
• 
Not related – an AE that is not related to the participation in the study. 
• 
Doubtful – an AE for which an alternate explanation is more likely (e.g. concomitant drug), or 
the relationship in time suggests that a causal relationship is unlikely. 
• 
Possible – an AE that might be a result of participation in the study. An alternative explanation is 
inconclusive and the relationship in time is reasonable so a causal relationship cannot be excluded. 
• 
Probable – an AE that might be a result of participation in the study. The relationship in time is 
suggestive (e.g. confirmed by the challenge). An alternative explanation is less likely. 
• 
Very Likely – an AE that is listed as a possible adverse reaction and cannot be reasonably 
explained by an alternative explanation. The relationship in time is very suggestive (e.g. 
confirmed by dechallenge and rechallenge). 
 
11.3.3 Procedures for Reporting Adverse Events 
All AEs will be reported from the time a signed and dated ICD is obtained until completion of the 
subject’s last study procedure or visit (or termination if the subject terminates early from the study for 
any reason). 
AEs that occur between end of study and 30 calendar days after completion of the study will only be 
reported to the Sponsor if they are serious.  SAEs are reportable beyond this period if the event is 
considered study-related. The Sponsor will evaluate any safety information that is spontaneously 
reported by the PI beyond the time frame specified in the protocol. 
Subjects are encouraged to report AEs spontaneously and in response to questioning during the visit 
(e.g. if they have had any side effects/issues or changes in their health). For each AE reported by the 
subject or observed by the study team, the study team member should notify the PI, Study Physician, 
or designee, who will collect information about the event. 
All AEs, regardless of seriousness, severity, or presumed relationship to study procedures, must be 
recorded using medical terminology on the Sponsor provided AE form and then entered into the 
Electronic Data Capture (EDC), Medidata Rave AE Universal Database. These events must then be 
entered into the Medidata Rave AE Universal Database within 5 business days of the site’s awareness. 
The DPR review of AEs/SAEs in Medidata Rave AE Universal Database will be conducted within 5 
business days of each entry into Medidata Rave AE Universal Database in order to escalate any 
potential safety signal to the Department Head. 
Whenever possible, diagnoses should be given when signs and symptoms are due to a common 
etiology (e.g., cough, runny nose, sneezing, sore throat, and head congestion should be reported as 
“upper respiratory infection”). The PI or, if the PI does not have a medical background, a medically 
qualified individual (MD/DO) designee, must record or confirm their opinion concerning the 

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seriousness, severity, and relationship of the AE to the study. All measures required for AE 
management must be recorded and reported according to Sponsor instructions. 
The PI or designee must also report AEs to the appropriate IRB unless otherwise required and 
documented by the IRB. 
If a SAE occurs, in addition to the above reporting procedures, the Site will immediately notify the 
Study Manager and Study Director by telephone or encrypted e-mail (see Appendix III for Contact 
Information) 
 
Subsequent to a telephone or encrypted e-mail report of an SAE, a Clinical Trial SAE Report Form 
(provided to the study site at the initiation of the study) must be completed by the investigational staff 
with as much information as possible (however at a minimum, the subject identification number,  
name of investigational product [if applicable], SAE description, investigator’s assessment of causality, 
and name of site personnel reporting event are required), signed by the PI (or the medically qualified 
designee), and securely transmitted to the Study Manager and Study Director within 24 hours of 
becoming aware of the event. 
This timeframe also applies to additional new information (follow-up) on previously forwarded SAE 
reports. 
In the rare event that the Investigator’s site does not become aware of the occurrence of a SAE 
immediately (e.g., if an outpatient study subject initially seeks treatment elsewhere), the Investigator’s 
site is to report the event immediately after learning of it as described and document the time of the 
study site’s first awareness of the SAE. 
 
The Study Manager or designee will notify the DPR within 1 calendar day of SAE information receipt. The 
DPR will request more information as necessary. The Study Manager or designee will send an e-mail 
appropriate document to Sponsor’s OCMS group per local procedures within the following timelines: 
 
• 
fatal/life-threatening reports: within 2 calendar days from regulatory clock start date 
• 
other SAEs and pregnancy exposure reports: within 3 calendar days from regulatory clock start 
date 
For all SAEs, the PI is obligated to pursue and provide information to the Sponsor in accordance with 
the timeframes for reporting specified above. In addition, the PI may be requested by the Sponsor to 
obtain specific additional follow-up information in an expedited fashion. This information may be 
more detailed than that captured on the AE Form. In general, this will include a description of the SAE 
in sufficient detail to allow for a complete medical assessment of the case and independent 
determination of possible causality. Information on other possible causes of the event, such as 
concomitant medications and illnesses, must be provided. 
In the case of a subject death, a summary of available autopsy findings (if available) and death 
certificate should be collected if permission is obtained from the subject’s family. 
For a hospitalization, a copy of the hospital discharge summary should be requested. If obtained, 
these documents (with subject’s personal identifiers redacted) should be securely submitted as soon 
as possible to the Sponsor or its designated representative. 

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11.3.4 Monitoring and Resolution of Adverse Events 
11.3.4.1 Non-Serious AEs 
All study-related AEs will be followed until resolution, until a stable clinical endpoint is reached, or at 
least 30 days post-study withdrawal/completion. This information will be captured in the source 
document and entered into Medidata Rave AE Universal Database. 
 
11.3.4.2 Serious AEs (SAEs) 
The PI or, if the PI does not have a medical background, the medically qualified designee (MD/DO) will 
monitor SAEs until resolution or until one of the conditions in 11.3.4.3 is met. The information will be 
captured in the source document and entered into Medidata Rave AE Universal Database. The 
PI/designee will also document follow-up information on an updated Clinical Trial SAE form, which will 
be reviewed by the PI or medically qualified individual designee and sent securely to the Study 
Manager or designee. The Study Manager or designee will forward the document(s) to the DPR and 
Study Director or designee, and to OCMS per local procedures. 
 
11.3.4.3 Resolution 
The PI will be required to assess the outcome of each AE as one of the following: 
Resolved; 
Not Resolved; 
Fatal; 
Resolved with sequelae; 
Resolving; 
Unknown. 
 
Serious AEs that have not been resolved by the end of the study, or that have not been resolved upon 
discontinuation of the subject’s participation in the study, must be followed until any of the following 
occurs: 
the event resolves 
the event stabilizes 
the event returns to baseline, if a baseline value is available 
the event can be attributed to factors unrelated to study conduct 
when it becomes unlikely that any additional information can be obtained (subject or 
healthcare practitioner refusal to provide additional information, lost to follow-up after 
demonstration of due diligence with follow-up efforts). 
 
11.3.5 Exposure In Utero 
For investigational products within clinical studies, an exposure in utero (EIU) occurs if: 
• 
A woman is exposed to the investigational product at any time between her last menses 
prior to conception through the delivery of the baby. 
If any study subject becomes or is found to be pregnant during the study subject’s participation, the PI 
must report the pregnancy to the Sponsor on a Pregnancy Notification Form (to be provided by the 
Sponsor when applicable). Initial notification via telephone to the Sponsor’s study team contact must 
occur immediately upon the Investigator site’s awareness of the pregnancy. The Pregnancy 
Notification Form must then be sent to the Sponsor within 24 hours of the site’s awareness. The 

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information submitted should include the anticipated date of delivery (see below for information to 
document termination of pregnancy). 
Follow-up is conducted to obtain pregnancy outcome information on all EIU reports. The PI will follow 
the pregnancy until completion or until pregnancy termination (i.e., induced abortion) and then notify 
the Sponsor of the outcome. The PI will provide this information as a follow-up to the initial Drug 
Exposure During Pregnancy Collection Form A and/or End of Pregnancy Collection Form B (provided by 
the Sponsor when applicable). The reason(s) for an induced abortion should be specified. An EIU 
report is not created when an ectopic pregnancy report is received since this pregnancy is not usually 
viable. Rather, a SAE case is created with the event of ectopic pregnancy. 
The PI should follow the procedures for reporting SAEs if the outcome of the pregnancy meets the 
criteria for immediate classification as a SAE (i.e., spontaneous abortion, stillbirth, neonatal death, or 
congenital anomaly [including that in an aborted fetus, stillbirth, or neonatal death]). In the case of a 
live birth, the “normality” of the newborn can be assessed at the time of birth (i.e., no minimum 
follow-up period of a presumably normal infant is required before an End of Pregnancy Collection 
Form B can be completed). The “normality” of an aborted fetus can be assessed by gross visual 
inspection, unless pre-abortion test findings are suggestive of a congenital anomaly. 
Additional pregnancy outcomes that are classified as SAEs and should be reported as such include: 
 
“Spontaneous abortion” includes miscarriage and missed abortion; 
All neonatal deaths that occur within 1 month of birth, without regard to causality; 
Any infant death after 1 month that the PI assesses as possibly related to in utero exposure to 
the investigational product. 
 
12 ETHICAL CONSIDERATIONS 
The privacy information such as the ICD and health related questionnaire of the subjects will be kept 
confidential during the study and clearly separated from the TMF. 
 
12.1 
STUDY SUBMISSION TO INSTITUTIONAL REVIEW BOARD/ INDEPENDENT ETHICS COMMITTEE 
OR HEALTH AUTHORITIES 
This study (protocol, ICD, recruiting material [advertisements, phone script, etc.], and all addenda) will 
be reviewed and approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
contacted by the Study Site. 
Details of the IRB/IEC for this study are in Appendix I. 
It is the responsibility of the PI to have approval of the study protocol, protocol amendments, ICD(s), 
and other relevant documents, e.g., advertisements, if applicable from the IRB/IEC. 
The study will not be activated, subjects will not be recruited, consented, or receive test materials 
until such time as the IRB/IEC as approved the required documentation. In addition, the IRB/IEC will 
review the study before any significant change in the protocol is initiated. After each review, the 
IRB/IEC’s approval letter will be forwarded to the Sponsor. 
All correspondence with IRB/IEC should be retained in the SMF. Copies of IRB/IEC approvals should be 
forwarded to the Sponsor and will be filed in the TMF. 

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source documents to confirm that the data recorded is complete and accurate. The PI and institution 
will allow the Sponsor’s monitor(s) or its designee and appropriate regulatory authorities direct access 
to source documents to perform this verification. If there are any issues noted, the PI will be notified. 
Any contact concerning this study should be made with the Study Manager or the Study Director (see 
Appendix I). 
The study site may be subject to review by the IRB/IEC, and/or to quality assurance audits performed 
by the Sponsor, and/or to inspection by appropriate regulatory authorities. 
It is important that the PI and his/her relevant personnel are available during monitoring and possible 
audits or inspections and that sufficient time is devoted to the process. 
 
 
15 SPONSOR DISCONTINUATION CRITERIA 
Premature termination of this clinical trial may occur because of a change in opinion of the IRB/IEC, 
investigational product or study safety or at the discretion of the Sponsor. If a trial is prematurely 
terminated or discontinued, the Sponsor will promptly notify the PI. After notification, the PI or 
designated staff must contact all participating subjects within 10 business days (phone, voicemail, or 
certified letter), as applicable. As directed by Sponsor, all trial materials must be collected, all CRFs 
completed to the greatest extent possible, and termination reported to the IRB/IEC. 
 
16 FINAL REPORT 
The draft report will be submitted to the Sponsor for review and changes and may be made to the 
draft report at the Sponsor’s request. Upon Sponsor’s/study team’s approval, the report will be 
finalized and forwarded to the Sponsor. 
The final report will include (but is not limited to) the following information: study design and protocol, 
subject population demographics statistical methods used, results, description of adverse events (if 
any), discussions, and conclusions. 
 
17 CONFIDENTIALITY 
All the information, data and results of the study will be confidential. Every person having access to 
these data will be informed of this confidentiality. 
Medical information concerning the subjects obtained by the investigator during the recruitment and 
admission will be handled confidentially. 
 
18 PUBLICATION 
The publication agreement, if any, between the Sponsor and the site is detailed in the clinical trial 
agreement. 

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19 BIBLIOGRAPHIC REFERENCES 
1. Mills OH, Berger RS, Stephens TJ, Drake K, Fisher L. Assessing acnegenic and acne aggravating 
potential. American Academy of Dermatology, 46th Annual Meeting, 1987;108. 
 
2. Mills OH, Kligman AM. A human model for assessing comedogenic substances. Arch. Dermatol. 
1982;118(11):903-5. 
 
3. Mills OH, Kligman AM. The follicular biopsy. Dermatologica. 1983;167(2):57-63. 

Protocol Title: Human Comedogenicity Test 
Protocol identification: CO-161115154122-SACT- date: 08FEB2017 Final Version (1) 
 
 
Appendix II. Contact Information 
SPONSOR: 
• 
Study Manager: 
 
 
 
 
 
 
 
 
• 
Study Director: 
 
 
 
 
 
 
 
 
• 
Department Head: 
 
 
 
 
 
 
 
 
STUDY SITE: 
 
 
 
 
 
 
 
 
• Principal Investigator: 
 
 
 
 
 
IRB: 
 
 
• Investigational Review Board (IRB): 
 
 
 
 
 
 
• 
Study Monitor: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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