Conditions: Diabetes Complications
Keywords: cutaneous complication of DM
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 528
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and efficacy of the CeraVe Diabetic Skin Line for the improvement of skin condition in patients with diabetes mellitus.

Detailed description:

Arms:
arm 1: Participants in this group will receive the CeraVe Hydrating Cleanser and Moisturizing Cream for 28 days.

Interventions: intervention 1: CeraVe Hydrating Cleanser intervention 2: CeraVe Moisturizing Cream
Intervention descriptions: intervention 1: topical cleanser applied twice a day for 28 days intervention 2: topical cream applied twice a day for 28 days

Protocol document:
Prot_001.pdf: 
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PRO 2020-06 
Clinical evaluation of CeraVe Hydrating Cleanser and Moisturizing Cream for the 
improvement of skin condition in patients with diabetes mellitus related skin changes 
Original Protocol  
Investigator-Initiated Trial 
NCT#04724967 
 
 
Sponsor and Principal 
Investigator (PI): 
Robert S. Kirsner, MD PhD FRCPC 
 
Sponsor/PI Address 
University of Miami 
Dr. Phillip Frost Dept. of Dermatology and Cutaneous Surgery 
1295 NW 14th St K-M 
Miami, FL  
33136, United States 
 
Date: 
24 July 2020 
 
 
 
Confidentiality Statement 
 
This document contains confidential information belonging to Robert S. Kirsner that must not be 
disclosed to anyone other than the recipient study staff and members of the independent ethics 
committee, institutional review board, or authorized regulatory agencies. This information 
cannot be used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Robert S. Kirsner. 
 


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SIGNATURE PAGE 
PROTOCOL NUMBER: 
PRO-2020-06 
PROTOCOL VERSION: 
6.0 
PROTOCOL DATE: 
24 July 2020 
PROTOCOL TITLE: 
Clinical evaluation of the CeraVe Hydrating Cleanser and 
Moisturizing Cream for the improvement of skin condition 
in patients with diabetes mellitus  
 
 
 
 
Signatures of the below individual indicates that all agree this version is final: 
 
 
 
________________________________________            ____________________ 
Robert S. Kirsner                                                                                Date 
Sponsor/Principle Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1 
TABLE OF CONTENTS 
SIGNATURE PAGE .............................................................................................................. 2 
1 
TABLE OF CONTENTS ................................................................................................ 3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................... 5 
2 
INTRODUCTION............................................................................................................ 6 
3 
STUDY OBJECTIVES .................................................................................................... 6 
4 
INVESTIGATIONAL PLAN ......................................................................................... 6 
4.1 
Overall Study Design ................................................................................................. 6 
4.2 
Number of Study Centers .......................................................................................... 7 
4.3 
Duration of Participation ........................................................................................... 7 
4.4 
Duration of Study ...................................................................................................... 7 
4.5 
Sample size ................................................................................................................ 7 
4.6 
Inclusion Criteria ....................................................................................................... 7 
4.7 
Exclusion Criteria ...................................................................................................... 7 
4.8 
Analysis Populations ................................................................................................. 7 
4.9 
Primary Endpoint ....................................................................................................... 8 
4.10 Beginning and End of Study ...................................................................................... 8 
4.11 Subject Withdrawal Criteria ...................................................................................... 8 
4.11.1 Replacement of Subjects ...................................................................................... 9 
4.12 Treatments ................................................................................................................. 9 
4.12.1 Dosage and Formulations .................................................................................... 9 
4.12.2 Method of Packaging, Labeling, Storage, and Dispensing .................................. 9 
4.12.3 Study Product Accountability .............................................................................. 9 
4.12.4 Prior and Concomitant Medications .................................................................... 9 
4.12.5 Assessment of Compliance ................................................................................ 10 
4.13 Study Procedures ..................................................................................................... 10 
4.13.1 Written Informed Consent ................................................................................. 11 
4.13.2 Significant Medical History/Demographic Information .................................... 11 
4.13.3 Adverse Events and Serious Adverse Events Assessment ................................ 11 
4.13.4 Unscheduled Visit .............................................................................................. 11 
4.14 Efficacy Endpoints .................................................................................................. 11 
4.14.1 Primary Efficacy Endpoint ................................................................................ 11 
4.14.2 Other Efficacy Endpoints ................................................................................... 12 
4.14.3 Definitions of Terms .......................................................................................... 14 
4.14.3.1 Adverse Event .......................................................................................... 14 
4.14.3.2 Suspected Adverse Reaction .................................................................... 14 
4.14.3.3 Unexpected Adverse Event ...................................................................... 14 
4.14.3.4 Serious Adverse Event ............................................................................. 14 
4.14.3.5 Mandatory problem reporting .................................................................. 15 
4.14.4 Assessment of Adverse Events .......................................................................... 15 
4.14.4.1 Assessment of Severity ............................................................................ 15 
4.14.4.2 Assessment of Causality .......................................................................... 15 
4.14.5 Reporting Safety Observations .......................................................................... 15 
5 
ETHICS .......................................................................................................................... 16 
5.1 
Informed Consent .................................................................................................... 16 
5.2 
Institutional Review Board (IRB) ............................................................................ 16 
5.3 
Subject Confidentiality ............................................................................................ 16 


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DATA HANDLING AND RECORDKEEPING ......................................................... 17 
6.1 
Site Regulatory Documents Required for Initiation ................................................ 17 
6.2 
Maintenance and Retention of Records ................................................................... 17 
6.2.1 Case Report Forms (CRFs) ................................................................................ 17 
6.2.2 Primary Source Documents ............................................................................... 17 
6.3 
Study Monitoring ..................................................................................................... 18 
6.4 
Completion of the Study .......................................................................................... 18 
7 
CONFIDENTIALITY, USE OF INFORMATION, AND PUBLICATION ............ 18 
8 
REFERENCES ............................................................................................................... 19 
9 
APPENDIX 1 .................................................................................................................... 8 
10 APPENDIX 2 .................................................................................................................... 9 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Term 
Definition 
AE 
Adverse event 
CRF 
Case report form, paper or electronic 
EOS 
End of study 
GCP 
Good Clinical Practice 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
OTC 
Over-the-counter 
PI 
Principal investigator 
PP 
Per-protocol 
SAE 
Serious adverse event 
TEAE 
Treatment-emergent adverse event 


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2 
INTRODUCTION 
Diabetes Mellitus (DM) is a common and debilitating disease that also affects the skin.1,2 
Between 30% and 70% of patients with DM, both type 1 and type 2, will present with a 
cutaneous complication of DM. Dermatologic conditions linked with DM vary in severity and 
can be benign, deforming, and even life-threatening.1These skin conditions can offer insight 
into patients’ glycemic control and may be the first sign of DM in undiagnosed patients. 
Recognition and management of these conditions is important in maximizing the quality of life 
and in avoiding serious adverse effects. 
 
DM can be associated with pruritus, more often localized than generalized. Affected areas can 
include the scalp, ankles, feet, trunk, or genitalia. Pruritus is more likely in DM who have dry 
skin or diabetic neuropathy. Cutaneous disorders associated with DM commonly bother and 
cause pain and severely impact quality of life, including interpersonal relationships.1 
 
CeraVe Skincare contains a unique combination of three ceramides. Ceramides are key 
physiologic lipids required for construction and maintenance of the epidermal barrier. 
 
3 
STUDY OBJECTIVES 
To evaluate the safety and efficacy of the CeraVe Hydrating Cleanser and Moisturizing Cream 
for the improvement of dry skin in patients with diabetes mellitus. 
 
4 
INVESTIGATIONAL PLAN 
4.1 
Overall Study Design 
This is a multicenter, open-label, cohort study designed to clinically evaluate the CeraVe 
Hydrating Cleanser and Moisturizing Cream for the improvement of dry skin in patients with 
diabetes mellitus. All subjects meeting inclusion/exclusion criteria will receive unblinded 
product. This is a single cohort study, with no placebo or randomization schedule.  
 
Visit Schedule: 
 
Visit 1 / Day -30 to 0 – Screening* 
Visit 1 or 2 / Day 0 – Baseline*  
Visit 3 / Day 28 (± 5 days) – End of study (EOS) 
 
* Visits 1 and 2 may be combined to occur on same day. 
 
Evaluations include: 
1. Physician-assessed Dry Skin Classification Scale 
2. Physician-assessed Global Aesthetic Improvement Scale 
3. Subject-assessed Dry Skin Classification Scale 
4. Subject satisfaction with treatment outcomes, regimen and product features 
5. Safety will be assessed by monitoring adverse events (AEs) at all study visits 
 


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4.2 
Number of Study Centers 
Approximately 10 sites in the United States. 
 
4.3 
Duration of Participation 
Subjects will participate in the study for approximately 28 (± 5) days from the time they sign 
the informed consent form (ICF) through the EOS visit. 
 
4.4 
Duration of Study 
The study will require approximately 6 months from the first subject signing the ICF to the EOS 
visit for the last subject. 
 
4.5 
Sample size 
There is no formal sample size calculation for this study. The sample size is based on clinical 
considerations and not statistical power calculations. Sixty (60) subjects will be recruited. 
 
4.6 
Inclusion Criteria 
1. 
Men or women between the ages of 18 and 75 years of age. 
2. 
Willing to provide written informed consent. 
3. 
A diagnosis of diabetes mellitus (DM). 
4. 
DM-related dry skin changes such as xerosis or xeroderma. 
 
4.7 
Exclusion Criteria 
1. 
History of allergy, anaphylaxis or hypersensitivity to any of the ingredients in 
CeraVe Hydrating Cleanser or Moisturizing Cream. 
2. 
History of allergic contact dermatitis secondary to cleansers or moisturizers. 
3. 
Has a heightened immune response to common allergens, especially inhaled, 
topical or food allergens (atopy). 
4. 
Has any clinical manifestation in the treatment are(s) or other disorders that, in 
the investigator’s opinion, may affect assessments or results of the study 
products. 
5. 
Inability to attend all study visits and follow treatment regimen. 
 
 
 
4.8 
Analysis Populations 
• 
 Intent-to-treat (ITT/safety) population: All enrolled subjects who received study 
products. 
• 
Per-protocol (PP): All enrolled subjects who met all inclusion/exclusion criteria; 
received study products, completed all visits within the specified window; 
completed assessments and had no significant protocol violations that would 
affect the treatment evaluation. 
 


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Safety analyses will be performed on the ITT population. The frequency and percentage of 
subjects reporting adverse events (AEs) will be tabulated by preferred terms and further by 
severity and relationship to study product(s). 
 
Efficacy analyses will be performed on the ITT and PP populations, with ITT as the primary 
population and PP supportive.  
 
4.9 
Primary Endpoint 
The primary efficacy endpoints are the Physician-assessed Global Aesthetic Improvement Scale 
and Physician-assessed Dry Skin Classification Scale, at Visit 3. 
 
4.10 Beginning and End of Study 
A subject is considered to be enrolled in the study when he/she has provided written informed 
consent and has received the investigational products. 
A subject is considered to have completed the study after he/she has completed Visit 3. 
A subject is considered to have withdrawn after he/she has withdrawn consent or has been 
withdrawn under the conditions specified in Section 4.11. 
A subject is considered to have been lost to follow-up if he/she cannot be contacted by the 
investigator. The investigator will document efforts to attempt to reach the subject. The end of 
participation for a subject lost to follow-up is documented as the date of last contact. 
Each subject will be monitored for the occurrence of AEs, including serious adverse events 
(SAEs), starting immediately after the subject has received the investigational products. Each 
subject will be followed for safety monitoring until he/she is discharged from the study. 
Follow-up procedures related to AEs or SAEs may continue beyond the end of the study. 
Each subject will participate in the study for approximately 1 month. It is anticipated that the 
duration of this study will be 6 months from the first subject signing the ICF to the EOS visit 
last subject.  
 
4.11 Subject Withdrawal Criteria 
A subject may withdraw from the study at any time for any reason. 
A subject will be withdrawn from the study if his/her safety or well-being is determined to be at 
risk. Withdrawal will be made at the discretion of the investigator or at the subject’s request. 
A subject must withdraw from the study for any of the following reasons: 
• The subject withdraws consent 
• There is a significant protocol violation as determined by the Sponsor or medical 
monitor. 
A subject may be withdrawn from the study for any of the following reasons: 
• Lost to follow-up 
• Investigator discretion 
Withdrawal is permanent; after a subject has been withdrawn, he/she will not be allowed to 
enroll again. 


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If a subject is withdrawn from the study for any reason, relevant information including the date 
and primary reason for withdrawal, must be documented on the EOS case report form (CRF) 
and source document. 
If a subject withdraws from the study at any time due to an AE, the reason for withdrawal, the 
nature of the AE, and its clinical course must be fully documented. The investigator must strive 
to follow the subject until the AE has resolved, become clinically insignificant, is stabilized, or 
the subject is lost to follow-up. For any SAE, follow the procedures provided in Section 4.14.5. 
 
4.11.1 Replacement of Subjects 
A subject who withdraws from the study will not be replaced.  
 
4.12 Treatments 
The investigator will take responsibility for and will take all steps to maintain appropriate 
records and ensure appropriate supply, handling, storage, distribution, and use of study 
materials in accordance with the protocol and any applicable laws and regulations. 
 
4.12.1 Dosage and Formulations 
The study product will be used in the study and provided by the Sponsor: 
A description of the investigational products are presented in Appendix 1 and 2. 
 
4.12.2 Method of Packaging, Labeling, Storage, and Dispensing 
The investigational products will be labelled as per the manufacturer’s packaging.  Products 
must be used prior to the expiration date printed on the package.  
The investigator agrees to store and administer the study product only at the site approved by 
the independent research board (IRB). The investigator, sub-investigator(s), or qualified 
designees also agree that the study product will be administered only to subjects who have 
provided written informed consent and have met all entry criteria. Study product may not be 
used for any purpose other than as stated in the protocol. 
 
4.12.3 Study Products Accountability 
Study product will be available on site for each subject. Receipt of study product will be 
documented. The administration of study product will be recorded on the Study Product 
Dispensing Log. The site monitor will periodically check the supply of study product held by 
the investigator to ensure accountability.  
Inventory records must be readily available for inspection by the study monitor and/or auditor, 
and open to inspection by regulatory authorities at any time. 
 
4.12.4 Prior and Concomitant Medications 
All medications, supplements, over-the-counter (OTC) products and other treatments taken by 
the subject during the study are to be recorded on the CRF using their generic name, if known, 
with the corresponding indication.  


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4.12.5 Assessment of Compliance 
Administration of the study product by the investigator is documented on the CRF. 
Subject compliance with treatment regimen will be documented at Visit 3. 
 
4.13 Study Procedures 
The schedule of study activities is summarized in Table 1.  
All clinical assessments must be conducted by qualified investigators who have been delegated 
these tasks by the study Sponsor. The PI may delegate this task only to physicians who have 
documented training for this protocol and past experience conducting the assessment. 
To minimize variability of evaluations, the same investigator/sub-investigator should perform 
these assessments for any given subject and anticipate evaluating the subject at each visit, to the 
extent possible. 
A unique subject number will be assigned to each subject.  
 
Table 1. Study procedures. 
Visit 
Visit 1 
Visit 1 or 2 
Visit 3 
Screening 
Baseline 
End of Study 
Timeline 
Day -30 to 0 
Day 0 
Day 28 +/- 5 days 
Informed consent 
X 
 
 
Concomitant 
medications and 
procedures 
X 
 
 
Demographics 
X 
 
 
Eligibility 
X 
 
 
Physician-assessed 
Dry Skin Scale 
X 
X* 
X 
Daily product 
administration 
 
X 
X 
Subject-assessed Dry 
Skin Scale 
 
X 
X 
Subject-assessed 
quality of life 
measurements 
 
X 
X 
Subject satisfaction 
questionnaires 
 
 
X 
Assessment of 
adverse events 
 
 
X 
Assessment of 
compliance 
 
 
X 
*Skip this procedure if Visit 1 and 2 are combined on same day. 
 
 
 


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Study Initiation 
The investigational staff may not enroll any subjects prior to completion of a site initiation visit. 
This visit will include, but is not limited to, an inventory of study supplies (if present) and a 
detailed review of the protocol, CRFs, and the investigator’s responsibilities. 
 
4.13.1 Written Informed Consent 
The study personnel will review the ICF with each subject and give the subject an opportunity 
to have all questions answered before proceeding with any study procedures. A copy of the 
signed ICF will be given to every subject and the original will be maintained with the subject’s 
records. 
4.13.2 Significant Medical History/Demographic Information 
Medical history and demographic information will be obtained at Screening. The medical 
history will include a complete review of all current diseases and their respective durations and 
treatments. Demographic information will include date of birth, sex at birth and ethnicity. 
 
4.13.3 Adverse Events and Serious Adverse Events Assessment 
See Section 4.14.3.1 for instructions on the assessment and reporting of AEs and SAEs and 
Section 4.14.5. for instructions on reporting SAEs to the Sponsor. 
 
4.13.4 Unscheduled Visit 
An unscheduled visit is allowed at any time if in the investigator’s opinion it is warranted. The 
following procedures may be performed at the Unscheduled Visit if required. 
 
4.14 Efficacy Endpoints 
4.14.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is the physician-assessed GAIS at Visit 3. 
GAIS 
 


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4.14.2 Other Efficacy Endpoints  
 
Physician-assessed Dry Skin Classification Scale 
 
 
Subject-assessed Dry Skin Classification Scale 
 
Subject satisfaction with treatment outcomes 
 
Overall level of satisfaction with product results (check one) 
  
  
  
  
  
Extremely 
satisfied 
Satisfied 
Neutral 
Dis-satisfied 
Extremely 
dissatisfied 
 
 
 
 
 
 


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Subject satisfaction with treatment regimen  
 
Overall level of satisfaction with treatment regimen (check one) 
  
  
  
  
  
Extremely 
satisfied 
Satisfied 
Neutral 
Dis-satisfied 
Extremely 
dissatisfied 
 
Subject-assessed product features 
 
My skin feels sufficiently clean after using the cleanser 
  
  
  
  
  
Strongly 
disagree 
Disagree 
Neutral 
Agree 
Strongly agree 
 
 
My skin feels sufficiently moisturized after using the moisturizer 
  
  
  
  
  
Strongly 
disagree 
Disagree 
Neutral 
Agree 
Strongly agree 
 
Subject’s overall assessment 
 
I would continue to use the treatment regimen outside of the study 
  
  
  
  
  
Strongly 
disagree 
Disagree 
Neutral 
Agree 
Strongly agree 
 
Quality of life assessments 
 
              
 
Over the last week, how embarrassed or self conscious have you been 
because of your skin? 
  
  
  
  
Very much 
A lot 
A little 
Not at all 
 
 


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Over the last week, how much has your skin affected any social or leisure 
activities? 
  
  
  
  
Very much 
A lot 
A little 
Not at all 
 
 
Over the last week, has your skin prevented you from working or studying? 
  
  
  
  
Very much 
A lot 
A little 
Not at all 
 
4.14.3 Definitions of Terms 
4.14.3.1 Adverse Event 
An AE is defined as any untoward medical occurrence associated with the use of an 
investigational product in humans, whether or not considered product-related as per ICH E2D. 
An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally 
associated with the use of a product, without any judgment about causality. 
 
4.14.3.2 Suspected Adverse Reaction 
A suspected adverse reaction (SAR) is defined as any AE for which there is reasonable 
possibility that the product caused the AE (21 CFR 312.32 (a)). 
 
4.14.3.3 Unexpected Adverse Event 
An AE or SAR is considered unexpected if it is not consistent with the risk information 
described in the labeling for the study products.  
 
4.14.3.4 Serious Adverse Event 
An SAE is defined as any AE or SAR that, in the view of the investigator or Sponsor, results in 
any of the following outcomes (21 CFR 312.32 (a)): 
• Death 
• Life-threatening  
• Inpatient hospitalization or prolongation of existing hospitalization.  
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly/birth defect 
• Required intervention to prevent permanent impairment/damage 
 


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4.14.3.5 Mandatory problem reporting 
All AEs must be documented in the CRFs and source documents. The qualified investigator is 
required to report serious adverse events to the study Sponsor within 72 hours of discovery.  
 
4.14.4 Assessment of Adverse Events 
4.14.4.1 Assessment of Severity 
Severity of AEs will be graded according to the following definitions: 
Mild: AE that was easily tolerated 
Moderate: AE sufficiently discomforting to interfere with daily activity 
Severe: AE that prevented normal daily activities 
 
4.14.4.2 Assessment of Causality 
A medically qualified investigator must assess the relationship of any AE (including SAEs) to 
the use of the study product as unlikely related, possibly related, or probably related based on 
available information, using the following guidelines:  
Unlikely related: no temporal association, or the cause of the event has been identified, 
or the study product cannot be implicated based on available information 
Possibly related: temporal association but other etiologies are likely to be the cause; 
however, involvement of the study product cannot be excluded based on available 
information 
Probably related: temporal association, other etiologies are possible, but unlikely based 
on available information. 
 
4.14.5 Reporting Safety Observations 
Any S/AE must be reported to the Sponsor or designee by telephone, email or through the study 
portal (https://medalogik.com) as soon as possible after the investigator or coordinator has 
become aware of its occurrence. The investigator/coordinator must complete an S/AE Form. 
Sponsor/Designee contact details:  
Kaitlyn M. Enright 
Medical Monitor 
Cell:  514-248-7033 
Email: 
Kaitlyn@rbcconsultants.com 
 
The investigator must be prepared to supply the medical monitor with the following 
information: 
1. Investigator name and site number 
2. Subject number 
3. Subject initials and date of birth 
4. Subject demographics 


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5. Clinical event 
a. description 
b. date of onset 
c. severity 
d. treatment (including hospitalization) 
e. relationship to study product 
f. action taken regarding study product 
g. outcome, if known 
 
5 
ETHICS 
5.1 
Informed Consent 
The principles of informed consent, according to TCPS 2 (2010) – 2nd edition of Tri-Council 
Policy Statement and the International Council on Harmonization (ICH) guidelines on GCP, 
will be followed. A copy of the proposed ICF must be submitted with the protocol to the IRB 
for approval. 
The informed consent process must be conducted and the ICF must be signed before each 
subject undergoes any screening procedures that are performed solely for the purpose of 
determining eligibility for the study, in compliance with 21 CFR Part 50. Each subject’s signed 
ICF must be kept on file by the investigator for inspection by regulatory authorities at any time. 
A copy of the signed ICF will be given to the subject. A notation will be made in the subject’s 
medical record indicating the date informed consent was obtained. 
 
5.2 
Institutional Review Board (IRB) 
The study protocol and ICF must be approved in writing by an appropriate IRB as defined by 
the regulations and other applicable requirements prior to enrollment of any study subjects. 
Any changes to the protocol or a change of investigator approved by the Sponsor must also be 
approved by the site’s IRB and documentation of that approval provided to the Sponsor or 
designee. Records of the IRB review and approval of all documents pertaining to this study 
must be kept on file by the investigator and are subject to inspection by regulatory authorities 
during or after completion of the study. SAEs must also be reported to the IRB. 
Periodic status reports must be submitted to the IRB at least annually, as well as notification of 
completion of the study and a final report within 1 month of study completion or termination. A 
copy of all reports submitted to the IRB must be sent to the Sponsor or designee. 
The investigator will ensure that an IRB that complies with the requirements set forth in by the 
authorities and will be responsible for the initial and continuing review and approval of the 
study. 
 
5.3 
Subject Confidentiality 
All subject data will be identified only by a subject identification number and subject initials. 
However, in compliance with federal guidelines regarding the monitoring of clinical studies and 
in fulfillment of his/her obligations to the Sponsor, the investigator must permit the study 


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monitor, Sponsor representative or auditor, and/or FDA or other regulatory authority to review 
the portion of the subject’s medical record that is directly related to the study. This shall include 
all study-relevant documentation including medical history to verify eligibility, 
admission/discharge summaries for hospital stays occurring while the subject is enrolled in the 
study, and autopsy reports if a death occurs during the study. 
As part of the required content of informed consent, each subject must be informed that his or 
her medical chart may be reviewed by the Sponsor, the Sponsor’s authorized representatives, 
FDA, or other regulatory authority. If access to the medical record requires a separate waiver or 
authorization, it is the investigator’s responsibility to obtain such permission from the subject in 
writing before the subject is entered into the study. 
 
6 
DATA HANDLING AND RECORDKEEPING 
6.1 
Site Regulatory Documents Required for Initiation 
The Sponsor or designee must receive the following documents prior to the initiation of the 
study: 
• Current curricula vitae, signed and dated, for the principal investigator (PI) and any 
co-investigators  
• Current license(s) number of the PI and co-investigators  
• A copy of the protocol signature page signed by the PI 
 
6.2 
Maintenance and Retention of Records 
The study will be conducted according to GCP as outlined in ICH guidelines. It is the 
responsibility of the investigator to maintain a comprehensive and centralized filing system of 
all relevant documentation. Investigators will be instructed to retain all study records required 
by the Sponsor and the regulations in a secure and safe facility with limited access. Regulations 
require retention for a period of at least 7 years for studies investigating non-regulated products. 
These regulatory documents should be retained for a shorter/longer periods if required by local 
regulatory authorities.  
These records include documents pertaining to the receipt and return of study product, IRB, 
informed consent, source documents, and final signed CRFs. No documents shall be destroyed 
without first notifying the Sponsor. 
 
6.2.1 Case Report Forms (CRFs)  
CRFs for individual subjects will be provided by the Sponsor or designee. CRFs must be legible 
and complete. CRFs for this study will be maintained in paper format and/or online in a fillable 
PDF document. All paper forms should be completed using a black ballpoint pen. Errors should 
be lined out, but not obliterated, and the correction inserted, initialed, and dated by designated 
study personnel.  
 
6.2.2 Primary Source Documents 
The investigator must maintain primary source documents supporting significant data for each 
subject’s medical notes.  


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The investigator must also retain all subject-specific printouts/reports of procedures performed 
as a requirement of the study. During monitoring visits the monitor will validate CRF entries 
against these data sources. 
 
6.3 
Study Monitoring 
The Sponsor or designee will be responsible for virtually monitoring the study according to 
GCP and applicable regulations. The study will be monitored by a Clinical Research Associate 
(CRA) in compliance with GCP, ICH guidelines, and applicable regulations. The coordinator 
and/or investigator should be available to answer questions or resolve data clarifications. 
 
6.4 
Completion of the Study 
The investigator is required to forward CRFs and all other relevant data and records to the 
Sponsor or designee. The investigator will complete and report (submission of CRFs) his/her 
study in satisfactory compliance with the protocol as soon as possible. 
The Sponsor will submit a final report to the IRB following study completion or early 
termination. 
7 
CONFIDENTIALITY, USE OF INFORMATION, AND PUBLICATION 
All information related to this study that is supplied by the Sponsor and not previously 
published is considered confidential information. This information includes but is not limited to 
data, materials (protocol, CRFs), equipment, experience (whether of a scientific, technical, 
engineering, operational, or commercial nature), designs, specifications, know-how, product 
uses, processes, formulae, costs, financial data, marketing plans and direct selling systems, 
customer lists, and technical and commercial information relating to customers or business 
projections used by the Sponsor in its business. Any data, inventions, or discoveries collected or 
developed as a result of this study are considered confidential. This confidential information 
shall remain the sole property of the Sponsor, shall not be disclosed to any unauthorized person 
or used in any unauthorized manner without written consent of the Sponsor, and shall not be 
used except in the performance of the study. 
The information developed during the course of this study is also considered confidential and 
will be used by the Sponsor in the development of the study medication. The information may 
be disclosed as deemed necessary by the Sponsor. To allow the use of the information derived 
from this study, the investigator is obliged to provide the Sponsor with complete test results and 
all data developed in the study. The information obtained during this study may be made 
available to other investigators who are conducting similar studies. 
The investigator shall not make any publication related to this study without the express written 
permission of the Sponsor. If the investigator wants to publish or present the results of this 
study, he or she agrees to provide the Sponsor with an abstract, manuscript, and/or presentation 
for review 60 days prior to submission for publication or presentation. The Sponsor retains the 
right to delete confidential information and to object to suggested publication/presentation 
and/or its timing (at the Sponsor’s sole discretion). 
 
 
 
 


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REFERENCES 
 
1. Kirsner RS, Yosipovitch  G, Hu S, Andriessen A. Diabetic skin changes can benefit from 
moisturizer and cleanser use: A review. J Drugs Dermatol. 2019;18(12):1211-1217. 
 
2.  Guenther L, Lynde CW, Andriessen A et al. Pathway to dry skin prevention and treatment. J 
Cutan Med Surg 2012;16(1):23-31


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9 
APPENDIX 1  
 
 
 
CeraVe Hydrating Cleanser Fact Sheet 
Developed with dermatologists, CeraVe offers a complete line of skincare products that 
contain ceramides 1, 3 and 6-II to help restore the skin’s natural protective barrier. CeraVe 
Hydrating Cleanser removes dirt and oil from the skin, leaving it cleansed and hydrated. 
Suitable for normal to dry skin.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DID YOU KNOW? 
 
The skin naturally contains 
ceramides that may become 
depleted over time, contributing 
to dry and irritated skin. 
  
WHAT ARE CERAMIDES? 
 
Part of the glue that holds skin cells 
together, ceramides keep moisture in 
and irritants out, while maintaining the 
skin’s barrier. To replenish the vital 
ceramides healthy skin needs, CeraVe 
products are formulated with 
ceramides 1, 3 & 6-II 
HOW DOES IT WORK? 
 
CeraVe products use patented 
Multivesicular Emulsion (MVE) 
technology that releases ingredients 
slowly over time, allowing them to 
absorb into the skin to hydrate & nouris
as well as restore & maintain the skin’s
natural barrier. 
Hyaluronic Acid 
Help retain skin’s natural 
moisture 
MVE Delivery Technology  
Controlled release for all day 
hydration 
Accepted by the National 
Eczema Association 
Key Features: 
•
Gentle cleanser that is non-drying. 
•
Formula is both fragrance-free and non-comedogenic. 
•
Hydrates skin and helps restore the skin’s protective 
barrier. 
How To Use: 
•
Wet skin with lukewarm water 
•
Massage cleanser into skin in a gentle, circular motion 
•
Rinse 
2021506 4 - Ingredients: 
AQUA / WATER, GLYCERIN, CETEARYL ALCOHOL, 
PEG-40 STEARATE, STEARYL ALCOHOL, POTASSIUM 
PHOSPHATE, CERAMIDE NP, CERAMIDE AP, 
CERAMIDE EOP, CARBOMER, GLYCERYL STEARATE, 
BEHENTRIMONIUM METHOSULFATE, SODIUM 
LAUROYL LACTYLATE, SODIUM HYALURONATE, 
CHOLESTEROL, PHENOXYETHANOL, DISODIUM 
EDTA, DIPOTASSIUM PHOSPHATE, TOCOPHEROL, 
PHYTOSPHINGOSINE, XANTHAN GUM, CETYL 
ALCOHOL, POLYSORBATE 20, ETHYLHEXYLGLYCERIN 
(Code F.I.L D214629/4) 
 
 


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APPENDIX 2  
 
 
 
 
CeraVe Moisturising Cream Fact Sheet 
Developed with dermatologists, CeraVe offers a complete line of skincare products that 
contain ceramides 1, 3 and 6-II to help restore the skin’s natural protective barrier. CeraVe 
Moisturising Cream is a rich, non-greasy formula that provides all-day hydration with a soft, 
powdery finish and helps restore the protective skin barrier. Suitable for dry to very dry skin 
on the face and body. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Key Features: 
•
Formulated with Hyaluronic Acid to help retain skin’s 
natural moisture. 
•
Features an oil-free formula with hyaluronic acid 
that is non-comedogenic. 
How To Use: Apply liberally as often as needed. 
 
2021500 - Ingredients: 
AQUA / WATER, GLYCERIN, CETEARYL ALCOHOL, 
CAPRYLIC/CAPRIC TRIGLYCERIDE, CETYL ALCOHOL, 
CETEARETH-20, PETROLATUM, POTASSIUM 
PHOSPHATE, CERAMIDE NP, CERAMIDE AP, 
CERAMIDE EOP, CARBOMER, DIMETHICONE, 
BEHENTRIMONIUM METHOSULFATE, 
SODIUM LAUROYL LACTYLATE, SODIUM 
HYALURONATE, CHOLESTEROL, 
PHENOXYETHANOL, DISODIUM EDTA, 
DIPOTASSIUM PHOSPHATE, TOCOPHEROL, 
PHYTOSPHINGOSINE, XANTHAN GUM, 
ETHYLHEXYLGLYCERIN (Code F.I.L. D213768/2) 
DID YOU KNOW? 
 
The skin naturally contains 
ceramides that become 
depleted over time, leading to 
dry and irritated skin. 
  
WHAT ARE CERAMIDES? 
 
Part of the glue that holds skin cells 
together, ceramides help skin keep 
moisture in and irritants out, while 
maintaining the skin’s barrier.  
To replenish the vital ceramides healthy 
skin needs, CeraVe products are 
formulated with ceramides 1, 3 & 6-II. 
HOW DOES IT WORK? 
 
CeraVe products use patented 
Multivesicular Emulsion (MVE) 
technology that releases ingredients 
slowly over time, allowing them to 
absorb into the skin to hydrate & nourish,
as well as restore & maintain the skin’s 
natural barrier. 
Hyaluronic Acid  
Helps retain skin’s natural moisture 
MVE Delivery Technology  
Controlled release for all day hydration 
Accepted by the National Eczema 
Association