Evaluation of the Ulthera System for Treating Axillary Hyperhidrosis
Phase: NA
Conditions: Axillary Hyperhidrosis
Sponsor: Ulthera, Inc



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SPONSOR AGREEMENT 
Ulthera, Inc. (hereinafter “Study Sponsor”) maintains responsibility for the ongoing safety of this clinical trial involving the evaluation of 
the Ulthera System®.  Study Sponsor will promptly notify all investigators, the responsible IRB(s)or Ethics Committee(s) (EC), and the 
regulatory authorities of any findings from ongoing trial monitoring activities that could adversely affect the safety of subjects, impact the 
conduct of the clinical study, or alter the IRB’s or EC’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) or EC(s) with a copy of a final clinical study report.  
INVESTIGATOR AGREEMENT AND CERTIFICATION 
I hereby agree to participate in this clinical trial 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 trial 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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PROTOCOL SYNOPSIS 
Company Name: 
Ulthera, Inc., Merz Device Innovation Center (MDIC) 
Protocol Number: 
ULT-218 
Protocol Title: 
Evaluation of the Ulthera® System for Treating Axillary Hyperhidrosis 
Investigational Device: 
Ulthera® System 
Development Phase: 
Pilot 
Study Objective: 
To evaluate the Ulthera® System and the 7-3.0mm transducer for treating axillary 
hyperhidrosis. 
Study Design: 
Prospective, multi-site, non-randomized 
Number of Subjects:  
N = 20 treated subjects; subjects enrolled may be greater than subjects treated 
Study Treatment 
Groups: 
Enrolled subjects will receive treatment at a 3.0mm depth and 0.30 J of energy.  
Treatment will be delivered in a 3 x 4 grid, 12 treatment squares, delivering 60 lines of 
treatment per square, i.e., 720 lines per axilla in each treatment (1440 lines total per 
treatment.) 
Subject Population: 
Adults between 18 - 75 years of age who meet the inclusion/exclusion criteria. 
Inclusion Criteria: 
1. Male or female, age 18-75 years. 
2. Subject in good health. 
3. Diagnosis of bilateral axillary hyperhidrosis refractory to previous topical 
therapies. 
4. At least 50 mg of spontaneous resting axillary sweat production in each axilla 
measured gravimetrically at room temperature/humidity (20 - 25.6°C/20-
80%) over a period of 5 minutes. (Patients should be at rest for at least 30 
minutes after physical exercise including walking.) 
5. HDSS score of 3 or 4. An attempt will be made to approximate an equal 
number of scores 3 and 4. 
6. Understands and accepts the obligation not to undergo any other procedures 
in the areas to be treated through the follow-up period. 
7. Willingness and ability to comply with protocol requirements, including 
returning for follow-up visits and abstaining from exclusionary procedures for 
the duration of the study. 
8. 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 for at least 12 months prior to study; 
b. Without a uterus and/or both ovaries; or  
c. 
Bilateral tubal ligation at least six months prior to study enrollment. 
9. Absence of physical or psychological conditions unacceptable to the 
investigator. 
10. Willingness to refrain from use of aspirin, Ibuprofen, Naproxen or any other 
NSAID, and Vitamin E in the 2 weeks prior to each study treatment . 
11. Willingness and ability to provide written informed consent prior to 
performance of any study-related procedure. 
Exclusion Criteria: 
1. Dermal disorder including infection at anticipated treatment sites in either 

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axilla. 
2. Previous botulinum toxin treatment of the axilla in the past year. 
3. Expected use of botulinum toxin for the treatment of any other disease during 
the study period. 
4. Known allergy to starch powder, iodine, lidocaine, or epinephrine. 
5. Secondary hyperhidrosis, for example, hyperhidrosis that is secondary to 
other underlying diseases including hyperthyroidism, lymphoma and malaria. 
6. Previous surgical treatment of hyperhidrosis including sympathectomy, 
surgical debulking of the sweat glands, subcutaneous tissue curettage and 
ultrasonic surgery. 
7. Unwillingness to wash off antiperspirants and abstain use 72 hours prior to 
treatments or assessments. 
8. Subjects with a history of a bleeding disorder 
9. Active implants (e.g., pacemakers or defibrillators), or metallic implants in the 
treatment areas.) 
10. Use of cholinomimetics, anticholinergics, or any oral herbal medicine 
treatments for hyperhidrosis. 
11. Inability to withhold use of antiperspirants or any other topical treatments for 
hyperhidrosis within 72 hours prior to study treatments and assessments. 
12. Unwillingness for complete shaving or removal of underarm hair within 12 
hours prior to study treatments and follow-up visits.   
13. Women who are pregnant, lactating, possibly pregnant or planning a 
pregnancy during the study period. 
14. Inability to understand the protocol or to give informed consent. 
15. History of chronic drug or alcohol abuse. 
16. History of chronic or frequently recurring episodic (recurrent episode in past 
12 months) autoimmune diseases such as Multiple Sclerosis, Crohn’s Disease, 
Psoriasis, Myasthenia Gravis, Lambert-Eaton Syndrome that has required 
immune suppressant therapy (such as biologic drug or corticosteroid 
treatment).. 
17. Concurrent therapy that, in the investigator’s opinion, would interfere with 
the evaluation of the safety or efficacy of the study device. 
18. Subjects who anticipate the need for surgery or overnight hospitalization 
during the study. 
19. Subjects who, in the investigator’s opinion, have a history of poor 
cooperation, noncompliance with medical treatment, or unreliability. 
20. Concurrent enrollment in any study involving the use of investigational 
devices or drugs. 
21. Use of antiplatelet agents / Anticoagulants (Coumadin, Heparin, Plavix) in the 
past 6 weeks; 
a. Psychiatric drugs that in the investigators opinion would impair the 
subject from understanding the protocol requirements. 
Treatment Outline: 
1. Screening/Baseline/Treatment Visit #1: 
a. Obtain Informed Consent and medical history; 
b. Screen for general inclusion/exclusion criteria; 
c. 
Obtain axillary ultrasound images of each axilla; 
d. Perform pregnancy screening test, if applicable; 

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e. Complete baseline evaluations: HDSS, gravimetric, and starch iodine 
test with digital images of the result; 
f. 
Administer local anesthetic to both axillas;  
g. 
Perform bilateral Ultherapy treatment;  
h. Assess Numeric Rating Scale for Pain; and  
i. 
Assess for adverse events. 
2. Post-treatment #1 telephone contact: 
a.    Capture adverse events (7±2 days). 
3. Treatment Visit #2, 30 + 7 days post-treatment #1: 
a. Complete HDSS, gravimetric, and starch iodine test with digital 
images of the result; 
b. Perform pregnancy screening test, if applicable; 
c. 
Administer local anesthetic to both axillas; 
d. Perform bilateral Ultherapy treatment;  
e. Assess Numeric Rating Scale for Pain; and 
f. 
Assess for adverse events. 
4. Post-treatment #2 telephone contact: 
a.    Capture adverse events (7±2 days). 
5. Follow-up Visits post-treatment #2 for efficacy evaluation: 
a. 30 + 7 days 
i. Complete HDSS, gravimetric test, and starch iodine test with 
digital images of the result; and 
ii. Assess for adverse events. 
b. 90 + 7 days 
i. Complete HDSS, gravimetric test, and starch iodine test with 
digital images of the result; 
ii. Assess for adverse events; and 
iii. Perform pregnancy screening test, if applicable. 
Primary Endpoint: 
HDSS score reduction from a 3 or 4 at baseline to a 1 or 2 at 30 days post-treatment 
#2. 
Secondary Endpoints: 
1. Reduction in spontaneous axillary sweat production assessed by a gravimetric 
method at 90 days post treatment #2, as measured by a 50% reduction or 
more compared to baseline. 
2. HDSS score reduction from a 3 or 4 to a 1 or 2 at 90 days post treatment #2. 
3. Starch iodine test to assess area of efficacy with digital images. 
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. 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. Additional pregnancy 
screening tests will be performed (if applicable) prior to treatment #2 and at the 180-
day follow-up visit. 
Study Duration: 
Given two months for recruitment and with two study treatments provided 30 days 
apart, the anticipated study duration is six months. 
 
 
 

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TABLE OF CONTENTS 
Signature Page ....................................................................................................................... i 
Sponsor Contact Information ................................................................................................. ii 
Sponsor Agreement ................................................................................................................ i 
Investigator Agreement and Certification ............................................................................... i 
Protocol Synopsis .................................................................................................................. ii 
Study Overview ..................................................................................................................... v 
List of Acronyms and Definitions ........................................................................................... vi 
List of Figures and Tables ....................................................................................................... x 
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 ............................................................................................................3 
1.4 
Device Overview ...................................................................................................................4 
1.5 
Preclinical Studies .................................................................................................................5 
1.6 
Clinical Studies .....................................................................................................................6 
1.6.1 
Clinical Safety Study at MEEI ................................................................................................................. 6 
1.6.2 
Clinical Safety and Effectiveness Study at Northwestern University ..................................................... 6 
1.6.3. 
Clinical Safety and Effectiveness Study at The University of Texas Southwestern Medical Center 
(UTSW) 7 
1.6.4 
Prospective, Multi-center, Pivotal Trial Evaluating the Safety and Effectiveness of the Ulthera® 
System for Improvement in Lines and Wrinkles of the Décolletage ..................................................................... 8 
1.6.5 
Hyperhidrosis Pilot Study ....................................................................................................................... 9 
2. Study Objective and Design .............................................................................................. 10 
2.1 
Study Objective .................................................................................................................. 10 
2.2 
Type and Design of Study .................................................................................................... 10 
2.3  
Duration of Study ............................................................................................................... 10 
3. Study Procedures ............................................................................................................. 10 
3.1 
Schedule of Assessments at Each Study Visit ....................................................................... 10 
4. Subject Selection and Pre-Treatment ................................................................................ 11 
4.1  
Pre-treatment Recruiting/Screening .................................................................................... 12 

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4.2  
Informed Consent ............................................................................................................... 12 
4.3  
Eligibility ............................................................................................................................ 12 
4.3.1 
Inclusion Criteria .................................................................................................................................. 12 
4.3.2 
Exclusion Criteria ................................................................................................................................. 13 
4.4 
Screen Failures ................................................................................................................... 14 
4.5 
Subject Randomization and Treatment Group Assignment................................................... 14 
4.6 
Study Images ...................................................................................................................... 14 
5. Treatment of Subjects and Follow-up ............................................................................... 14 
5.1 
Study Treatment ................................................................................................................. 14 
5.1.1 
Transducers.......................................................................................................................................... 14 
5.1.2 
Pre-Treatment Medications ................................................................................................................. 14 
5.1.3  
Subject Preparation for Treatment ...................................................................................................... 14 
5.1.4 
Treatment ............................................................................................................................................ 15 
5.1.5 
Acute Responses .................................................................................................................................. 15 
5.2 
Safety Variables .............................................................................................................. 1615 
5.3 
Outcome Measures ............................................................................................................ 16 
5.3.1 
Primary Endpoint ................................................................................................................................. 16 
5.3.2 
Secondary Endpoints ........................................................................................................................... 16 
5.4 
Follow-up ........................................................................................................................... 17 
5.5 
Protocol Deviations ............................................................................................................ 17 
5.6  
Withdrawal Criteria and Procedures .................................................................................... 17 
5.7  
End of Study (Completion) .................................................................................................. 17 
6. Statistical Analysis ........................................................................................................1817 
6.1 
Efficacy Analysis ................................................................................................................. 18 
6.2 
Safety Analyses .................................................................................................................. 18 
7. Evaluation of Adverse Events ........................................................................................... 18 
7.1 
Definitions.......................................................................................................................... 18 
7.2 
Relationship to the Investigational Device ........................................................................... 19 
7.3 
Unanticipated Adverse Device Effects (Events) .................................................................... 19 
7.4 
Serious Adverse Event ........................................................................................................ 20 
7.5 
Reporting Requirements for Serious Adverse Events............................................................ 20 
7.6 
Severity .............................................................................................................................. 20 
7.7 
Deaths................................................................................................................................ 21 

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7.8 
Pre-Existing Conditions ....................................................................................................... 21 
8. Risk Analysis .................................................................................................................... 21 
8.1 
Potential Risks .................................................................................................................... 21 
8.2 
Minimization of Potential Risks ........................................................................................... 22 
8.3 
Potential Benefits ............................................................................................................... 22 
8.4 
Justification for the Clinical Study........................................................................................ 22 
9. Device Management ........................................................................................................ 22 
9.1 
Packaging ........................................................................................................................... 22 
9.2 
Storage............................................................................................................................... 22 
9.3 
Accountability .................................................................................................................... 23 
10. Regulatory and Ethical Requirements ............................................................................. 23 
10.1 
Informed Consent ........................................................................................................... 23 
10.2 
Institutional Review Board or Ethics Committee ............................................................... 23 
10.3 
Confidentiality of Subject Records ................................................................................... 23 
11. Reports and Records Management ................................................................................ 24 
11.1 
Investigator Records ........................................................................................................ 24 
11.2 
Investigator Reports ........................................................................................................ 24 
11.3 
Data Collection ................................................................................................................ 25 
11.4 
Source Documents .......................................................................................................... 25 
11.5 
Records Retention at the Study Site ................................................................................. 26 
12. Monitoring Procedures .................................................................................................. 26 
12.1  
Monitoring ...................................................................................................................... 26 
12.2 
Pre-Study Monitoring Procedures .................................................................................... 26 
12.2.1 
Selection of Monitors .......................................................................................................................... 26 
12.2.2 
Clinical Investigators ............................................................................................................................ 27 
12.3 
Site Initiation Visit ........................................................................................................... 27 
12.4 
Periodic Monitoring Visits ............................................................................................... 27 
12.5 
Frequency of Monitoring Visits ........................................................................................ 28 
12.6 
Study Closure .................................................................................................................. 28 
12.7 
Reports of Monitoring Visits ............................................................................................ 28 

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12.8 
Additional Auditing ......................................................................................................... 28 
13. Premature Termination or Suspension of the Investigation or an Investigation Site ........ 29 
14. Confidentiality ............................................................................................................... 29 
15. Amendment Policy ......................................................................................................... 29 
16. Study Investigators ........................................................................................................ 30 
References........................................................................................................................... 31 
Attachment A: Hyperhidrosis Disease Severity Scale............................................................. 32 
Attachment B: Numeric Rating Scale .................................................................................... 33 
 
 
LIST OF FIGURES AND TABLES 
Figure 1.2-1. SKIN & SWEAT GLAND ANATOMY ............................................................................................................ 2 
FIGURE 1.4-1 PRIMARY COMPONENTS .......................................................................................................................... 4 
TABLE 1.4-1 TRANSDUCER TYPES .................................................................................................................................. 5 
TABLE 1.4-2 TRANSDUCER ENERGY LEVELS ................................................................................................................... 5 
TABLE 3.1-1 SCHEDULE OF ASSESSMENTS ................................................................................................................... 11 
FIGURE 5.1.3-1 TARGET TREATMENT AREAS ............................................................................................................... 15 
Figure 7.1.1.  EVENT REPORTING ................................................................................................................................. 19 
TABLE 7.2-1. RELATIONSHIP BETWEEN ADVERSE EVENTS AND INVESTIGATIONAL DEVICE ........................................ 19 
Table 8.1.1 EXPECTED TREATMENT EFFECTS ............................................................................................................... 21 

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1. INTRODUCTION 
1.1 
DEVICE NAME AND INDICATIONS 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 trial described in this protocol evaluates clinical outcomes associated with the non-invasive treatment 
for axillary hyperhidrosis. The investigator will assess the subjects for hyperhidrosis using gravimetric 
measurement and assess the area of efficacy using a Starch Iodine test. Subjects will evaluate their conditions 
using the Hyperhidrosis Disease Severity Scale (HDSS) (Attachment A). 
1.2 
BRIEF AGING BACKGROUND AND TREATMENT OVERVIEW 
Hyperhidrosis is a disease characterized by perspiration in excess of the physiologic amount necessary to maintain 
thermal homeostasis[1]. Hyperhidrosis can have very significant effects on patients’ lives, causing physical 
discomfort and social embarrassment and negatively impacting occupational and daily activities.  
 
Primary or idiopathic hyperhidrosis and secondary hyperhidrosis are the two main categories[2]. Patients can have 
excessive sweating either in a localized area (focal) or over the entire body (generalized). Primary disease is usually 
focal, affecting the soles, palms, and axillae in various combinations and with varying degrees of severity. 
Secondary hyperhidrosis can be generalized or focal. In secondary hyperhidrosis the symptoms are due to one of a 
large number of medical conditions, including endocrine disorders, neurological problems, use of certain drugs, 
cancer, chronic infections, dermatologic syndromes, and conditions associated with excess catecholamine 
discharge[3]. Occasionally hyperhidrosis can be seen on the head and face as a primary disorder or become 
apparent as gustatory sweating secondary to parotid surgery or diabetes. This study focuses on primary 
hyperhidrosis of the axillae. 
 
Sweat glands in patients with hyperhidrosis are not histopathologically different from those in normal patients, nor 
is there an increase in the number or size of glands. The condition is caused by hyperfunction of the sweat glands 
rather than hypertrophy[4]. Patients with primary hyperhidrosis have a higher-than-normal basal level of sweat 
production as well as an increased response to normal stimuli such as emotional or physical stress.  
 
Humans have up to four million sweat glands distributed over the body, of which about three million are eccrine 
sweat glands. Eccrine glands secrete an odorless, clear fluid that serves to aid in the regulation of body 
temperature by allowing heat loss by evaporation. Eccrine glands are in higher density on the soles of the feet and 
the forehead, followed by the palms and the cheeks.[5, 6]  Apocrine sweat glands are located in limited areas—the 
axilla and urogenital regions—and produce a thick, odorless fluid that undergoes bacterial decomposition, leading 
to substances with strong odors. The ratio of apocrine to eccrine glands is one to one in the axillae and one to ten 
elsewhere.[5] 
 

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Botulinum toxin A injection has been used successfully to reduce excessive sweating in all of the body areas 
affected in primary hyperhidrosis: axillary, palmoplantar, and facial/gustatory. Characterized as a “minimally 
invasive treatment option” compared to local surgery and endoscopic thoracic sympathectomy, the use of 
botulinum toxin has become an important treatment option for patients not responding to more conservative 
therapies.[7] Botulinum toxin A has been approved for use in hyperhidrosis in Canada, the U.K. and other countries 
in Europe and South America (more than 23 countries total). In 2004, the US Food and Drug Administration (FDA) 
approved botulinum toxin type A for the treatment of severe primary axillary hyperhidrosis in patients unable to 
obtain relief using antiperspirants. 
Systemic medication can be used for the treatment of generalized or focal hyperhidrosis.[10] Many of the drugs 
reported useful for hyperhidrosis have not been studied in controlled trials, their use being based only on 
anecdotal evidence. Furthermore, at the doses likely to inhibit hyperhidrosis, side effects can be limiting.[12] In 
addition many of these drugs are not approved by the US Food and Drug Administration specifically for the 
treatment of hyperhidrosis. 
The most invasive treatment for hyperhidrosis is the surgical interruption of the thoracic sympathetic chain, a 
procedure done with the goal of permanently stopping sweating in the area innervated by the involved ganglia. 
Sympathectomy has been shown to be very effective for palmar sweating, but is less effective for axillary 
symptoms.[1] Although now done as a minimally invasive technique using video-assisted endoscopy, the 
procedure is still associated with complications that lead most clinicians to reserve this procedure for patients with 
severe symptoms who have failed to improve with more-conservative treatment.[10] 
Treatment of severe hyperhidrosis by excision of sweat glands is clearly only feasible for axillary disease. The 
eccrine sweat glands are located in the deep dermis and in the upper subcutaneous layer.[15] There have been 
many different procedures used to remove axillary sweat glands; they can be grouped into three major 
categories.[16] Excision of both skin and underlying sweat glands is the most radical approach. Removing 
subcutaneous glands through a small incision by scraping the glands from the undersurface of the dermis with a 
curette or by liposuction are two major variants of the same approach. The third category is a mixture of the first 
two—a limited central excision is combined with curettage of the surrounding axillary subcutaneous glands.[1] All 
of these procedures can be done under tumescent local anesthesia. 
1.3 
MECHANISM OF ACTION 
The Ulthera® System images and delivers focused ultrasound energy to a specific soft tissue layer under the 
superficial layers of epidermis. Ultrasound treatment creates focal micro-coagulation zones in the skin, causing 
thermally induced contraction of tissue and a “wound-healing” response to stimulate the formation of new tissue 
and collagen, and to cause a skin-tightening/wrinkle-reduction effect. 
As stated earlier, it is hypothesized that the creation of focal lesions at the depth of the sweat glands, will 
effectively damage the glands without surface effects and result in a reduction of sweat. 
 
The device is designed and configured to produce small (approximately 1mm3) micro-coagulation zones in the mid 
to deep reticular layer of dermis and sub-dermis, while sparing overlying papillary dermal and epidermal layers of 
skin. The device also incorporates an ultrasound imaging capability to evaluate the skin tissue. 
 
 

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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 STUDIES 
Three clinical studies have been conducted using the Ulthera® System: a clinical safety study at MEEI (Protocol 
Number 05-06-032), a pivotal study at Northwestern University in Chicago (Protocol Number 1253-014, IDE 
G060261), and a clinical safety and effectiveness Study at the University of Texas Southwestern Medical Center 
(UTSW) (Protocol Number 00000404). During these studies, in which the Ulthera® System was extensively used, 
safe and efficacious energy delivery protocols were established. 
1.6.1 CLINICAL SAFETY STUDY AT MEEI 
A prospective, open-label clinical safety study was conducted at MEEI in 15 subjects who were scheduled to 
undergo a limited rhytidectomy (mini-facelift) procedure (Protocol Number 05-06-032). The study was approved 
by the MEEI Human Studies Committee (the Institutional Review Board [IRB]), and all subjects signed the informed 
consent document. The objective of this clinical study was to confirm the conclusion that the Ulthera® System 
provides controlled thermal micro-coagulative zones in the dermis while sparing the epidermis. Safety was 
assessed in terms of skin inflammation, pain, adverse events, and histology. 
Subjects were treated with the Ulthera® System either approximately 24 hours before or 4 to 12 weeks before 
undergoing a mini-facelift. The investigator performed treatment using the Ulthera® System according to the 
instructions provided in the protocol and based upon the treatment plans verified and validated in prior preclinical 
testing. The investigator selected the transducer and then performed one of three treatment plans on the portion 
of the face and neck that would be subsequently excised during the mini-facelift. 
Fifteen subjects were treated; 7 subjects underwent the facelift surgery within 24 hours following treatment with 
the Ulthera® System and 8 subjects underwent the facelift surgery within 4 to 12 weeks after treatment. During 
treatment, 1,300 ultrasound exposure pulses were delivered using three different transducers, including the 7-
4.5mm, 7-3.0mm, and 4-4.5mm transducers. There was no disruption to the epidermis noted in any subject, no 
adverse events noted, and no delayed adverse sequelae to the treated skin. The skin tissue was excised during the 
mini-facelift procedure either immediately or 4 to 12 weeks after treatment. The tissue was frozen, sectioned, and 
stained for gross and histopathology evaluation. Histopathology analysis of acute samples of skin tissue treated 
with the Ulthera® System (within 24 hours) showed thermal coagulative zones below the skin epidermis with 
complete epidermal preservation. Histopathology was also performed on the tissue excised from those subjects 
who underwent a delayed facelift (4 to 12 weeks following treatment with the Ulthera® System). No definitive 
findings of discrete coagulative changes were observed in the delayed cases, and there were no findings of 
extensive fibrous tissue or tissue scarring. 
The Ulthera® System was determined to be safe for delivery of targeted, precise, and consistent regions of thermal 
coagulation in the dermis and subcutaneous tissues while sparing of the epidermis. 
1.6.2 CLINICAL SAFETY AND EFFECTIVENESS STUDY AT NORTHWESTERN UNIVERSITY 
A prospective, open-label clinical study was conducted at Northwestern University (Protocol Number 1253-014, 
G060261). The study was approved by the IRB at Northwestern University, and all subjects signed the informed 
consent document. The objectives of this clinical study were to: 1) demonstrate the safety of the Ulthera® 

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treatment and 2) achieve eyebrow elevation resulting from tissue coagulation and tightening. Thirty-five subjects 
were enrolled in the study. Enrolled subjects were of either sex over the age of 21, who had a desire to obtain an 
improvement of eyebrow elevation and had chosen to receive an Ultherapy™ treatment. Enrollment was open to 
all skin types (Fitzpatrick 1-VI). 
Subjects were treated with the Ulthera® System on their faces and necks. The investigator performed treatments 
using the Ulthera® System according to the instructions provided in the protocol. The investigator selected the 
transducer and treatment plan for each individual subject. Thirty-five subjects were treated using the Ulthera® 
System and all three transducers were used. All subjects were followed for over 90 days to assess safety and 
effectiveness. 
All subjects completed and tolerated the procedure well. There was no disruption to the epidermis observed in any 
subject and no adverse events were observed. Further there was no evidence of skin hyper- or hypo-pigmentation 
in subjects for up to 10 months following treatment. 
A masked, clinical assessment of eyebrow position was performed by evaluating pre- and post-treatment images 
to determine efficacy. Subjects underwent standardized photographic evaluations on Day 0, pre-treatment, and 
Day 90, post-treatment. Three board-certified physicians assessed the eyebrow height and characteristics by 
reviewing in a randomized order the Day 0 and Day 90 images of each subject. The cumulative result of the three 
masked reviewers was an 85.7% “Improved” evaluation for the 35 subjects. Twenty-four subjects treated with the 
Ulthera® System completed a Patient Satisfaction Survey at 8 to 10 months post-treatment. The survey 
demonstrated that 75% of the subjects were either satisfied or very satisfied with improvement in their eyebrow 
position after the Ulthera® treatment. In addition, 75.7% of the subjects demonstrated a measurable improvement 
in eyebrow height at Day 90 post-treatment. 
This clinical study using the Ulthera® System to treat the face and neck demonstrated safe and efficacious delivery 
of ultrasound energy. The thermal coagulative tissue effect in skin resulted in a clinically significant improvement 
of the eyebrow position in the majority of subjects, while preserving the epidermis. 
1.6.3. CLINICAL SAFETY AND EFFECTIVENESS STUDY AT THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL 
CENTER (UTSW) 
An open-label, prospective, non-randomized, clinical trial 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 

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(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 mm2 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. 
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.  
1.6.4 PROSPECTIVE, MULTI-CENTER, PIVOTAL TRIAL EVALUATING THE SAFETY AND EFFECTIVENESS OF THE 
ULTHERA® SYSTEM FOR IMPROVEMENT IN LINES AND WRINKLES OF THE DÉCOLLETAGE 
An open-label, prospective, non-randomized multi-center clinical trial was conducted evaluating the safety and 
efficacy of the Ulthera System to achieve improvement of lines and wrinkles of the décolleté.  The clinical study’s 
protocol was approved under IDE G120004 (Protocol Number ULT-129) for enrolling up to 130 female subjects 
between the ages of 35-60 at up to four clinical sites with a 90 and 180 day follow up.     The Fabi-Bolton Scale, a 
published validated scale, was prospectively defined to evaluate wrinkle improvement. However, successful 
validation of the Fabi-Bolton Scale during the clinical trial could not be accomplished due to kappa scores for both 
intra-rater and inter-rater reproducibility being low. Therefore, the primary endpoint was changed from the Fabi-
Bolton Scale to a post-hoc retrospective masked assessment of pre and 180 day post treatment photographs. 
There were no pre-specified success criteria of the masked assessment established at the beginning of the clinical 
trial. In addition to masked assessment, there was also an unmasked assessment called the Clinician Global 
Aesthetic Improvement Scores (CGAIS). Finally, patient satisfaction questionnaires were also measured to assess 
improvement. 
Upon analysis of all the photographs used in the clinical study, 54 of 108 day 180 photos were identified as having 
inconsistencies in photo quality (changes in lighting, color, focus, patient positioning, cropping, etc.). Therefore a 
sub-set analysis was conducted using the primary endpoint of masked assessment on the remaining 54 day 108 
evaluable photo sets that were deemed the most consistent in photo quality.  The results of the sub-set analysis 
demonstrated improvement of lines and wrinkles based on masked assessment of pre- and post-treatment 
photographs in 36 of 54 (~67%) evaluable subjects with the most consistent photo quality after one Ultherapy® 
treatment 180 days post-treatment.  Subjects’ overall aesthetic improvement was based on CGAIS assessment by 
the study clinician. Subjects rated at some degree of improvement (very much improved, much improved or 
improved) were 76% and 65% at 90 and 180 days, respectively. Patient satisfaction questionnaires (PSQ), 
completed at 90 and 180 days post-treatment captured whether subjects were satisfied with their Ultherapy® 
treatment and if they noticed improvement in their décolleté area.  At 90 days, 62% and 81% of the subjects were 
satisfied with their Ultherapy® treatment and noticed improvement in their décolleté area, respectively.  This 
response continued through 180 days post-treatment, where 65% and 85% of the subjects were satisfied and 
noticed improvement in their décolleté area, respectively.  Device safety was demonstrated as there were no 
serious adverse events (SAEs) or unanticipated adverse device effects (UADEs) related to treatment with the 

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Ulthera System. Of the adverse events, all but two were mild. Only two events were moderate, one of which was 
not device-related. All events resolved. 
This study demonstrated that Ultherapy® is safe and efficacious for the improvement of lines and wrinkles of the 
décolleté. 
 
1.6.5 HYPERHIDROSIS PILOT STUDY 
A randomized, double-blind, controlled pilot study was conducted to evaluate the efficacy and safety of the 
Ulthera® System for the treatment of primary axillary hyperhidrosis.  The objective of study was to evaluate the 
efficacy and safety of the Ulthera® System for treatment of primary axillary hyperhidrosis.   
 
Twenty subjects meeting inclusion and exclusion criteria were enrolled.  These criteria included a score of 3 or 4 on 
the Hyperhidrosis Disease Severity Scale (HDSS) as well as >50mg/5 min of sweat production in both axilla as 
measures by gravimetric method.  Active-treated subjects (N=12)  received two treatments 28 days apart 
consisting of 240 lines each, using both 4MHz-4.5mm and 7MHz-3.0mm transducers, for a total of 480 lines per 
axilla.   No energy was delivered during a similar treatment for Sham-treated subjects (N=8).  Both groups received 
pre-treatment injections of lidocaine plus epinephrine.  Efficacy at 7, 14, 30, 37, 44, 60, 90, and 120 days was 
measured by Hyperhidrosis Disease Severity Scale, gravimetric sweat production, and starch iodine test.   Patient 
satisfaction was assessed at 30, 60, and 90 days (trial days 60, 90 and 120) after second treatment.  The primary 
endpoint was response at 60 days (30 days after second treatment), defined as HDSS score of 1 or 2.  Adverse 
events were collected at all follow-up time points and spontaneous reports were also collected. 
 
Subjects were an average age 34 (range 21-52), 30% were female, 30% Caucasian, 50% Hispanic/Latino, 15% 
African American, and 5% Asian.   No subjects responded to sham treatment, either at the primary endpoint visit 
or at any other visit throughout the study.   
 
At 30 days after second treatment (day 60 of trial), the response rate, as measured by HDSS, in the active 
treatment group was 67%, a significant difference compared to 0% in the sham group (p = 0.005, two-sided 
Fisher’s exact test (FET)).  Response to active treatment peaked 7 days after the second treatment (83%) and was 
sustained for the remainder of the trial.   Ninety days after the second treatment (day 120 of the trial), 67% of 
subjects were still in response.  Gravimetric measurement of sweat production showed similar results.  At all 
follow-up study visits, sweat production decreased from baseline by at least 50% in the active treatment group but 
not in the sham group.  Regardless of study visit, percent change from baseline in gravimetric measurement was 
significantly greater in the active treatment group than in the sham group (p < 0.0001, rank-based repeated 
measures analysis of variance).  In the active treatment group, the greatest change from baseline (73.1%) was at 
90 days after the second treatment (day 120 of the trial).  Starch iodine testing qualitatively supported a reduction 
in sweat production in the active-treated subjects compared to sham-treated subjects.   All but one subject at 30 
and 90 days after second treatment and two subjects at 60 days after second treatment in the active-treated 
group were satisfied or very satisfied.   None of the sham-treated reported satisfaction at any time point after the 
second treatment.   Treatment-related AEs reported in the active-treated group were bruising in 3 subjects (15%) 
with an average duration of 3.3 days (range 2-5 days), soreness or tenderness in  subjects (83%) lasting an average 
of 12.9 days (range 4-31 days) during which only 2 subjects took a single dose of ibuprofen the day after 
treatment, numbness in 1 subject (8%) lasting 13 days, and paresthesia in 3 subjects (25%) lasting an average of  
13.3 days (range 10-18 days).   Treatment related AEs reported in the sham-treated group were soreness in 2 
subjects (25%) lasting1 day, and paresthesia in 1 subject (12.5%) lasting 1 day.  Average pain scores for both 
transducers during both treatments for the sham-treated group were 0.8 (range 0-5) while pain scores averaged 
1.8 (range 0-5 for the active-treated group suggesting that blinding was sufficient. 

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Pilot study results suggest the Ulthera® System may be efficacious and safe for the treatment of axillary 
hyperhidrosis. 
 
2. STUDY OBJECTIVE AND DESIGN 
2.1 
STUDY OBJECTIVE 
The objective of this study is to evaluate the effect of Ultherapy using the 7-3.0mm transducer on axillary sweat 
glands. 
2.2 
TYPE AND DESIGN OF STUDY 
This study is a prospective, multi-center, non-randomized clinical trial. Up to 20 subjects who are naïve to 
Ultherapy for treatment of hyperhidrosis will be enrolled if all entrance criteria are met confirming eligibility for 
study treatment.  Subjects will be treated using the Ulthera® System by the study investigator, sub-investigator or 
delegated clinician, receiving treatment in a 3 x 4 grid, 12 treatment squares, 60 lines of treatment per square, at 
one treatment depth (3.0mm), at 0.30 J of energy.  
 
Ultrasound images will be captured of each axilla prior to the first study treatment to assess dermal thickness and 
depth of sweat glands.  A gravimetric measurement of sweat production, starch iodine test, and pregnancy 
screening test, if applicable, will be performed prior to each study treatment.  Digital images of the starch iodine 
test will be obtained. HDSS scores will be obtained prior to each treatment.  During treatment, the average 
Numeric Rating Scale (NRS) score will be obtained by axilla treated.  
 
Following the completion of study treatment(s), follow-up visits will be at 30, and 90 days post-treatment to assess 
safety and efficacy.  Gravimetric sweat production measures and starch iodine tests will be completed at 
treatment visit #2 and at all follow-ups for all study groups.  Digital images of the starch iodine test will be 
obtained.  HDSS scores will be obtained at the treatment visit(s) and at all follow-ups for all study groups.  
 
Efficacy will be determined by HDSS score reduction from a 3 or 4 at baseline to a 1 or 2 at 30 days post-treatment. 
Subject Gravimetric results, Starch iodine results, and HDSS scores at all follow-ups will also be analyzed as 
secondary outcomes. 
2.3  
DURATION OF STUDY 
Recruitment for this study may take approximately two months. Subjects will receive two study treatments 
provided 30 days apart.  Following the treatment visit #2, subjects will be followed for a total duration of 90-days. 
Therefore, the anticipated total duration of the study is approximately six months. 
3. STUDY PROCEDURES 
3.1 
SCHEDULE OF ASSESSMENTS AT EACH STUDY VISIT 
Table 3.1-1 provides an overview of the subject screening procedure, baseline evaluation, treatment plan, and 
follow-up requirements. 

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4.1  
PRE-TREATMENT RECRUITING/SCREENING 
Subjects will be recruited from the study site’s patient database and screened.  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  
INFORMED CONSENT 
Written informed consent will be obtained from all subjects (or their guardians 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 or EC. Each Informed Consent Form will include the 
elements required by FDA regulations in 21 CFR Part 50. 
The IRB- or EC-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  
ELIGIBILITY 
4.3.1 INCLUSION CRITERIA 
Subjects must meet all of the following criteria for study enrollment: 
1. Male or female, age 18-75 years. 
2. Subject in good health. 
3. Diagnosis of bilateral axillary hyperhidrosis refractory to previous topical therapies. 
4. At least 50 mg of spontaneous resting axillary sweat production in each axilla measured gravimetrically at 
room temperature/humidity (20 - 25.6°C/20-80%) over a period of 5 minutes. (Patients should be at rest 
for at least 30 minutes after physical exercise including walking.) 
5. HDSS score of 3 or 4. An attempt will be made to approximate an equal number of scores 3 and 4. 
6. Understands and accepts the obligation not to undergo any other procedures in the areas to be treated 
through the follow-up period. 
7. Willingness and ability to comply with protocol requirements, including returning for follow-up visits and 
abstaining from exclusionary procedures for the duration of the study. 
8. 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 for at least 12 months prior to study; 
b. Without a uterus and/or both ovaries; or  
c. 
Bilateral tubal ligation at least six months prior to study enrollment. 
9. Absence of physical or psychological conditions unacceptable to the investigator. 

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10. Willingness to refrain from use of aspirin, Ibuprofen, Naproxen or any other NSAID, and Vitamin E in the 2 
weeks prior to each study treatment. 
11. Willingness and ability to provide written informed consent prior to performance of any study-related 
procedure. 
4.3.2 EXCLUSION CRITERIA 
Subjects will be excluded if they meet any of the following criteria: 
1. Dermal disorder including infection at anticipated treatment sites in either axilla. 
2. Previous botulinum toxin treatment of the axilla in the past year. 
3. Expected use of botulinum toxin for the treatment of any other disease during the study period. 
4. Known allergy to starch powder, iodine, lidocaine, or epinephrine. 
5. Secondary hyperhidrosis, for example, hyperhidrosis that is secondary to other underlying diseases 
including hyperthyroidism, lymphoma and malaria. 
6. Previous surgical treatment of hyperhidrosis including sympathectomy, surgical debulking of the sweat 
glands, subcutaneous tissue curettage and ultrasonic surgery. 
7. Unwillingness to wash off antiperspirants and abstain use 72 hours prior to treatments or assessments. 
8. Subjects with a history of a bleeding disorder 
9. Active implants (e.g., pacemakers or defibrillators), or metallic implants in the treatment areas.) 
10. Use of cholinomimetics, anticholinergics, or any oral herbal medicine treatments for hyperhidrosis. 
11. Inability to withhold use of antiperspirants or any other topical treatments for hyperhidrosis within 72 
hours prior to study treatments and assessments. 
12. Unwillingness for complete shaving or removal of underarm hair within 12 hours prior to study 
treatments and follow-up visits.   
13. Women who are pregnant, lactating, possibly pregnant or planning a pregnancy during the study period. 
14. Inability to understand the protocol or to give informed consent. 
15. History of chronic drug or alcohol abuse. 
16. History of chronic or frequently recurring episodic (recurrent episode in past 12 months) autoimmune 
diseases such as Multiple Sclerosis, Crohn’s Disease, Psoriasis, Myasthenia Gravis, Lambert-Eaton 
Syndrome that has required immune suppressant therapy (such as biologic drug or corticosteroid 
treatment).. 
17. Concurrent therapy that, in the investigator’s opinion, would interfere with the evaluation of the safety or 
efficacy of the study device. 
18. Subjects who anticipate the need for surgery or overnight hospitalization during the study. 
19. Subjects who, in the investigator’s opinion, have a history of poor cooperation, noncompliance with 
medical treatment, or unreliability. 
20. Concurrent enrollment in any study involving the use of investigational devices or drugs. 
21. Use of antiplatelet agents / Anticoagulants (Coumadin, Heparin, Plavix) in the past 6 weeks; 
22. Psychiatric drugs that in the investigators opinion would impair the subject from understanding the 
protocol requirements. 
After subjects have provided informed consent and met the inclusion/exclusion criteria, the study procedures 
described in the following section will be performed. Subjects can be enrolled in the study and treated according 
to this protocol on the same day. 
 
 

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4.4 
SCREEN 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. Screen failure subjects will be included in the total number of subjects enrolled (i.e., all subjects 
consented), but not counted towards the total subjects treated. 
4.5 
SUBJECT RANDOMIZATION AND TREATMENT GROUP ASSIGNMENT  
Subjects are not randomized in this study. They will all be treated using the same treatment approach (see Section 
5.1 for Study Treatment details). 
4.6 
STUDY IMAGES 
Ultrasound images will be obtained of each axilla using the Ulthera® System at baseline.  All starch iodine tests will 
be captured with digital images.  All images will be captured using a 2D digital imaging system. 
5. TREATMENT OF SUBJECTS AND FOLLOW-UP 
This study involves two treatments 30 days apart completed at the treatment visit #1 and treatment visit #2 after 
obtaining informed consent, screening for inclusion/exclusion, confirming the completion of a washout period of 
at least 2 weeks from use of aspirin, Ibuprofen, Naproxen or any other NSAID, and Vitamin E, if applicable, 
complying with protocol specified photography requirements, completing a pregnancy test, if applicable, and 
completing any study specific baseline assessments. 
5.1 
STUDY TREATMENT 
5.1.1 TRANSDUCERS 
One transducer will be used during this trial – a 7 MHz transducer with 3.0mm focal depth. 
The location to be treated, the transducer, and the energy level will be recorded on the Treatment Parameter 
System Record. 
5.1.2 PRE-TREATMENT MEDICATIONS 
All study subjects will receive injections of 1% lidocaine with epinephrine to each axilla prior to each study 
treatment.     
5.1.3  SUBJECT PREPARATION FOR TREATMENT 
a. The investigator, sub-investigator, or delegated clinician will first assess the subject's hyperhidrosis based on: 
 
Starch iodine test 
 
Amount of subcutaneous soft tissue in region to be treated and the area to be treated 
 
The treatment map identifies the areas and pattern where the Ulthera® treatment is to be performed (Figure 
5.1.3-1). Treatment schematic is for illustrative purposes only. Treatment records for all regions will be maintained 
in accordance with this protocol. 
 
 

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FIGURE 5.1.3-1 TARGET TREATMENT AREAS  
 
5.1.4 TREATMENT 
All study treatments will be performed by the investigator, sub-investigator, or delegated clinician (i.e., study 
treatment clinician as designated by the principal investigator.)  
Ultrasound gel will be applied to the transducer, which will then be placed on the targeted skin surface, and an 
ultrasound image will be obtained. Each area of the proposed treatment will be imaged first with the ultrasound 
device to ensure appropriate 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) above will be administered in a 3 x 4 grid (minimum), 
resulting in at least 12 treatment squares, depending on the size of each subject’s axilla. Two Ultherapy® 
treatments will be provided at a 3.0mm depth, 30 days apart.  At each treatment, study subjects should receive a 
minimum of 720 treatment lines, +10% variance, to each axilla (minimum of 1440 total lines of treatment for both 
axillae) delivering 60 treatment lines per treatment square.  The treatment lines must be delivered in multiple 
passes, with no more than 10 lines delivered per treatment square with each pass, for a total of at least 6 passes 
per square.  When delivering passes of treatment, all 12 treatment squares should be treated with 10 lines in 
sequential order (square 1, square 2 and so on), then once complete with the first pass the sequence is followed 
again to deliver a second pass of 10 lines per square until all 6 passes of 10 lines per square are completed.    
 
The purpose of specifying the number of lines per pass and number of total passes is to minimize the risk of 
adverse events (AE).  In a prior clinical trial, it was observed that AE rates were lower when this high-density 
treatment was delivered as stated above.  The subject will be monitored during the treatment.  
 
5.1.5 ACUTE 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. Short-term post-treatment adverse events will be assessed via phone 
contact with study subjects following each study treatment at 7±2 days post-treatment. 
 
 

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5.2 
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 (Attachment B). Pain scores should be obtained following 
each completed pass for each axilla treated. The average pain score for the entire axilla treated will then 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. Additional pregnancy screening tests will be 
performed (if applicable) prior to treatment #2 and at the 90-day follow-up visit. 
5.3 
OUTCOME MEASURES 
The Hyperhidrosis Disease Severity Scale (HDSS) 
The Hyperhidrosis Disease Severity Scale (HDSS) (Attachment A) is a validated scale used for primary 
axillary/underarm hyperhidrosis patients.  It provides a qualitative measure of the severity of their condition based 
on how it affects their daily activities.  Patients select the statement that best reflects their experience with 
underarm sweating. It is a 4-point scale, with the following descriptors:  
1. My underarm sweating is never noticeable and never interferes with my daily activities  
2. My underarm sweating is tolerable but sometimes interferes with my daily activities  
3. My underarm sweating is barely tolerable and frequently interferes with my daily activities  
4. My underarm sweating is intolerable and always interferes with my daily activities 
Gravimetric Sweat Production 
Reduction of at least 50% from baseline in the average spontaneous axillary sweat production per subject (left and 
right axilla), i.e., up to 40 data points per time point, assessed by gravimetric method.  
 
Gravimetric method is performed by drying the surface of the skin, then applying a pre-weighed filter paper to the 
axilla for a period of time (5 min) measured by a stopwatch. The paper is then weighed and the rate of sweat 
production is calculated in mg/5 min based on the difference in end weight and pre-weight. 
 
Start Iodine Test  
Performed to assess area of efficacy. Starch Iodine test is performed by applying an iodine solution to the sweaty 
area.  After it dries, starch is sprinkled on the area. The starch-iodine combination turns a dark blue color wherever 
excess sweat is present. Digital images of the starch iodine test will be obtained. 
5.3.1 PRIMARY ENDPOINT 
The primary endpoint of this study is HDSS score reduction from a 3 or 4 at baseline to a 1 or 2 at 30 
days post-treatment #2. 
 
5.3.2 SECONDARY ENDPOINTS 
The secondary endpoints of this clinical trial include: 
1. A reduction in spontaneous axillary sweat production assessed by gravimetric method at all time points 
following completion of study treatment(s), as measured by a 50% reduction or more compared to 
baseline.  

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a. Gravimetric method is performed by drying the surface of the skin, then applying a pre-weighed 
filter paper to the axilla for a period of time measured by a stopwatch. The paper is then weighed 
and the rate of sweat production is calculated in mg/min. 
2. HDSS score reduction from a 3 or 4 to a 1 or 2 at 90 days post treatment #2.  
3. Starch iodine test to assess area of efficacy.   
a. Starch Iodine test is performed by applying an iodine solution to the sweaty area.  After it dries, 
starch is sprinkled on the area. The starch-iodine combination turns a dark blue color wherever 
excess sweat is present. Digital images of the starch iodine test will be obtained. 
5.4 
FOLLOW-UP 
Subjects will be asked to return to the clinic for follow-up visits at 30 and 90 days post-treatment #2.  
The following assessments will be completed at all follow-up visits: gravimetric assessment, starch iodine test, and 
HDSS.  Digital images of the starch iodine test will be obtained.  At the last follow-up visit, a pregnancy screening 
test will be completed, if applicable.  Safety endpoints and adverse events will be monitored at all follow-up visits.   
5.5 
PROTOCOL 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 or EC 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  
WITHDRAWAL 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  
END OF STUDY (COMPLETION) 
All subjects who have signed an Informed Consent Form, except for screen failures, will be considered enrolled in 
the study. Subjects who 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 six weeks after the last 

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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 ANALYSIS 
For a given parameter, data will be summarized for each time point for which data for that parameter are 
available.  Summaries will be displayed by time point.  Subjects with incomplete data will be included in summaries 
for which they have data available.  Baseline will be defined as the most recent observation before the first 
treatment.  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.  For the primary efficacy outcome, two-sided 95% confidence intervals will be calculated for differences in 
proportions between study groups.  All programs for data output and analyses will be written in SAS® version 9.2 
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 a follow-up visit at 30-days post-treatment #2 will 
be included in the analysis using the Last Value Carried Forward method.  Analyses of safety will include all 
subjects who received (complete or incomplete) study treatment. 
Efficacy will be the proportion of treated subjects determined to be improved by the reduction in the number of 
sweat glands from baseline to 30-days post-treatment #2. 
6.2 
SAFETY ANALYSES 
All adverse events and device related adverse events will be presented as the number of subjects reporting each 
event. 
7. EVALUATION OF ADVERSE EVENTS 
7.1 
DEFINITIONS 
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, defined as: any typical treatment side-effect of 
Ultherapy® of mild to moderate severity and lasting up to a typical maximum duration (See Table 8.1.1 for typical 
maximum durations), or as 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 
RELATIONSHIP TO THE INVESTIGATIONAL 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 
UNANTICIPATED ADVERSE DEVICE EFFECTS (EVENTS) 
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 IRB OR 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 
SERIOUS 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: 
Death 
Death was an outcome of the adverse event.  
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. 
Hospitalization (initial or prolonged) 
Admission to the hospital or prolongation of hospitalization was a result of the adverse event. 
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. 
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. 
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. 
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 
REPORTING 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 or EC according to the IRB or EC 
regulations at the study site. 
7.6 
SEVERITY 
Each adverse event should be assessed for its severity, or the intensity of an event experienced by the subject, 
using the following classifications: 

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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 
7.7 
DEATHS 
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 or EC according to the IRB or EC regulations at the study site. 
7.8 
PRE-EXISTING 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 
POTENTIAL 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 in Table 8.1.1 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 1 week  
Acute Pain 
Immediate/momentary (while energy is being delivered) - 2 hours 
Induration 
Up to 12 weeks 
Pruritus 
Up to 2 weeks 
Welting/Raised Areas of Edema 
Up to 4 weeks 
Skin Burn, Scarring, Change in pigmentation 
Up to 8 weeks  
Tenderness/Soreness/Pain/Sensitivity to Touch   
Up to 3 weeks  
/Muscle 
Twitching/Tingling/Paresthesia/Numbness 
Up to 5 weeks 
Reduced Range of Motion 
Up to 3 weeks 
Skin Peeling 
Up to 2 weeks 
 
Additional potential risks include: nerve injury, arterial blood spasm, change in axilla odor, and reduction of 
underarm hair growth. 
The risks from lidocaine with epinephrine may include pain and discomfort from the injections, infection at the 
anesthetic site, lightheadedness, nervousness, mood change, tinnitus, blurred vision, vomiting, sensations of heat, 
cold or numbness, tremors, seizures, or unconsciousness.  Additional uncommon side effects may include 
bradycardia, hypotension and cardiac arrest.  Allergic reactions may appear as skin rashes, swelling or anaphylaxis.  

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Risk associated with a starch iodine test may include an allergic reaction to iodine solution or starch powder.  No 
risks are anticipated from completion of a gravimetric sweat test or ultrasound imaging.   
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 
MINIMIZATION OF POTENTIAL RISKS 
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 
POTENTIAL BENEFITS 
There is a potential benefit to participants of this study who are seeking temporary relief of axillary hyperhidrosis 
symptoms.  Results of the study may contribute to developing an ultrasound-based, non-invasive axillary 
hyperhidrosis procedure. 
8.4 
JUSTIFICATION 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 
amended clinical plan outlined herein is expected to result in a reduction of hyperhidrosis symptoms, and 
achievement of a positive clinical outcome. 
9. DEVICE MANAGEMENT 
9.1 
PACKAGING 
On a site-specific basis, the Ulthera® System will be shipped in a hard case designed to protect the system during 
delivery.  
9.2 
STORAGE 
Shipping and storage conditions include: 
Shipping and Storage, System without Transducers 
 
 
 
 
 
 
Shipping and Storage, with Transducers 
 
 
 
 

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9.3 
ACCOUNTABILITY 
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 
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) or Ethics Committee Regulations (ICH Guidelines); the Financial Disclosure by Clinical Investigators 
Regulations (21 CFR Part 54); and the Investigational Device Exemptions Regulations (21 CRF Part 812). 
10.1 INFORMED CONSENT 
Informed consent will be obtained from all subjects prior to study participation. 
10.2 INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE 
Prior to initiation of any study procedures, the protocol, informed consent, and operators manual will be 
submitted to a duly constituted IRB or EC for view and approval. In addition, any amendments to the protocol or 
Informed Consent Form will be reviewed and approved by the IRB or EC. The Sponsor must receive a letter 
documenting IRB or EC 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 or EC during the course of 
the clinical study. These reports will include: 
 
Informing the IRB or EC 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; 
 
Reporting any deviations from the clinical protocol to protect the life or well-being of a subject in the case 
of an emergency within five working days after the emergency occurred; 
 
Reporting the use of the device without obtaining informed consent from a subject within five working 
days of the event; and  
 
Providing any other reports requested by the IRB or EC. 
The IRB or EC must be notified of study completion 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 CONFIDENTIALITY 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. 

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11. REPORTS AND RECORDS MANAGEMENT 
This investigational study will comply with investigator reporting and record keeping requirements specified in 21 
CFR Part 812. These requirements are summarized below. 
11.1 INVESTIGATOR RECORDS 
Prior to participation in the investigation, the investigator must provide the following documentation to the 
Sponsor:  
 
Investigator Agreement, signed by the investigator, which lists any physicians who will be involved in 
conducting the investigation under the direction of the primary investigator; 
 
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 or EC overseeing the conduct of this study indicating that the 
IRB or EC has reviewed and approved this investigational plan; and 
 
A copy of the IRB- or EC-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 INVESTIGATOR 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 or EC of a subject death as specified by the IRB or EC. 
 
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 or EC of any unanticipated adverse 
device effects, as soon as possible, but no later than 10 working days after learning of the effect. 

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 
The investigator will notify the Sponsor of the withdrawal of IRB or EC 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 or EC at regular 
intervals and at least on an annual basis. 
 
The investigator will notify the Sponsor and reviewing IRB or EC 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 or EC 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. 
 
The investigator will provide a final summary report to the Sponsor and reviewing IRB or EC within three 
months after termination or completion of the study. 
 
The investigator will provide any other information upon the request of an IRB or EC, FDA, or the Sponsor. 
11.3 DATA 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 trial, 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 SOURCE 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. 
 
 

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11.5 RECORDS 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. 
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  MONITORING 
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 trial, 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 PRE-STUDY MONITORING PROCEDURES 
12.2.1 SELECTION 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. 
 
 

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12.2.2 CLINICAL INVESTIGATORS 
Upon receipt of a signed Investigator Agreement and IRB or EC approval letter, investigators will be sent the 
appropriate clinical study materials. 
12.3 SITE INITIATION 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; 
 
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 or EC review and approval of the clinical 
investigation before it is initiated and to ensure continuing review of the study by the IRB or EC in 
accordance with 21 CFR Part 56, and to keep the Sponsor informed of all IRB or EC 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 or EC approval and a signed investigator 
agreement. 
12.4 PERIODIC 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 or EC 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 or EC and Sponsor. 
 
The appropriate staff is conducting study activities. 
The investigator or designee must, upon request, provide to the Sponsor 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 

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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 FREQUENCY 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. 
12.6 STUDY 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 and IRB or EC. 
12.7 REPORTS 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 ADDITIONAL 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. 
 
 

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13. PREMATURE TERMINATION OR SUSPENSION OF THE INVESTIGATION OR AN 
INVESTIGATION SITE 
The investigation or an investigation site can be prematurely terminated or suspended by the sponsor. Reasons for 
termination of the investigation or an investigation site may include, but are not limited to, the following: 
 
Subject enrolment is unsatisfactory. 
 
The risks and benefits of continuing the investigation have been reassessed, and the risks outweigh any 
potential benefits. 
 
The incidence of AEs constitutes a potential health hazard to the subjects. 
 
New scientific data on the device do not justify a continuation of the investigation. 
 
The investigator or investigation site exhibit serious and/or persistent non-adherence to the clinical 
protocol, the Declaration of Helsinki, EN ISO 14155, and/or applicable regulatory requirements. 
 
The sponsor decides to terminate the investigation at any time for any other reason. 
 
Furthermore, the investigation may be prematurely ended if the regulatory authority or the EC has 
decided to terminate or suspend approval for the investigation, the investigation site, or the investigator. 
If the investigation is prematurely terminated or suspended for any reason, the investigator must inform the 
subjects and assure appropriate follow-up treatment. Within the timeframes noted in applicable regulations, the 
sponsor will promptly inform the investigators, investigation sites, the EC, and regulatory authorities of the 
termination or suspension of the investigation, as well as provide reasons for the action. The sponsor will notify 
the administration departments of clinical investigation of all clinical trial institutions within five days, and specify 
reasons in a written form. 
14. 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. 
15. AMENDMENT POLICY 
The investigator will not make any changes to this protocol without prior written consent from the Sponsor and 
subsequent approval by the IRB or EC, 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 or EC 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 

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the IRB or EC identified with this responsibility. Except for “administrative amendments”, investigators must await 
IRB or EC 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 or EC, 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. 
16. STUDY INVESTIGATORS 
All investigators will be experienced with the cosmetic treatments using a variety of accepted clinical modalities. 
 
 

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REFERENCES 
1. 
Atkins JL and Butler PE, Hyperhidrosis: a review of current management. Plast Reconstr Surg, 2002. 110(1): 
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Boni R, Generalized hyperhidrosis and its systemic treatment. Curr Probl Dermatol, 2002. 30: p. 44-47. 
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Adar R, Kurchen A, Zweig A, Mozes M, Palmar hyperhidrosis and its surgical treatment: a report of 100 
cases. Ann Surg, 1977. 186: p. 34-41. 
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Heckmann M, Hyperhidrosis of the axilla. Curr Probl Dermatol, 2002. 30: p. 149-155. 
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Stolman LP, Treatment of hyperhidrosis. Dermatol Clin, 1998. 16: p. 863-869. 
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Anliker MD, Kreyden OP, Tap water iontophoresis. Curr Probl Dermatol, 2002. 30: p. 48-56. 
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Altman RS, Schwartz RA, Emotionally induced hyperhidrosis. Cutis, 2002. 69: p. 336-338. 
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Lillis PJ, Colemen W Jr, Liposuction for treatment of axillary hyperhidrosis. Dermatol Clin, 1990. 8: p. 479-
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Hafner J, Beer GM, Axillary sweat gland excision. Curr Probl Dermatol, 2002. 30: p. 57-63. 
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Kennedy JE, Ter Haar GR, Cranston D, High intensity focused ultrasound: surgery of the future? Br J Radiol, 
2003. 76(909): p. 590-9. 
 
 
 

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ATTACHMENT B: NUMERIC RATING SCALE