Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using the Dermal and Sub-dermal (SubQ) Cartridges for the Treatment of Cellulite
Phase: NA
Conditions: Cellulite
Sponsor: Syneron Medical

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 1 of 37 
 
 
 
 
 
 
 
 
Title: 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound 
System Using the Dermal and SubQ Cartridges for the Treatment of Cellulite 
Protocol Number: 
DHF21711 
Study Type: 
Prospective Clinical Study 
Date: 
November 17, 2017 
Study Devices: 
Profound 
Sponsor: 
Syneron Medical Ltd. 
Industrial Zone, Tavor Building 
P.O.B. 160 Yokneam Illit, 
20692 Israel 
Project Lead: 
Ruthie Amir MD 
Global Vice President of Clinical & Regulatory Affairs 
ruthiea@syneron.com  
+ 972-73-244-2349 
This document contains confidential information. 
This study will be performed in accordance with applicable regulatory requirements and Good Clinical 
Practice (GCP). This clinical investigation will follow the principles outlined by the International Conference 
on Harmonization (ICH). 
 
 
 
This document is the property of Syneron Medical Ltd. No part of 
this document may be reproduced, stored in retrieval system, or 
transmitted in any form or any means, electronic, mechanical, 
photocopying, recording or otherwise without prior written 
permission from Syneron Medical Ltd. 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 2 of 37 
 
Principal Investigator and study site: 
Site: 
 
Principal Investigator’s Signature 
I, _______________________________ have carefully read the foregoing protocol # DHF21711: 
“Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using the 
Dermal and SubQ Cartridges for the Treatment of Cellulite” and agree that it contains all the 
necessary information for conducting this study safely.  I will conduct this study in strict 
accordance with this protocol, Good Clinical Practices, and local regulatory guidelines, and will 
attempt to complete the study within the time designated.  I will provide copies of the protocol 
and all other information relating to pre-clinical and prior clinical experience submitted by the 
Sponsor to all personnel responsible to me who participate in the study.  I will discuss this 
information with them to assure that they are adequately informed regarding the study product 
and conduct of the study.  I agree to keep records on all subject information (case report forms, 
shipment and product return forms and all other information collected during the study) in 
accordance with GCP and Health Canada regulations. 
ACCEPTED AND AGREED: 
_______________________________  
            ____________________ 
Investigator’s Signature                                                                           Date 
_______________________________  
            ____________________ 
Ruthie Amir, M.D.  
 
 
 
 
                 Date 
 
 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 3 of 37 
 
Table of Contents 
Glossary ........................................................................................................................................... 6 
Table 1- Study Synopsis ................................................................................................................... 7 
Introduction and rationale ............................................................................................................ 10 
Background ................................................................................................................................ 10 
Device Description: Profound .................................................................................................... 11 
Principles of operation .............................................................................................................. 12 
Study design overview ................................................................................................................... 13 
Study Objective ............................................................................................................................. 13 
Primary Objective ...................................................................................................................... 13 
Primary Safety Objective ........................................................................................................... 14 
Secondary Objectives ................................................................................................................ 14 
Primary Efficacy Endpoint ..................................................................................................... 14 
Secondary Efficacy Endpoint ................................................................................................. 14 
Primary Safety Endpoint ........................................................................................................ 15 
Study population ........................................................................................................................... 15 
Number of Subjects ................................................................................................................... 15 
Subject Withdrawal and Replacement ...................................................................................... 15 
Inclusion Criteria ........................................................................................................................ 15 
Exclusion Criteria ....................................................................................................................... 16 
STUDY PROCEDURES ..................................................................................................................... 17 
Enrollment and Screening ......................................................................................................... 17 
Table 2 – Clinical Evaluation Measurements and Tools ........................................................ 18 
Pre-Treatment Procedures ........................................................................................................ 19 
Screening ............................................................................................................................... 19 
Baseline ................................................................................................................................. 20 
Treatment/s Procedure ............................................................................................................. 20 
Post Treatment Procedures ....................................................................................................... 20 
Follow-Up and Return Visits ...................................................................................................... 21 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 4 of 37 
 
DATA ANALYSIS.............................................................................................................................. 23 
Recording ................................................................................................................................... 23 
Demography and Baseline Measurements ........................................................................... 23 
Treatment Visit ...................................................................................................................... 23 
Follow-up Visit Measurements .............................................................................................. 23 
Safety ..................................................................................................................................... 23 
Protocol Revisions and/or Deviations ....................................................................................... 23 
ADVERSE EVENTS (AE) ................................................................................................................... 24 
Anticipated Adverse Effects ...................................................................................................... 24 
Unanticipated Adverse Device Effects ...................................................................................... 25 
Reporting Adverse Events (AE) and Serious Adverse Events (SAE) ........................................... 26 
Measures taken to protect the rights and welfare of subject............................................... 26 
RISK/BENEFIT ANALYSIS................................................................................................................. 26 
Risks ........................................................................................................................................... 26 
Potential benefits to participating individuals and to society ................................................... 27 
Conclusion: ................................................................................................................................ 27 
Payment for Participation ......................................................................................................... 27 
ETHICS AND GOOD CLINICAL PRACTICE ........................................................................................ 28 
QUALITY ASSURANCE AND STUDY MONITORING ......................................................................... 28 
Study Monitoring/Auditing/Inspection ..................................................................................... 28 
ADMINISTRATIVE PROCEDURES .................................................................................................... 29 
Supply and Disposition of Study Device .................................................................................... 29 
Control & Disposition of the Investigational Device ................................................................. 29 
Informed Consent ...................................................................................................................... 29 
Monitoring Plan ......................................................................................................................... 29 
Case Report Forms .................................................................................................................... 29 
Record Maintenance ................................................................................................................. 30 
PUBLICATION POLICY..................................................................................................................... 30 
BIBLIOGRAPHY ............................................................................................................................... 31 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 5 of 37 
 
Appendix I – Study Summary ........................................................................................................ 32 
Appendix II – Photography Guidelines .......................................................................................... 34 
Appendix III – Assessment scales .................................................................................................. 35 
Appendix IV - Pain assessment ...................................................................................................... 37 
 
 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 6 of 37 
 
GLOSSARY 
 
ADE 
Adverse Device Effect 
AE 
BMI 
Adverse Event 
Body Mass Index 
CFR 
Code of Federal Regulations 
Cm 
Centimeter 
CRF 
Case Report Form 
FDA 
Food & Drug Administration 
FU 
GCP 
Follow-up 
Good Clinical Practice 
ICF 
Informed Consent Form 
IEC 
Institutional Ethics Committee 
IRB 
Institutional Review Board 
Kg 
Kilogram 
Min 
Minute 
wk 
Weeks 
PI 
Principal Investigator 
USAE 
Unanticipated, serious adverse event 
USADE 
Unanticipated, serious adverse device effect 
SAE 
Serious Adverse Event 
Tx 
 
Treatment 
 
 
 
 
 
 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 7 of 37 
 
TABLE 1- STUDY SYNOPSIS 
Proprietary Name 
Profound device utilizing the Dermal and SubQ Cartridges 
Design 
Prospective, open-label, baseline-controlled, clinical study to evaluate the 
Profound device using the Dermal and SubQ Cartridges for minimally-invasive 
treatment of cellulite appearance, skin laxity and subcutaneous fat deposits in 
the upper arms, above the knees and bra bulges. 
 
Eligible subjects will undergo a single treatment with the Profound device using 
the Dermal and/or SubQ cartridges, based on treating physician discretion. 
 
Study Population 
Up to 60 healthy female volunteers, seeking cellulite treatment, 18 to 60 years of 
age from 2 investigational sites. 
Treatment 
and 
Duration 
Eligible subjects will undergo a single treatment with the Profound device, using 
the Dermal and/or SubQ cartridges, based on treating physician’s discretion. Each 
subject will be treated on both left and right body sides of one of the treatment 
areas: upper arms, above the knees or the bra bulge area. 
Treatment areas will be assessed at the next visits:  
1. One-week post treatment follow-up (1wk FU) – safety only 
2. One-month post treatment follow-up (1M FU) 
3. Three-month post treatment follow-up (3M FU) 
4. Six-month post treatment follow-up (6M FU)  
Total expected study duration is up to 7 months. 
Objective 
The objective of this trial is to evaluate the safety and efficacy of the Profound 
device utilizing the Dermal and SubQ Cartridges for minimally-invasive treatment 
of the upper arms, above the knees and bra bulges to improve the appearance of 
cellulite, skin laxity and subcutaneous fat deposits.  
Primary Objective 
Statistically significant improvement in global aesthetic appearance of cellulite, 
skin laxity and subcutaneous fat deposits of the upper arms, above the knees and 
bra bulges, following dermal and/or subcutaneous Profound treatment, as 
assessed by blinded evaluators at 3M post last treatment (3M FU) versus 
baseline. 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 8 of 37 
 
Primary Safety 
Objective 
1. Evaluate the safety of cellulite treatment with the Profound device 
utilizing the Dermal and/or SubQ Cartridges for entire duration of study 
(1wk Post first treatment, 1 month, 3 month and 6 month post last 
treatment) 
2. Comfort level during treatment: 
Comfort assessment will be performed independently by the subject 
using NSR scale. Subjects will be asked to fill out a questionnaire after 
treatment 
Secondary 
Objectives 
1. Statistically significant improvement in global aesthetic appearance of 
cellulite, skin laxity and subcutaneous fat deposits of the upper arms, 
above the knees and bra bulges, following dermal and/or subcutaneous 
Profound treatment, as assessed by study investigator at all post 
treatment visits, except the 1-week safety evaluation (1M FU, 3M FU & 
6M FU) versus baseline. 
2. Investigator satisfaction: 
Satisfaction assessment will be performed by study investigator using a 
pre-defined scale questionnaire. The investigator will fill out 
questionnaire at each post treatment follow-up visit (1M FU, 3M FU & 
6M FU). 
3. Subject improvement and satisfaction: 
Improvement 
and 
satisfaction 
assessment 
will 
be 
performed 
independently by the subject using a pre-defined scale questionnaire. 
Subjects will fill out questionnaires at each follow-up visit (1M FU, 3M FU 
& 6M FU). 
Efficacy Endpoints 
Primary and secondary objectives will be assessed for treated areas, using the 
following efficacy endpoints: 
1. Global aesthetic improvement, using a using a 5-point grading scale 
(0=No change, 1=1%-24%%, 2=25%–49%, 3=50%-74% improvement, and 
4=75%-100%) (Error! Reference source not found. – Table 6) 
2. Skin tightening improvement (Appendix III – Table 7) 
3. Investigator satisfaction using a pre-defined scale (Appendix III – Table 8) 
4. Subject assessments (Appendix III – Tables 7-10)  
Safety Endpoints 
1. Number, severity and type of any adverse event recorded throughout the 
study and post treatment (immediate and delayed response) 
2. Pain assessment using NSR scale 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 9 of 37 
 
3. Investigator assessment of immediate response 
4. Subject 1-week post first treatment follow-up visit (1wk Post Tx.1 FU) - 
discomfort assessment and duration of side-effect will be conducted 
Statistical Methods 
 
 
Descriptive statistics will be used to present changes in assessments along the 
study course. Global aesthetic improvement assessments, subject assessments 
and investigator satisfaction data will be analyzed using two-tailed Wilcoxon 
Signed Rank test and/or paired t-test (alpha=0.05) to analyze the data difference 
from baseline and longitudinal change.   
 
 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 10 of 37 
 
INTRODUCTION AND RATIONALE 
Background 
This is a prospective clinical study to determine the efficacy of Profound device for treatment of 
cellulite in the upper arms, above the knees and the bra bulge area. The Profound system received 
FDA 510(k) clearance in 2009 under K082391, and is intended for use in dermatologic and general 
surgical procedures for hemostasis and electrocoagulation and the percutaneous treatment of 
facial wrinkles. In addition, the Profound device received FDA 510(K) clearance in 2016 under 
K161043, and is intended for use in dermatologic and general surgical procedures for 
electrocoagulation and hemostasis, percutaneous treatment of facial wrinkles, and improvement 
in the appearance of cellulite (supported by long-term clinical data - 6 months). 
Cellulite is an aesthetically unacceptable cosmetic problem for many post-adolescent women.  It 
is largely observed in the gluteal-femoral regions with an “orange-peel” or “cottage cheese” 
appearance [1].  The condition is not specific to overweight issues although increased adiposity 
will exacerbate the cosmetic issue.  
Recent research papers on cellulite anatomical features have shown specific features in the 
dermal and subcutaneous layers of the skin which are characteristic of cellulite presence [1-5].  
First, superficial fat lobules called papillae adiposae were shown to be protruding within the 
dermal layer in the form of intrusion pockets.  Figure 1 - Fat indentation invading the dermal layer 
shows a gross histology of the dermis/subcutis transition where the fat pockets are present. 
 
 
Figure 1 - Fat indentation invading the dermal layer 
 
Second, tissue observations from autopsy on female subjects with cellulite have suggested a 
higher percentage of fibrous septae oriented perpendicular to the skin surface as opposed to 
males who tend to have the septae organized in a criss-cross fashion.  The arrangement of fibrous 
septae perpendicular to the skin surface in a female is shown in Figure 2 - Fibrous septae in 
subcutis perpendicular to the skin surface.   

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 11 of 37 
 
 
Figure 2 - Fibrous septae in subcutis perpendicular to the skin surface 
 
This subcutaneous fibrous strand organization tends to create uneven appearance of the skin 
surface, which is characteristic of cellulite.  Therefore, it is thought that treatments targeting the 
dermis and subcutaneous layers of the skin could have beneficial effects on the appearance of 
cellulite.  Indeed, a treatment which would increase the dermal thickness would create a 
condition where the hypodermal fibrous strand organization described above would have fewer 
tendencies to deform the skin surface and improve the appearance of cellulite.    Furthermore, a 
remodeling of the subcutaneous fibrous band organization following fractional thermal injuries, 
in conjunction with a volumetric reduction of the fat lobules would decrease the local tension 
forces responsible for the presence of cellulite.   
This study presents a one arm investigation aimed at using fractional energy delivery targeting 
the dermal and subcutaneous tissue together. 
Device Description: Profound   
The main intent of the System is to utilize a minimally-invasive approach to directly deliver RF 
energy into tissue through pairs of micro-electrode needles and use temperature sensors within 
the needles to reliably create fractional thermal injuries within the skin.  The System, shown in 
Figure 3 – Cartridge, Handpiece, and Console, consists of: 
• 
Console to allow physician to set treatment parameters and delivers RF energy to a re-
useable Handpiece and Cartridge;  
• 
Two types of re-useable Handpieces (SubQ Handpiece and Dermal Handpiece) to enable 
subject treatment by making the link between the Console and a single-use sterile 
Cartridge; and 
• 
Two types of single-use sterile Cartridges to deliver RF energy: 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 12 of 37 
 
• 
SubQ Cartridge (75⁰) delivers RF energy to the subcutaneous through the 
dermal layer of the skin, which creates fractional thermal injuries to ablate 
the targets – the dermal and subcutaneous layers. 
• 
Dermal Cartridge (25⁰) delivers RF energy to the dermal layer of the skin, 
which creates fractional thermal injuries to ablate dermal targets. 
 
Figure 3 – Cartridge, Handpiece, and Console 
 
The Console includes a color touch screen with a Graphical User Interface (GUI) which is mainly 
used to select two treatment parameters – the target temperature and the application time, 
communicate messages to the user, and setup preferences.   
Principles of operation 
The System uses a minimally invasive approach to deliver bipolar non-ablative radiofrequency 
(RF) energy to the dermal layers of the skin. The physician first selects two treatment parameters, 
target tissue temperature and application time, by interacting with the GUI of the Console.  Using 
the Handpiece and Cartridge connected to the Console, the physician then inserts the array of 
micro-needle electrode pairs into the dermal layer of the skin.  Within each pair, a temperature 
sensor is located at the distal tip of the electrode to provide real-time feedback of target tissue 
temperature from within the forming thermal injury.  This temperature feedback information 
allows the console to deliver RF energy to the needles to reach and maintain the physician-
selected target temperature.  The system allows it to precisely, predictably, and reliably reach and 
maintain tissue temperature regardless of skin impedance, as shown in peer-reviewed 
publications [6-11].   

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 13 of 37 
 
STUDY DESIGN OVERVIEW 
This study is a prospective, open-label, baseline-controlled, clinical study, to evaluate cellulite 
appearance, skin laxity and subcutaneous fat following Profound treatment, using the Dermal 
and/or SubQ Cartridges for minimally-invasive treatment targeted to both dermal and 
subcutaneous layer of the skin in the upper arms, above the knees and bra bulges [area between 
the armpits and chest].  
Up to 60 Healthy subjects at 2 investigational sites will be enrolled in this study. All subjects will 
undergo an assessment of their general health. Treatment areas will undergo a single Dermal 
and/or SubQ treatment, depending on the body location, thickness of fat in the treatment area 
and proximity to bone. The treatment will be according to physician discretion, as both treating 
physicians are highly experienced Profound users. Global aesthetic improvement (GAI) will be 
assessed at each follow-up visit starting from the 1-month follow-up. 
Before treatment (15-20 minutes) the tissue to be treated will be injected with tumescence 
solution. 
All treatment areas will undergo a single treatment with the Profound device, utilizing the Dermal 
and/or SubQ Cartridges. 
During the follow-up period, 4 visits will be conducted as follows: one-week post first treatment 
safety follow-up visit (1wk FU post Tx.1) and efficacy and safety follow-up visits at the 1-month 
(1M FU), 3-month (3M FU) and 6-month (6M FU) post treatment visits.  
Improvement in cellulite appearance will be assessed at each post baseline visit. Additionally, 
investigator and subject questionnaires will be completed.  Finally, photography will be 
performed under visible light conditions of the front, right, left and back view.  Most assessments 
will be performed at all study visits. 
STUDY OBJECTIVE 
The objective of this trial is to evaluate the safety and efficacy of the Profound device utilizing the 
Dermal and SubQ Cartridges for minimally-invasive cellulite treatment in the upper arms, above 
the knees and bra bulge areas. 
Primary Objective 
The objective of this trial is to evaluate the efficacy of the Profound device for improving the global 
aesthetic appearance (GAI) of cellulite, skin laxity and subcutaneous fat deposits of the upper 
arms, above the knees and bra bulges, following dermal and/or subcutaneous Profound 
treatment, as assessed by blinded evaluators at 3M post last treatment (3M FU) versus baseline. 
Evaluation by blinded evaluators will be based on a 5-point grading scale (0=No change, 1=1%–
24%, 2=25%–49%, 3=50%-74% and 4=75%-100%) (Appendix III – Table 6): 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 14 of 37 
 
Primary Safety Objective 
1. Evaluate the safety of cellulite treatment with the Profound device utilizing the Dermal 
and SubQ Cartridges during all study 
2. Comfort level during treatment: 
Comfort assessment will be performed independently by the subject using NSR scale. 
Subjects will be asked to fill out a questionnaire after the treatment/s (Tx.1/ Tx.2) 
Secondary Objectives 
1. Statistically significant improvement in appearance of cellulite, skin laxity and 
subcutaneous fat deposits (Appendix III – Tables 6 and 7) of the upper arms, above the 
knees and bra bulges, following dermal and/or subcutaneous Profound treatment, as 
assessed by study investigator at all post treatment visits (1M FU, 3M FU & 6M FU) versus 
baseline.  
2. Investigator satisfaction: 
Satisfaction assessment will be performed by the study investigator using a pre-defined 
scale questionnaire (Appendix III – Table 8). The investigator will fill out the questionnaire 
at each post treatment follow-up visit (1M FU, 3M FU & 6M FU). 
3. Subject improvement and satisfaction: 
Subject assessments will be performed independently by the subject using a pre-defined 
scale questionnaire (Appendix III – Tables 7-10). Subjects will fill out the questionnaire at 
each follow-up visit (1M FU, 3M FU & 6M FU). 
Primary Efficacy Endpoint 
Blinded evaluation of global aesthetic improvement (GAI) in the appearance of cellulite, skin laxity 
and subcutaneous fat deposits of the upper arms, above the knees and bra bulges, using a 5-point 
grading scale (Appendix III – Table 6).  Efficacy is assessed by correctly identifying the correct pre- 
and post-treatment photos of the same subject, and having at least 50% or greater (Grade of 3 or 
4) global aesthetic improvement at the 3-month follow-up visit relative to baseline photos. 
Improvement reflects improvement in cellulite appearance, skin laxity or visible reduction in 
localized fat deposits in the treated areas. There will be two blinded evaluators to assess the 
photos.  
The study primary endpoint is achieved when 80% subjects show at least 50% improvement at 
the 3-month follow-up visit relative to baseline photos. 
Secondary Efficacy Endpoint 
Secondary objectives will be assessed using the next efficacy endpoints: 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
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1. Investigator Assessment of global aesthetic improvement (Appendix III – Table 6) and skin 
laxity scale (Appendix III – Table 7), using before and after photographs. 
2. Investigator satisfaction using a pre-defined scale (Appendix III – Table 8).  
3. Subject assessments, using a pre-defined scale questionnaire (Tables 7-10). 
Primary Safety Endpoint 
1. The number, severity and type of any adverse event recorded throughout the study and 
post treatment (discomfort (pain), immediate and delayed response). 
2. Occurrence of expected post treatment immediate response during all study period based 
on predefined scale (Appendix III; Table 4). 
3. Discomfort (pain) level using a 10-point visual analog scale will also be recorded after each 
benign pigmented lesion clearance treatment– by Numerical Scale Response (NSR), 
according to Appendix IV - Pain assessment. 
4. Subjects 1-week post treatment follow-up visit (1wk FU) - discomfort assessment and 
side-effect duration will be conducted. 
STUDY POPULATION 
Number of Subjects 
This study will be comprised of up to 60 female subjects at two (2) investigational sites. Subjects 
who meet all the inclusion and none of the exclusion criteria will be enrolled. 
Subject Withdrawal and Replacement 
Subjects enrolled in the study can discontinue their participation at any time for any reason 
without prejudice or reduction in the quality of their medical care.  The investigators or sponsor 
can terminate a subject's participation in this study to protect the subject's health or if the subject 
fails to follow directions resulting in noncompliance to study procedures.  Subjects who withdraw 
or are terminated from the study may be replaced to ensure at least 60 subjects have completed 
the study.  Subjects who fail to complete the treatment will be replaced and will not be evaluable.  
Inclusion Criteria 
A subject is eligible to participate in the study if he/she meets all the following inclusion criteria: 
1. Signed informed consent to participate in the study. 
2. Healthy male or female subjects,  18 and  60 years of age at the time of enrollment. 
3. Fitzpatrick Skin Type I to VI. 
4. Subjects seeking treatment of cellulite/skin tightening in the upper arms, above the knees 
or bra bulge area. 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
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Rev. Date 
November 17, 2017 
Page 16 of 37 
 
5. Clinically appreciable cellulite, skin laxity or subcutaneous fat deposits in the treatment 
areas, as determined by the study investigator. 
6. Not pregnant, lactating and must be either post-menopausal, surgically sterilized, or using 
a medically acceptable form of birth control at least 3 months prior to enrollment (i.e., 
oral contraceptives, contraceptive implant, barrier methods with spermicide or 
abstinence). 
7. Negative urine pregnancy test as tested prior to each treatment and at the last visit for 
women of child bearing potential (e.g. not menopause). 
8. General good health confirmed by medical history and skin examination of the treated 
area. 
9. Willing to receive the proposed Profound treatment. 
10. Willing to follow the treatment and follow-up schedule and post-treatment care 
instructions. 
11. Willing to have photographs and images taken of the treated areas to be used de-
identified in evaluations, publications and presentations. 
Exclusion Criteria 
A subject is not eligible for participation in this study if he/she meets any of the following exclusion 
criteria: 
1. Subject had surgery or any other procedure for cellulite in the last 6 months. 
2. Pregnant or planning to become pregnant, having given birth less than 3 months ago, 
and/or breast feeding. 
3. Known allergy to lidocaine or epinephrine or antibiotics. 
4. Active malignancy or history of malignancy in the treatment area in the past 5 years. 
5. Having any active electrical implant anywhere in the body, such as a pacemaker or an 
internal defibrillator. 
6. Suffering from significant concurrent illness, such as cardiac disorders, diabetes (type I or 
II), lupus, porphyria, or pertinent neurological disorders (i.e. any disease state that in the 
opinion of the Physician would interfere with the anesthesia, treatment, or healing 
process). 
7. Having a known anti-coagulative or thromboembolic condition or taking anticoagulation 
medications one week prior to and during the treatment course (to allow inclusion, 
temporary cessation of use as per the subject’s physician discretion). 
8. History of immunosuppression/immune deficiency disorders (including HIV infection or 
AIDS) or currently using immunosuppressive medications. 
9. Suffering from hormonal imbalance, whether related to thyroid, pituitary, or androgen. 
10. History of significant lymphatic drainage problems. 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
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Rev. Date 
November 17, 2017 
Page 17 of 37 
 
11. History of cancer which required lymph node biopsy or dissection. 
12. Suffering from significant skin conditions in treatment areas or inflammatory skin 
conditions, including, but not limited to, open lacerations or abrasions, hidradenitis, or 
dermatitis of the treatment area prior to treatment (duration of resolution as per the 
Investigator’s discretion) or during the treatment course. 
13. History of keloid scarring, abnormal wound healing and / or prone to bruising. 
14. History of epidermal or dermal disorders (particularly if involving collagen or 
microvascularity), including collagen vascular disease or vasculitic disorders. 
15. Use of isotretinoin (Accutane®) within 6 months of treatment or during the study. 
16. Subject on systemic corticosteroid therapy 6 months prior to and throughout the course 
of the study. 
17. Dysplastic nevi in the area to be treated. 
18. Participation in a study of another device or drug within 3 months prior to enrollment or 
during this study. 
19. Subject has palpable lymphadenopathy at any visit. Standard palpation techniques will be 
used. 
20. Subjects with history of severe edema. 
21. As per the Investigator’s discretion, any physical or mental condition that might make it 
unsafe for subject to participate in this study. 
STUDY PROCEDURES 
Enrollment and Screening  
During the first visit, the investigator/ research staff will screen the subject for eligibility to 
participate.  The inclusion/exclusion criteria will be reviewed, the subject’s medical history, an 
examination of the subject’s skin in the treatment areas will be conducted.   
 
The subject will review the informed consent form and the study will be explained to the subject 
including all risks, potential benefits, procedures, visit requirements, and other alternative 
treatment options.   If the subject qualifies and wishes to participate they will complete the ICF 
with a signature and date.  The original will be retained with subject’s records and a copy will be 
provided to the subject. 
The following measurements will be performed and recorded at the specified times throughout 
the study. 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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Table 2 – Clinical Evaluation Measurements and Tools 
Claim/ Task 
When to conduct 
Method 
ICF process, eligibility 
screening and medical 
history 
Screening/ Baseline 
Physician or staff will complete the form with 
the study subject 
Weight 
Screening/ Baseline, prior to treatment 
Tx.1, and at all follow-up visits (1wk 
FU, 1M FU, 3M FU and 6M FU) 
Scale 
Photographs 
Standardized digital photographs 
Global aesthetic 
improvement & Skin laxity 
At all post treatment follow-up visits, 
except 1-week FU (1M FU, 3M FU and 
6M FU) 
Physician will assess treated areas, using the 
scales in Appendix III – Tables 6 & 7 
Antibiotic prescription for 
subject 
Evening prior to treatment procedure 
for seven days post procedure 
Physician may prescribe antibiotic for the 
subject. Antibiotic will be taken for total of 8 
days (optional). 
Urine pregnancy test 
Baseline, prior to treatment Tx.1, and 
at the last follow-up visit (6M FU) 
Urine pregnancy test 
Treatment-associated pain 
Immediately post treatment: 
 
Subject will be asked to rank/ assess pain level 
during treatment based on the Numerical Scale 
Response (NSR scale - Appendix IV - Pain 
assessment) 
Daily diary 
Post treatment, for 1-week period 
Subjects will be requested to fill daily diary 
with data regarding their comfort, AE, and 
activity (7 days of follow-up post treatment) - 
Post Treatment Side Effect Severity Scale 
(Table 4 - Post Treatment Side Effect 
Severity Scale) 
Compression Garment 
wear 
Immediately post treatment, for 1-
week period 
Subject may wear Compression Garment wear 
for 1-week period after treatment/s (except 
from bath time) - optional. 
Investigator satisfaction 
At all post treatment follow-up visits, 
except 1-week FU (1M FU, 3M FU and 
6M FU) 
 
Satisfaction Questionnaire (Error! Reference s
ource not found.) 
Subject assessments 
Subject questionnaire (Tables 7-10). 
Safety 
Throughout the study.  
Skin examination in treated areas, subject 
interview, Adverse Events form, occurrence of 
adverse events and severity ratings: as well as 
relation to treatment, action taken and 
outcome 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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Protocol # 
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Rev. Date 
November 17, 2017 
Page 19 of 37 
 
 
Baseline
Tx.1
1 Month Follow-Up 
(1M FU Post Tx.2)
3 Month Follow-Up 
(3M FU Post Tx.2)
6 Month Follow-Up 
(6M FU Post Tx.2)
Day -1
Day 0
Month 1
Month 3
Month 6
1 Week Follow-Up 
(1wk FU Post Tx.1)
Day 7
 
Figure 4: Study Flow-Chart (Visits at the Clinic) 
 
Pre-Treatment Procedures 
Screening and Baseline procedures can be conducted at the same visit day, and at least one day 
prior to the first treatment.  It is expected that screening and baseline procedures are conducted 
during the same visit, while the first treatment visit will occur one day or up to 14 days post 
baseline. 
Screening 
1. ICF – should be obtained prior to any study procedures.  When subject fully understands 
all potential risks and benefits of the study, subject will be asked to sign and date the 
consent form.  The subject will be given a copy of the signed ICF. 
2. Subject ID - subjects will be assigned a study subject ID number.  
3. Medical History - A medical history will be obtained to determine if the subject meets 
study criteria, including a list of all prescribed and over the counter medications taken 
within the previous 6 months will be recorded.   
4. Weight measurements will be taken. 
5. Pregnancy Screen - Subjects who are capable of becoming pregnant will undergo a urine 
pregnancy test. This will be repeated prior to all treatments and at the end of the study 
(last FU visit/ 6M FU). 
6. Skin Exam - The subject will undergo a routine skin examination to determine study 
eligibility including the presence of clinically appreciable cellulite, skin laxity or 
subcutaneous fat deposits in the treatment areas. 
7. Scheduling: Subjects will be scheduled to return for the baseline and treatments visit 
within 14 days following the screening visit. It is preferable the baseline procedures are 
conducted at the day of screening, while Tx.1 will be conducted one day after the 
Screening visit. 

 
 
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8. Subjects may be prescribed Antibiotics (type and dosing will be determined by study 
investigator) for 1 week, starting in the evening prior to treatment until 7 days post 
procedure (optional). 
Baseline 
1. Unwanted hair should be removed from the treated area by study staff prior to treatment 
at the clinic. 
2. Photography – Baseline photographs will be obtained using consistent camera and 
subject placement settings (Appendix II – Photography Guideline). 
Treatment/s Procedure 
In accordance with the Profound User’s Manual: 
1. Both upper arms or knees or bra bulges will be treated (right and left). 
2. Subjects should wear disposable underwear. 
3. Subject weight will be taken. 
4. Clean with two passes of iodine-based skin sterilizing solution such as Betadyne.  Allow to 
dry completely, without wiping off. 
5. Local infiltration of tumescence solution which consists of 1% lidocaine with 1:100,000 
epinephrine diluted in a 1:3 sterile normal saline to a final concentration of 0.25% 
lidocaine with 1:400,000 epinephrine, will be performed throughout the treatment area 
to manage pain and bleeding/bruising.  This will be performed 15-20 minutes prior to the 
start of treatment to allow vasoconstriction. 
6. Tumescence amount for adequate pain control will be administered at the discretion of 
the Investigator throughout the treatment process. 
7. Profound thermal settings of 67°C, 4 sec will be used for all subjects. 
8. Cold air will be used to cool down the treated skin for increased comfort - optional. 
9. Spacing between adjacent Profound needle insertions will be between 3-4mm. 
10. Connect the Dermal/ SubQ Cartridge targeted dermal/ subcutaneous layer of the skin, 
respectively, according to investigator discretion. 
Post Treatment Procedures 
1. Pain assessment – immediately after each treatment subjects will be asked to rank pain 
sensation experienced during treatment using Numerical Scale Response (NSR; see 
Appendix IV - Pain assessment) for the Profound procedure 
2. Safety aspect will be assessed before and after each treatment: 

 
 
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i. 
Clinical effects - All visible and palpable immediate response will be recorded for 
the entire treatment area using a 4-point severity scale (Table 4 - Post Treatment 
Side Effect Severity Scale). 
ii. 
Adverse Events – Record the number, severity and type of any adverse event 
occurred before, through and after treatments. 
3. If prescribed, subject should continue taking the antibiotics prescribed by investigator, 
starting from the evening prior the treatment till 7 days post treatment (optional). 
4. If suggested by investigator, subjects should apply a thin coat of Vaseline Petroleum Jelly 
with Bactroban (mupirocin) antibiotic to the treated area per standard medical 
procedure. 
5. Subjects will receive daily diary post first treatment which they will be requested to fill 
out with data regarding their comfort, adverse events, and daily activities (7 days of 
follow-up post treatment). 
6. Subject may be instructed to wear Compression Garment covering the treated area 
(supplied by the study sponsor) for 1 week, starting immediately post treatment 
(optional). The Garment should be worn 24 hours a day, seven days a week and removed 
only for bath (optional).  
7. Subjects should be advised to contact their study physician if they have any concerns 
about how their treatment areas are responding to treatment or how they are healing. 
Follow-Up and Return Visits 
1. All subjects will be requested to return to the clinic at the following time-points during 
the study in order to assess the clinical performance (safety & efficacy) of the device: 
i. 
FU1 – 1 week (±2 days) post treatment (1wk FU) -Safety only. 
ii. 
FU2 – 1 month (±7 days) post treatment (1M FU). 
iii. 
FU3 – 3 month (±14 days) post treatment (3M FU). 
iv. 
FU4 – 6 month (±14 days) post treatment (6M FU). 
2. At 1wk FU visit the following tasks will be conducted and data recorded: 
i. 
Review changes in medication, medical history, and AE, if applicable from last 
visit. 
ii. 
If taken, verify subject completed the course of antibiotic. 
iii. 
If used, verify subject removed the Compression Garment. 
iv. 
Photographs of treated area. 
v. 
Subject’s weight will be recorded. 
vi. 
Completion of subject safety assessment questionnaire (daily dairy) according to 
pre-defined scale (Table 4 - Post Treatment Side Effect Severity Scale & Table 5 - 

 
 
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Post Treatment Side Effect Duration). Relevant forms should be filled out as 
necessary. 
3. At post-treatment follow-up visits (FU2, FU3 and FU4) the following tasks will be 
conducted and data recorded: 
i. 
Review changes in medication, medical history, and AE, if applicable from last 
visit. 
ii. 
Photographs of treated area (as needed, un-wanted hair will be removed from 
the treated area by study staff at the clinic).  
iii. 
Subject’s weight will be recorded. 
iv. 
Global Aesthetic Improvement (GAI) scale and Skin Tightening scales – will be 
completed (Appendix III – Tables 6 & 7). 
v. 
Completion of Physician satisfaction rating (Table 8).  
vi. 
Completion of Subject assessments (Table 6 –Global Aesthetic Improvement 
(GAI) Scale). 
vii. 
At the final visit (6M FU) a urine pregnancy test will be performed for women of 
childbearing potential. 
 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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November 17, 2017 
Page 23 of 37 
 
DATA ANALYSIS 
Recording 
All data will be recorded in source documents and transcribed onto Case Report Forms (CRFs). 
Site will be monitored by Syneron staff or designees to assure adherence to the clinical trial 
requirements, subject safety, protocol procedures, and for data accuracy. The Case Report Forms 
and images will be reviewed and retrieved during the monitoring visit.  All source documentation 
will remain in the subject's files at the site. 
Review and Analysis of all data collected will be conducted by the Sponsor or designee as 
described for this protocol with the following data:  
Demography and Baseline Measurements 
Demographic and baseline/screening measurements (e.g., age, weight, cellulite assessment, and 
digital images) will be collected and descriptively presented. 
Treatment Visit 
Skin assessment by the PI, photographs of the treated region, and pain scores will be collected 
used to document any adverse events to assess the device performance. 
Follow-up Visit Measurements 
Follow-up measurements (e.g.: weight), assessment (e.g.: global aesthetic improvement) and 
digital images will be used for comparative measurements with their respective measurement at 
baseline.  Primary endpoints will be evaluated at the 3-month follow-up after the Profound 
treatment. Secondary endpoints may be evaluated at all visits.  
Safety 
Safety of device procedure will be evaluated through skin assessments by the PI and research 
staff.  The occurrence and severity of all complications from the start of the study will be 
documented.   
Protocol Revisions and/or Deviations 
With the exception of emergency situations, no changes or deviations in the conduct of this 
protocol will be permitted without the prior approval of the sponsor. 
The IRB/IEC that granted original approval for the study must be notified of all changes in the 
protocol, and will approve any change or deviation that may increase risk to the subject, and/or 
that may adversely affect the rights of the subject or validity of the investigation. 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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November 17, 2017 
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In the event of an emergency, the Investigator will institute any medical procedures deemed 
appropriate. However, all such procedures must be promptly reported to the sponsor and the 
IRB/IEC. 
ADVERSE EVENTS (AE) 
An adverse event (AE) is any adverse change in health or side effect that occurs in a study 
participant during their participation in the study. 
Anticipated Adverse Effects 
Following treatment with the Profound the following local adverse effects could occur 
(anticipated): 
➢ Ecchymosis 
➢ Numbness 
➢ Hyperpigmentation 
➢ Infection 
➢ Hypopigmentation 
➢ Itching 
➢ Bruising 
➢ Scarring 
➢ Swelling 
➢ First degree burns 
➢ Twinge (pain) 
➢ Second degree burns 
➢ Loss of sensation 
➢ Nerve damage 
An adverse event (AE) is any undesired clinical occurrence in a study subject as indicated by signs, 
symptoms, illnesses, events that develop or worsen in severity in association with the study when 
deemed by the Investigator to be related to use of the device or study procedures. The 
Investigator will document all adverse signs and symptoms regardless of severity or frequency 
that are either volunteered by subjects or observed during the course of the study that are related 
to the device.  The Investigator will also record adverse experiences of subjects resulting from 
concurrent illnesses, reactions to concurrent medications, or progression of disease states that 
the Investigator deems related to the device. Included in the description will be the nature of the 
sign or symptom, the date of onset, whether the event was serious, the severity, the relationship 
to study procedures or investigational device, the action taken, the date of resolution, and the 
outcome. The Principal Investigator will determine the relationship of the adverse device effect 
to the investigational device. 
Anticipated effects from the injected local or tumescent anesthetic if used may be allergic 
reaction, feeling anxious, shaky, dizzy, restless, or depressed; drowsiness, vomiting, ringing in the 
ears, blurred vision; confusion, twitching, seizure (convulsions); fast heart rate, rapid breathing, 
feeling hot or cold; weak or shallow breathing, slow heart rate, weak pulse; or feeling like passing 
out. Less serious side effects include: mild bruising, redness, local scars, itching, or swelling where 
the medication was injected; mild dizziness; nausea. 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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Unanticipated Adverse Device Effects 
For device studies, part 21 CRF 812.3(s) uses the term unanticipated adverse device effect which 
is defined as any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with the device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects.  
Significant device failure may constitute an adverse event if an undesirable experience occurs.  
This definition includes any event resulting from insufficiencies or inadequacies in the instructions 
for use or the deployment of the device, or any event that is a result of a user error. 
All unanticipated adverse effects will be graded as follows: 
Mild: 
Sign or symptom, usually transient, non-life-threatening requiring no special 
treatment and generally not interfering with usual activities. 
Moderate: 
Sign or symptom, non-life-threatening which may be ameliorated by simple 
therapeutic measures, and may interfere with usual activity. 
Major: 
Sign or symptom that is intense or debilitating but non-life-threatening and 
that interferes with usual activities. Recovery is usually aided by 
therapeutic measures and the discontinuation of the study device may be 
required. 
Severe: 
Any untoward medical occurrence that at any time results in death or life-
threatening illness, resulting in persistent or significant disability/incapacity.   
The relationship of the adverse effect to the study is defined as follows: 
Probable: 
An adverse event has a strong temporal relationship to study device, and 
another etiology is unlikely or significantly less likely. 
Possible: 
An adverse event has a strong temporal relationship to the study device, 
and an alternative etiology is equally or less likely compared to the 
potential relationship to study device.  
Probably not: 
An adverse event has little or no temporal relationship to the study device 
and/or a more likely alternative etiology exists. 
Not related: 
An adverse event has no temporal relationship to study device or has a much 
more likely alternative etiology.  
 
 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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Reporting Adverse Events (AE) and Serious Adverse Events (SAE) 
Anticipated Adverse Events:  Anticipated adverse events in this study include ecchymosis, 
hyperpigmentation, hypopigmentation, bruising, swelling, twinge (pain), numbness, infection, 
itching, scarring, burns, nerve damage, and/or loss of sensation. If an unanticipated adverse event 
occurs at any time during or after the use of the Profound device, the Investigator must report it 
to Syneron.  
The Investigator must report all unanticipated adverse device effects that are serious in nature to 
the clinical study monitor immediately or within twenty-four hours by telephone (see below). If 
such an unanticipated adverse device effect is reported after normal working hours, the 
Investigator will leave a voice message at the monitor’s telephone number with accompanying 
report of the unanticipated adverse device effect faxed or sent to the fax number/e-mail address 
below:             
Ruthie Amir, MD, Global VP of Clinical Affairs   
                  
Telephone/Fax No.:      From the U.S.  
011 (972) 73-244-2349 
                                               
 
 
 
011 (972) 54-300-3164 (cell)  
                             E-mail:       
               ruthiea@syneron.com  
 
A written report prepared by the Principal Investigator must follow within five working days to 
both the IRB and to Syneron and should include a full description of the event and sequence. 
Measures taken to protect the rights and welfare of subject 
Research records will be available to study personnel, the sponsor, Ethics Review Committee and 
regulatory agencies as required.  Research records may be used for purposes of medical 
education, after removal of subject names or other identifying information.  In the ICF the subjects 
will be informed that the photographs and video taken of them during the study may be made 
available to the sponsor for marketing and instructional purposes, after removal of identifying 
information.  All images collected will be stored without personal subject identifiers at the site 
and at Syneron. 
RISK/BENEFIT ANALYSIS 
Risks 
Syneron has determined that the Profound is non-significant risk device for the treatment of 
cellulite. As indicated in the AE section, the risks associated with the device are: 
➢ Ecchymosis 
➢ Erythema 
➢ Edema 
➢ Scaring 
➢ Infection 
➢ Pain 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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Anticipated adverse events in this study include: 
➢ Bruising 
➢ Numbness 
➢ Hyperpigmentation 
➢ Infection 
➢ Hypopigmentation 
➢ Itching 
➢ Swelling 
➢ First degree burns 
➢ Twinge (pain) 
➢ Second degree burns 
➢ Loss of sensation 
➢ Nerve damage 
Subjects worldwide participated in clinical research and underwent treatment with the profound 
device. The Profound device will be used in this study was previously used in study and emitted 
the same energy. To date, no serious adverse events or unanticipated AEs have been reported. 
The reported AEs relate to dermal and subcutaneous tissue, confined to the treatment area and 
were all mild in nature and resolved within the study period. 
Potential benefits to participating individuals and to society 
Subjects may or may not benefit from improvement in cellulite appearance on the treated area 
via a minimal-invasive technique.  All subjects in the treatment groups are expected to have some 
benefit from the treatment procedures as would be expected for the commercial I device. Subject 
will receive treatment/s procedures at no cost.  This study will benefit the advancement of 
medicine by generating data on safety and efficacy that will aid in the development of an 
alternative treatment options to procedures with higher potential risks subjects.  The results of 
this study will help to determine whether this device is safe and effective for improvement of 
cellulite appearance. 
Conclusion: 
In light of the potential benefits of minimal-invasive cellulite appearance relative to its risks, the 
potential benefits associated with the use of the Profound System outweigh its risks, supporting 
study initiation. 
Payment for Participation 
Subjects will be paid a total of $200 for all study visits and evaluations.  Payments will be issued 
at the last FU visit.  Subjects will not pay for office visits, examinations or procedures that are part 
of this clinical study. After treatment, subjects who do not complete all study-related procedures 
and requirements will not be paid nor will they receive partial payments for completed visits.  
 
 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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ETHICS AND GOOD CLINICAL PRACTICE 
This study will be carried out in compliance with the following: 
• 
Syneron Standard Operating Procedures. 
• 
Declaration of Helsinki, concerning medical research in humans (Recommendations 
Guiding Physicians in Biomedical Research Involving Human Subjects, Helsinki 1964, 
amended Tokyo, 1975, Venice 1983, and Hong Kong 1989). 
• 
US Code of Federal Regulations (Title 21CFR including parts 50, 56 and 812 governing 
informed consent and IRB regulations). 
• 
International Conference on Harmonization (ICH) Harmonized Tripartite Guideline for 
Good Clinical Practice (GCP), 1996. 
QUALITY ASSURANCE AND STUDY MONITORING 
Study Monitoring/Auditing/Inspection 
The Study Monitor will be responsible for monitoring the study sites to review the data being 
collected. The sponsor shall implement and maintain quality control and quality assurance 
procedures with written standard operating procedures (SOPs) to ensure that the trial is being 
conducted and data are generated, documented and reported in compliance with the protocol, 
Good Clinical Practice (GCP) and applicable regulatory requirements. Visits will be made prior to 
the initiation of the study, at scheduled intervals throughout the study, and at termination of the 
study. 
Once enrollment and treatments have begun, monitoring visits will take place more frequently 
pending enrollment and study activities.    
The sponsor and site will maintain regular phone and e-mail correspondence throughout the 
study to confirm compliance of study procedures.   
 The investigator/institution agrees to allow the monitor and other authorized personnel direct 
access to source data/ documents for trial related monitoring, the clinical supplies storage/ 
dispensing area and to provide all documents in the Investigator Regulatory Binder for review, 
and to assist site auditors in their activities if requested. Requests by the Health Canada or 
regulatory agencies of other countries to inspect the study site may be made after adequate 
notification. The investigator may be required to assist the regulatory inspectors in their duties, if 
requested. 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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November 17, 2017 
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ADMINISTRATIVE PROCEDURES 
Supply and Disposition of Study Device 
The Profound Dermal and SubQ handpieces and/or cartridges will be supplied to the participating 
clinics.  
Control & Disposition of the Investigational Device 
The Profound device will be used according to the instructions of the Sponsor and manufacturer, 
Syneron Medical.   
Informed Consent 
Study Personnel will obtain written Informed Consent prior to the subject’s participation in any 
study procedures.  The Study Personnel will inform the subjects of the experimental procedure to 
be utilized and assure the subjects that their decision regarding participation in the study will have 
no bearing on the quality of medical care received and that their decision whether to participate 
in the study is strictly voluntary.  
 
During the initial interview, the subject will be assured that they are free to change their mind 
and will be allowed to participate in the study or withdraw from the study with no adverse effect 
on their standard medical care.   
Monitoring Plan 
At least 3 monitoring visits are projected during the whole study. The frequency of which will be 
based on enrolment, study activities and the study visit scheduled.  The first visit is scheduled at 
the initiation of the study prior to the first subject treatment in the study.  The second visit is 
scheduled after enrolment and treatment has been initiated and a third visit will be for a close-
out visit for the study.  Interim visits may be conducted as needed to assure compliance to the 
study protocol and regulatory requirements.   The number and frequency of monitoring visits may 
also be increased per the sponsor decision to collect data and images post treatment.  
Case Report Forms 
Paper case report forms will be used in this trial. All protocol-required information collected 
during the study must be entered in the appropriate field of the case report form (CRF). The 
investigator, or designated representative, should complete the appropriate CRF fields as soon as 
possible after information is collected. The information must match the information that exists as 
source documents in the clinic chart, hospital chart, and/or investigator’s files. An explanation 
should be given for all missing data. 

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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It is the investigator’s responsibility to assure the accurate completion, review, and approval of 
all CRFs and the timely completion and submission of all adverse event forms. 
Record Maintenance 
The investigator shall retain a copy of all study documents in accordance with the FDA regulations 
which specify that records should be kept for a period of two years: 1) following the date a 
marketing application either is approved or disapproved for the use, or 2) following notification 
to FDA that no application is being filed and/or that the study has been discontinued.  
If an investigator leaves the study site before record retention obligations have expired, the 
sponsor should be notified in writing of the person designated to retain the study documents 
during and after the study. 
Handling of clinical data.  The data are entered into a secure database that only the sponsor has 
access to.  Admission to the database requires access to a password-protected network secured 
by the Sponsor. This database is maintained by Syneron that performs backups, data verification, 
and application upgrades. All equipment housing the clinical data is located in locked rooms or a 
secure computer network.  The only individuals, who view, extract and analyze data for protocol 
reports and publications are physicians and nurses who are members of the study team or 
Sponsors. Only authorized personnel of the Sponsors have access to databases.  
Any paper copies of subject medical records or research records are stored in secure cabinets at 
the study site.  
PUBLICATION POLICY 
The investigator will not publish the study results and will not disclose confidential information 
received from Syneron without prior written agreement from Syneron. Such confidential 
information shall include any and all information relating to this study as described in the Clinical 
Trial Agreement.  In the event that Syneron consents to the publication of data from this study, 
the investigator will provide Syneron manuscripts for review thirty days before submission for 
publication. Syneron will have no editorial rights over manuscripts. The investigator will also 
provide Syneron with advance notice of at least (30) days, of any presentation, lecture, abstract 
session, etc., in which any results from the study will be disclosed.  

 
 
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Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
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Protocol # 
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Rev. Date 
November 17, 2017 
Page 31 of 37 
 
BIBLIOGRAPHY 
 
[1]  Rawlings AV. Cellulite and its treatment.  Intl J of Cosmetic Science, 2006; 28: 175-190. 
[2] Rossi AB, Vergnanini AL.  Cellulite: a review.  JEADV 2000; 14: 251-262. 
[3] Perin F, Perrier C, Pittet JC, et al.  Assessment of skin improvement treatment efficacy using 
the photograding of mechanically-accentuated macrorelief of thigh skin.  Int J of Cosmetic 
Science, 2000; 22: 147-156. 
[4] DiBernardo B. Treatment of cellulite using a 1440-nm pulsed laser with one-year follow-up.  
Aesthetic Surg J; 31(3): 328-341. 
[5] Hexsel DM, Dal’Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. JEADV 
2009 May;23(5):523-8. 
[6] Hantash BM, Renton B, Berkowitz RL, et al. Pilot clinical study of a novel minimally invasive 
bipolar microneedle radiofrequency device. Lasers Surg Med 2009;41:87–95. 
[7] Hantash BM, Ubeid AA, Chang H, et al. Bipolar fractional radiofrequency treatment induces 
neoelastogenesis and neocollagenesis. Lasers Surg Med 2009;41:1–9. 
[8] Berube D, Renton B, Hantash BM. A predictive model of minimally invasive bipolar fractional 
radiofrequency skin treatment. Lasers Surg Med. 2009;41:473–8. 
[9] Willey A, Kilmer S, Newman J, et al. Elastometry and clinical results after bipolar 
radiofrequency treatment of skin” Dermatol Surg. 2010;36:877–84. 
[10] Alexiades M, Rosenberg D, Renton B, et al. Blinded, randomized, quantitative grading 
comparison of minimally Invasive, fractional radiofrequency and surgical face-lift to treat 
skin laxity, Arch dermatol. 2010; 146(4):396-405. 
[11] Alexiades-Armanakas M, Newman J, Willey A.  Prospective Multicenter Clinical Trial of a 
Minimally Invasive Temperature-Controlled Bipolar Fractional Radiofrequency System for 
Rhytid and Laxity Treatment. Dermatol Surg 2013;1–11. 
 
 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 32 of 37 
 
APPENDIX I – STUDY SUMMARY 
Table 3 - Study Schematics 
 
Task                Visit 
                             (Interval) 
 
Screening/ 
Baseline 
Tx.1 1 
1 day ±14 
days post 
baseline  
1 Week FU 
1 week 
post Tx.1 
±2 days 
1 Month FU 
1 month 
post Tx.1 
±7 days 
3 Month FU 
2 month 
post Tx.1. 
±14 days 
6 Month FU 
3 month 
post Tx.1. 
±14 days 
Informed Consent 
Process 
X 
 
 
 
 
 
Eligibility Screening  
X 
 
 
 
 
 
Medical History & 
Change in Medical 
History 
X 
X 
X 
X 
X 
X 
Global aesthetic 
improvement & 
Skin Tightening 
Improvement 
(Error! Reference s
ource not found.) 
 
 
 
X 
X 
X 
Photographs 
(Appendix II – 
Photography 
Guideline) 
X 
X 
 
X 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
Antibiotic 
prescription for 
subject (optional) 
X2 
 
X2 
 
 
 
Treatment 
 
X 
 
 
 
 
Urine Pregnancy 
tests 
X 
X 
 
 
 
X 
Subject Pain 
Assessment (Error! R
eference source 
not found.) 
 
X 
 
 
 
 
 
 
                                                          
1 The screening and baseline visit should preferably occur together and one day prior to 1st 
treatment visit or within 14 days. 
2 Physician may prescribe antibiotic for the subjects starting from the evening prior treatment, 
until 7 days post treatment (optional).   
3 Subject may start Compression Garment wear immediately post treatment for 1-week period 
(the Garment can be removed for bath only) - optional. 
4  If worn, subject will stop wearing the Compression Garment wear at 1wk FU post treatment. 
 
 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 33 of 37 
 
 
Task                Visit 
                             (Interval) 
 
Screening/ 
Baseline 
Tx.1 1 
1 day ±14 
days post 
baseline  
1 Week 
FU 
1 week 
post Tx.1 
±2 days 
1 Month FU 
1 month 
post Tx.1. 
±7 days 
3 Month FU 
2 month 
post Tx.1 
±14 days 
6 Month FU 
3 month 
post Tx.1 
±14 days 
Daily diary for 
comfort, AE and 
activity FU post 
treatment 
 
X 
X 
 
 
 
Compression 
Garment wear 
(optional) 
 
X3 
X4 
 
 
 
Subject Safety 
Assessment 
(Error! Reference 
source not found. 
and Table 5 - 
Post 
Treatment Side 
Effect 
Duration) 
 
 
X 
 
 
 
Subject 
Assessments 
(Error! Reference s
ource not found.) 
 
 
 
X 
X 
X 
Investigator 
Satisfaction Rating  
(Error! Reference s
ource not found.) 
 
 
 
X 
X 
X 
Adverse Events 
and Serious 
Adverse Events 
X 
X 
X 
X 
X 
X 
End of 
participation 
(Termination) 
 
 
 
 
 
X 
 
 
 
                                                          
1 The screening and baseline visit should preferably occur together and one day prior to 1st 
treatment visit or within 14 days. 
2 Physician may prescribe antibiotic for the subjects starting from the evening prior treatment, 
until 7 days post treatment (optional).   
3 Subject may start Compression Garment wear immediately post treatment for - week period 
(the Garment can be removed for bath only) - optional. 
4  If worn, subject will stop wearing the Compression Garment wear at 1wk FU post treatment. 
 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 34 of 37 
 
APPENDIX II – PHOTOGRAPHY GUIDELINES 
 
At each time point (before the treatments and at the follow‐up visits); photographs of the treated 
areas should be taken in a standardized manner. 
o Photographs should be taken in a private room or area of the clinic under controlled 
conditions, including the distance from the camera to the subject, height of the camera, 
background, camera positioning, subject's positioning and lighting in order to achieve 
high quality before & after sets. 
o Subject’s hair should be removed at all photographs at all-time points. Unwanted hair at 
the treated area will be shaved by study staff at the clinic. 
o For consistency purposes, the same person should ideally take all study photographs, 
especially per subject. 
o The digital files should follow a consistent standard naming scheme (including: date, 
subject study ID, subject initials, for example: 001TS_Tx.1_Mar 21 2015, etc.) 
Specific photography details for treatment area: 
o Front 
o Back 
o 90º from the right side and left side 
o 45º from the right side and left side 
 
 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 35 of 37 
 
APPENDIX III – ASSESSMENT SCALES 
Table 4 - Post Treatment Side Effect Severity Scale 
(0) Absent / None 
❑ 
(1) Mild 
❑ 
(2) Moderate 
❑ 
(3) Severe 
❑ 
Table 5 - Post Treatment Side Effect Duration 
(0) None – Side effect not observed 
❑ 
(0.5) Day of Treatment 
❑ 
(1) 1 day after Treatment 
❑ 
(2) 2 days after Treatment 
❑ 
(3) 3 days after Treatment 
❑ 
(4) 4 days after Treatment 
❑ 
(5) 5-7 days after Treatment 
❑ 
Table 6 –Global Aesthetic Improvement (GAI) Scale 
(0) No change  
❑ 
(1) 1%-24% 
❑ 
(2) 25%-49% 
❑ 
(3) 50%-74% 
❑ 
(4) 75%-100% 
❑ 
Table 7 – Skin Laxity/Tightening Improvement Scale 
(0) No tightening/firmness 
❑ 
(1) Slightly visible tightening/firmness 
❑ 
(2) Visible tightening/firmness 
❑ 
(3) Very visible tightening/firmness 
❑ 
 
 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 36 of 37 
 
Table 8–Satisfaction Scale 
 
(2) Very satisfied 
❑ 
(1) Satisfied 
❑ 
(0) No opinion 
❑ 
(-1) Dissatisfied 
❑ 
(-2) Very dissatisfied 
❑ 
 
Table 9–Subject Overall Aesthetic Improvement Scale 
 
(0) No change  
❑ 
(1) Minimal improvement  
❑ 
(2) Moderate improvement  
❑ 
(3) Good improvement  
❑ 
(4) Excellent improvement  
❑ 
 
Table 10–Subject Recommendation of Treatment Scale 
 
(2) Highly recommended procedure 
❑ 
(1) Recommended procedure 
❑ 
(0) Neutral 
❑ 
(-1) Not recommended procedure 
❑ 
(-2) Very not recommended procedure 
❑ 
 
 

 
 
Syneron Medical Ltd. 
Confidential 
 
Clinical Study to Evaluate the Safety and Efficacy Performance of the Profound System Using 
the Dermal and SubQ Cartridges for the Treatment of Cellulite  
Protocol # 
DHF21711 
Rev. Date 
November 17, 2017 
Page 37 of 37 
 
 
APPENDIX IV - PAIN ASSESSMENT 
 
Immediately after treatment the subject will be asked to rate treatment related pain. Pain will be 
assessed post treatment based on the Numerical Scale Response (NSR). The subject will be 
presented a scale (below) with words along a horizontal line and asked to make a mark along the 
scale to rate their pain from no pain to worst possible pain.  A number will be derived by the 
research staff by measuring up to the point the subject has indicated versus the entire line.