A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal
Phase: NA
Conditions: Tattoo Removal
Sponsor: Cutera Inc.

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
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Version 5.0, March 02, 2017 
 
 
 
 
 
 
 
TITLE PAGE 
 
 
 
Protocol Number: 
C-16-EN13 
Protocol Version: 
Version 5.0,  March 02, 2017 
Protocol Title: 
A Prospective, Multi-Center Pivotal Clinical Evaluation of a 
Novel Multi-Wavelength Laser for Tattoo Removal 
 
Sponsor: 
 
Cutera, Inc. 
3240 Bayshore Boulevard 
Brisbane, CA 94005 
(888) 4-CUTERA 
 
 
Principal Investigator 1: 
 
 
 
 
 
Principal Investigator 2: 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Statement of Compliance  
The study will be conducted in accordance with the design and specific provisions of this IRB/EC-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 Independent Review Board/Ethics Committee. 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-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
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Protocol Signature Page – Principal Investigator 
 
 
PROTOCOL C-16-EN13 
 
 
Study Title:  A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser 
for Tattoo Removal 
 
 
 
 
 
 
Protocol Version 5.0, March 02, 2017 
 
I have received and read the protocol dated March 02, 2017 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 Independent Review Board 
(IRB)/Ethics Committee (EC), 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/EC 
requirements. I agree to commence this study only after documented IRB/EC approval is obtained. 
 
 
 
 
Principal 
Investigator 
 
 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Printed Name 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
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Table of Contents 
PROTOCOL SUMMARY ..................................................................................................................................... 5 
1 
PURPOSE ................................................................................................................................................. 6 
2 
BACKGROUND INFORMATION .................................................................................................................. 6 
2.1 
TATTOO REMOVAL ........................................................................................................................................... 6 
2.2 
ONGOING CLINICAL STUDIES USING THE CUTERA PICOSECOND Q-SWITCHED ND:YAG ................................................ 8 
3 
STUDY OBJECTIVES ................................................................................................................................... 9 
4 
STUDY DESIGN ......................................................................................................................................... 9 
4.1 
STUDY ENDPOINTS ........................................................................................................................................... 9 
4.1.1 
Efficacy endpoints ................................................................................................................................... 9 
4.1.2 
Safety Endpoint ..................................................................................................................................... 10 
4.2 
STUDY DURATION .......................................................................................................................................... 10 
4.3 
BLINDING AND RANDOMIZATION OF PHOTOGRAPHS ............................................................................................ 10 
4.3.1 
Blinding ................................................................................................................................................. 10 
4.3.2 
Randomization of Photographs ............................................................................................................ 10 
4.4 
STUDY EFFECTIVENESS ASSESSMENTS ................................................................................................................ 11 
4.4.1 
Blinded Assessments ............................................................................................................................. 11 
4.4.2 
Investigator Assessments ...................................................................................................................... 11 
4.4.3 
Subject Assessments ............................................................................................................................. 11 
4.5 
STUDY SAFETY ASSESSMENTS ........................................................................................................................... 12 
4.5.1 
Incidence and Severity of Adverse Events: ............................................................................................ 12 
4.5.2 
Treatment-related Discomfort .............................................................................................................. 12 
4.6 
PHOTOGRAPHS .............................................................................................................................................. 12 
4.7 
STUDY DISCONTINUATION ............................................................................................................................... 12 
4.8 
INVESTIGATOR SELECTION ............................................................................................................................... 12 
5 
STUDY POPULATION ............................................................................................................................... 12 
5.1 
STUDY SUBJECT RECRUITMENT AND SELECTION ................................................................................................... 12 
5.1.1 
Inclusion Criteria ................................................................................................................................... 13 
5.1.2 
Exclusion Criteria ................................................................................................................................... 13 
5.2 
SUBJECT NUMBERING ..................................................................................................................................... 14 
5.3 
SUBJECT DISCONTINUATION CRITERIA ............................................................................................................... 14 
6 
STUDY PROCEDURES .............................................................................................................................. 15 
6.1 
SCREENING / ENROLLMENT PROCEDURES .......................................................................................................... 15 
6.2 
LASER TREATMENT VISITS – PRE-TREATMENT PROCEDURES .................................................................................. 15 
6.3 
LASER TREATMENT PROCEDURES ...................................................................................................................... 15 
6.4 
FOLLOW-UP VISITS ........................................................................................................................................ 16 
7 
ADVERSE DEVICE EFFECTS ....................................................................................................................... 17 
7.1 
DEFINITIONS ................................................................................................................................................. 17 
7.1.1 
Adverse Device Effect ............................................................................................................................ 17 
7.1.2 
Serious Adverse Device Effect ............................................................................................................... 17 
7.2 
RECORDING ADES AND SADES ........................................................................................................................ 20 
7.3 
FOLLOW-UP OF SUBJECTS AFTER ADES AND SADES: ........................................................................................... 20 
8 
POTENTIAL RISKS / BENEFITS .................................................................................................................. 20 
8.1 
POTENTIAL RISKS ........................................................................................................................................... 20 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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8.2 
POTENTIAL BENEFITS ...................................................................................................................................... 22 
9 
RISK MANAGEMENT ............................................................................................................................... 22 
10 
DATA ANALYSIS PLAN  ............................................................................................................................. 22 
10.3.2 
ANALYSIS SETS ............................................................................................. ERROR! BOOKMARK NOT DEFINED. 
10.3.3 
Analysis of Primary Endpoint ............................................................................................................ 22 
THE CATEGORICAL PRIMARY EFFICACY VARIABLE DATA WILL BE ANALYZED USING THE ONE-SAMPLE WILCOXON RANK TEST. .... ERROR! 
BOOKMARK NOT DEFINED. 
10.1 
SAMPLE SIZE ................................................................................................................................................. 23 
10.2 
DEMOGRAPHICS AND SUBJECT CHARACTERISTICS AT BASELINE ................................. ERROR! BOOKMARK NOT DEFINED. 
10.3 
STATISTICAL ANALYSIS METHODS ........................................................................ ERROR! BOOKMARK NOT DEFINED. 
10.3.1 
General Methods ................................................................................. Error! Bookmark not defined. 
10.3.4 
Analyses of Secondary Endpoints ..................................................................................................... 23 
10.3.5 
Safety Analyses .................................................................................... Error! Bookmark not defined. 
11 
SUBJECT PAYMENT ................................................................................................................................. 23 
12 
STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES ................................................................... 24 
12.1 
TRAINING AND MONITORING ........................................................................................................................... 24 
12.2 
INFORMED CONSENT ...................................................................................................................................... 24 
12.3 
PROTOCOL COMPLIANCE ................................................................................................................................. 25 
12.3.1 
Protocol Amendments ...................................................................................................................... 25 
12.3.2 
Protocol Deviations ........................................................................................................................... 25 
12.4 
STUDY PERSONNEL ......................................................................................................................................... 25 
12.5 
DISCLOSURE OF FINANCIAL INTEREST ................................................................................................................. 25 
12.6 
DATA COLLECTION, RECORD KEEPING AND STORAGE ........................................................................................... 25 
13 
SUBJECT CONFIDENTIALITY ..................................................................................................................... 26 
14 
PUBLICATION POLICY .............................................................................................................................. 27 
REFERENCES ................................................................................................................................................... 28 
APPENDIX 1: STUDY SCHEDULE ....................................................................................................................... 30 
APPENDIX 2: PAIN RATING SCALE ................................................................................................................... 31 
APPENDIX 3: FITZPATRICK SKIN TYPE CLASSIFICATION ..................................................................................... 32 
APPENDIX 4:  BEFORE AND AFTER TREATMENT INSTRUCTIONS ....................................................................... 33 
APPENDIX 5:  IMMEDIATE POST-TREATMENT SUBJECT QUESTIONNAIRE ......................................................... 34 
APPENDIX 6:  FOLLOW-UP SUBJECT QUESTIONNAIRE ...................................................................................... 35 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
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Protocol Summary 
 
Title 
A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-
Wavelength Laser for Tattoo Removal 
 
Objective 
 
To evaluate the safety and efficacy of an investigational version of the 
Cutera enlightenTM laser that offers multiple wavelengths for tattoo 
removal. 
Study Design 
A multi-center prospective, open-label, uncontrolled study. 
Enrollment 
Up to 40 subjects 
Primary Endpoint 
 Green and blue tattoo ink clearing of ≥ 50% at 6 weeks post-
final treatment as assessed by independent blinded 
reviewers (Global Assessment of Improvement) in 80% of 
treated subjects.   
Secondary Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Population 
Female or male subjects, age 18 to 65 years, Fitzpatrick skin types I-VI 
Planned Schedule 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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1 
 PURPOSE 
The purpose of this investigation is to evaluate the safety and efficacy of an investigational version of 
the Cutera enlightenTM laser for tattoo removal. Currently, the enlightenTM laser offers two wavelengths: 
532nm and 1064nm. The version of the laser under investigation offers a third wavelength of 670nm. 
2 
 BACKGROUND INFORMATION 
2.1 
Tattoo Removal 
Millions of people thought to have tattoos in the western world.  Recently, the numbers have been 
increasing due to high demand for tattoos especially among teens and younger adults.  As a result of this 
high demand, tattoo removal has become a common cosmetic procedure [1]. 
 
Tattoos are exogenous (foreign) pigment particles implanted into the dermis.  They vary in size, 
composition and dermal depth. There are five types of tattoos: professional, amateur, cosmetic, 
traumatic, and medical [2-5].  Tattoos are created using a variety of pigments and/or combinations 
comprised of inorganic and/or organic compounds, such as chromium, mercury, iron, copper, carbon 
and polycyclic compounds[6].   
 
The non-selective tattoo removal mainly consists of the mechanical, such as salabrasion, and excision; 
chemical, such as trichloroacetic acid; and thermal methods such as electrocautery, cryotherapy, and 
continuous wave laser therapy[4].  These invasive methods vary in effectiveness and always result in 
scarring and dyspigmentation.  
 
Recent technology involves 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. This concept is based on the principle of selective photothermolysis which imply (1) the 
use of the wavelength matching the absorption spectra of the tattoo pigment and (2) the delivery of the 
heat to target pigment particle within pulse duration shorter than its thermal relaxation time.  This 
allows selective destruction of target chromophore in the skin without damage to the surrounding 
tissue. 
 
Currently, there are four different types of nanosecond QS lasers widely used for tattoo removal: 532 
nm, 1064 nm, 755 nm and 694 nm wavelengths.  1064 nm and 755 nm wavelengths are used for black 
and blue tattoos, 694 nm wavelength for blue, black and green tattoos; 532 nm wavelength for red 
tattoos. Besides tattoo color, tattoo type, tattoo age, tattoo location, patient age, and patient skin type 
are also part of considerations for the selection of optimal laser(s) and parameters in each patient. 
Depending on the composition of colors used in tattoos, more than one laser may be used.   
 
To date, nanosecond QS lasers have been successfully used and found to be safe and effective for tattoo 
removal [7-18]. Transient or permanent hypopigmentation may be observed with shorter wavelengths, 
such as 532 nm 755 nm and 694 nm as they compete with the melanin in the epidermis.  Thus, shorter 
wavelengths are not recommended for treatments in darker skin types. Longer wavelength 1064 nm, on 
the other hand, is considered to be safe in darker skin types because of decreased melanin absorption. 
Still, lower fluences are recommended for treatment of darker skin patients with Nd:YAG lasers.  
Scarring is rarely observed following treatments with QS lasers as water is no longer the target 
chromophore. 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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There are some challenges associated with tattoo removal. If mixtures of pigments and/or multicolors 
are used, a complete clearing of the tattoo may not be achieved with lasers[19].  Different colors are 
usually mixed to achieve various levels of brightness and lightness. Another contributing factor to 
unsuccessful outcome is that most tattoo pigments are not regulated and may include various elements 
and chemical compounds.  When the exact compound of the tattoo pigment is not known, paradoxical 
darkening of the pigment may happen following tattoo removal, which may be difficult to remove [20-
23].  Additionally, white, orange, yellow and brown tattoo inks are particularly difficult to treat[24]. 
 
Although the mechanism of action is not clearly understood, the effects of the lasers on the pigment are 
thought to be: 1) photothermal/photochemical and 2) photoacoustic/photomechanical[25, 26].  
Conversion of absorbed energy into heat (photothermal effect) breaks the chemical bonds inside the 
pigment and causes pigment modification.  At the same time, the ultrashort heating of the particle shell 
may cause heating of the surrounding tissue via rapid thermal expansion resulting in shock waves. These 
shock waves may help destroy the surrounding cellular structures and tattooed compounds 
mechanically (photoacoustic/photomechanical). The resultant fragmented particles are then removed 
by three mechanisms: 1) transepidermal elimination, 2) removal via lymphatics, and 3) rephagocytosis 
by other cells (inflammatory or resident cells) in the dermis. 
 
Histological examinations show that the tattoo pigments are exclusively found intracytoplasmatically in 
lysosomes which is a result of active phagocytosis in dermal cells, such as macrophages and 
fibroblasts[27, 28]. In electron microscopy of black tattoos immediately after treatment with 1064 nm 
Nd:YAG, vacuoles were observed in the dermis [29].  Vacuoles were lined by remnants of pigment-
containing cells, flattened cell nuclei and disrupted lysosomes. Cells without pigment located close to 
the vacuoles were not affected. One week after treatment, a moderate chronic inflammatory infiltrate 
was observed in the dermis and all tattoo particles were phagocytosed and intracellular within 
fibroblasts and macrophages. At one month post-treatment, all residual pigment particles were within 
lysosomes with mild residual inflammatory infiltrate around dermal vessels. 
 
Although nanosecond QS lasers are safe and effective in the treatment of tattoos, treatment sessions 
are often painful and as many as 6 to 10 treatments are necessary to achieve acceptable clearance. It 
could be argued that this is a result of most tattoo particles ranging in size from 40 to 300 nm in vivo and 
their thermal relaxation times being mostly in the picosecond range[30].  For example, the most 
common pigment particle, carbon black in india ink, which is shown to be about 40 nm in diameter, will 
approximately have a thermal relaxation time of 1 nanosecond[31]. In that case, a thermally confined 
disruption of the particle can only be achieved via picosecond pulses.  This suggests that energy delivery 
in the picosecond range be more effective and require lower fluences than the nanosecond range.  
Moreover, the resultant ultra-short pulses with higher peak temperatures should decrease adverse 
effects, such as dyspigmentation as the heat transfer to the surrounding tissue is significantly minimized.   
 
Up to date, various studies of picosecond QS lasers, both in vitro and in vivo, have been conducted to 
test the hypotheses on the potential benefits of picosecond QS lasers[30-34].  In a split-tattoo study, 
Ross et al reported better clearing in 75% (12/16) of tattoos with on picosecond side than the clearing 
on the nanosecond side following 4 treatments with QS Nd:YAG[31]. Electron microscopic findings were 
similar for both picosecond and nanosecond exposures and no adverse events were noted. In an animal 
study comparing a picosecond titanium:sapphire (795 nm, 500 picoseconds) laser with QS alexandrite 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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4.1.1.2 Secondary Efficacy Endpoints 
 
 
 
 
 
 
4.1.2 Safety Endpoint 
 Incidence and severity of adverse device effects during the study period, including subject pain 
level during laser treatment. 
 
4.2 
Study Duration 
 
 
 
 
 
   
 
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/EC-approved 
Informed Consent Form prior to the commencement of any study-related procedures and device 
treatments. 
 
 
 
 
 
 
 
4.3 
Blinding and Randomization of Photographs 
4.3.1 Blinding 
A panel of independent reviewers will assess subject photographs taken at baseline and 6 weeks post-
final treatment. The reviewers will be blinded to the type of treatment device, the parameters used, the 
subject data, the temporal order of photographs (before and after), and follow-up time point. 
4.3.2 Randomization of Photographs 
The presentation order of subject photographs will be randomized. First, a unique identification number 
will be assigned to each pair of subject photographs (1 baseline and 1 post-treatment), then the order of 
photograph presentation will be assigned by randomizing the identification numbers. In addition, the 
location of the baseline photograph on the assessment page will be randomized such that each 
photograph pair will be arranged with the baseline photograph located either on the right side or left 
side of the page. Minitab statistical package, version 16.2.2.0 (Minitab Inc., State College, Pennsylvania) 
will be used to do randomizations. The photograph pairs from each subject will be then organized 
according to randomization and will be presented to the blinded reviewers for assessment. 
 

Cutera, Inc. 
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“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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4.5 Study Safety Assessments 
4.5.1 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: 
 
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. 
4.5.2 Treatment-related Discomfort 
Subjects will be asked to rate the average amount of discomfort experienced during laser treatment 
using the Pain Rating Scale found in Appendix 2. 
4.6 Photographs 
Standardized digital photographs will be taken of each subject’s treatment area at baseline, prior to all 
laser treatments, immediately following laser treatments and at each follow-up visit. Any jewelry will be 
removed from the area being photographed. 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 (including any flash settings) should 
remain the same for all photographs and the highest resolution settings should be utilized. 
4.7 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. 
4.8 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.  
5 
STUDY POPULATION 
5.1 Study Subject Recruitment and Selection 
Thirty male or female subjects, ages 18 to 65, with Fitzpatrick Skin Type I-VI who desire laser treatment 
for tattoo removal will be studied. 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 study eligibility 
criteria and who provide written informed consent will be enrolled into the study. 
 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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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 65 years of age (inclusive). 
2.  
Fitzpatrick Skin Type I – VI (Appendix 3). 
3.  
Target tattoo contains single or multi-color ink, and must include blue and/or green ink. 
4.  
Target tattoos must be older than 6 months. 
5.  
Target treatment area not to exceed 12 square inches. 
6.  
Subject must be able to read, understand and sign the Informed Consent Form. 
7.  
Must be willing and able to adhere to the treatment and follow-up schedule and post-
treatment care instructions. 
8.  
Wiling to cover tattoos with a bandage or clothing; and/or have very limited sun 
exposure and use an approved sunscreen of SPF 50 or higher on the treated area starting 
2 to 4 weeks before the treatment and/or every day for the duration of the study, 
including the follow-up period. 
9.  
Willing to have digital photographs taken of the treatment area and agree to use of 
photographs for presentation, educational or marketing purposes. 
10.  
Agree to not undergo any other procedure(s) for tattoo removal during the study (as 
applicable). 
11.  
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 for the duration of the study. 
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 a drug or another device in the target area during the 
study. 
2.  
Target tattoo contains only black ink. 
3.  
History of allergic reaction to pigments following tattooing. 
4.  
History of allergy to local anesthetics. 
5.  
History of allergy to topical antibiotics. 
6.  
History of malignant tumors in the target area. 
7.  
Skin abnormalities in the target area, e.g., cuts, scrapes, wounds, scars, large moles. 
8.  
Pregnant and/or breastfeeding.  
9.  
Having an infection, dermatitis or a rash in the treatment area. 
10.  
Significant concurrent illness, such as diabetes mellitus or cardiovascular disease, 
e.g., uncontrolled hypertension. 
11.  
Suffering from coagulation disorders or taking prescription anticoagulation 
medications.  
12.  
History of keloid scarring, hypertrophic scarring or of abnormal wound healing.  
13.  
History of immunosuppression/immune deficiency disorders or currently using 

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immunosuppressive medications per investigator’s discretion.  
14.  
History of vitiligo, eczema, or psoriasis. 
15.  
History of connective tissue disease, such as systemic lupus erythematosus or 
scleroderma.  
16.  
History of seizure disorders due to light. 
17.  
Any use of medication that is known to increase sensitivity to light according to 
Investigator’s discretion. 
18.  
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 
19.  
History of radiation to the treatment area or undergoing systemic chemotherapy for 
the treatment of cancer.  
20.  
History of pigmentary disorders, particularly tendency for hyper- or hypo-
pigmentation. 
21.  
Systemic use of corticosteroid or isotretinoin, as applicable, within 6 months of study 
participation.  
22.  
Anytime in life, having used gold therapy (gold salts) for disorders such as 
rheumatologic disease or lupus. 
23.  
Excessively tanned in areas to be treated or unable/unlikely to refrain from tanning 
during the study.  
24.  
Current smoker or history of smoking within 6 months of study participation. 
25.  
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. 
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“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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Cutera, Inc. 
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criteria? 
yes 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
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Subjects will be asked to wear eye protection during the procedure to prevent eye damage. 
 
Any of these risks, discomforts and adverse device effects may occur with greater frequency or severity 
than previously reported and may necessitate additional medical treatment.  
8.2 
Potential Benefits 
The subjects may or may not benefit from the treatment with the study device. Potential benefit of laser 
treatment for tattoos is lightening or complete removal of tattoo. There is no guarantee of success.  
9 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 enlightenTM laser system by a 
representative of Cutera. 
10   DATA ANALYSIS PLAN  
10.1 
Analysis Sets 
 
 
 
 
. 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. 
10.2 
Analysis of Primary Endpoint 
The primary endpoint is subject success, based on achieving ≥50% lightening of the tattoo at 6 weeks 
post-final treatment as assessed by blinded review. The primary statistical hypothesis will be to 
demonstrate that at least 50% of subjects achieve a successful study outcome.  In formal terms, this is: 
 
HO: π = 0.50 
vs. 
HA: π > 0.50, 
where π is the population success rate.   
 
The primary analysis will place an exact one-sided exact 97.5% lower confidence bound on the observed 
success rate in the study. If this lower bound exceeds 50% the null hypothesis will be rejected and the 
success rate will be deemed greater than 50%. To achieve a successful study outcome, at least 17 of 23 
subjects (74%) must have ≥50% clearance (equivalent to improvement score ≥ 2). It is recognized that 
some subjects may desire to have more than one tattoo removed in the study. Rather than asking the 
investigator to designate one tattoo as primary, 100 separate analyses will be performed in which one 
tattoo is randomly selected from each subject each time.  The median p-value from these 100 analyses 
will be the final study p-value. In addition, as a secondary analysis, the overall success rate will be 
calculated based on all tattoos removed.     
 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
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10.3 
Sample Size 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 treatments is in the subject’s best medical interest. 
10.6 
Safety Analyses 
Safety variables will be analyzed descriptively. 
 
The safety variables for this study are: 
 
 Subject discomfort (pain) during and after treatment (to be descriptively displayed).  
 Incidence and severity of adverse effects during study duration to be displayed as counts 
and frequency distributions. 
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. 
 
11 
  SUBJECT PAYMENT 
 
 
  

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
Page 24 of 35                                                       
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12 
   STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES  
 12.1 Training and Monitoring 
 
 
  
 
  
 
 
 
. 
12.2 
Informed Consent 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
  

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
Page 26 of 35                                                       
Version 5.0, March 02, 2017 
5. 
 
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
  
13 
   SUBJECT CONFIDENTIALITY 
 
   
 
 
 
  
 
 
 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
Page 27 of 35                                                       
Version 5.0, March 02, 2017 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
14 
   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-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
Page 28 of 35                                                       
Version 5.0, March 02, 2017 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
Page 29 of 35                                                       
Version 5.0, March 02, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
Page 31 of 35                                                       
Version 5.0, March 02, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN13 
“A Prospective, Multi-Center Pivotal Clinical Evaluation of a Novel Multi-Wavelength Laser for Tattoo Removal“ 
 
Confidential and Proprietary 
Page 33 of 35                                                       
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