A Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis Followed by Radiofrequency Treatment for Submental and Submandibular Contouring
Phase: NA
Conditions: Body Fat Disorder
Sponsor: Zeltiq Aesthetics

ZELTIQ Aesthetics – Confidential and Proprietary 
Part Number: CS-302106
Revision: 02
Page 1 of 39
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular
Contouring
Note: Check with Document Control for current revisions of all referenced documents.
ZELTIQ P/N: CS-302106-02
Protocol Number: ZA18-002
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ.
FEASIBILITY STUDY TO EXPLORE THE SAFETY AND 
EFFICACY OF CRYOLIPOLYSIS FOLLOWED BY 
RADIOFREQUENCY TREATMENT FOR SUBMENTAL AND 
SUBMANDIBULAR CONTOURING
Investigational Plan
Sponsor
ZELTIQ, an Allergan Affiliate
4410 Rosewood Drive
Pleasanton, CA 94588
Protocol Number:
ZA18-002
Protocol Version:
2.0
Protocol Date: 
February 19, 2019
Product:
ZELTIQ CoolSculpting® System
Investigator/Co-
Investigator(s): 
Innovation Research Center
4410 Rosewood Dr.
Pleasanton, CA 94588
Sponsor Contact
PH: 
Fax: 
CS-310562-01_Appendix A_Clinical Protocol _Feasibility Study of CS and RF for Submental, ZA18-002
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ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 4 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
 
INVESTIGATOR SIGNATURE PAGE 
 
For protocol number ZA18-002 
 
 
I agree to: 
 
• Implement and conduct this study diligently and in strict compliance with this 
protocol, GCP, and all applicable laws and regulations. 
 
• Maintain all information supplied by the Sponsor, ZELTIQ Aesthetics, an Allergan affiliate, in 
confidence and, when this information is submitted to an Ethics Committee (EC), or another 
group, it will be submitted with a designation that the material is confidential. 
 
I have read this protocol in its entirety and I agree to all aspects. 
 
 
 
__         _______________         _______________________                     _______________   
Investigator printed name                 Signature 
 
                        Date 
 
 
 
 
         
_         ___
                     
   
Co- Investigator printed name          Signature 
 
                        Date  
 
 
RETURN PAGE TO SPONSOR 
 
 
 
 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 5 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
Table of Contents 
 
1. 
Protocol Summary ................................................................................................. 7 
2. 
Introduction ............................................................................................................ 8 
2.1. 
Background ................................................................................................................. 8 
2.2. 
Device Description .................................................................................................... 10 
2.3. 
Regulatory Status ...................................................................................................... 11 
3. 
Study Protocol ...................................................................................................... 12 
3.1. 
Design ........................................................................................................................ 12 
3.2. 
Study Duration ........................................................................................................... 12 
3.3. 
Physician Participants .............................................................................................. 12 
3.4. 
Site Requirements ..................................................................................................... 12 
3.5. 
Subject Recruitment ................................................................................................. 12 
3.6. 
Sample Size ............................................................................................................... 13 
3.7. 
Subject Eligibility ...................................................................................................... 13 
3.8. 
Informed Consent ...................................................................................................... 14 
3.9. 
Screening Procedures .............................................................................................. 14 
Screening Visit; Required; Day -45 to Day 0 ...................................................................................... 14 
3.10. 
Study Enrollment ....................................................................................................... 15 
3.11. 
Study Treatment Procedures ................................................................................... 16 
3.11.1. 
Treatment Visit #1; Required: Day 0 ................................................................................. 16 
3.11.2. 
Treatment Visit #2; Group B; Week 12 post-Treatment #1 (± 2 weeks) ........................... 17 
3.12. 
Follow-up Procedures ............................................................................................... 18 
3.12.1. 
1-Week Follow-Up Visit; Required: Day 7 (± 3 days) ....................................................... 18 
3.12.2. 
12-Week Final Follow-Up Evaluation; Required (12 weeks ± 2 weeks post final treatment)
 
18 
3.13. 
Assessments ............................................................................................................. 21 
3.13.1. 
Safety Assessments.......................................................................................................... 21 
3.13.2. 
Photography ...................................................................................................................... 21 
3.13.3. 
Caliper Measurement ........................................................................................................ 21 
3.13.4. 
Ultrasound Measurements ................................................................................................ 22 
3.13.5. 
Skin Elasticity Measurement ............................................................................................. 23 
3.13.6. 
Thermographic Imaging .................................................................................................... 23 
3.13.7. 
Global Aesthetic Improvement Scale ................................................................................ 23 
3.13.8. 
Subject Satisfaction........................................................................................................... 23 
3.14. 
Endpoints ................................................................................................................... 24 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 6 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
3.14.1. 
Primary Endpoints ............................................................................................................. 24 
3.14.2. 
Secondary Endpoints ........................................................................................................ 24 
3.15. 
Statistical Analysis Plan ........................................................................................... 25 
3.15.1. 
Statistical Methods: Overall Plan ...................................................................................... 25 
3.15.2. 
Analysis Population ........................................................................................................... 25 
3.15.3. 
Endpoint Analysis .............................................................................................................. 26 
Primary Safety Endpoint: ............................................................................................................................... 26 
Primary Efficacy Endpoint: Investigator Graded Global Aesthetic Improvement Scale (IGAIS) .................... 26 
3.16. 
Protocol Adherence .................................................................................................. 27 
3.17. 
Adverse Events ......................................................................................................... 27 
3.18. 
Reportable Incidents ................................................................................................. 29 
4. 
Study Management and Quality Control ............................................................ 30 
4.1. 
Study Data Collection ............................................................................................... 30 
4.2. 
Confidentiality ........................................................................................................... 30 
4.3. 
Investigator Responsibilities ................................................................................... 30 
4.3.1. 
General Responsibilities ................................................................................................... 30 
4.3.2. 
Investigator Records ......................................................................................................... 31 
4.3.3. 
Investigator Reports .......................................................................................................... 32 
4.4. 
Sponsor Responsibilities ......................................................................................... 33 
4.4.1. 
General Responsibilities ................................................................................................... 33 
4.4.2. 
Training ............................................................................................................................. 33 
4.4.3. 
Monitoring ......................................................................................................................... 34 
4.4.4. 
Final Report ....................................................................................................................... 35 
4.4.5. 
Trial Registration ............................................................................................................... 35 
5. 
Data Ownership .................................................................................................... 35 
6. 
Publication Policy ................................................................................................ 35 
7. 
Risk/Benefit Analysis ........................................................................................... 36 
7.1. 
Benefits ...................................................................................................................... 36 
7.2. 
Risks ........................................................................................................................... 36 
8. 
References ............................................................................................................ 39 
 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 7 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
1. Protocol Summary 
 
Title 
Feasibility study to explore the safety and efficacy of cryolipolysis followed by 
radiofrequency treatment for submental and submandibular contouring 
Design 
Prospective, randomized, interventional cohort 
Purpose 
The purpose of this study is to evaluate the safety and efficacy of sequential use of 
CoolSculpting (Cryolipolysis) and radiofrequency treatment of the submental and 
submandibular area 
Enrollment 
Up to forty (40) subjects 
Clinical Site 
Up to three (3) investigational sites 
Subject 
Population 
Healthy adult men and women with skin fold thickness of > 1 cm in the submental 
and submandibular area who desire reduction of submental and submandibular fat 
Primary 
Endpoint 
Safety endpoint: Incidence of unanticipated adverse device effects (UADE).  It is 
expected there will be zero UADEs.  
 
Efficacy Endpoint:  
Assessment of overall treatment outcome in submental and submandibular area 
using Investigator-graded Global Aesthetic Improvement Scale (IGAIS) at 12-
weeks post final treatment.  
Secondary 
Endpoint 
Efficacy Endpoints:  
1. Assessment of overall treatment outcome in submental and submandibular area 
using Subject-graded GAIS (SGAIS) administered at 12 weeks post-final 
treatment.  
2. Subject Satisfaction as assessed by the Subject Self-Rating Scale score (SSRS). 
3. Subject satisfaction as assessed by questionnaire administered at 12-weeks post 
treatment.   
4. Reduction in fat layer thickness, as measured by caliper at 12 weeks post-final 
treatment. 
 
Sponsor 
ZELTIQ, an Allergan Affiliate 
4410 Rosewood Drive 
Pleasanton, CA 94588 
 
 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 8 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
2. Introduction 
2.1. 
Background 
Fat reduction and body contouring procedures, which include invasive, minimally-invasive, and 
non-invasive procedures, have become increasingly popular aesthetic procedures. Patients who 
are obese and do not have specific fat bulges but require significant fat reduction to achieve 
aesthetic results are candidates for invasive and minimally-invasive procedures, such as 
liposuction and laser-assisted liposuction. Although effective at reducing fat, these invasive and 
minimally-invasive procedures involve significant patient pain, expense, downtime, and the risks 
typically associated with surgical procedures. As a result, patients who do not require significant 
fat reduction to achieve meaningful aesthetic results typically seek non-invasive fat reduction and 
body contouring procedures to avoid the pain, expense, downtime, and surgical risks associated 
with invasive and minimally-invasive procedures. 
 
ZELTIQ Aesthetics has developed and commercialized a technology to non-invasively reduce 
subcutaneous fat.  The ZELTIQ technology utilizes the sensitivity of fat cells to cold injury in 
order to selectively eliminate subcutaneous fat tissue without affecting the skin or other 
surrounding tissues. Termed cryolipolysis, this technology enables a non-invasive alternative 
for subcutaneous fat reduction through cellular apoptosis. The ZELTIQ CoolSculpting System, 
which is cleared for use in the United States for an indication of fat layer reduction in the flanks, 
abdomen, thighs, bra fat, back fat, banana roll, upper arms, and submental and submandibular 
areas through cold-assisted lipolysis, has been clinically proven to reduce fat bulges, allowing 
patients to achieve noticeable and measurable aesthetic results without the pain, expense, 
downtime, and risks associated with existing invasive and minimally-invasive procedures.  
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ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 10 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
Note: Check with Document Control for current revisions of all referenced documents. 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
2.2. 
Device Description 
 
The CoolSculpting System is comprised of a control unit (Figure 3) which houses the system 
controller and power source, and detachable applicators such as the CoolMini (Figure 4), that are 
used to apply the cooling and/or warming to the treatment site. The vacuum applicators use 
vacuum pressure to draw tissue into the cup shaped applicator. Tissue drawn into the cup will be 
treated using a cooling parameter of -11◦C for up to 45 minutes. 
 
 
 
 
 
Figure 3.  CoolSculpting System Control Unit. 
 
 
 
Figure 4:  CoolMini Applicator. 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 11 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
2.3. 
Regulatory Status 
The ZELTIQ System received market clearance on August 24, 2010 for “use as a non-invasive 
dermatological aesthetic treatment to affect the appearance of flanks” (DEN090002). On May 9, 
2012, the ZELTIQ System received market clearance for treatment of the abdomen (K120023); 
on April 9, 2014 the System received market clearance for treatment of the thighs (K133212); 
and on September 24, 2015 the System received market clearance for treatment of the submental 
area (K151179). Subsequently, the System received clearance for bra fat, back fat and banana 
roll (K160259), upper arms (K162050), the submandibular area (K181740), and can affect the 
appearance of lax tissue after submental treatment (K172144).  FDA clearance allows treatment 
duration of up to 120 minutes, and at temperatures as low as -15ႏ.    
 
This study will investigate the use of the FDA-cleared ZELTIQ CoolSculpting System and the 
CoolMini vacuum applicator for treatment of subcutaneous fat in the submental and 
submandibular area followed by radiofrequency treatment either immediately post cryolipolysis 
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ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 12 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
or 10-14 weeks later. Results from this clinical trial will be used to further support safety and 
efficacy of using the Zeltiq CoolSculpting System sequentially with radiofrequency for fat 
reduction/improved aesthetic outcome in the submental and submandibular areas. 
3. Study Protocol 
3.1. 
Design 
Prospective, randomized, interventional cohort. 
3.2. 
Study Duration  
Enrollment and follow-up is expected to take up to six (6) months for each subject. 
3.3. 
Physician Participants 
Study investigators must be practicing medical physicians with experience in the use of the 
ZELTIQ CoolSculpting System and radiofrequency energy device. 
3.4. 
Site Requirements 
Site investigators should have at least one study coordinator with experience in conducting 
clinical research and with sufficient time to conduct the study. 
3.5. 
Subject Recruitment 
Subjects who seek reduction of fat in the submental area and submandibular area will be 
recruited from the general population. 
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ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 13 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
3.6. 
Sample Size 
A maximum of forty (40) subjects will be treated at up to three investigational sites. 
3.7. 
Subject Eligibility 
To be eligible to participate in the study, subjects must meet all the inclusion criteria and 
none of the exclusion criteria listed in Table 1. 
Table 1.  Eligibility criteria. 
Inclusion Criteria 
a) Male or female subjects ≥22 years of age and ≤65 years of age. 
b) Treatment area skin fold thickness > 1cm (measured by caliper). 
c) Dissatisfaction with the treatment area expressed by the subject as a rating of 0, 
1 or 2 using the Subject Self Rating Scale (SSRS) as determined at Screening 
visit.  
d) No weight change exceeding 5% of body weight in the preceding month. 
e) Agreement to maintain his/her weight (i.e., within 5%) by not making any major 
changes in diet or exercise routine during the course of the study.  
f) Subject has signed a written informed consent form. 
Exclusion Criteria 
a) Body Mass Index ≥ 46.2 as determined at screening. 
b) Excessive skin laxity in the treatment area for which reduction of subcutaneous 
fat may, in the opinion of the investigator, result in an unacceptable aesthetic 
result.  
c) Prominent platysmal bands at rest which may interfere with assessment of 
treatment area. 
d) Evidence of any cause of enlargement in the treatment area other than localized 
subcutaneous fat, such as swollen lymph nodes or ptotic submandibular glands. 
e) Significant enlargement on the anterior neck that may prevent the proper 
placement of the applicator e.g. enlarged thyroid glands. 
f) Treatment with dermal fillers, chemical peels, radiofrequency or laser procedures 
that may affect contour in the treatment area within the past 6 months. 
g) Botulinum toxin, deoxycholic acid, or other aesthetic drug injections within the 
treatment area in the past 6 months. 
h) History of facial nerve paresis or paralysis (such as Bell's palsy).  
i) History of a fat reduction procedure (e.g., liposuction, surgery, lipolytic agents, 
etc.) or implant in or adjacent to the area of intended treatment. 
j) History of prior neck surgery, or prior surgery in the area of intended treatment. 
k) Current infection in and adjacent to treatment area. 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 14 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
l) Known history of cryoglobulinemia, cold urticaria, cold agglutinin disease or 
paroxysmal cold hemoglobinuria. 
m) Known history of Raynaud’s disease, or any known condition with a response to 
cold exposure that limits blood flow to the skin. 
n) History of bleeding disorder or is taking any medication that in the investigator’s 
opinion may increase the subject’s risk of bruising. 
o) Currently taking or has taken diet pills or weight control supplements within the 
past month. 
p) Any dermatological conditions, such as scars in the location of the treatment area 
that may interfere with the treatment or evaluation. 
q) Active implanted device such as a pacemaker, automatic implantable 
cardioverter/defibrillator (AICD), drug delivery system, or any other implantable 
electrical device. 
r) Pregnant or intending to become pregnant in the next 6 months. 
s) Lactating or has been lactating in the past 6 months. 
t) Unable or unwilling to comply with the study requirements including remaining 
clean shaven for all study visits. 
u) Currently enrolled in a clinical study of an unapproved investigational drug or 
device. 
v) Any other condition or laboratory value that would, in the professional opinion 
of the investigator, potentially affect the subject’s response or the integrity of the 
data or would pose an unacceptable risk to the subject. 
3.8. 
Informed Consent  
Study candidates shall receive an explanation of the study objectives, possible risks and 
benefits of the study, and be given adequate time to read the information included in the 
informed consent document. Candidates will be given an opportunity to ask questions 
about any of the information contained in the informed consent. Candidates must verbally 
acknowledge understanding of the informed consent and sign the consent form 
accordingly. This form must have prior approval of the Institutional Review Board (IRB).  
3.9. 
Screening Procedures 
Screening Visit; Required; Day -45 to Day 0 
The subject shall be consented for study participation as described in Section 3.8.  After 
the informed consent is signed, subjects will be screened for eligibility.  Each subject will 
be evaluated to determine that all eligibility criteria are met.  The investigator or designee 
shall complete a brief medical history and examine the subject to confirm eligibility for 
the study. 
 

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Part Number: CS-302106 Revision: 02 
Page 15 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
1. Obtain height and weight. 
2. Obtain Subject Self-Rating Scale score.  
3. Visually assess and palpate the intended treatment area to determine if it is 
appropriate for treatment. 
4. Assess oral cavity for current dental infection or evidence of dry mouth.  
5. Assess function of the marginal mandibular nerve (grimace with ability to show 
lower teeth) and hypoglossal nerve (tongue does not deviate upon protrusion).  
6. Assess upper neck to rule out enlarged lymph nodes or glands.  
7. Measure the skin fold thickness of the intended treatment areas using a caliper. 
8. Assess for dermatological conditions or implantable devices that may lead to 
exclusion of a subject from the study. 
9. Document potential candidate’s medication use (including over-the-counter 
medications, vitamins and herbs), Fitzpatrick Skin Type, race and ethnicity as well 
as any skin irregularities (e.g. moles, birth marks, scars, stretch marks, 
discoloration) at the intended treatment area.  
 
All female subjects of childbearing potential will be assessed for the start date of their 
last menstrual cycle to determine if they may be pregnant.  If unsure, a pregnancy test 
(urine) may be taken at the screening visit.  If the subject is pregnant, she will be 
excluded from participation.  Subjects will also be advised to avoid becoming pregnant 
during the course of the study by using a medically accepted form of contraception if 
they are sexually active.  If the subject becomes pregnant during the course of the study, 
she will not be treated subsequently with the study device or be required to have follow-
up photographs taken.   
 
All subjects will be asked to maintain their weight by not making any major changes to 
their diet or exercise regimen during the course of the study.  If a subject’s weight change 
is more than 5% at 12 weeks after the final treatment, the subjects’ data will be excluded 
from the primary effectiveness analyses. Subjects who do not maintain their weight 
within 5% will continue in the study, however their data will be excluded from efficacy 
analyses.   
 
Subjects who meet all of the inclusion criteria and none of the exclusion criteria shall be 
eligible to participate in the study and the first treatment will be scheduled. 
3.10. 
Study Enrollment 
Study candidates who sign the informed consent and meet eligibility criteria a and desire 
to be in the study are considered enrolled. 

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ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 25 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
x Subject satisfaction as assessed by questionnaire administered at 12-weeks post-final 
treatment.   
 
3.15. 
Statistical Analysis Plan 
3.15.1. 
Statistical Methods: Overall Plan 
Data will be summarized based on the nature of the data.  Dichotomous (e.g., 
gender, independent photographic review) and ordinal (e.g., Fitzpatrick Skin 
type) data will be tabulated by category.  The mean, standard error, 
maximum and minimum will be tabulated for continuous data (e.g., age,).  
The significance level will be two-sided 0.05 for all statistical tests. 
3.15.2. 
Analysis Population 
Analysis Populations are defined as following: 
Per-protocol Population (PP): 
The Per-protocol Population will consist of all treated subjects followed for 
12 weeks post final treatment and with weight change of no more than five 
percent at the time the 12-week post final treatment images are taken.  Since 
a weight change of more than 5 percent will affect the images, the primary 
efficacy analysis will be performed based on this study population. Subjects 
who do not complete treatment will not be included in the primary and 
secondary efficacy analyses. 
 
As-Treated Population (AT): 
This population consists of all treated subjects regardless of whether they 
become pregnant or undergo weight change during the study.   
 
Safety Population (SA): 
This population will consist of all treated subjects with safety evaluation after 
the treatment.  This population should be identical to the AT population.  The 
safety data analyses will be performed based on the Safety Population. 
 
Sample Size Requirement 

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Part Number: CS-302106 Revision: 02 
Page 27 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
 
3.16. 
Protocol Adherence 
The study investigators are responsible for performing the study in compliance with the 
protocol.   Non-adherence to the protocol is to be classified as a protocol violation or 
protocol deviation, as defined below. 
 
Protocol Violation 
 
Non-adherence to the protocol that may result in significant additional risk to the subject 
(e.g., enrollment of a subject who does not meet the study criteria).  Or, non-adherence to 
Good Clinical Practices (GCP) that may impact patient safety (e.g., failure to obtain 
proper consent prior to performing study procedures).  Violations should be reported to 
the study Sponsor and the IRB within 5 working days if they occur. 
 
Protocol Deviation 
 
Non-adherence to study procedures which does not result in additional risk to the subject 
(e.g., subject missed visit).  Protocol deviations are not required to be reported to the 
IRB; however, they must be recorded on the study case report forms and may be reported 
and reviewed in conjunction with the progress report as part of the annual review process. 
3.17. 
Adverse Events 
Adverse events (AE) will be assessed continuously throughout the study. An adverse 
event is defined as any untoward medical occurrence in a subject, regardless of whether 
the event is related to the device. 
 
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ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 28 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
All AEs and device deficiencies will be recorded on the corresponding CRF for the 
subject. 
 
Adverse Device Effect (ADE) 
 
Any sign, symptom, or disease in a study subject that occurs during the course of a 
clinical trial that is determined by the investigator to have a causal relationship or 
possible causal relationship with the device under investigation. 
 
Device Deficiencies 
 
A device deficiency is defined in accordance with ISO 14155 as inadequacy of a medical 
device including issues with respect to its identity, quality, durability, reliability, safety, 
or performance. Device deficiencies include malfunctions, use errors, and inadequate 
labeling. 
 
If a device deficiency occurs, the investigational site will document the event using the 
CRF. Device deficiencies will be documented throughout the study and appropriately 
managed and reported to regulatory authorities and IRBs as required by Federal 
regulations. 
 
Serious Adverse Event (SAE) 
 
Any untoward medical occurrence in a subject, regardless of whether the event is related 
to the device that: 
 
a. results in death; 
b. results in a life-threatening illness or injury; 
c. results in a permanent impairment of a body structure or body function;  
d. requires in-patient hospitalization or prolongation of existing hospitalization 
e. results in medical or surgical intervention to prevent impairment to body structure or 
function; 
f.    results in fetal distress, fetal death, or a congenital abnormality/birth defect. 
 
Unanticipated Adverse Device Effect (UADE) 
 
Any serious adverse effect on health and safety or any life-threatening problem or death 
caused by, or associated with a device, if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the investigational plan 
or application, or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects.  

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 29 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
 
The Investigator shall be responsible for determination of the causal relationship of all 
adverse events to the device and/or procedure.  The Principal Investigator is responsible 
for monitoring the safety of the subjects enrolled.   
 
The Sponsor is responsible for the ongoing safety evaluation of the product(s). The 
Sponsor shall be responsible for adjudication of all reported adverse events to determine 
whether the event is reportable under federal regulations (i.e., 21 CFR812.150[b][1]). The 
Sponsor will promptly notify all participating investigators and regulatory authorities, as 
appropriate, of findings that could affect adversely the safety of subjects, impact the 
conduct of the trial or alter the IRB’s approval opinion to continue the trial. 
 
3.18. 
Reportable Incidents 
Serious adverse events (SAEs) and unanticipated adverse device effects (UADEs) must 
be recorded and reported to the manufacturer of the study device and to the Sponsor or 
designee within 24 hours of knowledge of the event.  
 
ZELTIQ, an Allergan Affiliate 
4410 Rosewood Drive 
Pleasanton, CA 94588 
 (cell) 
 (office) 
 (fax) 
 
A full reporting of the event shall be provided within 10 working days of the event.  The 
Sponsor is then responsible for notifying the IRB, as required.  
Other adverse events, deemed by the investigator to be non-serious, should be provided 
to the Sponsor as soon as possible and not later than 1 week after knowledge of the event. 
This will be forwarded to the Product Surveillance team within 24 hours of receipt by the 
Sponsor Contact.  
Additional information obtained by the Clinical Site regarding any adverse event, both 
serious and non-serious, will be reported to the Sponsor within 24 hours of awareness.  
PPD
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ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 30 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
4. Study Management and Quality Control  
4.1. 
Study Data Collection   
Standardized Case Report Forms (CRFs) will be provided to all participating sites.  Data 
will be reviewed by the study monitor and Sponsor data management personnel to 
identify inconsistent or missing data and to ensure compliance with the study protocol. 
4.2. 
Confidentiality 
All information and data concerning study subjects will be considered confidential, and 
handled in compliance with all applicable regulations including the requirements of the 
Health Insurance Portability and Accountability Act (HIPAA) of 1996. 
Only authorized site staff, the study Sponsor or the Sponsor’s designee and IRB will have 
access to these confidential files. A unique identification code will be assigned to each 
subject participating in this trial. All data used in the analysis, reporting and publication 
of this clinical trial will be maintained without identifiable reference to the subject. Any 
data that may be published in abstracts, scientific journals, or presented at medical 
meetings will reference a unique subject code and will not reveal the subject’s identity. 
4.3. 
Investigator Responsibilities 
4.3.1. 
General Responsibilities   
Investigators are responsible for ensuring the investigation is conducted 
according to all signed agreements, the Investigational Plan, and applicable 
regulations.  The investigator must protect the rights, safety, privacy and 
welfare of the subjects under the Investigator’s care. Investigators will 
assume overall responsibility and accountability for study site staff and for 
the clinical data obtained during the study.  The investigator assumes all 
responsibilities per applicable regulations, including but not limited to: 
IRB Approval 
The investigator may not begin the study until the governing institutional 
review board (IRB) provides written approval of the study protocol and 
consent form.  The investigator is also responsible for fulfilling any 
conditions of approval imposed by the IRB. 
Informed Consent 
The investigator must ensure that informed consent is obtained from each 
prospective study subject and that the study is not commenced until IRB 
approval has been obtained.   

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 31 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
Device Accountability 
Device accountability is not applicable for this non-significant risk study.  
Financial Disclosure 
Investigators shall provide financial disclosure according to federal 
regulations.  
Study Coordinator 
To assure proper execution of the study protocol, each investigator must 
identify a study coordinator for the site who will work with and under the 
authority of the investigator to assure that study requirements are fulfilled as 
appropriate. 
4.3.2. 
Investigator Records 
The investigator and study staff must maintain accurate, complete, and 
current records relating to the conduct of the investigation.  Records must be 
retained for a period of two years following (1) the date the investigation was 
completed or terminated, or (2) the records are no longer required to support 
a regulatory submission or completion of a product development protocol, 
whichever is longer.  Participating investigators shall maintain the following:  
x All correspondence with the Sponsor, another investigator, the IRB, 
and a monitor 
x Records of all persons authorized to conduct the study (e.g. 
Delegation of Duties/Signature Authorization, CV) 
x Records of receipt, use or disposition of the device 
x Informed Consent documentation for all enrolled subjects 
x Records of each subject's case history, including study-required Case 
Report Forms and source documentation (e.g. physician notes, lab 
reports, study worksheets, clinic charts) 
x All relevant observations of adverse device effects 
x Records of any protocol deviations 
x The condition of each subject upon entering and during the course of 
the investigation and any relevant medical history and results of any 
diagnostic tests 
x Record of each subject’s exposure to the device, including the date 
and time of use 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 32 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
x Investigational plan with all amendments 
x Current IRB approved informed consent and all previously approved 
versions 
x Signed Investigator agreement 
x Investigators will be responsible for the accurate and timely 
completion of CRFs during the trial.   
These records must be available and suitable for inspection at any time by 
Sponsor representatives (monitor), or the reviewing IRB. The Investigator 
will supply access to study-related medical records, original laboratory data, 
and other records and data as they relate to the trial.  The investigator will 
ensure that both he/she and his/her study staff have adequate time and 
resources to devote to the study, including study enrollment, subject 
evaluations, study documentation and site monitoring. 
4.3.3. 
Investigator Reports 
The investigator is responsible for preparation and submission of the 
following reports: 
x Report of any unanticipated adverse device effects shall be submitted 
to the Sponsor within 24 hours and no later than 10 working days 
after the Investigator first learns of the effect. 
x Withdrawal of IRB approval of the investigator’s part in the 
investigation shall be reported to the Sponsor within 5 working days. 
x Progress reports on the investigation to the sponsor, the monitor, and 
the reviewing IRB annually. Alternatively, the Sponsor may prepare 
the report.  
x Deviations from or violations of the investigational plan shall be 
reported to the Sponsor, and the IRB as required. 
x Failure to obtain informed consent prior to use of a device in a subject 
shall be reported to the Sponsor and IRB within 5 working days after 
the use occurs. 
A final report shall be submitted to the Sponsor and IRB within 3 months 
after termination or completion of the investigation, or the investigator’s part 
of the investigation. 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 33 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
4.4. 
Sponsor Responsibilities  
4.4.1. 
General Responsibilities 
As the Sponsor, ZELTIQ assumes overall responsibility for the conduct of 
the study including assurance that the study satisfies FDA regulatory 
requirements. ZELTIQ assumes all responsibilities per applicable 
regulations, and shall: 
IRB approval 
Ensure IRB approval for the investigation. Ensure IRB approval for a 
supplemental application before beginning that portion of the investigation.  
Investigators 
Select investigators qualified by training and experience, and providing them 
with the information they need to conduct the investigation properly.  Obtain 
a signed Investigator Agreement from each participating investigator. Study 
sites will be evaluated to ensure that they have an adequate subject base and 
can provide sufficient staff and documentation support to conduct the study 
properly. 
Monitoring 
Select monitors qualified by training and experience to monitoring the study 
and ensure proper monitoring of the investigation. 
Investigational devices 
Not applicable. This is a non-significant risk study 
Data Management and Analysis 
 
Ensure data collection, verification, analysis, records storage, etc. Sponsor  
will assist with presentation(s) and/or publication(s). 
4.4.2. 
Training 
Study Training 
To ensure uniform data collection and protocol compliance, Sponsor 
personnel will provide an educational session to study site personnel as 
needed, which will cover the protocol, techniques for the identification of 
eligible subjects, data collection and form completion, and the device 
directions for use.  The investigator and study staff will be trained on the 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 34 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
study device and protocol, applicable regulations and requirements, and 
expectations of the study, enrollment expectations, subject selection, 
informed consent, required clinical data and record keeping, etc.   
Device Use and Procedure 
 
Representatives of the Sponsor will train study site staff in use of the study 
device.  Sponsor representatives may be present at study procedures. 
4.4.3. 
Monitoring 
The Sponsor will ensure that qualified clinical monitors are available to 
monitor and oversee the conduct of the trial and that monitoring is performed 
in accordance with the Sponsor’s approved procedures or third-party 
procedures approved by the Sponsor.  
The clinical monitors will evaluate compliance with the protocol, any 
specific recommendations made by the site’s IRB and the signed Investigator 
Agreement.   
Site Qualification Visit 
A pre-study meeting will occur with the study site to evaluate the site’s 
qualification to conduct the study.  
Monitoring Visits 
On-site monitoring visits will assess the progress of the clinical study and 
identify any concerns that result from device performance or review of the 
investigator’s study records, study management documents, and informed 
consent documents.   
Monitoring will ensure continued protocol compliance, accurate data 
reporting, and adequate accounting of shipments of study devices. 
Monitoring visits will occur after enrollment of every 10 subjects and at a 
minimum one more visit before study close-out. 
During monitoring visits, the monitor will compare subject records and other 
supporting documents with reports at the site to determine that: 
x The facilities used by the investigation continue to be acceptable for 
the purposes of the clinical study. 
x Informed consent was properly obtained and documented for all 
enrolled study participants. 
x The Investigational Plan is being followed, and only eligible subjects 
are being enrolled into the study. 

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 35 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
x Deviations to the Investigational Plan have been reported to ZELTIQ 
and the IRB, as appropriate. 
x Adverse events are promptly being reported. 
x Information recorded in the case report forms and study reports are 
accurate, complete, legible and consistent with source documentation. 
x Subjects failing to complete the clinical study and the reason for 
failure are recorded. 
x Missed follow-up visits are noted in the study documentation.   
Study Site Closeout   
At the close of the study at a clinical site, the monitor will conduct site close 
out per Sponsor’s standard procedure.  
4.4.4. 
Final Report  
A final report will be prepared at the conclusion of the trial. A copy of the 
final report will be provided to each investigator and to the respective IRBs. 
4.4.5. 
Trial Registration  
Prior to study initiation, the trial will be registered on a publicly accessible 
study database such as clinicaltrials.gov when applicable. 
5. Data Ownership 
ZELTIQ, the study Sponsor, retains ownership of all data generated in this study, and controls 
the use of the data for purposes of regulatory submissions to the US and/or other governments. 
Investigator(s) and institution(s) (which shall include their employees, agents, and 
representatives) may not issue or disseminate any press release or statement, nor initiate any 
communication of information regarding this study (written or oral) to the communications 
media or third parties without the prior written consent of the Sponsor.  
CCI

CCI

CCI

CCI

ZELTIQ Aesthetics – Confidential and Proprietary  
 
 
Part Number: CS-302106 Revision: 02 
Page 39 of 39 
Title: Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis 
Followed by Radiofrequency Treatment for Submental and Submandibular 
Contouring 
 
 
ZELTIQ P/N: CS-302106-02 
Protocol Number: ZA18-002 
This document and the contents hereof are considered proprietary and confidential information of ZELTIQ Aesthetics, Inc. 
Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without prior written consent of 
ZELTIQ. 
8. References 
1. Kilmer, S. L, Burns, A. J., Zelickson, B. D. (2016). Safety and Efficacy of Cryolipolysis 
for Non-Invasive Reduction of Submental Fat. Lasers Surg Med. 48(1), 3-13.  
2. Bernstein, E. F. & Bloom, J. D. (2017). Safety and Efficacy of Bilateral Submental 
Cryolipolysis with Quantified Three-Dimensional Imaging of Fat Reduction and Skin 
Tightening. JAMA Facial Plastic Surgery. April 2017.  
3. Suh, D. H., Park, J. H., Jung, H. K., et al. (2017). Cryolipolysis for submental fat 
reduction in Asians. Journal of Cosmetic and Laser Therapy.  
4. Fitzpatrick R, Geronemus R, Goldberg D, Kaminer M, et al. Multicenter study of 
noninvasive radiofrequency for periorbital tissue tightening.  Lasers Surg Med. 
2003;33:232-42. 
5. Carruthers J, Fabi S, Weiss R.  Monopolar Radiofrequency for Skin Tightening: Our 
Experience and a Review of the Literature.  Dermatol Surg. 2014;40:S168-S173. 
Signature:
Email:
PPD

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