An Open Label, Split-tattoo Study Comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal
Phase: NA
Conditions: Tattoo Removal
Sponsor: Cutera Inc.

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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TITLE PAGE 
 
 
 
Protocol Number: 
C-16-EN15 
Protocol Title: 
An Open Label, Split-tattoo Study comparing the Safety 
and Efficacy of the 670nm Picosecond Laser Versus the 
755 nm Picosecond Laser for Tattoo Removal 
 
Sponsor: 
 
Cutera, Inc. 
3240 Bayshore Boulevard 
Brisbane, CA 94005 
Telephone: 1-415-657-5722 
Fax:  1-415-715-3722 
Contact:  Emily Hu, Clinical Project Manager 
Email:  ehu@cutera.com 
 
 
Principal 
Investigator: 
 
 
 
 
 
 
 
 
 
 
  
 
 
Version, Date: 
Version 2.0  Dated  September 29, 2016 
 
 
 
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-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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Protocol Signature Page – Principal Investigator 
 
 
PROTOCOL C-16-EN15 
 
 
Study Title:   An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm 
Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal 
 
 
Protocol Version 2.0, Dated September 29, 2016 
 
I have received and read the protocol dated September 29, 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 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-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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Table of Contents 
Protocol Summary ..........................................................................................................................................6 
1 
PURPOSE ................................................................................................................................................7 
2 
BACKGROUND INFORMATION ...............................................................................................................7 
2.1 
Tattoo Removal ...................................................................................................................................7 
3 
STUDY OBJECTIVES ...............................................................................................................................10 
4 
STUDY DESIGN ......................................................................................................................................10 
4.1 
Study Endpoints ................................................................................................................................10 
4.1.1 
Efficacy endpoints .........................................................................................................................10 
4.1.1.1 
Primary Efficacy Endpoint ..........................................................................................................10 
4.1.1.2 
Secondary Efficacy Endpoints ....................................................................................................10 
4.1.2 
Exploratory Efficacy .......................................................................................................................11 
4.1.3 
Safety Endpoint .............................................................................................................................11 
4.2 
Study Duration ..................................................................................................................................11 
4.3 
Assignment of Treatment Arms ........................................................................................................11 
4.4 
Blinding and Randomization of Photographs ...................................................................................11 
4.4.1 
Blinding ..........................................................................................................................................11 
4.4.2 
Randomization of Photographs .....................................................................................................11 
4.5 
Study Effectiveness Assessments ......................................................................................................12 
4.5.1 
Investigator Assessments ..............................................................................................................12 
4.5.2 
Subject Assessments .....................................................................................................................12 
4.5.3 
Exploratory Blinded Assessment ...................................................................................................12 
4.6 
Study Safety Assessments..........................................................................................................13 
4.7 
Photographs ..................................................................................................................................13 
4.8 
Study Discontinuation ...................................................................................................................13 
4.9 
Investigator Selection ....................................................................................................................13 
5 
STUDY POPULATION .............................................................................................................................13 
5.1 
Study Subject Recruitment and Selection .....................................................................................13 
5.1.1 
Inclusion Criteria ....................................................................................................................14 
5.1.2 
Exclusion Criteria ....................................................................................................................14 
5.2 
Subject Numbering ........................................................................................................................15 
5.3 
Subject Discontinuation Criteria....................................................................................................15 
6 
STUDY PROCEDURES ............................................................................................................................15 
6.1 
Screening / Enrollment Procedures ..................................................................................................15 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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6.2 
Laser Treatment Visits – Pre-Treatment Procedures ........................................................................16 
6.3 
Laser Treatment Procedures – All Visits ...........................................................................................16 
6.4 
Follow-Up Visits .................................................................................................................................17 
6.5 .............................................................................................................................................................17 
6.6 
Biopsy Suture Removal Visit (as applicable) ..................................................................................18 
7 
ADVERSE DEVICE EFFECTS ....................................................................................................................18 
7.1 
Definitions .........................................................................................................................................18 
7.1.1 
Adverse Device Effect ....................................................................................................................18 
7.1.2 
Serious Adverse Device Effect .......................................................................................................18 
7.1.2.1 
Anticipated Serious Adverse Device Effect (ASADE) ...................................................................19 
7.1.2.2 
Unanticipated Serious Adverse Device Effect (USADE/UADE) ...................................................19 
7.2 
Recording ADEs and SADEs ...............................................................................................................21 
7.3 
Follow-up of Subjects after ADEs and SADEs: ...................................................................................21 
8 
POTENTIAL RISKS / BENEFITS ...............................................................................................................21 
8.1 
Potential Risks ...................................................................................................................................21 
8.2 
Potential Benefits ..............................................................................................................................23 
9 
RISK MANAGEMENT .............................................................................................................................23 
10 DATA ANALYSIS PLAN ............................................................................................................................23 
10.1 Sample Size ........................................................................................................................................23 
10.2 Demographics and Subject Characteristics at Baseline ....................................................................23 
10.3 Statistical Analysis Methods ..............................................................................................................23 
10.3.1 
Analysis Sets ..................................................................................................................................23 
10.3.2 
Analysis of Primary Endpoint.........................................................................................................23 
10.3.3 
Analyses of Secondary Endpoints ..................................................................................................23 
10.3.4 
Safety Analyses ..............................................................................................................................24 
11 SUBJECT PAYMENT ...............................................................................................................................24 
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 .........................................................................................................26 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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12.6 Data Collection, Record Keeping and Storage ...................................................................................26 
13 SUBJECT CONFIDENTIALITY ..................................................................................................................27 
14 PUBLICATION POLICY............................................................................................................................27 
REFERENCES .................................................................................................................................................29 
Appendix 1: Study Schedule .........................................................................................................................31 
Appendix 2: Pain Rating Scale ......................................................................................................................32 
Appendix 3: Fitzpatrick Skin Type Classification ..........................................................................................33 
Appendix 4:  Before and After Treatment Instructions ...............................................................................34 
Appendix 5:  Follow-Up Subject Questionnaire ...........................................................................................35 
Appendix 6: Before and After Biopsy Instructions .......................................................................................37 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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Protocol Summary 
 
Title 
An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 
670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo 
Removal 
Objective 
 
To evaluate the safety and efficacy of an investigational version of the 
Cutera enlightenTM laser as compared to treatment with the Cynosure 
PicosureTM laser for tattoo removal 
Study Design 
An open-label, split-tattoo, single-center, prospective, comparison 
study. 
Enrollment 
A maximum of 20 subjects 
Primary Endpoint 
• Degree of tattoo clearing at 6 weeks post-final treatment as 
assessed by the Investigator (Physician’s Global Assessment 
of Improvement). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
). 
Subject Population 
Female or male subjects, age 18 to 65 years, Fitzpatrick skin types I-VI 
Planned Schedule 
First subject enrolled:  September 2016 
Last subject last visit:  December 2018 
 
 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond 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 as compared to treatment with the Cynosure PicosureTM laser. 
The version of the enlighten laser under investigation allows the user to treat at a wavelength of 670 nm 
as well as 532 nm or 1064 nm. 
 
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 
(Nd:YAG), 1064 nm (Nd:YAG), 755 nm (Alexandrite) and 694 nm (Ruby) wavelengths.  1064 nm (Nd:YAG) 
and 755 nm (Alexandrite) wavelengths are used for black and blue tattoos, 694 nm (Ruby) wavelength for 
blue, black and green tattoos; 532 nm (Nd:YAG) 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 (Nd:YAG) 755 nm (Alexandrite) and 694 nm (Ruby) 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 (Nd:YAG), 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 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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skin patients with Nd:YAG lasers.  Scarring is rarely observed following treatments with QS lasers as water 
is no longer the target chromophore. 
 
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 
all 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 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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4.1.3 
Safety Endpoint 
• Incidence and severity of adverse device effects during the study period, including subject pain 
level during laser treatment. 
 
4.2 
Study Duration 
Subjects enrolled in this trial will be asked to participate for up to 15 months, 
 
. 
 
, and 1 required follow-up visit at 6 weeks 
 
) post-final treatment.
 
 
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 
Assignment of Treatment Arms 
Subjects will be assigned to either the single arm group or the split-tattoo treatment group in a 1:1 ratio. 
For the split-tattoo treatment group, the investigational treatment will be assigned to either part A 
(right/top side) or part B (left/lower side) of the tattoo (based on patient’s left and right).  
4.4 
Blinding and Randomization of Photographs 
4.4.1 
Blinding 
A panel of independent reviewers may assess subject photographs taken at baseline, 6 weeks and 12 
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. 
4.4.2 
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. Statistical software will be used to perform 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. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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4.6 
Study Safety Assessments 
4.6.1 
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. 
4.6.2 
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. 
4.7 
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. 
4.8 
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. 
4.9 
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 
Up to 20 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. 
 
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.  

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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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.  
4.  
Subject must be able to read, understand and sign the Informed Consent Form. 
5.  
Must be willing and able to adhere to the treatment and follow-up schedule and post-
treatment care instructions. 
6.  
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. 
7.  
Willing to have digital photographs taken of the treatment area and agree to use of 
photographs for presentation, educational or marketing purposes. 
8.  
Agree to not undergo any other procedure(s) for tattoo removal during the study (as 
applicable). 
9.  
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 
immunosuppressive medications.  
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. 

Cutera, Inc. 
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“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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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 within 6 months of study participation.  
22.  Anytime in life, having have 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.  
 
6 
 
 
 
 
 
 
 

Cutera, Inc. 
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Cutera, Inc. 
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“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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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 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 enlighten laser system by a 
representative of Cutera. 
10  DATA ANALYSIS PLAN  
10.1 Sample Size 
Up to 20 subjects will be enrolled in this safety and efficacy 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 
10.3.1 Analysis Sets 
The efficacy analysis set will include all subjects who received at least one laser treatment session and 
complete the 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. 
10.3.2 Analysis of Primary Endpoint 
Formal statistical analysis is not planned for this study. The primary efficacy endpoint data, degree of 
tattoo clearing at 6 weeks post-final treatment as assessed by the Investigator (Physician’s Global 
Assessment), will be summarized descriptively.  
 
 
  
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
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10.3.4 Safety Analyses 
Safety variables will be analyzed descriptively. 
 
The safety variables for this study are: 
 
1. 
Subject discomfort (pain) during and after treatment (to be descriptively displayed).  
2. 
Incidence and severity of adverse effects during study duration (to be displayed descriptively 
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. 
 
 
 
 
 
 
  
12   STUDY MANAGEMENT AND ADMINISTRATIVE PROCEDURES  
 
 
 
 
  
 
 
 
 
12.2 Informed Consent 
 
 
 
 
 
 
 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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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/EC 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 the IRB/EC 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 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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(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-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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13   SUBJECT CONFIDENTIALITY 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
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 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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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-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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1 Optional 12-week follow-up visit, at Investigator’s discretion 

Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
Page 34 of 37                                                       
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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Cutera, Inc. 
Protocol # C-16-EN15 
“An Open Label, Split-tattoo Study comparing the Safety and Efficacy of the 670nm Picosecond Laser Versus the 755 nm Picosecond Laser for Tattoo Removal” 
 
Confidential and Proprietary 
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