Rollover Study to Evaluate Histological Results of Radiofrequency Device Treatments on the Flanks
Phase: NA
Conditions: Skin Laxity
Sponsor: Cynosure, Inc.

PROTOCOL #: CYN20-FIRM-LIPO-ROLLOVER  
 
   
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Identifiers: 
NCT04881149 
Unique Protocol ID: CYN20-FIRM-LIPO-ROLLOVER 
 
Title: 
 
Rollover Study to Evaluate Histological Results of Radiofrequency 
Device Treatments on the Flank 
 
  
 
Document Date: February 2, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 

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INVESTIGATIONAL PLAN 
 
PROTOCOL #: CYN20-FIRM-LIPO-ROLLOVER 
 
ROLLOVER STUDY TO EVALUATE HISTOLOGICAL RESULTS OF 
RADIOFREQUENCY DEVICE TREATMENTS ON THE FLANKS  
 
 
 
 
 
CONFIDENTIAL 
 
THIS INVESTIGATIONAL PLAN CONTAINS CONFIDENTIAL INFORMATION FOR USE BY 
THE INVESTIGATORS AND THEIR DISIGNATED REPRESENTITIVES PARTICIPATING IN 
THIS STUDY.  IT SHOULD BE HELD CONFIDENTIAL AND MAINTAINED IN A SECURE 
LOCATION.  IT SHOULD NOT BE COPIED OR MADE AVAILABLE FOR REVIEW BY ANY 
UNAUTHORIZED ENTITY. 
 
 
 
 
 
 
 
SPONSOR: 
CYNOSURE, LLC 
5 CARLISLE ROAD 
WESTFORD, MA 01886 
PHONE: 800-886-2966 
FAX: 978-256-6556 
 
 
 

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ROLLOVER STUDY TO EVALUATE HISTOLOGICAL RESULTS OF RADIOFREQUENCY DEVICE 
TREATMENTS ON THE FLANKS 
 
INVESTIGATOR AGREEMENT 
 
I agree to conduct the study in accordance with the relevant, current protocol and will only make changes in a protocol after notifying the 
sponsor, except when necessary to protect the safety, rights, or welfare of subjects. 
 
I agree to personally conduct or supervise the described investigation. 
 
I agree to inform any patients, or any persons used as controls if applicable, that the device(s) is/are being used for investigational purposes 
and I will ensure that the requirements relating to obtaining informed consent in and institutional review board (IRB) review and approval 
are met. 
 
I agree to report to the sponsor adverse experiences that occur in the course of the investigations.  I have read and understand the information 
in the device manual, including the potential risks and side effects of the device. 
 
I agree to ensure that all associates, colleagues, and employees assisting in the conduct of the study are informed about their obligations in 
meeting the above commitments.  
 
I agree to maintain adequate and accurate records and to make those records available for inspection. I further agree that Cynosure, LLC 
or their designees shall have access to any source documents from which case report form information may have been generated. 
 
I will ensure that an IRB that complies with the requirements of 21 CFR Part 56 will be responsible for the initial and continuing review 
and approval of the clinical investigation. I also agree to promptly report to the IRB all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others.  Additionally, I will not make any changes in the research without IRB approval, 
except where necessary to eliminate apparent immediate hazards to human subjects. 
 
I agree to comply with all other requirements regarding the obligations of clinical investigators. 
 
I will comply with the International Conference on Harmonization (ICH), Good Clinical Practice (GCP) guidance E6, FDA Good Clinical 
Practice Regulations (21 CFR parts 50, 56, and 812), Declaration of Helsinki (DoH) and the Health Human Service (HHS) Belmont Study 
Principals and Guidelines during the conduct of this study. 
 
I have read the foregoing protocol and agree that it contains all necessary details for carrying out this study. I will conduct the study as 
outlined herein and will complete the study within the time designated. 
 
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who assist in the conduct of this 
study.  I will discuss this material with them to ensure they are fully informed regarding the study device the conduct of the study.  
 
I will disclose financial arrangements and interests in accordance with Financial Disclosure Rules (21 CFR part 54) and FDA Form 3455. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
Name of Investigator (Typed or Printed) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Address of Investigator (Typed or Printed) 
 
 
 

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SITE #1 CONTACT INFORMATION: 
Principal Investigator Information: 
David H. McDaniel, M.D., F.A.A.D. 
McDaniel Institute of Anti-Aging Research 
125 Market Street 
Virginia Beach, VA 23462 
Phone: 757-437-8900 
Email: DHM@miaar.com  
 
SITE #2 CONTACT INFORMATION: 
Principal Investigator Information: 
Bruce Katz, M.D. 
JUVA Skin & Laser Center 
60 East, 56th Street, Suite 2 
New York, NY 10022 
Phone: 888-729-6399 
 
SITE #3 CONTACT INFORMATION: 
Principal Investigator Information: 
Jeremy A. Brauer, M.D. 
175 Purchase Street 
Rye, NY 10580 
Phone: (917) 841-4111 
Email: drbrauer@brauerderm.com 
 
SITE #4 CONTACT INFORMATION: 
Principal Investigator Information: 
Thomas Griffin, Jr. M.D 
Dermatology Associates of Plymouth Meeting 
531 W Germantown Pike, Second Floor 
Plymouth Meeting, PA 19462 
Email:  thomas.griffin1@gmail.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
SPONSOR CONTACT INFORMATION: 
Jennifer Civiok 
Director, Clinical Development  
5 Carlisle Road 
Westford, MA 01886 
Phone: 978-399-4343 
Email: Jennifer.Civiok@cynosure.com 
 
Jill Ashley 
Clinical Project Manager 
New York, NY 10022 
Phone: 917-627-7011 
Email: Jill.Ashley@cynosure.com 
 
David Canavan 
Sr. Clinical Project Manager 
5 Carlisle Road 
Westford, MA 01886 
Phone: 978-551-5786 
Email: david.canavan@cynosure.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
1.0 
PURPOSE  
1.1 
Name and Intended Use 
1.2 
Objectives  
1.3 
Duration of the Investigation 
1.4 
Context of the Proposed Investigation 
2.0 
PROTOCOL  
2.1 
Protocol Methodology and Analysis 
2.2 
Protocol Study Design  
2.3 
Subject Selection Criteria 
2.4 
Screening 
2.5 
Informed Consent Process and Enrollment 
2.6 
Pre-Biopsy Procedures 
2.7 
Biopsy Procedures 
2.8 
Post Biopsy Instructions 
2.9 
Follow Up 
2.10 
Unscheduled Visits  
2.11 
Replacement of Subjects 
2.12 
Schedule of Visits and Procedures  
2.13 
Evaluation Methods 
2.14 
Adverse Event Recording  
3.0 
RISK MANAGEMENT  
4.0 
MONITORING PROCEDURES  
5.0 
CONSENT MATERIALS 
6.0 
INSTITUTIONAL REVIEW BOARD INFORMATION 
7.0 
OTHER INSTITUTIONS  
8.0 
ADDITIONAL RECORDS AND REPORTS 
9.0 
SUBJECT WITHDRAWAL 
10.0 
PHOTOGRAPHY 
11.0 
ADVERSE REACTIONS DEFINITIONS AND REPORTING REQUIREMENTS 
12.0 
PROTOCOL DEVIATIONS 
13.0 
CONFIDENTIALITY AND DISCLOSURE OF MEDICAL INFORMATION 
14.0 
CLINICAL RESEARCH CONDUCT  
15.0 
REPORTING FOR THE STUDY 
16.0 
DISCLOSURE 
17.0 
RESPONSIBILITY OF THE INVESTIGATOR 
18.0 
PROCEDURE FOR AMMENDMENTS TO PROTOCOL  
19.0 
TERMINATION OF STUDY 
20.0 
DATA SECURITY 
21.0 
REPORT OF PRIOR INVESTIGATIONS 
 
APPENDICES 
A. 
Protocol Revisions Tracker 
 
 

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ATTACHMENTS/REFERENCES 
I. 
Informed Consent Form  
II. 
Post Treatment Instructions 

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1.0       PURPOSE 
1.1 Name and Intended Use  
The purpose of this study is to evaluate histological results of the treatments with the TempSure 
Firm handpiece on the flanks performed in the CYN20-FIRM-LIPO study. 
 
1.2 Objectives   
Primary Objective:  
 Evaluate histological tissue response as seen in biopsies. 
 
1.3 Duration of the Investigation 
The sponsor anticipates that all subjects can be enrolled within 3 months.  If subject participates in 
all required visits, then the subject’s participation in this study may last up to 1 month. It is 
anticipated that it will take approximately 3 months to analyze the data collected during this study. 
The total duration of this study is anticipated to last approximately 7 months. 
 
1.4 Context of the Proposed Investigation 
Radiofrequency (RF) technology is commonly used in surgery, noninvasive treatments and 
aesthetic applications. RF technology is a safe method for non-ablative (A non-wounding device 
treatment which heats underlying skin) treatment because energy can be precisely delivered 
through the skin to the dermal tissue beneath without damaging the epidermis.  
 
Aging skin shows decreased collagen synthesis and alteration of fiber networks. By gently heating 
dermis tissue (which is comprised of collagen, elastic fibers and ground substance), both 
immediate effects (collagen contraction) and long-term effects (wound-healing response with 
neocollagen production) will occur. RF-induced thermal injury to the dermal tissue will produce a 
microinflammatory response to induce collagen denaturation, contraction, and subsequent 
synthesis as well as elastin and ground substance production.1 This, in turn, creates a tightening 
effect that helps to eliminate skin wrinkles and is used also for other cosmetic treatments on the 
body.2 
 
The extent of collagen shrinkage, fibroblast activation, fibroplasia and neocollagenesis in the 
different skin layers is based on a complex multivariate mechanism, which depends on the 
temperature distribution and timing.2 Further investigation of parameter optimization is necessary 
to achieve safe and efficacious results.    
 
2.0 
PROTOCOL 
2.1 Protocol Methodology and Analysis 
Methodology: 
Subjects are to be enrolled in this clinical study if they have completed their participation in the 
CYN20-FIRM-LIPO study. Up to 10 subjects will be enrolled at up to 4 study centers. Subjects 
will receive 2 biopsies, 1 biopsy in the treatment area on the flank and 1 biopsy on the contralateral 
side to serve as a control. 
 
 
 
 
 

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Analysis: 
Upcoming generations are proving to have an interest in non-ablative aesthetic treatments and will 
drive demand for innovated products, procedures, and practice design.3 Due to this shift in patient 
base, practices need to evolve to adapt to the newer generational ideologies. There have been rapid 
advances in RF technology over the past few years and the nonsurgical treatment using this energy 
source offers great promise to our aging population.4 Radiofrequency technology for the treatment 
of abdominal wrinkles needs to be further investigated to optimize treatment parameters for safe 
and effective non-ablative aesthetic treatments.  
 
Relevance: 
Over time, skin structure degrades due to a variety of internal and external conditions. As enzymes 
break down collagen and elastin, skin loses its suppleness and becomes loose.  UV exposure, diet, 
and smoking among other behaviors all contribute to the skin becoming lax.  Body wrinkles, 
particularly on the abdomen, are a sign of aging and are also a prevalent concern with postpartum 
women or subjects who have lost weight. It is estimated that adult skin loses approximately 1% of 
its dermal collagen content on an annual basis due to increased collagen degradation and decreased 
collagen synthesis.2 Radiofrequency, ultrasound, non-ablative fractional technology, and ablative 
technology have all been used to varying degrees of success.  The limitations of current products 
on the market include different side effect profiles and modes of administration. 
 
Testability: 
The improvement in the appearance of skin has been previously linked to a histological evaluation 
of the treatment area and can be used to verify an increase in collagen after a radiofrequency 
treatment.  Dr. Neil Sadick in 2008 published an article titled Tissue Tightening Technologies: 
Fact or Fiction which discusses the link between changes in collagen and improvement in skin 
tightening, including wrinkles.  The collection of biopsies will allow a histological evaluation of 
the treatment area to confirm the device is safely and effectively affecting the collagen in the 
dermis.   
 
Compatibility: 
Not applicable – feasibility study. 
 
Predictive power: 
While this study will observe the effects of the handpieces on the flanks, results could potentially 
be applied to a variety of body areas and other potential applications.  Assuming that there is 
significant improvement, it would be appropriate to expect results in different areas where other 
products and devices have significant results. 
 
2.2 Protocol Study Design 
This is a prospective, multi-center clinical study to evaluate histological results of treatments with 
the TempSure™ Firm handpiece. 
 
2.3 Subject Selection Criteria 
Subjects will meet the criteria described below: 
 

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Inclusion Criteria: 
 Subject has completed their participation in the CYN20-FIRM-LIPO study no more than 6 
months prior. 
 
Exclusion Criteria: 
 The subject has not had any other treatment in the treatment area after their involvement in 
the CYN20-FIRM-LIPO study. 
 The subject has any condition or is in a situation which in the investigators opinion may put 
the subject at significant risk, may confound study results or may interfere significantly with 
the subject’s participation. 
 
2.4 Screening  
Subjects will undergo the screening procedures in the CYN20-FIRM-LIPO study. 
 
 
2.5 Informed Consent Process and Enrollment 
Subjects will be asked to review the post treatment instructions prior to signing the informed 
consent form and their involvement in the study. Subjects will be informed of standard COVID-19 
procedures that adhere to federal and state guidelines at this time. Subjects will be de-identified 
through their subject identification number, which will be stored in a secure location. Subject 
identification numbers will be generated chronologically and assigned only to subjects who have 
met all the study selection criteria and have signed the informed consent form.  The informed 
consent will be obtained prior to a subject’s involvement in any study related procedures. A 
subject will be considered enrolled in the study once they have signed the informed consent form.  
 
2.6 Pre-Biopsy Procedures 
If the subject is of childbearing potential (i.e. females not post-menopausal or not surgically 
sterile), they will be asked if they are pregnant, the date of their last menstrual cycle, and perform a 
urine pregnancy test. A urine pregnancy test will be performed on all women of childbearing 
potential prior their biopsies. A urine pregnancy test may also be conducted at the Investigator’s 
discretion at any time during the study. If a urine pregnancy test is conducted, then a negative 
result must be obtained within 24 hours prior to the treatment. 
 
Urine Pregnancy Test Procedure: 
1. A urine sample is tested mid-stream or by cup sample with an indicator stick.  
2. Negative results are indicated on the indicator stick. 
 
 The biopsy area will be identified and may be marked with a surgical or permanent marker. 
 Photographs will be taken prior to the biopsy and may be taken during and/or after treatment.  
 
 
2.7 Biopsy Procedures 
 Biopsy subjects will receive 2 biopsies, 1 in the treatment area and 1 on the contralateral 
side of the treatment area to serve as a control. 
 A local anesthetic, such as lidocaine, will be injected to the area prior to biopsy. 
 A 2 mm or 3mm punch biopsy (based on Physician assessment) will be taken. 

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 Sutures may be used to close the incision site. 
 
2.8 Post Biopsy Instructions 
 Slight redness, initial tenderness to the wound site is normal; however, if you experience 
more redness, swelling, pain, pus, or drainage contact the office immediately, 
 If the biopsy site begins to bleed, apply direct pressure for 10-20 minutes. If it continues to 
bleed, call the study site immediately. 
 Keep the wound dry today and remove bandage in 24 hours and leave off. 
 Avoid hot tubs, pools, and ocean until sutures are removed.  Avoid soaking in water until 
14 days after your biopsy. 
 When showering, wash carefully and do not scrub or traumatize the treated skin, or allow 
spray of shower to strike the skin directly.  If the skin is treated harshly, this can increase 
the risk of scarring. 
 After showering, lightly pat dry the wound or let it air dry, then cover the biopsy site with 
an application of Vaseline (or petroleum jelly) at least 1-2 times daily.  Keeping the wound 
moist reduces infection, minimizes scarring, and prevents crust formation over the wound.  
 Band-Aids (or any generic Adhesive Bandages) may be used for sleeping or in daily 
routines where the area may be rubbed/irritated.   Whenever possible, keep Band-Aid (or 
generic Adhesive Bandage) off of the area and keep the area moist with Vaseline (or 
petroleum jelly) as previously described but do not allow drying out and forming a hard 
scab.  
 For any wound discomfort, you may take Tylenol as needed, or use cold compresses for up 
to 20 minutes hourly as needed.  If using ice, it should be wrapped in a plastic and then a 
cloth to avoid burning your skin and wetting your bandage. 
 Avoid picking at the wound site, which increases risk of infection and scarring. 
o In order for the wound to heal properly and not leave bumpy scars, be careful not to 
overstretch the wound site area.  As a wound heals, it will be weaker than the 
surrounding skin and can even "pop open" the sutures (stitches) if stretched too 
much.  Sport or strenuous exercises that can pull at the wound site are best avoided 
for at least the next 3 days and up to one week. 
 Return for suture removal within 7 - 10 days as instructed per study protocol. If applied, 
Steri-strips must be kept dry as they are more likely to separate when wet. Steri-strips will 
usually fall off by themselves or you may be advised by the study doctor to remove them 
when the wound healed. 
 ONCE SUTURES ARE OUT: To minimize sore formation and to improve the final 
appearance of your skin, it is very important to keep the wound site area covered with the 
Vaseline for the next few days, until there is no more crust forming and the skin has 
completely healed.  
 Temporary discoloration at the wound site is normal and should gradually fade over the 
next few months.  Please protect newly healed biopsied area with SPF and avoid sunburn. 
 
2.9 Follow Up 
 The subject may be asked to attend a 1 week (7-10 days) post biopsy follow up visit to remove 
the sutures.   

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 Photographs may be taken, and adverse events will be documented at this follow up visit.  
 
2.10 Unscheduled Visits 
An unscheduled visit may be performed at any time during the study at the subject’s request or as 
deemed necessary by the site Investigator. The date and reason for the unscheduled visit will be 
recorded in the source documentation. 
 
2.11 Replacement of Subjects 
Replacement of subjects who have withdrawn or been withdrawn from the study will not be 
allowed to be replaced without prior approval from the sponsor and/or IRB. 
 
2.12 Schedule of Visits and Procedures 
 
 
Visit #1 
Visit #2 
(optional) 
Procedure 
Biopsy  
Follow Up  
1 Week Post 
Biopsy 
(7-10 Days) 
Pregnancy 
Verification* 
X 
 
Biopsy 
X 
 
Suture Removal 
 
X 
Photographs  
X 
X 
Adverse Events 
Assessment 
X 
X 
*Pregnancy verification required before biopsy only for women of childbearing potential. 
 
2.13 Evaluation Methods 
Skin Biopsies: 
Biopsies will be obtained to examine the effects on the skin following radiofrequency treatments. 
Sections of skin will be removed using the punch biopsy technique to render a microscopic 
diagnosis. Each specimen will first be preserved with a fixative and then stained using 
Hemotoxylin & Eosin, Verhoeff and Masson Red/Fast Green and/or nitroblue tetrazolium chloride 
(NBTC) staining methods. If using Hemotoxylin & Eosin, Verhoeff and Masson Red/Fast Green 
staining, samples will be assessed and evaluated by the amount of collagen and elastin stained. If 
using NBTC staining, samples will be assessed and evaluated to differentiate between the blue-
stained viable cells and the unstained thermally damaged cells. A report will be provided for each 
sample by the pathologist or the Investigator. 
 
2.14 Adverse Event Recording 
All data captured must be supported by the Investigator’s timely assessment and documentation of 
the adverse event in the case report forms or source documents.  All documented adverse events 
will be reviewed by the Sponsor or designee to determine whether the adverse event meets 

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regulatory reporting requirements and to ensure timely adverse event reporting to meet local and 
global regulatory requirements. All adverse events must be followed until their resolution. 
 
Biopsies 
Complication with biopsies can include pain, redness, swelling, infection, bleeding, scarring and 
skin texture irregularities. 
 
 
Lidocaine 
1% lidocaine (Lidocaine) Injection with or without Epinephrine 
You may experience pain and numbness at the site of the injection. You may also experience 
redness, rash, infection, skin damage or nerve damage at the site of the injection. You may 
experience temporary loss of sensation and muscle function at the site of injection. 
 
Lidocaine with epinephrine contains the preservative sodium metabisulfite which may cause 
allergic-type reactions including anaphylactic symptoms and life-threatening or less severe 
asthmatic episodes in certain susceptible people. 
 
Adverse Events Pertaining to Surgical Marker: 
Using surgical marker has minimal risks and may produce effects on the body such as redness or a 
rash. Markings may remain visible for a few days or may be removed with alcohol.  
 
 
3.0 
 RISK MANAGEMENT  
The Investigator in this clinical trial has been invited to participate based on his/her previous 
experience with the use of the system and/or similar systems and industry experience.  Experience 
with biopsies is the most critical element in managing subject risk in this trial. 
 
In addition, as with any study, there is a risk of bias. Objective evaluation methods will be used.  
The value of the compensation to the clinical investigator for conducting the study is not influenced 
by the study outcome.   
 
All other known risks will be disclosed to the subject via the informed consent process. Since this 
is an elective procedure and the subjects are volunteers, it can be assumed that their signature on 
the informed consent is indicative of their agreement to accept the risks involved. 
 
The risks to the subjects who participate in this study are the same as those for most subjects 
undergoing biopsies when enrolled in a non-ablative radiofrequency study.  
 
 
4.0 
MONITORING PROCEDURES  
The Sponsor Standard Operating Procedure (SOP) for monitoring the investigative site will be 
followed. The sponsor will train the site following sponsor SOP’s and may be present at initiation 
of treatment.  The sponsor will also monitor the site periodically. The Investigator/Institution will 
permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspections by providing 
direct access to source documents.  The sponsor may request intermediate data following each visit 

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to evaluate treatment progress. Case Report Forms will be reviewed for current data and 
Regulatory Binders will also be reviewed for correct documents. The sponsor will collect data at 
the end of the follow up period. The sponsor will list the study on clinicaltrials.gov when required 
by FDA regulations.  
 
The monitoring plan for this study is outlined in the Cynosure Monitoring Plan.  
 
ASSIGNED CLINICAL RESEARCH MONITOR: 
Monitor #1 
Name: Kristy Luis 
Institution: Cynosure, LLC 
Address: 5 Carlisle Rd. Westford, Ma  
 
5.0  
CONSENT MATERIALS 
Forms and informational materials which are provided to the subject during the informed consent 
process are listed below: 
 
Form/Informational Material 
Description 
Post Treatment Instructions 
Informed Consent Form 
 
 
6.0  
INSTITUTIONAL REVIEW BOARD INFORMATION 
This protocol, informed consent forms, and any amendments to the protocol will be reviewed by 
the appropriate Institutional Review Board prior to initiation.  The study will not be initiated 
without the approval from the Institutional Review Board.  
 
IRB Contact Information: 
IRB Name: Allendale Investigational Review Board 
IRB Chairperson: Robert Staab 
IRB Address: 30 Neck Rd. Old Lyme, CT 06371 
Phone: 860-434-5872 
Fax: 860-434-5892 
Email: Rta1ali1@aol.com 
 
7.0  
OTHER INSTITUTIONS  
If a part of the study is conducted by an institution that has not previously been identified within 
the Investigational plan each institution’s contact information will be documented below; 
 
No other institutions will be part of this study. 
 
8.0  
ADDITIONAL RECORDS AND REPORTS  

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If this is an IDE study, additional records and reports will be maintained on the investigation in 
addition to those prescribed in 21 CFR 812 sub-part G. If this is a non-IDE study, the study 
summary will be maintained on the investigation and may include those prescribed in 21 CFR 812 
sub-part G.   
 
Additional Records and Reports: 
Report    
Submit To   
Description/Constraints 
N/A 
N/A 
This is a non-IDE study; no additional records or 
reports will be maintained. 
 
 
9.0      SUBJECT WITHDRAWAL  
The subject is free to withdraw from this study at any time. The subject must inform the Investigator 
immediately if they intend to withdraw. To terminate the subject’s participation in this study, they 
must contact the Investigator at the contact information listed on page one of the informed consent 
form. They will be asked to come to the study clinic or Investigators office to complete a final follow 
up visit and may be asked to perform end of study procedures.  Their decision to participate in this 
study or to withdraw from this study will not influence the availability of their future medical care and 
will involve no penalty or loss of benefits to which they are otherwise entitled. 
 
The Investigator in charge of the study can remove the subject from this study without their consent 
for any reason, including, but not limited to: 
a) His/her judgment that any condition or circumstance may jeopardize their welfare or the integrity 
of the study. 
b) Their failure to follow the instructions of the Investigator(s). 
c) If the study is stopped by the sponsor and/or Investigators participating in the study prior to 
completion. 
 
Data collected prior to withdrawal will be used in data analysis but after withdrawal no further data 
will be collected.  
 
10.0  PHOTOGRAPHY 
Standardized photography may be taken of the biopsy site. Photographs will be taken with an 
appropriate high-resolution digital camera. Camera settings (lighting, distance, background, 
polarization, etc.) will be reproduced at each visit, so that photographs are suitable for comparison.  
Photographs will be taken of the treatment area for study purposes.  If the subject does not wish to 
have their photographs taken, they cannot be in the study.  
 
11.0  ADVERSE REACTIONS DEFINITIONS AND REPORTING REQUIREMENTS 
All adverse events that occur, starting from the time of the first treatment, will be recorded in the 
source documents and Case Report Forms (CRF). 

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Adverse Events (AE) occurring will be captured and followed until the condition resolves, 
stabilizes, is otherwise explained, or the subject is lost to follow-up. Subjects will be instructed that 
they may contact the Investigator at any time throughout the course of the study. 
The Investigator and/or designated study staff will review each event and assess its relationship to 
the study device (not related, unlikely, possible, probable, and highly probable). The following 
definitions will be used for rating relationship to the TempSure™ treatments:  
 Not related – The event is clearly related to other factors such as the subject’s clinical state, 
therapeutic interventions, or concomitant medications administered to the subject. 
 Unlikely – The event was most likely produced by other factors such as the subject’s clinical 
state, therapeutic interventions, or a concomitant medication administered to the subject; and 
does not follow a known response pattern to the investigational product. 
 Possible – The event follows a reasonable temporal sequence from the time of investigational 
product administration; and/or follows a known response pattern to the study sampling 
sessions; but could have been produced by other factors such as the subject’s clinical state, 
therapeutic interventions, or concomitant medications administered to the subject. 
 Probable – The event follows a reasonable temporal sequence from the time of investigational 
product administration; and follows a known response pattern to the investigational product; 
and cannot be reasonably explained by other factors such as the subject’s clinical state, 
therapeutic interventions, or concomitant medications administered to the subject. 
 Highly Probable – The event follows a reasonable temporal sequence from the time of 
investigational product administration; and follows a known response pattern to the 
investigational product; and cannot be reasonably explained by other factors such as the 
subject’s clinical state, therapeutic interventions, or concomitant medications administered to 
the subject; and either occurs immediately following investigational product administration, or 
improves on stopping the investigational product, or reappears on repeat exposure, or there is a 
positive reaction at the application site. 
 
Each adverse event reported will be graded on a 3-point severity. Using the following 
definitions for rating severity will be used: 
 Mild – easily tolerated, causing minimal discomfort, and not interfering with normal everyday 
activities. 
 Moderate – sufficiently discomforting and may interfere with normal everyday activities. 
 Severe – incapacitating and/or preventing normal everyday activities. 
 
A Serious Adverse Event (SAE) is any adverse device experience that results in any of the 
following outcomes:  death, a life-threatening adverse device experience, in-patient hospitalization 
or prolongation of hospitalization, a persistent or significant disability/incapacity, or a congenital 
anomaly/birth defect. Important medical events that may or may not result in death, be life-
threatening, or require hospitalization may be considered a serious adverse device experience 
when, based upon appropriate medical judgment, they may jeopardize the subject or subject may 
require medical or surgical intervention to prevent one of the outcomes listed in this definition 
 

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If any of the above adverse events are serious as defined by the FDA Code of Federal Regulations 
(CFR), Title 21, special procedures will be followed.  All serious adverse events will be reported 
within 24 hours of acknowledgment to the Sponsor whether or not the serious events are deemed 
sampling session-related.  All serious event reporting will adhere to 21 CFR part 812 and the IRB 
will be notified accordingly.  
 
  
The SAE information will be entered into the database and a desk copy of the complete SAE 
report will be submitted to the study file.  
 
Adverse events, whether serious or non-serious, will be followed until the condition is resolved, 
stabilized, otherwise explained or the subject is lost to follow-up.  Adverse events will be captured 
throughout the study and where appropriate, medical tests and examinations will be performed to 
document the resolution of event(s). Outcomes may be classified as resolved, improved, 
unchanged, worse, fatal, unknown or lost to follow-up.  Following the resolution of any study-
associated adverse events there will be no further adverse event reports for that subject. 
 
Reporting Adverse Events: 
Report    
Submit To   
Description/Constraints 
Adverse 
Events, 
Unanticipated 
Adverse 
Device 
Effect  
 
IRB 
and 
Sponsor 
If an unforeseen complication is determined to be 
an unanticipated adverse device effect, the 
investigator’s report must be submitted within 10 
working days after the investigator first learns of 
the effect. 
Serious 
Adverse 
Events 
IRB 
and 
Sponsor 
The sponsor must be notified within 24 hours of 
serious adverse events. The IRB must be notified 
within 10 working days of serious adverse events 
as defined by FDA guidelines.  
 
 
12.0  PROTOCOL DEVIATIONS 
All requests for protocol deviations by the Investigator have to be communicated to the sponsor in 
writing and if accepted by the Sponsor must be approved by the IRB.  If a deviation occurs, the 
Investigator must inform the Sponsor as soon as possible.  The Sponsor will notify the IRB in 
accordance with IRB specific policies. 
 
13.0  CONFIDENTIALITY AND DISCLOSURE OF MEDICAL INFORMATION 
As part of this study the Investigator and the team at the research facility will keep records of subject 
participation in the study.  These study records will include personal information that the subjects 
provide including age, sex, etc., the results of the study, information about response to treatments, 
photographs taken during the study and other medical information relating to participation in the 
study.   
 

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Under federal law the study records cannot be used or disclosed by the Investigator for research 
purposes unless subjects sign the informed consent authorization. 
 
Some or all of the test results, photographs and other information will be reported to Cynosure, LLC, 
the manufacturer of the test device (Sponsor), and consultants that are helping conduct the study.  
The Sponsor and its consultants will analyze and evaluate these results and information and may 
report them to the U.S. Food Administration and the FDA, Institutional Review Board or other 
regulatory agencies in the United States and/or foreign countries.  The subject’s study records will 
be assigned a code number by the study team and they will ordinarily not be identified by name in 
the study records that are sent to the Sponsor and its consultants.  However, The Sponsor, the 
Institutional Review Board and its consultants will have the right to see the complete study records, 
including the subject’s name, and might choose to do so.  If reports or articles are written about the 
study, the subject will not be identified by name in them however your study information and 
photographs may be used. 
 
The research facility will review and use the study records only for purposes of this study.  They 
will keep the subject’s identity confidential and, except for the disclosures described above, will not 
disclose the study records to other parties unless disclosure is required by law.  Once the research 
facility discloses information in the study records, photographs or medical records to the Sponsor or 
its consultants, the information will no longer be protected by federal law.  Because of the need to 
release information to these parties, absolute confidentiality cannot be guaranteed.  However, the 
Sponsor and its consultants will only use information for purposes of the study and will not disclose 
your study records to parties other than; the FDA or other regulatory agencies in the United States 
and/or foreign countries, unless disclosure is required by law.  If reports or articles are written about 
the study, subjects will not be identified by name in them however, subject study information and 
photographs may be used. 
 
Study records will be kept at the research facility according to applicable regulations and policies 
and may be kept indefinitely following the completion of the study. Subjects will not have the right 
to review their records while the research is in progress.  However, they will be able to review their 
records after the research has been completed. 
 
14.0  CLINICAL RESEARCH CONDUCT 
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) GCP guidelines, applicable regulations and guidelines governing clinical 
study conduct and ethical principles that have their origin in the Declaration of Helsinki.  The 
investigator must ensure that the study is conducted in accordance with the provisions as stated in 
the FDA regulations and complies with the applicable local or regional regulatory requirements. 
 
15.0  REPORTING FOR THE STUDY 
A study summary report will be generated.  It will include a description of the clinical conduct of 
the study and results. 
 
Study Summary Reporting:                     
 

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Report 
Submit To 
Description/Constraints 
Deviation 
from 
Investigational 
Plan 
IRB 
and 
Sponsor 
A deviation performed in an emergency to protect 
the life or physical well-being of a patient 
necessitates notification of the IRB and sponsor. 
The Investigator’s report must be submitted within 
5 working days after the emergency occurred. 
Deviations in a non-emergency situation require 
notification to sponsor prior to implementation 
Failure to 
Obtain 
Informed 
Consent 
 
IRB 
and 
Sponsor 
 
 
The Investigator must make notification within 5 
working days after device use, using the Protocol 
Deviation CRF. The report must include a brief 
description of the circumstances justifying the 
failure to obtain informed consent. 
Final Report 
IRB 
and 
Sponsor 
The Investigator must submit a final report within 3 
months after termination or completion of the 
investigation. 
Withdrawal of 
IRB approval 
Sponsor 
 
The Investigator must report a withdrawal of the 
reviewing IRB approval within 5 working days. 
 
Progress 
Report 
IRB, Monitor 
and 
Sponsor 
The Investigator must submit progress reports at 
regular intervals, and as required by the IRB, but in 
no event less than annually. 
 
 
16.0  DISCLOSURE 
The Principal Investigator and Cynosure employees and consultants have signed confidentiality 
agreements with the sponsor.  This confidentiality agreement ensures that all information provided 
to the Investigator or Data Management and Statistics group dealing with the study and information 
obtained during the course of the study will be regarded as confidential. 
 
17.0  RESPONSIBILITY OF THE INVESTIGATOR 
The Investigator is responsible for ensuring that the clinical study is performed in accordance with 
the International Conference on Harmonization (ICH), Good Clinical Practice (GCP) guidance E6, 
FDA Good Clinical Practice Regulations, Declaration of Helsinki (DoH) and the Health Human 
Service (HHS) Belmont Study. Investigators will supply information to the sponsor such that the 
sponsor can comply with the Financial Disclosure Rules. 
 
18.0  PROCEDURE FOR AMMENDMENTS TO PROTOCOL 
No deviations from this protocol will be permitted, except in a medical emergency, without the 
approval of the Sponsor.  Any amendment to this study will be discussed by the Investigator and the 
Sponsor.  If agreement is reached concerning the need for modification, this will be made in a formal 
amendment to the protocol. 

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All revisions and/or amendments to the protocol must be approved in writing by the appropriate 
Institutional Review Board. 
 
19.0  TERMINATION OF STUDY 
The Sponsor reserves the right to discontinue this study for administrative reasons at any time.  The 
Investigator reserves the right to discontinue the study for safety reasons at any time in collaboration 
with the Sponsor. 
 
20.0  DATA SECURITY 
To ensure the privacy and confidentiality of data for this protocol, the data will be stored on a 
restricted access location on a company server. Access to the project directory containing the data 
will be limited to the Investigators and research staff.  Information about data security awareness is 
promoted through user training and education, supplemented by policies and procedures. Password 
protection will be used for all transactions that allow viewing, editing, and analysis of data, or that 
provide access to data fields derived from the original source documents. 
 
21.0  REPORT OF PRIOR INVESTIGATIONS 
 
The report of prior investigations or predicates are: 
 
Protocol 
Device 
IRB Name 
Determination 
Initial IRB 
Approval Date 
CYN20-FIRM-LIPO 
TempSure 
NEIRB 
Meets the criteria for 
exemption from IDE 
regulations, non-significant 
risk 
07/21/2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX A: 
Protocol Revisions Tracker 
 
Version 
Date 
Editor 
Description 
December 10, 2020 
Kristy Luis 
IRB Submission 
February 2, 2021 
Kristy Luis 
IRB Response, Removed Weiss and replaced 
with Brauer, Added site #4 (Griffin), Added to 
inclusion criteria that subjects must be 
enrolled within 6 months of completion of 
prior study. 
 
 
 
 
 
  
 
 
 

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REFERENCES 
 
1 Levy, Adam S. et al. (2016). Radiofrequency Physics for Minimally Invasive Aesthetic Surgery. Clinics 
in Plastic Surgery, 43(3), 551 – 556. doi: https://doi.org/10.1016/j.cps.2016.03.013 
2 Stampar, M. (2011). The Pelleve Procedure: An Effective Method for Facial Wrinkle Reduction and Skin 
Tightening. Facial Plastic Surgery Clinics of North America, 19(2), 335-345. 
doi:10.1016/j.fsc.2011.05.012 
3 Sherber, N. S., MD FAAD. (2018). The Millennial Mindset. Journal of Drugs in Dermatology, 17(12), 
1340-1342. 
4 Elsaie, M. (2009). Cutaneous Remodeling and Photorejuvenation Using Radiofrequency Devices. Indian 
Journal of Dermatology, 54(3), 201. doi:10.4103/0019-5154.55625