A Multi-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 
INVESTIGATOR’S STATEMENT OF AGREEMENT ................................................................. 5 
CLINICAL SITES..................................................................................................................................... 6 
STUDY SYNOPSIS ................................................................................................................................... 7 
INTRODUCTION .................................................................................................................................. 11 
OVERVIEW ........................................................................................................................................................... 11 
CELLULITE .......................................................................................................................................................... 11 
ZELTIQ AESTHETICS, INC.’S RAPID ACOUSTIC PULSE (RAP) DEVICE WITH CELLULITE 
CARTRIDGE ......................................................................................................................................................... 11 
PHYSICAL EFFECTS.......................................................................................................................................... 12 
PROOF OF CONCEPT (POC) OF SAFETY AND TOLERABILITY OF RAP CELLULITE 
CLINICAL TRIAL ............................................................................................................................................... 12 
SAFETY CONCLUSION ..................................................................................................................................... 13 
PIVOTAL STUDY OF SAFETY AND EFFICACY OF RAP CELLULITE CLINICAL TRIAL ............ 13 
STUDY DESIGN .................................................................................................................................... 17  
SELECTION OF STUDY POPULATION ......................................................................................................... 17 
INCLUSION CRITERIA ...................................................................................................................................... 17 
EXCLUSION CRITERIA .................................................................................................................................... 18 
STUDY VISITS ..................................................................................................................................................... 19 
VISIT 1 BASELINE SCREENING AND CONSENT FORM (DAY -30 TO DAY 0) ................................ 19 
VISIT 2 TREATMENT ........................................................................................................................................ 19 
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) ............................ 20 
VISIT 6 FOLLOW UP VISIT 52-WEEKS POST 2ND TREATMENT (+/- 14 DAYS)  ........................... 21 
RISKS AND BENEFITS ...................................................................................................................... 22 
KNOWN SIDE EFFECTS OF RAP TREATMENT ........................... ERROR! BOOKMARK NOT DEFINED. 
KNOWN TREATMENT ADVERSE EVENTS. ......................................... ERROR! BOOKMARK NOT DEFINED. 
RISK MITIGATIONS .......................................................................................................................................... 22 
REPORTING ADVERSE EVENTS AND COMPLICATIONS............................................................ 24 
ADVERSE EVENTS ............................................................................................................................................. 24 
DEVICE MALFUNCTIONS................................................................................................................................ 27 
STUDY PARTICIPANT INFORMED CONSENT ............................................................................... 27 
RECORDS MANAGEMENT ............................................................................................................. 28 
INVESTIGATIONAL DEVICE ACCOUNTABILITY AND STORAGE ............................................ 29 
REGULATORY AND ETHICAL COMPLIANCE ...................................................................... 29 
QUALITY ASSURANCE AND MONITORING ........................................................................... 29 
STUDY RESULTS/ANALYSIS .......................................................................................................... 30 
SUSPENSION OR PREMATURE TERMINATION OF STUDY ...................................................... 31 
PUBLICATION POLICY .................................................................................................................... 31 
STUDY COMPLETION ....................................................................................................................... 31 
REFERENCES ....................................................................................................................................... 32 
TABLES .................................................................................................................................................... 33 
TIMELINE AND EVENTS SCHEDULE ........................................................................................................... 33 
STUDY SCALES AND ASSESSMENTS ......................................................................................... 33 

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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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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 
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.  

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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:  
ii. Advised by the Sponsor or designee. 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 
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 

 
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