An Evaluation of the Effect of the Erchonia® LunulaLaser™ for the Treatment of Toenail Onychomycosis
Phase: NA
Conditions: Onychomycosis of Toenail
Sponsor: Erchonia Corporation

 
 
 
 
 
 
ERCHONIA® LUNULALASER™ 
 
 
 
An Evaluation of the Effect of the 
Erchonia® LunulaLaser™ for the  
Treatment of Toenail Onychomycosis  
 
 
 
 
 
ERCHONIA CORPORATION 
 
 
 
 
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April 18, 2017 

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TABLE OF CONTENTS 
 
STUDY INFORMATION .............................................................................................. 2 
SPONSOR .................................................................................................................. 2 
CLINICAL CONSULTANT ........................................................................................... 2 
REGULATORY CONSULTANT ................................................................................... 2 
MONITORS ................................................................................................................. 2 
PRINCIPAL CLINICAL INVESTIGATORS & TEST SITES .......................................... 3 
INSTITUTIONAL REVIEW BOARD ............................................................................. 3 
PURPOSE OF STUDY ................................................................................................ 3 
LABELING ................................................................................................................... 3 
INDICATION FOR USE ............................................................................................... 3 
REGULATORY HISTORY ........................................................................................... 3 
FDA RESOURCES UTILZED ...................................................................................... 4 
DEVICE INFORMATION: ERCHONIA LUNULALASER .............................................. 5 
STUDY INDICATION AND RATIONALE, THEORY OF MECHANISM OF                      
OPERATION & SUPPORTING MATERIALS ............................................................. 13 
STUDY DESIGN ....................................................................................................... 23 
STUDY PROCEDURE  ............................................................................................. 25 
STUDY TEST BATTERY ........................................................................................... 25 
STUDY PROCEDURE PROTOCOL .......................................................................... 29 
PRE-TREATMENT ACTIVITIES ................................................................................ 29 
STUDY QUALIFICATION EVALUATION ............................................................... 29 
BASELINE ASSESSMENT .................................................................................... 32 
TREATMENT ADMINISTRATION PHASE ................................................................. 32 
GENERAL ASSESSMENT CONDITIONS ............................................................. 32 
TREATMENT ADMINISTRATION PROTOCOL ..................................................... 32 
STUDY EVALUATION TIMELINE AND MEASURES ................................................ 34 
TABLE OF SUBJECT EVENTS ................................................................................. 35 
SAFETY AND CONFIDENTIALITY ........................................................................... 37 
STATISTICAL ANALYSIS PLAN ............................................................................... 38 
 
 
APPENDICES 
APPENDIX A: GIMP 2.8 SOFTWARE MEASUREMENT METHODOLOGY INSTRUCTION 
SHEET 
APPENDIX B: ESTABLISHMENT OF NON-SIGNIFICANT RISK 
APPENDIX C: CASE REPORT FORMS 
APPENDIX D: INFORMED CONSENT FORM  
APPENDIX E: ERCHONIA CORPORATION CLINICAL TRIAL MONITORING 
PROCEDURES 
APPENDIX F: ERCHONIA CORPORATION CLINICAL TRIAL INVESTIGATOR 
RESPONSIBILITIES PROCEDURE 
 
 

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STUDY INFORMATION 
 
SPONSOR 
Erchonia Corporation 
650 Atlantis Rd.  
Melbourne, FL  32904 
Contact: Mr. Steven Shanks, President 
Telephone: 321-473-1251 
E-mail: sshanks@erchonia.com 
 
CLINICAL CONSULTANT 
Regulatory Insight, Inc.  
Nashville Office 
1503 Red Oak Drive 
Brentwood TN 37027 
Contact: Elvira Cawthon, Clinical Consultant 
Telephone: 615-712-9743 
Fax: 615-712-9852 
e-mail: elvira@reginsight.com 
 
REGULATORY CONSULTANT 
Regulatory Insight, Inc.  
Denver Office 
33 Golden Eagle Lane 
Littleton CO 80127 
Contact: Kevin Walls, Principal Consultant 
Telephone: 720-962-5412 
Fax: 720-962-5413 
e-mail: kevin@reginsight.com 
 
MONITORS 
1. Erchonia Corporation 
650 Atlantis Rd.  
Melbourne, FL  32904 
Contact: Mr. Joe Zapolsky 
Telephone: 321-473-1251 
E-mail: jzapolsky@erchonia.com 
 
2. Regulatory Insight, Inc.  
Nashville Office 
1503 Red Oak Drive 
Brentwood TN 37027 
Contact: Elvira Cawthon, Clinical Consultant 
Telephone: 615-712-9743 
E-mail: elvira@reginsight.com 
 
 
PURPOSE OF STUDY 
The purpose of this clinical study is to demonstrate the efficacy of the Erchonia LunulaLaser™, 
manufactured by Erchonia Corporation (the Sponsor) for the treatment of onychomycosis of the 
toenail. 

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The Sponsor intends to submit the data and analysis from this study via a 510(k) application to 
obtain FDA clearance to market the laser device for the intended indication. 
 
LABELING 
Once cleared for market in the U.S., the Erchonia LunulaLaser™ laser device will be labeled as 
prescription devices, per 21 CFR § 801.109. 
 
INDICATION FOR USE 
The results of this clinical study will be used to support the following indication for use 
statement: “The Erchonia LunulaLaser™ laser device is indicated for the treatment of 
onychomycosis of the toenail (dermatophytes Trichophyton rubrum and T. mentagrophytes,).”  
 
REGULATORY HISTORY 
On June 3, 2016, the FDA issued the following 510(k) clearance for the Erchonia® 
LunulaLaser™ under K153164: “The LunulaLaser™ device is indicated for use for the 
temporary increase of clear nail in patients with onychomycosis (e.g. dermatophytes 
Trichophyton rubrum and T. mentagrophytes, and/or yeasts Candida albicans, etc.)” 
 
 
FDA RESOURCES UTILIZED 
 
¾ Medical Devices and Clinical Trial Design for the Treatment or Improvement in the 
Appearance of Fungally-Infected Nails;  
Draft Guidance for Industry and Food & Drug Administration Staff;  
January 27, 2015. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Office of Device Evaluation 
Division of Surgical Devices 
 
¾ Feedback and recommendations made by the FDA through the review of Q-Subs Q161189 
and Q161189/S001. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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              DEVICE INFORMATION: ERCHONIA LUNULA™LASER 
 
REGULATORY HISTORY 
 
510(k)# K153164: On June 3, 2016, the FDA issued the following 510(k) clearance for the 
Erchonia Corporation LunulaLaser 
 
510(K) Number: 
 
K153164 
Device Name: 
 
LunulaLaser™ 
Device Classification Name: Lasers For Temporary Increase Of Clear Nail In Patients With 
Onychomycosis 
Regulation Number: 
 
878.4810 
Classification Product Code: PDZ   
Decision Date: 
 
06/03/2016 
 
Indications For Use (IFU) Statement: “The LunulaLaser™ device is indicated for use for the 
temporary increase of clear nail in patients with onychomycosis (e.g. dermatophytes 
Trichophyton rubrum and T. mentagrophytes, and/or yeasts Candida albicans, etc.)” 
 
DEVICE DESCRIPTION AND SPECIFICATIONS 
  
The Erchonia® LunulaLaser™ to be evaluated in this clinical study is identical in appearance, 
technical specifications and output parameters to the device cleared under K153164. 
 
The Erchonia® LunulaLaser™ is a dual-diode laser of 635 nm and 405 nm wavelength. The 
light emitting diodes are manufactured by DLC and classified by the Center for Devices and 
Radiological Health (CDRH) as Class II laser diodes.  
 
The LunulaLaser™ is an easy to use, compact, all in one AC powered portable floor device that 
is easy to carry.  The laser output heads are located in the enclosure, a fixed position that 
allows optimal coverage of the nail bed. 
 
By design of the device, it is not possible for the patient to move the foot’s position to any 
significant degree that would impact the intended exposure to the laser procedure, particularly 
considering that the laser beam is designed to cover the entire treated toe region. With the 
creative enclosure design, the laser light is confined to the treatment area, ensuring that there is 
no possible instance of residual laser energy or light beyond the enclosure. 
 
The user interface is a touch screen which communicates with the PLC to initiate, stop, pause 
or set the energy flow to the diodes. The diode can only be on or off; there is no user interface 
that allows the end user to alter the diode output. The protocol software is factory set and 
cannot be altered by the end user. 
 
The LunulaLaser™ has the following specifications:  
 
Device 
x Weight: 23lbs / 10.43 kg 
x Height:16in/40cm, Width:12in/30cm, Depth: 10in/25.40cm (38cm with platform extended) 
x Full Color TFT Touch Screen Control Center 
x Chassis: Powder Coated Aircraft Aluminum Base Plate and Door  

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x Housing: Injection Molded Process with Non-Allergen Material/Plastic 
x Applied Part: Type B 
 
Laser 
x 2 line generating diode modules  
x Wavelength: 635 nm & 405nm ± 10nm 
x Output: 635nm: 17.25 ± 1.25mW / 405nm: 23.00 ± 2.00mW 
x Modulation: Constant Wave (CW) 
 
Power 
x Source: 100-240VAC, 50-60Hz 
x Fuse Rating: T2AH 250V 
x Treatment time: 12 minutes 
 
The Erchonia LunulaLaser™ Laser is shown in Figure 1 below: 
 
            Figure 1: The Erchonia® LunulaLaser™  
 
 
Placement of the target toenail inside the Erchonia® 
LunulaLaser™ during treatment administration is 
shown in Figure 2 to the right.  
 
 
 
Figure 2: Placement of Toenail Inside the Erchonia® 
LunulaLaser™ During Treatment  
 

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The dimensions of the Erchonia® LunulaLaser™ are shown in Figure 3 below. 
 
 
 
 
 
Figure 3: Dimension of the Erchonia® LunulaLaser™ 
 
DEVICE SYSTEM COMPONENTS 
 
The Erchonia® laser package is comprised of (1) LunulaLaser™ device, (1) Power Cord, (2) 
Keys, (1) Patient Glasses and the Operation and Maintenance Manual. 
 
The individual system components of the Erchonia LUNULA™ are displayed in Figures 4, 5 and 
6 below, respectively, with each individual system component described in the associated text 
below the respective figure. 
 
 
Figure 4: System components 1 through 6 of the Erchonia LunulaLaser™ 
 
1. Power Indicator Light 
2. Pull Knobs / Stops 
3. Door / Foot Platform 
4. Touch Screen 
5. Key Switch 
6. Diode Light Indicator 

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1. Power Indicator Light 
 
When the LunulaLaser™ is ON, the power indicator light shows GREEN. When the device is 
OFF, the LED is NOT lit. 
 
2. Pull Knobs / Stops 
 
On both sides of the door, there are protrusions that function as pull knobs when the door is 
closed. Pulling on these opens the door. Once the door is open, the protrusions function as 
stops, supporting the weight of the patient’s foot. 
 
3. Door / Foot Platform 
 
In the closed position, this element is a door. The door / foot platform is multifunctional, 
when open, the inside of the door becomes the back half of the treatment platform. 
 
4. Touch Screen  
The touch screen functions as a display screen and an input panel, providing information to 
the user and a means to operate the device by touching the appropriate icon. 
 
5. Key Switch 
 
The Key Switch is the outwardly visible portion of an internal locking mechanism below the 
touch screen [4] that comes with an external key. Together they allow the end user to turn 
the device ON or OFF.  (“O” = OFF and “|” = ON) In the OFF position the device is locked.  
From the locked position the external key can be removed. This is a code-regulated feature 
installed to ensure no unauthorized use of the laser device. The device will not operate if the 
key is in the OFF position. Turning the key to the OFF position while the device is in 
operation will immediately shut down the device. The key switch has a failsafe system which 
ensures the 110/240 voltage from a wall socket can never come in contact with the user.  
The device uses a 2 amp fuse, which will only require replacement if there is an issue. 
 
NOTE: Two keys are included with the LunulaLaser™. The key is brass with Nickel plating, 
approximately 1.17 inch long.  The device requires (1) key to operate; the key cannot be 
removed unless in the “O” OFF position.   
 
 
 
 
 
 
6. Diode Light Indicator 
When the device is ON and in-treatment, these lights are lit, showing that each diode is 
emitting device light. 
 
OFF 
ON 

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Figure 5: System components 7 and 8 of the Erchonia LunulaLaser™ 
 
7. Laser Output Heads 
8. Magnetic Latch 
 
7. 
Magnetic Latch 
 The Door / Foot Platform are held in the closed position by this magnetic latch. 
 
8. 
Laser Output Heads 
Each one of the two output heads emits laser light, one a 405nm violet beam and the other 
a 635nm red beam 
 
 
 
 
 

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Figure 6: System components 9 through 12 of the Erchonia LunulaLaser™ 
 
 9.  Handle 
10. Compliance Label 
11. Serial Number 
12. Power Inlet / Fuse Holder 
 
9. Handle 
The handle enables the user to pick up, carry and / or move the device with ease. 
 
10. Compliance Label 
Contains all the governing agencies required information regarding the device, including but 
not limited to the US FDA device classification, EU classification, output information and 
power inlet symbols.  Also includes the manufacturer name and address. 
 
 
 

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11. Serial Number 
This is the unique identifier for the device.  All information regarding this device is 
associated with the serial number. 
 
12. Power Inlet Module/Fuse Holder 
The device contains a flexible detachable power cord. NOTE:  Make sure the power cord is 
plugged into device at this location prior to plugging into a wall socket.  The power inlet 
module also contains a fuse holder.  Replacing the fuses is the only service that can be 
conducted by the end-user.  Fuses to be rated a T2AH 250V with an input to cover 100 – 
240V~ .5-1.5A, 50-60 Hz. 
 
 
The power cord does not contain any operator-serviceable components.  If the power cord 
needs replacement, contact an Erchonia Corporation representative. 
 
The device includes a transformer which converts AC power to match the power output (i.e. 
110V or 240V).  Only a 3 plug prong adaptor is required (Hospital Grade Only).  Once the 
adaptor is affixed to the plug end of power inlet, put into wall socket. Input: 1.5A/100VAC & 
0.5A/240VAC, 50-60 Hz. 
 
PROTECTIVE EYEWEAR 
 
The Erchonia LunulaLaser™ is classified by the FDA/IEC as a Class 2 laser device. This 
designation represents a current standard for use in order to ensure the safety of the patient. A 
Class 2 laser is determined to have a chronic viewing hazard. Pointing the laser beam directly 
into the eye and maintaining it there for an extended period of time could prove to be damaging. 
 
To ensure there is no possible instance of residual effect, a pair of specialty glasses (shown in 
Figure 7 below) is provided for use during in-office procedure applications with the Erchonia 
LUNULA™ laser device. These safety glasses are Kentek Corporation Filter #6101 light blue 
glasses with approximate VLT 63% that sufficiently and effectively block the laser light spectrum 
of the LUNULA™ laser device as follows: 405nm (OD 1.22) & 635nm (OD 2.07). 
 
 
 
 
 
 
 
 
 
Figure 7: Kentek Corporation Filter #6101 Safety Glasses 
 
 

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PERFORMANCE STANDARDS 
 
The LunulaLaser™ complies with FDA's performance standards for light-emitting products (21 
CFR Part 1040). 
 
COMPLIANCE WITH VOLUNTARY STANDARDS 
 
The LunulaLaser™ complies with the following voluntary standards: 
 
x 
ES60601-1:2005/(R) 2012 and C1:2009/(R)2012 and, A2:2010/(R)2012 (consolidated text) 
Medical Electrical Equipment - part 1: General Requirements for Basic Safety and Essential 
Performance (IEC 60601-1:2005, mod). (General II (ES/EMC)) 
x 
IEC 60601-1-2 Edition 3: 2007-03, medical electrical equipment - part 1-2: general 
requirements for basic safety and essential performance - collateral standard: 
electromagnetic compatibility - requirements and tests. (General II (ES/EMC)) 
x 
IEC 60825-1 Edition 2.0 2007-03, safety of laser products - part 1: equipment classification, 
and requirements [including: technical corrigendum 1 (2008), interpretation sheet 1 (2007), 
interpretation sheet 2 (2007)]. 
 
 
 
 
 
 
 
 

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STUDY INDICATION AND RATIONALE, THEORY OF MECHANISM OF 
OPERATION, & SUPPORTING MATERIALS 
 
STUDY INDICATION: TOENAIL ONYCHOMYCOSIS    
 
Definition 
An infection of toenail fungus, or onychomycosis, occurs when fungi infect the nail. A nail fungal 
infection may begin as a white or yellow spot under the tip of the toenail. As the nail fungus 
spreads deeper into the nail, it may cause nail discoloration, thickening and the development of 
crumbling edges, all of which can lead to an unsightly and potentially painful problem. 
Onychomycosis may be difficult to treat, and infections may recur easily. Toenail fungus affects 
approximately 23 million people in the US – about 10% of all adults.  
 
Symptoms 
The primary symptoms of onychomycosis are nails that are:   
 
thickened 
 
brittle, crumbly or ragged  
 
distorted in shape  
 
dull, lacking luster or shine  
 
a dark color, caused by debris building up under the nail  
 
Additional symptoms may include: 
 
separation of the nail from the nail bed (onycholysis) 
 
pain in the toes  
 
a slightly foul odor.  
 
Causes 
Fungi are microscopic organisms that don't need sunlight to survive. Nail fungal infections are 
typically caused by a fungus that belongs to a group of fungi called dermatophytes, but may 
also be caused by yeasts and molds.  
 
All of these microscopic organisms live in warm, moist environments, including swimming pools 
and showers. They can invade the skin through tiny invisible cuts or through a small separation 
between the nail and the nail bed. They cause problems only if the nails are continually exposed 
to warmth and moisture — conditions perfect for the growth and spread of fungi.  
 
Infection with nail fungus occurs more commonly in toenails than in fingernails because toenails 
are often confined in a dark, warm, moist environment inside shoes — where fungi can thrive. 
Another reason may be the diminished blood circulation to the toes as compared with the 
fingers, which makes it harder for the body's immune system to detect and eliminate the 
infection.  
 
Risk factors 
¾ Onychomycosis is more common among older adults for several reasons, including 
diminished blood circulation and more years of exposure to fungi. Also, nails may grow more 
slowly and thicken with age, making them more susceptible to infection.  
¾ Onychomycosis tends to affect men more often than it does women, particularly those 
with a family history of the infection.  
 
 

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¾ Other factors that can increase the risk of developing nail fungus include:  
 perspiring heavily  
 working in a humid or moist environment  
 having the skin condition psoriasis  
 wearing socks and shoes that hinder ventilation and don't absorb perspiration  
 walking barefoot in damp public places, such as swimming pools, gyms and shower 
rooms  
 having athlete's foot (tinea pedis)  
 having a minor skin or nail injury, a damaged nail or another infection  
 having diabetes, circulation problems or a weakened immune system  
 
Potential Complications 
The potential complications of onychomycosis include: 
 pain in the nails 
 permanent damage to the nails.  
 leading to other serious infections that can spread beyond the feet for individuals with a 
suppressed immune system due to medication, diabetes or other conditions, such as 
leukemia and AIDS. 
 For diabetes patients in particular, toenail onychomycosis can lead to impairment of the 
blood circulation and nerve supply to the feet and a greater risk for cellulitis, a potentially 
serious bacterial skin infection.  
 
Current Available Treatments 
Nail fungus can be difficult to treat, and repeated infections are common. The currently available 
treatments for onychomycosis are the following:  
 
¾ Oral antifungal medications 
Studies have shown the most effective treatments to be terbinafine (Lamisil) and 
itraconazole (Sporanox). Oral antifungal medications help a new nail grow free of infection, 
thereby slowly replacing the infected portion of the nail. These medications are usually taken 
for 6 to 12 weeks, but it may take four months or longer to eliminate the infection and for the 
nail to grow back completely. Recurrent infections are possible, especially if the nails 
continue to be exposed to warm, moist conditions.  
 
Antifungal drugs may cause side effects ranging from skin rashes to liver damage. 
Therefore, doctors may not prescribe them for people with liver disease or congestive heart 
failure or for those taking certain medications. 
  
¾ Antifungal lacquer 
The antifungal nail polish called ciclopirox (Penlac) is often prescribed for cases of mild to 
moderate onychomycosis. The polish is painted onto the infected nails and surrounding skin 
once a day. After seven days, the piled-on layers are wiped clean with alcohol and fresh 
applications are begun. Daily use of Penlac for about one year has been shown to help clear 
some nail fungal infections.  
 
¾ Topical medications 
Other topical over-the-counter antifungal creams containing urea can be used to help speed 
up absorption. Topical medications usually don't provide a cure, but may be used in 
conjunction with oral medications.  
 
¾ Surgery 

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If the nail infection is severe or extremely painful, the nail may be surgically removed. A new 
nail will usually grow in its place, though it will come in slowly and may take as long as a 
year to grow back completely. Sometimes surgery is used in combination with ciclopirox to 
treat the nail bed.  
 
¾ Photodynamic therapy 
      A laser is applied to irradiate the nail after it's been treated with an acid.  
 
STUDY RATIONALE AND JUSTIFICATION: LOW LEVEL LASER THERAPY AS A 
TREATMENT FOR TOENAIL ONYCHOMYCOSIS    
 
Presently, there is no perfect cure for toenail fungus. Even the most effective oral medications 
are successful only about half of the time. Topical medications are successful less than 10% of 
the time. As 10% of the adult population is affected by toenail onychomycosis, the need for a 
more effective and lasting cure is evident.  
 
Recently, application of low level laser therapy to the affected toenail over a four-week period 
using the Erchonia® LunulaLaser™ device has been clinically demonstrated to effect increase 
in clear nail in onychomycosis-infected toenails, and the device subsequently received FDA 
clearance to be marketed for this indication (K153164) based on this clinical outcome.  
 
Unlike medication-driven treatments for toenail fungus which can have many side effects 
including serious ones such as liver toxicity, low level laser therapy presents minimal risk of side 
effects. Laser therapy is applied to toenail onychomycosis by shining a laser light through the 
toenail. The laser light vaporizes the fungus while leaving the skin and surrounding tissue 
unharmed, in a simple, quick, non-invasive and pain-free manner. 
 
The goal of this current study is to expand the present indication for use for the Erchonia® 
LunulaLaser™ of: “The LunulaLaser™ device is indicated for use for the temporary increase of 
clear nail in patients with onychomycosis (e.g. dermatophytes Trichophyton rubrum and T. 
mentagrophytes, and/or yeasts Candida albicans, etc.)” (K153164) from the aesthetic claim of 
changing the nail appearance to the medical claim of eradicating the underlying fungal infection. 
As such, this clinical study protocol design is intended to provide data to support an indication 
for use of ‘treatment of onychomycosis’ through application of the Erchonia® LunulaLaser™. 
 
Prior clinical trials evaluating application of the Erchonia® LunulaLaser™ to toenail 
onychomycosis have reported negative culture results at completion of treatment administration, 
providing support and justification for conducting a controlled clinical trial to specifically assess 
and support a claim of treatment of onychomycosis for the Erchonia® LunulaLaser™ device.  
 
THEORY OF MECHANISM OF OPERATION 
 
The most common form of onychomycosis, which is the subject of evaluation in this clinical 
study, is distal lateral subungual onychomycosis (DLSO), a condition wherein the fungus 
spreads from plantar skin and progresses towards the underside of the nail through the 
hyponychium or the distal lateral nail bed. An inflammatory response is quickly upregulated in 
the area of infection, generating the physical signs of DLSO. The onset of fungal infection is 
caused by three main classes of fungi: dermatophytes, yeasts, and nondermatophyte molds. 
The most common cause of onychomycosis worldwide is due to the infection of dermatophytes, 
including the genera Epidermophyton, Microsporum, and Trichophyton. There are two major 

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pathogens that account for a majority of onychomycosis cases, T rubrum and Trichophyton 
mentagrophytes. 
Laser therapy operates under the principle of photochemistry with a photoacceptor molecule 
absorbing the emitted photons and inducing a biological cascade. Like our eukaryotic cell, fungi 
contain the highly complex organelle the mitochondria, which is responsible for the 
manufacturing of the energy molecule ATP. Within the inner mitochondrial membrane is 
cytochrome c oxidase, an identified photoacceptor molecule. It is believed that laser therapy 
could perhaps provide a means to photo-destroy the fungi responsible for onychomycosis by 
inducing the release of highly reactive superoxides. Moreover, laser therapy has been shown to 
promote superoxide dismutase (SOD), a process responsible for the destruction of foreign 
invaders. Extracellular release of low levels of mediators associated with SOD can increase the 
expression of chemokines, cytokines, and endothelial leukocyte adhesion molecules, amplifying 
the cascade that elicits the inflammatory response. The physiologic function of hydrogen 
peroxide, superoxide anion, and hydroxyl free radical is to destroy phagocytosed microbes. By 
enhancing the natural processes of the immune system and impacting the structural integrity of 
the fungi strain, it is believed that laser therapy may provide a means for clinicians to effectively 
treat onychomycosis without the onset of any adverse events.  
The wavelengths that will be utilized in this study will be a violet (405nm) and red (635nm) 
combination. The wavelengths were chosen based on the theory of electron volt stimulation.  
When studying the light spectrum chart, there is an inverse relationship between wavelength 
and the individual energy level of the photon (electron volt). As we move towards lower 
wavelengths, the energy of the emitted photon increases; for instance, a radio wave has far less 
electron volts (energy per photon) than the photons of an x-ray. Within the visible light spectrum, 
the highest electron volt levels are observed towards the lower end of the spectrum, therefore 
greater biological stimulation can occur with a 400 nm and 635nm wavelength.  
Work from several laboratories has demonstrated that visible light and NIR photoirradiation 
improves various cellular functions and can accelerate wound healing and tensile strength in 
both normal and impaired tissues and that the effects are not related to alterations in tissue 
temperatures [1-18]. Increased cellular metabolism and ATP production have been shown to 
occur as a result of photostimulation of cytochromes and other cellular energy transport 
compounds [4-6, 10, 11], as well as through cellular responses induced by changes in reactive 
oxygen species (ROS), nitric oxide (NO) and other inflammatory mediators orchestrated by light 
exposure [6-8, 10-16]. Some of these pathways are illustrated in the figures below.
Source: Huang YY, Chen AC, Carroll JD, Hamblin MR: Biphasic Dose Response in 
Low Level Light Therapy. Dose-Response 2009; 7: 358-383.
B
A

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Photoacceptors in the tissue cells’ mitochondria absorb visible and NIR light inducing a 
cascade of events that results in the production of ROS, NO and RNS (Figures A & B). 
Source: http://www.mrc-mbu.cam.ac.uk/research/mitochondrial-dysfunction/measuring-
mitochondrial-reactive-oxygen-species(C); 
http://www.bioscience.org/2009/v14/af/3509/fig8.jpg (D)
These in turn cause a series of downstream events and effects. These ROS and RNS 
compounds are lethal to fungi and bacteria (Figures C & D), while promoting stimulatory, 
immune modulatory and anti-inflammatory effects in the adjacent tissues.
The Erchonia® LunulaLaser™activates the mitochondria within the cells within the germinal 
layer which activates the production of nitric oxide which in turn produces vasodilation, 
Vasodilation evokes increased blood flow and local circulation to the targeted region. This 
results in an increase in oxygenation and nutrition to the germinal matrix layer and nail bed. 
Nitric oxide also decreases production of cytokines and other mediators affecting immune cells 
that promote inflammation that effects accelerated nail growth. This is a similar mechanism as 
that contributing to accelerated hair growth. 
The local circulatory effects are demonstrated in the following flow Doppler ultrasound images of 
a great toe before and after LunulaLaser™therapy. The blood flow in the before treatment 
image is noted at the level of the inter-phalangeal joint, and there is some vascular activity 
present in the germinal nail matrix which clearly ends where the nail plate begins. The after 
ultrasound image was taken just after treatment with the LunulaLaser™. It demonstrates the 
dramatic increase in circulation that encompasses the entire germinal matrix layer, the nail bed 
and nail. There is a marked increase in blood flow involving the entire toe.
D
C

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This phenomenon induced by the LunulaLaser™ low level laser device, occurs without the 
generation of heat. This is unlike a Class 4 laser, such as the PinPointe® FootLaser™, which 
relies on heat for its clinical effect [5].  
 
The target sites for treating onychomycosis are the nail plate, nail bed and nail matrix. Where a 
topically administered antifungal drug concentration typically only permeates through to the nail 
plate level, laser light has the ability to penetrate through to the nail matrix, thus providing 
therapeutic intervention across the entire nail barrier.  
 
It is also noted that treatment inhibits or destroys the fungus present which ultimately results in 
clearing of the nail as a result of changing the counterpoised outward growth of the nail versus 
the inward “growth” or progression of the fungal infection. The stimulation of nail growth and 
clearing is therefore due in part due to photostimulation of the nail matrix coupled with an 
antifungal effect.  
 
References: 
 
1. Ortiz A.E., Avram M.M., Waner M.A.: A Review of Lasers and Light for the Treatment of 
Onychomycosis. Lasers Surg Med 2014; 46:117-124. 
2. Stadler I, Lanzafame RJ, Evans R, Narayan V, Dailey, Buehner N, Naim JO: 830-nm 
Irradiation Increases the Wound Tensile Strength in a Diabetic Murine Model. Lasers Surg 
Med 2001; 28:220-226. 
 

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3. 
Lanzafame RJ, Stadler I, Kurtz AF, Connelly, Peter TA, Brondon P, Olson D: Reciprocity of 
Exposure Time and Irradiance on Energy Density During Photoradiation on Wound Healing 
in a Murine Pressure Ulcer Model. Lasers Surg Med 2007; 39: 534-542. 
4. 
Tuner J., Hode L. (2011). The New Laser Therapy Handbook*UनQJHVEHUJ3ULPD%RRNV
840pp. 
5. 
Yu W, Naim JO, McGowan M, Ippolito K, Lanzafame RJ: Photomodulation of Oxidative 
Metabolism and Electron Chain Enzymes in Rat Liver Mitochondria. Photochem Photobiol 
1997; 66(6): 866-871. 
6. 
Hamblin MR, Demidova TN: Mechanisms of Low Level Light Therapy. SPIE Proc. 2006; 
6140: 1-12. 
7. 
Kushibiki T, Hirasawa T, Okawa S, Ishihara M: Blue Laser Irradiation Generates 
Intracellular Reactive Oxygen Species in Various Types of Cells. Photomed Laser Surg 
2013; 31(3) 95-104. 
8. 
Kashiwagi S, Yuan J, Forbes B, Hibert ML, Lee ELQ, et al.: Near-Infrared Laser Adjuvant 
for Influenza Vaccine. PLoS ONE 2013; 8(12): e82899. doi:10.1371/ journal.pone.0082899 
9. 
Carlos E. Pinfildi, Érika P. Rampazo da Silva, Roberta A.C. Folha, Paola C.G. Turchetto, 
Paola PKP Monteiro, Arainy Antunes, Bernardo S. Hochman: Mast Cell Curve-Response in 
3DUWLDO$FKLOOHV7HQGRQ5XSWXUH$IWHUௗQP3KRWRWKHUDS\. Photomed Laser Surg 2014; 
32(2): 88-92. 
10. Karu T: Is It Time to Consider Photobiomodulation As a Drug Equivalent? Photomed. Laser 
Surg 2013; 31(5): 188-191. 
11.  Silveira PC, Streck EL, Pinho RA: Evaluation of mitochondrial respiratory chain activity in 
wound healing by low-level laser therapy. J. Photochem. Photobiol. B. 2007; 86(3):279-
282. 
12.  Fonseca As, Moreira TO, Paixao DL. Farias FM, Guimaraes OR, dePaoli S, Geller M, 
dePaoli F: Effect of Laser Therapy on DNA Damage. Lasers Surg Med 2010; 42: 481-488. 
13. Kim SW, Kim JS, Lim WB, Jeon SM, Kim OS, Koh J, Kim C, Choi HR, Kim OJ: In vitro 
Bacteriocidal effects of 635, 525 and 425 nm Wavelength (Red, Green and Blue) Light-
Emitting Diode Irradiation. Photomed Laser Surg 2013; 31(11): 554-562. 
14.  Guffey JS, Wilborn J: Effects of Combined 405-nm and 880-nm Light on Staphylococcus 
aureus and Pseudomonas aeruginosa in Vitro. Photomed Laser Surg 2006; 24(6): 680-683. 
15. deSousa NTA, Guirro RBD, Santana HF, Silva CCM: In Vitro Analysis of Bacterial 
Morphology by Atomic Force Microscopy of Low Level Laser Therapy 660, 830 and 904 
nm. Photomed Laser Surg 2012; 30(5):281-285. 
16. Roehlecke C, Schumann U, Ader M, Brunssen C, Bramke S, Morawietz, Funk RHW: 
Stress Reaction in Outer Segments of Photoreceptors after Blue Light Irradiation. PLoS 
ONE 2013; 8(9): e71570. doi:10.1371/journal.pone.0071570.  
17. Crisan B, Soritau O, Baciut M, Campian R, Crisan L, Baciut G: Influence of three laser 
wavelengths on human fibroblasts cell cuture. Lasers Med Sci 2013; 28: 457-463. 
18.  Avci P., Gupta G. K., Clark J., Wikonkal N., Hamblin M. R.: Low-Level Laser (Light)    
Therapy (LLLT) for Treatment of Hair Loss. Lasers Surg Med 2014; 46: 144-151.  
 
 

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SUPPORTING MATERIALS 
 
Below are summaries of trial results that present both mycological and clinical evidence to 
support the anticipated efficacy of the Erchonia® LunulaLaser™ for the treatment of 
onychomycosis, to be demonstrated in this current clinical study as the presence of complete 
clear nail with simultaneous negative mycological testing following treatment administration with 
the Erchonia® LunulaLaser™.

 
 
¾ AN EVALUATION OF THE EFFECT OF THE ERCHONIA LUNULA™ ON TREATING 
TOENAIL ONYCHOMYCOSIS CLINICAL STUDY; Version 7.0; December 27, 2012; 
Erchonia Corporation: Mycology Results 
 
This study was pre-established as a positive mycology study such that as a condition of study 
enrollment, all subjects were required to have a positive mycology for onychomycosis as 
confirmed through toenail cultures taken during study qualification evaluation and sent to an 
independent laboratory to be grown in an agar solution used to clinically identify dermatophites 
that are consistent with a definitive and verifiable diagnosis of the presence of onychomycosis.  
 
The mycology testing was performed at Lawrence Laboratories in Dublin, Ireland. It was 
established, registered and certified as a Manufacturer of pharmaceutical preparations on 
August 21, 1972 (Registration #38315), and was dissolved on December 16, 2013. 
 
The methodology used for the mycology testing was the following: 
 
x 
Core samples were obtained from under the nail plate as close as possible to viable tissue 
x 
Cultures were then grown in a neutral dermatophie medium (peptone-glucose agar 
solution) with cycloheximide 
x 
The presence of verifiable dermatophites was confirmed by the agar solution turning a pink 
color. The presence of verifiable dermatophites is considered consistent with the condition 
known as onychomycosis.  
x 
The samples were monitored for up to 21 days, with evaluations recorded on Days 3, 7, 14 
and 21, as applicable. 
 
In all instances of enrolled toenails, the presence of dermatophites was confirmed by the agar 
solution turning a pink color. Furthermore, the onychomycosis strain of Trichophyton rubrum (T. 
rubrum) was present on almost all slides. T. rubrum is established as the most common cause 
of onychomycosis in Europe and North America. 
 
Mycology testing was repeated for all enrolled subject toenails at 2 weeks post baseline 
evaluation. The results demonstrated the conversion from positive mycology to negative 
mycology as a result of the treatment administration with the Erchonia® LunulaLaser™ for all 
enrolled and treated study subject toenails. 
 
Specifically, mycology testing results were as follows: 
 
x 
Baseline (Pre-Treatment) Evaluation: Baseline results for all study toenails was a positive 
mycology for onychomycosis, denoted by detection of the presence of verifiable 
dermatophites consistent with onychomycosis. The culture results also indicated the positive 
presence of the Trichophyton rubrum strain for all samples. Trichophyton rubrum is the most 
common cause of onychomycosis in North America and Europe. The presence of 

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dermatophites was detected by day 3 or day 7, and the species identified as T. rubrum by 
day 7 or 14 in most cases, at which time the sample was destroyed.    
 
x 
Two Weeks Post-Baseline Evaluation: All samples were found to have a negative mycology, 
consistent with the absence of onychomycosis. There was no change seen across all 
evaluation points, and the sample was destroyed following Day 21 evaluation. 
 
 
The results summary of the culminating trial that resulted in the FDA’s clearance for K153164 
for the Erchonia® LunulaLaser™ is provided below: 
 
¾ A 
RETROSPECTIVE 
EVALUATION 
OF 
THE 
EFFECT 
OF 
THE 
ERCHONIA 
LUNULALASER™ ON THE INCREASE OF CLEAR NAIL IN PATIENTS WITH TOENAIL 
ONYCHOMYCOSIS; Version 1.0; September 29, 2015 
 
BACKGROUND: The purpose of this study was to demonstrate through retrospective analysis 
the efficacy of the Erchonia LunulaLaser™, manufactured by Erchonia Corporation, for the 
increase of clear nail in patients with toenail onychomycosis, when applying the LunulaLaser™ 
to the toenail for 12 minutes one time per week for a total of 4 procedure administrations.  
 
STUDY DESIGN: This study was a retrospective analysis of a compilation of pre-procedure and 
six-month post-procedure photographs of fifty-four (54) great toenails with varying degrees of 
onychomycosis disease involvement selected from amongst an existing pool of photographs 
taken during three prior Erchonia Corporation research studies wherein 4 sequential weekly 12-
minute procedures with the LunulaLaser™ were administered. The evaluating investigator was 
blinded to corresponding pre- and post-procedure photographs through application of a 
randomized numeric coding methodology.  
 
STUDY MEASURES: The linear measurement of millimeter (mm) of clear nail from the proximal 
nail fold to the most proximal area of nail dystrophy was objectively measured from unmarked 
digital photographic images using the validated GNU Image Manipulation Program (GIMP 2.8) 
software system, a multi-platform image/photo manipulation software system, at baseline 
evaluation (prior to LunulaLaser™ procedure administration) and at 6 months following 
completion of the LunulaLaser™ procedure administration protocol. 
 
STUDY PROCEDURE: Study great toenails had received 4 procedure administrations with the 
Erchonia LunulaLaser™ across a consecutive 3-week period: each procedure administration 7 
days apart. Exposure time to the laser was 12 minutes, directed at and about 4 inches above 
the great toenail. 
 
SUBJECTS AND SAMPLE: Fifty-four (54) treated great toenails of varying degrees of 
onychomycosis involvement at study entry were evaluated in this study. Subjects were 18 years 
or older with current bacterial/fungal infection classified by the investigator and confirmed 
through lab testing as positive for onychomycosis. 
 
STUDY RESULTS 
 
Primary Outcome Measure: Change in mm of Clear Nail from Baseline to Study Endpoint: 
The primary efficacy outcome measure in this study was the mm of clear nail growth at 6 
months post procedure administration end relative to Baseline (pre-procedure administration). 
Individual toenail success was defined as 3 mm or more of clear nail growth at 6 months post-

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procedure end relative to baseline. Overall study success was defined as an anticipated 60% of 
treated toenails meeting the individual toenail success criteria.  
 
Sixty seven per cent (67%) of all study treated toenails evaluated in this study met the study 
individual toenail success criteria, exceeding the pre-established overall study success goal of 
60% by 7%. The magnitude of the mean change in mm of clear nail from baseline to 6 months 
post-procedure for all treated toenails was an increase of 5.18 mm, 2.18 mm in excess of the 
pre-established 3 mm increase success criteria. A t-test for paired samples found this mean 
change of +5.18 mm in clear nail to be statistically significant (t=-8.0; df=53; p<0.0001).  
 
ADVERSE EVENTS: No adverse event was reported or observed for any subject throughout 
any of the three clinical trials from which this study’s retrospective sample was drawn. 
 
CONCLUSION: The Erchonia LunulaLaser™ is an effective tool for increasing clear nail in 
toenails infected with onychomycosis, significantly increasing mm of clear nail over a 6 month 
period following completion of the 4-week procedure administration phase. 
 
 
 
 
 
 
 
 

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STUDY DESIGN 
 
STUDY TREATMENT GROUP  
 
There will be an active test treatment group only in this study such that all study subjects will 
receive the active laser treatments with the Erchonia® LunulaLaser™. The absence of a control 
group was stipulated by FDA through prior Pre-IDE reviews and was subsequently established 
and accepted through the Erchonia® LunulaLaser™ Retrospective Analysis Study whose 
results successfully supported clearance of the Erchonia® LunulaLaser™ for the increase in 
clear nail in patients with toenail onychomycosis, under K153164. 
 
BLINDING DESIGN 
 
Given that there is only an active treatment group in this study, there is no need for blinding of 
either the subject or the study investigator administering the study treatments with the Erchonia 
LUNULA™ device. All subjects and investigators will be aware that the study treatment being 
administered will be the true active laser treatment.  
 
RANDOMIZATION 
 
Given that there is only an active treatment group in this study; randomization to treatment 
group is not applicable. 
 
SUBJECTS  
 
Recruitment  
The recruitment process will work as follows: 
 
1. An individual voluntarily schedules an appointment at the physician’s office (that in the 
context of this clinical study also functions as the investigator’s test site) regarding his or her 
toenail fungus. 
2. Through this visit, if the physician perceives that the patient may satisfy the study 
qualification criteria (i.e. there are no obvious indicators that may exclude him or her), then 
the physician will present the option of being a subject in the study.        
3. If the patient is interested in possibly taking part in the study, the physician – now in the role 
of study investigator – will personally review the informed consent form with the individual 
and answer any questions. The individual may sign the informed consent form at that visit or 
he or she may think about it for a while and sign the informed consent form at a later time 
(taking as long as desired, from hours to days, to sign as long as study enrollment is 
continuing at the time the decision to sign is made) or he or she may refuse to participate. 
4. An individual who chooses to sign the informed consent form and proceed with study 
participation will receive a subject ID and proceed to the study qualification evaluation phase.  
5. An individual who decides not to participate in the study will continue to work with the 
physician to determine a treatment plan for his or her toenail onychomycosis.   
 
Compensation  
A subject will not be offered money or any other form of compensation to participate in the 
clinical study. However, he or she will also not be charged for the cost of the study treatments 
with the Erchonia® LunulaLaser™, the cost of the mycological lab testing or for the cost of any 
other directly-related evaluations or measurements that occur as part of his or her participation 
in the study.  

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Sample size  
There will be 66 qualified subjects/great toenails enrolled in this clinical study across three test 
sites, approximately 22 subjects/great toenails per test site. 
 
Rationale for sample size  
The sample size of 66 subjects/great toenails was calculated based upon the 95% one-sided 
FRQILGHQFHLQWHUYDOLHORZHUERXQGRQO\DURXQGWKHREVHUYHGUHVSRQVHUDWHRIEHLQJ
50% (56%) yielding a pre-determined final sample size of 60 subjects/great toenails. From here, 
it is anticipated that about one-twelfth of subjects overall may withdraw or be terminated from 
the study prior to completion for various reasons. Therefore, the following formula is used to 
determine the final needed starting sample size for each procedure arm: 
 
Final sample size = sample size X 1/(1-d); where d = # expected dropouts/# subjects enrolled 
Final sample size = 60 X 1/(1-0.082) 
Final sample size = 60 X 1/0.917 = 60 X 1.091 = 66 subjects 
 
Therefore, a minimum starting sample size of 66 subjects is needed to insure that a sufficient 
number remains at the end of the treatment administration phase (60 subjects), assuming a 
drop-out rate of around one-twelfth, for a positive study outcome to be considered statistically 
valid, clinically meaningful and representative of the general population being sampled.  
 
Subject Recruitment Advertisement  
 
Toenail Fungus  
Research Study 
 
This study is to see if the Erchonia LunulaLaser™,  
a non-invasive device that uses low-level laser light  
to grow new nail in toenails with toenail fungus can 
help to get rid of the fungus in the toenail altogether. 
 
The study involves 12 visits to a test site  
over about 14 months. 
 
Please contact  
<Test Site/PI name> at <phone#> or 
 <e-mail> for details. 

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STUDY PROCEDURE 
STUDY TEST BATTERY 
 
The following assessment tools will be used in this study. For each study phase, the precise tool 
that will be employed will be specified.  
 
BASELINE VARIABLES  
 
BASELINE TARGET TOENAIL VARIABLES 
 
(i) Location of target toenail: right foot; left foot.  
(ii) Duration of onychomycosis in target toenail: months/years since observed onset  
(iii) Notation of any other toenail(s) on the target foot that appear to be infected with 
onychomycosis. 
 
PRIOR TREATMENT APPROACHES 
 
Recording of any and all prior treatments that the subject has tried to manage his or her 
onychomycosis of the target toenail, including: 
 
(i) 
Over-the-counter (OTC) medications and treatments (oral and topical) 
(ii) Prescription medications and treatments (oral and topical) 
(iii) Herbal supplements (oral and topical) 
(iv) Traditional therapies (e.g. surgery, YAG laser therapy) 
(v) Alternative therapies (e.g. acupuncture) 
 
Noting, for each medication/treatment/therapy tried: 
(i) 
Date(s) of use/application 
(ii) Duration of use/application 
(iii) Perceived effectiveness 
 
CONCOMITANT MEDICATIONS  
 
Recording pf any and all current medications that the subject is taking for any reason, including: 
 
(i) 
Over-the-counter (OTC) medications and treatments  
(ii) Prescription medications and treatments 
(iii) Herbal supplements  
 
Noting, for each medication: 
 
(i) 
Indication for use 
(ii) Dosage and frequency of use  
(iii) Duration of use 
 
 
SUBJECT DEMOGRAPHICS 
 
(i) 
Gender 
(ii) Age 
(iii) Ethnicity  
 

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CLINICAL AND OUTCOME EVALUATION TOOLS 
 
MYCOLOGICAL EVALUATION: BIOMED INTRAY™ DM CULTURE 
 
The BioMed InTray™ DM Culture will be used to determine the presence or absence of fungal 
organisms and to identify the type of dermatophyte in the case of a positive fungal 
determination. 
 
The BioMed InTray™ DM Culture device allows for simultaneous detection and observation of 
the dermatophyte fungal group, including detection of dermatophytes of Microsporum, 
Epidermophyton and Trichophyton (T. rubrum), as well as C.albicans. 
 
The InTray™ DM Culture testing will be performed from the same target toenail for each subject 
at each administration. For cultures positive for the presence of fungal organisms, the type of 
dermatophyte identified will also be recorded. 
 
PHOTOGRAPHIC DOCUMENTATION 
 
A photograph of the study great toenail will be taken with the great toe placed in a horizontal-
vertical mm scale measurement recording device. This device is designed to maintain the great 
toenail in the same position at each photographic time point to ensure consistency of 
measurements across all evaluation time points and all toenails, and to provide a mm reference 
scale in the event that measurement of mm of clear nail is necessitated.  
 
An image of the mm scale recording device and its application is shown below in Figure 8. 
 
 
 
Figure 8: Positioning of the great toenail in the mm scale recording device 
 
The photograph of the study great toenail will be taken using a high resolution digital camera, 
following a standardized methodology, ensuring consistency of equipment, lighting, distance, 
resolution, etc. between and across all subjects, test sites and measurement time points 
 
 
 
 
 

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MM OF CLEAR NAIL MEASUREMENT TOOL: THE GNU IMAGE MANIPULATION 
PROGRAM (GIMP 2.8)  
 
The GNU Image Manipulation Program (GIMP 2.8) will be employed in this study for the 
measurement of the linear millimeters (mm) of clear nail bed. 
 
The GNU Image Manipulation Program (GIMP 2.8) was originally released in January 1996 as 
the General Image Manipulation Program, having been created by Spencer Kimball and Peter 
Mattis as the result of a college project at the University of California, Berkeley. In 1997, the 
definition of the acronym ‘GIMP’ was changed to mean the GNU Image Manipulation Program, 
by permission of Richard Stallman, to also reflect its existence under the GNU Project.  
 
The GNU Image Manipulation Program (GIMP 2.8) is a multi-platform image/photo manipulation 
software. It is a raster editor, such that it performs operations directly on the pixels that make up 
the image and not a vector editor.  
 
GIMP is suitable for a variety of image manipulation and analysis tasks, including photo 
retouching, image composition, and image construction. It has many capabilities. It can be used 
as a simple paint program, an expert quality photo retouching program, an online batch 
processing system, a mass production image renderer, an image format converter, etc. It is 
designed to be augmented with plug-ins and extensions to do just about anything. The 
advanced scripting interface allows everything from the simplest task to the most complex 
image-manipulation procedures to be easily scripted. 
 
Complete details of GIMP, its specifications, operations and applications can be found on the 
website: www.gimp.org. 
 
Erchonia Corporation conducted a validation study of the GIMP 2.8 software to validate both the 
method/tool and the measurement methodology for the specific application of the measurement 
of linear mm of clear nail prior to the initial LunulaLaser™ trial. The results of the validation 
study have been reviewed and accepted by the FDA as a validated means of measuring linear 
mm of clear nail in onychomycosis-infected toenails. 
 
In this study, GIMP 2.8 will be used to measure the 
linear mm of clear nail of the onychomycosis 
infected great toenail from the digital toenail images 
captured, defined as the distance from the proximal 
nail fold to the most proximal area of nail dystrophy. 
A straight line will be created between the two 
points, and the GIMP 2.8 system software will 
formulate a measurement of that line. An example is 
shown in Figure 9 to the right, demonstrating how 
total nail length and linear measurement of mm of 
clear nail from the proximal nail fold to the most 
proximal area of nail dystrophy is determined.   
Figure 9: Application of the GIMP 2.8  
to measurement of mm clear nail length 
 
The ‘GIMP 2.8 Software Measurement Methodology Instruction Sheet’ contained in Appendix 
A details the instructions for operation and application of the GIMP 2.8 software system for 
measurement of linear mm clear nail measured from the proximal nail fold to the most proximal 
dystrophic component that will be followed by the study investigators. 

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NAIL ETCHING 
 
A shallow etched horizontal line will be placed in the target study toenail, at the proximal-most 
area of dystrophy and aligned parallel to the horizontal portion of the proximal nail fold. This line 
will serve as both a marker for measuring nail growth rate as well as distance from the proximal 
nail fold to the most proximal point of the nail dystrophy. 
 
PERCENTAGE OF CLINICAL ONYCHOMYCOSIS INVOLVEMENT DETERMINATION 
 
Visual estimation of the % of clinical onychomycosis disease involvement in the target great 
toenail will be determined by the investigator based upon his or her professional and clinical 
knowledge and experience.  
 
SUBJECT DAILY DIARY 
 
On each day of the study, the subject will record the following measures in a Daily Diary 
supplied by the investigator at the test site on the day of the first treatment administration. 
 
9 Compliance with abstinence from other (non-study) treatments for toenail fungus 
9 Compliance with abstinence from the use of nail cosmetics on study toes 
9 Any changes in medication use and/or therapies engaged in from those reported at 
baseline evaluation 
9 Potential perceived adverse events, as described in the ‘Adverse Events’ evaluation tool 
listed below. 
9 Any study-related comments, if and as desired  
 
ADVERSE EVENTS EVALUATION  
 
Prior clinical trials applying the Erchonia® LunulaLaser™ to toenail onychomycosis have not 
yielded any adverse events or reactions. Numerous additional clinical trials applying Erchonia® 
low level laser for various different indications have also not yielded any adverse events or 
reactions. Therefore, it is unlikely and not expected that any adverse events will result from 
implementation of this clinical study protocol.  
 
However, potential adverse events that may feasibly occur from application of the Erchonia 
LunulaLaser™ include, but are not necessarily limited to: skin irritation, discoloring, rash, 
indentations and re-infection.  
 
Adverse events evaluation will include formal evaluation of the treatment area and surrounding 
skin area by the investigator at each subject test site visit as well as review of any potential 
events reported or recorded in the Subject Daily Diary by the subject. Adverse events evaluation 
will be conducted for all toenails on the foot with the study treated toenail. 
 
Any and all observation(s)/report(s) of potential adverse events, whether observed by the 
investigator or reported by the subject, whether anticipated or unanticipated, will be recorded on 
the Adverse Events case report form and subsequently evaluated by the investigator for its 
relation to the study procedure and whether or not any corrective action needs to be taken. All 
potential adverse events recorded will be appropriately reported to the governing IRB, as 
applicable. 
 

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STUDY PROCEDURE PROTOCOL 
 
PRE-TREATMENT ACTIVITIES 
 
STUDY QUALIFICATION EVALUATION: PROGRESSIVE EVENTS  
 
SIGNING OF INFORMED CONSENT FORM 
The PI commences by presenting and reviewing in detail the items in the informed consent form 
with the individual and answering any questions he or she may have. To proceed, the individual 
must willingly sign the informed consent form. 
 
ASSIGNMENT OF SUBJECT IDENTIFICATION NUMBER 
The subject is assigned a unique subject identification number based upon his or her order of 
entry into the study. Additional information about the informed consent and subject ID number 
assignment is contained in a later section of the protocol titled, “SAFETY AND 
CONFIDENTIALITY ISSUES.” 
 
INCLUSION/EXCLUSION CRITERIA 
 
MYCOLOGICAL CRITERIA EVALUATION  
The BioMed InTray™ DM culture will be performed on the intended study great toenail: 
 
Inclusion Criteria: The subject will continue to the Clinical Criteria Evaluation phase if the results 
of the InTray™ DM culture results satisfy both of the following inclusion criteria: 
 
¾ Detection of the presence of fungal infection  
¾ Identification of Trichophyton rubrum (T. rubrum) or other common dermatophyte  
 
Exclusion Criteria: The subject’s participation in the study will end at this time if the results of the 
InTray™ DM culture satisfies either or both of the following exclusion criteria: 
 
¾ Lack of detection of the presence of fungal infection  
¾ Identification of a fungal species other than Trichophyton rubrum (T. rubrum) or other 
common dermatophyte, such as C. albicans or mixed dermatophyte/Candida infection or 
non-fungal organisms such as mold or bacteria 
 
CLINICAL CRITERIA EVALUATION  
 
Inclusion Criteria: The subject will continue to the Baseline Assessment phase if all of the 
following clinical inclusion criteria are satisfied: 
 
¾ Visual clinical presentation of onychomycosis in the target great toenail is distal subungual 
onychomycosis (DSO), visualized as a nail with normal surface texture and thickness but 
variable “bays” of white nail that extend from the distal nail tip proximally into the area of the 
nail bed 
¾ Clinical involvement of onychomycosis in the target toenail is between 20%–50%   
¾ Subject is willing and able to refrain from employing other (non-study) treatments (traditional 
or alternative) for his or her toenail onychomycosis throughout study participation. 
¾ Subject is willing and able to refrain from the use of nail cosmetics such as clear and/or 
colored nail lacquers throughout study participation 
¾ Male or female 
¾ 18 years of age or older 

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Exclusion Criteria: The subject’s participation in the study will end at this time of any one or 
more of the following clinical exclusion criteria are satisfied: 
 
¾ Visual clinical presentations of onychomycosis in the target great toenail that are 
inconsistent with the clinical presentation of distal subungual onychomycosis (DSO), in 
whole or in part (i.e. indicative of mixed etiology); specifically visual clinical presentations 
consistent with one or more of the following:  
 
x Proximal subungual onychomycosis (PSO): visualized as a white discoloration below the 
nail plate at the base of the nail, near the lunula. The distal nail retains normal 
appearance and texture. PSO involves infection near the matrix, deep to the nail. It may 
be associated with trauma to the nail or to immune compromise 
x Superficial white onychomycosis (SWO): visualized by the appearance of a white coating 
on the nail surface that can be eliminated by filing or buffing the surface of the affected 
portion of the nail 
x Complete dystrophy: Nails which are 100% dystrophic are manifested by yellowing and 
thickening of the entire nail unit 
x Other nail changes: Nails that visually present with changes that appear as parallel lines, 
small pinpoint depressions, brown spots, black or brown linear streaks, complete 
yellowing of all nails without textural change, green debris below the nail, or notches in 
the nail margin  
 
¾ Less than 2mm clear (unaffected) nail plate length beyond the proximal fold 
¾ Presence of dermatophytoma (thick masses of fungal hyphae and necrotic keratin between 
the nail plate and nail bed)  
¾ Infection involving lunula e.g., genetic nail disorders, primentary disorders 
¾ Severe plantar (moccasin) tinea pedis 
¾ Psoriasis of the skin and/or nails, lichen planus, or other medical conditions known to induce 
nail changes  
¾ Onychogryphosis 
¾ Trauma from ill-fitting shoes, running, or overly-aggressive nail care 
¾ Previous toenail surgery 
¾ Uncontrolled diabetes mellitus 
¾ Peripheral vascular disease 
¾ Recurrent cellulitis 
¾ Lymphatic insufficiency 
¾ Immune compromise (whether due to underlying medical disorders or immunosuppressive 
treatments)  
¾ Other compromised states of health 
¾ Known photosensitivity disorder 
¾ Use of oral antifungal drugs in the prior 6 months 
¾ Use of topical treatment of the skin or nails within the prior 2 months 
¾ Any abnormality of the toenail that could prevent a normal appearing nail from occurring if 
clearing of infection is achieved.  
¾ Current trauma, open wound on or about the treatment area  
¾ Deformity of the target toe/toenail secondary to fungal infection/onychomycosis due to prior 
injury, surgical procedures or another medical condition 
¾ Pregnant or planning pregnancy prior to the end of study participation 
¾ Serious mental health illness such as dementia or schizophrenia; psychiatric hospitalization 
in the past two years 

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¾ Developmental disability or cognitive impairment that would preclude adequate 
comprehension of the informed consent form and/or ability to follow study subject 
requirements and/or record the necessary study measurements 
¾ Involvement in litigation and/or receiving disability benefits related in any way to the 
parameters of the study 
¾ Participation in a clinical study or other type of research in the past 30 days. 
 

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BASELINE ASSESSMENT 
 
BASELINE VARIABLES 
 
¾ Baseline Target Toenail Variables 
¾ Prior Treatment Approaches 
¾ Concomitant Medications And Therapies 
¾ Notation of any other toenail(s) on the target foot that appear to be infected with 
onychomycosis.  
¾ Subject Demographics 
 
CLINICAL AND OUTCOME EVALUATIONS   
 
¾ Nail Etching 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage Of Clinical Onychomycosis Involvement Determination  
 
 
TREATMENT ADMINISTRATION PHASE 
 
GENERAL ASSESSMENT CONDITIONS 
Subjects must agree to not partake in any non-study treatment(s) for toenail onychomycosis 
(including oral medications and nail lacquer, non-alternative therapies such as acupuncture and 
home remedies), or to use any toenail cosmetics throughout the course of study participation. 
 
TREATMENT ADMINISTRATION PROTOCOL   
¾ The treatment administration phase of the study will last 11 months, comprised of an initial 
weekly treatment administration phase followed by an every two month maintenance 
treatment administration phase. 
¾ The treatment administration phase of the study will commence on the same day as the 
Baseline Assessment visit, following completion of all activities related to the Baseline 
Assessment visit. 
¾ The initial weekly treatment administration phase will last three weeks and involve four in-
office treatment administrations with the Erchonia® LunulaLaser™, each one week (7 days) 
apart (i.e. Days 1, 8, 15 and 22).  
¾ The maintenance treatment administration phase involves the subject returning to the test 
site one time every eight weeks (2 months) following the final weekly treatment 
administration for a single maintenance treatment administration with the Erchonia® 
LunulaLaser™ (i.e. end of months 3, 5, 7, 9 and 11).  
¾ Each treatment administration lasts 12 minutes. 
¾ Each treatment administration is administered by the study investigator at the test site. 
   
 
 
 
 
 
 

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The treatment administration protocol for each of the Erchonia® LunulaLaser™ laser treatment 
administration is as follows: 
 
1. The subject is seated comfortably with the LunulaLaser™ placed on the floor in front. 
2. The subject is fitted with the safety glasses. 
3. The subject places the foot with the infected great toenail to be treated in this study on the 
treatment platform inside the Erchonia LunulaLaser™ laser device – heel on the back, toes 
on the front platform under the laser output heads, as shown in the figure below. 
 
 
 
4. The Erchonia LunulaLaser™ is activated such that the laser light is directed at the great 
toenail at a distance of approximately 4 inches above the toenail.  
5. The dual wavelengths of 405 nm and 635nm are activated simultaneously for 12 minutes of 
total treatment administration time. 
 
By design of the device, it is not possible for the subject to move the foot’s position to any 
significant degree that would impact the intended exposure to the laser procedure, 
particularly considering that the laser beam is designed to cover the entire treated toe 
region. The exception would be if the subject withdrew his or her foot entirely from the laser 
device mid-treatment administration, in which case, the foot would be re-inserted at once 
and the remaining minutes of exposure completed such that the total maximum exposure 
time in one session would not ever exceed the pre-determined 12-mintues. If the subject 
was unable or refused to re-insert his or her foot for any reason, the subject would be 
disqualified from further study participation at that time.   
 
6. The subject removes his or her foot from the Erchonia LunulaLaser™. 
7. The laser treatment administration is complete. 
8. The subject removes the safety glasses, and the treatment procedure administration 
protocol is completed. 
 
 
 
 
 

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STUDY EVALUATION TIMELINE AND MEASURES 
 
The evaluation time points and associated measures (as outlined in the STUDY TEST 
BATTERY section above) to be evaluated during the course of this study are as follows:  
 
DAILY COMMENCING ON THE DAY OF THE FIRST TREATMENT ADMINISTRATION 
THROUGH TO STUDY END  
 
¾ Subject Daily Diary 
 
AT EACH TREATMENT ADMINISTRATION AND EVALUATION VISIT 
 
¾ Adverse Events Evaluation  
 
AT EACH TREATMENT ADMINISTRATION VISIT COMMENCING WITH THE FOURTH 
WEEKLY TREATMENT ADMINISTRATION (END OF WEEK 4, MONTHS 3, 5, 7, 9, AND 11)  
 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage of Clinical Onychomycosis Involvement Determination 
¾ Mycological Evaluation: InTray™ DM Culture   
 
STUDY ENDPOINT EVALUATION: 12 MONTHS FOLLOWING THE INITIAL TREATMENT 
ADMINISTRATION  
 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage of Clinical Onychomycosis Involvement Determination 
¾ Mycological Evaluation: InTray™ DM Culture   
 
TWO 
MONTHS 
AFTER 
STUDY 
ENDPOINT 
EVALUATION 
POST-TREATMENT 
EVALUATION  
 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage of Clinical Onychomycosis Involvement Determination 
¾ Mycological Evaluation: InTray™ DM Culture   
 
 
 
 
 

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TABLE OF SUBJECT EVENTS 
 
The following table provides a progressive summary of subject events throughout this study.  
PRE-TREATMENT ACTIVITIES  
 
  STUDY QUALIFICATION EVALUATION   
 
¾ A potentially well-suited and interested candidate for participation in the study attends the 
investigator’s office. 
¾ The investigator reviews the informed consent form with the candidate.  
¾ If the candidate continues to be interested and voluntarily signs the informed consent 
form, Study Qualification Evaluation is performed: Mycological Evaluation followed by 
Clinical Evaluation criteria. 
¾ A fully qualified subject progresses to the Baseline Assessment phase. 
 
BASELINE ASSESSMENT 
 
BASELINE VARIABLES 
 
¾ Baseline Target Toenail Variables 
¾ Prior Treatment Approaches 
¾ Concomitant Medications and Therapies 
¾ Notation of all infected toenails on the target foot 
¾ Subject Demographics 
 
CLINICAL AND OUTCOME EVALUATIONS  
 
¾ Nail Etching 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage of Clinical Onychomycosis Involvement Determination 
 
TREATMENT ADMINISTRATION PROTOCOL  
 
Each participant receives 4 12-minute treatment administrations with the Erchonia® 
LunulaLaser™ over 4 consecutive weeks, each 7 days apart, followed by one treatment 
every two months thereafter. Each treatment is administered at the test site. 
 
 
 

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STUDY EVALUATION TIMELINE AND MEASURES 
 
DAILY COMMENCING ON THE DAY OF THE FIRST TREATMENT ADMINISTRATION 
THROUGH TO STUDY END 
 
¾ Subject Daily Diary 
 
AT EACH TREATMENT ADMINISTRATION AND EVALUATION VISIT  
 
¾ Adverse Events Evaluation  
 
AT EACH TREATMENT ADMINISTRATION AND EVALUATION VISIT COMMENCING WITH 
THE FOURTH WEEKLY TREATMENT ADMINISTRATION  
 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage of Clinical Onychomycosis Involvement Determination  
¾ Mycological Evaluation: InTray™ DM Culture     
 
STUDY ENDPOINT EVALUATION: 12 MONTHS FOLLOWING THE INITIAL TREATMENT 
ADMINISTRATION  
 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage of Clinical Onychomycosis Involvement Determination 
¾ Mycological Evaluation: InTray™ DM Culture     
 
TWO 
MONTHS 
AFTER 
STUDY 
ENDPOINT 
EVALUATION 
POST-TREATMENT 
EVALUATION  
 
¾ Photographic Documentation 
¾ Measurement of mm of Clear Nail 
¾ Percentage of Clinical Onychomycosis Involvement Determination 
¾ Mycological Evaluation: InTray™ DM Culture   
 
 
 
 
 

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SAFETY AND CONFIDENTIALITY 
 
ADVERSE EVENTS  
At each evaluation and measurement point throughout the clinical study (as outlined in the 
STUDY EVALUATION TIMELINE section above), and at any other time throughout the duration 
of the clinical trial that is necessary, any and all potential adverse events reported by a subject 
or observed by an investigator will be recorded on the case report form, and subsequently 
evaluated by the investigator for its relation to the study procedure and whether or not any 
corrective action needs to be taken. All potential adverse events recorded will be applicably and 
appropriately reported to the governing IRB. 
 
It is unlikely and not expected that any adverse events will result from implementation of this 
clinical study protocol. Prior clinical trials using Erchonia® low level lasers, including the 
LunulaLaser™ have not yielded any adverse events or reactions. However, potential adverse 
events that may feasibly occur from application of the Erchonia LunulaLaser™ and that will be 
specifically evaluated during scheduled adverse events evaluations include, but are not 
necessarily limited to: skin irritation, discoloring, rash, indentations and infection. Adverse 
events evaluation will be conducted for all toes/toenails on the study treated foot. 
 
PRIVACY AND CONFIDENTIALITY 
Records for each subject in this clinical study will be maintained in separate files in a locked 
filing cabinet at the respective test site. The investigator at the test site will be responsible for 
ensuring that all records for a subject pertaining to his or her participation in the clinical study 
are stored in that subject’s file at all times other than when information is being recorded on 
them.   
 
Copies of all of the subject case report forms will be made and supplied to Regulatory Insight, 
Inc. and Erchonia Corporation. Regulatory Insight, Inc. and Erchonia Corporation will maintain 
these copies in a separate clinical study file that is kept in a locked filing cabinet on their 
respective premises. The original records will be maintained at the respective test sites.  
 
Subjects’ identities will be kept confidential by assigning each subject a subject ID upon 
acceptance into the study. The subject ID will comprise the investigator’s two initials (first and 
last name initials) and a three-digit number that will be based upon the subject’s order of entry 
into the clinical study. Each test site will be assigned a unique range of numbers. Test site #1 
will be assigned numbers 001 to 100. Test site #2 will be assigned numbers 101 to 200, and so 
on. For example, the eighth subject to be enrolled at test site #2 with Principal Investigator John 
Black would have a subject ID of JB108. Neither the study Sponsor nor Regulatory Insight, Inc. 
will receive any additional identifying information about a subject and will therefore have no way 
of linking a subject ID to a particular subject and his or her results.   
 
MONITORING OF THE CLINICAL STUDY 
 
Training, set-up and monitoring of the clinical study will be according to all of the applicable 
protocols and procedures contained within the Erchonia Corporation Clinical Trials Monitoring 
Plan, Version 2.0, March 15, 2015, contained in Appendix E of this clinical study protocol 
document. 
 
Furthermore, monitors will train the study investigators to the following document: Erchonia 
Corporation Clinical Trial Investigator Responsibilities Procedure, Version 1.0, April 3, 2015, 
contained in Appendix F of this clinical study protocol document. 

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STATISTICAL ANALYSIS PLAN 
 
The aim of this study is to determine if there is a treatment effect of application of the Erchonia® 
LunulaLaser™ for individuals with onychomycosis of the great toenail.  
 
PRIMARY EFFICACY OUTCOME EVALUATION  
 
The primary efficacy outcome measure in this study is the Complete Cure Rate at study 
endpoint. 
 
Individual Subject Success Criteria: ‘Complete Cure’ criteria is defined as a subject/toenail 
satisfying both the ‘Clinical Cure’ and the ‘Mycological Cure’ criteria in order to be considered a 
study responder, defined as follows: 
 
(i) Clinical Cure: Measurement of clear nail increase as the following: 
 
x 
at least 12 mm increase in clear nail of the great toenail, with evidence of distal growth of 
the affected area, 12 months after the first treatment; 
or 
x 
complete clearance 12 months after the first treatment if less than 12 mm distal nail was 
involved prior to treatment. 
  
The response should be progressive in at least 2 sequential timepoints that are at least 3 
months apart, with projected increase of at least 1 mm per month. 
 
(ii) Mycologic Cure: Negative Fungal Culture results 
 
Overall Study Success Criteria is defined as both of: 
 
(i) 
a minimum 70% Clinical Cure Clear Nail Responder Rate;  
 
AND 
 
(ii) Among toenails which are deemed responders based on the Clinical Cure Clear Nail 
criteria, at least 80% will also demonstrate Mycological Cure. 
 
STUDY END POINT EVALUATION  
 
The study end point evaluation at which Individual Great Toenail Success and Overall Study 
Success will be evaluated is at 12 months following initiation of the treatment administration 
phase. 
 
HYPOTHESES 
 
¾ Null Hypothesis: The Responder Rate for subjects/toenails attaining Clinical Cure will be 
70% or greater and 80% or more of those subjects will also attain Mycological Cure.  
¾ Alternative Hypothesis: The Responder Rate for subjects/toenails attaining Clinical Cure 
will be less than 70% and/or fewer than 80% of those subjects will also attain Mycological 
Cure.  
 

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PRIMARY EFFICACY OUTCOME STATISTICAL EVALUATION METHODS 
 
¾ Intent to Treat (ITT) Principle: Primary efficacy analysis will be according to the intent to 
treat (ITT) principle; wherein subjects will be included in the analysis if they had a valid 
Baseline Assessment visit.  
 
¾ Missing data will be handled through Last Observation Carried Forward (LOCF): by carrying 
forward the last recorded observation to fill in the subsequent missing value.  
 
Subjects who drop out or are lost to follow-up will be considered as treatment failures (non-
responders) in the statistical evaluation.  
 
¾ Per-Protocol Analysis will also be performed for the set of all subjects who completed the 
study according to the full protocol.  
 
¾ Primary analysis of efficacy according to intent to treat (ITT) analysis will be through 
determination of satisfaction of the Overall Study Success Criteria.  
 
SECONDARY EFFICACY OUTCOME EVALUATION  
 
The pre-specified secondary efficacy endpoints are  
(i) 
Clinical Efficacy Rate at week 52, defined as < 10% affected target nail area 
(ii) 
Mycological Cure Rate at week 52 (negative culture), and  
(iii) 
Unaffected New Nail Growth at week 52 (change from baseline in healthy nail 
measurement).  
 
Secondary endpoints will be measured in sequential order. 
 
ADDITIONAL SUPPORTIVE OUTCOME EVALUATIONS  
 
¾ Responder Rates across progressive evaluation visits 
¾ Percentage of clinical onychomycosis involvement determinations across progressive 
evaluation visits 
¾ Change in mm clear nail across progressive evaluation visits. 
 
SUBGROUP AND COVARIATE ANALYSES 
 
Study outcome will also be performed for the following subgroups and covariates, as applicable: 
 
¾ Study test site 
¾ Category of % of baseline toenail onychomycosis involvement:  
x 20%-34% toenail onychomycosis involvement  
x 35%-50% toenail onychomycosis involvement  
 
¾ Baseline Fungal Culture Results Category according to type of organism identified.  
¾ Baseline % of toenail onychomycosis disease involvement 
¾ Right versus left great toenail  
¾ Duration of toenail onychomycosis at baseline 
¾ Age 
¾ Gender 
¾ Ethnicity 

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EVALUATION OF SUBJECT DAILY DIARY MEASURES 
 
The information recorded by the subjects in the Subject Daily Diary on each day of the study 
evaluation period will be evaluated as follows: 
 
¾ The impact on study outcome of reported notable non-compliance with other (non-study) 
toenail fungus treatment abstinence.  
¾ The impact on study outcome of reported notable non-compliance with abstinence from use 
of toenail cosmetics on the study great toenail(s)  
¾ Any changes in medication and therapy use across study progression relative to that 
reported at baseline and the impact on study outcome. 
¾ Any potential perceived adverse events will be reported and evaluated 
¾ Any comments provided by subjects will be reported and evaluated. 
 
SAFETY ANALYSES  
 
Safety analyses will be based on all subjects who signed the informed consent form and were 
enrolled in the study. Safety will be assessed by evaluating the incidence, frequency and 
severity of observed and/or reported adverse events. Specific safety evaluation will be made 
with respect to re-infection rate, as applicable. Safety evaluation will be conducted for all 
toenails on the study treated foot, as applicable. 
 
INFORMED CONSENT 
 
x Informed consent will be an agreement between the individual investigator and each subject, 
having the capacity to understand and make an informed decision. Consent will be obtained 
prior to each potential subject’s participation in this clinical study. 
x Each subject participating in this clinical study will be made aware of the fact that his or her 
participation involves research and the intent of the research, the expected duration of his or 
her participation and a description of the procedures that will be followed.   
x Each subject will be made aware of the reasonably expected benefits he or she might 
receive, as well as any risks or potential discomfort that are involved.   
x Each subject will also be made aware of alternative treatments available to him or her.   
x Each subject will be made aware that his or her records will remain confidential, but that the 
FDA and the IRB has the right to inspect his or her records.   
x Each subject will be told that his or her participation in the clinical study is voluntary, without 
force or influence from the investigator or sponsor. 
x Each subject will be given the name and method of contacting the appropriate person(s) to 
answer his or her questions about the research and in the event of a research-related injury.