A Single-Center 2-Arm Study of the Enlighten and Excel V Laser for Lentigines on the Hands
Phase: NA
Conditions: Lentigines
Sponsor: Cutera Inc.

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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TITLE PAGE 
 
Protocol Number: 
C-16-EV09 
Protocol Title: 
A Single-Center, 2-Arm Study of the Enlighten™  and Excel V™ 
Lasers for Lentigines on the Hands 
 
Sponsor: 
 
Cutera, Inc. 
3240 Bayshore Boulevard 
Brisbane, CA 94005 
Principal Investigator: 
Site: 
Kelly Stankiewicz, MD FAAD 
DuPage Medical Group 
2155 City Gate Lane 
Suite 225 
Naperville, IL 60563 
(630) 547-5040 
 
Version, Date: 
Version 1.0 Dated April 06, 2016 
Statement of Compliance  
The study will be conducted in accordance with the design and specific provisions of this IRB approved protocol, in 
accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent 
with Good Clinical Practice (GCP) and the applicable regulatory requirement(s).  
 
 
 
NOTE:  The confidential information in the following document is provided to you as an investigator, potential investigator, or consultant for 
review by you, your staff, and applicable Institutional Review Board. By accepting this document, you agree that the information contained 
herein will not be disclosed to others, without written authorization from Cutera, Inc. except to the extent necessary to obtain informed 
consent from those persons to whom the device will be administered. 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
Page 2 of 23                                                       
Version 1.0  06 APR 2016 
 
Protocol Signature Page – Principal Investigator 
 
 
 
 
 
Study Title:   
A Single-Center 2-Arm Study of the Excel V™ and Enlighten™ Lasers for Lentigines on the Hands 
 
 
Protocol Version 1.0, Dated Apr 06, 2016 
 
I have received and read the protocol dated April 06, 2016 and agree to adhere to the requirements. I am aware 
that my adherence to the above protocol is mandatory and that any changes in the protocol or informed consent 
form must first be approved by Cutera, Inc. and the Institutional Review Board (IRB), except those changes necessary 
to eliminate apparent immediate hazards to subjects.  I will provide copies of this protocol and all pertinent 
information to the study personnel under my supervision. I will discuss this material with them and ensure they are 
fully informed regarding their role in the study. I will ensure that the study is conducted in compliance with the 
protocol, Good Clinical Practice (GCP), and all applicable regulatory requirements, and with the reviewing IRB 
requirements. I agree to commence this study only after documented IRB approval is obtained. 
 
 
 
 
Principal 
Investigator 
 
 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Printed Name 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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Table of Contents 
Protocol Summary ........................................................................................................................................................ 5 
1 
BACKGROUND INFORMATION ............................................................................................................................. 6 
2 
STUDY PURPOSE AND OBJECTIVES ...................................................................................................................... 7 
3 
STUDY DESIGN ...................................................................................................................................................... 7 
3.1 
Study Endpoints ................................................................................................................................................ 7 
3.1.1 
Primary Endpoint .......................................................................................................................................... 7 
3.1.2 
Secondary Endpoints .................................................................................................................................... 8 
3.3 
Study Assessments ............................................................................................................................................ 8 
3.3.1 
Percent Reduction in the Number of Lentigines .......................................................................................... 8 
3.3.2 
Physician’s Global Assessment Scale ............................................................................................................ 8 
3.3.3 
Subject Assessments ..................................................................................................................................... 9 
3.4 
Photographs .................................................................................................................................................. 9 
3.5 
Study Discontinuation ................................................................................................................................... 9 
3.6 
Investigator Selection ................................................................................................................................... 9 
4 
STUDY POPULATION ............................................................................................................................................. 9 
4.1 
Study Subject Recruitment and Selection including procedures for randomization .................................... 9 
4.2 
Subject Selection ......................................................................................................................................... 10 
4.2.1 
Inclusion Criteria ................................................................................................................................. 10 
4.2.2 
Exclusion Criteria ................................................................................................................................ 10 
4.3 
Subject Discontinuation Criteria ................................................................................................................. 11 
5 
STUDY PROCEDURES .......................................................................................................................................... 11 
5.1 
Screening Visit ................................................................................................................................................. 11 
5.2 
Laser Treatment Visit(s) .................................................................................................................................. 11 
5.3 
Final Follow-Up Visit ....................................................................................................................................... 13 
6 
ADVERSE EVENTS ............................................................................................................................................... 13 
6.1 
Reporting of Adverse Events ...................................................................................................................... 14 
6.2 
Follow-up of Subjects after AEs .................................................................................................................. 14 
7 
POTENTIAL RISKS / BENEFITS ............................................................................................................................. 14 
7.1 
Potential Risks ................................................................................................................................................. 14 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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7.2 
Potential Benefits ............................................................................................................................................ 14 
7.3 
Risk Management ........................................................................................................................................... 15 
8 
TRAINING AND MONITORING ............................................................................................................................ 15 
9 
DATA ANALYSIS PLAN .......................................................................................................................................... 15 
9.1 
Sample Size Calculation .................................................................................................................................. 15 
9.2 
Data Analysis ................................................................................................................................................... 15 
10 
INFORMED CONSENT ......................................................................................................................................... 15 
11 
DATA COLLECTION AND RECORD KEEPING......................................................................................................... 16 
12 
SUBJECT CONFIDENTIALITY ................................................................................................................................ 16 
13 
PUBLICATION POLICY ......................................................................................................................................... 17 
REFERENCES ................................................................................................................................................................ 18 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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1 
 BACKGROUND INFORMATION 
Non-invasive treatment options are in high demand by patients wanting to improve the appearance of their skin 
without surgical intervention. As a result, patients now have a variety of options for non-invasive skin treatments, 
from laser and light-based treatments to devices that utilize ultrasound and radiofrequency, however this was not 
always the case. Initial skin improvement procedures utilized ablative lasers, such as the carbon dioxide (CO2) and 
erbium:yttrium-aluminum-garnet (Er:YAG), and resulted in substantial improvement in skin appearance, texture, 
rhytides and laxity[1-3]. However, since ablative treatments destroy the epidermal layer of the skin in order to 
penetrate and heat the deeper dermal layers, ample post-procedure recovery time is required and patients may 
experience side effects lasting for a few weeks. Furthermore, hypo- or hyperpigmentation, prolonged wound 
healing and even scarring can occur following ablative procedures [4-6]. Treatment methods with less risk of side 
effects and post-treatment down time are in high demand. As such, the choices are vast and varied, ranging from 
fractional non-ablative laser devices to those that use radiofrequency [7-15]. Fractional lasers inflict microscopic 
zones of thermal damage in the dermal layers of the skin without destruction of the epidermis, thereby reducing 
recovery time significantly as compared to ablative procedures[16]. Treatment with non-fractional, non-ablative 
laser devices requires little to no post-procedure recovery time. Nonablative lasers of various wavelengths are 
effective for improvement of skin appearance based on the principle of selective photothermolysis, whereby laser 
light is absorbed by hemoglobin in blood vessels and melanin in pigment-producing skin cells [17, 18]. Absorption 
of laser light by these molecular chromophores results in the production of heat, leading to destruction of 
unwanted blood vessels and pigment cells. Heat production within the dermis by the laser light also results in 
immediate collagen contraction and heat-induced wound healing that, over time, causes a cascade of cellular 
events leading to new collagen production and improved skin appearance [8, 10, 19-23].  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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1 = Mild Improvement 
 
 
 
 
0 = No Change 
 
3.3.3 
Subject Assessments 
3.3.4 
At 4 weeks post-final treatment, subjects will be asked to complete a questionnaire to rate their level of 
satisfaction with the laser treatment outcome and the overall laser treatment procedure 
 
   
 
 
 
 
  
 
3.4 
Photographs 
Standardized digital photographs will be taken of each subject’s hand(s) at baseline, prior to all laser treatments, 
immediately after each laser treatment, and at the end of study visit. 
 
 
 
 
  
3.5 
Study Discontinuation 
The sponsor (Cutera, Inc.) has the right to terminate this study at any time.  Reasons for terminating the study may 
include, but are not limited to, the following: incidence or severity of adverse events in this or other studies 
indicates a potential health hazard to subjects; subject enrollment is unsatisfactory; number of protocol deviations 
is unacceptable; data recording is inaccurate or incomplete; or questionable study site compliance with ICH-E6, 
Good Clinical Practice. 
3.6 
Investigator Selection 
The investigator will be invited to participate in the study based on his/her medical specialty, experience 
conducting clinical research studies and experience in the use of light-based devices for aesthetic indications. 
Access to potential study subjects and the investigator’s sincere interest in this study along with expressed 
willingness to cooperate with the study process and requirements will also be considered.  
4 
STUDY POPULATION 
4.1 
Study Subject Recruitment and Selection including procedures for randomization 
 male or female subjects who desire laser treatment for lentigines on the hand(s) will be studied for each 
of the laser treatments. Subjects will be recruited to participate from the local population. Subjects may also be 
recruited from the investigator’s existing patient database or from patients who present themselves to the study 
site requesting treatment. Only subjects who meet all eligibility criteria and who provide written informed 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
Page 10 of 23                                                       
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consent will be enrolled into the study.  After verification of eligibility, there will be randomization into one laser 
group.   
4.2 
Subject Selection 
Each subject will be evaluated by the investigator to assess his/her suitability for entry into the study according to 
the following inclusion and exclusion criteria.  
4.2.1 
Inclusion Criteria 
To be included in the study, subjects must meet all of the following Inclusion Criteria: 
1.  
Female or Male, 30-90 years of age (inclusive). 
2.  
Fitzpatrick Skin Type I – III. 
3.  
Desires non-invasive and non-ablative treatment of lentigines on the hand(s). 
4.  
Have 4 or more lentigines on the hand(s).  
5.  
Subject must be able to read, understand and sign the Informed Consent Form. 
6.  
Must be willing and able to adhere to the treatment and follow-up schedule and post-treatment 
care instructions. 
7.  
Willing to have very limited sun exposure and use an approved sunscreen of SPF 50 or higher on 
the treatment area every day for the duration of the study, including the follow-up period. 
8.  
Willing to have digital photographs taken of the treatment area and agree to use of photographs 
for presentation, educational or marketing purposes. 
9.  
Agree to not undergo any other procedure(s) for treatment of lentigines during the study, 
including but not limited to chemical peel, laser and light based device treatment, and home-use 
device treatment. 
10.  
Agree to not undergo any injection of botulinum toxin, collagen, hyaluronic acid filler or other 
dermal filler to the treatment area during the study. 
 
 
4.2.2 
Exclusion Criteria 
Subjects will be excluded from the study if they meet any of the following Exclusion Criteria: 
 
1.  
Participation in a clinical trial of another device or drug in the target area within 6 months prior 
to enrollment or during the study. 
2.  
Any type of prior cosmetic treatment to the target area within 6 months of study participation, 
such as laser or light-based procedures or surgery. 
3.  
Systemic use of retinoid, such as isotretinoin, within 6 months of study participation.  
4.  
Use of topical medications on the hands, such as antibiotics, benzoyl peroxide, retinoids 
(isotretinoin), corticosteroids, hydroquinone, or products containing dihydroxyacetone or alpha-
hydroxy with concentration > 8%, within 1 month of participation. 
5.  
History of malignant tumors in the target area. 
6.  
Skin abnormalities in the target area, e.g., cuts, scrapes, wounds, scars, large moles. 
7.  
Pregnant. 
8.  
Having an infection, dermatitis, or a rash in the treatment area. 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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9.  
History of keloid scarring, hypertrophic scarring or of abnormal wound healing.  
10.  
Any use of medication that is known to increase sensitivity to light according to investigator’s 
discretion. 
11.  
History of radiation to the treatment area or undergoing systemic chemotherapy for the 
treatment of cancer.  
12.  
History of pigmentary disorders, particularly tendency for hyper- or hypo-pigmentation. 
13.  
Anytime in life, having have used gold therapy (gold salts) for disorders such as rheumatologic 
disease or lupus. 
14.  
Excessively tanned in areas to be treated or unable/unlikely to refrain from tanning during the 
study.  
15.  
In the opinion of the investigator, any physical or mental condition which might make it unsafe 
for the subject to participate in this study or which requires systematic therapy that could 
interfere with this research study. 
4.3 
Subject Discontinuation Criteria 
Participation in this study is completely voluntary and a subject can choose to withdraw from the study at any 
time.  In addition, a subject can be discontinued for any of the following reasons: the principal investigator 
decides that continuing in the study would not be in the subject’s best interest, a subject is noncompliant with the 
protocol, a subject has a serious reaction to the treatment, or the study is stopped by the study sponsor. In 
addition, subjects will be discontinued from the study if s/he develops any of the exclusion criteria.  
5 
STUDY PROCEDURES 
 
5.1 
Screening Visit 
The following procedures will be performed prior to the first laser treatment for both types of laser treatments: 
 
1. Informed consent. 
2. Investigator assessment of treatment area for study eligibility. 
3.  Review of medical history. 
4. Subject will be randomly assigned to either the Enlighten cohort or the Excel V cohort. 
5. Assessment of concomitant medications. 
6. Pre-treatment digital photographs of the subject’s treatment area will be taken. 
7. Provide and explain the before / after treatment instructions to the subject. 
 
Once it has been determined that the subject meets all criteria to be included in the study and informed consent 
has been obtained, the subject will be enrolled in the study.  
5.2 
Laser Treatment Visit(s) 
 
  

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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6.1 
Reporting of Adverse Events  
If any serious adverse event (SAE), anticipated or unanticipated, occurs at any time during or after the use of the 
device within the study period, the investigator must report it to Cutera within 24 hours using the Cutera Serious 
Adverse Event Report Form.  
If the SAE is unanticipated in nature, severity or degree of incidence, Cutera will notify all events that fulfill the 
following criteria to the Institutional Review Board (IRB) within ten (10) working days using the IRB Unanticipated 
Problem/Event Report Form: 
• 
Serious (i.e., death, a life-threatening adverse experience, inpatient hospitalization or prolongation of 
existing hospitalization, a persistent or significant disability or incapacity, or a congenital anomaly or birth 
defect) [21 CFR 312.32(a)], AND 
• 
Unexpected (i.e., not described in the Informed Consent Document), AND 
• 
Related to the study design, procedures, or device (possibly, probably or definitely related, or unknown). 
OR 
• 
Any event that, in the opinion of the investigator, may adversely affect the rights, welfare or safety of 
subjects in the study. 
6.2 
Follow-up of Subjects after AEs 
All reported AEs should be followed until resolution or until the subject’s participation in the study ends.  All AEs 
assessed by the investigator as probably related or possibly related to the study device should be followed until 
they resolve or until the investigator assesses them as “chronic” or “stable”.  Resolutions of such events are to be 
documented on the appropriate CRF pages.  All AEs that result in permanent discontinuation from this clinical 
trial, whether serious or not, should also be reported on the Subject Non-Completion of Study Form. 
7 
POTENTIAL RISKS / BENEFITS 
7.1 
Potential Risks 
 
 
 
 
 
 
 
7.2 
Potential Benefits 
The subjects may or may not benefit from the treatment. There is no guarantee of success.  

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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7.3 
Risk Management 
The investigator participating in this study was chosen based on extensive and safe experience with the use of lasers 
in dermatology applications. This is the most critical element in managing subject risk. In addition, study 
investigators will be trained on the use of both the Cutera Enlighten and Excel V laser systems by a representative 
of Cutera. 
8 
TRAINING AND MONITORING 
 
 
 
9 
 DATA ANALYSIS PLAN  
9.1 
Sample Size Calculation 
The planned sample size of up to 24 subjects for each laser cohort was determined based on clinical judgment to 
provide sufficient information to evaluate reduction in the number of lentigines in the hands. 
9.2 
Data Analysis 
Descriptive statistics and 95% confidence intervals and will be calculated for percent reduction in the number of 
hand lentigines, at 4 weeks 
  
Descriptive statistics and 95% confidence intervals and will be calculated separately for improvement in skin 
texture, and overall appearance of the hands, based on the Physician’s Global Improvement Assessment 
evaluation, and also for the Subject Satisfaction Scale evaluations. 
Safety measures include the incidence of treatment-related AEs, the proportion of subjects who prematurely 
terminate from the study due to a treatment-related AE
 
   
10 INFORMED CONSENT 
 
 
 
 
 
 
 
  
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EV09 
“A Single-Center, 2-Arm Study of the Enlighten™ and Excel V™ Lasers for Lentigines on the Hands” 
 
Confidential and Proprietary 
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13 PUBLICATION POLICY 
 
 
 
 
 
 
  
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a trials registration 
policy as a condition for publication. This policy requires that all clinical trials be registered in a public trials registry 
such as ClinicalTrials.gov, which is sponsored by the National Library of Medicine. It is the responsibility of the 
sponsor to register this trial in ClinicalTrials.gov. Any clinical trial starting enrollment after September 27, 2007 must 
be registered either on or before the onset of patient enrollment.