A Single-Center, Prospective Study to Evaluate the Safety and Effectiveness of Multi-Treatment Regimen With Zeltiq Aesthetics, Inc. Rapid Acoustic Pulse (RAP)™ Device for the Improvement in the Appearance of Cellulite
Phase: PHASE4
Conditions: Cellulite
Sponsor: Zeltiq Aesthetics



 
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CONFIDENTIALITY STATEMENT 
This document contains confidential information that is the property of ZELTIQ 
Aesthetics, Inc., and may not be disclosed to anyone other than the recipient clinical 
Investigator or his or her staff.  
This information cannot be used for any purpose other than the evaluation and conduct of 
the clinical investigation without the prior written consent of ZELTIQ Aesthetics, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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TABLE OF CONTENTS 
 
CLINICAL SITE ....................................................................................................................................... 6 
STUDY SYNOPSIS ................................................................................................................................... 7 
INTRODUCTION .................................................................................................................................. 11 
OVERVIEW ........................................................................................................................................................... 11 
CELLULITE .......................................................................................................................................................... 11 
ZELTIQ AESTHETICS, INC.’S RAPID ACOUSTIC PULSE (RAP) DEVICE WITH CELLULITE 
CARTRIDGE ......................................................................................................................................................... 12 
PHYSICAL EFFECTS.......................................................................................................................................... 12 
PROOF OF CONCEPT (POC) OF SAFETY AND TOLERABILITY OF RAP CELLULITE 
CLINICAL TRIAL ............................................................................................................................................... 13 
SAFETY CONCLUSION ..................................................................................................................................... 13 
PIVOTAL STUDY OF SAFETY AND EFFICACY OF RAP CELLULITE CLINICAL TRIAL ............ 13 
PROTOCOL 2021-06 STUDY OBJECTIVES AND ENDPOINTS .............................................................. 14 
STUDY DESIGN .................................................................................................................................... 17 
SELECTION OF STUDY POPULATION ......................................................................................................... 18 
INCLUSION CRITERIA ...................................................................................................................................... 18 
EXCLUSION CRITERIA .................................................................................................................................... 18 
STUDY VISITS ..................................................................................................................................................... 19 
VISIT 1 BASELINE SCREENING AND CONSENT FORM (DAY -30 TO DAY 0) ................................ 19 
VISIT 2 TREATMENT ........................................................................................................................................ 20 
VISIT 3 FOLLOW UP VISIT 4-WEEKS POST 1ST TREATMENT (+/- 14 DAYS) AND 2ND 
TREATMENT ........................................................................................................................................................ 20 
VISIT 4 FOLLOW UP VISIT 12-WEEKS POST 2ND TREATMENT (+/- 14 DAYS) AND 3RD 
TREATMENT ........................................................................................................................................................ 21 
VISIT 5 FOLLOW UP VISIT 12- WEEKS POST 3RD TREATMENT (+/- 14 DAYS) ........................... 22 
VISIT 6 FOLLOW UP VISIT 26- WEEKS POST 3RD TREATMENT (+/- 14 DAYS) ......................... 22 
VISIT 7 FOLLOW UP VISIT 52- WEEKS POST 3RDTREATMENT (+/- 14 DAYS) ............................ 22 
RISKS AND BENEFITS ...................................................................................................................... 23 
CLINICAL BENEFIT........................................................................................................................................... 23 
KNOWN PHYSIOLOGICAL RESPONSES OF RAP TREATMENT ......................................................... 23 
RISK MITIGATIONS .......................................................................................................................................... 25 
REPORTING ADVERSE EVENTS AND COMPLICATIONS ................................................ 25 
ADVERSE EVENTS ............................................................................................................................................. 25 
DEVICE MALFUNCTIONS................................................................................................................................ 28 
STUDY PARTICIPANT INFORMED CONSENT ....................................................................... 28 
RECORDS MANAGEMENT ............................................................................................................. 29 
INVESTIGATIONAL DEVICE ACCOUNTABILITY AND STORAGE .............................. 30 
REGULATORY AND ETHICAL COMPLIANCE ...................................................................... 30 
QUALITY ASSURANCE AND MONITORING ........................................................................... 31 
STUDY RESULTS/ANALYSIS .......................................................................................................... 31 
SUSPENSION OR PREMATURE TERMINATION OF STUDY ............................................ 32 
PUBLICATION POLICY .................................................................................................................... 32 
STUDY COMPLETION ....................................................................................................................... 32 
THE IRB MUST BE NOTIFIED OF COMPLETION OF THIS STUDY. ......................................... 32 

 
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REFERENCES ....................................................................................................................................... 33 
TABLES .................................................................................................................................................... 34 
TIMELINE AND EVENTS SCHEDULE ........................................................................................................... 34 
STUDY SCALES AND ASSESSMENTS ......................................................................................... 35 
 
 
 
 
 
 
 
 
 

 
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INVESTIGATOR’S STATEMENT OF AGREEMENT 
I have read the foregoing protocol and agree that it contains all necessary details for 
conducting the study. I will conduct the study as outlined herein and will complete the 
study within the time designated. 
I agree to conduct this protocol in accordance with local regulations, external standards 
and applicable ICH and Good Clinical Practice (GCP) guidelines. 
I will provide copies of the protocol, including any amendments, 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 
ZELTIQ Aesthetics, Inc. device and the conduct of the study.  
I further agree to provide access to ZELTIQ Aesthetics Inc, its designees, or regulatory 
authorities to any source documents from which case report form information may have 
been generated.  
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.  
 
 
_______________________________________________________________ 
 
 
Principal Investigator  
(Print name) 
 
__________________________________  
______________________ 
Principal Investigator   
 
 
            Date  
(Principal Investigator’s signature) 
 
 
 
 
 

 
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STUDY SYNOPSIS 
Purpose 
The purpose of this single-site clinical study is to evaluate the 
safety and effectiveness of three (3) treatments sessions with the 
ZELTIQ Aesthetics, Inc. Rapid Acoustic Pulse (RAP) device for 
the improvement in the appearance of cellulite.
Primary 
Effectiveness 
Objective 
 RAP treatment effectiveness: The primary effectiveness 
objective will demonstrate improvement in the appearance of 
cellulite as determined by correct identification of baseline vs 
12-weeks post final treatment images 
 
 by at least 2 of 3 blinded 
independent physician reviewers (IPR). 
Primary Safety 
Objective 
 
 RAP treatment safety: The primary safety objective is to 
evaluate the safety of the RAP (Rapid Acoustic Pulse) device 
for cellulite treatments through the monitoring of the 
incidence of adverse events (AEs) and adverse device effects 
(ADEs); serious adverse events (SAEs) and SADEs (serious 
adverse device effects) and pain assessments.
Secondary 
Effectiveness 
Objective 
 RAP treatment effectiveness: The secondary effectiveness 
objective is to demonstrate the improvement in the 
appearance of cellulite as determined by the study 
participants selecting “Agree” or “Strongly Agree” as 
answers to the Participant Satisfaction Survey (Assessment 
3):  when comparing side-by-side before and after 
photographs.
Test Device 
ZELTIQ Aesthetics, Inc. Rapid Acoustic Pulse (RAP) device.
Treatment 
Each cellulite treatment session will consist of RAP treatment 
 to bilateral thigh and/or buttock areas using 
the same treatment settings for both sides.  
The participants will have three (3) separate cellulite treatment 
sessions. The second treatment session will occur four (4) weeks 
post the initial treatment. The third treatment session will occur 
twelve (12) weeks post the second treatment.
Control  
For each cellulite treatment area, the pre-treatment photos of the 
thighs and/or buttocks area will serve as a control. 
Study Design 
Non-significant risk, single-site, prospective clinical trial.
Planned Number 
of Sites / 
Countries 
One clinical trial site located in the United States. 
 

 
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Inclusion Criteria 
 Healthy candidates ages 18-50 years. 
 Seeking treatment of cellulite in the thigh and/or buttock 
areas. 
 Areas of moderate to severe cellulite on bilateral thigh and/or 
buttock using the Cellulite Dimple – At Rest Scale at Baseline 
with grades of 2 or 3 based on review of photos taken under 
the same lightening conditions planned for the trial. 
 Participant will not have had minimally invasive, invasive, or 
energy-based cellulite (liposuction, subcision, RF, laser, 
ESWT, cryo-lipolysis, muscle stimulation, etc.) treatments in 
the treatment areas in the prior 12 months. 
 Participant will not have used topical based cellulite 
treatments for prior 3 months and will not use during the trial. 
 Participant will not have used spray-on tanning treatments for 
3 months prior to or during the term of the trial.  
 Participant must be able to provide written informed consent, 
understand and is willing to comply with all study-related 
procedures and follow-up visits.  
 
Exclusion Criteria 
 
 Participant is unwilling to have research photos and/or videos 
taken of treatment areas in the presence of or by Sponsor’s 
research team. 
 Participant is unwilling to have RAP treatment provided in the 
presence of Sponsor’s research team. 
 Participant is pregnant or planning to become pregnant during 
the duration of the study. 
 Participant is unwilling to commit to follow-up visits. 

 
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 Metal or plastic implants (vascular stent, or implants in the 
hips, knees, etc.) in the treatment areas. 
 Active electronic implants such as pacemakers and 
defibrillators.  
 History of coagulopathy and/or on anticoagulant medication. 
 Skin disorders (skin infections or rashes, psoriasis, etc.) in the 
treatment areas. 
 Medical disorder that would hinder wound healing or immune 
response.  
 Any surgical procedure in the treatment areas in the prior 3 
months or planned during the duration of the study. 
 Any other condition/disease/situation which, as deemed by 
the PI, would preclude participant from safely participating in 
or completing the study visits or that may confound study 
results. 
 
INTRODUCTION 
Overview 
 
The Rapid Acoustic Pulse (RAP) is an electrohydraulic (EH) device designed to improve 
the appearance of cellulite. Devices using RAP technology have been successfully used in 
seven human clinical trials to accelerate laser-based tattoo removal, a proof of concept 
(POC) and pivotal clinical trials to improve the appearance of cellulite without the 
occurrence of device related UAEs or SAEs. The purpose of this single-site, multi-
treatment clinical study is to evaluate the safety and effectiveness of ZELTIQ Aesthetics, 
Inc.’s Rapid Acoustic Pulse (RAP) device for the improvement of cellulite.  
Cellulite 
 
Cellulite is the often aesthetically displeasing rippling or dimpling of the skin most 
commonly located on the thighs and buttocks of women. Its appearance and texture are 
often likened by laypeople to that of “cottage cheese” or an orange peel [1].  
In a paper discussing anatomical approaches to treating cellulite by Christman et al [1], “In 
normal skin, there is a support network of fibrous septa running through the subcutis, 
separating the adipose cells into chambers resembling a quilt. Magnetic resonance imaging 
demonstrates that in cellulite, these fibrous septa are contracted and sclerosed, ultimately 
tethering the skin at a fixed length. Concurrently, the adipose cells expand with weight gain 
or water absorption, promoting herniation, or outpouching of fat into the dermis. This 
results in skin dimpling creating the characteristic cellulite appearance. Two distinct 
morphologies of cellulite may be identified, sometimes coexisting in the same patient: 1) 
diffuse rippling in patients with increased adiposity and/or increased skin laxity and 2) 
dimpling, with discrete ellipsoid or linear depressions, in patients with good skin tone [1].” 

 
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STUDY DESIGN 
This is a non-significant risk, single-center, prospective trial for safety, and effectiveness 
using ZELTIQ Aesthetics, Inc.’s RAP device for the improvement in the appearance of 
cellulite performed at 1 clinical research site in the United States. 
Up to fifteen (15) healthy participants between the age of 18-50 will be enrolled in this 
study. 

 
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Participants who sign the informed consent form and meet all the eligibility criteria will be 
enrolled in the study. Each participant will undergo acoustic rapid pulse (RAP) treatments 
on both of their thighs and/or buttocks.  
Total study duration is anticipated to be at or less than 72 weeks from the first participant 
visit to the last participant observation visit. A total of up to 7 visits are planned for this 
study 
.  
Selection of Study Population 
 
The clinical study can fulfill its objectives only if appropriate participants are enrolled. 
The following criteria are designed to select participants for whom protocol requirements 
are considered appropriate. 
Participants who meet all inclusion criteria and none of the exclusion criteria will be 
enrolled in the study and assigned a participant No./ID in sequential order (i.e., 01, 02, 03, 
etc.) 
Inclusion Criteria 
 
 Healthy candidates ages 18-50 years 
 Seeking treatment of cellulite in the thigh and/or buttock areas 
 Areas of moderate to severe cellulite on bilateral thigh and/or buttock using the 
Cellulite Dimple – At Rest Scale at Baseline with grades of 2 or 3 based on review of 
photos taken under the same lightening conditions planned for the trial. 
 Participant will not have had minimally invasive, invasive or energy-based cellulite 
(liposuction, subcision, RF, laser, ESWT, cryo-lipolysis, muscle stimulation, etc.) 
treatments in the treatment areas in the prior 12 months. 
 Participant will not have used topical based cellulite treatments for prior 3 months and 
will not use during the trial. 
 Participant will not have used spray-on tanning treatments for 3 months prior to or 
during the term of the trial.  
 Participant must be able to provide written informed consent, understand and is willing 
to comply with all study-related procedures and follow-up visits.  
 
Exclusion Criteria 
 
 Participant is unwilling to have research photos and/or videos taken of treatment areas 
in the presence of Sponsor’s research team. 
 Participant is unwilling to have RAP treatment provided in the presence of Sponsor’s 
research team. 
 Participant is pregnant or planning to become pregnant during the duration of the study. 
 Participant is unwilling to commit to follow-up visits. 

 
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Visit 2 Treatment  
Pre-treatment Activities 
 Review concomitant medication 
 Take vital signs  
 Urine pregnancy test for women of childbearing potential 
 Adverse event evaluation  
 Confirm eligibility 
 
 
 2DPhotos of the treatment area taken pre and post marking  
 
 
Note: Visits 1 and 2 may be combined if feasible at time of screening and enrollment. 
Treatment 
 Administer treatment in accordance with Treatment Recommendations (See Appendix 
A, Treatment Recommendations) 
 
 
Immediate Post-Treatment Activities 
 Adverse event evaluation 
 
 
Visit 3 Follow Up Visit 4-Weeks Post 1st Treatment (+/- 14 days) and 2nd 
Treatment 
Pre-treatment Activities 
 Review concomitant medication 
 Take vital signs  
 Weight 
 Urine pregnancy test for women of childbearing potential 
 Adverse event evaluation  
 Confirm eligibility 
 Collect Diary – Treatment 1 
 
 
2D Photos of the treatment area taken pre and post marking 

 
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Visit 5 Follow Up Visit 12- Weeks Post 3rd Treatment (+/- 14 days)  
 Weight  
 Review concomitant medication  
 Adverse Event evaluation 
 
 
 2D Photos of the treatment area  
 
  
Visit 6 Follow Up Visit 26- Weeks Post 3rd Treatment (+/- 14 days)  
 Weight  
 Review concomitant medication  
 Adverse Event evaluation 
 Review Participant Pre and Post Treatment Instructions 
 2D Photos of the treatment area  
 
Visit 7 Follow Up Visit 52- Weeks Post 3rdTreatment (+/- 14 days)  
 Weight  
 Review concomitant medication 
 Adverse Event evaluation 
 2D Photos of the treatment area  
 
* Local, national, or federal holidays may occur during the timeframe of this study, which 
may alter the follow up dates. 
PHOTOGRAPHY 
Baseline photographs will be taken under standardized lighting and equipment settings. 

 
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UNSCHEDULED VISITS 
An unscheduled visit may be performed at any time during the study at the participant’s 
request or as deemed necessary by the study investigator. The date and reason for the visit 
will be recorded in the source document.  
 
PARTICIPANT WITHDRAWALAND EARLY TERMINATION 
Participants may withdraw from the study at any time at their own request or withdrawn 
from at any time at the discretion of the Investigator for safety, behavioral, or 
administrative reasons. The Investigator should inquire about reason for withdrawal, 
request the participant to return for a final visit, and follow up with any unresolved adverse 
events. The Investigator should notify the Sponsor of any participants withdrawal or 
discontinuance.  
RISKS AND BENEFITS 
Clinical Benefit 
There is no clinical benefit in this study. The participant may experience an improvement 
in the aesthetic appearance of the treated areas. 
 

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Risk Mitigations 
 
The Investigator in this clinical study has been invited to participate in this study based 
on his/her previous experience with the use of energy-based systems and other novel 
modalities in aesthetic dermatology and plastic surgery. Experience with cosmetic 
treatments is the most critical element in managing participant risk in this trial. All other 
known risks will be disclosed to the participant via the informed consent process. Risks 
have been mitigated by the specific design employed in manufacturing the device. 
 
REPORTING ADVERSE EVENTS AND COMPLICATIONS 
Adverse Events 
 
The Investigator is responsible for the detection and documentation of events meeting the 
criteria and definition of an AE or SAE, as provided in this protocol. During the study when 
there is a safety evaluation, the Investigator or site staff will be responsible for detecting, 
documenting, and reporting AEs and SAEs as detailed in this Section of the protocol. 
At the treatment and follow-up visits, participants will be assessed for known physiological 
responses and adverse events.  
Adverse Event (AE) 
o An adverse event (AE) is defined as any unfavorable or unintended sign, 
symptom, or disease that occurs or is reported by the participant to have 
occurred, or a worsening of a pre-existing condition. An adverse event may or 
may not be related to the study treatment.  
o AEs will be elicited through direct questioning and participant reports. Any 
abnormality in physical examination findings that the investigator believes is 
clinically significant (CS) to the research participant and that occurred after 
initiation of the first study treatment will be reported as AEs. Abnormal findings 
that are NOT clinically significant should not be recorded as an AE. 
Adverse Device Effect (ADE) 
o An ADE is defined as an adverse event related to the use of an investigational 
medical device. This definition includes any adverse events resulting from 
insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical 

 
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device as well as any event resulting from use error or from intentional misuse 
of the investigational medical device. This includes “comparator” if the 
comparator is a medical device. 
1. Reporting of Adverse Events 
o Report initiation for all AEs and SAEs will begin at the time of the first 
treatment and continue until the end of the final study observation visit. All 
events will be followed to resolution or until the participant completes the study. 
A final assessment of outcome will be made at that time.  
o All AEs must be recorded in the participant’s medical records and in the case 
report form. AEs will be reported using customary medical terminology along 
with the following information: the onset and end dates, whether the event is an 
SAE, the impact the event had on study treatment, the severity of the event, the 
causality of the event, whether treatment was given as a result of the event, and 
the outcome of the event. 
2. Impact on Study Treatment 
o The impact the event had on the study treatment will be assessed as either: none, 
study treatment interrupted, study treatment discontinued, or not applicable. 
The “not applicable” assessment will be used only when the participant is in the 
observation phase of the protocol. 
3. Causality Assessment 
o AEs will be assigned a relationship (causality) to the study treatment. The 
Investigator will be responsible for determining the relationship between an AE 
and the study treatment. The type of event, organ system affected, and timing 
of onset of the event will be factors in assessing the likelihood that an AE is 
related to the study treatment. Relationship of AEs to study treatment will be 
classified as follows: 
i. Definitely related: This category applies to those AEs that the 
Investigator feels are incontrovertibly related to the study treatment.  An 
AE may be assigned an attribution of definitely related if or when it 
meets all of the following criteria: (1) it follows a reasonable temporal 
sequence from administration of the study treatment; (2) it could not be 
reasonably explained by the known characteristics of the participant’s 
clinical state, environmental or toxic factors, or other modes of therapy 
administered to the participant; (3) it follows a known response pattern 
to treatment with the study treatment. 
ii. Probably related: This category applies to those AEs which, after careful 
medical consideration at the time they are evaluated, are felt with a high 
degree of certainty to be related to the study treatment. An AE may be 
considered probable if or when (must have three): (1) it follows a 
reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by participant’s 
clinical state, environmental or toxic factors, or other therapies 
administered to the participant. (3) Disappears or is decreased upon 

 
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discontinuation of the study treatment. (4) It follows a known response 
pattern to treatment with the study treatment.  
iii. Possibly related: This category applies to those AEs which, after careful 
medical consideration at the time they are evaluated, are judged unlikely 
but cannot be ruled out with certainty to the study treatment. An AE 
may be considered possible if or when (must have two): (1) it follows a 
reasonable temporal sequence from administration of the study 
treatment. (2) It could not readily have been produced by participant’s 
clinical state, environmental or toxic factors, or other therapies 
administered to the participant. (3) Disappears or is decreased upon 
discontinuation of the study treatment. (4) It follows a known response 
pattern to treatment with the study treatment.  
iv. Remotely related: In general, this category can be considered applicable 
to those AEs which, after careful medical consideration at the time they 
are evaluated, are judged likely to be unrelated to the study treatment. 
An AE may be considered unlikely if or when (must have two): (1) it 
does not follow a reasonable temporal sequence from administration of 
the study treatment. (2) It could not readily have been produced by 
participant’s clinical state, environmental or toxic factors, or other 
therapies administered to the participant. (3) Disappears or is decreased 
upon discontinuation of the study treatment. (4) It does not follow a 
known response pattern to treatment with the study treatment.  
v. Unrelated: This category applies to those AEs which, after careful 
consideration at the time they are evaluated, are clearly and 
incontrovertibly due to extraneous causes (disease, environment, etc.) 
and determined with certainty to have no relationship to the study 
treatment. 
4. Outcome Assessment 
o The outcome of the event will be assessed as either: resolved, resolved with 
sequelae, ongoing, or death. Only one AE per participant is allowed to have an 
outcome assessment as “death.”  If there are multiple causes of death for a given 
participant, only the primary cause of death will have an outcome of death. 
5. Serious Adverse Events 
o A Serious Adverse Event (SAE) is defined as any AE that: 
i. Results in death 
ii. Is life threatening (the participant is at immediate risk of dying from the 
adverse experience) 
iii. Requires participant hospitalization or prolongs existing hospitalization 
iv. Results in persistent or significant disability/incapacity 

 
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the scope of the study. It is the Investigator’s or designee’s responsibility to ensure that 
participants understand that participation in the study is voluntary, and that the quality of 
their medical care will not be adversely affected if they decline to participate in the study. 
Adequate time for any questions and explanations will be provided. Participant will have 
the opportunity to discuss the study with their surrogates and have time to think about it 
prior to participating. Participants may withdraw their consent at any time throughout the 
course of treatment. Once the participant understands the informed consent, he/she will be 
allowed to voluntarily agree to participate by signing the document. The 
investigator/designee is responsible for obtaining informed consent prior to enrollment in 
the study and ensuring that participant have a copy of the document for their records. The 
participant is considered enrolled in the study after the informed consent has been signed 
and it has been verified that the participant meets all inclusion criteria and none of the 
exclusion criteria.  
RECORDS MANAGEMENT  
Study Records Retention: Each site will maintain appropriate medical records for 
this study in accordance with institutional requirements including, but not limited to, 
hospital records, laboratory tests, pharmacy dispensing records, x-rays, and clinical charts. 
As part of study participation, each site will permit the Sponsor ZELTIQ Aesthetics, Inc., 
or its designee, to examine (and when required by applicable law, to copy) clinical records 
for the purposes of quality assurance reviews, audits and evaluation of study safety and 
progress. 
i. Essential documents, as listed below, must be retained by the site until at least 
2 years after completion or termination of the investigation, or longer if 
advised by the Sponsor or designee.  
ii. If the Investigator relocates, retires, or for any reason cannot keep study 
records, the records may be transferred to an acceptable designee. The 
Sponsor or its designee must be notified in writing of the name, address, and 
telephone number of the person designated to retain the study records. By 
signing the protocol, the Investigator agrees to adhere to the document 
retention procedures. 
iii. Essential documents may include: 
1. IRB approvals for the study protocol and all amendments 
2. Participant’s informed consent forms 
3. All source documents 
4. Case Report Forms 
5. Data change forms or data queries 
6. Monitoring logs and appointment schedules 
7. Investigators CVs, medical license information, and financial 
disclosure documentation 

 
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8. All sponsor representative/investigator correspondence, including 
telephone logs 
9. Any other pertinent study documents 
Protocol Deviations: Protocol deviations occur when there are variations in the 
approved study protocol, criteria, or procedure. An example of this would be a participant 
visit conducted outside the follow-up schedule. As protocol deviations may increase the 
risk or decrease the benefit of the intervention and/or affect the participant’s rights, safety, 
welfare and/or integrity of the resultant data, investigators are required to record and report 
all incidences in a deviation log for adjudication during data analysis. 
iv. All protocol deviations must be reported to Sponsor in a timely manner of 
their occurrence. Evaluation of the deviation and its impact on the study 
protocol will be adjudicated on a case-by-case basis. Data discrepancies or 
questions resulting from reported protocol deviations will be managed 
between Sponsor and the site investigator or their designee. 
Protocol Violation: A violation is any non-adherence to the protocol that may result 
in significant additional risk to the participant (e.g., enrollment of a participant who does 
not meet the study criteria). A protocol violation can also be an event of non-adherence to 
GCPs that may impact participant safety (e.g., failure to obtain proper consent before 
performing study procedures). Violations should be reported to the study sponsor and the 
IRB within 5 working days if they occur. 
INVESTIGATIONAL DEVICE ACCOUNTABILITY AND STORAGE 
The Sponsor will maintain full device accountability. The Investigator will maintain 
adequate records documenting all materials received and returned, and shipping 
information of the device. All used materials will be discarded by the Investigator after 
each treatment has been completed. 
 
REGULATORY AND ETHICAL COMPLIANCE  
1. The Study will comply with all instructions, regulations, and agreements in this 
protocol. In addition, the study will comply with all local regulations, external 
standards and applicable ICH and Good Clinical Practice (GCP) guidelines. 
 
2. Institutional Review Board: The site that is participating in this study must have this 
protocol and the associated informed consent approved through the IRB. Any 
amendments to the protocol or informed consent will be routed through IRB for 
approval prior to use.  
 
3. Participant Confidentiality: Participant confidentiality for all data collected during the 
course of treatment will be maintained by the Investigator, on-site staff, and the 
Sponsor. All pictures of the participant’s test areas will be de-identified, secure, 
privileged, and compliant with all HIPAA guidelines. A unique participant 
identification (ID) code will be assigned to each participant in the study. This ID code 
will be used throughout the course of treatment to ensure that no identifying 

 
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information exists on any Case Report Forms. The document which contains the 
participant ID key will be stored in a locked cabinet and will only be accessible by 
authorized study personnel. Private and confidential information about each participant 
will be preserved in any report or publication of the clinical investigation data. 
 
4. Investigator Conflict of Interest: The proposed study will be conducted in accordance 
with signed investigator statements.  
 
5. Funding Source: Funding for this study is provided by ZELTIQ Aesthetics, Inc. 
 
6. Changes to Final Protocol: ZELTIQ Aesthetics, Inc. may amend the protocol at any 
time. All protocol modifications that could potentially affect data collection practices, 
study scope, participant safety, or scientific quality will be submitted to the IRB for 
approval prior to implementing the changes.  
QUALITY ASSURANCE AND MONITORING  
All participant data will be entered into a study database created and controlled by ZELTIQ 
Aesthetics, Inc.  
The Sponsor will train the study site and be present at the initiation of treatment. The 
Sponsor will monitor the site at various intervals during the study. Monitoring activities 
may be on site or remote. Case Report Forms and source documents will be reviewed to 
verify adherence to the protocol; for completeness, accuracy, and consistency of data; and 
adhere to local regulations on the conduct of clinical research. The Sponsor will collect 
data throughout the study and at the end of the follow up period. 
The investigational site will provide direct access to all trial-related site’s source 
data/documents, and reports for the purpose of monitoring and auditing by ZELTIQ 
Aesthetics, Inc. or designee, and inspection by local and regulatory authorities (as 
appropriate). 
The investigational site will have established standard operating procedures (SOPs) for 
quality management. Data will be evaluated for compliance with the protocol and accuracy 
in relation to source documents. The study will be conducted in accordance with 
procedures identified in the protocol.  
The data and any research conducted will be controlled by ZELTIQ Aesthetics, Inc. 
STUDY RESULTS/ANALYSIS 
Sample Size Determination: Up to fifteen (15) participants will be enrolled and 
treated in this study. The sample size is based on clinical and practical exploratory 
considerations and not a formal statistical power. 
Demographics and Baseline Characteristics: Demographic and baseline 
characteristics will include age, sex, ethnicity, race, gender identity, height, and weight, 
Fitzpatrick Skin Type, and Cellulite Dimple assessment of bilateral posterior thighs 
and/or buttocks.  

 
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Study Analysis Populations: The Full Analysis Set (FAS) will include all 
participants who meet all the inclusion and none of the exclusion criteria, received 
assigned three treatments with the device and completed the 12-week, follow-up visits 
per the protocol. The FAS will be treated as the primary analysis set.  
Effectiveness Parameter Analysis: Descriptive statistics will be performed on the 
population per protocol, all participants completing the study without major protocol 
deviations. Descriptive statistics (i.e., mean, standard deviation, etc.) will be provided for 
all continuous variables, percentages and frequencies for all categorical variables 
collected in this study.  
Summary tables will be used to present population characteristics at Baseline. For 
categorical parameters, the number and percentage of participants in each category will 
be presented. The denominator for percentage will be based on the number of participants 
appropriate for the purpose of analysis. For continuous parameters, descriptive statistics 
will include n (number of participants), mean, standard deviation, median, and range. No 
imputation will be used to account for missing data. No processing for outliers will be 
performed. Data will be presented as reported on the CRF. 
Safety Analysis: The Safety Analysis Set will consist of all enrolled participants who 
receive RAP treatment (started or completed).  
Safety analyses will be performed in terms of incidence and severity of adverse events. 
These will be tabulated and a complete listing of all reports of adverse and/or 
unanticipated events will be presented.  
SUSPENSION OR PREMATURE TERMINATION OF STUDY 
The Sponsor reserves the right to suspend or prematurely terminate the study in its entirety 
or at an investigational site for significant and documented reasons. An Investigator, IRB, 
or regulatory authority may suspend or prematurely terminate participation in the clinical 
investigation for which they are responsible at any time in collaboration with the Sponsor. 
PUBLICATION POLICY   
Any investigator who wishes to develop a publication or presentation based on the results 
from this study must obtain written approval from ZELTIQ Aesthetics, Inc. prior to 
submission. ZELTIQ Aesthetics, Inc. may grant the investigator the freedom to publish 
any scientific or medical results deemed by the author to be of medical or scientific 
significance, provided that the information is scientifically sound, does not duplicate a 
previous or already planned publication, and is not being released prematurely. 
STUDY COMPLETION 
The IRB must be notified of completion of this study.

 
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REFERENCES 
 
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approach to evaluating and treating ccellulite," J Drugs Dermatol , vol. 16, no. 1, pp. 
58-61, 2017. 
[2] M. Lokhandwalla, J. A. McAteer, J. C. Williams and B. Sturtevant, "Mechanical 
haemolysis in shock wave lithotripsy (SWL): II. In vitro cell lysis due to shear," 
Phys. Med. Biol. , vol. 46, p. 1245–1264, 2001. 
[3] J. B. Freund, T. Colonius and A. P. Evan, "A cumulative shear mechanism for tissue 
damage initiation in shock-wave lithotripsy," Ultrasound Med Biol. , vol. 33, no. 9, 
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[4] D. Howard and B. Sturtevant, "In vitro study of the mechanical effects of shock-
wave lithotripsy," Ultrasound in Med. & Biol., vol. 23, no. 7, pp. 1017-1122, 1997. 
[5] H. Jookaki and M. V. Panzer, "Skin mechanical properties and modeling: A review," 
Proc IMechE Part H: J Engineering in Medicine, 2018. 
[6] D. Hexsel, S. Fabi, G. Sattler, R. Bartsch and e. al, "Validated assessment scales for 
cellulite dimples on the buttocks and thighs in female patients," Dermatologic 
Surgery, 2019. 
[7] M. S. Kaminer, W. P. Coleman, R. A. Weiss, D. M. Robinson, W. P. Coleman and 
C. Hornfeld, "Multicenter pivotal study of vacuum-assisted precise tissue release for 
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[8] T. A. Perry, R. Avelar, J. Schwab, Z. Dominguez and et al, "Devices and methods 
for reducing the appearance of cellulite". US Patent 10117892, 6 Nov 2018.
[9] A. C. Elliot, WINKS SDA Statisical Data Analysis, CreateSpace Independent 
Publishing Platform; 7th edition, 2013. 
 
 
 
 

 
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