A Prospective Post Market Clinical Follow-up Investigation With Epaderm® Cream to Confirm Performance and Safety Parameters
Phase: NA
Conditions: Eczema, Psoriasis, Dry Skin; Eczema
Sponsor: Molnlycke Health Care AB

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 1(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
 
CLINICAL INVESTIGATION PLAN (CIP) 
INVESTIGATIONAL DEVICE: 
EPADERM® Cream 
INVESTIGATION TITLE:  
A prospective post market clinical follow-up investigation with Epaderm® Cream 
to confirm performance and safety parameters 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CO-ORDINATING INVESTIGATOR: 
Suzannah August 
 
SPONSOR 
MÖLNLYCKE CLINICAL STUDY  
MANAGER: 
 
Catharina Flodin 
Mölnlycke Health Care 
P.O Box 130 80 
402 52 Gothenburg, Sweden 
Phone: +46 31 722 30 xx 
Fax: +46 31 722 34 91 
 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 2(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
CLINICAL INVESTIGATION PLAN (CIP) SYNOPSIS 
 
INVESTIGATION TITLE:  
A prospective post market clinical follow-up investigation with Epaderm® Cream 
to confirm performance and safety parameters 
 
Objectives 
To confirm safety and performance of Epaderm Cream when used as intended in daily practice 
Overall Design 
This investigation is designed as a prospective, non-randomised, single arm clinical 
investigation. Data will be collected from approximately 120 evaluable subjects, divided into 
three groups of approximately 40 subjects; infants (0-36 months old), children (3-18 years old) 
and adults (>18 years old), with the following indications: eczema, psoriasis and other dry skin 
conditions. Each subject will be followed during 4 weeks treatment, with a visit at baseline (visit 
1), at 2 weeks (visit 2) and at 4 weeks (visit 3) treatment. 
Primary Endpoint 
Subject evaluation of skin moisturisation (hydration) after treatment with Epaderm Cream up to 
4 weeks, using a questionnaire. 
Secondary Endpoints 
1. Subject evaluation of skin softness after treatment up to 4 weeks, using a questionnaire. 
2. Evaluation of the subject’s dry skin/xerosis after treatment with Epaderm Cream up to 4 
weeks, by investigator/nurse using “Overall dry skin score, ODS”, (Masson P, 1995). 
3. Skin hydration after treatment with Epaderm Cream up to 4 weeks, using a non-invasive 
device MoistureMeterEpiD. 
4. Subject evaluation regarding: 
 Frequency of application and amount used of Epaderm Cream 
 Comfort during treatment  
 Time of onset of effect (moist and soft) 
 Overall effect 
 Was the investigational device used as a skin cleanser? 
5. Concomitant and previous medication and treatment 
6. Number of Adverse Device Effects (ADEs) related to the use of Epaderm Cream during the 
investigation. 
Inclusion Criteria 
1. Subjects suitable for treatment with Epaderm Cream, as deemed by the investigator and 
according to intended use (eczema, psoriasis and other dry skin conditions). 
2. Subject or subject’s legal representative must be able to read and sign the Patient 
Information and Consent Form. 
Exclusion Criteria 
1. Known allergy/hypersensitivity to any of the components of Epaderm Cream. 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 3(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
2. Subject not suitable for the investigation according to the investigator’s judgement. 
3. Subject participating in other ongoing similar clinical studies or other clinical studies which 
could interfere with this investigation, as judged by the investigator. 
4. Subject previously enrolled in the current clinical investigation. 
Investigational Device 
Epaderm Cream 
Mölnlycke will provide the investigational device, to the investigation sites and subjects, free of 
charge. The treatment with the investigational device will be according to the prescription by the 
investigator together with the instruction stated on the investigational device (e.g. when used as 
an emollient: Apply liberally to the affected area and massage well into the skin. Use as often as 
required or as directed by your health care professional. When used as a skin cleanser: Use as 
required when washing or in the shower.).

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 4(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
TABLE OF CONTENTS 
1. INTRODUCTION AND BACKGROUND ................................................................... 7 
2. OBJECTIVES ........................................................................................................... 7 
3. CLINICAL INVESTIGATOR(S) AND INVESTIGATION ADMINISTRATIVE 
STRUCTURE .................................................................................................................. 7 
3.1 
PI at Investigation Sites ............................................................................................................................. 7 
3.2 
Mölnlycke Investigation Personnel ........................................................................................................ 7 
3.3 
Other Participants ....................................................................................................................................... 7 
4. INVESTIGATION PLAN AND PROCEDURES ........................................................ 7 
4.1 
Overall Design ............................................................................................................................................. 7 
4.2 
Investigation Endpoints ............................................................................................................................ 8 
4.2.1 
Primary Endpoint ...................................................................................................................................... 8 
4.2.2 
Secondary Endpoints ............................................................................................................................... 8 
4.3 
Procedures and Assessments ................................................................................................................. 8 
4.3.1 
Schedule of Assessments ....................................................................................................................... 9 
4.4 
Selection of Population for Investigation ............................................................................................. 9 
4.4.1 
Inclusion Criteria ....................................................................................................................................... 9 
4.4.2 
Exclusion Criteria .................................................................................................................................... 10 
4.4.3 
Discontinuation of treatment and Lost to follow-up ............................................................................ 10 
4.4.4 
Withdrawal of Subjects from treatment ................................................................................................ 10 
4.5 
Investigational Device .............................................................................................................................. 10 
4.5.1 
Labelling ................................................................................................................................................... 10 
4.5.2 
Accountability .......................................................................................................................................... 11 
4.5.3 
Storage conditions .................................................................................................................................. 11 
4.5.4 
Method of Assigning Subjects to Product Groups ............................................................................. 11 
4.6 
Concomitant Treatments......................................................................................................................... 11 
4.7 
Performance and Safety .......................................................................................................................... 11 
4.7.1 
Non-invasive device measuring skin hydration .................................................................................. 11 
4.7.2 
Subject Characteristics .......................................................................................................................... 12 
4.7.3 
Performance Measurements and Variables ....................................................................................... 12 
4.7.4 
Safety Measurements and Variables ................................................................................................... 14 
4.7.5 
Anticipated ADEs .................................................................................................................................... 14 
4.8 
Data Quality Assurance ........................................................................................................................... 14 
4.8.1 
Monitoring, Audits and Inspections .................................................................................................. 1415 
4.8.2 
Training of Staff ....................................................................................................................................... 15 
4.8.3 
Data Management .................................................................................................................................. 15 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 5(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
4.9 
Statistical Methods and Determination of Sample Size .............................................................. 1516 
4.9.1 
Analysis populations ........................................................................................................................... 1516 
4.9.2 
Statistical Evaluation .............................................................................................................................. 16 
4.9.3 
Determination of Sample Size .............................................................................................................. 16 
4.10 
Changes to the Clinical Investigation Plan .................................................................................... 1617 
5. STATEMENTS OF COMPLIANCE ......................................................................... 17 
5.1 
Ethics ........................................................................................................................................................... 17 
5.1.1 
Ethics review............................................................................................................................................ 17 
5.1.2 
Ethical Conduct of the Investigation ..................................................................................................... 17 
5.1.3 
Subject Information and Consent Form ............................................................................................... 17 
5.2 
Regulatory and standards ...................................................................................................................... 17 
5.2.1 
Standards and other ........................................................................................................................... 1718 
5.2.2 
Subject data protection and confidentiality ..................................................................................... 1718 
5.3 
Subject Protection Procedures ............................................................................................................. 18 
5.3.1 
Procedures in Case of Medical Emergency ........................................................................................ 18 
5.3.2 
Insurance ................................................................................................................................................. 18 
5.4 
Use of Information and Publications ................................................................................................... 18 
5.5 
Record Retention ...................................................................................................................................... 18 
5.6 
Public Domain Access to the Clinical Investigation ........................................................................ 18 
6. INVESTIGATION TIMETABLE AND TERMINATION ............................................ 18 
7. LITERATURE REVIEW AND REFERENCES .................................................... 1819 
8. DEFINITIONS AND PROCEDURES FOR REPORTING OF ADVERSE DEVICE 
EFFECT, SERIOUS ADVERSE DEVICE EFFECT AND DEVICE DEFICIENCY ......... 19 
 
 
 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 6(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
LIST OF APPENDICES 
Appendix A  F-449 Clinical Investigation Plan Appendix A, Core Signatures 
 
F-583 Clinical Investigation Plan Principal Investigator Signature 
Appendix B  F-173 Patient Information and Consent Forms 
Appendix C F-542 All variables to be obtained during the Investigation 
Appendix D Instructions for Use of Epaderm Cream, Printing Illustration PD-537170 
Appendix E Instructions for Use of non-invasive device, MoistureMeterEpiD from Delfin 
Technologies 
Appendix F Questionnaires/Forms 
Appendix G MoistureMeterEpiD rapid measurement of skin deep hydration 
LIST OF ABBREVIATIONS  
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CIP 
Clinical Investigation Plan 
eCRF 
Electronic Case Report Form 
DD 
Device Deficiency 
EC 
Ethics Committee 
IRB 
Institutional Review Board 
PMCF 
Post-Market Clinical Follow-up Investigation 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
Clarification 
Investigator/Nurse: 
In the CIP, it refers to the Physician(s) and Nurse(s) participating in 
the investigation. 
 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 7(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
1. INTRODUCTION AND BACKGROUND 
Epaderm® Cream is an emollient formulated with ingredients that hydrate, aid moisture retention 
and soften the skin. Epaderm Cream provides all the protective benefits of paraffin-based 
emollients and can be used in the management of eczema, psoriasis and other dry skin 
conditions. The emollient can also be used as a skin cleanser. Epaderm Cream is suitable for all 
ages including babies (PD-537170-01, appendix G). This emollient is a low risk device (Class 
IIa device under Medical Device Directive MDD 93/42/EEC) and is formulated with well-
established ingredients commonly used in topical formulations. Epaderm Cream has been on 
the market in its present formulation since 2012 and with over 5.8 million sold items. 
The ingredients of Epaderm Cream moisturise and softens the skin. Yellow soft paraffin and liquid 
paraffin are used for the softening and moisturising characteristics and to reduce water loss from 
the skin. Epaderm Cream also contains glycerine which is used for its hydration properties. 
Whilst there is no need for a Post-Market Clinical Follow-up investigation (PMCF) from a safety 
perspective for Epaderm Cream, there is a need for a PMCF investigation to confirm the 
performance of Epaderm Cream in accordance with MEDDEV 2. 12/2 Rev: 2, see Clinical 
Evaluation Report PD-420529 Rev: 02. The investigation should cover dry skin conditions, 
eczema and psoriasis, as well as different age groups including babies. 
2. OBJECTIVES 
To confirm safety and performance of Epaderm Cream when used as intended in daily practice. 
3. CLINICAL INVESTIGATOR(S) AND INVESTIGATION 
ADMINISTRATIVE STRUCTURE 
3.1 PI at Investigation Sites 
Name and addresses of Principal Investigators are listed in appendix A. 
3.2 Mölnlycke Investigation Personnel 
Relevant personnel, included in appendix A. 
3.3 Other Participants 
Supplier of the eCRF system  
PCG Clinical Services AB 
Viedoc 
Kungsängsvägen 19, 1 tr. 
753 23 Uppsala, Sweden 
4. INVESTIGATION PLAN AND PROCEDURES 
4.1 Overall Design 
This investigation is designed as a prospective, non-randomised, single arm clinical 
investigation. Data will be collected from approximately 120 evaluable subjects, divided into 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 8(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
three groups of approximately 40 subjects; infants (0-36 months old), children (3-18 years old) 
and adults (>18 years old), with the following indications: eczema, psoriasis and other dry skin 
conditions. Each subject will be followed during 4 weeks treatment, with a visit at baseline (visit 
1), at 2 weeks (visit 2) and at 4 weeks (visit 3) treatment. An evaluable subject is a subject with 
a baseline visit and at least one follow-up visit. 
4.2 Investigation Endpoints 
4.2.1 Primary Endpoint 
Subject evaluation of skin moisturisation (hydration) after treatment with Epaderm Cream up to 
4 weeks, using a questionnaire. 
4.2.2 Secondary Endpoints 
7. Subject evaluation of skin softness after treatment up to 4 weeks, using a questionnaire. 
8. Evaluation of the subject’s dry skin/xerosis after treatment with Epaderm Cream up to 4 
weeks, by investigator/nurse using “Overall dry skin score, ODS”, (Masson P, 1995). 
9. Skin hydration after treatment with Epaderm Cream up to 4 weeks, using a non-invasive 
device MoistureMeterEpiD. 
10. Subject evaluation regarding: 
 Frequency of application and amount used of Epaderm Cream 
 Comfort during treatment  
 Time of onset of effect (moist and soft) 
 Overall effect 
 Was the investigational device used as a skin cleanser? 
11. Concomitant and previous medication and treatment 
12. Number of Adverse Device Effects (ADEs) related to the use of Epaderm Cream during the 
investigation. 
4.3 Procedures and Assessments 
Data will be collected at the baseline visit, visit 1 (day 0), at visit 2 (2 weeks, day 14) and at visit 
3 (4 weeks, day 28). Collected data will be entered into an eCRF (electronic Case Report 
Form). 
The subject should be instructed not to shower or put on Epaderm Cream before the follow-up 
visits. 
If the subject cannot come to a follow-up visit, the investigator/nurse should collect as much 
information as possible (at least one documented attempt to reach the subject) and enter this 
into the eCRF. 
 
 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 9(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
4.3.1 Schedule of Assessments 
Visits 
Baseline Visit  
Visit 1 
Day 0 
Follow up visit 
Visit 2 
Day 14 (+/-2) 
Final visit 
Visit 3 
Day 28 (+/-2) 
Informed consent, dated and 
signed 
 
 
 
Inclusion/Exclusion criteria 
 
 
 
Subject’s age and sex 
 
 
 
Relevant medical history 
 
 
 
Relevant previous medication or 
treatment 
 
 
 
Concomitant medication/ 
treatment relevant for the 
investigation 
 
 
 
Did the subject have a shower 
before the visit 
 
 
 
Skin disease/condition 
 
 
 
Severity of disease/condition 
 
 
 
Subject’s evaluation of itching in 
relation to skin 
condition/diagnosis (VAS scale) 
 
 
 
Ongoing flare 
 
 
 
Overall Dry Skin Score (ODS) 
 
 
 
Body location of target area for 
skin hydration evaluation 
 
 
 
Non-invasive device measuring 
skin hydration 
 
 
 
Subject’s treatment compliance 
 
 
 
Subject Questionnaire 
 
 
 
Investigator/nurse Questionnaire 
 
 
 
Non-invasive device measuring 
skin hydration 
 
 
 
New relevant medical events 
 
 
 
ADE/DD/SADE 
 
 
 
4.4 Selection of Population for Investigation 
4.4.1 Inclusion Criteria 
1. Subjects suitable for treatment with Epaderm Cream, as deemed by the investigator and 
according to intended use (eczema, psoriasis and other dry skin conditions). 
2. Subject or subject’s legal representative must be able to read and sign the Patient 
Information and Consent Form. 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 10(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
4.4.2 Exclusion Criteria 
1. Known allergy/hypersensitivity to any of the components of Epaderm Cream. 
2. Subject not suitable for the investigation according to the investigator’s judgement. 
3. Subject participating in other ongoing similar clinical investigation or other clinical 
investigations which could interfere with this investigation, as judged by the investigator. 
4. Subject previously enrolled in the current clinical investigation. 
4.4.3 Discontinuation of treatment and Lost to follow-up 
Subjects will be categorised as lost to follow-up when the investigation staff has done at least 
one documented attempt to reach the subject, after the baseline visit. When a subject 
discontinues investigation, the reason will be reported in the eCRF. 
4.4.4 Withdrawal of Subjects from treatment 
Subjects are free to discontinue participation from the investigation at any time, and without 
prejudice to further treatment. Subjects who withdraw from the investigation should always be 
asked about the reason(s) for the discontinuation and about the presence of any Adverse 
Device Effect (ADE) and, if possible, be assessed by an investigator. 
Subjects may be withdrawn from investigation treatment and assessments at any time, at the 
discretion of the investigator. 
4.5 Investigational Device 
Epaderm Cream  
Mölnlycke will provide the investigational device, to the investigation sites and subjects, free of 
charge. The treatment with the investigational device will be according to the prescription by the 
investigator together with the instruction stated on the investigational device (e.g. when used as 
an emollient: Apply liberally to the affected area and massage well into the skin. Use as often as 
required or as directed by your health care professional. When used as a skin cleanser: Use as 
required when washing or in the shower.) 
Epaderm Cream is an emollient formulated with ingredients that hydrate, aid moisture retention 
and soften the skin. It provides all the protective benefits of paraffin-based emollients and can 
be used in the management of eczema, psoriasis and other dry skin conditions. The emollient 
can also be used as a skin cleanser. Epaderm Cream is suitable for all ages including babies. 
Epaderm Cream is a Class IIa device. This device is CE-marked and has been on the market in 
its present formulation since 2012. The ingredients of Epaderm Cream are listed below: 
Ingredients 
 
% (w/w) 
Yellow Soft Paraffin BP 
15 
Liquid Paraffin Ph.Eur 
10 
Glycerine BP 
5 
Cetomacrogol Emulsifying Wax BP (SLS Free) 
5 
Chlorocresol 
0.1 
Purified Water EP 
64.9 
4.5.1 Labelling 
Labelling of the investigational device, will be in accordance with ISO 14155, the Medical 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 11(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
Devices Directive (MDD) and Mölnlycke Quality Management System. 
4.5.2 Accountability 
At the follow-up visits (at 2 and 4 weeks), the subject will be asked by the investigator/nurse 
about treatment compliance. The subject will be asked by the investigator/nurse if the 
investigational device was used according to instructions and frequency of application: 
Frequency of application: 
 Once a day 
 Twice a day 
 Three times a day 
 Four times a day 
 More than four times a day 
Daily use: 
 Every day 
 5 days or more per week 
 2-4 days per week 
 Less than 2 days a week 
Number of bottles used: 
 Less than one bottle 
 At least one bottle 
 At least two bottles 
 At least three bottles 
 At least four bottles 
4.5.3 Storage conditions 
A description of the appropriate storage is specified on the investigational device label. 
According to the instructions, the Epaderm Cream should be stored in dry conditions, below 
25°C. Epaderm Cream should be kept out of the reach of children.  
4.5.4 Method of Assigning Subjects to Product Groups 
N.A. 
4.6 Concomitant Treatments 
Concomitant treatment relevant for the investigation and the skin disease/condition, according 
to the investigator’s judgement, will be recorded in the electronic Case Report Form (eCRF). 
4.7 Performance and Safety 
4.7.1 Non-invasive device measuring skin hydration 
As an additional measurement of skin hydration, besides the subjective scale used for both 
investigator/nurse and subject, a non-invasive device, MoistureMeterEpiD from Delfin 
Technologies, will be used (please see appendix E for instructions on use). 
The MoistureMeterEpiD is an all-in-one measurement unit that is composed of an integrated 
probe, a built-in contact force sensor and a display. The OLED display shows non-invasively 
measured values in percentage of local tissue water (0 to 100 %) effectively in the epidermis 
and normal values are typically between 30-50 %. Change of some %-units of percentage 
tissue water means improvement of hydration. 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 12(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
Measurement principle 
The MoistureMeterEpiD generates a high frequency, low power electromagnetic (EM) wave into 
the skin. The reflected EM wave is analysed and the obtained value is a tissue dielectric 
constant (TDC), which is proportional to the water content of the measured site. This TDC value 
is converted to water percentage and displayed. The value increases with increasing hydration. 
4.7.2 Subject Characteristics 
See appendix C for details. 
 Dated and signed informed consent 
 Age (months, years) 
 Sex 
 Skin disease e.g. eczema, psoriasis and other dry skin conditions 
4.7.3 Performance Measurements and Variables 
Primary Endpoint Variable 
Subject evaluation of skin moisturisation (hydration) after treatment with Epaderm Cream up to 
4 weeks (at 2 and 4 weeks), using a questionnaire (the evaluations should be done on the same 
affected spot): 
 Improved Moisturisation (Strongly agree, Agree, Neither agree nor disagree, 
Disagree, Strongly disagree) 
Secondary Endpoints Variables 
1. Subject evaluation of skin softness after treatment up to 4 weeks (at 2 and 4 weeks), using 
a questionnaire (the evaluations should be done on the same affected spot). 
 Improved Softness (Strongly agree, Agree, Neither agree nor disagree, Disagree, 
Strongly disagree) 
2. Evaluation of the subject’s dry skin/xerosis after treatment with Epaderm Cream up to 4 
weeks (at baseline, 2 and 4 weeks), by investigator/nurse using “Overall dry skin score, 
ODS”. ODS, a scoring scale combining all the major and minor signs of dry skin (xerosis),  
0= Absent 
1= Faint scaling, faint roughness and dull appearance  
2= Small scales in combination with a few larger scales, slight roughness, whitish 
appearance 
3= Small and larger scales uniformly distributed, definite roughness, possibly slight 
redness and possibly a few superficial cracks 
4= Dominated by large scales, advanced roughness, redness present, eczematous 
changes and cracks 
3. Skin hydration using non-invasive device MoistureMeterEpiD (measuring the same treated 
spot on the skin during baseline and follow-up visits). The device displays percentage 
water content (%) in the epidermis (appendix G). 
4. Subject evaluation (at 2 and 4 weeks), regarding: 
a. Frequency of application and amount used of Epaderm Cream (please see 
Accountability 4.5.2) 
b. Comfort during treatment (Very poor/Poor/Average/Good/Excellent) 
c. Time of onset of effect, regarding moist and soft skin 
 Immediately 
 Within 2 weeks 
 Within 2 to 4 weeks 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 13(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
 Not at all 
d. The overall effect of the investigational device (Very 
poor/Poor/Average/Good/Excellent) 
e. Did you use the investigational device as a skin cleanser (Yes/No)? 
5. Concomitant and previous medication and treatment 
6. Number of Adverse Device Effects (ADEs) related to the use of Epaderm Cream during the 
investigation. 
Further investigation variables/data  
Baseline procedure as specified in appendix C: 
1. Subject’s age and sex 
2. Relevant Medical History (skin condition, date of diagnosis past/current, ongoing 
medication) 
a. Classification (eczema, psoriasis and other dry skin conditions) 
b. Location (Please specify) 
c. Duration (Weeks/Months/Years) 
d. Severity of diagnosis/condition according to local definition (Mild/Moderate/Severe) 
3. Type of Relevant Previous Treatment 
a. Topical: which type of medication/treatment 
b. Systemic: which type of medication/treatment 
c. Phototherapy 
4. Concomitant medication or treatment relevant for the investigation 
5. Instructions on frequency of treatment with Epaderm Cream 
6. Did the subject shower and put on a moisturiser in the morning before visit? Instruct the 
subject not to shower nor put on Epaderm Cream before the follow-up visits. 
7. Is the subject experiencing a flare of his/her skin condition at present (Yes/No/Not 
applicable)  
8. Subject evaluation of itching in relation to skin condition/diagnosis (VAS scale) 
Follow- Up visit, Visit 2 procedure will be registered for all enrolled subjects as specified in 
appendix C: 
1. New relevant medical event? If Yes, please specify 
2. Did the subject shower and put on a moisturiser in the morning before visit? (Yes/No) 
3. Is the subject experiencing a flare of his/her skin condition at present (Yes/No/Not 
applicable)  
4. Subject evaluation of itching in relation to skin condition/diagnosis (VAS scale) 
5. Changes of concomitant treatment relevant for the investigation 
a. Topical: which type of medication/treatment 
b. Systemic: which type of medication/treatment 
c. Phototherapy 
End of Investigation Visit/Visit 3 procedure will be registered for all enrolled subjects as 
specified in appendix C: 
1. New relevant medical event? If Yes, please specify 
2. Did the subject shower and put on a moisturiser in the morning before visit? (Yes/No) 
3. Is the subject experiencing a flare of his/her skin condition at present (Yes/No/Not 
applicable)  
4. Subject evaluation of itching in relation to skin condition/diagnosis (VAS scale) 
5. Changes of concomitant treatment relevant for the investigation 
a. Topical: which type of medication/treatment 
b. Systemic: which type of medication/treatment 
c. Phototherapy 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 14(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
4.7.4 Safety Measurements and Variables 
Only events related to the use of the investigational device and events related to inadequacies 
of the investigational device and the non-invasive device measuring the skin hydration, will be 
recorded as safety issues i.e. Adverse Device Effect (ADE), Serious Adverse Device Effect 
(SADE) and Device Deficiencies (DD). The definition of ADE, SADE and DD and procedures for 
reporting SADE and DD that could have led to a SADE are presented in section 8 of this CIP. 
All ADE, SADE and DD must also be recorded in the appropriate section of the eCRF. It is of 
utmost importance that all staff involved in the clinical investigation are familiar with the content 
of section 8. It is the responsibility of the Principal Investigator to ensure this. 
4.7.5 Anticipated ADEs  
Epaderm Cream has been on the market in its present formulation since 2012 with over 5.8 
million sold items (PD-420529 Rev: 02). Epaderm Cream has a low risk and is formulated with 
well-established ingredients commonly used in topical formulations.  
The following events have been identified in the Product Risk Management Record: 
 1 skin reaction registered as Adverse Event – Non-reportable. 
 7 cases of skin reaction (3), rash (3) or burning skin (1) were registered as Adverse 
Events – Non-reportable in the Mölnlycke Quality Management System during the 
period July 2015 to Oct 2017. 
The conclusion of the Product Risk Management Record is as following: Residual risks are 
negligible/tolerable and will be managed through provision of information from a Health Care 
professional, information on the product package or patient information. 
Individuals hypersensitive to any of the ingredients may experience skin irritation. Epaderm 
Cream should not be used if you have any known allergy or sensitivity to any of the ingredients. 
The Investigational Device should be used according to instructions for use (appendix D). 
4.8 Data Quality Assurance 
4.8.1 Monitoring, Audits and Inspections 
During the investigation, the monitor will have regular contacts with the investigation site. This 
contact will include visits to confirm that the facilities remain adequate to specified standards 
and that the investigation site team is carrying out the procedure stated in the CIP and supports 
the investigator. All data must be accurately recorded in the eCRF. Source data verification (a 
comparison of data in the eCRF with the subject’s hospital/practice and other records at the 
investigation site) with direct access to records will also be performed. 
The monitor, delegate or other Mölnlycke personnel will be available between visits if the 
investigator or other staff at the site needs information and/or advice. 
Authorised representatives of Mölnlycke and/or a Competent Authority (CA) and/or the Ethics 
Committee (EC)/Institutional Review Board (IRB) may visit the investigation site to perform 
audits/inspections, including source data verification. 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 15(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
4.8.2 Training of Staff 
The Principal Investigator will ensure that appropriate training relevant to the investigation is 
given to the medical, nursing and other staff at the site involved and that new information of 
relevance to the performance of this investigation is forwarded to the staff involved. 
4.8.3 Data Management 
The Data Management process includes all activities related to data handling regarding: 
 Set-up of eCRF and database 
 Specification of on-line checks 
 Data entry / Data editing 
 Export of data from Viedoc to SAS 
 Creation of post-entry checks and listings 
 Reconciliation of SADE, ADE and DD 
 Clean-file process including execution of post-entry checks and listings 
 Post clean-file tasks 
Viedoc, a web based electronic CRF system, will be used to capture data in this investigation. 
The eCRF system complies with FDA Title 21 CFR part 11 (ER/ES) requirement. 
eCRF training will be given to appropriate personnel before/at initiation of the investigation sites. 
Data entry will be performed by investigators and other authorised personnel at the sites. When 
entering data, on-line checks are incorporated in Viedoc for consistency and validation. 
Pharma Consulting Group will support with a helpdesk function taking care of system user 
questions regarding Viedoc. 
When data has been entered, authorised personnel at Mölnlycke can immediately view the 
data, send queries if necessary and lock eCRF pages when they have been validated.  
All data entered in Viedoc will be encrypted. The physical database will be stored in Sweden. 
Programs for post-entry checks and data listings will be created and executed for validation of 
data. 
Completeness will be checked by authorised personnel at Mölnlycke so that there are no 
unexplainable empty fields in Viedoc. This is done to prevent data have being overlooked by 
personnel entering the data. 
A clean-file meeting will be held prior to database lock. All decisions on the evaluability of the 
data from each individual subject for the statistical analysis must be made and documented 
before locking the database. 
4.9 Statistical Methods and Determination of Sample Size 
4.9.1 Analysis populations 
Safety population 
The safety population includes all subjects who had applied Epaderm Cream. 
Intention to treat population 
The intention to treat population consists of all subjects attending the baseline visit and meets 
the Inclusion/Exclusion criteria. 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 16(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
Per protocol population 
An evaluable subject is a subject with a baseline visit and at least one follow-up visit. At the 
clean file meeting a decision will be made as to which patients to include in the per protocol 
population. These decisions will be based on the protocol violations affecting skin hydration. 
4.9.2 Statistical Evaluation 
The results from the investigation period will be presented with descriptive statistics by visit. For 
continuous variables mean, standard deviation, median, minimum and maximum will be 
presented and for categorical data number and percentage will be presented. 
To evaluate change in skin hydration (Improved Moisturisation) evaluated by subject from 
baseline to 4 weeks (strongly agree/agree/neither agree nor disagree/disagree/strongly 
disagree) Sign test will be used. This will be made totally and for each of the three groups 
(infants, children and adults). This will be presented descriptively. 
Change over time for continuous variables will be tested using Wilcoxon signed rank test and for 
ordered categorical and dichotomous variables signed rank test will be used. 
All tests are two-sided with alpha 0.05. 
All efficacy analyses will be performed for an ITT/Full analysis set and also for a per protocol 
population. The safety variables will be studied for the Safety population. All results will be 
presented totally and for the three groups (infants, children and adults). 
Applicable data will be collated into summary tables and figures. Those summary tables and 
figures will be integrated into the body of the Clinical Investigation Report. Data listings will be 
prepared for all captured data. The listings will be incorporated into applicable appendices of the 
Clinical Investigation Report (CIR). 
4.9.3 Determination of Sample Size 
The sample size is based on that the investigation is looking at performance of Epaderm Cream 
measured as Improved Moisturisation evaluated by the subject. The answers will be recoded as 
three categories strongly agree/agree/neither agree nor disagree/disagree/strongly disagree. 
The expected distribution of the answers is strongly agree/agree 40%, neither agree or disagree 
50% and disagree/strongly disagree 10%. Assuming a power of 80% and using a Sign test a 
total of approximately 40 subjects is needed in each subgroup (infants, children and adults). 
4.10 Changes to the Clinical Investigation Plan 
No change in the investigation procedure will be effected without the mutual agreement 
between the Principal Investigator and Mölnlycke. 
An amendment to the CIP may require notification or approval from EC/IRB and, in many 
countries, also the CA before implementation. Local requirements must be followed. 
Mölnlycke will distribute CIP amendments to the Principal Investigator who is responsible for the 
distribution of these documents to the EC/IRB and staff concerned at his/her site. The 
distribution of these documents to the CA will be handled according to local practice.

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 17(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
5. STATEMENTS OF COMPLIANCE 
5.1 Ethics 
5.1.1 Ethics review 
The final CIP, including the final version of the Subject Information and Consent Form, must be 
approved or given a favourable opinion in writing by an EC in accordance with local 
requirements before enrolment of any subject into the investigation. 
The Principal Investigator is responsible for informing the EC of any amendment to the CIP in 
accordance with local requirements. 
5.1.2 Ethical Conduct of the Investigation 
The clinical investigation will be performed in accordance with the ethical principles that have 
their origin in the most recent version of the Declaration of Helsinki, and with applicable 
regulatory requirements. 
5.1.3 Subject Information and Consent Form 
The Principal Investigator will ensure that the subject/subject’s legal representative is given full 
and adequate oral and written information about the nature, purpose, possible risks and benefits 
of the investigation. Subjects/subject’s legal representative must also be notified that they are 
free to discontinue participation in the investigation at any time. The subject/subject’s legal 
representative should be given the opportunity to ask questions and time for consideration. The 
subject/subject’s legal representative signed informed consent must be obtained before 
conducting any procedure specifically for the investigation. The original must be filed by the 
Principal Investigator. A copy of the Patient Information including the signed Consent Form 
should be given to the subject. 
A sample of the Patient Information and Consent Form is enclosed (appendix B). If 
modifications are made according to local requirements, the new version must be approved by 
Mölnlycke. 
If subject’s legal representative is a parent, both parents’ signatures are required. 
The ICF process should be reflected in the source documents. 
5.2 Regulatory and standards 
5.2.1 Standards and other 
The most recent version of ISO 14155 will be followed in addition to national regulations. 
5.2.2 Subject data protection and confidentiality 
The written Subject Information explains that the data will be stored in a computer database, 
maintaining confidentiality in accordance with national data legislation and that authorised 
representatives of Mölnlycke and/or a CA and/or EC/IRB, require direct access to those parts of 
the hospital/practice records relevant to the investigation, including medical history, for 
verification of data. All data computerised by Mölnlycke will be identified by subject number only. 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 18(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
The clinical investigation will be conducted in accordance with EU General Data Protection 
Regulation 2016/679. 
5.3 Subject Protection Procedures 
5.3.1 Procedures in Case of Medical Emergency 
The Principal Investigator is responsible for ensuring that procedures and expertise are 
available to cope with medical emergencies during the investigation. 
5.3.2 Insurance 
Mölnlycke has product liability insurance. 
5.4 Use of Information and Publications 
The investigation data will be used internally by Mölnlycke in accordance with its post-market 
surveillance activities. The data may be used by Molnlycke without revealing the identity of the 
subject. It may be used in printed and digital (e.g. websites) forms for internal and external 
scientific, educational and promotional purposes, e.g. peer-reviewed journal articles, conference 
posters, conference presentations, brochures, training materials, etc. 
5.5 Record Retention 
The Sponsor will retain all investigation documents for 10 years after the device leaves the 
market. The site is required to keep the documentation in accordance with local regulation. 
5.6 Public Domain Access to the Clinical Investigation 
A description of this clinical investigation will be available on http://www.ClinicalTrials.gov 
together with the NHI website. 
6. INVESTIGATION TIMETABLE AND TERMINATION 
Investigation start: 
Anticipated Q1 2019 
Inclusion completed: 
Anticipated Q3 2019 
Last subject out: 
Anticipated Q3 2019 
Data base lock: 
Anticipated Q3 2019 
Investigation Report: Anticipated Q4 2019 
Mölnlycke retains the right to suspend or terminate this investigation at any time. The 
investigation could be prematurely discontinued if the investigation site is unable to fulfil the 
inclusion period according to the Clinical Investigation Agreement. 
7. LITERATURE REVIEW AND REFERENCES 
To determine the scientific background for this clinical investigation as well as to assess 
risks/benefits of the device, a literature review was conducted. The literature listed below was 
evaluated before serving as background information. 
1. Medical Device Directive MDD/93/42/EEC as amended. 
2. Clinical Evaluation MEDDEV 2.7/1, Rev 4; Jun 2016. 
3. Post Market Clinical Follow up Studies MEDDEV 2.12/2 Rev 2; Jan 2012. 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 19(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
4. Internal Report: Clinical Evaluation Report, Epaderm Cream with Glycerine (SLS free), PD-
420529 Rev: 02 
5. Masson P, Rodrigues FL, Berardesca E, Leveque JL, Loden M, Pierard G et al. EEMCO 
guidance for the assessment of dry skin (xerosis) and ichthyosis: Clinical scoring systems. 
Skin Res. Technol. 1995, 1, 109-114 
8. DEFINITIONS AND PROCEDURES FOR REPORTING OF 
ADVERSE DEVICE EFFECT, SERIOUS ADVERSE DEVICE 
EFFECT AND DEVICE DEFICIENCY 
Definitions: 
Device Deficiency (DD) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or 
performance. 
Note: Device Deficiencies include malfunctions, use errors, and inadequate labelling. 
All Device Deficiencies that might have led to a Serious Adverse Device Effect shall be reported 
in accordance with Serious Adverse Event reporting procedures, as specified below. 
Adverse Event (AE)  
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the investigational medical device 
Note:  
 
This definition includes events related to the investigational medical device or the 
comparator. 
 
This definition includes events related to the procedures involved. 
 
For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
Adverse Device Effect (ADE) 
Adverse Event related to the use of the investigational medical device and the hydration 
measuring device. 
Note: 
 This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, or operation, or any malfunction of the 
investigational medical device. 
 This definition includes any event resulting from use error or from intentional misuse of 
the investigational medical device. 
Serious Adverse Event (SAE) 
Adverse Event that: 
a) led to death, 
b) led to a serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 20(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
3) in-patient hospitalisation or prolonged hospitalisation or, 
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
c) led to foetal distress, foetal death or a congenital abnormality or birth defect. 
Note: Planned hospitalisation for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
 
Serious Adverse Device Effect (SADE) 
Adverse Device Effect that has resulted in any of the consequences characteristic of a Serious 
Adverse Event. 
PROCEDURES FOR SAE AND/OR SADE REPORTING OR REPORTING OF DD THAT 
COULD HAVE LED TO A SADE 
The investigator must inform Mölnlycke within 1 calendar day of awareness of the event. When 
a SAE/SADE has been entered into the eCRF by the investigator /authorised site staff, the 
eCRF system will automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com. 
In case of problem with the eCRF, a paper based version of the SAE/SADE report form 
(available in the investigator Site File) shall be used and sent by email to: 
Clinical_Investigations_Event_Reporting@molnlycke.com. 
All SAEs/SADEs that occurs during the Clinical Investigation shall be reported, whether or not 
they are considered causally related to the investigational device. 
Device Deficiencies that might have led to SADE if either a) suitable action had not been taken, 
b) if intervention had not been made, or c) if circumstances had been less fortunate must be 
reported as a SADE. 
The investigator is responsible for informing the EC/IRB and/or the Competent Authority of the 
SAE/SADE as per local requirements. 
PROCEDURES FOR DD REPORTING 
All DD shall be reported to Mölnlycke as soon as possible, without unjustified delay. If the DD 
might have led to a SADE, the reporting requirements for SADE described above must be 
followed. DDs can be either subject related or non-subject related depending on if the 
investigational device was used by a subject or not. Separate forms are used for subject related 
and non-subject related DDs. When a subject related DD has been entered into the eCRF by 
the investigator /authorised site staff, the eCRF system will automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com 
Non-subject related DDs are reported using the paper based report form located in the 
Investigator Site File. The completed form shall be sent by email to 
Clinical_Investigations_Event_Reporting@molnlycke.com  
Procedures for ADE reporting 
All ADE shall be reported by the investigator to Mölnlycke as soon as possible without 
unjustified delay. When a ADE has been entered into the eCRF by the investigator /authorised 
site staff, the eCRF system will automatically generate a report to: 
Clinical_Investigations_Event_Reporting@molnlycke.com 

 
Clinical Investigation Plan 
Document ID:  PD-551934 Rev: 01 
 
 
Title: Epaderm01 CIP with Integrated Central Amendment 1 
Page 21(21) 
Investigation Code Epaderm01 
Final Version 
Approval date 2018-12-10 
 
 
Central Amendment 1 Approval date 
2019-03-14 
 
Document template: F-167 Clinical Investigation Plan 
Rev: 10 
 
 
Causality Assessment 
The relationship between the use of the investigational device and the occurrence of each 
ADE/SADE shall be assessed by the investigator and the sponsor and classified as device 
related or not related to the device.