EpiCeram for Skin Protection in Healthcare Workers Using Personal Protective Equipment
Phase: NA
Conditions: Irritant Contact Dermatitis
Sponsor: Primus Pharmaceuticals

Protocol 
Statistical Analysis Plan 
 
EpiCeram for skin protection in healthcare workers using personal 
protective equipment 
 
NCT04793711 
 
March 1, 2021 

EpiCeram for skin protection in healthcare workers using personal protective equipment. 
 
Protocol:  
 
 
PPE-01 
 
Sponsor:  
 
 
Primus Pharmaceuticals, Inc. 
 
 
 
 
Study Director:  
Robert Levy, MD                
 
 
 
Tel: 480-483-1410 
 
 
   
 
 
Study Project Manager:  
Mary Sanstead, BSN 
 
 
 
 
Tel: 480-250-6689 
 
 
 
            7373 N. Scottsdale Rd. 
 
 
 
 
Suite B-200 
 
    
 
 
Scottsdale, AZ 85253 
 
  
 
 
 
 
 
 
 
 
Study Statistician:                  Methods Consultants 
 
 
 
 
27 E. Cross St. 
Ypsilanti, MI 
734-544-8038 
 
Date: November 5, 2020    
Version: 1 
 
Date: January 21, 2021 
Version: 2 
 
Date: February 16, 2021 
Version: 3 
 
Date: March 1, 2021 
Version: 3.1 
 
 
This document is a confidential communication of the Clinical Development Department of 
Primus Pharmaceuticals, Inc.  Acceptance of this document constitutes agreement that the 
recipient will not disclose or publish any of the information contained herein without prior written 
permission from Primus.  The only exception to this rule is that the information may be given to a 
properly constituted IRB with the understanding that they are requested to keep it confidential. 
 
 
 

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understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
Guideline Signature and Financial Disclosure 
This guideline has been written by Primus Pharmaceuticals, Inc. 
Director of Clinical Development, Robert M. Levy, M.D. 
 
 
March 1, 2021 
Director Signature 
 
 
 
 
    Date 
 
 
Protocol Signature and Financial Disclosure Page 
 
I have read and I understand all the provisions and requirements of this protocol, EpiCeram for skin 
protection in healthcare workers using personal protective equipment. Protocol # PPE-01. 
 
I agree to perform the investigator’s responsibilities exactly as set forth in the protocol according to 
the principles of Good Clinical Practice. I further understand that all information pertaining to this 
protocol is confidential and may not be disclosed in personal communications or professional 
presentations without the prior written consent of Primus, Inc.  
 
________________________________________ ___________  
Investigator signature/ Date  
 
I certify that, other than the investigator stipend agreed upon in the contract and budget for this study, 
I have no other financial interest in Primus Pharmaceuticals, Inc. or any of its present or future 
products.  
 
_______________________________________ ____________  
Investigator signature/ Date 
 
 
 

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ABBREVIATIONS 
 
 
AE 
Adverse Event 
AMP 
Antimicrobial Peptides 
CRF 
Case Report Form 
COVID-19 Coronavirus Disease 2019 
DDC 
Direct Data Capture 
EDC 
Electronic Data Capture 
FDA 
U. S. Food and Drug Administration 
FFA 
Free Fatty Acids 
HCW 
Healthcare Workers 
HIPAA 
Health Insurance Portability and Accountability Act 
ICD 
Informed Consent Document 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
IRB 
Institutional Review Board 
PPE 
Personal Protective Equipment 
qPCR 
Quantitative Polymerase Chain Reaction 
SAE 
Serious Adverse Events 
SCH 
Stratum Corneum Hydration 
TEWL 
Transepidermal Water Loss 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
 
EpiCeram for skin protection in healthcare workers using personal protective equipment. 
Synopsis 
Protocol #: PPE-01 
Background 
During the current COVID-19 pandemic, health care workers (HCW) report that the prolonged 
use of personal protective equipment (PPE), particularly gloves and face covering, results in 
irritant contact dermatitis manifested by symptoms of pain, itching, burning and non-specific 
discomfort of the hands and face and associated visible physical changes of erythema, dryness, 
roughening and cracking of the affected skin (Jiang, et al 2020). These changes are aggravated 
by frequent hand washing and antimicrobial alcohol use. These irritative changes are likely 
associated with defects in the normal barrier structure and function of the skin, including, but not 
limited to, lowering of surface pH, excessive water loss, alteration of skin microbiome, lowered 
resistance to penetration by allergens and pathogens and immunological dysfunction. It is 
unknown whether these changes could increase the likelihood of S. aureus skin contamination or, 
in people exposed to, but not systemically ill with, COVID-19 to act as “silent” carriers of 
coronavirus. 
 
EpiCeram, a three, lipid emollient, has been shown to improve barrier structure and function, 
reduce skin pH, helps restore the microbiome toward normal, improve immunological function 
and reduce symptoms associated with disrupted skin surfaces (Elias 2014, Elias 2019 and Kircik 
2014). In contrast, some readily available over the counter skin care products may actually 
increase barrier dysfunction and aggravate skin disease (Li 2017, Elias 2019). 
 
Study Objectives 
1. To evaluate the ability of EpiCeram to reduce signs and symptoms of skin irritation in HCW 
using PPE on the face and hands. 
2. To evaluate the ability of EpiCeram to improve measurements of skin barrier function during 
continued use of PPE on the face and hands.  
3. To evaluate the ability of EpiCeram to reduce skin surface S. aureus load. 
 
Study design 
This will be a one (1) month, open label study. Subjects must be HCW who have used face and 
hand PPE at least four (4) days a week for a minimum of one (1) month (or, depending on shift 
work, at least 24 hours/week) and who have new (after March 1, 2020) symptomatic skin 
irritation on the hands and/or face. No change to required hand washing protocols or other 
protective measures will be required. 
 
 
 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
At Visit 1 (Screening) the study will be explained, and an informed consent document (ICD) 
signed. Subjects will be entered into the electronic data capture (EDC) system using a direct data 
capture (DDC) tablet. Subjects will complete an overall skin irritation assessment on 0-10 scale 
where 0 = none and 10 = worst. If it is equal to or greater than 4, the subject may proceed to 
enrollment provided all other inclusion and exclusion are met.  
 
If the subject has not used any lotions and emollients for the previous one (1) week on the face 
and hands, washout is not necessary, and Baseline visit activities may be performed at the 
Screening visit. Subjects requiring washout, will refrain from using any lotions and emollients 
for one (1) week between Visits 1 and 2 and then, for the duration of the study. Visit 2 (Baseline) 
will occur seven (7) days after Visit 1.  
 
At Visit 2, subjects will complete an overall skin irritation assessment on a 0-10 scale where 0 = 
none and 10 = worst. Subjects will complete skin symptom scales of pain, redness, dryness, 
roughness, itching and cracking on a scale on a 0-10 scale where 0 = none and 10 = worst. 
A manual describing detailed steps for collection of laboratory, photographic and skin surface 
measurements will be provided to the site by the sponsor. Vendors will supply training and 
references for the camera and EDC system.  
Photographs: Digital 3D photographs will be taken of the face and back of the hand. The face 
photo will be a two (2) inch by three (3) inch area of the cheek without identifying features. The 
hand photo will be the worst area of involvement as selected by the subject.  
Skin Function Testing: Measurements of transepidermal water loss (TEWL) with stratum 
corneum hydration (SCH) and surface skin pH will be taken on the web between the 3rd and 4th 
metacarpophalangeal (MCP) joints on the dorsum of the dominant hand used.    
Laboratory Testing: Two types of specimens will be obtained; a swab and tape stripping. A 
single skin swab for bacterial qPCR will be obtained from the palm of the dominant hand. Non-
invasive tape stripping of surface cells (3 strips/sample) will be performed at 2 sites; on the web 
between the 3rd and 4th metacarpophalangeal (MCP) joints on the dorsum of the dominant hand 
for antimicrobial peptides (AMP) and three (3) strips/sample from the web between the 2nd and 
3rd MCP joints on the dominant hand for free fatty acids. See the manual for detailed instructions 
on specimen collection. The subject will then be directed to apply EpiCeram to the hands (wrist 
to fingertips, back and front) and face at least three (3) times daily (about every 8-10 hours), 
more often if the subject wishes.  
 
At Visit 3 (Final), 28 days later subjects will complete an overall skin irritation assessment on a 
0-10 scale where 0 = none and 10 = worst. Subjects will complete skin symptom scales of pain, 
redness, dryness, roughness, itching and cracking on a scale on a 0-10 scale where 0 = none and 
10 = worst. Photos, skin function, swab and tape stripping will be in the same location as Visit 2. 
Photographs: Digital 3D photographs will be taken of the face and back of the hand. The face 
photo will be a two (2) inch by three (3) inch area of the cheek without identifying features. The 
hand photo will be the worst area of involvement as selected by the subject.  

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
Skin Function Testing: Measurements of transepidermal water loss (TEWL) with stratum 
corneum hydration (SCH) and surface skin pH will be taken on the dominant hand on the dorsum 
of the 3rd and 4th metacarpal phalanges.  
Laboratory Testing: Two types of specimens will be obtained; a swab and tape stripping. A 
single skin swab for bacterial qPCR will be obtained from the palm of the dominant hand. Non-
invasive tape stripping of surface cells (3 strips/sample) will be performed at 2 sites; on the web 
between the 3rd and 4th metacarpophalangeal (MCP) joints on the dorsum of the dominant hand  
for antimicrobial peptides (AMP) and three (3) strips/sample from the web between the 2nd and 
3rd MCP joints on the dominant hand for lipids. The subject will then be directed to apply 
EpiCeram to the hands and face at least three (3) times daily (about every 8-10 hours), more 
often if the subject wishes.  
 
Primary Endpoint 
1. Change in patient reported outcome of face and hand skin symptoms from baseline to Day 
28, of at least 2 points on a 0-10 point scale where 0 = none and 10 = worst.  
a. pain  
b. redness  
c. dryness  
d. cracking  
e. roughness 
f. itching 
g. overall skin irritation 
Secondary endpoints 
1. Change from baseline to Day 28 in pH. 
2. Change from baseline to Day 28 in TEWL. 
3. Change in S. aureus colonization from baseline to Day 28.  
Inclusion Criteria 
1. HCW using PPE at least 6 hours/day, 4 days/week or, depending on shift work, 24 
hours/week, for at least one (1) month, 
2. Men or women, any age 
3. Overall skin irritation score of at least 4 on 0-10 scale where 0 = none and 10 = worst 
4. Must be willing to stop use of any other emollient and lotion for one (1) week between 
screening and baseline visit and for the duration of the study. 
5. Participant is willing to stop use of, or not begin, use of any topical corticosteroids, 
emollients and lotions to the hands and face for the duration of the trial. 
 
 
 

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Exclusion Criteria 
1. History of any skin disorder existing prior to March 1, 2020 characterized by chronic visible 
lesions or skin irritation symptoms including, but not limited to atopic dermatitis, eczema, 
moderate-severe acne, chronic dry skin and psoriasis. 
2. Use of topical or systemic corticosteroids within one (1) month of baseline visit. 
3. History of any significant medical condition that, in the opinion of the investigator, might put 
the subject at risk in this trial.  
4. Participation in another clinical trial within 30 days or 5 half-lives of the study agent, 
whichever is longer. 
Study test item 
EpiCeram® 90 gram tubes 
 
Number Subjects 
Fifty (50) subjects will be evaluated in this study. Accordingly, 55 subjects will be enrolled to 
allow for a 10% drop out rate. 
 
Efficacy Measurements 
1. Symptom scales 
a. pain  
b. redness  
c. dryness  
d. cracking  
e. roughness 
f. itching 
g. overall skin irritation 
2. Surface Skin pH  
3. TEWL  
4. SCH 
5. Antimicrobial peptides (LL-37, HBD-2) 
6. Free fatty acids 
7. Bacterial qPCR 
a. S. aureus 
      b.   MRSA 
            c. S. epidermidis 
Safety Measurements 
Adverse Events 
 
Statistics 
Descriptive statistics will be calculated for all demographic and clinical characteristics at 
baseline and study outcomes for each time period.  Means and standard deviations will be 
presented for continuous variables (e.g., age) and proportions and frequencies for categorical 

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variables (e.g., sex). Paired t-tests will be used to assess unadjusted differences in primary 
outcomes of face and hand skin irritation symptoms (pain, redness, dryness, cracking, roughness, 
itching and overall skin irritation) and secondary outcomes of pH, TEWL, and S. aureus 
colonization level between the baseline visit and Day 28 follow-up visit. Analysis will be 
performed on the Intention-to-Treat (ITT) sample. Standard data quality checks will be 
performed. The sample size of n = 50 is sufficiently powered (1 – β = 0.80) to identify a medium 
effect size of d = 0.4 in a two-tailed test with α set at 0.05. Given the multiple primary endpoints, 
p-values will be reported with high precision (four percentage points) to allow for multiple 
comparisons adjustments as desired. 
 
 

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understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
EpiCeram for skin protection in healthcare workers using personal protective equipment. 
Protocol #: PPE-01 
1. Introduction: 
During the current COVID-19 pandemic, health care workers (HCW) report that the prolonged 
use of personal protective equipment (PPE), particularly gloves and face covering, results in 
irritant contact dermatitis manifested by symptoms of pain, itching, burning and non-specific 
discomfort of the hands and face and associated visible physical changes of erythema, dryness, 
roughening and cracking of the affected skin (Jiang, et al 2020). These changes are aggravated 
by frequent hand washing and antimicrobial alcohol use. These irritative changes are likely 
associated with defects in the normal barrier structure and function of the skin, including, but not 
limited to, lowering of pH, excessive water loss, alteration of skin microbiome, lowered 
resistance to allergens and pathogens and immunological dysfunction. It is unknown whether 
these changes could increase the likelihood of S. aureus skin contamination or, in people exposed 
to, but not systemically ill with, COVID-19 to act as “silent” carriers of coronavirus. 
 
EpiCeram, a marketed product, is a three lipid emollient that has been shown to improve barrier 
structure and function, reduce skin pH, helps restore the microbiome components toward normal, 
improve immunological function and reduce symptoms associated with disrupted skin surfaces 
(Elias 2014, Elias 2019 and Kircik 2014). In contrast, some readily available over the counter 
skin care products may actually increase barrier dysfunction and aggravate skin disease (Li 2017, 
Elias 2019). 
 
2. Hypotheses 
a. The signs and symptoms of skin irritation secondary to extensive use of PPE will be 
accompanied by measurable defects in skin barrier structure and function. 
b. EpiCeram will improve measurements of skin barrier integrity. 
c. Signs and symptoms of skin irritation will improve after one month of EpiCeram use. 
d. Improvement of skin barrier function will restore reduce skin colonization by 
pathogenic bacteria. 
 
3. Study design 
This will be a one (1) month, open label study. Subjects must be HCW who have used 
face and hand PPE at least four (4) days a week for a minimum of one (1) month (or, 
depending on shift work, at least 24 hours/week) and who have new (after March 1, 
2020) symptomatic skin irritation on the hands and/or face. No change to required hand 
washing protocols or other protective measures will be required. 
At Visit 1, Screening the study will be explained and an informed consent document (ICD) 
signed. Subjects will be entered into the electronic data capture (EDC) system using a direct data 
capture (DDC) tablet. Subjects will complete an overall skin irritation assessment on 0-10 scale 
where 0 = none and 10 = worst. If it is equal to or greater than 4, the subject may proceed to 

Primus Pharmaceuticals, Inc. 
PPE-01 v 3.1 
10 
The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
enrollment provided all other inclusion and exclusion are met. If the subject has not used any 
lotions and emollients for the previous one (1) week on the face and hands, washout is not 
necessary, and Baseline visit activities may be performed at the Screening visit. Subjects 
requiring washout, will refrain from using any lotions and emollients for one (1) week between 
Visits 1 and 2 and then, for the duration of the study. Visit 2 (Baseline) will occur seven (7) days 
after Visit 1.  
 
At Visit 2, subjects will complete an overall skin irritation assessment on a 0-10 scale where 0 = 
none and 10 = worst. Subjects will complete skin symptom scales of pain, redness, dryness, 
roughness, itching and cracking on a scale on a 0-10 scale where 0 = none and 10 = worst. 
A manual describing detailed steps for collection of laboratory, photographic and skin surface 
measurements will be provided to the site by the sponsor. Vendors will supply training and 
references for the camera and EDC system.  
Photographs: Digital 3D photographs will be taken of the face and back of the hand. The face 
photo will be a two (2) inch by three (3) inch area of the cheek without identifying features. The 
hand photo will be the worst area of involvement as selected by the subject.  
Skin Function Testing: Measurements of transepidermal water loss (TEWL) with stratum 
corneum hydration (SCH) and surface skin pH will be taken on the web between the 3rd and 4th 
metacarpophalangeal (MCP) joints on the dorsum of the dominant hand used.  
Laboratory Testing: Two types of specimens will be obtained; a swab and tape stripping. A 
single skin swab for bacterial qPCR will be obtained from the palm of the dominant hand. Non-
invasive tape stripping of surface cells (3 strips/sample) will be performed at 2 sites; on the web 
between the 3rd and 4th metacarpophalangeal (MCP) joints on the dorsum of the dominant hand 
for antimicrobial peptides (AMP) and three (3) strips/sample from the web between the 2nd and 
3rd MCP joints on the dominant hand for free fatty acids. See the manual for detailed instructions 
on specimen collection. The subject will then be directed to apply EpiCeram to the hands (wrist 
to fingertips, back and front) and face at least three (3) times daily (about every 8-10 hours), 
more often if the subject wishes. 
 
At Visit 3 (Final), 28 days later subjects will complete an overall skin irritation assessment on a 
0-10 scale where 0 = none and 10 = worst. Subjects will complete skin symptom scales of pain, 
redness, dryness, roughness, itching and cracking on a scale on a 0-10 scale where 0 = none and 
10 = worst. Photos, skin function and laboratory testing will be in the same location as Visit 2. 
Photographs: Digital 3D photographs will be taken of the face and back of the hand. The face 
photo will be a two (2) inch by three (3) inch area of the cheek without identifying features. The 
hand photo will be the worst area of involvement as selected by the subject.  
Skin Function Testing: Measurements of transepidermal water loss (TEWL) with stratum 
corneum hydration (SCH) and surface skin pH will be taken on the dominant hand on the dorsum 
of the 3rd and 4th metacarpal phalanges.  
Laboratory Testing: Two types of specimens will be obtained; a swab and tape stripping. A 
single skin swab for bacterial qPCR will be obtained from the palm of the dominant hand. Non-
invasive tape stripping of surface cells (3 strips/sample) will be performed at 2 sites; on the web 
between the 3rd and 4th metacarpophalangeal (MCP) joints on the dorsum of the dominant hand 

Primus Pharmaceuticals, Inc. 
PPE-01 v 3.1 
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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
for antimicrobial peptides (AMP) and three (3) strips/sample from the web between the 2nd and 
3rd MCP joints on the dominant hand for free fatty acids. See the manual for detailed instructions 
on specimen collection. The subject will then be directed to apply EpiCeram to the hands (wrist 
to fingertips, front and back) and face at least three (3) times daily (about every 8-10 hours), 
more often if the subject wishes. The investigator will assess the subject’ Response to Therapy 
on a scale of 1-5 with 1 = no response and 5 = best response. Subjects may then be discharged 
from the study.  
4. Primary endpoints 
a. Change in patient reported outcome of overall face and hand skin irritation symptoms 
from baseline to Day 28, of at least 2 points on a 0-10 point scale where 0 = none and 
10 = worst.  
b. Change in any two of the following specific skin irritation symptoms of at least 2 
points on a 0-10 point scale where 0 = none and 10 = worst.  
1. pain  
2. redness 
3. dryness  
4. cracking  
5. roughness 
6. itchiness 
7. overall skin irritation 
 
5. Secondary endpoints 
a. Reduction from baseline to Day 28 in pH 
b. Reduction from baseline to Day 28 in TEWL 
c. Reduction in S. aureus colonization from baseline to Day 28  
 
6.  Subject Selection Criteria 
6.1 
Inclusion Criteria 
a. HCW using PPE at least 6 hours/day, 4 days/week or, depending on shift    
work, 24 hours/week, for at least one (1) month 
b. Men or women, any age 
c. Overall skin irritation score of at least 4 on 0-10 scale where 0 = none and  
   10 = worst 
d. Willing to stop use of any other emollient and lotion for one (1) week 
between screening and baseline visit and for the duration of the study. 
e. Participant is willing to stop use of or not begin use of any topical 
corticosteroids, emollients and lotions to the hands and face for the duration 
of the trial. 
 
6.2 
Exclusion Criteria 
a. History of any skin disorder existing prior to March 1, 2020 characterized by 
chronic visible lesions or skin irritation symptoms including, but not limited to 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
atopic dermatitis, eczema, moderate-severe acne, chronic dry skin and 
psoriasis. 
b. Use of topical corticosteroids within one (1) month of baseline visit.  
c. History of any significant medical condition that, in the opinion of the 
investigator, might put the subject at risk in this trial.  
d. Participation in another clinical trial within 30 days or 5 half-lives of the study 
agent, whichever is longer. 
 
7. Test Item and Proscribed Treatments 
This is an open label study. All subjects will receive EpiCeram, delivered in 90 gm tubes. 
The EpiCeram cream will be applied to face and hands at least three (3) times per day, 
about every 8 hours taking care to apply after bathing and before applying any makeup. 
Subjects are prohibited from using any other skin lotion by prescription or over the 
counter. Subjects are specifically prohibited from using any corticosteroid containing 
skin products. 
8. Number of Subjects 
Fifty (50) subjects will be evaluated in this study. To account for subjects who fail to 
complete the trial fifty-five (55) subject will be enrolled. 
9. Safety measurements 
Adverse events 
10. Efficacy measurements 
a. Symptom scales 
b. TEWL 
c. Hydration 
d. Skin pH 
e. Skin surface bacterial qPCR 
 
11. Study Procedures 
11.1 Screening visit 
At least one (1) week prior to the baseline visit patients will be evaluated for inclusion in 
the study.  Patients will have the study thoroughly explained to them and all their questions 
will be answered.  Patients will sign the Informed Consent Document (ICD) before any 
study related procedures are performed.  By definition, a patient becomes a study subject 
once he/she has signed the informed consent document.  Every patient must have the 
opportunity to take home an unsigned copy of the ICD to discuss the study with family or 
friends and consider their decision whether to participate.   
Screening and Baseline procedures may occur on the same day the study is first presented 
if the patient elects to proceed at that time and meets the inclusion and exclusion criteria 
including the washout requirement. A manual describing detailed steps for collection of 
laboratory, photographic and skin surface measurements will be provided to the site by the 
sponsor. 

Primus Pharmaceuticals, Inc. 
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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
At the Screening visit, each subject will be entered into the EDC system using a DDC tablet 
which will issue a unique identifier.  
Subjects who agree to participate will perform the following: 
a. Review and sign the Informed Consent Document including consent for photos. 
b. Assess for overall irritation score of > 4 on the previously described scale of 0-10. 
c. Assess for meeting all inclusion and exclusion criteria. 
d. The subject will be instructed to stop using (washout) emollients and lotions currently 
in use on the hands and face for one (1) week and for the duration of the study. 
e. The subject will be instructed to return in one (1) week for the Baseline visit. If 
washout requirement is met, Baseline visit activities may be performed at the 
Screening visit. Instruct subjects to refrain from washing hands and face for 2-hours 
prior to each visit. 
 
11.2 Baseline Visit 
Perform photos, skin function testing and laboratory testing in the order listed below. 
a. Assess for overall irritation score of > 4 on the previously described scale of 0-10. 
b. Assess for adverse events and changes to skin routine. 
c. Complete skin symptom rating scales.  
d. Take digital photos of hand and face.  
e. Measure skin surface TEWL and SCH. 
f. Measure face and hand skin surface pH. 
g. Swab the dominant hand for bacterial qPCR.  
h. Perform tape stripping for free fatty acids and AMPs.  
i. Dispense one unit of EpiCeram. 
j. Subject will apply EpiCeram TID at home to clean face and hands (wrist to fingertips, 
back and front). 
11.3 Final Visit (4 weeks) 
Perform photos, skin function testing and laboratory testing in the order listed below. 
a. Assess for overall irritation score of > 4 on the previously described scale of 0-10. 
b. Assess for adverse events and changes to skin routine. 
c. Complete skin symptom rating scales. 
d. Take digital photos of hand and face. 
e. Measure skin surface TEWL and SCH. 
f. Measure face and hand skin surface pH.  
g. Swab the dominant hand for bacterial qPCR. 
h. Perform tape stripping for free fatty acids and AMPs.  
i. Investigator assessment of subject’s Response to Therapy on a 1 – 5 scale, with 1 = 
no response and 5 = best response. 
j. Resolve AEs.  
 
 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
12.0     Study Withdrawal 
Subjects may be withdrawn from the study for one or more of the following reasons. 
a. Request for withdrawal by the subject for any reason whether or not related to an AE. 
b. Lost to follow-up.  
c. Noncompliance with the protocol.  
d. Unacceptable adverse event.  In this case the decision to remove the subject from the 
study may be made by the subject, the investigator or Primus.  
e. Determination by the investigator or Primus, that, withdrawing from the study is in 
the best medical interest of the subject. 
f. Administrative reasons such as early termination of the study. 
g. Treatment failure requiring an increase or addition of concomitant medication (s) or 
the use of any excluded medication.   
h. If the subject is discontinued prior to receiving the first dose of study product AEs 
and SAEs will be collected until the termination visit.  If the subject has received 
study medication AEs and SAEs will be collected until the termination visit or until 
30 days after the last dose of study product, whichever is later All AEs and SAEs 
must be followed until resolution or stability.  
According to FDA and the Declaration of Helsinki a subject in a clinical trial has the right to 
withdraw at any time and for any reason without prejudicing his/her future medical care at the 
investigative site. In the case of early withdrawal of a subject, the investigator should make all 
reasonable efforts to have the subject attend a termination visit and document all details of the 
early termination on the appropriate data collection tool/CRF. 
13.0     Early Termination Visit Procedures 
If a subject wishes to end his/her participation in the study prematurely, whether because of an AE 
or any other reason, he/she should be asked to complete a termination visit at the next scheduled 
appointment or within 14 days, whichever is more convenient.  The investigator should make 
every reasonable attempt to perform the final assessment.  Whenever possible, all final visit 
procedures should be performed at the time of an early termination visit.  All outstanding AEs 
should be followed to resolution or stability.  The reason for early termination should be clearly 
stated in the source and data collection tool. 
 
All adverse events that result in a subject’s withdrawal from the study must be reported to the 
Project Manager of Clinical Investigation, Mary Sanstead, BSN (480-250-6689 cell), within 24 
hours.  
 
14.0   Safety 
14.1     Definition of Adverse Event 
An AE is any untoward or unexpected medical occurrence in a subject participating in a clinical 
study whether or not there is a possible relationship between the investigative agent and the 
event and regardless of whether or not the subject has received any study product.  Once a 
patient signs an informed consent document, he/she becomes a study subject and AE data will 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
be collected from that point until the end of the study or 30 days after the last dose of study 
product, whichever is longer.  An AE may be an untoward, unintended or unexpected sign, 
symptom, disease or worsening of disease, an abnormal laboratory finding considered by the 
investigator to be clinically significant. Laboratory tests that deviate significantly from the 
normal range should be repeated with prior permission of the sponsor.  If the abnormality 
persists and the investigator considers this a clinically significant abnormality, then efforts 
should be made to ascertain the etiology.  If the abnormality is increasing, particularly if it was 
not there at baseline, the Director of Clinical Investigation should be notified. 
14.2    Serious Adverse Events 
SAEs require special attention, management and documentation.  All SAEs must be 
reported to Primus within 24 hours whether or not they are considered by the 
investigator to be related to the study agent (s).  Although cancer is no longer considered 
an SAE by the USFDA, Primus requires notification of such diagnoses within 48 hours of 
the time the investigator first learns of the event. An SAE is any medical event that: 
a. results in death 
b. is life threatening—the investigator believes the subject’s life is in immediate 
danger. This does not include events that, had they been more severe, might have 
been life threatening. 
c. requires in-patient hospitalization or prolongation of an existing hospitalization. 
d. results in permanent disability. 
e. is a congenital anomaly or birth defect. 
f. requires medical or surgical intervention to prevent one of the outcomes above. 
14.3           Severity of Adverse Events 
The investigator must rate every AE for severity according to the following guidelines: 
• mild                       does not interfere with daily activities. 
• moderate               discomfort and/or dysfunction enough to interfere with, but  
                                    not prevent, daily activities 
• severe                    significant impairment of ability to perform daily activities. 
 
       14.4           Assessment of Causality 
Investigators will be responsible for determining the relationship of the study product(s) to 
the AE and will record their conclusions on the data collection tool, adverse event page.  It 
is recognized that causality often cannot be established with certainty.  Investigators must 
use their best clinical judgment keeping in mind the following questions: 
a. Was study product administered? 
b. What was the temporal relationship between the administration of study product and the 
AE?  Was this consistent with the nature of the AE? 
c. Was there another obvious or possible cause for the AE? 
d. Was the AE consistent with the known effects of the study product? 
e. Were there any features of the subject’s clinical state, concomitant medications or 
diseases or environmental factors that could have caused or modified the AE? 

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understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
f. Did the AE resolve, improve, remain stable or worsen after the study product was 
stopped or the dose reduced? 
g. If the subject was re-exposed to the study product (re-challenge), did the AE recur, 
worsen or remain unchanged?  Re-challenge should be attempted only after careful 
consideration and only after discussion with Primus. 
 
 
Investigators should use their best clinical judgment and the guidelines above to assign all 
AEs and SAEs to one of the following four categories: 
 
Not Related                Those AEs for which other etiologies can clearly and  
                                    conclusively be defined. 
Possibly Related         Those events for which other etiologies cannot be clearly  
demonstrated, and for which a relationship to the study  
                                    agent cannot be positively excluded. 
Probably Related        After careful scrutiny of the available medical facts, there is  
                                    a reasonable, but inconclusive, certainty that the event is  
                                    related to the study product. 
Definitely Related      After careful medical evaluation there is little or no doubt  
                                    that the study product is the direct etiologic cause of the  
 
 
 
AE. This situation is most commonly seen when an AE  
 
 
 
recurs after re-challenge with study product. 
 
14.5     Reporting Serious Adverse Events 
SAEs must be reported to Primus by telephone or, if from a non-U.S. site, by e-mail within 
24 hours from the time the investigator first learns of them.  This should be followed by a 
faxed report outlining the details of the event and the investigator’s assessment of the 
severity and relationship of the event to the study agent.  All SAEs will be reported on both 
the AE and SAE pages of the data collection tool/case report forms.  In addition: 
a. A new SAE form must be completed and faxed to Primus within 24 hours. 
b. Follow-up SAE forms must be completed and faxed to Primus whenever new 
information becomes available about the event. 
c. A final SAE report must be completed and faxed to Primus when the event has 
resolved or its consequences have stabilized and all relevant information (including 
hospital records, laboratory and pathology reports, autopsy reports, etc.) have been 
received.  It is the responsibility of the investigator to obtain copies of all relevant 
information in a timely manner. 
d. It is the responsibility of the investigator to determine the severity and causality of the 
SAE. 
e. The initial SAE report and all subsequent reports must be retained in the subject’s 
study file together with a telephone log of all contacts with Primus and the 
subject.  These should be recorded at the time of the conversation, dated and signed 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
by the investigator or his/her representative and should include the name of the 
person with whom the conversation was held. 
 
 
 
Telephone contact should be made with Robert Levy, MD, Director Clinical Development 
480-483-1410 (office) 
480-415-6779 (mobile) 
Fax 480-483-2604 
 
If Dr. Levy is unavailable contact: 
Mary Sanstead, BSN, Project Manager 
480-483-1410 
480-250-6689 (cell) 
Fax 480-483-2604 
 
Primus will review all SAEs with the investigator and a decision will be made regarding 
the need for further action.  Primus’ primary concern will be subject safety, both for the 
subject having the event as well as for the other subjects in the study.  If, after detailed 
review, it is determined that a subject safety issue exists, Primus will notify all investigators 
participating in any trial with the same study product and the IRB(s) overseeing those trials, 
and may require one or more of the following: 
a. Discontinuation or suspension of the study 
b. Modification of the protocol 
c. Modification of the informed consent document to reflect additional risk(s) to be 
signed by current and future subjects. 
d. Addition of newly discovered adverse events to the investigator’s brochure 
14.6     Follow-Up of Adverse Events 
All adverse events, whether serious or non-serious, must be followed until resolution or 
stability.  This follow-up may extend beyond the end of the study.  Primus considers AE 
follow-up to be part of a study.  Therefore, a study cannot be closed at an investigative site 
if an AE is outstanding. Any serious AE occurring after the conclusion of a study must be 
reported to Primus if the investigator thinks the event may be causally related to the study 
agent. 
 
14.8     Deaths 
All deaths, regardless of cause, that, occur between the time a subject signs an informed 
consent document and the final study visit or 30 days after the last dose of study product, 
whichever is longer, must be reported to Primus by telephone with a follow-up fax within 
24 hours of the investigator becoming aware of the death.  This applies whether or not the 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
subject has received study product and whether or not the study product is thought to be 
causally related to the death. It is the investigator’s responsibility to obtain all relevant 
medical records and autopsy reports and forward them to Primus as soon as possible. 
 
14.9     Reporting Safety Information to IRB 
It is the responsibility of the investigator to notify his/her IRB of any unexpected or 
unknown risk to study subjects.  This includes death from any cause and all SAEs.  The 
investigator should make this report within 14 days of the onset of the SAE.  The report 
should include any action taken after discussion of the SAE with Primus. 
 
14.10   Managing Adverse Events 
All AEs and SAEs should be medically managed according to the best medical standards 
available in the investigator’s community.  Except in the case of emergent treatment and 
routine care, the management of the event should be discussed with Primus.  Decisions 
regarding re-challenge with study drug must be made in consultation with Primus. 
 
14.11   Pregnancy 
EpiCeram is device whose ingredients include at least 2 occlusive products (petrolatum, 
dimethicone) that prevent systemic uptake and therefore the device has no impact on the 
reproductive system of the user. Pregnancy data will not be collected during this study. 
 
DEFINITION OF DEVICE PER FDA:  Per Section 201(h) of the Food, Drug, and 
Cosmetic Act, a device is: An instrument, apparatus, implement, machine, contrivance, 
implant, in vitro reagent, or other similar or related article, including a component part, or 
accessory which is: 
…3. intended to affect the structure or any function of the body of man or other animals, 
and which does not achieve its primary intended purposes through chemical action within 
or on the body of man or other animals and 
which does not achieve its primary intended purposes through chemical action within or 
on the body of man or other animals and which is not dependent upon being metabolized 
for the achievement of its primary intended purposes. The term "device" does not include 
software functions excluded pursuant to section 520(o). 
 
15.0       Ethical Considerations 
This study will be conducted in accordance with the principles of the Declaration of Helsinki, ICH 
guidelines and Good Clinical Practices (GCPs) and US FDA regulations.   
 
15.1     Informed Consent 
All patients must read and sign the institutional review board (IRB) approved Research 
Subject Information and Consent Form before they can be subjects in this research study. 
It is the investigator’s responsibility to fully inform the patient about the procedures, risks 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
and benefits of the study and to answer, in a manner clearly understandable to the 
patient.  The consent must be obtained and documented according to the instructions of the 
IRB. A copy of the signed and dated document must be given to the subject.  The IRB 
approved document must not be modified in any way from its original form.  The original 
copy must be retained with the subject’s study file and is subject to inspection by 
representatives of Primus and regulatory agencies. 
 
All written material read by or distributed to a subject during the study must be written in 
a language the subject can read and understand and approved by the IRB. 
 
15.2   Institutional Review Board (IRB) 
For all studies performed in the United States, Primus will assume responsibility for 
submitting the required documents to a central IRB.   Before this can be done each 
investigator must submit the following to Primus: 
a. Signed and dated protocol signature page. 
b. Completed, signed and dated FDA Form 1572, when required. 
c. Completed, signed and dated W-9 form. 
d. Current curriculum vitae for investigator and all sub-investigators, signed and dated. 
e. Investigator conflict of interest form. 
If an investigator wishes to use an IRB other than that selected by Primus, he/she may do 
so after obtaining approval from Primus.  In this case, the investigator will be responsible 
for all required submissions.  Non-U.S.A. investigative sites will have IRB approval 
arranged by the contract research organization (CRO) engaged by Primus for the 
execution of the study.  Any changes to the model consent must be first approved by 
Primus, in writing. The investigator must agree to all protocol amendments and, if 
necessary, make appropriate changes in the consent.  The IRB should be notified of any 
such changes and IRB approval must be sought for any changes involving subject safety. 
Serious or unexpected adverse events must be reported to the IRB according to their 
instructions. 
All investigators will be responsible for completing reports as required by the IRB.  One 
copy of those reports should be kept in the study regulatory file and another submitted to 
Primus. 
15.3   Subject Confidentiality 
Subject identities should always be protected.  This is the legal responsibility of the 
investigator.  Subjects should be identified in study documents only by initials and study 
number on any document sent to Primus or a regulatory agency.  Documents that are only 
for office use must be kept in strict confidence.  It is strongly recommended that the 
investigative site have its own HIPAA document in place and that patients read, sign and 
date this at the same time they sign the consent. 
 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
Investigators must allow representatives of Primus or government regulatory agencies to 
inspect study records with subject de-identification in place. 
 
16.0     Administrative and legal obligations 
16.1     Pre-study Documentation 
Before an investigator can begin screening subjects and before shipment of study product can 
commence the investigator must complete and return the following to Primus: 
a. Signed and dated protocol signature page  
b. Completed, signed and dated FDA Form 1572, when required  
c. Copy of IRB approved consent  
d. Copy of IRB approval letter  
e. Current CVs of the investigator and all sub-investigators, signed and dated  
f. Name, address and telephone number of any local laboratories to be used in the study  
g. Normal values for local laboratory  
h. Agreement to dispose of unused drug supplies per their community requirements  
i. Signed and dated contract to conduct the study under the conditions and financial 
arrangements specified  
j. Financial disclosure form  
k. Name and contact information of person(s) responsible for the day to day 
management of the study  
16.3           Protocol Amendments 
Protocol amendments may be made only by Primus.  The investigator’s IRB must be informed 
of any amendments that may affect subject safety or the conduct of the study.  The IRB must 
issue a letter of approval of such amendments.  The investigator must keep the original letter 
in the study’s regulatory binder and forward a copy of the letter to Primus. 
 
16.4           Study Termination 
Both the investigator and Primus have the right to terminate their participation in the study.  If 
this is done by the investigator, he/she must provide a detailed explanation of the action to 
Primus and the IRB and a copy of this account must be retained with the regulatory file. 
 
Upon completion of the study the investigator is required to send a summary of his/her 
experience to Primus and to the IRB.  This should include an impression of clinical response 
and an accounting of any AEs or SAEs thought to be possibly associated with the study 
product. 
                                                                                                         
16.5           Source Documents 
FDA regulations (21 CFR 312.62b) require an investigator “to prepare and maintain adequate 
and accurate case histories that record all the data and other observations pertinent to the 
investigation on each individual” participating in a clinical investigation whether or not they 
were administered the investigational product.  “Case histories include the case report forms 
and supporting data including, for example, progress note of the physician, the individual’s 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
hospital charts, and nurses’ notes.  The case history for each individual shall document that 
informed consent was obtained prior to participation in the study.”   Source documents may be 
reviewed and compared with data collection tool/CRFs at all monitoring visits.  All source 
documents and data collection tool/CRFs should be complete and up to date and filed in 
chronological order in the subject’s study file.   
The investigative site must maintain logs for the following: 
a. Screening visits  
b. Randomization  
c. Study product dispensed and returned  
d. Monitor visits  
e. Study personnel  
f. Telephone contact  
 
16.6          Data Collection Tools/Case Report Forms  
Primus will provide investigators with data collection tool (hard copy or electronic) bearing 
information identifying the study site and the principal investigator.  All data obtained during 
the study will be recorded on the data collection tool.  This data will be reviewed on site or 
electronically by a Primus clinical monitor (or an agent of Primus such as a contract research 
organization) who will forward one copy to Primus (if hard copy), the original to remain with 
the subject’s study data file. 
 
The data collection tool contains the critical study data and are the basis from which results are 
tabulated, analyses performed, and final reports made.  Therefore, it is essential that data 
recorded be legible, complete and accurate.  Forms should be typed or completed in black ball 
point ink (if hard copy).  Corrections should be made by placing a single line through the error, 
adding the correct data then signing and dating the correction.  Under no circumstances should 
the original entry be erased, overwritten, or obscured by white-out or some other method. The 
data collection tool should contain only de-identified information.  All data points must be 
answered.  If the information is unknown or unavailable the terms “NA” (not available), “ND” 
(not done), “SU” (subject unable) or “DP” (data pending) may be used. 
 
The investigator must maintain all records in a complete and current state.  All source 
documents and supporting materials must be available for inspection by Primus personnel or 
representatives of government agencies. 
 
16.7     Final Study Documentation and Storage 
Investigators must retain all study records in a secure location, safe from environmental 
damage, for the maximum time required by the FDA, Primus or his/her institution, 
whichever is longest.  These records should include, but are not limited to, the following: 
• Source documentation 
• Data collection tool/CRFs  

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understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
• Original reports of tests results 
• Protocols with amendments 
• Original signed and dated ICF(s) 
• Product accountability and dispensing logs 
• Correspondence with Primus, IRB and governmental agencies 
 
The investigator must complete a summary report (form provided) and submit it to Primus 
upon completion of the study. All data and other information may be submitted to the 
governmental regulatory agencies as required by the regulations. No study document may 
be destroyed without the written permission of Primus.  Any change in storage location or 
assignation of the records to another party must first be approved, in writing, by Primus.  If, 
for any reason, the investigator becomes unable to store study documents Primus must be 
notified.  Study documents should never be destroyed without the written consent of 
Primus. 
 
 
17.0     Summary of Investigator responsibilities 
Investigator responsibilities include, but are not limited to: 
a. Will conduct the study according to the protocol and will make no changes without the 
consent of the sponsor.  This requirement is not intended to limit the investigator’s ability to 
deviate from the protocol to protect the health and welfare of a subject.  
b. Will comply with all applicable regulatory requirements.  
c. Will personally supervise the conduct of the study.  
d. Will report any adverse events that occur during the study.  
e. Will promptly treat or arrange for treatment of any AE or SAE.  
f. Has read and understands the information contained in the investigator’s Brochure or product 
information document. 
g. Will attend any investigator meetings conducted by Primus. 
17.1     Data Collection and Study Monitoring 
This study will be monitored, in person or electronically, by Primus personnel or by clinical 
research associates (CRAs) employed by Primus for this project.  Site visits, if necessary, will be 
scheduled at pre-established intervals and will be scheduled in advance.  All site visits will be 
conducted according to Primus’ standard operating procedures (SOPs).  The monitor must be 
allowed free access to all study records and supporting in order to verify the accuracy, consistency 
and completeness to ensure the study is being conducted in accordance guidelines of good clinical 
practice.  Some site visits may be conducted remotely using an internet, based system with which 
the monitor and coordinator can view and speak to each other and work simultaneously on 
documents in real time. Study coordinators must be available and be able to devote the required 
time to the site visit. The primary investigator or sub-investigator should also be available to offer 
comments and resolve any issues that may arise.  
 
18.0     Audits 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
The investigative site may be subject to audit by Primus or by regulatory agencies.  All areas of 
the site will be examined including, but not limited to, subject treatment rooms, laboratory, product 
storage and preparation areas, and document storage.  To prepare for any audit all data and 
documentation must be complete and organized chronologically by document type. If a site is 
notified of impending regulatory agency audit the primary investigator should promptly inform 
Primus to arrange for audit preparation assistance. 
 
19.0     Primus contacts 
Questions related to study conduct, supplies or administrative matters should be directed to: 
Ms. Mary Sanstead, BSN 
Project Manager  
480-483-1410 (Primus office) or 
480-250-6689 (mobile) 
 
 
 
Questions related to SAE’s, medical observations or interventions should be directed to: 
Robert Levy, MD 
Director of Clinical Development 
480-483-1410 (Primus office) or 
480-415-6779 (mobile) 
 
Primus Pharmaceuticals, Inc. 
7373 N. Scottsdale Rd. 
Ste. B-200 
Scottsdale, AZ 85253 
Tel: 480-483-1410 
Fax: 480-483-2604 
 
20.0     Publication/presentation of data         
            Primus regards all information obtained from the conduct of this study as  
            confidential.  If an investigator wishes to publish or present in oral or written form  
            all or part of the data obtained during the study he/she must first submit a  
            complete copy of such presentation to the director of Clinical Investigation for  
            review and approval.  This submission must occur no later than sixty (60) days  
            before the anticipated date of presentation.  The investigator will be required to  
            incorporate any suggestions made by Primus consistent with its right to protect  
            the confidentiality of the information. 
 
21.0     Statistical considerations 
Descriptive statistics will be calculated for all demographic and clinical characteristics at 
baseline and study outcomes for each time period.  Means and standard deviations will be 

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understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
presented for continuous variables (e.g. age) or proportions and frequencies for categorical 
variables (e.g., sex) to describe the sample. 
 
Paired t-tests will be used to assess differences in the primary outcomes of face and hand skin 
irritation symptoms (pain, redness, dryness, cracking, roughness, itching and overall skin 
irritation) between the baseline visit and Day 28 follow-up visit. The same analysis will be 
conducted for the secondary outcomes of pH, TEWL, and S. aureus colonization level. All 
statistical tests for the primary outcomes will be conducted will be two-tailed with α set at 0.05.  
All p-values will be reported with high precision (to the 4th decimal place) so that multiple 
comparisons adjustments may be applied, as desired. Table 1 below shows how the results will 
be presented. 
 
The analysis will be performed on the Intention-to-Treat sample. If there is attrition over the 
course of the study, attritors will be compared to completers in terms of measures taken at 
baseline. Any significant differences will be reported.  
 
All variables will be checked for outliers and skewness by visually examining boxplots.  Further 
evaluation of any outliers identified through visual checks will be conducted to assess if any 
participants should be excluded from the analysis.  The assumptions for each inferential 
statistical test will be evaluated.  In the event assumptions are not met, results from a Wilcoxon 
signed rank test will also be reported. 
 
 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
22.0 
References 
Czarnowicki T, Krueger JG, Guttman-Yassky E. Novel concepts of prevention and treatment of  
   atopic dermatitis through barrier and immune manipulations with implications for the atopic  
   march. Clin Rev Allergy Immunol. 2017.June:1723-32. 
Elias PM Lipid abnormalities and lipid based repair strategies in atopic dermatitis. Biochim  
   Biophys Acta. 2014.184:323-30. 
Elias PM, Wakefield JS, Man MQ. Moisturizers versus current and next generation 
   barrier repair therapy for the management of atopic dermatitis. Skin Pharmacol Physiol.  
   2019.32:1-7. 
Jiang Q, Song S, Zhou J, et al. Status of skin injury caused by personal protective equipment  
   among medical staff in fighting COVID-19: a multicenter, cross sectional study. Adv Wound  
   Care. 2020.9:357-64. 
Kircik LH. Effect of skin barrier emulsion cream vs a conventional moisturizer on transdermal  
   water loss and corneometry in atopic dermatitis, I pilot study. J Drugs Derm. 2014.13:1482-4 
Li Z, Hu L, Elias PM, et al. Skin care products can aggravate epidermal barrier function: studies  
   in a murine model suggest a pathogenetic role in sensitive skin. DOI. 10.1111/cod.12909 
 
 
 

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
Appendix I 
 
The World Medical Association  
Declaration of Helsinki  
World Medical Association Declaration of Helsinki: Recommendations Guiding Medical 
Doctors in Biomedical Research Involving Human Subjects  
Adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and as revised by 
the World Medical Assembly in Tokyo, Japan in 1975, in Venice, Italy in 1983, and in 
Hong Kong in 1989.  
 
Introduction  
It is the mission of the physician to safeguard the health of the people. His or her knowledge and 
conscience are dedicated to the fulfillment of this mission.  
The Declaration of Geneva of the World Medical Association binds the physician with the 
words, "The health of my patient will be my first consideration," and the International Code of 
Medical Ethics declares that, "A physician shall act only in the patient's interest when providing 
medical care which might have the effect of weakening the physical and mental condition of the 
patient."  
The Purpose of biomedical research involving human subjects must be to improve diagnostic, 
therapeutic and prophylactic procedures and the understanding of the etiology and pathogenesis 
of disease.  
In current medical practice most diagnostic, therapeutic or prophylactic procedures involve 
hazards. This applies especially to biomedical research.  
Medical progress is based on research which ultimately must rest in part on experimentation 
involving human subjects.  
In the field of biomedical research a fundamental distinction must be recognized between 
medical research in which the aim is essentially diagnostic or therapeutic for a patient, and 
medical research, the essential object of which is purely scientific and without implying direct 
diagnostic or therapeutic value to the person subjected to the research.  
Special caution must be exercised in the conduct of research which may affect the environment, 
and the welfare of animals used for research must be respected.  
Because it is essential that the results of laboratory experiments be applied to human beings to 
further scientific knowledge and to help suffering humanity, the World Medical Association has 
prepared the following recommendations as a guide to every physician in biomedical research 
involving human subjects. They should be kept under review in the future. It must be stressed 
that the standards as drafted are only a guide to physicians all over the world. Physicians are not 
relieved from criminal, civil and ethical responsibilities under the laws of their own countries.  
I. Basic Principles  
1. Biomedical research involving human subjects must conform to generally accepted 
scientific principles and should be based on adequately performed laboratory and animal 
experimentation and on a thorough knowledge of the scientific literature.  

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The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
2. The design and performance of each experimental procedure involving human subjects 
should be clearly formulated in an experimental protocol which should be transmitted for 
consideration, comment and guidance to a specially appointed committee independent of 
the investigator and the sponsor provided that this independent committee is in 
conformity with the laws and regulations of the country in which the research experiment 
is performed.  
3. Biomedical research involving human subjects should be conducted only by scientifically 
qualified persons and under the supervision of a clinically competent medical person. The 
responsibility for the human subject must always rest with a medically qualified person 
and never rest on the subject of the research, even though the subject has given his or her 
consent.  
4. Biomedical research involving human subjects cannot legitimately be carried out unless 
the importance of the objective is in proportion to the inherent risk to the subject.  
5. Every biomedical research project involving human subjects should be preceded by 
careful assessment of predictable risks in comparison with foreseeable benefits to the 
subject or to others. Concern for the interests of the subject must always prevail over the 
interests of science and society.  
6. The right of the research subject to safeguard his or her integrity must always be 
respected. Every precaution should be taken to respect the privacy of the subject and to 
minimize the impact of the study on the subject's physical and mental integrity and on the 
personality of the subject.  
7. Physicians should abstain from engaging in research projects involving human subjects 
unless they are satisfied that the hazards involved are believed to be predictable. 
Physicians should cease any investigation if the hazards are found to outweigh the 
potential benefits.  
8. In publication of the results of his or her research, the physician is obliged to preserve the 
accuracy of the results. Reports of experimentation not in accordance with the principles 
laid down in this Declaration should not be accepted for publication.  
9. In any research on human beings, each potential subject must be adequately informed of 
the aims, methods, anticipated benefits and potential hazards of the study and the 
discomfort it may entail. He or she should be informed that he or she is at liberty to 
abstain from participation in the study and that he or she is free to withdraw his or her 
consent to participation at any time. The physician should then obtain the subject's freely-
given informed consent, preferably in writing.  
10. When obtaining informed consent for the research project the physician should be 
particularly cautious if the subject is in a dependent relationship to him or her or may 
consent under duress. In that case the informed consent should be obtained by a physician 
who is not engaged in the investigation and who is completely independent of this official 
relationship.  
11. In case of legal incompetence, informed consent should be obtained from the legal 
guardian in accordance with national legislation. Where physical or mental incapacity 
makes it impossible to obtain informed consent, or when the subject is a minor, 
permission from the responsible relative replaces that of the subject in accordance with 
national legislation. Whenever the minor child is in fact able to give a consent, the 
minor's consent must be obtained in addition to the consent of the minor's legal guardian.  

Primus Pharmaceuticals, Inc. 
PPE-01 v 3.1 
28 
The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
12. The research protocol should always contain a statement of the ethical considerations 
involved and should indicate that the principles enunciated in the present Declaration are 
complied with.  
II. Medical Research Combined with Professional Care (Clinical Research)  
1. In the treatment of the sick person, the physician must be free to use a new diagnostic and 
therapeutic measure, if in his or her judgment it offers hope of saving life, reestablishing 
health or alleviating suffering.  
2. The potential benefits, hazards and discomfort of a new method should be weighed 
against the advantages of the best current diagnostic and therapeutic methods.  
3. In any medical study, every patient--including those of a control group, if any--should be 
assured of the best proven diagnostic and therapeutic method.  
4. The refusal of the patient to participate in a study must never interfere with the physician-
patient relationship.  
5. If the physician considers it essential not to obtain informed consent, the specific reasons 
for this proposal should be stated in the experimental protocol for transmission to the 
independent committee (I,2).  
6. The physician can combine medical research with professional care, the objective being 
the acquisition of new medical knowledge, only to the extent that medical research is 
justified by its potential diagnostic or therapeutic value for the patient.  
III. Non-Therapeutic Biomedical Research Involving Human Subjects (Non-Clinical 
Biomedical Research)  
1. In the purely scientific application of medical research carried out on a human being, it is 
the duty of the physician to remain the protector of the life and health of that person on 
whom biomedical research is being carried out.  
2. The subjects should be volunteers--either healthy persons or patients for whom the 
experimental design is not related to the patient's illness.  
3. The investigator or the investigating team should discontinue the research if in his/her or 
their judgment it may, if continued, be harmful to the individual.  
4. In research on man, the interest of science and society should never take precedence over 
considerations related to the well-being of the subject.  
 
 
 
 
 
 
 
 
 
 
 
 
 

Primus Pharmaceuticals, Inc. 
PPE-01 v 3.1 
29 
The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
Appendix II 
Schedule of Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Perform in the order listed. ** Instruct subject to stop washing hands and face for 2-hours prior to visit. 
 
 
 
 
 
VISIT 
V1 
V2 
V3 
WEEK 
Screen 
Baseline** 
DAY 28** 
Window 
-7 d 
+/- 2d 
+/- 2d 
Informed Consent/Photo 
Consent 
X 
 
 
Inclusion/Exclusion 
X 
 
 
Demographics 
X 
 
 
Current Face & Hand Treatment 
X 
 
 
Medical History of Skin Disease 
X 
 
 
Overall symptom rating 
X 
X 
X 
Skin symptoms rating 
 
X 
X 
Photos of face and hand* 
 
X 
X 
TEWL and SCH face and hand* 
 
X 
X 
Skin pH face and hand* 
 
X 
X 
Swab of dominant hand* 
 
X 
X 
Tape Strip dominant hand*  
 
X 
X 
Subject Response per PI 
 
 
X 
Dispense Product 
 
X 
 
Collect Product 
 
 
X 
Adverse Events 
 
X 
X 
Changes to skin care 
 
X 
X 

Primus Pharmaceuticals, Inc. 
PPE-01 v 3.1 
30 
The information contained in this document is confidential. It is intended solely for the Investigators, potential Investigators, consultants, or applicable independent ethics committees. It is 
understood that this information will not be disclosed to others without prior written authorization from the sponsor, except where required by applicable local laws. 
Appendix III 
Subject Questionnaire  
 
PPE Use 
1. Does your employer provide PPE? 
2. Are you able to choose the type of mask? 
3. What is the average number hours PPE used per week? 
4. Do you work directly with COVID-19 patients?  
5. What is the average number of hours you work, per week, in contact with COVID-19 
patients? 
6. Do you re-use PPE intended for single use?  
7. Does your employer provide hygiene guidelines?  
8. Do the enhanced hygiene measures plus PPE, affect your ability to perform your work? 
9. Which mask do you use at work, mainly? 
a. N 95 
b. Cotton 
c. Paper 
d. Polyester containing 
e. none 
f. Other: __________ 
10. Which mask do you use at home, mainly? 
a. N 95 
b. Cotton 
c. Paper 
d. Polyester containing 
e. none 
f. Other: __________ 
 
Quality of Life 
11. On average how many days in a row do you work? 
12. How much does skin irritation interfere with your daily life? 
13. Do skin symptoms interfere with your sleep? 
Care 
14. What is the average number of times per day you wash your hands? 
15. What is the average number of times per day you use a sanitizer? 
16. Does your employer provide skin care products for work hours?  
17. Do you use vitamin supplements intended for skin health? 
18. Do you take a multiple vitamin? 
19. What is the average number of glasses of water you drink per day?