A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation
Phase: NA
Conditions: Rejuvenation
Sponsor: Cutera Inc.

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Version 2.0, 28 Sep 2016 
 
 
 
 
TITLE PAGE 
 
 
 
Protocol Number: 
C-16-EN12 
Protocol Title: 
A Single-Center, Open-Label Exploratory Study of a Novel 
Laser for Skin Rejuvenation  
Sponsor: 
 
Cutera, Inc. 
3240 Bayshore Boulevard 
Brisbane, CA 94005 
Telephone: 1-415-657-5543 
Contact:  Emily Hu 
Email:  ehu@cutera.com 
 
 
Principal Investigator: 
 
 
 
 
 
 
 
Version, Date: 
Version 2.0  September 28, 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-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Protocol Signature Sheet – Principal Investigator 
 
 
PROTOCOL C-16-EN12 
 
 
Study Title:   A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation 
 
 
Protocol Version 2.0, September 28, 2016 
 
I have received and read the protocol dated September 28, 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, 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 Institutional Review Board (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-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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TABLE OF CONTENTS 
Protocol Summary 
5 
 
PURPOSE 
6 
 
BACKGROUND INFORMATION 
6 
2.1 
PHOTO-REJUVENATION 
6 
2.2 
STUDY DEVICE 
6 
2.3 
ONGOING CLINICAL STUDIES USING THE CUTERA PICOSECOND Q-SWITCHED ND:YAG 
7 
 
STUDY OBJECTIVES 
8 
 
STUDY DESIGN 
8 
4.1 
STUDY ENDPOINTS 
8 
4.1.1 
Exploratory Endpoints 
8 
4.2 
STUDY DURATION 
9 
4.3 
STUDY EFFECTIVENESS ASSESSMENTS 
9 
4.3.1 
Investigator Assessments 
9 
4.3.2 
Subject Assessments 
9 
4.4 
Study Safety Assessments 
9 
4.4.1 
Incidence and Severity of Adverse Events: 
9 
4.4.2 
Treatment-related Discomfort 
10 
4.4.3 
Phone Follow-up 
10 
4.5 
PHOTOGRAPHS 
10 
4.6 
STUDY DISCONTINUATION 
10 
4.7 
INVESTIGATOR SELECTION 
10 
 
Study Population 
10 
5.1 
STUDY SUBJECT RECRUITMENT AND SELECTION 
10 
5.1.1 
Inclusion Criteria 
11 
5.1.2 
Exclusion Criteria 
11 
5.2 
SUBJECT NUMBERING 
12 
5.3 
SUBJECT DISCONTINUATION CRITERIA 
12 
 
Study Procedures 
13 
6.1 
SCREENING / ENROLLMENT 
13 
6.2 
LASER TREATMENT 1 TO 7 – VISIT WINDOW AND PRE-TREATMENT PROCEDURES 
13 
6.3 
LASER TREATMENT PROCEDURES 
13 
6.4 
FOLLOW-UP VISITS 
15 
6.5 
BIOPSY PROCEDURE (OPTIONAL) 
15 
 
ADVERSE DEVICE EFFECTS 
16 
7.1. DEFINITIONS 
16 
7.1.1 
Adverse Device Effect 
16 
7.1.2 
Serious Adverse Device Effect 
16 
7.2 
RECORDING ADES AND SADES 
19 
7.3 
FOLLOW-UP OF SUBJECTS AFTER ADES AND SADES: 
19 
 
Potential Risks / Benefits 
19 
8.1 
POTENTIAL RISKS 
19 
8.2 
POTENTIAL BENEFITS 
20 
 
Risk Management 
20 
 
DATA ANALYSIS PLAN 
21 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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10.1 
SAMPLE SIZE 
21 
10.2 
DEMOGRAPHICS AND SUBJECT CHARACTERISTICS AT BASELINE 
21 
10.3 
STATISTICAL ANALYSIS METHODS 
21 
10.3.1 
Analysis Sets 
21 
10.3.1.3 
Exploratory Analyses 
Error! Bookmark not defined. 
 
SUBJECT PAYMENT 
22 
12 
STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES 
22 
12.1 
TRAINING AND MONITORING 
22 
12.2. 
INFORMED CONSENT 
22 
12.3 
PROTOCOL COMPLIANCE 
23 
12.3.1  
Protocol Amendments 
23 
12.3.2 
 Protocol Deviations 
23 
12.4 
STUDY PERSONNEL 
23 
12.5 
DISCLOSURE OF FINANCIAL INTEREST 
23 
12.6 
DATA COLLECTION, RECORD KEEPING AND STORAGE 
23 
13  
Subject Confidentiality 
24 
 
Publication Policy 
25 
Appendix 1: Study Schedule 
28 
Appendix 2: Fitzpatrick Skin Type Classification 
29 
Appendix 3:  Before and After Laser Treatment Instructions 
30 
Appendix 4:  Subject Questionnaire 
31 
Appendix 5:  Phone Follow-Up Questionnaire 
32 
Appendix 6:  Post-Biopsy Care Instructions 
33 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Protocol Summary 
 
Title 
A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin 
Rejuvenation 
Objective 
 
1. To evaluate the safety of an investigational version of the 
enlighten™ 532nm /1064nm/670nm laser for photo-
rejuvenation. 
 
2. To evaluate the efficacy of an investigational version of the 
enlighten™ 532nm /1064nm/670nm laser for photo-
rejuvenation. 
Study Design 
A single-center prospective, open-label uncontrolled exploratory 
study. 
Subjects will receive 
 laser treatments, 
 
 and will be followed at 2
 
 12 weeks 
) post-final treatment. In addition, after each 
treatment, subjects will complete a 3 day post treatment phone 
follow-up.  
 
 
Enrollment 
A maximum of 20 subjects 
 
 
 
Study Endpoints 
 
 
 Incidence and severity of adverse device effects at 2 weeks post-
first treatment. 
 Incidence and severity of adverse device effects during the study 
period, including subject pain level during laser treatment. 
 Degree of improvement in the treated are at 12 weeks post-final 
treatment as assessed by the Investigator (Physician’s Global 
Assessment of Improvement). 
 
 
Subject Population 
Female or male subjects, age 18 to 75 years, Fitzpatrick skin types I-VI 
Planned Schedule 
First subject enrolled:  September2016 
Last subject last visit:  August 2018 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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 PURPOSE 
The purpose of this exploratory investigation is to evaluate the safety and efficacy of an investigational 
version of the Cutera enlighten™ laser for skin rejuvenation, specifically improvement of acne scars, fine 
rhytides, lentigines, pigmentation, erythema and skin texture. The version of the laser under investigation 
allows the user to treat using a wavelength between 660 nm – 690 nm as well as 532 nm or 1064 nm. 
 
 BACKGROUND INFORMATION 
2.1 
Photo-Rejuvenation 
Non-invasive treatment options are in high demand by patients wanting to improve their appearance 
without surgical intervention. As a result, patients now have a variety of options for non-invasive skin 
rejuvenation, from laser and light-based treatments to devices that utilize ultrasound and radiofrequency, 
however this was not always the case. Initial skin rejuvenation 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]. 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 non-ablative laser devices to those 
that use radiofrequency [7-15].  
 
Laser therapy often includes the use of pulsed lasers, namely Q-Switched or Quality-Switched (QS) lasers 
which produce nanosecond laser pulses by suddenly releasing all of the excited-state energy from the 
laser medium [16]. This concept is based on the principle of selective photothermolysis which imply: (1) 
the use of the wavelength matching the absorption spectra of the pigment; and (2) the delivery of the 
heat to target pigment particle within pulse duration shorter than its thermal relaxation time [17].  This 
allows selective destruction of target chromophore in the skin with minimal damage to the surrounding 
tissue. 
 
Nanosecond QS lasers have been widely used for more than 20 years as a safe and effective treatment for skin 
rejuvenation [18-24]. Laser wavelengths and pulse durations currently available for nanosecond QS laser 
treatment of pigmented lesions include 532 nm Nd:YAG, 1064 nm Nd:YAG, 755 nm Alexandrite and 694 nm 
Ruby with pulse durations from 5 to 10 ns (Nd:YAG), 50 to 70 ns (Alexandrite) 25 to 30 ns (Ruby). These 
wavelengths in the visible and infrared ranges are appropriate for the absorption spectrum of melanin. 
Melanin, the target pigment for these lasers, is largely present in basal keratinocytes in benign pigmented 
lesions. During laser procedures, the melanosomes, the organelle which hold the melanin in melanocytes, are 
rapidly heated [25, 26]. This rapid heating and evaporation of the melanosomes in the skin result in 
vacuolization. 
 
The current proposed exploratory clinical study described herein intends to evaluate the safety and 
effectiveness of the investigational laser and the optimal range of treatment parameters for use in skin 
rejuvenation. 
 
2.2 
Study Device 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
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4.2 
Study Duration 
Subjects enrolled in this trial will participate for approximately 5 to 16 months, 
 
 
 
 
  
 
 
 
 
 
 
The screening and first laser treatment may be combined into one visit provided that the informed 
consent process has been completed (see Section 12.2) and the subject has signed the IRB-approved 
Informed Consent Form prior to the commencement of any study-related procedures and device 
treatments. 
4.3 Study Effectiveness Assessments 
4.3.1 
Investigator Assessments 
4.3.1.1 Investigator’s Global Assessment of Improvement 
At 12 weeks post-final treatment, the Investigator will be asked to rate the degree of improvement in the 
appearance of the subject’s treated area from baseline using the Physician’s Global Assessment Scale:  
 
4 = Very Significant or Complete Clearing (
 
3 = Significant Clearing 
 
2 = Moderate Clearing (
 
1 = Mild Clearing 
 
 
0 = No Clearing 
 
4.3.2 Subject Assessments 
4.3.2.1 
 
 
 
  
 
 
 
 
 
 
 
 
 
4.4 
Study Safety Assessments 
 
4.4.1 Incidence and Severity of Adverse Events: 
Following the first laser treatment, adverse device effects (ADEs) will be assessed post-treatment and at 
each subsequent subject visit using the following scale: 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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1= mild: requires minimal or no treatment and does not interfere with the Subject’s daily activities. 
2= moderate: may cause some interference with functioning.  
3= severe: interrupts Subject’s usual daily activity and may require treatment. 
4.4.2 Treatment-related Discomfort 
After each laser treatment, subjects will be asked to rate the average amount of discomfort experienced 
during treatment and immediately after laser treatment.   
4.4.3 Phone Follow-up 
Phone follow-up will be conducted for all subjects by the Investigator’s staff at 3 days after each laser 
treatment.  Data recorded on the phone follow-up questionnaire will be evaluated for adverse events, 
event duration and adverse event resolution.  The Phone Follow-up Questionnaire is presented in 
Appendix 5. 
4.5 
Photographs 
Standardized digital photographs will be taken of each subject’s treatment area at baseline, prior to all 
laser treatments and at each follow-up. Any jewelry will be removed from the area being photographed. 
For facial photographs, hair will be pulled away from the face with a headband and subject will have 
recently cleansed skin. Photographs will be taken prior to all laser treatments and at each follow-up visit. 
Facial photographs will be obtained from 3 angles: with the subject facing forward, 90° to the right and 
90° to the left. Photographs will be taken in the same windowless room equipped with adequate lighting. 
The room lighting, camera positioning and subject positioning should be consistent for all study visit 
photographs. Digital camera settings should remain the same for all photographs and the highest 
resolution settings should be utilized.  
4.6 
Study Discontinuation 
Cutera, Inc. (the sponsor) 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. 
4.7 
Investigator Selection 
The Investigator will be invited to participate in the study based on his or 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 was also considered.  
 
Study Population 
5.1 
Study Subject Recruitment and Selection 
Up to 20 male or female subjects, ages 18 to 75, with Fitzpatrick Skin Type I-VI who desire laser treatment 
for skin rejuvenation on the face. 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 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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present themselves to the study site requesting treatment. Only subjects who meet all eligibility criteria 
and who provide written informed consent will be enrolled into the study. 
 
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.  
5.1.1 
Inclusion Criteria 
To be included in the study, subjects must meet all of the following Inclusion Criteria: 
1.  
Female or Male, 18 to 75 years of age (inclusive). 
2.  
Fitzpatrick Skin Type I – VI (Appendix 2). 
3.  
Desires photo-rejuvenation of the skin or improvement in the appearance of acne 
scarring. 
4.  
Subject has visible signs of acne scarring or moderate sun-damaged and/or aging skin in 
the treatment area with visible areas acne lesions and scars, fine rhytides, lentigines or 
pigmentation, diffused redness erythema and skin texture 
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), including injectable agents, for skin 
rejuvenation during the study and has no intention of having such procedures 
performed during the course of the study. 
10.  
Post-menopausal or surgically sterilized, or using a medically acceptable form of birth 
control at least 3 months prior to enrollment and during the entire course of the study, 
and no plans to become pregnant. 
5.1.2 
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 drug, or device administered to the target area, 
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.  
Prior injection of botulinum toxin, collagen, hyaluronic acid filler or other dermal filler 
within 6 months of study participation. 
4.  
History of malignant tumors in the target area. 
5.  
Skin abnormalities in the target area, e.g., cuts, scrapes, wounds, large moles. 
6.  
Pregnant and/or breastfeeding.  
7.  
Having an infection, dermatitis or a rash in the treatment area. 
8.  
Significant concurrent illness, such as diabetes mellitus or cardiovascular disease, e.g., 
uncontrolled hypertension. 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
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9.  
History of keloid scarring, hypertrophic scarring or of abnormal wound healing.  
10.  
History of immunosuppression/immune deficiency disorders or currently using 
immunosuppressive medications per investigator’s discretion.  
11.  
History of vitiligo, eczema, or psoriasis. 
12.  
History of connective tissue disease, such as systemic lupus erythematosus or 
scleroderma.  
13.  
History of seizure disorders due to light. 
14.  
Any use of medication that is known to increase sensitivity to light according to 
Investigator’s discretion. 
15.  
History of disease stimulated by heat, such as recurrent herpes simplex and/or herpes 
zoster (shingles) in the treatment area, unless treatment is conducted following a 
prophylactic regimen 
16.  
History of pigmentary disorders, particularly tendency for hyper- or hypo-pigmentation. 
17.  
Systemic use of retinoid, such as isotretinoin, as applicable, within 6 months of study 
participation.  
18.  
Topical use of retinoid, such as isotretinoin, as applicable, on the treatment area within 
1 month of participation. 
19.  
Anytime in life, having have used gold therapy (gold salts) for disorders such as 
rheumatologic disease or lupus. 
20.  
Excessively tanned in areas to be treated or unable/unlikely to refrain from tanning during 
the study.  
21.  
Current smoker or history of smoking within 6 months of study participation. 
22.  
As per the Investigator’s discretion, any physical or mental condition which might make 
it unsafe for the subject to participate in this study. 
5.2 
Subject Numbering  
If a subject meets the study eligibility criteria and is willing to participate, the subject will be assigned a 
study subject identification number. This number is comprised of a sequential subject number and the 
subject initials (first and last names). 
5.3 
Subject Discontinuation Criteria 
If possible, every subject should remain in the study until completion of the required follow-up period. 
However, participation in this study is completely voluntary and a subject can choose to withdraw from 
the study at any time.  Decision to withdraw will not affect or prejudice the subject’s continued medical 
care in any way. In those instances, the investigator will attempt to obtain a final clinical assessment and 
an adverse device effect evaluation for the subject prior to this withdrawal. A subject will be considered 
lost to follow-up only after three unsuccessful, documented attempts to contact the subject have been 
made.   
 
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, a subject develops any of the exclusion 
criteria during the study period or the study is stopped by the study sponsor.  

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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 ADVERSE DEVICE EFFECTS  
7.1. Definitions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 18 of 33                                                       
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Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
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.  
8.2 
Potential Benefits 
The subjects may or may not benefit from the treatment with the study device. Potential benefit of laser 
treatment for photo-rejuvenation is improved appearance of treated area. There is no guarantee of 
success.  
 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 the Cutera Enlighten laser system by a 
representative of Cutera. 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
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 DATA ANALYSIS PLAN  
10.1 Sample Size 
Up to 20 subjects will be enrolled in this exploratory study. 
10.2 
Demographics and Subject Characteristics at Baseline 
Subject demographics, medical history, concomitant medications will be tabulated and summarized 
descriptively. 
10.3 
Statistical Analysis Methods 
This is an exploratory study to evaluate safety and efficacy of the investigational enlighten device, 
therefore, formal statistical analyses are not planned.   
 
Outcome measures will be assessed around multiple endpoints.  These measures will be: degree of 
improvement as assessed by the Investigator, 
 and safety. Additional assessments 
may also be performed but are not considered part of the analysis (i.e. subject post-treatment 
questionnaire).  The specific assessment tools, collection method and time points are listed herein.   
10.3.1 Analysis Sets 
The efficacy analysis set will include all subjects who received at least one laser treatment session and 
complete at least one follow-up visit. The safety analysis set will include all subjects enrolled in the study 
who had at least one laser treatment session. 
 
Missing data will not be imputed for efficacy or safety endpoints. 
10.3.1.1  
 Efficacy Analyses 
Descriptive statistics such as mean, standard deviation, median and range will be performed for: 
 
 The degree of improvement at 12 weeks post-final treatment as assessed by the Investigator, using 
the Physician’s Global Assessment tool. 
 
 
 
10.3.1.2   
Safety Analyses 
The safety variables for this study are: 
 
 Incidence and severity of adverse effects during study duration (to be displayed descriptively as 
counts and frequency distributions)  
 Subject discomfort (pain) during treatment (to be descriptively displayed). 
 
Enrolled subjects who received at least one treatment will be included in the safety analyses. Device-
related and procedure-related adverse effects (AEs) and subjects who prematurely terminate from the 
study due to an adverse device effect, including the treatment-related pain ratings, as reported on case 
report forms will be tabulated and analyzed. For a given AE term, counting will be done by subject, not by 
event, i.e. for a subject reporting the same AE more than once, the event will be counted only once, at the 
most severe and most-related occurrence.  The number and percentage of subjects experiencing each AE 
Term will be descriptively summarized. Statistical hypothesis testing will not be performed for safety data. 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
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Interim analyses of adverse events and adverse device effect incidence and severity will be performed 
when all treated subjects have completed the 12 week post-final treatment visit.  At the conclusion of 
the study, complete analyses of the safety variables will be displayed descriptively.   
 SUBJECT PAYMENT 
 
 
 
 
12 
STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES  
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
  
 
 
’ 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
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12.3 
Protocol Compliance 
The principal investigator must comply with all terms of the protocol. 
12.3.1  Protocol Amendments 
Neither the principal investigator nor the sponsor will modify or alter this protocol without first obtaining 
the concurrence of the other party (with the exception of amendments which involves mitigating a 
medical emergency or immediate health risk to the subject). The party initiating an amendment must 
confirm it clearly in writing and it must be signed and dated by the sponsor and the principal investigator. 
IRB approval must be obtained before implementation of an amendment. 
12.3.2  Protocol Deviations 
All protocol deviations must be clearly described on the case report form (i.e., Cutera Protocol Deviation 
Form). Deviations from the protocol may include but are not limited to subject’s failure to attend 
scheduled visit during a visit window, use of out of range treatment parameters and incomplete or 
incorrect study procedures. Any medical emergency or immediate health risk to the subject which results 
in a protocol deviation and must be reported to the sponsor within 5 working days 
 
Significant protocol deviations must be reported to IRB according to their policies. 
12.4 
Study Personnel 
Prior to the start of the study, the investigator must supply the sponsor with a list of the names and 
curricula vitae that describe the professional backgrounds of the clinically responsible study investigators 
(principal, sub-investigators), research nurses, and other possible participants (e.g. medical doctor, nurse, 
etc.). 
12.5 
Disclosure of Financial Interest 
Each investigator [principal and sub-investigator(s)] is required to disclose sufficient accurate financial 
information to the sponsor, to allow sponsor to submit complete and accurate certification or disclosure 
statements. 
12.6 
Data Collection, Record Keeping and Storage 
 
 
  
 
 
 
 
 
 
  

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
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13  Subject Confidentiality 
This study preserves the confidentiality of all subjects under the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA) Privacy Rule. The following safeguards will be in place to protect the 
privacy of the individuals who are the subjects of the health information to be used in the research and 
the confidentiality of that information:   
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 25 of 33                                                       
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The subjects will be informed by the investigator or the investigator’s designee that their medical records 
will be kept as confidential as possible but may be subject to review by: (1) Cutera, or its representative; 
(2) reviewing IRB; and/or (3) by appropriate regulatory bodies (e.g. the US Food and Drug Administration 
(FDA), Department of Health and Human Services (DHHS) agencies).  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
.  
 
 Publication Policy 
The investigator shall have the right to publish the results of the study. Unless mutually agreed upon in 
writing, prior to submission for publication of any manuscript, poster, presentation, abstract or other 
written or oral material describing the results of the study, the investigator shall allow sponsor to review 
manuscript, poster presentation, abstract or other written or oral material which describes the results of 
the study for the purpose only of determining if any patentable information is disclosed. At the sponsor’s 
request, the investigator shall withhold any publication or presentation to permit sponsor to seek patent 
protection and to remove any confidential information from all publications.  
 
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. 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 26 of 33                                                       
Version 2.0, 28 Sep 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 27 of 33                                                       
Version 2.0, 28 Sep 2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 28 of 33                                                       
Version 2.0, 28 Sep 2016 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 29 of 33                                                       
Version 2.0, 28 Sep 2016 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 30 of 33                                                       
Version 2.0, 28 Sep 2016 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 31 of 33                                                       
Version 2.0, 28 Sep 2016 

Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 32 of 33                                                       
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Cutera, Inc. 
Protocol # C-16-EN12 
“A Single-Center, Open-Label Exploratory Study of a Novel Laser for Skin Rejuvenation” 
 
Confidential and Proprietary 
Page 33 of 33                                                       
Version 2.0, 28 Sep 2016