Open-label, Prospective Evaluation of the Ulthera® System for Lifting Submental (Under the Chin) and Neck Tissue in Chinese Patients
Phase: NA
Conditions: Mild to Moderate Skin Laxity Under the Chin, Mild to Moderate Skin Laxity on Neck
Sponsor: Merz North America, Inc.

Asentral, Inc. Institutional Review Board Approved – July 28, 2017 
 
 
 
 
CLINICAL PROTOCOL NUMBER ULT-302 
 
OPEN-
LABEL,
 PROSPECTIVE EVALUATION OF THE 
ULTHERA® SYSTEM FOR LIFTING SUBMENTAL (U
NDER THE 
CHIN)
 AND NECK TISSUE IN CHINESE SUBJECTS 
 
CONFIDENTIAL – PROPRIETARY I
NFORMATION 
 
DATE:
 J
ANUARY 26,
 2018 
NCT03351335, redacted 
version v1.0, 25Jul2019
NCT03351335, redacted 
version v1.0, 25Jul2019

Asentral, Inc. Institutional Review Board Approved – July 28, 2017 
 
CONFIDENTIAL – PROPRIETARY INFORMATION 
Protocol Number ULT-302   FINAL_v4_26JAN2018    
  
 
  
 
Page | ii 
I
NVESTIGATOR SIGNATURE PAGE 
 
Investigator Signature: 
By signing this page, I agree to follow this Study Protocol and all applicable regulations. 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
Principal Investigator Signature    
  
  
  
Date 
 
 
 
 

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Page | iii 
SPONSOR CONTACT I
NFORMATION 
 
Protocol Title: 
Open-label, Prospective Evaluation of the Ulthera® System for Lifting Submental 
(Under the Chin) and Neck Tissue in Chinese Patients 
 
Protocol Number:  
 
ULT-302 / M960001052 
 
Sponsor:  
  
 
Merz North America 
  
  
  
 
6501 Six Forks Road 
Raleigh, NC  27615 
 
 
  
  
  
  
 
 

Asentral, Inc. Institutional Review Board Approved – July 28, 2017 
 
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Protocol Number ULT-302   FINAL_v4_26JAN2018    
  
 
  
 
Page | i 
SPONSOR AGREEMENT 
Merz North America (hereinafter “Study Sponsor”) maintains responsibility for the ongoing safety of this clinical study involving the 
evaluation of the Ulthera System®.  Study Sponsor will promptly notify all investigators, the responsible IRB(s), and the regulatory 
authorities of any findings from ongoing study monitoring activities that could adversely affect the safety of subjects, impact the conduct 
of the clinical study, or alter the IRB’s approval to continue the study, specifically within 5 working days of making an Unanticipated 
Adverse Device Effect (UADE) determination or 15 working days after first receiving notice of the UADE, within 10 days for Serious 
Adverse Event reports, and at least annually for routine reports.  In the event that participant safety could be directly affected by study 
results after the study has ended, Study Sponsor will notify all investigators of these results to enable investigators to consider informing 
participants as soon as possible or at least within one year of study closure.  Within 6 months of study completion and final data analysis, 
Study Sponsor will provide the responsible IRB(s) with a copy of a final clinical study report.  
I
NVESTIGATOR AGREEMENT AND CERTIFICATION 
I hereby agree to participate in this clinical study sponsored by Study Sponsor. I agree to conduct this investigation according to the 
requirements of the protocol provided by the Study Sponsor and in accordance with Part 812 and other applicable FDA regulations, and 
regulations of other relevant regulatory authorities and conditions imposed by the reviewing Institutional Review Board (IRB) or Ethics 
Committee (EC).  I agree to ensure that appropriate informed consent is obtained from all subjects prior to inclusion in this study.  I also 
agree to supervise all testing of the device involving human subjects. I am aware that the Study Sponsor reserves the right to discontinue 
this investigation at any time. 
I understand that this investigation will be monitored by the Study Sponsor and/or a designee employed by the Study Sponsor. This 
monitoring will involve periodic inspection of my investigational site and ongoing review of the data that is submitted by me to the Study 
Sponsor. All study data will be entered within 1 week after the targeted study follow‐up visit. I am also aware that I may be inspected by 
a representative of the relevant regulatory authorities, including the United States Food and Drug Administration, to verify compliance 
with applicable regulations related to clinical research on human subjects. 
My current curriculum vitae and the curriculum vitae of physicians/licensed practitioners at this institution who will participate as co-
investigators/sub-investigators in this study will be provided to the Study Sponsor. These curriculum vitae will include the extent and type 
of our relevant experience with pertinent dates and locations. 
I certify that I have not been involved in an investigation that was terminated for non-compliance at the insistence of the Study Sponsor, 
the IRB or EC, or other regulatory authorities. I agree to provide the Study Sponsor sufficient, accurate financial disclosure information.  I 
also agree to update financial disclosure information if any relevant changes occur during the investigation and for one year following the 
completion of the study. 
I understand that this study protocol and the study results are confidential, and I agree not to disclose any such information to any 
person other than a representative of the Study Sponsor or the relevant competent authorities without the prior written consent of the 
Study Sponsor. 
Accepted by: 
  
  
  
  
  
  
  
  
  
  
  
  
 
Principal Investigator Signature  
  
  
  
 
Date 
 
  
  
  
  
  
  
  
  
 
Principal Investigator Name 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
Co-/Sub-Investigator Signature  
  
  
  
 
Date 
  
  
  
  
  
  
  
  
 
Co-/Sub-Investigator Name 

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Page | ii 
PROTOCOL SYNOPSIS 
Company Name: 
Ulthera, Inc. 
Protocol Number: 
ULT-302 
Protocol Title: 
Open-label, Prospective Evaluation of the Ulthera® System for Lifting Submental 
(Under the Chin) and Neck Tissue in Chinese Patients 
Investigational Device: 
Ulthera® System 
Development Phase: 
Pilot 
Study Objective: 
To evaluate the Ulthera® System for lifting submental (under the chin) and neck tissue 
in Chinese patients 
Study Design: 
Prospective, multi-site  
Number of Subjects:  
N = Up to 60 treated subjects (Up to 20 subjects in each of the three energy levels)   
Study Treatment 
Groups: 
Enrolled subjects will receive a dual depth Ultherapy® treatment using the 4-4.5mm 
and 7-3.0mm transducers. Treatments will be provided to the lower face, submental 
(under the chin) and neck area.  Twenty enrolled subjects will be treated at each of 
three energy levels (EL2, EL3, and EL4).  
Subject Population: 
Adults between 35 and 65 years of age who meet the inclusion/exclusion criteria. 
Inclusion Criteria: 
1. Male or female, age 35 to 65 years. 
2. Both parents of full Chinese decent. 
3. Mild to moderate skin laxity of the submental (under the chin) and neck tissue 
as determined by the physician and trained assessors. 
4. Adequate menton area to allow for quantitative analysis, as confirmed by 
photography images. 
5. Willingness and ability to comply with protocol requirements, including 
returning for follow-up visit and abstaining from any other procedures in the 
areas to be treated through the follow-up period. 
6. Subjects of childbearing potential must have a negative urine pregnancy test 
result and must not be lactating at the Screening Visit and be willing and able 
to use an acceptable method of birth control (e.g. barrier methods used with 
a spermicidal agent, hormonal methods, IUD, surgical sterilization, 
abstinence) during the study. Women will not be considered of childbearing 
potential if one of the following conditions is documented on the medical 
history:  
a. Postmenopausal with last menstrual bleeding  at least 12 months 
prior to study; and  
b. Without a uterus and/or both ovaries.  
7. Willing to take 600mg Ibuprofen as pre-treatment medication, at least 60 
minutes but not more than two hours prior to study treatment. 
8. Willingness and ability to provide written consent for study-required 
photography and adherence to photography procedures (i.e., removal of 
jewelry and makeup). 
9. Willingness and ability to provide written informed consent prior to 
performance of any study-related procedure. 
Exclusion Criteria: 
1. Presence of an active systemic or local skin disease that may affect wound 
healing. 
2. Presence of any hemorrhagic disorder or hemostatic dysfunction, herpes 
simplex, diabetes, epilepsy, bell’s palsy or any physical or psychological 
condition that is deemed unacceptable by the investigator for participation in 
this study. 
3. Severe solar elastosis. 

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Page | iii 
4. Excessive subcutaneous fat in the area(s) to be treated. 
5. Excessive skin laxity on the area(s) to be treated. 
6. Significant scarring in the area(s) to be treated that would interfere with 
assessing results. 
7. Open wounds or lesions in the area(s) to be treated. 
8. Severe or cystic acne on the area(s) to be treated. 
9. Active implants (e.g., pacemakers or defibrillators), or metallic implants in the 
treatment areas (dental implants not included.) 
10. Inability to understand the protocol or to give informed consent. 
11. Allergy or sensitivity to pre-treatment medication (ibuprofen). 
12. Microdermabrasion, or prescription level glycolic acid treatment to the 
treatment area(s) within four weeks prior to study participation or during the 
study. 
13. Marked asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, 
or thick sebaceous skin in the area(s) to be treated. 
14. BMI greater than or equal to 30. 
15. History of chronic drug or alcohol abuse. 
16. More than 2-3 doses of any NSAID in any 2-week period prior to and 
throughout study. 
17. History of autoimmune disease. 
18. Concurrent therapy that, in the investigator’s opinion, would interfere with 
the evaluation of the safety or efficacy of the study device.  
19. Subjects who anticipate the need for inpatient surgery or overnight 
hospitalization during the study. 
20. Subjects who, in the investigator’s opinion, have a history of poor 
cooperation, noncompliance with medical treatment, or unreliability. 
21. Concurrent enrollment or enrollment in any study involving the use of 
investigational devices or drugs within the past three months. 
22. Current smoker as defined by 
a. Having smoked one or more cigarettes per day on a daily basis within 
the past year; or  
b. Smoke cessation within the past 6 months. 
23. Current user of any nicotine-containing products, e.g., e-cigarettes, Nicorette 
gum, nicotine patches, etc. 
24. History of the following cosmetic treatments in the area(s) to be treated: 
a. Skin tightening procedure within the past year; 
b. Injectable filler of any type within the past: 
i. 9 months for Hyaluronic acid fillers (e.g. Restylane) 
ii. 24 months for Ca Hydroxyapatite fillers (e.g. Radiesse) 
iii. 12 months for Long-lasting Hyaluronic acid (Juvéderm 
Voluma)  
iv. 24 months for Poly-L-Lactic acid fillers (e.g. Sculptra); and 
v. Ever for permanent fillers (e.g. Silicone, Artecoll) 
c. Neurotoxins within the past three months; 
d. Ablative resurfacing laser treatment; 
e. Nonablative, rejuvenative laser or light treatment within the past six 
months; 
f. Surgical dermabrasion or deep facial peels; 
g. Facelifts within the past year; or 
h. Any history of contour threads. 
25. History (in the prior year) or current use of the following prescription 
medications: 

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Page | iv 
a. Accutane or other systemic retinoids within the past six months; 
b. Topical Retinoids within the past two weeks; 
c. Antiplatelet agents/Anticoagulants (Coumadin, Heparin, Plavix); 
d. Psychiatric drugs that in the investigators opinion would impair the 
subject from understanding the protocol requirements or 
understanding and signing the informed consent. 
Treatment Outline for 
Enrolled Efficacy 
Endpoint Subjects: 
1. Screening Visit: 
a. Obtain informed consent 
b. Screen for inclusion/exclusion criteria; (obtain height and weight for 
BMI)  
c. Pregnancy screen (if applicable)  
d. Assess photography image for adequate menton area to allow for 
quantitative assessment 
e. Enrollment eligibility, based on degree of submental (under the chin) 
and neck tissue laxity (must be mild to moderate), will be determined 
by the physician and trained assessor’s review and approval of 
screening images 
2. Baseline / Treatment Visit (The screening visit may not be more than 14 days 
prior. Greater than 14 days between baseline/treatment visit and screening 
visit will require that the subject be re-screened to confirm enrollment 
eligibility.): 
a. Confirm eligibility for participation; 
b. Perform baseline photography using Vectra 3D photography system 
before treatment 
c. Complete subject lower face, submental (under the chin) and neck 
treatment 
3. Post-treatment telephone contact 
a. 7±3 days – Capture adverse events 
4. Follow-up Visits for efficacy evaluation: 
a. 90 ± 14 days  
i. Obtain Vectra 3D photography images (for quantitative 
measure and masked assessment); 
ii. Obtain height and weight for BMI 
iii. Obtain physician and subject global aesthetic improvement 
scores (GAIS);  
iv. Obtain subject satisfaction scores and  
v. Pregnancy screen (if applicable). 
5. Visits for safety evaluation: 
a. Treatment Visit 
i. Pain assessment during treatment 
b. Immediately post-treatment  
i. Assess for adverse events. 
c. Day 7 Telephone Follow-up Visit 
i. Assess for adverse events 
d. Day 90 follow-up visit 
i. Assess for adverse events. 
Primary Endpoint: 
Assess improvement in overall lifting of submental (under the chin) and neck tissue as 
determined by a quantitative measure of tissue lift in the area using photographs 
taken with Mirror Photofile software and a Vectra 3D digital imaging system in each of 
the treatment groups 90 days post treatment in Chinese subjects. 
Secondary Endpoints: 
In each of the treatment groups, assess: 
1. Improvement in overall lifting and tightening of skin as determined by subject 

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Page | v 
response rate (improved, much improved or very much improved) on 
Physician Global Aesthetic Improvement Scale (PGAIS) as determined by live 
assessment at 90 days post-treatment compared to baseline photograph. 
2. Improvement in overall lifting and tightening of skin as determined by subject 
response rate (improved or much improved) on Subject Global Aesthetic 
Improvement Scale (SGAIS) as determined by live assessment at 90 days post-
treatment compared to baseline photograph. 
3. Improvement in overall lifting and tightening of skin as determined by a 
masked, qualitative assessment of photographs at 90 days post-treatment 
compared to baseline. 
4. Subject satisfaction and subject reported improvement at 90 days post-
treatment. 
Safety Variables: 
Prior to treatment, the subject’s medical history will be reviewed, a urine pregnancy 
test will be performed (if applicable), and a physical examination will be conducted. 
During Ultherapy® treatment, the subject’s pain levels will be monitored using a 
validated Numeric Rating Scale [7]. Pain scores should be obtained following each 
region treated and for each transducer used during treatment. The patient reported 
average pain score for the entire region treated by each transducer will be recorded. In 
addition, the patient will be asked to provide an overall rating of their pain at the end 
of treatment. At each subsequent visit, the subject will be queried about adverse 
events and changes in concomitant medications, and the treatment area will be 
visually examined. A second pregnancy screening test will be performed at the 90-day 
follow-up visit. 
Statistical Analysis: 
Descriptive statistics will be used to compare the submental lift, secondary endpoints 
and safety assessments between the 3 treatment groups at day 90 in this 
observational trial. 
Study Hypothesis: 
The hypothesis for this study is improvement in overall lifting and tightening of skin 
from baseline to 90 days post-treatment. For each treatment group (energy level), the 
measure of pre and Day 90 post treatment area of the chin and neck will determine 
the amount of tissue lift.  
Study Duration: 
Estimated timeline: Up to 12 months 
 

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CONTENTS 
Signature Page 
......................................................................................................................... i
 
Sponsor Contact Information 
.................................................................................................. iii
 
Sponsor Agreement 
.................................................................................................................. i
 
Investigator Agreement and Certification 
................................................................................. i
 
Protocol Synopsis 
..................................................................................................................... ii
 
Study Overview ...................................................................................................................... vi 
List of Acronyms and Definitions 
............................................................................................. 
vii 
List of Figures and Tables 
.........................................................................................................xi 
1. Introduction 
......................................................................................................................... 1
 
1.1 Device Name and Indications for Use ..................................................................................... 1 
1.2 Brief Aging Background and Treatment Overview .................................................................. 1 
1.3 Mechanism of Action ............................................................................................................. 2 
1.4 Device Overview .................................................................................................................... 2 
1.5 Preclinical Studies .................................................................................................................. 4 
1.6 Clinical Study 
.......................................................................................................................... 4 
1.6.1 
Clinical Safety and Effectiveness Study at The University of Texas Southwestern Medical Center 
(UTSW)  4 
2. Study Objective and Design ................................................................................................. 5
 
2.1 Study Objective 
...................................................................................................................... 5 
2.2 Type and Design of Study 
....................................................................................................... 5 
2.3  Duration of Study 
................................................................................................................... 5 
3. Study Procedures 
................................................................................................................. 6
 
3.1 Schedule of Assessments at Each Study Visit 
.......................................................................... 6 
TABLE 3.1-1 SCHEDULE OF ASSESSMENTS 
................................................................................ 6
 
4. Subject Selection and Pre-Treatment 
................................................................................... 7
 
4.1  Pre-treatment Recruiting/Screening 
....................................................................................... 7 
4.2  Informed Consent .................................................................................................................. 7 
4.3  Eligibility ................................................................................................................................ 7 
4.3.1 
Inclusion Criteria 
.................................................................................................................................... 7 

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4.3.2 
Exclusion Criteria ................................................................................................................................... 8 
4.4 Screen Failures 
....................................................................................................................... 9 
4.5 Subject Treatment Group Assignment 
.................................................................................... 9 
4.6 Study Images 
........................................................................................................................ 
10 
5. Treatment of Subjects and Follow-up 
................................................................................. 10 
5.1 Study Treatment .................................................................................................................. 
10 
5.1.1 
Transducers.......................................................................................................................................... 
10 
5.1.2 
Pre-Treatment Medications 
................................................................................................................. 
10 
5.1.3  Subject Preparation for Treatment 
...................................................................................................... 
10 
5.1.4 
Treatment 
............................................................................................................................................ 
13 
5.1.5 
Acute Responses 
.................................................................................................................................. 
13 
5.2 Safety Variables ................................................................................................................... 
13 
5.3 Outcome Measures 
.............................................................................................................. 
13 
5.3.1 
Primary Endpoint 
................................................................................................................................. 
14 
5.3.2 
Secondary Endpoints 
........................................................................................................................... 
14 
5.4 Follow-up 
............................................................................................................................. 
14 
5.5 Protocol Deviations 
.............................................................................................................. 
15 
5.6  Withdrawal Criteria and Procedures 
..................................................................................... 
15 
5.7  End of Study (Completion) 
.................................................................................................... 
15 
6. Statistical Analyses 
............................................................................................................ 15 
6.1 Efficacy Analysis 
................................................................................................................... 
15 
6.3 Safety Analyses 
.................................................................................................................... 
16 
7. Evaluation of Adverse Events 
............................................................................................. 16 
7.1 Definitions ........................................................................................................................... 
16 
7.2 Relationship to the Investigational Device 
............................................................................ 
17 
7.3 Unanticipated Adverse Device Effects (Events) 
..................................................................... 
17 
7.4 Serious Adverse Event 
.......................................................................................................... 
18 
7.5 Reporting Requirements for Serious Adverse Events 
............................................................ 
18 
7.6 Severity 
................................................................................................................................ 
18 
7.7 Deaths 
.................................................................................................................................. 
19 
7.8 Pre-Existing Conditions 
......................................................................................................... 
19 
8. Risk Analysis 
...................................................................................................................... 19 

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8.1 Potential Risks 
...................................................................................................................... 
19 
8.2 Minimization of Potential Risks 
............................................................................................ 
19 
8.3 Potential Benefits 
................................................................................................................. 
20 
8.4 Justification for the Clinical Study 
......................................................................................... 
20 
9. Device Management 
.......................................................................................................... 20 
9.1 Packaging 
............................................................................................................................. 
20 
9.2 Storage ................................................................................................................................ 
20 
9.3 Accountability 
...................................................................................................................... 
20 
10. Regulatory and Ethical Requirements 
.............................................................................. 20 
10.1 
Informed Consent 
............................................................................................................. 
21 
10.2 
Institutional Review Board 
................................................................................................ 
21 
10.3 
Confidentiality of Subject Records .................................................................................... 
21 
11. Reports and Records Management 
.................................................................................. 21 
11.1 
Investigator Records 
......................................................................................................... 
21 
11.2 
Investigator Reports ......................................................................................................... 
22 
11.3 
Data Collection ................................................................................................................. 
23 
11.4 
Source Documents 
............................................................................................................ 
23 
11.5 
Records Retention at the Study Site 
.................................................................................. 
23 
12. Monitoring Procedures 
.................................................................................................... 24 
12.1  Monitoring ....................................................................................................................... 
24 
12.2 
Pre-Study Monitoring Procedures 
..................................................................................... 
24 
12.2.1 Selection of Monitors .......................................................................................................................... 
24 
12.2.2 Clinical Investigators 
............................................................................................................................ 
24 
12.3 
Site Initiation Visit ............................................................................................................ 
24 
12.4 
Periodic Monitoring Visits 
................................................................................................. 25 
12.5 
Frequency of Monitoring Visits 
......................................................................................... 
25 
12.6 
Study Closure 
.................................................................................................................... 
26 
12.7 
Reports of Monitoring Visits ............................................................................................. 
26 
12.8 
Additional Auditing 
........................................................................................................... 
26 
13. Confidentiality 
................................................................................................................. 26 

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14. Amendment Policy 
........................................................................................................... 26 
15. Study Investigators 
.......................................................................................................... 27 
References 
............................................................................................................................. 27 
Attachments: Outcome Measures ......................................................................................... 28 
Attachment A: Quantitative Methodology 
...................................................................................... 
28 
Attachment B: Physician Global Aesthetic Improvement Scale (PGAIS) 
........................................... 
31 
Attachment C: Subject Global Aesthetic Improvement Scale (SGAIS) 
.............................................. 
32 
Attachment D: Patient Satisfaction Questionnaire 
.......................................................................... 
33 
Attachment E:  Numeric Rating Scale 
.............................................................................................. 
34 
Attachment F:  Qualitative Methodology 
........................................................................................ 
35 
 
 
LIST OF FIGURES AND TABLES 
FIGURE 1.2-1 SKIN ANATOMY 
........................................................................................................................................ 1 
FIGURE 1.4-1 PRIMARY COMPONENTS 
.......................................................................................................................... 2 
TABLE 1.4-1 TRANSDUCER TYPES .................................................................................................................................. 3 
TABLE 1.4-2 TRANSDUCER ENERGY LEVELS 
................................................................................................................... 3 
TABLE 3.1-1 SCHEDULE OF ASSESSMENTS 
..................................................................................................................... 6 
FIGURE 5.1.3-1 TARGET TREATMENT AREAS 
............................................................................................................... 
12 
Figure 7.1.1.  EVENT REPORTING 
................................................................................................................................. 
17 
TABLE 7.2-1. RELATIONSHIP BETWEEN ADVERSE EVENTS AND INVESTIGATIONAL DEVICE 
........................................ 
17 
Table 8.1.1 EXPECTED TREATMENT EFFECTS 
............................................................................................................... 
19 

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1. I
NTRODUCTION 
1.1  D
EVICE NAME AND I
NDICATIONS FOR USE 
The Ulthera® System is indicated for use as a non-invasive dermatological aesthetic treatment to lift the eyebrow, 
lift lax submental (under the chin) and neck tissue, and improve lines and wrinkles of the décolleté.  
The Ulthera System, in conjunction with the Ulthera DeepSEE transducer, allows for ultrasonic visualization of 
depths up to 8mm below the surface of the skin. The indicated use of the imaging is to visualize the dermal and 
subdermal layers of tissue to ensure proper coupling of the transducer to the skin and confirm appropriate depth 
of treatment such as to avoid bone. 
The clinical study described in this protocol evaluates clinical outcomes associated with the non-invasive treatment 
to improve skin laxity and tightening.  The Global Aesthetics Improvement Scale (GAIS) (Attachment B and C) to 
assess overall aesthetic improvement will be collected from both the study investigator and subject. Overall 
change will be measured at all study visits using Mirror Photofile software with a Vectra 3D digital imaging system. 
Subject satisfaction will be measured at protocol-specified visits using a Patient Satisfaction Questionnaire 
(Attachment D). 
1.2  B
RIEF AGING BACKGROUND AND TREATMENT OVERVIEW 
Normal aging results in characteristic changes in the skin and underlying connective tissue of the face, generally 
described as the “Aging Face Syndrome.” These biologic changes, which include facial rhytids and laxity, result 
from cutaneous photo damage after repeated sun exposure and other factors, such as genetic predisposition. 
These factors change the three dimensional structure of skin collagen (e.g. crosslinking and altered 3D structure) 
leading to a loss of its inherent elasticity. In order to develop a treatment plan customized for each subject, a 
thorough knowledge of basic skin anatomy is essential (Figure 1.2-1). Treatment is then based on an individual’s 
clinical presentation. 
FIGURE 1.2-1 SKIN ANATOMY  
Various energy delivery devices have been developed in an effort to treat facial rhytids and skin laxity[1, 2]. These 
devices create thermal injuries which in turn induce a “wound healing” response, in which fibroblasts synthesize 

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1.5 PRECLINICAL STUDIES 
The Ulthera® System has been evaluated in a series of preclinical studies to demonstrate that the device performs 
as intended, meets its specifications, and is safe and suitable for clinical use. These studies verified and validated 
electrical safety, electromagnetic compatibility, mechanical properties, and software performance. In addition, 
functional preclinical studies were conducted to verify and validate device performance. 
Preclinical studies were conducted at Massachusetts Eye and Ear Infirmary – Harvard Medical School (MEEI) and 
Ulthera laboratories using a porcine skin model, which has a similar skin structure to human. These studies 
demonstrated that the Ulthera® System reliably creates small, micro-coagulative zones in the reticular dermis 
layer. 
Similar findings have been confirmed in human cadaver studies at the University of California at San Diego (UCSD, 
MEEI, and Wellman Lab – Harvard Medical School). Cadaver skin tissue was treated using the Ulthera® System at 
frequencies of 4-7 MHz. The focal depths of the 4 MHz transducer were 4.5mm and 6mm. The focal depths of the 
7MHz transducer were 3mm and 4.5mm. These studies further demonstrated that the Ulthera® System reliably 
creates small, well-confined micro-coagulative zones. 
1.6 CLINICAL STUDY 
1.6.1 CLINICAL SAFETY AND EFFECTIVENESS STUDY AT THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL 
CENTER (UTSW) 
An open-label, prospective, non-randomized, clinical study was conducted at UTSW (Protocol Number 00000404) 
to examine the safety and efficacy of the Ulthera® System for treating the lower face, submentum and neck to 
achieve improvement in submental and neck skin laxity.  The study was approved by the IRB at UTSW, and all 
subjects signed the informed consent document.  The objectives of this clinical study were to: 1) demonstrate the 
safety of the Ulthera® treatment and 2) demonstrate improvement in jawline definition and submental laxity by 
quantitative assessment of the amount of visible tissue lift. 
In this study, 70 subjects (ranging in age from 35 to 58 years), received Ultherapy® (low density treatment of 290 
lines) on the lower face and submentum with both the 7 MHz 3.0 mm transducer and either the 7 MHz 4.5 mm 
transducer or the 4 MHz 4.5 mm transducer, as determined by the investigator for each subject.  Improvement in 
jawline definition and submental laxity was assessed at 90 days by quantitative assessment of the amount of 
visible tissue lift seen in the photographs and comparison of pre- and post-treatment photographs by three 
masked clinician reviewers.  All subjects were followed for over 90 days to assess safety and effectiveness.  
Additionally, patient satisfaction was assessed at 90 and 180 days post-treatment. 
Study subjects were assessed for adverse events immediately post-procedure, and then at 60, 90 and 180 days.  A 
total of seven adverse events were reported; however, only three were considered device/procedure related 
(welting of the skin within the treated area).  All of the events resolved with no residual sequelae.  The three device 
related adverse events were considered mild in nature. 
The quantitative assessment for the right and left side of the face yielded a response rate of 72.9% (51 out of 70) of 
subjects that had a visible tissue lift of ≥ 20.0 mm
2 of the submental area when comparing the pre-treatment and 
90-day post-treatment photos. The average area of tissue lift in the study subjects who were considered 
responders were 71.97 mm2 and 71.69 mm2 for their left and right sides, respectively. The quantitative results 
were consistent for both the right and left side of the face.  Additionally, 84.3% of subjects who were identified as 
responders by quantitative assessment were also identified as responders in the qualitative masked assessment. 

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Based on the masked assessment conducted by three experienced clinicians of pre- and 90-day post-treatment 
photograph pairs, 68.6% of subjects had improvement (visibly observable tissue lift) in the submental area 
(beneath the chin) and neck.   The patient satisfaction questionnaire indicated that 67% of the subjects saw an 
improvement in face and neck characteristics. 
This study demonstrated that Ultherapy® is safe and efficacious for the improvement in submental (beneath the 
chin) and neck skin laxity.  
 
2. STUDY OBJECTIVE AND DESIGN 
2.1  S
TUDY OBJECTIVE 
Assess improvement in overall lifting of submental (under the chin) and neck tissue as determined by a 
quantitative measure of tissue lift in the area using photographs taken with Mirror Photofile software and a Vectra 
3D digital imaging system in each of the treatment groups in Chinese subjects. 
2.2  S
TUDY DESIGN 
This study is an open-label, non-randomized clinical study to be conducted at up to seven clinical sites. 
Approximately 60 subjects (20 subjects per treatment group) who meet the eligibility criteria will be enrolled and 
treated with the Ulthera® System. Enrollment eligibility will be determined by the physician and trained assessors’ 
review and approval of screening images.   
Eligible subjects enrolled in the study will be treated using the Ulthera® System by the study investigator and/or 
trained clinician. Standardized images will be taken at screening, baseline (prior to treatment) and following 
treatment (30 to 60 minutes post-treatment) and at the 90-day post treatment visit using Mirror Photofile 
software and a Vectra 3D digital imaging system.   
2.3   D
URATION OF STUDY 
Following the treatment visit, subjects will be followed for a total duration of up to 104 days.   
 
 
 
 
 

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4. SUBJECT SELECTION AND PRE-T
REATMENT  
The study population will consist of healthy Chinese (both parents of full Chinese descent) males and females 
between 35 to 65 years of age with mild to moderate submental (under the chin) and neck tissue laxity and 
adequate menton area to allow for quantitative analysis, who have chosen to participate in this clinical study as 
evidenced by execution of the informed consent document.  A physician assessor will confirm subjects eligibility 
based on submental (under the chin) and neck tissue laxity.  Screening photos will be provided in a blinded manner 
so the trained assessor has no knowledge of what site is considering enrolling the patient.   
4.1
   P
RE-
TREATMENT RECRUITING/SCREENING 
Subjects will be recruited from the study site’s patient database and IRB approved advertisements.  Study site 
personnel will explain the design and purpose of the study to potential study subjects. Subjects interested in 
participating will visit the study site where informed consent will be obtained. 
4.2
   I
NFORMED CONSENT 
Written informed consent will be obtained from all subjects (or legal representatives) before any study-related 
procedures, including any pre-treatment screening procedures, are performed. Investigators or delegated study 
personnel may discuss the availability of the study and the possibility for entry with a potential subject without 
first obtaining consent. Informed consent must be obtained and documented prior to initiation of any procedures 
that are performed solely for the purpose of determining eligibility for research. 
Investigators have ethical and legal responsibilities to ensure that the protocol is clearly explained to each subject 
considered for enrollment in the study. Compliance with this requirement should be documented on a written 
Informed Consent Form approved by the reviewing IRB.  
The IRB-approved Informed Consent Form will be signed by the study personnel obtaining consent. The subject will 
be given a copy of the signed Informed Consent Form. The investigative site will keep the original on file.  
4.3   E
LIGIBILITY 
4.3.1  I
NCLUSION CRITERIA 
Subjects must meet all of the following criteria for study enrollment: 
1. Male or female, age 35 to 65 years. 
2. Both parents of full Chinese descent. 
3. Mild to moderate skin laxity of the submental (under the chin) and neck tissue as determined by physician 
and trained assessors. 
4. Adequate menton area to allow for quantitative analysis, as confirmed by photography images. 
5. Willingness and ability to comply with protocol requirements, including returning for follow-up visit and 
abstaining from any other procedures in the areas to be treated through the follow-up period. 
6. Subjects of childbearing potential must have a negative urine pregnancy test result and must not be 
lactating at the Screening Visit and be willing and able to use an acceptable method of birth control (e.g. 
barrier methods used with a spermicidal agent, hormonal methods, IUD, surgical sterilization, abstinence) 
during the study. Women will not be considered of childbearing potential if one of the following 
conditions is documented on the medical history:  
a. Postmenopausal with last menstrual bleeding at least 12 months prior to study; and 

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b. Without a uterus and/or both ovaries.  
7. Willing to take 600mg Ibuprofen as pre-treatment medication at least 60 minutes but not more than two 
hours prior to study treatment. 
8. Willingness and ability to provide written consent for study-required photography and adherence to 
photography procedures (i.e., removal of jewelry and makeup). 
9. Willingness and ability to provide IRB approved written informed consent prior to performance of any 
study-related procedure. 
4.3.2  E
XCLUSION CRITERIA 
Subjects will be excluded if they meet any of the following criteria: 
1. Presence of an active systemic or local skin disease that may affect wound healing. 
2. Presence of any hemorrhagic disorder or hemostatic dysfunction, herpes simplex, diabetes, epilepsy, 
bell’s palsy or any physical or psychological condition that is deemed unacceptable by the investigator for 
participation in this study. 
3. Severe solar elastosis. 
4. Excessive subcutaneous fat in the area(s) to be treated. 
5. Excessive skin laxity on the area(s) to be treated. 
6. Significant scarring in the area(s) to be treated that would interfere with assessing results. 
7. Open wounds or lesions in the area(s) to be treated. 
8. Severe or cystic acne on the area(s) to be treated. 
9. Active implants (e.g., pacemakers or defibrillators), or metallic implants in the treatment areas (dental 
implants not included.) 
10. Inability to understand the protocol or to give informed consent. 
11. Allergy or sensitivity to pre-treatment medication (ibuprofen). 
12. Microdermabrasion, or prescription level glycolic acid treatment to the treatment area(s) within four 
weeks prior to study participation or during the study. 
13. Marked asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin in 
the area(s) to be treated. 
14. BMI greater than or equal to 30. 
15. History of chronic drug or alcohol abuse. 
16. More than 2-3 does of any NSAID in any 2-week period prior to and throughout study. 
17. History of autoimmune disease. 
18. Concurrent therapy that, in the investigator’s opinion, would interfere with the evaluation of the safety or 
efficacy of the study device.  
19. Subjects who anticipate the need for inpatient surgery or overnight hospitalization during the study. 
20. Subjects who, in the investigator’s opinion, have a history of poor cooperation, noncompliance with 
medical treatment, or unreliability. 
21. Concurrent enrollment or enrollment in any study involving the use of investigational devices or drugs 
within the past three months. 
22. Current smoker as defined by: 
a. Having smoked one or more cigarettes per day on a daily basis within the past year; or 
b. Smoke cessation within the past 6 months. 
23. Current user of any nicotine-containing products, e.g., e-cigarettes, Nicorette gum, nicotine patches, etc. 
24. History of the following cosmetic treatments in the area(s) to be treated: 
a. Skin tightening procedure within the past year; 

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b. Injectable filler of any type within the past: 
i. 9 months for Hyaluronic acid fillers (e.g. Restylane) 
ii. 24 months for Ca Hydroxyapatite fillers (e.g. Radiesse) 
iii. 12 months for Long-lasting Hyaluronic acid (Juvéderm Voluma)  
iv. 24 months for Poly-L-Lactic acid fillers (e.g. Sculptra); and 
v. Ever for permanent fillers (e.g. Silicone, Artecoll) 
c. Neurotoxins within the past three months; 
d. Ablative resurfacing laser treatment; 
e. Nonablative, rejuvenative laser or light treatment within the past six months; 
f. Surgical dermabrasion or deep facial peels; 
g. Facelifts within the past year; or 
h. Any history of contour threads. 
25. History (in the prior year) or current use of the following prescription medications: 
a. Accutane or other systemic retinoids within the past six months; 
b. Topical Retinoids within the past two weeks; 
c. Antiplatelet agents/Anticoagulants (Coumadin, Heparin, Plavix); 
d. Psychiatric drugs that in the investigators opinion would impair the subject from understanding 
the protocol requirements or understanding and signing the informed consent. 
After subjects have provided informed consent and met the inclusion/exclusion criteria, the study procedures 
described in the following section will be performed.  
4.4  S
CREEN FAILURES 
A screen failure subject is one from whom informed consent is obtained and is documented in writing (i.e., subject 
signs an Informed Consent Form), but who does not receive a study treatment because of failure to meet all of the 
eligibility criteria.  
4.5  S
UBJECT TREATMENT GROUP ASSIGNMENT  
Subjects are not randomized in this study.  All subjects will receive an Ultherapy ™ treatment at dual depth using 
the 4-4.5mm and 7-3.0mm transducers.  Treatments will be provided to the lower face, submental (under the chin) 
and neck area. See Section 5.1 for Study Treatment details. Enrolled subjects will be assigned to one of 3 treatment 
groups:   
Group EL2: Subjects will receive an Ultherapy ™ treatment at energy level 2 (EL2). 
Group EL3: Subjects will receive an Ultherapy ™ treatment at energy level 3 (EL3).   
 
Group EL4: Subjects will receive an Ultherapy ™ treatment at energy level 4 (EL4). 
Twenty subjects will be enrolled in each group.  Enrollment from the original protocol was in the following order:  
EL3, EL4 and EL2.  This amendment (dated 26JAN2018) is to change the order of enrollment.  Following 
amendment approval, approximately20 patients will be enrolled in EL2, EL3 and EL4 respectively.  Enrollment will 
continue at an energy level until that treatment group is complete.  
 

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FIGURE 5.1.3-1 TARGET TREATMENT AREAS  
 

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5.1.4  T
REATMENT 
All study treatments will be performed by the study investigator and/or trained clinician.  
Ultrasound gel will be applied to the transducer, which will then be placed on the targeted skin surface, and 
ultrasound image will be obtained. Each area of the proposed treatment will be imaged first with the ultrasound 
device to ensure coupling between the transducer and skin. During the treatment procedure, the study treatment 
clinician will place multiple Ultherapy® treatment lines close to each other (2 to 3mm) in the selected area, with 
each treatment line requiring about 3 seconds. Treatment lines can be a maximum length of 25mm and will 
produce a series of thermal coagulative zones. 
Treatment lines to the area highlighted in (Figure 5.1.3-1) will be administered as specified by Treatment Group in 
Section 4.5. These energy settings should not be altered for any study treatments.  The first transducer to be used 
in treatment is the 4-4.5mm, followed by the 7-3.0mm. All study treatments will begin with the 4.5mm depth. The 
entire 4.5mm depth treatment will be completed prior to continuing to the 3.0mm depth treatment.  Treatment 
will be delivered in a lined pattern. The subject will be monitored during the treatment.  
5.1.5  A
CUTE RESPONSES 
For all exposures, acute responses (e.g., erythema or edema) will be observed by the study treatment clinician and 
photographically recorded within 30-60 minutes after exposure. If any Serious Adverse Events (SAE) are noted, an 
SAE Form should be completed.   
5.2  S
AFETY VARIABLES 
Prior to treatment, the subject’s medical history will be reviewed, a urine pregnancy test will be performed (if 
applicable), and a physical examination will be conducted. During Ultherapy® treatment, the subject’s pain levels 
will be monitored using a validated Numeric Rating Scale (Attachment E). Average pain scores should be obtained 
following each region treated and for each transducer used during treatment. The average pain score for the 
entire region treated by each transducer will be recorded. At each subsequent visit, the subject will be queried 
about adverse events and changes in concomitant medications, and the treatment area will be visually examined. 
A second pregnancy screening test will be performed at the 90-day follow-up visit.     
5.3  O
UTCOME MEASURES 
Quantitative submental lift measurements calculated as detailed in Attachment A, comparing improvement in 
overall lift, will be obtained based on Vectra 3D study images obtained at 90-day follow-up visit post-treatment 
compared to baseline.  The quantitative scale used in the US Pivotal study was designed to measure a quantitative 
lift however; it was based on Caucasian anatomy.  It measured the 2D submental/neck area using 5 quadrants 
from the menton/neck transition point back toward the neck.  In Asian patients the distance from the 
menton/neck back towards the neck is not as long[6].  Therefore the 5th quadrant was dropped from the measure 
to account for this anatomical difference.    This study will observe the amount quantitative lift by treatment group 
in this Chinese population. 
The Global Aesthetic Improvement Scale (GAIS) (Attachments B and C) is a 5-point scale that rates global aesthetic 
improvement from the pretreatment appearance. The ratings are much worse, worse, no change, improved, and 
much improved. In this study both live observation and photo review are utilized by the physician (PGAIS) and 
subject (SGAIS) in order to assign a score. The PGAIS must be performed by the principal investigator. Both the 
PGAIS and SGAIS should be completed based on a live assessment of the subject while referring to the subject’s 

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pre-treatment photographs on a sponsor-supplied electronic tablet (subjects should be given a hand mirror for 
assessment). 
Comparison of improvement data for overall lifting and tightening of skin as determined by a masked, qualitative 
assessment of photographs obtained at follow-up visits post-treatment compared to baseline as detailed in 
Attachment F. 
A validated Numeric Rating Scale (0-10) (Attachment E) will be used to record subject reported pain scores during 
study treatment and following treatment completion. Scores will be obtained for each region treated, for each 
transducer used, and for the overall treatment. 
A Patient Satisfaction Questionnaire (PSQ) (Attachment D) will be completed at the 90-day follow-up visit. The 
subject should complete this assessment while referring to baseline photos on a sponsor-supplied electronic tablet 
and using a hand mirror. 
5.3.1  P
RIMARY ENDPOINT 
The primary endpoint is an assessment of the mean change (improvement) in overall lifting and tightening of skin 
in Chinese subjects at 90-days compared to baseline in each of the treatment groups as determined by a modified 
version of the validated quantitative measure of tissue lift in neck/submentum using photographs taken with 
Mirror Photofile software and a Vectra 3D digital imaging system.  
5.3.2  S
ECONDARY ENDPOINTS 
The secondary endpoints of this clinical study include for each treatment group: 
1. Improvement in overall lifting and tightening of skin as determined by subject response rate (improved or 
much improved) on Physician Global Aesthetic Improvement Scale (PGAIS) as determined by live 
assessment compared to baseline photograph. 
2. Improvement in overall lifting and tightening of skin as determined by subject response rate (improved or 
much improved) on Subject Global Aesthetic Improvement Scale (SGAIS) as determined by live 
assessment compared to baseline photograph. 
3. Improvement in overall lifting and tightening of skin as determined by a masked, qualitative assessment 
of photographs at 90 days post-treatment compared to baseline. 
4. Subject satisfaction and subject reported improvement at 90 days post-treatment. 
 
5.4  F
OLLOW-
UP 
Subjects will be asked to return to the clinic for follow-up visits at 90 days post-treatment.  At all visits, subjects will 
be assessed for safety and efficacy, standardized images will be taken (refer to study sponsor’s study specific 
photography guidelines and procedures document), adverse events and protocol deviations will be assessed, and 
study outcome measures (GAIS, other study-specific assessments) will be completed.  
At the 90-day follow-up appointment in addition to the above referenced assessments, the subject will complete a 
Patient Satisfaction Questionnaire and a pregnancy test, if applicable.   
Subjects will be asked to return to the site for repeat image if 90-day follow-up image shows photography issues 
such as lighting inconsistencies, subject positioning, and/or shadowing as determined by photography consultant 
review.  

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5.5  P
ROTOCOL DEVIATIONS 
This study should be conducted as described in this protocol, except for an emergency situation in which the 
protection, safety, and well-being of a subject requires a protocol deviation, based on the judgment of the 
investigator (or a responsible, appropriately trained professional designated by the investigator). If the deviation 
from the protocol is necessary to protect the physical well-being of a subject in an emergency, such protocol 
deviations must be reported to the Sponsor and the reviewing IRB as soon as possible, but no later than five 
working days after the emergency occurred.  
In the event of a significant deviation from the protocol due to an accident or mistake, the investigator or designee 
must contact the Sponsor at the earliest possible time by telephone to discuss the deviation and its impact on the 
study and subject continuation in the study. These discussions will be documented by the investigator and the 
Sponsor, and reviewed by the monitor. 
5.6   W
ITHDRAWAL CRITERIA AND PROCEDURES 
All subjects have the right to withdraw at any point during the study without prejudice. The investigator can 
discontinue any subject, at any time, if medically necessary. The reason for subject’s withdrawal should be 
documented on the appropriate study-specific data form. The subject must undergo the recommended follow-up 
assessments specified for the last study visit unless contraindicated due to a medical condition. Withdrawn 
subjects will not be replaced. 
5.7   E
ND OF STUDY (C
OMPLETION) 
All subjects who have signed an Informed Consent Form, except for screen failures, will be considered enrolled in 
the study. Subjects who were treated and complete the study duration will be considered to have completed the 
study. Any subject who does not return for a scheduled follow-up visit will be contacted at least twice by 
telephone to determine the cause for the missed visit and to try to get the subject scheduled for the follow-up. A 
new visit will be scheduled as soon as possible. All subjects should be followed until completing the study follow-
up or until study discontinuation (withdrawal) for other reasons. The reason for study discontinuation should be 
documented for each subject. Subjects will be deemed “Lost-to-Follow-up” if they have not returned within two 
weeks after the last follow-up target. For any subject lost to follow-up at least three attempts to contact the 
subject must be documented; the attempts must be two phone calls/emails and a registered letter. 
6. STATISTICAL ANALYSES 
For primary and secondary endpoints, data will be summarized for each time point for which data for that 
parameter are available. Subjects with incomplete data will be included in summaries for which they have data 
available.  Categorical variables will be summarized as frequencies and percentages in each category.  Continuous 
and ordinal variables will be summarized as numbers of subjects, means, standard deviations, medians, and 
ranges.   Graphical presentation of data will be provided, if deemed appropriate. All programs for data output and 
analyses will be written in SAS® version 9.4 or higher (SAS Institute, Inc., Cary, NC).  
6.1  EFFICACY ANALYSIS 
The primary analysis of efficacy will be based on the evaluable treated subjects, hence, only those subjects who 
received a complete or partial study treatment and completed the follow-up visit, and who have evaluable images 

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at baseline and 90-days post-treatment will be included in the analysis.  No imputations will be performed for 
missing data. 
The primary efficacy endpoint is the amount of improvement from baseline at 90 days after treatment.  
Descriptive statistics will compare mean values  of improvement between the 3 treatment groups and 95% 
confidence intervals (CIs) will be calculated for each group.  Additionally, the proportion of subjects achieving 
various levels of improvement may be calculated along with exact 95% CIs. 
Any deviations from this statistical analysis plan will be documented with justification in the final report. 
6.2  SECONDARY ANALYSES  
The frequency and percentage for each of the following secondary endpoints will be reported for available data for 
the total population and by treatment group.   
1. Improvement in overall lifting and tightening of skin as determined by subject response rate (improved, or 
much improved) on Physician Global Aesthetic Improvement Scale (PGAIS) as determined by live 
assessment at 90 days post-treatment compared to baseline photograph.   
2. Improvement in overall lifting and tightening of skin as determined by subject response rate (improved, 
 
or much improved) on Subject Global Aesthetic Improvement Scale (SGAIS) as determined by live 
assessment at 90 days post-treatment compared to baseline photograph. 
3. Improvement in overall lifting and tightening of skin as determined by a masked, qualitative assessment 
of photographs at 90 days post-treatment compared to baseline. 
4. Subject satisfaction and subject reported improvement at 90 days post-treatment. 
6.3  SAFETY ANALYSES 
All adverse events (AE) and device related adverse events  will be collected and reported during this study.  AEs will 
be summarized overall, by seriousness and device relatedness including count. proportion of subjects experiencing 
each type of AE for  all subjects and by treatment group will be provided.   
Patient reported pain assessments collected throughout this study using the validated numeric scale will also be 
reported by treatment group and time point using descriptive statistics and include mean, standard deviation, 
median and range at minimum.   
6.4  I
NTERIM ANALYSES 
. If there is a need for an interim reporting of data, this will be outlined in the statistical analysis plan.  
7. EVALUATION OF ADVERSE EVENTS 
7.1  D
EFINITIONS 
An adverse event is defined as any new medical problem, or exacerbation of an existing problem, experienced by a 
subject while enrolled in the study, whether or not it is considered device-related by the investigator.  Reported 
events will be categorized as Expected Treatment Effects, i.e., any typical treatment side-effect of Ultherapy® of 
mild to moderate severity and lasting up to a typical maximum duration, or Adverse Events based on severity, 
duration and relationship to the Ulthera® device or Ultherapy® procedure/technique.  See Figure 7.1.1. 

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FIGURE 7.1.1.  EVENT REPORTING 
 
7.2  R
ELATIONSHIP TO THE I
NVESTIGATIONAL DEVICE 
The investigator should assess the relationship of the adverse event to the investigational device. The relationship 
should be assessed using the categories presented in Table 7.2-1. 
TABLE 7.2-1. RELATIONSHIP BETWEEN ADVERSE EVENTS AND INVESTIGATIONAL DEVICE 
Definite 
Definite relationship exists between the device/procedure and an adverse 
event 
Probably Related 
A reasonable causal relationship between the device/procedure and an 
adverse event is more likely than not. 
Possibly Related 
A reasonable relationship exists between the device/procedure and an adverse 
event, but the causal relationship is unclear or lacking. 
Not Likely Related 
A temporal relationship exists between the device/procedure and an adverse 
event, but there is no reasonable causal relationship. For example the adverse 
event occurs in a time frame, which makes a causal relationship to device 
treatment improbable. 
Unrelated 
No relationship between treatment with the device/procedure and the 
adverse event exists. 
7.3  U
NANTICIPATED ADVERSE DEVICE EFFECTS (E
VENTS) 
An unanticipated adverse device effect is defined as “any serious adverse effect on health or 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 (including 
supplementary application), or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects.” 
If an unanticipated adverse device effect occurs, the investigator should notify the Sponsor as soon as possible of 
such an event. The investigator must promptly notify the reviewing EC of such an event as soon as possible, but no 
later than 10 working days after learning of the event. 

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7.4  S
ERIOUS ADVERSE EVENT 
Each adverse event should be assessed for its seriousness. The definition below should be used for this 
assessment. Please note that the term serious adverse event is not synonymous with a “severe” adverse event, 
which may be used to describe the intensity of an event experienced by the subject. (Please refer to Section 7.6 for 
severity definitions.) 
An adverse event should be classified as serious if it meets any of the following criteria: 
a. Death 
Death was an outcome of the adverse event.  
b. Life-threatening 
The subject was at substantial risk of dying at the time of the adverse event, or use or continued use 
of the device. 
c. Hospitalization (initial or prolonged) 
Admission to the hospital or prolongation of hospitalization was a result of the adverse event. 
d. Disability or Permanent Damage 
The adverse event resulted in a substantial disruption of a person's ability to conduct normal life 
functions, i.e., the adverse event resulted in a significant, persistent or permanent change, 
impairment, damage or disruption in the patient's body function/structure, physical activities and/or 
quality of life. 
e. Congenital Anomaly/Birth Defect 
Exposure to a medical product prior to conception or during pregnancy may have resulted in an 
adverse outcome in the child. 
f. Required Intervention to Prevent Permanent Impairment or Damage (Devices) 
Medical or surgical intervention was necessary to preclude permanent impairment of a body 
function, or prevent permanent damage to a body structure, either situation suspected to be due to 
the use of a medical product. 
g. Other Serious (Important Medical Events) 
The event does not fit the other outcomes, but the event may jeopardize the subject and may require 
medical or surgical intervention (treatment) to prevent one of the other outcomes. 
 
Non-serious adverse events are all events that do not meet the criteria for a “serious” adverse event. 
7.5  R
EPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS 
Serious adverse events must be reported to the Sponsor as soon as possible, preferably within 24 hours but in no 
event later than 72 hours. The adverse event must be recorded on the subject’s study-specific data form. The 
Sponsor will conduct an investigation. If the Sponsor determines that the investigation presents an unreasonable 
risk to subjects, all investigations or parts of the investigation presenting that risk will be terminated as soon as 
possible. The investigator must report serious adverse events to the reviewing IRB according to the IRB regulations 
at the study site.  
7.6  S
EVERITY 
Each adverse event should be assessed for its severity, or the intensity of an event experienced by the subject, 
using the following classifications: 
1 = Mild  
Discomfort noticed, but no disruption to daily activity 
2 = Moderate Discomfort sufficient to reduce or affect normal daily activity 
3 = Severe 
Inability to work or perform normal daily activity 

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7.7  D
EATHS 
The investigator must notify the Sponsor as soon as possible, preferably within 24 hours but in no event later than 
48 hours, of learning of a subject’s death, regardless of whether the death is related or unrelated to the 
investigational device. The investigator should attempt to determine, as conclusively as possible, whether the 
death is related to the device. The cause of death and the investigator’s discussion regarding whether or not the 
death was device-related should be described in a written report. The investigator mush report death to the 
reviewing IRB according to the IRB regulations at the study site. 
7.8  P
RE-E
XISTING CONDITIONS 
A pre-existing condition should not be reported as an adverse event unless there has been a substantial increase in 
severity or frequency of the problem that has not been attributed to natural history. 
8. RISK ANALYSIS 
8.1  P
OTENTIAL RISKS 
This treatment modality was designed to inherently minimize the risk to the subject. However, ultrasound 
exposure with subsequent heating of the soft tissue could involve the risks listed below: 
TABLE 8.1.1 EXPECTED TREATMENT EFFECTS  
Expected Treatment Effects 
Duration 
Bruising/Ecchymosis  
Up to 3 weeks 
Edema/Swelling 
Up to 2 weeks 
Erythema/Redness 
Up to 24 hours 
Local Muscle Weakness/Paresis  
Up to 6 weeks 
Nodules  
Up to 4 weeks 
Acute Pain 
Immediate/momentary (while energy is 
being delivered) - 2 hours 
Skin Burn 
Up to 4 weeks 
Tenderness/Soreness/Pain/Sensitivity to 
Touch   
Up to 6 weeks 
Tingling/Paresthesia/Numbness 
Up to 6 weeks 
Welting/Raised Areas of Edema 
Up to 4 week 
Common risks associated with Ibuprofen include nausea, diarrhea, dizziness, headaches and hypertension.  
NSAIDS (e.g., Ibuprofen) should not be given to patients who have experienced asthma, urticaria, or allergic-type 
reactions after taking aspirin or other NSAIDs.   
These risks will be minimized or reduced by monitoring the subject during the treatment and observing the skin’s 
response to receiving the treatment. If the treatment is not tolerated, the investigator must stop administering 
treatment for the subject’s safety, and the subject will be followed for adverse events for 90 days. 
Previous clinical studies with the Ulthera® System have shown that the sensory response was tolerable from the 
subject’s and investigator’s perspectives. The discomfort was transient and no subject had any residual pain 
beyond 30 minutes. 
8.2  M
INIMIZATION OF POTENTIAL RISKS 

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The risks listed above are minimized by performing two to three treatment line exposures and noting the subject’s 
sensation and inflammatory response. Risks have also been minimized by prior testing (including preclinical, 
animal, and clinical) conducted with the Ulthera® System. 
8.3  P
OTENTIAL BENEFITS 
There is a potential benefit to participants of this study who are seeking lifting of submental (under the chin) and 
neck tissue laxity. Results of the study may contribute to further development of the ultrasound-based, non-
invasive tissue-tightening procedure in Chinese patients. 
8.4  J
USTIFICATION FOR THE CLINICAL STUDY 
The current clinical study is justified based on the previous safe clinical experience with the Ulthera® System for 
cosmetic applications to facial skin, and the efficacy in related cosmetic applications for skin tightening. The 
current clinical plan is expected to result in lifting and tightening of the skin and achievement of a positive clinical 
outcome in Chinese patients. 
9. DEVICE MANAGEMENT 
9.1  P
ACKAGING 
On a site-specific basis, the Ulthera® System will be shipped in a hard case designed to protect the system during 
delivery. Upon arrival at the clinical site, the Ulthera® System will be set up by Ulthera personnel for pre-study 
testing to ensure that the system is functioning properly. 
9.2  S
TORAGE 
Shipping and storage conditions include: 
Shipping and Storage, System without Transducers 
 
 
 
Shipping and Storage, with Transducers 
 
 
9.3  A
CCOUNTABILITY 
The investigator, or designee, must maintain an inventory record of study devices received, used for treatment, 
and returned to the Sponsor to ensure that the investigational device will not be dispensed to any person who is 
not a subject under the terms and conditions set forth in this protocol. There will be 100% accountability for all 
investigational Ulthera® Systems and transducers. 
10. REGULATORY AND ETHICAL REQUIREMENTS 

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This clinical study will be conducted in accordance with the Protection of Human Subjects Regulations, including 
Subpart B Informed Consent of Human Subjects (21 CFR Part 50); the Institutional Review Board Regulations (21 
CFR Part 56); the Financial Disclosure by Clinical Investigators Regulations (21 CFR Part 54); and the Investigational 
Device Exemptions Regulations (21 CRF Part 812). 
10.1  I
NFORMED CONSENT 
Informed consent will be obtained from all subjects prior to study participation. 
10.2  I
NSTITUTIONAL REVIEW BOARD 
Prior to initiation of any study procedures, the protocol, informed consent, and operators manual will be 
submitted to a duly constituted IRB for view and approval. In addition, any amendments to the protocol or 
Informed Consent Form will be reviewed and approved by the IRB. The Sponsor must receive a letter documenting 
IRB approval at the clinical site prior to the initiation of the study. 
The investigator is responsible for providing the appropriate reports to its reviewing IRB during the course of the 
clinical study. These reports will include: 
• Informing the IRB of the study progress periodically as required, but at least annually; 
• Reporting any unanticipated adverse device effects within 10 working days of first learning of the event; 
• Timely reporting any deviations from the clinical protocol to protect the life or well-being of a subject in 
the case of an emergency after the emergency occurred; 
• Timely reporting the use of the device without obtaining informed consent from a subject;   
• Providing any other reports requested by the IRB. 
The IRB must be notified of study within 30 days of the final visit of the last subject and should be provided with a 
summary of the results of the study by the investigator. 
10.3  C
ONFIDENTIALITY OF SUBJECT RECORDS 
All information generated in this study must be considered highly confidential and must not be disclosed to any 
persons not directly concerned with the study without prior written permission from the Sponsor. Authorized 
regulatory officials and Sponsor personnel (or its representatives) will be allowed full access to inspect the records. 
All investigational devices and/or other materials collected will be used solely in accordance with this protocol, 
unless otherwise agreed to in writing by the Sponsor.  
Subjects should be identified only by initials and unique subject numbers on study-specific data forms. If necessary, 
their full names may be made known to a regulatory agency or other authorized officials. 
11. REPORTS AND RECORDS MANAGEMENT 
This investigational study will comply with investigator reporting and record keeping requirements specified in 
“Medical Device Clinical Practice (GCP)”, which FDA published. These requirements are summarized below. 
11.1  I
NVESTIGATOR RECORDS 
Prior to participation in the investigation, the investigator must provide the following documentation to the 
Sponsor:  

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• Investigator Agreement, signed by the investigator and GCP office; 
• A copy of  the principal investigator’s, sub-investigator’s, other delegated study clinicians’  curriculum 
vitae; 
• A letter signed by the chairperson of the IRB overseeing the conduct of this study indicating that the IRB 
has reviewed and approved this investigational plan; and 
• A copy of the IRB-approved Informed Consent Form. 
During the study, investigators are required to maintain on file the following accurate, complete, and current 
records relating to this study as described in 21 CFR §812.140. A summary of these records is listed below: 
•  All correspondence and required reports, which pertain to the study. 
• Records of receipt, use, or disposition of study devices, including the type and quantity of devices; the 
dates of receipt; the serial numbers; the names of all persons who received, used or disposed of each 
device; and why and how many units of the device have been returned to the Sponsor, repaired, or 
otherwise disposed. 
• Records of each subject’s case history and exposure to the device. 
• Signed and dated consent forms. 
• Relevant observations, including records concerning adverse events, condition of each subject upon 
entering and results of diagnostic tests. 
• Study-specific data forms and corrections to the forms. 
• Protocol and amendments. 
• Subject recruiting materials. 
• Investigator curriculum vitae. 
 
11.2  I
NVESTIGATOR REPORTS 
Investigators are required to prepare and submit to the Sponsor the following complete, accurate, and timely 
reports on this investigation when are required. These reports, which are listed below, are required by 21 CFR 
§812.150; additional reports may be requested by the Sponsor: 
• The investigator will notify the Sponsor of a subject death occurring during the investigation, as soon as 
possible, preferably within 24 hours of learning of the subject’s death, but in no event later than 48 hours. 
The investigator will notify the reviewing IRB of a subject death as specified by the IRB. 
• The investigator will notify the Sponsor of any unanticipated adverse device effects within 48 hours after 
learning of the effect. The investigator will notify its reviewing IRB of any unanticipated adverse device 
effects, as soon as possible, but no later than 10 working days after learning of the effect. 
• The investigator will notify the Sponsor of the withdrawal of IRB approval, as soon as possible, but no 
later than five working days after learning of the withdrawal. 
• The investigator will provide current progress reports to the Sponsor and reviewing IRB at regular 
intervals and at least on an annual basis. 
• The investigator will notify the Sponsor and reviewing IRB of any deviation from the investigational plan 
to protect the life and physical well-being of a subject in an emergency, as soon as possible, but no later 
than five working days after the emergency occurred. 
• The investigator will notify the Sponsor and reviewing IRB that an informed consent was not obtained 
from a subject, as soon as possible, but no later than five working days after such an occurrence. 

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• The investigator will provide a final summary report to the Sponsor and reviewing IRB within three 
months after termination or completion of the study. 
• The investigator will provide any other information upon the request of an IRB, FDA, or the Sponsor. 
11.3  D
ATA COLLECTION 
During each subject’s visit to the clinic, an investigator participating in the study will record progress notes to 
document all significant observations. In addition, any contact with a subject by telephone or other means that 
provides significant clinical information will also be documented in the progress notes as described above. 
For transmission to the Sponsor, information from the study progress notes and other source documents will be 
promptly transcribed to study-specific data forms, or study data may be recorded directly onto study-specific data 
forms. In this clinical study, study-specific data forms may also serve as source documents. Transcription of study 
data onto study-specific data forms should be completed within 7 days of the study visit. 
Any changes to information in the study progress notes, other source documents, and data forms will be initialed 
and dated in ink on the day the change is made by a site study staff member authorized to make the change. 
Changes will be made by striking a single line through erroneous data, and clearly entering the correct data. If the 
reason for the change is not apparent, a brief explanation for the change will be written in the source 
documentation by the clinician. 
11.4  S
OURCE DOCUMENTS 
Source documents are defined as the results of original observations and activities of a clinical investigation. 
Source documents will include, but are not limited to, study-specific data forms, progress notes, electronic data, 
computer printouts, screening logs, and recorded data from automated instruments. All source documents 
pertaining to this study will be maintained by the investigators and made available for inspection by authorized 
persons.  The Ultherapy® treatment parameter system record will be considered the source document for the 
study treatment.  
 
11.5  R
ECORDS RETENTION AT THE STUDY SITE 
The investigator is responsible for retaining the necessary records, including a copy of the protocol, device labeling, 
study-specific data forms, medical records, original reports of test results, all study-related correspondence, a 
record of written informed consent, and any other documents pertaining to the conduct of this study. 
FDA regulations require all investigators participating in investigational device studies to maintain detailed clinical 
records during the investigation and for a period of at least two years after the latter of the following two dates: 
1. The date on which the investigation is terminated or complete; or 
2. The date the records are no longer required for purposes of supporting a premarket approval application. 
The investigator must not dispose of any records relevant to this study without either: 
1. Obtaining written permission from the Sponsor; or 
2. Providing an opportunity for the Sponsor to collect such records. 

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The investigator shall take responsibility for maintaining adequate and accurate electronic or hard copy source 
documents of all observations and data generated during this study. Such documentation is subject to inspection 
by the Sponsor and the FDA. 
12. MONITORING PROCEDURES 
12.1   M
ONITORING 
The Sponsor has ethical, legal, and scientific obligations to carefully follow this study in a detailed and orderly 
manner in accordance with established research principles and FDA regulations. As part of a concerted effort to 
fulfill these obligations (maintain current personal knowledge of the progress of the study), the Sponsor’s monitors 
will visit the center during the study in addition to maintaining frequent telephone and written communication. 
The following guidelines are provided to describe the Sponsor’s procedures for monitoring the clinical studies, and 
meet the requirements specified in 21 CFR §812.46. If the investigator is not complying with the signed 
Investigator Agreement, the protocol, or any condition of the study (e.g., incomplete data forms), the Sponsor has 
the right to terminate the investigator’s participation in the study.  
The Sponsor is responsible for selecting study monitors qualified by training and experience to conduct monitoring 
of the study, and for ensuring the quality of the study monitoring visits by the monitor. 
The Sponsor’s general monitoring procedures for investigational studies are described below. 
 12.2  P
RE-S
TUDY MONITORING PROCEDURES 
12.2.1  S
ELECTION OF MONITORS 
There will be an overall study monitor, and additional monitors as needed, for the investigational study. The 
Sponsor determines the total number of monitors for its investigational studies based on the size and complexity 
of the study, the number and location of sites, the number of subjects, and the scope of the contractual 
obligations at each site. All monitors must be qualified by education, training, and experience. 
 
12.2.2  C
LINICAL I
NVESTIGATORS 
Upon receipt of a signed Investigator Agreement and EC approval letter, sites will be sent the appropriate clinical 
study materials. 
12.3  S
ITE I
NITIATION VISIT 
A monitor will be responsible for determining and documenting that each investigator clearly understands and 
accepts the responsibilities and obligations incurred in conducting a clinical study. The monitor or designated 
Ulthera representative will conduct an on-site site initiation visit where it will be ensured prior to study initiation 
that the investigator:  
• Understands the requirements for a well-controlled study; 
• Understands the clinical protocol; 
• Understands his/her reporting obligations; 
• Understands the requirements for device accountability; 

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• Understands and accepts the obligations to obtain informed consent in accordance with 21 CFR Parts 50 
and 56; 
• Understands and accepts the obligation to obtain IRB review and approval of the clinical investigation 
before it is initiated and to ensure continuing review of the study by the IRB in accordance with 21 CFR 
Part 56, and to keep the Sponsor informed of all IRB actions concerning the study; 
• Understands and accepts the requirements regarding financial disclosure of clinical investigations, 21 CFR 
Part 54; 
• Has adequate facilities and access to an adequate number of suitable subjects to conduct the 
investigation; and 
• Has the required documentation on file, including IRB approval and a signed investigator agreement. 
12.4  P
ERIODIC MONITORING VISITS 
Monitoring visits will be conducted in accordance with Guidance for Industry, Oversight of Clinical Investigations – 
A Risk-Based Approach to Monitoring, August 2013, and the study-specific monitoring plan. The monitor should 
visit each site at an appropriate frequency to ensure the following: 
• Facilities continue to be adequate and acceptable. 
• The protocol is being properly followed. 
• The IRB has approved or been notified of any protocol changes. 
• Accurate, complete, and current records are being maintained, and the information recorded and 
submitted to the Sponsor is representative of the subject’s records and other supporting documentation. 
• Accurate, complete, and timely adverse event reports are being submitted to the Sponsor. 
• Informed consent has been obtained. 
• The reason for a subject’s withdrawal from the study has been documented. 
• Reports are being submitted to the IRB and Sponsor. 
• The appropriate staff is conducting study activities. 
The investigator or designee must, upon request, provide to the Sponsor, monitor or FDA investigator the 
necessary study records for a thorough review of the study’s progress. These records include, but are not limited 
to, study-specific data forms and original documents and records such as clinic charts, subject informed consent 
forms, and treatment reports. 
All study-specific data forms and other documentation related to the study will be reviewed upon receipt, and the 
site will be promptly notified of any deficiencies. 
12.5  F
REQUENCY OF MONITORING VISITS 
The frequency of monitoring visits will be determined on the basis of several factors, including: 
• Duration of the study; 
• Number of outstanding issues from previous visits; 
• Number of subjects enrolled; 
• Number of investigators/sites; and 
• Complexity of the study. 
Each site will undergo a monitoring visit in compliance with the monitoring plan. 

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12.6  S
TUDY CLOSURE 
All routine monitoring functions must be performed prior to the study closure visit; the study closure visit may be 
combined with a monitoring visit. The following tasks should be completed at the last visit by the monitor: 
• Ensure that all forms and images have been sent to the Sponsor; 
• Ensure that the Ulthera® System, study transducers, photographic equipment, and any other study 
supplies or equipment provided to the study site for study use have been returned to the Sponsor;  
• Remind the investigator of the obligation to retain the records; and 
• Prepare final monitoring report for Sponsor. 
12.7  R
EPORTS OF MONITORING VISITS 
Monitoring reports must be completed for all visits. Reports must include the following information: 
• Date of the visit; 
• List of study site personnel present; and 
• A summary of the findings, problems, and actions taken to correct any deficiencies; 
• A follow-up communication to the Principal investigator and study site outlining the findings, problems, 
and actions taken to correct any deficiencies. 
12.8  A
DDITIONAL AUDITING 
Regulatory authorities worldwide may also audit the investigator during or after the study. The investigator should 
contact the Sponsor immediately if this occurs, and must fully cooperate with the audits conducted at a reasonable 
time in a reasonable manner. 
 
 
 
 
13. CONFIDENTIALITY 
All information generated in this study must be considered highly confidential and must not be disclosed to any 
persons not directly concerned with the study without written prior permission from the Sponsor. Authorized 
regulatory officials and Sponsor personnel (or their representatives) will be allowed full access to inspect and copy 
the records. All investigational devices, subject bodily fluids, and/or other materials collected should be used solely 
in accordance with this protocol, unless otherwise agreed to in writing by the Sponsor. 
Subject names and identifiers will be coded for privacy and subjects will be identified only by unique subject 
numbers on study-specific data forms. If necessary, their full names may be made known to a regulatory agency or 
other authorized officials. 
14. AMENDMENT POLICY 

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The investigator will not make any changes to this protocol without prior written consent from the Sponsor and 
subsequent approval by the IRB, except if the deviation from the protocol is necessary to protect the life and 
physical well-being of a subject in an emergency. Such protocol deviations must be reported to the Sponsor and 
the reviewing IRB as soon as possible, but no later than five working days after the emergency occurred. 
Any permanent change to the protocol, whether it is an overall change or a change for specific study center(s), 
must be handled as a protocol amendment. Any amendment to the protocol that appears indicated as the study 
progresses will be fully discussed by the investigator(s) and the Sponsor. If agreement is reached regarding the 
need for an amendment, the Sponsor will write it. The written amendment must be submitted to the chairman of 
the IRB identified with this responsibility. Except for “administrative amendments”, investigators must await IRB 
approval of protocol amendments before implementing the change(s). Administrative amendments are defined to 
have no effect on the validity of the data or information resulting from the completion of the approved protocol, 
or the relationship of likely patient risk to benefit relied upon to approve the protocol; the scientific soundness of 
the investigational plan or protocol; and the right, safety or welfare of the human subjects involved in the 
investigation. 
When, in judgment of the chairman of the IRB, the investigators and/or the Sponsor, the amendment to the 
protocol substantially alters the study design and/or increases the potential risk to the subject, the currently 
approved written Informed Consent Form will require similar modification. In such cases, repeat informed consent 
will be obtained from subjects enrolled in the study before continued participation. 
15. STUDY I
NVESTIGATORS 
All investigators will be experienced with the cosmetic treatments using a variety of accepted clinical modalities. 
 
 
 
 
 
REFERENCES 
1. 
Dobke, M.K., et al., Tissue restructuring by energy-based surgical tools. Clin Plast Surg, 2012. 39(4): p. 399-
408. 
2. 
Sadick, N., Tissue tightening technologies: fact or fiction. Aesthet Surg J, 2008. 28(2): p. 180-8. 
3. 
Hantash, B.M., et al., In vivo histological evaluation of a novel ablative fractional resurfacing device. Lasers 
Surg Med, 2007. 39(2): p. 96-107. 
4. 
Shamsaldeen, O., J.D. Peterson, and M.P. Goldman, The adverse events of deep fractional CO(2): a 
retrospective study of 490 treatments in 374 patients. Lasers Surg Med, 2011. 43(6): p. 453-6. 
5. 
Kennedy, J.E., G.R. Ter Haar, and D. Cranston, High intensity focused ultrasound: surgery of the future? Br J 
Radiol, 2003. 76(909): p. 590-9. 
6. 
Lam B, Ip M, Tench E, Ryan C. Craniofacial profile in Asian and white subjects with obstructive sleep 
apnoea. Thorax, 2005;60(6):504-510. 
7. 
"Pain Intensity Instruments". National Institutes of Health – Warren Grant Magnuson Clinical Center. July 
2003. Archived from the original (PDF) on 2012-09-14. 

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Attachments: Outcome Measures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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