Evaluation of the PicoWay™ Laser System With 730nm and Resolve™ Fusion Handpieces for Treatment of Benign Pigmented Lesions and Wrinkles
Phase: NA
Conditions: Benign Pigmented Lesions, Facial Wrinkles
Sponsor: Candela Corporation

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Protocol Title: 
Evaluation of the PicoWay® Laser System with 730 nm and 
Resolve™ Fusion Handpieces for Treatment of Benign 
Pigmented Lesions and Wrinkles 
 
Protocol Number: 
PWY18010 
 
NCT:  
NCT03774849 
 
Version: 
1.0 
 
Date: 
28 November 2018 
 
Sponsor: 
Candela Corporation 
530 Boston Post Road 
Wayland, MA 01778 
 
Sponsor Contact: 
Joseph A. Lowery 
Director, Clinical Affairs 
Phone: 508.358.7400, ext. 3219 
Ema                                    il:  
 
 
Principal Investigator: 
Khalil A. Khatri, MD 
Medical Director 
Syneron Candela Institute for Excellence 
530 Boston Post Road 
Wayland, MA  01778 
   xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
   xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
 
 
 
 
 
 
 
STATEMENT OF CONFIDENTIALITY 
The information contained herein is Confidential Information that remains the sole and exclusive 
property of Candela Corporation (the Sponsor) and is expressly subject to the terms and 
conditions of the Clinical Trial Agreement signed by the Investigator and the Sponsor. 

 
 
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Table of Contents 
1. 
Study Synopsis ............................................................................................................ 4 
2. 
Abbreviations ............................................................................................................... 8 
3. 
Study Objective ............................................................................................................ 9 
4. 
Background .................................................................................................................. 9 
5. 
Study Design ................................................................................................................ 9 
6. 
Study Overview ............................................................................................................ 9 
7. 
Study Population ........................................................................................................ 10 
8. 
Inclusion / Exclusion Criteria ...................................................................................... 11 
8.1. 
Inclusion Criteria............................................................................................... 11 
8.2. 
Exclusion Criteria ............................................................................................. 11 
9. 
Measurement Instruments .......................................................................................... 12 
9.1. 
Pigment Clearance Score (PCS) ...................................................................... 12 
9.2. 
Fitzpatrick Wrinkle Scale (FWS) ....................................................................... 12 
9.3. 
Subject Pain Scale ........................................................................................... 12 
9.4. 
Subject Satisfaction Survey .............................................................................. 12 
10. 
Study Visit Procedures ............................................................................................ 12 
10.1. 
Screening Visit .............................................................................................. 12 
10.2. 
Baseline and Treatment Visits ...................................................................... 13 
10.3. 
Follow-Up Visits ............................................................................................ 16 
11. 
Schedule of Events ................................................................................................. 17 
12. 
Study Compliance .........................................................................................17 
13. 
Study Device ................................................................................................ 18 
13.1. 
PicoWay® Laser System ............................................................................... 18 
13.2. 
Technical Specifications ............................................................................... 19 
13.3. 
Device Training ............................................................................................. 19 
14. 
Regulatory Approvals .............................................................................................. 19 
14.1. 
Indications for Use ........................................................................................ 20 
15. 
Non-Significant Risk Determination ......................................................................... 20 
16. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ................... 21 
17. 
Study Endpoints ........................................................................................... 21 
17.1. 
Primary Effectiveness Endpoints ............................................................................. 21 
17.2. 
Primary Safety Endpoint ......................................................................................... 21 
17.3. 
Secondary Endpoints .............................................................................................. 21 
17.4. 
Exploratory Endpoints ............................................................................................. 22 
18. 
Blinded Evaluation ....................................................................................... 22 
19. 
Statistical Methods ....................................................................................... 22 
19.1. 
Statistical Plan Overview......................................................................................... 22 
19.2. 
Hypotheses ............................................................................................................. 23 
19.3. 
Sample Size ................................................................................................................ 23 
19.4. 
Effectiveness Analyses ........................................................................................... 24 
19.5. 
Safety Analyses ...................................................................................................... 24 
20. 
Histological Analysis .................................................................................... 24 
20.1. 
Light Microscopy ..................................................................................................... 24 
20.2. 
Scanning Electron Microscopy ................................................................................ 25 
21. 
Risks and Benefits ....................................................................................... 25 
21.1. 
Potential Risks ........................................................................................................ 25 
21.2. 
Potential Benefits .................................................................................................... 25 
22. 
Adverse Device Effects ................................................................................ 25 
22.1. 
Definitions ............................................................................................................... 25 
22.2. 
Reporting ................................................................................................................ 26 

 
 
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22.3. 
Rating ..................................................................................................................... 26 
23. 
Investigational Sites ................................................................................................ 28 
24. 
Compensation ......................................................................................................... 28 
25. 
Monitoring Plan ....................................................................................................... 28 
26. 
Protocol Deviation Reporting .................................................................................. 28 
27. 
Record Retention .................................................................................................... 29 
28. 
Publication Policy .................................................................................................... 29 
29. 
References ............................................................................................................. 30 
30. 
Appendices ............................................................................................................. 31 
30.1. 
Appendix A:  Pigment Clearance Score Pigment Score .......................................... 32 
30.2. 
Appendix B:  Fitzpatrick Wrinkle Score (FWS) ........................................................ 33 
30.3. 
Appendix C:  Subject Pain Scale ............................................................................ 34 
30.4. 
Appendix D:  Subject Satisfaction Scale ................................................................. 35 
30.5. 
Appendix E:  Local Skin Response ......................................................................... 36 

 
 
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1. 
Study Synopsis 
 
 
Protocol Number 
PWY18010 
Protocol Version 
v 1.0 28NOV2018 
Protocol Title 
Evaluation of the PicoWay® Laser System with 730 nm and Resolve™ 
Fusion Handpieces for Treatment of Benign Pigmented Lesions and 
Wrinkles 
Short Title 
PicoWay 730 Resolve Fusion 
Device Description 
PicoWay® Laser System, Candela Corporation, Wayland, MA 
Study Design 
Prospective, non-randomized, multi-center, evaluator blinded, safety 
and efficacy clinical study 
Study Objective 
Evaluate the safety and efficacy of the PicoWay® Laser System with 
730 nm and Resolve™ Fusion handpieces for treatment of benign 
pigmented lesions including dyschromia, and wrinkles including fine 
lines 
Investigative Sites 
Up to two (2) investigational sites located in the United States 
Number of Subjects 
Up to 160 subjects 
Study Duration 
The overall duration of this study is not expected to exceed 24 months 
Study Overview 
Upon enrollment subjects will be assigned to one or possibly both of 
the following laser treatment groups based on their qualifying 
indications: 
Group A: Benign Pigmented Lesions including dyschromia 
Group B: Wrinkles including fine lines 
Subjects will receive up to 4 laser treatments at 6 ± 2 week intervals 
with the PicoWay® Laser System. Handpiece selection and specific 
treatment parameters will be determined by the clinician. 
The treatment area will be photographed at every visit. Baseline 
photographs will be compared to follow-up photographs to determine 
the effectiveness of the laser treatments. 
The Study Doctor or staff will contact subjects by telephone 10 days 
after each treatment visit to assess healing response. 
Optional skin punch biopsies may be collected prior to or immediately 
after laser treatment, or at follow-up visits at clinician’s discretion. 
Subjects must provide signed written consent prior to any biopsy 
procedure. Subjects may still participate in the study if they choose 
not to undergo biopsies. 
Subjects will be scheduled for follow-up visits at 4 ± 1 week, 8 ± 2 
weeks and 12 ± 2 weeks after the final laser treatment. Additional 
visits may be requested at the discretion of the clinician. 

 
 
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Study Population 
Adults seeking treatment of benign pigmented lesions including 
dyschromia and/or wrinkles including fine lines, and who satisfy all 
study inclusion and exclusion criteria, and who provide written 
informed consent will be considered eligible for this study. 
Study Eligibility 
Inclusion Criteria 
Subjects must meet all inclusion criteria to be enrolled in this study: 
1. 
Willing to provide signed informed consent 
2. 
Adults age 21 to 80 
3. 
Fitzpatrick Skin Type (FST) I to VI 
4. 
Presence of benign pigmented Lesions assessed at baseline as 
Pigment Severity Score (PSS) of “2” or higher and/or wrinkles 
assessed at baseline as Fitzpatrick Wrinkle Score (FWS) of “2” 
or higher 
5. 
Willing to allow photographs and/or video to be taken of treated 
areas for the purposes of this research study 
6. 
Willing to abstain from any other procedures for treatment of 
benign pigmented lesions or wrinkles in the laser treatment 
areas for the duration of the study including surgery, light, laser, 
ultrasound or radiofrequency treatments 
7. 
Willing to abstain from use of prescription cosmetic products for 
treatment of benign pigmented lesions or wrinkles in the laser 
treatment areas for the duration of the study including injections 
of neurotoxins or dermal fillers, skin lightening creams, and 
wrinkle creams 
8. 
Willingness to adhere to study treatment and follow-up visit 
schedules 
Exclusion Criteria 
Subjects who meet any exclusion criteria cannot be enrolled in the 
study: 
1. 
Pregnant, planning pregnancy or breast feeding 
2. 
Allergy to topical or injectable lidocaine or similar medications 
3. 
Allergy to topical steroid or similar medications 
4. 
Unprotected sun exposure in the six weeks prior to enrollment, 
or active tan in the laser treatment area 
5. 
History of melanoma in the intended treatment area 
6. 
History of keloid or hypertrophic scar formation 
7. 
Use of topical or systemic retinoid therapy during the past six (6) 
months 
8. 
Use of neurotoxins in the intended treatment area within the past 
three (3) months or throughout the duration of the study 
9. 
Use of dermal fillers in the intended treatment area within the 
last six (6) months or throughout the duration of the study 

 
 
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10. 
Severe immunosuppression resulting from medications and/or a 
medical condition that could impair healing after treatment. 
11. 
Open wound or infection in the intended treatment area 
12. 
History of light induced seizure disorders 
13. 
Dermatologic and/or cosmetic procedures in the intended 
treatment area(s) during the past six months 
14. 
The subject is not suitable, in the opinion of the clinician, for 
participation in the study due to medical or other reasons that 
could compromise the study integrity or subject safety 
Study Visit Outline 
NOTE: Screening Visit and Baseline/Treatment Visit #1 may occur on 
the same day 
Screening Visit: 
1. Informed Consent 
2. Inclusion and Exclusion Criteria Review 
3. Medical History Review 
4. Concomitant Medication Review 
5. Fitzpatrick Skin Type (FST) Evaluation 
6. Benign Pigmented Lesion and Wrinkle Evaluation 
Baseline / Treatment Visit #1: 
1. Clinical Photography 
2. Laser Treatment 
3. Local Skin Response Assessment 
4. Subject Pain Score Assessment 
5. Safety Assessment 
6. Skin Biopsy (optional) 
Telephone Contact 
1. 10 days +/- 7 days after each treatment 
Treatment Visits #2 to #4: 
1. Clinical Photography 
2. Subject Satisfaction Score 
3. Laser Treatment 
4. Local Skin Response Assessment 
5. Subject Pain Score Assessment 
6. Safety Assessment 
7. Skin Biopsy (optional) 
Follow-Up Visits: 4 ± 1 week, 8 ± 2 weeks, 12 ± 4 weeks. 
1. Clinical Photography 
2. Subject Satisfaction Score 
3. Local Skin Response Assessment 
4. Safety Assessment 
5. Skin Biopsy (optional) 
Measurement 
Instruments 
5-Point Pigment Clearance Scale (Appendix A) 
9-Point Fitzpatrick Wrinkle Scale (Appendix B) 

 
 
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11-Point Subject Pain Scale (Appendix C) 
5-Point Subject Satisfaction Scale (Appendix D) 
Local Skin Response (Appendix E) 
Primary Efficacy 
Endpoints 
1. Benign Pigmented Lesions 
Mean difference from Baseline to 12-week follow-up in Pigment 
Clearance Score (PCS) as determined by blinded evaluators from 
clinical photography 
2. Wrinkles 
Mean difference from Baseline to 12-week follow-Up in Fitzpatrick 
Wrinkle Score (FWS) as determined by blinded evaluators from clinical 
photography 
Secondary Efficacy 
Endpoints 
1. Benign Pigmented Lesions 
Percentage of subjects demonstrating Pigment Clearance Score 
(PCS) of 3 or 4 (> 50% improvement) comparing Baseline to 12-week 
follow-up as determined by blinded evaluators from clinical 
photographs 
2. Wrinkles 
Percentage of subjects demonstrating > 1 score improvement in 
Fitzpatrick Wrinkle Score (FWS) from Baseline to 12-week follow-up 
visit as determined by agreement of 2 out of 3 blinded evaluators from 
clinical photographs 
3. Subject Satisfaction 
Mean and distribution of Subject Satisfaction Scores at all visits 
beyond Treatment Visit #1 
4. Subject Pain 
Mean and distribution of Subject Pain Scores following each treatment 
Primary Safety 
Endpoint 
Incidence, severity and relatedness of adverse device effects based 
on total number of laser treatments performed 
Exploratory 
Endpoint 
Analysis of laser-tissue effects and/or healing response from pre- and 
post-treatment skin biopsies using light microscopy and/or scanning 
electron microscopy 

 
 
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2. 
Abbreviations 
 
 
ADE 
Adverse Device Effect 
cm, cm2 
Centimeter, Square Centimeters 
CFR 
Code of Federal Regulations 
Ø 
Diameter 
FDA 
Food and Drug Administration 
FST 
Fitzpatrick Skin Type 
FWS 
Fitzpatrick Wrinkle Score 
GCP 
Good Clinical Practice 
Hz 
Hertz 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
J 
Joule 
µbeam 
Microbeam 
µm 
Micron 
µs 
Microsecond 
mJ 
Millijoule 
mm 
Millimeter 
ms 
Millisecond 
nm 
Nanometer 
Nd:YAG 
Neodymium: Yttrium Aluminum Garnet (YAG) 
NSR 
Non-Significant Risk 
PCS 
Pigment Clearance Score 
PSS 
Pigment Severity Score 
ps 
Picosecond 
SE 
Side Effect 
SOP 
Standard Operating Procedure 
Tx 
Treatment 
UADE 
Unanticipated Adverse Device Effect 

 
 
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3. 
Study Objective 
The purpose of this study is to evaluate the PicoWay® Laser System with 730 nm handpiece 
and Resolve™ Fusion 1064 nm and 532 nm fractional handpieces for the treatment for 
benign pigmented lesions including dyschromia, and wrinkles including fine lines. 
 
4. 
Background 
The use of lasers to selectively target chromophores in the skin was first described by 
Anderson and Parrish in 19831 which led directly to the development of the first pulsed 
dye laser to be used in dermatology to treat vascular lesions. As laser technology 
advanced shorter pulse duration lasers, such as nanosecond pulse duration domain Q- 
switched Ruby and Nd:YAG lasers among others, were developed to safely and 
effectively remove tattoos and pigmented lesions using the same principles of selective 
photothermolysis.3-5 Further advances led to the introduction of lasers with pulse 
durations in the picosecond domain including the Nd:YAG at wavelengths of 532 
nm,1064 nm; and the alexandrite at 755 nm which have both been demonstrated as safe 
and effective for treatment of benign pigmented lesions, wrinkles, tattoo removal, and 
other indications.6-13 
 
5. 
Study Design 
This is a prospective, non-randomized, multi-center, evaluator blinded, safety and 
efficacy clinical study. Subjects will serve as their own control as the appearance of their 
benign pigmented lesions and/or wrinkles at baseline is compared to the appearance 
following laser treatment. 
 
6. 
Study Overview 
Subjects will participate in a Screening Visit to evaluate the presence of benign 
pigmented lesions including dyschromia, or wrinkles including fine lines. After evaluating 
all inclusion and exclusion criteria, and providing signed informed consent, subjects will 
be considered enrolled in the study and assigned a unique identification number that will 
appear on all records for that subject as the Subject ID. 
 
Subjects will then either be scheduled for the Baseline / Treatment Visit #1 at a later 
date, or the Screening and Baseline / Treatment #1 Visits may be combined into the 
same visit. 
 
Subjects will receive up to four (4) study laser treatments at 6 ± 2 week treatment 
intervals. 
 
NOTE: Fewer than four (4) Treatment Visits may be required to reach maximum 
expected clinical results in some subjects. Treatments may therefore be stopped, and 
subject placed into the Follow-Up phase at the discretion of the Investigator. 
 
The Study Doctor or staff will make up to three (3) attempts to contact subjects by 
telephone 10 days after each treatment to assess healing response. 

 
 
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After the final study laser treatment, subjects will be schedule for three (3) follow-up 
visits at 4 ± 2 week intervals, or approximately 1, 2 and 3 months. 
 
After successful completion of the 12 week follow-up visit, subjects will be exited from 
the study. 
 
7. 
Study Population 
Up to 160 subjects will be enrolled in this study at up to two (2) investigational sites in the 
United States. 
 
The Study Population will be enrolled at the discretion of the Investigator after 
determining that eligible subjects have unwanted benign pigmented lesions including 
dyschromia on the face, scalp, neck, chest, back, arms, hands, legs or feet; or wrinkles 
including fine lines on the face. 
 
Subjects will be assessed at the Screening Visit and allocated to one or both study sub- 
groups if eligible: 
 
Group A: Benign Pigmented Lesions including dyschromia 
Group B: Wrinkles including fine lines 
The logic scheme used for group allocation is provided below in Figure 1. 
Figure 1: Study Group Allocation Logic 
 
 
All subjects must satisfy the inclusion and exclusion criteria and provide signed informed 
consent to be eligible for participation in the study. Subjects enrolled in the study can 
discontinue their participation at any time for any reason without prejudice or reduction in 
the quality of their medical care. The Investigator or Sponsor can terminate a subject's 
participation in this study at any time to protect the subject's health or if a subject fails to 

 
 
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follow directions that result in noncompliance with study procedures. Subjects who 
withdraw or are terminated from the study prior to completion may be replaced. 
 
 
8. 
Inclusion / Exclusion Criteria 
 
8.1. Inclusion Criteria 
Subjects must meet all inclusion criteria to be enrolled in this study: 
 
1. 
Willing to provide signed informed consent 
2. 
Adults age 21 to 80 
3. 
Fitzpatrick Skin Type (FST) I to VI 
4. 
Presence of benign pigmented Lesions assessed at baseline as Pigment Severity 
Score (PSS) of “2” or higher and/or wrinkles assessed at baseline as Fitzpatrick 
Wrinkle Score (FWS) of “2” or higher 
5. 
Willing to allow photographs and/or video to be taken of treated areas for the 
purposes of this research study 
6. 
Willing to abstain from any other procedures for treatment of benign pigmented 
lesions or wrinkles in the laser treatment areas for the duration of the study 
including surgery, light, laser, ultrasound or radiofrequency treatments 
7. 
Willing to abstain from use of prescription cosmetic products for treatment of benign 
pigmented lesions or wrinkles in the laser treatment areas for the duration of the 
study including injections of neurotoxins or dermal fillers, skin lightening creams, 
and wrinkle creams 
8. 
Willingness to adhere to study treatment and follow-up visit schedules 
 
8.2. Exclusion Criteria 
Subjects who meet any exclusion criteria cannot be enrolled in the study: 
 
1. Pregnant, planning pregnancy or breast feeding 
2. Allergy to topical or injectable lidocaine or similar medications 
3. Allergy to topical steroid or similar medications 
4. Unprotected sun exposure in the six weeks prior to enrollment, or active tan in the 
laser treatment area 
5. History of melanoma in the intended treatment area 
6. History of keloid or hypertrophic scar formation 
7. Use of topical or systemic retinoid therapy during the past six (6) months 
8. Use of neurotoxins in the intended treatment area within the past three (3) months 
or throughout the duration of the study 
9. Use of dermal fillers in the intended treatment area within the last six (6) months or 
throughout the duration of the study 
10. Severe immunosuppression resulting from medications and/or a medical condition 
that could impair healing after treatment. 
11. Open wound or infection in the intended treatment area 
12. History of light induced seizure disorders 

 
 
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13. Dermatologic and/or cosmetic procedures in the intended treatment areas during 
the past six months that would compromise study integrity 
14. The subject is not suitable, in the opinion of the clinician, for participation in the 
study due to medical or other reasons that could compromise the study integrity or 
subject safety 
 
9. 
Measurement Instruments 
 
9.1. Pigment Clearance Score (PCS) 
Clearance of pigment following study treatment will be measured using a validated 5-point 
Pigment Clearance Scale (PCS) that categorizes improvement in the appearance of 
pigmented lesions from 0=0% or No Improvement to 4=75-100% or Excellent 
Improvement.14 The PCS scoring scale is provided in Appendix A. 
 
 
9.2. Fitzpatrick Wrinkle Scale (FWS) 
Improvement in the appearance of facial wrinkles following study treatment will be 
measured using the validated 9-point Fitzpatrick Wrinkle Scale (FWS) that categorized 
wrinkle severity from 1=Fine Wrinkles to 9=Deep Wrinkles.15 The FWS scoring scale is 
provided in Appendix B. 
 
9.3. Subject Pain Scale 
Immediately after each treatment subjects will be asked to rate the amount of pain 
experienced during treatment using an 11-point Subject Pain Scale ranging from 0=No Pain 
to 10=Extreme Pain. The Subject Pain Scale is provided in Appendix C. 
 
9.4. Subject Satisfaction Survey 
At each study visit beyond Treatment Visit #1 the subjects will be asked to rate their level 
of satisfaction with the treatment results so far using a 5-point Subject Satisfaction Survey 
ranging from -2=Extremely Dissatisfied to 2=Extremely Satisfied. The Satisfaction Survey 
is provided in Appendix D. 
 
10. 
Study Visit Procedures 
 
10.1. 
Screening Visit 
The following activities typically take place during the Screening Visit. 
 
Informed Consent 
The site will provide detailed information about the study, including study procedures, visit 
schedule, potential risks and benefits and alternative treatment options. The subject will 
be given time to review the informed consent form (ICF). If the subject wishes to 
participate, he/she will complete the ICF with a signature and date. The original will be 
retained with subject’s study records and a copy will be provided to the subject. 
 

 
 
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Medical History 
Subject’s medical history, including dermatological treatment history and assessment of 
medication use will be documented. 
 
Pregnancy Test 
Women of childbearing potential will undergo a urine pregnancy test. Subjects with a 
positive pregnancy test are ineligible for study participation. 
 
A woman of childbearing potential is defined as a premenopausal female capable of 
becoming pregnant. This includes women on oral, injectable, or mechanical 
contraception; women who are single; women whose partners have been vasectomized 
or whose partners are utilizing mechanical contraceptive devices. 
Treatment Area Examination and Lesion Identification 
Wrinkle evaluation will be performed using the Fitzpatrick Wrinkle Score. Benign 
pigmented lesions, a description of lesion type anatomical location, and size will be 
documented. 
 
Inclusion/Exclusion Criteria Review 
Study inclusion and exclusion criteria will be reviewed to verify study eligibility. 
 
10.2. 
Baseline and Treatment Visits 
The following activities typically take place during each Treatment Visit. 
 
Pregnancy Test 
Women of childbearing potential will undergo a urine pregnancy test. Subjects with a 
positive pregnancy test will be discontinued from the study. The subject will be followed 
until the outcome of pregnancy is determined. 
 
Photography 
Prior to each laser treatment the treatment areas will be photographed using a high- 
resolution digital camera. Camera settings and other parameters such as distance, 
lighting, background and polarization will be recorded and reproduced at subsequent 
photography sessions. 
 
Subject Satisfaction 
At each treatment visit beyond Treatment #1, subjects will be asked to rate their level of 
satisfaction with the study treatments thus far using the Subject Satisfaction Scale 
provided in Appendix D. 
 
Eye Safety 
The correct eye protection must be worn during all laser treatments by the subject, the 
treating Investigator, and all other study personnel or observers in the room during laser 
operation. 
 
Treatment Area Preparation 
The intended treatment area will be cleansed with isopropyl alcohol or similar prior to 
treatment to ensure the treatment area is free of any makeup, creams or lotions. 

 
 
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Skin Biopsy (Optional) 
Subjects may be asked if they will allow one or more skin punch biopsies to be performed 
at or near the treatment area prior to and/or immediately after treatment. Biopsies are 
optional and will only be performed after written consent is obtained from the subject. 
The Investigator will determine if biopsies are needed based on the condition being 
treated, location, or other factors. Performance of the biopsy typically follows these 
steps: 
 
a) Skin biopsies will be collected at or near the treatment area. 
b) Biopsy site will be cleansed with isopropanol alcohol or similar. 
c) Local anesthetic injection (lidocaine or similar medication) will be administered 
intradermally to the biopsy site prior to collection. 
d) Biopsy will be collected using sterile, single use disposable 2 mm to 4 mm punch 
biopsy. 
e) Sutures may be used to close the biopsy site as needed. 
f) Biopsies will be placed in a container labeled with Subject’s ID number and date of 
collection. 
g) Biopsies will be fixed and processed for hematoxylin and eosin staining and/or 
scanning electron microscopy according to laboratory guidelines. 
 
Anesthesia 
To reduce pain and discomfort during laser treatment, the Investigator may recommend 
use of a topical anesthetic product, such as EMLA or LMX-4 cream, which is applied to 
the intended treatment area for approximately 60 minutes prior to treatment. The 
Investigator may also recommend use of a local intradermal injection of anesthesia, such 
as lidocaine or similar medication. Nonmedicinal methods may also be offered such as 
simple ice packs, or devices that provide cold air , such as a Zimmer cooling device (Cryo 
6, Zimmer Medizin Systems, Irvine, CA). Subjects may also elect to be treated without 
anesthesia. 
 
Test Spots 
Test spots may be performed prior to treatment to help the Investigator establish 
appropriate treatment parameters to achieve the desired clinical endpoint such as 
erythema or whitening. Test spot parameters will be guided by subject skin type, lesion 
type, color or location among other factors. The procedure for test spots involves 
delivering a laser pulse to the skin at or near the treatment area using a low energy, 
fluence or other setting, and then increasing the relevant parameters until the desired 
clinical endpoint is achieved. For the PicoWay® laser system the clinical endpoint is most 
commonly erythema or whitening of the skin. 
 
Laser Treatment 
Study laser treatments will be administered using treatment parameters recommended by 
the manufacturer and study Sponsor, Candela Corporation. The treatment location, 
wavelength, handpiece, pulse energy, number of passes, and number of pulses will be 
documented in the case report form. 

 
 
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Benign pigmented lesions including dyschromia will typically be treated with either the 
532 nm or 1064 nm Resolve™ Fusion, or 730 nm handpiece. 
 
Wrinkles including fine lines will typically be treated with the 1064 nm Resolve™ Fusion 
handpiece. 
 
The investigator will determine the treatment specific parameters including wavelength, 
energy, fluence, spot size and repetition rate for each subject based on the type, color 
and location of the lesion among other factors. For darker skin types FST V and FST VI 
the 1064 nm wavelength is most commonly used. 
 
Pain Assessment 
Immediately after each treatment subjects will be asked to rate the amount of pain 
experienced during treatment using an 11-point Subject Pain Scale ranging from 0 (No 
Pain) to 10 (Extreme Pain). The Subject Pain Scale is provided in Appendix C. 
 
Local Skin Response Assessment 
Local skin responses will be assessed and recorded following each laser treatment, 
normally within the first 30 minutes. The Local Skin Response Form is provided in 
Appendix E and includes the following most commonly observed skin responses which 
are both anticipated and in some instances desired clinical endpoints: 
 
• 
Erythema 
• 
Edema 
• 
Whitening 
• 
Petechiae 
• 
Pinpoint Bleeding 
• 
Purpura 
• 
Crusting 
• 
Blistering 
• 
Burning 
 
Safety Assessment 
Local skin responses occurring from prior laser treatments that are deemed more serious 
due will be recorded as Adverse Device Effects (ADE) on the appropriate study case 
report form. Examples of anticipated ADE that can be observed following treatment with 
the PicoWay™ laser include: 
 
• 
Hyperpigmentation 
• 
Hypopigmentation 
• 
Scarring 
• 
Infection 
• 
Herpes Simplex Activation 

 
 
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Although highly uncommon in conjunction with PicoWay® laser treatments, any 
Unanticipated Adverse Device Effects (UADE) will also be recorded on case report forms 
and reported to the Sponsor and IRB as required. 
 
Post-Treatment Care Instruction 
Subjects will receive instructions on post-treatment care of their treated areas. These 
may include the application of a petrolatum gel (such as Aquaphor® or Vaseline®); use of 
a topical corticosterioid (such as Cortizone®); avoiding sun exposure or use of tanning 
equipment; and use of a sunscreen with sun protection factor (SPF) 30 or greater for the 
duration of study. 
 
Telephone Contacts 
The Study Doctor or staff will make up to three (3) attempts to contact subjects by 
telephone 10 days after each treatment (+/- 7 Days) to assess healing response. 
 
 
10.3. 
Follow-Up Visits 
Subjects will be scheduled for follow-up visits at 4 ± 1 weeks, 8 ± 2 weeks, and 12 ± 2 
weeks after their final study treatment visit, or approximately 1, 2 and 3 months. 
Additional visits may be scheduled by the Investigator as needed. 
 
Photography 
Treatment areas will be photographed at all follow-up visits using the same camera 
settings used previously at Baseline and Treatment Visits. 
 
Subject Satisfaction 
Subjects will be asked to rate their level of satisfaction with the study treatments thus far 
at each follow-up visit using the Subject Satisfaction Scale provided in Appendix C. 
 
Skin Biopsy (optional) 
Subjects who have provided prior written consent may have one or more skin biopsy 
taken from the treated area at the discretion of the Investigator. Biopsy procedure details 
are provided in the Treatment Visit section above. 

 
 
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11. 
Schedule of Events 
The Study Schedule of Events is provided in Table 1. 
 
NOTE: The Screening and Baseline / Treatment #1 Visits may be combined in the same 
visit. 
 
NOTE: Fewer than four (4) Treatment Visits may be required to reach maximum 
expected clinical results in some subjects. Treatments may therefore be stopped, and 
subject placed into the Follow-Up phase at the discretion of the Investigator. 
 
Table 1: Study Visits and Schedule of Events 
Activity 
Screening 
Baseline 
Tx 1 
Tx 2 
Tx 3 
Tx 4 
1 Month 
Follow- 
Up 
2 Month 
Follow- 
Up 
3 Month 
Follow- 
Up 
0 to -2 
Weeks 
Day 0 
Week 6 ± 
2 Weeks 
Week 12 ± 
2 Weeks 
Week 18 ± 
2 Weeks 
Week 22 ± 
2 Weeks 
Week 26 ± 
2 Weeks 
Week 30 ± 
4 Weeks 
Informed Consent 
X 
Medical 
History/Concomitant 
Medications 
X 
Inclusion/Exclusion 
Criteria 
X 
Treatment Site ID 
X 
Pregnancy Test 
X 
X 
X 
X 
X 
Skin Biopsy (Optional) 
X 
X 
X 
X 
X 
X 
X 
Telephone Contact* 
X 
X 
X 
X 
Photography 
X 
X 
X 
X 
X 
X 
X 
Laser Treatment 
X 
X 
X 
X 
Subject Pain Score 
X 
X 
X 
X 
Subject 
Satisfaction 
X 
X 
X 
X 
X 
X 
Safety Assessment 
(LSR, ADE, UADE) 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Study Exit 
X 
 
*10 Days post-treatment (+/- 7 Days) 
 
 
 

 
 
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12. 
Study Compliance 
This study will be conducted in compliance with this Protocol, guidelines as provided by 
the device manufacturer, Candela Corporation, in the PicoWay® User Manuals and 
Treatment Guides, Sponsor Standard Operating Procedures (SOP), and other applicable 
guidance as provided by 21CFR 812, ICH GCP EC(R2), or other local regulatory 
authorities. Confidentiality and privacy of subjects’ medical information will be maintained 
in compliance with the Health Insurance Portability and Accountability Act (HIPAA). 
 
13. 
Study Device 
 
13.1. 
PicoWay® Laser System 
The PicoWay® laser system is an alexandrite laser pumped, solid-state 
Neodymium:Yttruium Aluminum Garnet (Nd:YAG) laser emitting energy at user 
selectable wavelengths of 1064 nm, 532 nm, 785 nm or 730 nm xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
At the 1064 nm and 532 nm wavelengths the ZOOM handpiece is provided that allows 
the spot size of the beam delivered to the treatment area to be adjusted from a xxxxxxx 
xxxxxxx xxxxxxx in increments of xxxxxxx xxxxxxx. 
 
At the 785 nm and 730 nm wavelengths Titanium:Sapphire full surface handpieces are 
provided with selectable distance gauges that allow selection of xxxxxxx xxxxxxx 
xxxxxxx spot sizes. 
 
At the 1064 nm and 532 nm wavelengths, a Resolve™ fractional handpiece is provided 
which transforms the laser beam xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 
xxxxxxx xxxxxxx xxxxxxx xxxxxxx xxxxxxx 

 
 
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At the 1064 nm and 532 nm wavelengths, a Resolve™ Fusion fractional handpiece is 
provided which transforms the laser beam into a fractional 10 X 10 array of 101 individual 
microbeams equally spaced within a 6 mm X 6 mm square spot size. Each microbeam 
produced by the Resolve™ Fusion handpiece consists of a central beam of energy 
surrounded by an annular “ring beam”. 
 
Safety Eyewear is provided with each laser system and must be worn by all personnel in 
the treatment room while the laser is being used, including the patient. 
 
13.2. 
Technical Specifications 
Technical specifications for the PicoWay® Laser System are provided in Table 2. 
 
Table 2: Laser System Technical Specifications 
PicoWay™ Laser System 
Parameter 
Specifications 
Wavelength 
xx 
xx 
xx 
xx 
Pulse Duration (nominal) 
xx 
xx 
xx 
xx 
Maximum Radiant Energy 
xx 
xx 
xx 
xx 
Pulse Repetition Rate 
xx 
xx 
xx 
xx 
Fluence (max) ZOOM handpiece 
xx 
xx 
xx 
xx 
Fluence (max) Ti:Sapphire handpiece 
xx 
xx 
xx 
xx 
Energy (max) Resolve™ handpiece 
xx 
xx 
xx 
xx 
Energy (max) Fusion central beam 
Fluence (max) Fusion ring beam 
xx 
xx 
xx 
xx 
Safety Eyewear (minimum) 
xx 
xx 
xx 
xx 
Spot Size 
   Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx                                                         xxxxxxxxx 
Delivery System 
  Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx                                                         xxxxxxxxx 
Aiming Beam 
  Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx                                                         xxxxxxxxx 
 
[redacted due to confidential information] 
13.3. 
Device Training 
Qualified, designated study personnel at each investigational site will receive device 
specific training from the Sponsor on the PicoWay® laser system prior to performing 
study laser treatments. 
 
14. 
Regulatory Approvals 
The base system of the PicoWay® Laser System and handpieces at the 1064 nm, 785 nm 
and 532 nm wavelengths have received multiple 510(k) market clearances by the U.S. 
Food and Drug Administration (FDA) as shown in Table 3.  Specific cleared indications 
for use are also listed below. 

 
 
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The 730 nm and Resolve™ Fusion handpieces planned for use in this study are at this 
time considered Investigational Devices by the Food and Drug Administration and will 
therefore be labeled with the following statement: 
 
“CAUTION - Investigational Device. Limited by Federal (or United States) law to 
investigational use.” 
 
 
Table 3: FDA 510(k) Premarket Notifications for Candela PicoWay® Laser System 
 
510(k) Number 
Device Name 
K170597 
PicoWay Laser 
K162454 
PicoWay Laser 
K160607 
PicoWay Laser 
K153527 
PicoWay Laser 
K150326 
PicoWay Laser 
K142372 
PicoWay Laser 
 
 
14.1. 
Indications for Use 
The PicoWay® Laser System is indicated for the following at the specified wavelength: 
 
532nm: Removal of tattoos for Fitzpatrick skin types I-III to treat the following colors: 
red, yellow and orange. 
 
785nm: Removal of tattoos for Fitzpatrick skin types II-IV to treat the following tattoo 
colors: green and blue. 
 
1064nm: Removal of tattoos for all skin types (Fitzpatrick I-VI) to treat the following tattoo 
colors: black, brown, green, blue, and purple. 
 
The PicoWay® Laser System is also indicated for benign pigmented lesions removal for 
Fitzpatrick Skin Types I-IV. 
 
The Resolve™ handpiece (1064nm) is also indicated for the treatment of acne scars in 
Fitzpatrick Skin Types II-V. 
 
The Resolve™ handpieces are also indicated for treatment of wrinkles in Fitzpatrick Skin 
Types I-IV. 
 
15. 
Non-Significant Risk Determination 
In accordance with the definition of “Significant Risk Device” provided in the U.S. Code of 
Federal Regulation 21 CFR 812.3, each device to be used in the study has been 
determined to be a Non-Significant Risk (NSR) device based on the following: 

 
 
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a) 
It is not an implant 
b) 
It is not purported or represented to be for use in supporting or sustaining human 
life and do not present a potential for serious risk to the health, safety or welfare 
of a subject 
c) 
It is not for a use of substantial importance in diagnosing, curing, mitigating, or 
treating disease or otherwise preventing impairment of human health 
d) 
Use of the device poses no risk to the health, safety, or welfare of a subject 
 
 
16. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
This study will begin enrollment of subjects only after receiving written approval from the 
appropriate Institutional Review Board (IRB), Independent Ethics Committee (IEC) or 
other regulatory authorities deemed necessary depending on specific country or local 
requirements. Any sites selected outside of the United States will need to meet the 
country requirements for conducting human research studies. 
 
17. 
Study Endpoints 
 
17.1. 
Primary Effectiveness Endpoints 
 
Benign Pigmented Lesions 
Mean difference from Baseline to final 12-Week follow-up visit in Pigment Clearance 
Score as determined by blinded evaluators from clinical photographs. 
 
Wrinkles 
Mean difference from Baseline to final 12-Week follow-up in Fitzpatrick Wrinkle Score as 
determined by blinded evaluators from clinical photographs. 
 
 
17.2. 
Primary Safety Endpoint 
Analysis of the incidence, severity and relatedness of local skin responses and 
anticipated adverse device effects (ADE) and unanticipated adverse device effects 
(UADE). 
 
17.3. 
Secondary Endpoints 
 
1. Benign Pigmented Lesions 
Percentage of subjects demonstrating Pigment Clearance Score (PCS) of 3 or 4 (> 
50% improvement) comparing baseline to 12-week follow-up as determined by 
blinded physician evaluators from clinical photographs 
 
2. Wrinkles 
Percentage of subjects demonstrating > 1 score improvement in Fitzpatrick Wrinkle 
Score (FWS) from baseline to 12-week follow-up visit as determined by agreement 
of 2 out of 3 blinded physician evaluators from clinical photographs 

 
 
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3. Subject Satisfaction 
Mean and distribution of Subject Satisfaction Scores at all visits beyond Treatment 
Visit #1 
 
4. Subject Pain 
Mean and distribution of Subject Pain Scores following each treatment 
 
17.4. 
Exploratory Endpoints 
Histological analysis of laser-tissue effects and/or healing response from pre- and post- 
treatment skin biopsies using light microscopy and/or scanning electron microscopy. 
 
18. 
Blinded Evaluation 
Efficacy endpoints will be determined from the data gathered by blinded evaluators 
scoring clinical photography. Three qualified, non-treating clinicians will be trained to 
independently review Baseline and post-treatment photograph sets for each subject. The 
identity of the subjects will be masked when possible. No information will be provided to 
the evaluators that may allow them to determine the Baseline from the post-treatment 
photography. Evaluators will then examine pairs of Baseline and post-treatment 
photographs presented in a randomized fashion, and be asked to identify which is the 
Baseline, and to rate any perceived improvement using the Pigment Clearance Scale or 
Fitzpatrick Wrinkle Scale as appropriate for the condition treated. 
 
19. 
Statistical Methods 
 
19.1. 
Statistical Plan Overview 
The study will be conducted with two separate strata (pigment, wrinkles) which will be 
evaluated. Benign pigmented lesions including dyschromia (Group A) and wrinkles 
including fine lines (Group B) will be separately powered and analyzed for efficacy and 
safety while both groups will further be combined for safety analyses. All study sites will 
be eligible to enroll subjects into each stratum; no subject will be enrolled into both strata. 
 
Subjects participating in the pigment treatment stratum will be evaluated using the 
Pigment Clearance Score (Appendix A) while subjects participating in the wrinkle 
treatment stratum will be evaluated using the Fitzpatrick Wrinkle Score (Appendix B). All 
study subjects will also be evaluated using the Subject Pain Scale (Appendix C), Subject 
Satisfaction Survey (Appendix D), the Local Skin Response (Appendix E), and will be 
evaluated for safety according to 21 CFR Part 812 as well as ICH guidelines (E3 and E6) 
and ISO 14385:2016 as applicable. 
 
A statistical analysis plan (SAP) will be finalized prior to study initiation. The database 
will be constructed using Microsoft Office Excel (Microsoft, Redmond, WA). The 
database will be locked following a review of all protocol deviations to be classified as a 
major or minor deviation. Major and minor protocol deviations will be reviewed once all 
data undergo source document verification and prior to database lock. The independent 
biostatistician will determine major vs. minor protocol deviations. 

 
 
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Data analyses will be performed using SAS Version 9.3 or later (SAS Institute, Cary NC) 
and StatXact Version 10 or later (StatXact, Cambridge MA). All analyses will be 
performed in a GCP environment controlled by SOPs. 
 
19.2. 
Hypotheses 
 
Null and alternative hypotheses are stratum specific. They assess the change from 
Baseline to Week 12/study exit. 
 
Pigment effectiveness (5-point ordinal scale, 5 is best) will be evaluated according to the 
following null and alternative hypotheses for Group A: 
 
• 
Null Hypothesis: Less than 50% experience good to excellent improvement in the 
Pigment Clearance Score (PCS) 
• 
Alternative Hypothesis: At least 80% experience good to excellent improvement in 
PIS. 
 
Fitzpatrick Wrinkle Score (9-point ordinal scale, 1 is best) will be evaluated separately for 
peri-orbital wrinkles and peri-oral wrinkles as well as the sum according to the following 
null and alternative hypotheses for Group B: 
 
• 
Null Hypothesis: There is no mean improvement in the Fitzpatrick Wrinkle Score 
(FWS) 
• 
Alternative Hypothesis: There is at least a 2-point mean improvement in FWS. 
 
19.3. 
Sample Size 
The following summarizes the sample size required to achieve 80% power separately for 
pigmentation Group A and Group B for their respective primary efficacy endpoints. 
 
From Kung, et al, 2018, Graph 1 indicates that for clearance of pigmentation, 0% 
experienced complete improvement (Grade 5: >95%), 53.8% experienced excellent 
(Grade 4: 75-94%) improvement, while 30.8% experienced good (Grade 3: 50-74%) 
improvement from baseline. With 30 evaluable subjects, there is 80% power to reject a 
50% improvement rate in favor of a 75% improvement rate according to a two-sided 
exact binomial test with 5% Type I error. Statistical significance will be achieved if 69% 
improvement is observed at 12 week follow-up / study exit visit. 
 
From Fitzpatrick, et al, 1996, Table 2 indicates for peri-orbital and peri-oral wrinkles, the 
mean changes from baseline to study exit were 2.34 points and 2.25 points with 
standard deviations < 2 points. With 34 evaluable subjects, there is 80% power to 
detect a 1-point improvement from baseline according to a two-sided paired t-test with 
5% Type I error. Statistical significance will be achieved if a 0.7 mean improvement is 
observed from Baseline to 12 week follow-up / study exit with a 2-point standard 
deviation. 

 
 
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19.4. 
Effectiveness Analyses 
 
The skin pigmentation score will be evaluated using a paired t-test separately for the peri- 
orbital, peri-oral, and combined outcomes from baseline to study exit. In addition, the 
percentage achieving a 1-point improvement will also be displayed with two-sided 95% 
confidence intervals to support regulatory submissions requiring 1-point improvement 
analyses. 
 
Wrinkle score improvement will be evaluated using a two-sided exact binomial test. 
 
The Subject Pain Scale and Subject Satisfaction Score will be evaluated by displaying 
the distributions with the range, mean, and two-sided 95% confidence intervals provided. 
Results will be displayed separately for Groups A and Group B. 
 
The effectiveness analyses will be performed using a Per Protocol (PP) population which 
excludes subjects with major protocol deviations such as subjects withdrawn prior to final 
evaluation. 
 
 
19.5. 
Safety Analyses 
 
Safety will be evaluated using the Local Skin Response (Appendix E) which will 
specifically assess the following nine pre-defined safety endpoints: erythema, edema, 
whitening, petechiae, pinpoint bleeding, purpura, crusting, blistering, burn, as well as 
other to be graded on a 5-point ordinal score. 
 
Safety will be evaluated in the Intent to Treat (ITT) population which includes all treated 
subjects. Safety results will be displayed separately for Groups A and Group B. 
Analyses will include a summary of the incidence, severity, and relatedness of all 
reported local skin responses, adverse device effects, and unanticipated adverse device 
effects. In addition, the percentage with no adverse device effects will also be reported 
as well as the percentage according to worst overall degree; a similar evaluation will be 
performed for the worst degree for those at least related to the study treatment. The 
percent reporting each ordinal score per safety endpoint will be presented separately for 
each stratum and combined. 
 
20. 
Histological Analysis 
 
20.1. 
Light Microscopy 
 
Skin biopsies will be processed for routine hematoxylin and eosin (H&E) tissue staining to 
allow light microscopy analysis of laser-tissue effects such as acute skin and pigment 
changes, wound healing, or other morphologic changes. 

 
 
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20.2. 
Scanning Electron Microscopy 
 
Skin biopsies may be processed for scanning electron microscopy (SEM) by a third-party 
laboratory to allow analysis of laser-tissue effects such as acute skin and pigment 
changes, wound healing response, or other morphologic changes. 
 
21. 
Risks and Benefits 
 
21.1. 
Potential Risks 
The study treatments to be administered in this trial carry risks of local skin responses 
that are common, expected, and at times even desired with study treatments. The skin 
responses are typically only trace to moderate, and transient in nature, resolving within a 
few days after treatment. 
 
Common local skin responses or side effects of treatment include erythema, edema, 
whitening, petechiae, pinpoint bleeding, purpura, crusting, blistering, and burning 
following the treatment. 
 
Examples of less common but potentially more severe or lingering local skin responses 
associated with PicoWay™ laser treatment include hyperpigmentation, 
hypopigmentation, herpes virus activation, infection and scarring. 
 
Allergic reactions to the topical or injectable anesthesia products are also possible. 
 
There is also a risk of eye injury associated with the use of any laser device. This risk is 
very uncommon as it is easily prevented if proper safety eyewear is used as required. 
 
21.2. 
Potential Benefits 
Subjects may benefit from participation in this study by experiencing partial or complete 
clearance of their benign pigmented lesions including dyschromia, or their wrinkles 
including fine lines. However, there is no guarantee that subjects will experience any 
beneficial clinical result at all. 
 
22. 
Adverse Device Effects 
 
22.1. 
Definitions 
 
The following occurrences will be documented and reported as required for compliance 
with applicable regulations including 21CFR 812 and ICH GCP EC(R2). 
 
Adverse Device Effect 
An adverse device effect (ADE) is an adverse event related to the use of an 
investigational medical device in a subject, whether it is expected or unexpected. 
Unanticipated Adverse Device Effect 
An unanticipated adverse device effect (UADE) is any serious adverse effect on health or 
safety, any life-threatening problem or death caused by, or associated with a device, if 

 
 
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Page 26 of 35 
 
that effect, problem, or death was not previously identified in nature, severity, or degree 
of incidence in the protocol; or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. 
 
22.2. 
Reporting 
 
Anticipated device effects (ADE) and unanticipated adverse device effects (UADE) are 
collected from the time of subject consent until the subject exits the study. A description 
of the adverse event or device effect, date of onset, severity, action taken, relationship to 
study treatment and outcome are documented in the case report form. All adverse 
events or adverse device effects are followed until resolution. 
 
The Investigator will submit to Candela and to the reviewing IRB a report of any 
unanticipated adverse device effect (UADE) that might have led to a serious adverse event 
if suitable action had not been taken, intervention had not been made; or if circumstances 
had been less fortunate within 48 hours but in no event later than 10 working days after 
first learning of the effect. 
 
The Sponsor, upon learning of any unanticipated adverse device effect, shall immediately 
conduct an evaluation and report the results to IRB within 10 working days. 
 
22.3. 
Rating 
The Investigator will assess the severity and relationship of all adverse effects. The 
following definitions will be used for severity assessment: 
 
For all ADE and UADE reported, the Investigator will assign independent ratings for 
Severity and Relatedness to laser treatment in accordance with the descriptions found in 
Table 4 and Table 5, respectively. 
 
Table 4: Severity Rating System for ADE/UADE 
 
Score 
Severity 
Definition 
0 
None 
Normal 
1 
Trace 
Very minimal reaction resolved within 24 hours. 
Does not require medical intervention. No effect 
on daily activities. 
2 
Mild 
Noticeable reaction expected to resolve within 7 
days. Does not require medical intervention. No 
effect on daily activities. 
3 
Moderate 
Noticeable reaction lasting more than 2 weeks. 
Possibly requires some medical intervention. 
May interfere with some daily activities. 
4 
Severe 
Significant skin reaction lasting more than 6 
months, or deemed permanent by Investigator. 
Requires significant medical or surgical 
intervention. Debilitating and prevents normal 
everyday activities 

 
 
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Table 5: Relatedness Rating System for AE/UADE 
 
Score 
Relatedness to 
Treatment 
Definition 
0 
Not Related 
Clearly related to other factors and not to 
laser treatment 
1 
Possibly Related 
A reasonable temporal sequence from the 
time of study treatment but could have 
been produced by other factors 
2 
Probably Related 
A reasonable temporal sequence from the 
time of study treatment but cannot be 
reasonably explained by other factors. 
3 
Related 
A reasonable temporal sequence from the 
time of on stopping the investigational 
product, or reappears on repeat exposure, 
or there is a positive reaction at the 
application site. 
U 
Unable to 
Determine 
Insufficient information to make a rational 
determination. 
 
 
23. 
Investigational Sites 
Investigational sites will be identified by the Sponsor and pre-qualified for participation 
prior to site initiation or subject enrollment. 
 
24. 
Compensation 
Subjects will receive PicoWay™ laser treatments in this study at no cost. Subjects will 
also receive a one-time honorarium of $100.00 upon completion of the scheduled 12- 
week follow-up visit. Subjects consenting to skin punch biopsies will receive $250.00 for 
each biopsy taken. 
 
25. 
Monitoring Plan 
Study Monitoring will be performed by qualified personnel from or designated by the 
Sponsor to ensure data integrity, adherence to the protocol and protection of study 
subjects. It is anticipated that at least three study monitoring visits will be scheduled per 
site during this study, though the Sponsor may determine that additional monitoring visits 
are required. 
 
26. 
Protocol Deviation Reporting 
Subjects enrolled without meeting inclusion/exclusion criteria, enrolled without providing 
informed consent and any other major deviations from the protocol will be reported to the 
Sponsor as soon as possible after becoming aware of the deviation. Protocol deviations 
will be reported to the IRB in accordance with IRB guidelines. 

 
 
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27. 
Record Retention 
The Investigator will retain a copy of all study records in accordance with applicable 
regulations for a period of two (2) years after the study is terminated or completed. It is 
the responsibility of the Investigator to retain study records in a secure location at the site. 
 
28. 
Publication Policy 
Study Investigators agree not to publish the results from, or disclose confidential 
information related to, this study as described in the Clinical Trial Agreement without prior 
written agreement from the study Sponsor, Candela Corporation. If the Sponsor agrees 
to publish the results from this study, the Investigators will provide the Sponsor 
publication manuscript(s) for review at least thirty (30) days before submission for 
publication. Investigators will also provide the Sponsor advance at least (30) days’ notice 
of any planned presentation of study results. 

 
 
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29. 
References 
1) 
Anderson RR, Parrish JA. Selective photothermolysis: Precise microsurgery by 
selective absorption of pulsed radiation. Science. 1983; 220(4596):524-527. 
2) 
Polla LL, Tan OT, Garden JM, Parrish JA. Tunable pulsed dye laser for the 
treatment of benign cutaneous vascular ectasia. Dermatologica 1987;174:11-17. 
3) 
Taylor CR, Gange RW, Dover JS, et al. Treatment of tattoos by Q-switched ruby 
laser. A dose-response study. Arch Dermatol. 1990;126:893-899. 
4) 
Kilmer SL, Anderson RR. Clinical use of the Q-switched ruby and the Q-switched 
Nd:YAG (1064 nm and 532 nm) lasers for treatment of tattoos. J Dermatol Surg 
Oncol. 1993;19:330-338. 
5) 
Bernstein EF, Bhawalkar J, Clifford J, Hsia J. Treatment of tattoos with a 755-nm 
Q-switched alexandrite laser and novel 1064 nm and 532 nm Nd:YAG handpieces 
pumped by the alexandrite treatment beam. J Drugs Dermatol. 2010;9:1333-1339. 
6) 
Ross V, et al. Comparison of responses of tattoos to picosecond and nanosecond 
Q-switched neodymium:YAG lasers. Arch Dermatol. 1998;Feb 134(2):167-71. 
7) 
Bernstein EF, Schomacker KT, Basilavecchio LD, et al. A Novel Dual-Wavelength, 
Nd:YAG, Picosecond-Domain Laser Safely and Effectively Removes Multicolor 
Tattoos. Lasers Surg Med. 2015;47:542-548. 
8) 
Bernstein EF, Bhawalkar J, Schomacker KT, et al. A Novel Titanium Sapphire 
Picosecond-Domain Laser Safely and Effectively Removes Purple, Blue and 
Green Tattoo Inks. Lasers Surg Med. 4 May 2018. DOI 10.1002/lsm.22942. 
9) 
Forbat E, Ali FR, Al-Niaimi F. Applications of picosecond lasers beyond tattoos: 
Pigment reduction and tissue remodeling. Lasers Med Sci 2017. Jul;32(5):1219. 
10) 
Alegre-Sanchez A, Jimenez-Gomez N, Moreno-Arrones OM, et al. Treatment of 
flat and elevated pigmented disorders with a 755-nm alexandrite picosecond laser: 
clinical        and       histological       evaluation. 
Lasers 
Med 
Sci. 
2018;doi.org/10.1007;s10103-018-2459 [Epub ahead of print]. 
11) 
Kasai K. Picosecond Laser Treatment for Tattoos and Benign Cutaneous 
Pigmented Lesions. Laser Ther. 2017;Dec 31;26(4):274-281. 
12) 
Levin MK, Ng E, Bae YS, et al. Treatment of Pigmentary Disorders in Patients With 
Skin of Color With a Novel 755-nm Picosecond, Q-Switched Ruby, and Q- 
Switched Nd:YAG Nanosecond Lasers: A Retrospective Photographic Review. 
Lasers Surg Med. 2016;48:181-87. 
13) 
Negishi K, Akita J, Matsunaga Y. Prospective Study of Removing Solar Lentigines 
in Asians Using a Novel Dual-Wavelength and Dual-Pulse Width Picosecond 
Laser. Lasers Surg Med. 2018; Apr 2. doi: 10.1002/lsm.22820. [Epub ahead of 
print]. 
14) 
Kung K, Shek S Y-N, Yeung CK, Chan H H-L. Evaluation of the Safety and Efficacy 
of the Dual Wavelength Picosecond Laser for the Treatment of Benign Pigmented 
Lesions in Asians. Lasers Surg Med. 2018 Oct 25. doi: 10.1002/lsm.23028. [Epub 
ahead of print]. 
15) 
Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed Carbon Dioxide Laser 
Resurfacing of Photoaged Facial Skin. Arch Dermatol 1996; 132:395-402. 

 
 
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30. 
Appendices 
Appendix A: 
Pigment Improvement Score (PIS) 
Appendix B: 
Fitzpatrick Wrinkle Score (FWS) 
Appendix C: 
Subject Pain Scale 
Appendix D: 
Subject Satisfaction Survey 
Appendix E: 
Local Skin Response 

 
 
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30.1. 
Appendix A: Pigment Clearance Score Pigment Score 
 
 
 
 
 
Score 
Clearance 
Description 
1 
0% - 24% 
Poor response 
2 
25 - 49% 
Fair Response 
3 
50 - 74% 
Good response 
4 
75 - 94% 
Excellent response 
5 
> 95% 
Complete response 

 
 
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30.2. 
Appendix B: Fitzpatrick Wrinkle Score (FWS) 
 
 
 
 
Class 
Wrinkling 
Score 
Degree of Elastosis 
I 
Fine wrinkles 
(rhytides) 
1-3 
Mild (fine textural changes with subtly 
accentuated skin lines) 
II 
Fine to 
moderate 
depth wrinkles, 
4-6 
Moderate (distinct papular elastosis 
[individual papules with yellow 
translucency under direct lighting] and 
III 
Numerous 
lines, with or 
without redund 
ant skin folds 
Fine to deep 
wrinkles. 
7-9 
Severe (multipapular and confluent 
elastosis [thickened yellow and pallid] 
approaching or consistent with cutis 
rhomboidalis) 

 
 
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30.3. 
Appendix C: Subject Pain Scale 
 
 
 
 
Question: How much pain did you experience during the treatment today? 
No Pain 
Extreme 
Pain 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 

 
 
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30.4. 
Appendix D: Subject Satisfaction Scale 
 
 
 
 
 
Question: How satisfied are you with your pigment improvement at this 
point of the study? 
Score 
Definition 
-2 
Extremely Dissatisfied 
-1 
Somewhat Dissatisfied 
0 
Neither Satisfied nor Dissatisfied 
1 
Somewhat Satisfied 
2 
Extremely Satisfied 

 
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30.5. 
Appendix E: Local Skin Response 
 
 
Local Skin Response Assessment 
❑ None 
❑ N/A 
❑ Erythema 
❑ Edema 
❑ Whitening 
❑ Petechiae 
❑ Pinpoint 
Bleeding 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ Purpura 
❑ Crusting 
❑ Blister 
❑ Burn 
❑ Other: 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ Other: 
❑ Other: 
❑ Other: 
  
_ 
❑ Other: 
  
 
❑ Other: 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe 
❑ None 
❑ Trace 
❑ Mild 
❑ Moderate 
❑ Severe