Clinical Study To Assess The Safety, Parameters And Efficacy For Procedures Using A Radiofrequency Device
Phase: NA
Conditions: Tissue Heating, Coagulation
Sponsor: Cynosure, Inc.

 
 
Protocol: CYN17-RF-CLINIC                                                                                                                                    Cynosure, Inc. 
Version 13: March 20, 2019 
    
 
 
 
 
 
 
 
 
 
 
Protocol: 
CYN17-RF-CLINIC 
CLINICAL STUDY TO ASSESS THE SAFETY, PARAMETERS AND 
EFFICACY FOR PROCEDURES USING A RADIOFREQUENCY 
DEVICE 
NCT05166824   
 
 
 
Document Date: March 20, 2019 
Uploaded onto clinicaltrials.gov 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL #: CYN17-RF-CLINIC 
 
 
 
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INVESTIGATIONAL PLAN 
 
PROTOCOL #: CYN17-RF-CLINIC 
 
CLINICAL STUDY TO ASSESS THE SAFETY, PARAMETERS AND EFFICACY FOR 
PROCEDURES USING A RADIOFREQUENCY DEVICE 
 
 
 
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. 
 
 
 
 
 
 
 
CYNOSURE, INC. 
5 CARLISLE ROAD 
WESTFORD, MA 01886 
PHONE: 800-886-2966 
FAX: 978-256-6556 
 
 

PROTOCOL #: CYN17-RF-CLINIC 
 
 
 
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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 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 agree to inform any patients, or any persons used as controls, that the drugs 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 personally conduct or supervise the described investigation. 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 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 agree to maintain adequate and accurate records and to make those records available for 
inspection. I further agree that Cynosure, Inc. 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 during the conduct of this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator’s Signature  
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
Name of Investigator (Typed or Printed)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Address of Investigator (Typed or Printed) 

PROTOCOL #: CYN17-RF-CLINIC 
 
 
 
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Investigator Contact Information: 
 
SITE #1: 
Principle Investigator 
Sean Doherty, M.D. 
5 Carlisle Rd 
Westford, MA 01886 
Phone: (978) 369-4499 
 
Sub-Investigators 
Deb Bish, RN 
Felicia Whitney, RN 
 
Satellite Site: 
Boston Center for Facial Rejuvenation 
1 Brookline Place, Suite 427 
Brookline, MA 02442 
 
SITE #2 
Principle Investigator: 
Raminder Saluja, M.D. 
Saluja Cosmetic and Laser Center 
9615 Northcross Center Court, Suite B 
Huntersville, NC 28078 
Phone: 704-584-4071 
 
SITE #3 
Principle Investigator 
Barry DiBernardo, M.D 
New Jersey Plastic Surgery 
29 Park Street 
Montclair, NJ 07042 
Phone: 973-509-2000 
 
SITE #4 
Principle Investigator 
Edward Jaccoma, M.D. 
99 US Route 1 Byp, Ste A,  
Kittery, Maine, 03904. 
Phone: (207) 439-0410 
 
SITE #5 
Principle Investigator 
Jeffrey Dell, M.D. 
Institute of Female Pelvic Medicine 
10133 Sherrill Blvd. Suite 100 
Knoxville, TN 37932 
Phone: (865) 769-4488 
 

PROTOCOL #: CYN17-RF-CLINIC 
 
 
 
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Sponsor Contact Information: 
Jennifer Civiok 
Director, Clinical Development 
Cynosure Inc. 
5 Carlisle Road 
Westford, MA 01886 
Phone: 978-367-8775 
Fax: 978-256-6556 
Email: jciviok@cynosure.com 
 
Alexander Denis 
Clinical Data Associate 
Cynosure Inc.  
5 Carlisle Road 
Westford, MA 01886 
Phone: 978-367-2420 
Fax: 978-256-6556 
Email: adenis@cynosure.com 
 
 
IRB Contact Information: 
Allendale Investigational Review Board 
30 Neck Road 
Old Lyme, CT 06371

PROTOCOL #: CYN17-RF-CLINIC 
 
 
 
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TABLE OF CONTENTS 
1.0 
BACKGROUND  
2.0 
DEVICE DESCRIPTION AND SPECIFICATIONS 
3.0 
INTENDED USE 
4.0 
PROTOCOL 
4.1 
Purpose and Objectives  
4.2 
Protocol Summary 
4.3 
Protocol Study Design 
4.4 
Subject Selection Criteria 
4.5 
Screening 
4.6 
Informed Consent Process and Enrollment 
4.7 
Pretreatment 
4.8 
Treatment 
4.9 
Post-Treatment 
4.10 Follow Up 
4.11 Unscheduled Visits 
4.12 Replacement of Subjects 
4.13 Schedule of Activities and Observations 
4.14 Evaluation Methods 
4.15 Adverse Event Assessment 
4.16 Adverse Event Recording  
5.0 
PREGNANCY 
6.0 
SUBJECT WITHDRAWAL 
7.0 
PHOTOGRAPHY 
8.0 
RISK ANALYSIS AND MANAGEMENT 
9.0 
ADVERSE REACTIONS DEFINITIONS AND REPORTING REQUIREMENTS 
10.0 
PROTOCOL DEVIATIONS 
11.0 
DATA RECORDING, COLLECTION AND MONITORING 
12.0 
CONFIDENTIALITY AND DISCLOSURE OF MEDICAL INFORMATION 
13.0 
LABELING  
14.0 
CLINICAL RESEARCH CONDUCT  
15.0 
INFORMED CONSENT 
16.0 
DATA ANALYSIS  
17.0 
REPORTING FOR THE STUDY 
18.0 
DISCLOSURE 
19.0 
RESPONSIBILITY OF THE INVESTIGATOR 
20.0 
PROCEDURE FOR AMMENDMENTS TO PROTOCOL  
21.0 
INSTITUTIONAL REVIEW BOARD 
22.0 
TERMINATION OF STUDY 
23.0 
STUDY RECORDS 
24.0 
DATA SECURITY 
25.0 
CONFIDENTIALITY OF SUBJECT IDENTIFICATION 
 
APPENDICES: 
A. Protocol Revisions Tracker 
B. Universal Pain Assessment Tool 
 

PROTOCOL #: CYN17-RF-CLINIC 
 
 
 
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1.0 BACKGROUND 
Radiofrequency (RF) technology is commonly used in surgery, minimally invasive treatments 
and aesthetic applications. RF technology is a safe method for non-ablative (A nonwounding 
device treatment which stimulates collagen growth and tightens underlying skin) treatment 
because energy can be precisely delivered through the skin to the dermal tissue beneath without 
damaging the epidermis.  The gentle heating of deep dermal tissue induces collagen 
denaturation, contraction, and subsequent synthesis.  The collagen synthesis, in turn, creates a 
tightening effect that helps to eliminate mild to moderate facial wrinkles and rhytides (A wrinkle, 
typically a facial wrinkle secondary to muscular contraction patterns in the skin) and is used also 
for other cosmetic treatments on the body.  Radiofrequency surgery is currently used to remove 
lesions such as moles, warts and skin tags and perform cosmetic surgeries such as, but not 
limited to; blepharoplasties, abdominoplasties, breast augmentations, face lifts, labiaplasties, 
and vaginoplasties. It involves the passage of radio waves into the skin to perform the removal 
or reshaping of a lesion. Different types of electrodes are used depending on the type of lesion 
(e.g. fine needle, wire loop, scalpel blade etc.). 
 
In this study this family of generators will be tested for: 
General surgical procedures such as (but not limited to); 
o Urologic, thoracic, plastic, reconstructive and gynecological 
o Electrosurgical coagulation (hemostasis or coagulating) of tissue 
o Epilation and telangiectasia 
 
 Non-ablative/aesthetic treatments such as (but not limited to); 
• Facial wrinkles and rhytids 
• Heating for the purpose of elevating tissue temperature for selected medical conditions 
such as temporary relief of pain, muscle spasms, and increase in local circulation 
• Temporary reduction in the appearance of cellulite 
 
2.0 DEVICE DESCRIPTION AND SPECIFICATIONS 
The TempSure Class II Electrosurgical cutting and coagulation device and accessories used in 
this study received 510(k) clearance under K171262 on September 22, 2017 for: 
• The 10mm, 15mm, and 20mm TempSure Envi handpieces are indicated for non-
ablative treatment of mild to moderate facial wrinkles and rhytids. 
• The 18mm, 25mm, and 30mm TempSure Envi handpieces provide heating for the 
purpose of elevating tissue temperature for selected medical conditions such as 
temporary relief of pain, muscle spasms, and increase in local circulation. 
• The Massage device is intended to provide a temporary reduction in the appearance of 
cellulite. 
• Coagulation/Hemostasis: Using the surgical handpieces and accessories, general 
surgical procedures including urologic, thoracic, plastic, reconstructive, and gynecological 
procedures where electrosurgical coagulation of tissue is performed. 
And received 510(k) clearance under K182365 on October 24, 2018 for: 
• Cutting: snoring. submucosal palatal shrinkage, traditional uvulopalatoplasty (RAUP), 
myringotomy with effective hemorrhage control, epistaxis treatment, turbinate shrinkage, 
skin incisions, biopsy, cysts, abscesses, tumors, cosmetic repairs, development of skin 
flaps, skin tags and blepharoplasty. 

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• Blended Cutting and Coagulation: snoring, submucosal palatal shrinkage, traditional 
uvulopalatoplasty (RAUP), myringotomy with effective hemorrhage control, epistaxis 
treatment, turbinate shrinkage, skin tags, papilloma keloids, keratosis, verrucae, basal cell 
carcinoma, nevi, fistulas, epithelidma, cosmetic repairs, cysts, abscesses, and 
development of skin flaps. 
• Fulguration: basal cell carcinoma, papilloma, cyst destruction, tumors, verrucae, 
hemostasis. 
• Bipolar: pinpoint precise coagulation, pinpoint hemostasis in any field (wet or dry). 
Snoring, submucosal palatal, shrinkage, traditional uvulopalatoplasty (RAUP), 
myringotomy with effective hemorrhage control, epistaxis treatment and turbinate 
shrinkage 
 
The 60mm handpieces and flexible applicators used in this study are considered investigational 
in use because they have not been cleared by the FDA.   
 
The Pellevé has been cleared (510(k) K123366) by the U.S. Food and Drug Administration (the 
FDA) for:  
 
And under K132665 for indicated for non-ablative treatment of mild to moderate facial wrinkles 
and rhytids. 
 
The devices used in this study may be considered investigational because they may not be used 
within the currently cleared indications for use.  
   
The generators used in this study have multiple modes of operation and a selection of electrode 
tips and handpieces, the user can easily configure the system for a wide array of applications. 
 
This device study does not meet the FDA definition for a Significant Risk Device study per 21 
CFR 812.3(m).  The sponsor determines that this is a non-significant risk device study. 

PROTOCOL #: CYN17-RF-CLINIC 
 
 
 
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Significant risk device means an investigational device that: 
(1) Is intended as an implant and presents a potential for serious risk to the health, safety, or 
welfare of a subject; 
(2) Is purported or represented to be for a use in supporting or sustaining human life and 
presents a potential for serious risk to the health, safety, or welfare of a subject; 
(3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or 
otherwise preventing impairment of human health and presents a potential for serious risk to the 
health, safety, or welfare of a subject; or 
(4) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject. 
 
 
The Specifications for The Devices Are: 
Surgical Connector 
One bipolar and two monopolar surgical handpiece ports 
Neutral Connector  
One universal neutral connector compatible with Cynosure neutral 
electrodes 
Smart Handpiece 
Connectors  
One 4-pin circular connector for both RF energy delivery and 
temperature sensing (monopolar) 
Modes of 
Operation  
The user can select between different modes of operation. 
Maximum Power 
TempSure Handpiece 
60mm, Flexible Applicator 
300 Watts (+/- 20%) 
25mm, 30mm 
165 Watts (+/- 20%) 
10mm, 15mm, 20mm  
120 Watts (+/- 20%) 
Surgical  
Cut 
300 Watts (+/- 20%) 
Coag 
120 Watts (+/- 20%) 
Blend 
300 Watts (+/- 20%) 
Bipolar 
40 Watts (+/- 20%) 
Pellevé Mode/Character 
Cut 
120 Watts 
Coag 
60 Watts 
Blend 
90 Watts 
Fulgurate 
45 Watts 
Bipolar 
120 Watts 
 
 
3.0 INTENDED USE 
The radiofrequency device used in this study is intended for tissue heating, coagulation, and 
cutting. 
 
4.0 PROTOCOL 
 
4.1 Purpose and Objectives 
The purpose of this study is to develop parameters and assess the safety of the 
radiofrequency device for a variety of treatments.  Treatment results may also be 
evaluated. 
 
The Primary Objectives are: 
• To develop treatment parameters. 
• Assess the safety through recording of side effects during course of study. 
 

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The Secondary Objectives are: 
• Subject satisfaction via continuous verbal feedback during the procedure and at 
follow up visits. 
• Assess the ease of use, patient response, treatment time, functions of the new 
device.  
 
4.2 Protocol Summary 
Subjects are to be enrolled in this clinical study if they are 18 years of age or older. Up to 
225 subjects will be enrolled at 8 study centers. All subjects may receive up to 10 
treatments or multiple treatment areas.  Subjects will receive a phone call or attend a visit 
at 2 days and/or 1 week post treatment to record side effects.  If a side effect is tracked, 
the site will continue to call the subject until the event resolves.  If deemed necessary by 
the investigator, the subject may attend an unscheduled visit for side effect assessment. 
The subject may return for optional follow up visits at 30, 90 and 180 days post last 
treatment for side effect and efficacy assessments.  
 
4.3 Protocol Study Design 
This investigation is a multi-center, prospective, open label study.  
 
4.4 Criteria 
 
Subjects will meet the criteria described below. 
 
Inclusion Criteria: 
• A healthy male or female 18 years of age or older. 
• Understands and accepts obligation not to receive any other procedures on the 
treatment area through the length of the study. 
• Understands and accepts the obligation and is logistically able to be present for all 
visits. 
• Is willing to comply with all requirements of the study and sign the informed consent 
document. 
 
Exclusion Criteria: 
• Is pregnant or of child bearing potential and not using medically effective birth 
control or has been pregnant in the last 3 months, currently breast feeding or 
planning a pregnancy during the course of the study. 
• The subject has active or localized systemic infections. 
• The subject is currently enrolled in an investigational drug or device trial, or has 
received an investigational drug or been treated with an investigational device 
within in the area to be treated 6 months prior to entering this study. 
• Any other types of cosmetic treatments in the area to be treated in the past 6 
months are cautioned and determined at the discretion of the investigator.  
• The subject has a history of keloids. 
• The subject has evidence of active systemic or local skin disease that may alter 
wound healing. 
• The subject has scarring or wounds in the treatment area that would interfere with 
study assessments. 
• The subject has a metal implant (such as but not limited to; titanium orbit or metal 
chin repair) in the face or head that would interfere with study treatment, or subject 

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has an electronic implantable device (such as but not limited to; pacemakers and 
embedded defibrillators). 
• 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. 
 
4.5 Screening  
Medical history of each subject will be reviewed, and inclusion/exclusion criteria verified.  
Discontinuation of any concomitant medications or pretreatment instructions as 
determined by the investigator will be discussed.  Pre and Post-Treatment instructions will 
be reviewed with the subject prior to signing the informed consent. Subjects will be asked 
questions about their medical history and may have a limited physical exam (no pelvic or 
and rectal exam will be performed). 
 
Procedure for the Limited Physical Exam: 
If the investigator determines that a limited physical is necessary, the exam will be similar 
to that of a basic annual physical exam performed by a primary care doctor to determine 
general overall health. The limited medical exam may include all or any of the following; 
vital signs such as blood pressure, heart rate, respiratory rate and body temperature, 
general appearance, listening to the heart, lungs and abdomen with a stethoscope, head 
and neck exam such as looking at the throat, tonsils, teeth, ears, eyes and nose and 
neurological exam such as testing muscle strength, reflexes, balance, sensory changes of 
the extremities and mental state. 
 
 
4.6 Informed Consent Process and Enrollment 
Subjects meeting the subject selection criteria for the study will sign the informed consent 
form and be assigned a subject identification number. 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.  Non-English speaking individuals cannot be enrolled in 
this study.  Employees of the sponsor or the Investigator may be enrolled in this study. A 
subject will be considered enrolled in the study once they have signed the informed 
consent form. 
 
4.7 Pretreatment 
• Photographs, OCT, and Ultrasound measurements may be taken pretreatment. 
• 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 and the date of their last 
menstrual cycle.  A urine or serum pregnancy test may be conducted at the 
Investigators discretion at any time.  If the treatment area is on the abdomen, then 
urine or serum pregnancy test will be conducted.  If a urine or serum pregnancy test is 
conducted, then a negative result must be obtained within 24 hours prior to the 
procedure. 
• A treatment area will be identified by the investigator. Subjects may receive facial 
treatments or isolated areas of treatment on other areas of the body 
• A marker may be used to define the area. 

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• Standard pre-treatment instructions will be reviewed, and the subject will be instructed 
to adhere to the following: 
o Do not receive other treatments within the study area for the duration of the 
study. 
o If treatment is on the face; 
1. Do not apply any products or makeup to general eye area for 12 hours 
(or more) prior to each study visit. 
2. Remove makeup and wash facial area prior to treatment. 
o Please remove all makeup, and any lotions or sun block from the treatment 
area. Any preparations left on the skin will act as impedance to the energy and 
will diminish the effects. 
o The treatment area must be free of any open lesions or infections. 
o For an optimum treatment, hydrate by drinking water or hydrating fluids several 
days in preparation. Avoid alcohol if possible. The same procedure should be 
followed prior to each visit. 
 
4.8 Treatment 
• Radiofrequency Device Treatment: 
o The type of treatment will determine if gel should be applied to the skin prior to 
treatment. The gel is a conductive gel created for treatments that use radio 
frequency (RF) to ensure the proper connection between the hand piece and 
the skin. 
o A neutral pad will be used in accordance with the operator’s manual for the 
device.  
o The hand piece, applicator or tip will be placed in contact with the skin.  
o The entire defined treatment area will then be treated by delivering energy to 
the skin. 
o The hand piece, number of passes and parameters used for the treatment will 
be determined by the Investigator.  
o Parameters may be adjusted throughout the treatment to increase subject 
comfort. 
o Contact cooling built into the 60mm handpiece may be used to increase subject 
comfort. 
o Nitronox may be used to increase subject comfort and will be determined by the 
Investigator. 
• Procedural adverse events will be documented. 
• Subjects will be asked to report the general level of treatment discomfort/pain on a 
scale of 0 (none) to 10 (maximum intolerable pain). 
• Some subjects may have an incomplete response or no response by the end of the 
study. At the end of the study treatments using an FDA approved/cleared treatment 
method may be discussed with the subject and obtained at the cost of the subject. 
 
4.9  Post-Treatment 
• Photographs may be taken post treatment. 
• Standard post-treatment care instructions will be reviewed and may be instructed to 
adhere to the following: 
o Wash skin with tepid water and a gentle cleanser.   
o If the skin is slightly pink or red in areas following the treatment, avoid hot water 
when washing or showering until any erythema (redness) has subsided. 

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o Makeup (preferably mineral-based) is not encouraged but may be applied 
immediately post-treatment. 
o Soothing creams or moisturizers may be used. 
o If the treatment area may be exposed to the sun; use a sun block with an SPF 
of 30 or greater to help prevent sun damage. This treatment does not cause 
photosensitivity. 
• Subjects may be given a diary to assess recovery time to be completed during the 
week post the treatment. 
• Subjects and clinicians may be asked to complete a treatment experience 
questionnaire. 
 
4.10 Follow Up 
• Subjects will receive a phone call or attend a visit 2 days and/or 1-week post 
treatment to record side effects.  If a side effect is tracked, the site will continue 
to call the subject until the event resolves.  If deemed necessary by the 
investigator, the subject may attend an unscheduled visit for side effect 
assessment. 
• The subject may return for a follow up visit at 30, 90 and 180 days post last 
treatment for side effect and efficacy assessments. 
• The assessments listed in the schedule of activities and observations table 
(Section 4.13) will be performed at all follow up visits. 
• Adverse events will be assessed at all follow up visits. 
 
4.11 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. 
 
4.12 Replacement of Subjects 
Replacement of subjects who have withdrawn or been withdrawn from the study will be 
allowed to be replaced with prior approval from the sponsor and/or IRB.

 
 
Protocol: CYN17-RF-CLINIC                                                                                                                                    Cynosure, Inc. 
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4.13 Schedule of Activities and Observations 
 
Procedure 
Screening/ 
Pretreatment* 
Visit 1-5: 
Treatment 
Visits 
 
Visit 6: 
(optional) 
2 Day Post 
Last Treatment 
Visit or Phone 
Call 
Visit 7: 
1 Week Post 
Treatment 
Visit or Phone 
Call 
Visit 8: 
(optional) 
30 Day Post 
Last Treatment 
Visit 
Visit 9: 
(optional) 
90 Day Post 
Last Treatment 
Visit 
Visit 10: 
(optional) 
180 Day Post 
Last Treatment 
Visit 
Medical History 
X 
 
 
 
 
 
 
Pregnancy 
Verification 
X 
 
 
 
 
 
 
Informed 
Consent 
X 
 
 
 
 
 
 
Treatment 
Discomfort/ 
Pain Evaluation 
 
X 
 
 
 
 
 
Treatment 
 
X 
 
 
 
 
 
Photographs 
X 
X 
X 
X 
X 
X 
X 
Subject 
Experience  
 
X 
 
 
 
 
 
User 
Experience  
 
X 
 
 
 
 
 
Diary*** 
 
X 
 
X 
 
 
 
OCT*** 
X 
X 
 
X 
X 
X 
 
Ultrasound*** 
X 
X 
 
X 
X 
X 
 
Subject 
Satisfaction 
 
 
 
 
X 
X 
X 
Adverse Events 
Assessment ** 
 
X 
X 
X 
X 
X 
X 
* Screening/Pretreatment activities must be performed within 30 days prior to 1st treatment and may be performed on the same day as Visit 1. 
** If deemed necessary by the investigator, the subject may attend an unscheduled visit for side effect assessment. 
***Ultrasound (US), Optical Coherence Tomography (OCT), and the Diary are optional assessments. 
 
The sponsor anticipates that all subjects can be enrolled within 6 months. The subject participation in this study will last approximately to 
1-7 months.  The total duration of this study is anticipated to last approximately two years.  

 
 
Protocol: CYN17-RF-CLINIC                                                                                                                                    Cynosure, Inc. 
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4.14 Evaluation Methods 
Photographs: 
Photographs will be taken at all visits and will be used to assess safety and efficacy of 
treatment. 
 
Treatment Discomfort/Pain Evaluation: 
Subjects will be asked to report the general level of treatment discomfort on a scale of 0 
(none) to 10 (maximum intolerable pain) using the universal pain assessment tool 
(Appendix B) 
 
Subject Experience Evaluation: 
Subjects will be asked to complete a questionnaire to assess their treatment experience. 
 
User Experience Evaluation: 
The clinician will be asked to complete a questionnaire to assess the usability of the 
device. 
 
Diary: 
A subject diary may be collected to assess the recovery time of the treatment for 7 days 
post treatment. 
 
Subject Satisfaction:  
The subject will be asked their level of satisfaction using a 6-point Likert scale that ranges 
from “extremely satisfied” to “extremely unsatisfied.”  
 
Rating 
Description 
6 
Extremely Satisfied 
5 
Satisfied 
4 
Slightly Satisfied 
3 
Slightly Unsatisfied 
2 
Dissatisfied 
1 
Extremely Unsatisfied 
 
 
Ultrasound (U/S): 
An ultrasound scan is a medical test that uses sound waves to capture live images from 
the inside of the body. The subject will most likely be lying down on a table with a section 
of their body exposed for the test.  A special lubricating jelly will be applied to their skin. 
This prevents friction between the ultrasound transducer—similar in appearance to a 
microphone— and the skin. The jelly also helps transmit the sound waves. After the 
procedure, the gel will be cleaned off the subject. The whole procedure typically lasts less 
than 30 minutes. Following it, the subject will be free to go about their day and normal 
activities. 
 
Optical Coherence Tomography (OCT) 
An OCT device uses a very low power laser that is directed at the skin. The reflected light 
is captured by the device to provide images of the skin layer down to 1 millimeter depth. It 
may be used to help evaluate the effect of RF exposure on the skin. The subject will be 
asked to lay down and the device’s arm will be brought into contact with the skin area of 
interest. Depending on the area of skin to be measured, the exam will take 15 to 30 
minutes to perform. 

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4.15 Adverse Event Assessment 
Recording of adverse events will take place at all visits. 
 
4.16 Adverse Event Recording 
All data captured must be supported by the Investigator’s timely assessment and 
documentation of the 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 regulatory reporting requirements and to ensure timely 
adverse event reporting to meet local and global regulatory requirements.  
 
Adverse Events Pertaining to the Radiofrequency Device: 
Mild discomfort during treatment may be experienced by the subject. Typically, the 
discomfort is temporary and localized within the treatment area. Mild edema (swelling) and 
erythema (redness) may occur. Initial studies indicate that these side effects typically 
resolve within 2 to 24 hours. 
 
Other anticipated side effects may include; pain, skin burns, bleeding, scarring, crusting, 
bruising, infection, itching, prolonged edema (swelling), and erythema (redness), hardness, 
and nodules. Loss of hair pigment may also occur within and adjacent to the treatment 
area.  
 
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.  
 
Adverse Events Pertaining to Gel: 
The gel is a water-based gel that may be placed on the skin during an RF treatment. No 
known adverse events are documented. However, an allergic reaction is always possible 
when placing a topical gel onto the skin. Allergic reaction may include a mild reaction such 
as skin redness, irritation or hives. 
 
Eye injury due to direct ocular Radiofrequency exposure may occur: 
Corneal Eye Shields (sterile, plastic, non-conductive) must be used for any radiofrequency 
surgical procedure being performed over the globe of the eye. 
 
Adverse Events Pertaining to Cooling: 
Anticipated transient side effects associated with cooling may include tingling, itching, 
decreased sensation, numbness, redness and pain. 
 
Adverse Events Pertaining to Anesthetic: 
1% lidocaine (Lidocaine) with Epinephrine Injection 
Pain and numbness may be experienced at the site of the injection. Redness, rash, 
infection, skin damage or nerve damage at the site of the injection may also be 
experienced. Temporary loss of sensation and muscle function at the site of injection may 
be experienced. Lidocaine with epinephrine contains the preservative sodium metabisulfite 
which may cause allergic-type reactions or intolerances including anaphylactic symptoms 
such as itching, hives, swollen areas of the body, and/or trouble breathing and life-

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threatening or less severe asthmatic episodes in certain susceptible people. 
 
Adverse Events Pertaining to Nitronox: 
May experience nausea, vomiting, excessive sweating, euphoria, excitement, deep 
sedation, drowsiness, sleep, dizziness, lightheadedness, dysphoria, amnesia, and 
headaches. 
 
Adverse Events Pertaining to Ultrasound: 
Ultrasound imaging has minimal risks and may produce effects on the body such as 
redness and pockets of gas.  Skin rashes from use of the ultrasound gel may also occur. 
 
 
Other Anticipated Adverse Events: 
Incomplete response or no response is relatively common since some subjects may not 
respond to treatment. 
 
5.0 PREGNANCY 
Females may not participate in this study if they are pregnant, breastfeeding, were pregnant 
within the last three months or are planning a pregnancy during the course of the study.   
 
If the subject thinks they have become pregnant during the study it is important that they inform 
the Investigator immediately. If she becomes pregnant or thinks that she may be pregnant, she 
will be removed from the study and will be asked to perform a final evaluation similar to that of the 
final follow-up visit.  The Investigator may request to track the pregnancy and will report the 
pregnancy to the Sponsor. 
 
6.0 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. 
 
7.0 PHOTOGRAPHY 
Standardized photographs may be taken of the treatment area.  If photographs are taken of the 
face the subject will be asked to remove jewelry, make up and lotions prior to each photo session.  
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.  
 

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8.0 RISK ANALYSIS AND MANAGEMENT 
The Investigator in this clinical trial has been invited to participate based on his/her previous 
experience with the use of system, similar systems and industry experience. Experience with 
treatments is the most critical element in managing subject risk in this trial.  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. 
 
In addition, as with any study, there is a risk of bias. To minimize/avoid bias objective evaluation 
methods may also be used in conjunction with subjective evaluation methods when feasible. 
 
9.0 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. 
Adverse Events 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 device 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: 
 

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• 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 
 
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 files.  
 
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. 
 
10.0 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. 
 
11.0. DATA RECORDING, COLLECTION AND MONITORING 
The sponsor will train the site and may be present at initiation of treatment.  The sponsor will also 
monitor the site periodically.  The sponsor may request intermediate data following each visit 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 as required by FDA 
regulations. 
 
12.0 CONFIDENTIALITY AND DISCLOSURE OF MEDICAL INFORMATION 
As part of this study the Investigator and the team at the study center 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, 

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photographs taken during the study and other medical information relating to participation in the 
study.   
 
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, 
Inc. the manufacturer of the 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 their photographs and study 
information may be used. 
 
The study center 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 study 
center 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 their 
photographs and study information may be used. 
 
Study records will be kept at the study center 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. 
 
13.0 LABELING 
Sample labeling and directions for use are contained in the Operators Manual for the device. 
 
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 INFORMED CONSENT  
During the screening, the investigator or a representative on their behalf will perform the 
informed consent process and discuss all aspects of the study.  A signed informed consent form 

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(ICF) shall be obtained from the subject, clearly indicating his/her understanding of the study 
requirements, as well as the possible risks involved with study participation.  
 
16.0 DATA ANALYSIS 
All data will be analyzed at the end of the study.  The primary analysis will be performed by the 
intention-to-treat approach.  All subjects who begin the treatment is considered to be part of the 
study whether the subject completes the study or not.  Additional per-protocol analysis may also 
be performed on subjects who complete the entire clinical trial according to the protocol.  The 
most appropriate method of handling missing values will be chosen based on the particular trial's 
goals, endpoints and context. 
 
Endpoints will be summarized with descriptive statistics.  Continuous variables will be 
summarized with n, mean, standard deviation and range.  Frequency counts and percentage of 
subjects within each category will be presented for categorical data.  If applicable, Student’s t-
test may be used to determine if two sets of data are significantly different from each other and 
p-values will be reported.  If the calculated p-value is below the threshold chosen for statistical 
significance (0.05, or 0.01 level) then the null hypothesis is rejected in favor of the alternative 
hypothesis.  Subgroup analyses may be performed to identify a subject population that achieves 
the most benefit.  Interim results may also be collected and reported as deemed necessary. 
 
17.0 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. 
 
18.0 DISCLOSURE 
The Principal Investigator and Cynosure employees 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. 
 
19.0 RESPONSIBILITY OF THE INVESTIGATOR 
The Investigator is responsible for ensuring that the clinical study is performed in accordance with 
the Declaration of Helsinki (revised version of Edinburgh, Scotland, 2000 including notes of 
clarification, Washington, 2002 and Tokyo, 2004) and FDA Good Clinical Practice Regulations (21 
CFR parts 50, 56, and 812).  Investigators will supply information to the sponsor such that the 
sponsor can comply with the Financial Disclosure Rules (21 CFR part 54). 
 
20.0 PROCEDURE FOR AMMENDMENTS TO THE 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. 
 
All revisions and/or amendments to the protocol must be approved in writing by the appropriate 
Institutional Review Board. 
 
21.0 INSTITUTIONAL REVIEW BOARD 

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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.   
 
22.0  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. 
 
23.0  STUDY RECORDS  
All records and documents pertaining to the study will be maintained in appropriate permanent 
files as per the ICH guidelines for Essential Documents for the Conduct of a Clinical Trial and 21 
CFR 11, and will be available for inspection by the Sponsor, Sponsor designee, the U.S. Food 
and Drug Administration or applicable regulatory body at any time. 
 
24.0 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.  
 
25.0 CONFIDENTIALITY OF SUBJECT IDENTIFICATION 
After the informed consent has been signed, each subject will be entered on a 
screening/enrollment log, which will be kept with the study records.  Once a subject is 
consented, a unique subject identification number will be assigned. No two subjects will have the 
same subject identification number.  This subject identification number will identify the subject 
throughout the study and will be used for all source documents, and Data Collection Forms.  The 
subject identification number will be held confidential so far as permitted by law.  Investigative 
site staff, the Sponsor or its designee, and, under certain circumstances, the FDA and 
Institutional Review Board (IRB) will be able to inspect and have access to the subject 
identification number and the confidential data that it links to.  Any publication or presentation of 
data will not contain any identifiable subject information. 
 

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APPENDIX A: 
Protocol Revisions Tracker 
 
Version 
Date 
Editor 
Description 
January 6,2017 
Jennifer Civiok 
Initial Submission to the IRB 
January 12, 2017 
Jennifer Civiok 
Response to IRB conditional approval;  
May 3, 2017 
Jennifer Civiok 
Add Raminder Saluja, MD as a study center, 
increase # of study centers from 1 to 5, increase 
number of subjects from 50 to 150 
November 17, 2017 
Jennifer Civiok 
Add Barry DiBernardo, MD as a study center 
Updated FDA clearance, Clarify that the Pelleve 
and/or TempSure RF Device may be used, 
update treatment to list that a neutral pad will be 
used in accordance with the instructions for use,  
minor administrative edits.  
January 19, 2018 
Jennifer Civiok 
Add Edward Jaccoma, M.D. as a study center. 
 
April 9, 2018 
Kristy Maxfield  
Add Jeffrey Dell, M.D. as a study center, add 
60mm handpiece as investigational, expansion 
of subject enrollment (150 to 200) and number of 
sites (5 to 8), minor administrative edits.  
 
April 25, 2018 
Kristy Maxfield  
Add adverse event of hardness and nodules.  
July 12, 2018 
Kristy Maxfield 
Added contact cooling may be used during 
treatment. Added adverse events pertaining to 
cooling.  
October 11, 2018 
Kristy Luis 
Updates/edits to device specifications. Added 
follow up visits at 2 days and 7 days. Added 
anesthesia may be used and adverse events. 
Added additional evaluation methods (user and 
subject experience, optical coherence 
tomography, ultrasounds, and a diary). Minor 
administrative edits 
November 12, 2018 
Kristy Luis /  
Jill Ashley 
Update FDA clearance. Update 2 day visit as 
either a visit or phone call. Add the use of 
Nitronox and adverse events. Minor admin edits.  
November 16, 2018 
Kristy Luis 
Increase number of treatments from 5 to 10. 
Update to include side effect of loss of pigment 
in hair.  
February 4, 2019 
Kristy Luis 
Add satellite site for Dr. Doherty. Increase 
number of subjects from 200 to 225.  

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March 20, 2019 
Kristy Luis 
Added flexible applicator may be used. Updated 
TempSure Specifications chart. Admin edits. 

 
 
Protocol: CYN17-RF-CLINIC                                                                                                                                    Cynosure, Inc. 
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APPENDIX B: