A Double-blind, Placebo-controlled Randomized Evaluation of the Effect of the Erchonia® FX-635™ on Diabetic Peripheral Neuropathy Pain
Phase: NA
Conditions: Diabetic Peripheral Neuropathy
Sponsor: Erchonia Corporation

Erchonia® FX-635™ Diabetic Peripheral Neuropathy Pain Clinical Study Protocol  
Version 1.3 
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ERCHONIA® FX-635™ 
 
 
A double-blind, placebo-controlled  
randomized evaluation of the effect  
of the Erchonia® FX-635™  
on diabetic peripheral neuropathy pain  
clinical study protocol  
 
 
 
ERCHONIA CORPORATION 
 
 
Version 1.3 
March 21st, 2019 
 
Revision # 
Description of Changes 
Approved by: 
Date 
1.2 
Following the FDA Site Inspection of the Sponsor, 
the Sponsor revised the Protocol to include 
definitions of Adverse Events as well as Protocol 
Deviations and the necessary steps to report these 
incidents as applicable. Additionally, the Case Report 
Forms were also updated based on the FDA’s 
feedback on previous studies. These changes do not 
alter the WIRB approved information. No changes 
were made to any subject activity and there is no 
change in the level of risk to the subject.   
Steven Shanks,  
Sponsor 
02/19/2019 
1.3 
Changes were made to accommodate satisfaction of 
medication exclusion criteria prior to commencement 
of the washout phase; to remove redundancy 
between inclusion and exclusion criteria; to reword 
exclusion criteria to the affirmative; and to separate 
subject recorded measures and investigator 
recorded measures within a visit into separate CRFs. 
Steven Shanks, 
Sponsor 
03/21/2019 

Erchonia® FX-635™ Diabetic Peripheral Neuropathy Pain Clinical Study Protocol  
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TABLE OF CONTENTS 
 
STUDY INFORMATION............................................................................................... 1 
SPONSOR................................................................................................................... 1 
REGULATORY CONSULTANT ................................................................................... 1 
CLINICAL CONSULTANT ........................................................................................... 1 
MONITOR ................................................................................................................... 1 
PRINCIPAL CLINICAL INVESTIGATORS & TEST SITES ........................................... 1 
INSTITUTIONAL REVIEW BOARD  ............................................................................ 2 
PURPOSE OF STUDY ................................................................................................ 2 
INDICATION FOR USE ............................................................................................... 2 
EXPECTED RESULTS ................................................................................................ 2 
RESOURCES .............................................................................................................. 2 
STUDY INDICATION, THEORY OF MECHANISM OF OPERATION, STUDY 
RATIONALE & SUPPORTING   MATERIALS ............................................................. 3 
DEVICE INFORMATION: ERCHONIA® FX-635™ .................................................... 19 
STUDY DESIGN ........................................................................................................ 31 
STUDY PROCEDURE ............................................................................................... 36 
STUDY TEST BATTERY ........................................................................................... 36 
STUDY PROCEDURE PROTOCOL  ......................................................................... 40 
PRE-PROCEDURE ACTIVITIES ............................................................................... 40 
 STUDY QUALIFICATION .......................................................................................... 40 
PRE-PROCEDURE WASHOUT PHASE ................................................................... 43 
PRE-PROCEDURE EVALUATION  PHASE ............................................................... 43 
PROCEDURE ADMINISTRATION  PHASE ............................................................... 44 
PROCEDURE ADMINISTRATION PROTOCOL ........................................................ 44  
PROCEDURE ADMINISTRATION PHASE MEASURES ........................................... 44  
POST-PROCEDURE ACTIVITIES ............................................................................. 45  
POST-PROCEDURE EVALUATION  PHASE ............................................................ 45 
OPEN-LABEL PLACEBO SUBJECT PROCEDURE ADMINISTRATION  PERIOD ... 46 
TABLE OF SUBJECT EVENTS ................................................................................. 48 
ADVERSE EVENTS .................................................................................................. 50 
PROTOCOL DEVIATIONS AND VIOLATIONS ......................................................... 51 
PRIVACY AND CONFIDENTIALITY .......................................................................... 52 
MONITORING OF THE CLINICAL STUDY................................................................ 52 
STATISTICAL ANALYSIS .......................................................................................... 53 
INFORMED CONSENT ............................................................................................. 58 
CASE REPORT FORMS ........................................................................................... 58 
 
 
    APPENDICES 
    APPENDIX A: ERCHONIA CORPORATION JOURNAL ARTICLES 
    APPENDIX B: PI INSTRUCTIONS FOR VAS MEASUREMENTS  
    APPENDIX C: NPSI & RELATED JOURNAL ARTICLES 
    APPENDIX D: CASE REPORT FORMS 

 
 
 
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STUDY INFORMATION 
 
SPONSOR 
Erchonia Corporation 
650 Atlantis Rd.  
Melbourne, FL  32904 USA 
 
Contact: Mr. Steven Shanks, President 
Telephone: 321-473-1251 
E-mail: sshanks@erchonia.com 
  
REGULATORY CONSULTANT 
Regulatory Insight, Inc., Denver Office 
33 Golden Eagle Lane  
Littleton, CO 80127 USA 
Contact: Kevin Walls, Principal Consultant 
Telephone: 720-962-5412 
E-mail: kevin@reginsight.com  
 
CLINICAL CONSULTANT 
Regulatory Insight, Inc., Nashville Office 
219 East Harbor 
Hendersonville, TN 37075 USA 
Contact: Elvira Cawthon, Clinical Consultant 
Telephone: 615-447-5150 
E-mail: elvira@reginsight.com  
 
MONITOR 
Erchonia Corporation 
650 Atlantis Rd.  
Melbourne, FL  32904 
 
Contact: Rebecca Tucek 
Telephone: 321-473-1251 
E-mail: rtucek@erchonia.com 
 
PRINCIPAL CLINICAL INVESTIGATORS AND TEST SITES 
 Sandra Lee Franco, DPM, MS 
Hialeah Hospital Medical Plaza 
777 East 25th Street, Suite 502 
Hialeah, FL 33139, USA 
Telephone: 954.436.7400 
e-mail: info@francoandcompany.com 
IRB Study Number: 1251019 
 
 Matthew H. Etheridge, DPM 
Pensacola Podiatry, P.A. 
8333 N. Davis Highway 
Pensacola, FL 32514, USA 
Telephone: 850.969.2550 
e-mail: matthewetheridge@bellsouth.net 
 
 

 
 
 
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INSTITUTIONAL REVIEW BOARD 
Western Institutional Review Board® (WIRB®) 
1019 39th Avenue SE Suite 120 
Puyallup, WA 98374-2115, U.S. 
Telephone: 360-252-2500 
e-mail: info@clientservices.com 
IRB Tracking No. : 20150254 
 
PURPOSE OF STUDY 
The purpose of this clinical study is to determine the effectiveness of the Erchonia® FX-
635™, manufactured by Erchonia Corporation (the Company), in providing relief of foot 
pain in individuals with chronic painful diabetic peripheral neuropathy.  
 
INDICATION FOR USE 
The indication (claim) being sought through support of the results of this clinical study is: 
“The Erchonia® FX-635™ is indicated for adjunctive use in providing relief of chronic 
pain arising from diabetic peripheral neuropathy.”  
 
It is intended that the results of this clinical study be used to support a 510(k) submission 
to FDA for clearance to market the device for the intended indication. 
 
EXPECTED RESULTS 
Following completion of the study procedure protocol with the Erchonia® FX-635™ 
relative to baseline, it is anticipated that significantly more subjects in the test group than 
in the placebo group will show a 30% or greater reduction in self-reported VAS pain 
rating in the feet. 
 
RESOURCES  
This clinical study protocol design and content is based on the clinical study protocols 
whose implementation outcome was used to successfully support FDA clearances to 
market the Erchonia® 635nm red diode low level lasers for the following pain reduction 
related indications:  
 
1. K180197: Erchonia® FX-635: is indicated for the following two indications: 
a. as an adjunct to provide relief of minor chronic low back pain of musculoskeletal 
origin. 
b. as an adjunct to reducing chronic heel pain arising from plantar fasciitis. 
2. K132940: Erchonia® Allay™: is indicated as an adjunct to reducing chronic heel pain 
arising from plantar fasciitis. 
3. K072206: Erchonia® EML Laser: is indicated for the temporary reduction in post-
surgery pain at 24 hours after surgery following bilateral breast augmentation surgery. 
4. K041139: Erchonia® EML Laser: is indicated as an adjunct to liposuction procedures 
of the thighs, hips and stomach for reduction of pain associated with the recovery 
process. 
5. K012580: Erchonia PL2000: is indicated for adjunctive use in providing temporary relief 
of minor chronic neck and shoulder pain of musculoskeletal origin. 
. 
 
 

 
 
 
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STUDY INDICATION, THEORY OF MECHANISM OF OPERATION, STUDY 
RATIONALE & SUPPORTING MATERIALS 
 
STUDY INDICATION: CHRONIC PAINFUL DIABETIC PERIPHERAL NEUROPATHY 
 
The study indication to be evaluated in this study is the relief of chronic foot pain arising 
from diabetic peripheral neuropathy.  
 
STATISTICS 
 
Peripheral neuropathy is one of the most common chronic diseases and a leading cause 
of adult disability in the U.S. Of the over 100 known types of neuropathy, diabetic 
neuropathy represents over a third of all neuropathies, making diabetes the leading 
cause of peripheral neuropathy. Due to the increasing prevalence of diabetes, there are 
now about 15-18 million Americans with diabetic peripheral neuropathy, about 60% to 
70% of the 25.8 million adults and children in the U.S. with diabetes. U.S. (Source: The 
Neuropathy Association). In addition, there are 79 million individuals in the U.S. with pre-
diabetes who are at risk for developing diabetic peripheral neuropathy (Source: The 
Center for Disease Control). 
 
Living with neuropathy can cause tremendous frustration and social isolation for 
patients. The daily chronic pain impacts day-to-day functionality resulting in physical and 
psychological problems including impaired concentration, anxiety, depression, a decline 
in cognitive abilities, and sleep difficulties which in turn can lead to irritability and 
increased pain sensitivity. 
Additionally, the economic burden from medical costs and workplace productivity losses 
are high and on the rise as the incidence of peripheral neuropathy increases. 
Neuropathic pain patients are often high health care system users as they seek relief 
from persistent suffering. Those debilitated by neuropathy or coping with chronic pain 
are challenged with working full-time and may become unemployable or stay under-
employed. 
 
DESCRIPTION & DEFINITION 
 
Peripheral neuropathy describes damage to the peripheral nervous system, the vast 
communications network that transmits information from the brain and spinal cord 
(central nervous system) to every other part of the body. Peripheral nerves also send 
sensory information back to the brain and spinal cord, such as a message that the feet 
are cold, or a finger is burned. Damage to the peripheral nervous system interferes with 
these vital connections, distorting and sometimes interrupting messages between the 
brain and the rest of the body. 
 
 Classification of the Peripheral Neuropathies 
 
More than 100 types of peripheral neuropathy have been identified, each with its own 
characteristic set of symptoms, pattern of development and prognosis. Specific impaired 
function and symptoms depend on the type of nerves - motor, sensory, or autonomic - 
that are damaged: 
 
• Motor nerves control movements of all muscles under conscious control, such as 
those used for walking, grasping things, or talking 

 
 
 
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• Sensory nerves transmit information about sensory experiences, such as the feeling 
of a light touch or the pain resulting from a cut.  
• Autonomic nerves regulate biological activities that people do not control consciously, 
such as breathing, digesting food, and heart and gland functions.  
 
 Forms of Neuropathy 
 
• Mononeuropathies: Neuropathies that involve damage to only one nerve. 
• Polyneuropathies: Neuropathies that involve multiple nerves affecting all limbs. 
• Mononeuritis multiplex: Less commonly, neuropathies wherein two or more 
isolated nerves in separate areas of the body are affected 
 
Some neuropathies affect all three types of nerves, but most often, neuropathies 
primarily affect one or two types. Therefore, neuropathies may be further described as 
predominantly motor neuropathy, predominantly sensory neuropathy, sensory-motor 
neuropathy, or autonomic neuropathy. 
 
 Acute versus Chronic Neuropathies 
 
In acute neuropathies, such as Guillain-Barré syndrome, symptoms appear suddenly, 
progress rapidly, and resolve slowly as damaged nerves heal.  
 
In chronic neuropathies, symptoms begin subtly and progress slowly. There may be 
periods of relief followed by relapse. A plateau stage may be reached where symptoms 
stay the same for months or years. Some chronic neuropathies worsen over time, but 
fatality from neuropathy is extremely rare unless complicated by other diseases. 
Occasionally, neuropathy is a symptom of another disorder. 
 
 Acquired peripheral neuropathies 
 
Peripheral neuropathy may be either acquired or inherited. 
 
 Acquired vs. inherited peripheral neuropathies 
 
• Acquired peripheral neuropathies are grouped into three broad categories; those 
caused by: 
 systemic disease 
 trauma from external agents 
 infections or autoimmune disorders affecting nerve tissue 
 
Causes of acquired peripheral neuropathy include: 
 physical injury (trauma) to a nerve 
 tumors 
 toxins 
 autoimmune responses 
 nutritional deficiencies 
 alcoholism 
 vascular and metabolic disorders  
 

 
 
 
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• Inherited forms of peripheral neuropathy are caused by inborn mistakes in the 
genetic code or by new genetic mutations. Depending on the genetic 
error/mutation, inherited peripheral neuropathies can range from those with 
symptoms that begin in early adulthood and are minimal to more severe forms and 
symptoms/impairments that may begin in infancy or childhood. The most common 
inherited neuropathies are a group of disorders collectively referred to as Charcot-
Marie-Tooth disease that result from flaws in genes responsible for manufacturing 
neurons or the myelin sheath and are characterized by extreme weakening and 
wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon 
reflexes, and numbness in the lower limbs. 
 
 Diabetic Peripheral Neuropathy 
 
Diabetic peripheral neuropathy is a chronic acquired form of nerve damage that can 
occur in individuals with diabetes. High blood sugar can injure nerve fibers 
throughout the body, but diabetic neuropathy most often damages nerves in the legs 
and feet. 
 
ETIOLOGY 
 
The primary cause of diabetic peripheral neuropathy is damage to nerve fibers and 
blood vessels from prolonged exposure to high blood sugar (glucose). While the precise 
mechanism for this damage remains unclear, a combination of factors likely plays a role, 
including the complex interaction between nerves and blood vessels. High blood glucose 
interferes with the ability of the nerves to transmit signals and weakens the walls of the 
small blood vessels (capillaries) that supply the nerves with oxygen and nutrients. 
 
Other factors that may contribute to diabetic neuropathy include: 
 
• Inflammation in the nerves caused by an autoimmune response that occurs when the 
immune system mistakenly attacks part of the body as if it were a foreign organism. 
• Genetic factors unrelated to diabetes that make some people more susceptible to 
nerve damage. 
• Smoking and alcohol abuse which damage both nerves and blood vessels and 
significantly increase the risk of infections. 
 
Risk factors 
Anyone with diabetes can develop neuropathy, but the following factors increase the risk 
of susceptibility to nerve damage: 
 
• Poor blood sugar control is the greatest risk factor for every complication of diabetes, 
including nerve damage.  
• Duration of diabetes. The risk of diabetic neuropathy increases with increasing 
duration of diabetes, especially if there is also poo control of blood sugar. Peripheral 
neuropathy is most common in people who have had diabetes for at least 25 years. 
• Kidney disease. Diabetes can cause damage to the kidneys, which may increase the 
toxins in the blood and contribute to nerve damage. 
• Smoking narrows and hardens the arteries, reducing blood flow to the legs and feet, 
making it more difficult for wounds to heal and damages the integrity of the peripheral 
nerves. 

 
 
 
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PRESENTATION AND SYMPTOMS 
 
 Early, primary symptoms of diabetic peripheral neuropathy may include: 
 
• tingling, prickling, buzzing, pinching or burning feeling in the feet 
• pins and needles in the feet 
• sharp, jabbing, stabbing pains  
• cramps in the legs and feet 
• cold sensation 
• numbness or reduced ability to feel pain or changes in temperature, especially in 
the feet and toes 
 
Symptoms often worsen at night. 
 
 Progressive symptoms of diabetic peripheral neuropathy may include: 
 
• Touch sensitivity: heightened and/or extreme sensitivity to touch such as the 
weight of sheets or clothes being painful, or heightened tingling or numbness in 
the toes, feet, legs, or hands 
• Muscle weakness:  difficulty walking or getting up from a chair, grabbing things or 
carrying things with the hands as a result of muscle weakness from nerve damage 
• Balance problems: increased unsteadiness and incoordination when walking, 
occurring as the body adapts to changes brought on by muscle damage 
• Serious foot problems: such as ulcers, infections, deformities, and bone and joint 
pain 
 
 Complications: Diabetic neuropathy can cause numerous serious complications. 
Among the most serious are the following two complications: 
 
• Loss of a limb: As nerve damage can cause lack of feeling in the feet, cuts and 
sores can go unnoticed and eventually become severely infected or ulcerated. 
The risk of infection is high because diabetes reduces blood flow to the feet. 
Infections that spread to the bone and cause tissue death (gangrene) may be 
impossible to treat and require amputation of a toe, foot or even the lower leg. 
More than half the non-traumatic lower limb amputations performed every year in 
the United States are due to diabetes. 
• Charcot joint: This occurs when a joint, usually in the foot, deteriorates because of 
nerve damage. Charcot joint is marked by loss of sensation, as well as swelling, 
instability and sometimes deformity in the joint itself. 
• Neuropathic pain is difficult to control and can seriously affect emotional well-
being and overall quality of life. Neuropathic pain is often worse at night, seriously 
disrupting sleep and adding to the emotional burden of sensory nerve damage. 
 
DIAGNOSIS 
 
Patients being evaluated for diabetic peripheral neuropathy will have already been 
clinically diagnosed with diabetes and/or be evaluated for and diagnosed with diabetes 
prior to the evaluation for diabetic peripheral neuropathy. 
 
Diabetic neuropathy is diagnosed by a qualified physician based on a thorough 
evaluation of the patient’s symptoms, medical history and a physical exam that includes 

 
 
 
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assessment of blood pressure, heart rate, muscle strength and tone, tendon reflexes, 
and sensitivity to touch, position changes, temperature and vibration. 
A comprehensive foot exam assessing the skin, muscles, bones, circulation, and 
sensation of the feet is also performed as part of the diagnostic process.  
 
Specific tests that may be conducted as part of the diagnostic process include: 
 
• Filament test. Sensitivity to touch may be tested using a soft nylon monofilament or 
via pin prick. The inability to feel the filament on the foot or the pin prick is a sign that 
sensation in those nerves has been lost or diminished. 
• Tuning fork. A tuning fork is used for quantitative sensory testing to assess vibration 
and temperature change perception. 
• Nerve conduction studies or electromyography are sometimes used to help determine 
the type and extent of nerve damage. Nerve conduction studies check the 
transmission of electrical current through a nerve. Electromyography evaluates how 
well muscles respond to electrical signals transmitted by nearby nerves. These tests 
are rarely needed to diagnose neuropathy. 
 
CURRENT THERAPEUTIC APPROACHES TO THE MANAGEMENT OF CHRONIC 
PAINFUL DIABETIC PERIPHERAL NEUROPATHY    
 
Nerve pain from diabetic peripheral neuropathy can be severe, constant, and difficult to 
treat. As diabetic neuropathy is a many-faceted complication of diabetes, it is often best 
managed symptomatically with an array of drugs and/or treatments. In addition to 
optimal management of blood glucose levels (including a regimen of diet, exercise and 
medication), the following medications and therapies, and combinations therein, are 
used to assist in the management of painful diabetic peripheral neuropathy symptoms:  
 
(i) Over-the-counter (OTC) pain relief options: 
• OTC NSAIDs (nonsteroidal anti-inflammatory drugs), such as aspirin, ibuprofen 
(Advil, Motrin), and naproxen (Aleve) reduce inflammation and relieve pain. A 
downside of NSAIDs is the potential for harmful side effects such as stomach 
irritation and bleeding, or even kidney and liver damage, with prolonged use, which 
may be more likely in people with diabetes. 
• Acetaminophen medications relieve diabetes nerve pain without reducing 
inflammation and do not cause the stomach irritation of NSAIDs, but there is a risk 
of liver damage with excessive use.  
• Capsaicin is found naturally in chili peppers or in drug stores under various brand 
names, including Capzasin-P and Zostrix. Capsaicin is believed to ease pain by 
reducing a chemical called substance P, which is involved in transmitting pain 
signals through the nerves. Effective on a short-term basis, there are concerns 
about long-term consequences such as prevention wound healing, which is most 
serious in patients with diabetes. 
• Lidocaine is an OTC and/or prescription gel or cream anesthetic that numbs the 
area of application. Some product names include Topicaine and Xylocaine. 
• Other topical creams such as salicylate, a chemical similar to aspirin found in pain-
relieving creams like Aspercreme and Bengay; cortisone creams containing 
corticosteroids, potent anti-inflammatory drugs that can help relieve pain. However, 
there is no clear evidence that either helps relieve nerve pain from peripheral 
neuropathy. 

 
 
 
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(ii) Prescription pain relief options: 
• Prescription NSAIDs such as Celebrex, Lodine, and Relafen. As with the OTC 
NSAIDs, people with diabetes are at greater risk of kidney damage that can occur 
with prescription NSAIDs, and at greater risk of heart disease which may also be 
elevated with prescription NSAID use. 
• Antidepressants, such as: 
 Tricyclic antidepressants (TCAs) that primarily affect the levels of the brain 
chemicals norepinephrine and serotonin, such as Elavil, Pamelor and 
Norpramin. Side effects vary between the three, but can include drowsiness, 
weight gain, dry mouth, and dry eyes. For people with peripheral neuropathy, 
there may be additional side effects such as the development of blood 
pressure, heart rate problems and dizziness. 
 Selective serotonin reuptake inhibitors (SSRIs) that work by altering the 
amount of the brain chemical serotonin, but these are the least effective for 
pain management. 
 Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as Effexor and 
Cymbalta, affect the levels of the brain chemicals serotonin and 
norepinephrine. They are quite effective for pain relief with fewer side effects 
than the SSRIs or TCAs. Cymbalta is FDA-approved for painful neuropathy. 
• Antiseizure drugs that prevent epileptic seizures can also relieve neuropathic pain 
by controlling the abnormal firing of nerve cells. These drugs include: 
 Neurontin is most commonly used for nerve pain from peripheral neuropathy. 
Side effects include causing sedation or dizziness at higher doses.  
 Lyrica is FDA-approved for painful neuropathy. The most common side effects 
are dizziness and sleepiness.  
• Opioid medicines such as Ultram and Ultracet, are strong pain killers for when 
pain is very severe and immediate relief is needed. Ultram and Ultracet are FDA-
approved painkillers that contain tramadol, a weak opioid (morphine-like) 
substance. The drug also weakly affects the brain chemicals serotonin and 
norepinephrine, similar to antidepressants, which reduces the perception of pain. 
• Tramadol is often used as a back-up for "breakthrough pain" - pain that suddenly, 
for no apparent reason, is worse. Tramadol is a good replacement for over-the-
counter medications at those times. However, strong narcotic opioid medications 
can cause severe constipation and have the potential for addiction.  
 
(iii) Additional and Alternative Treatment Options: 
• Injections of local anesthetics such as lidocaine - or patches containing lidocaine 
– can be used to numb the painful area for severe, intractable diabetes nerve 
pain. 
• Surgical destruction of nerves or to relieve a nerve compression that causes pain. 
• Implantation of a device that relieves pain.  
• Transcutaneous electrotherapy and percutaneous electrical nerve stimulation are 
alternative therapies that provide electrical nerve stimulation wherein small 
amounts of electricity are used to block pain signals as they pass through the skin. 

 
 
 
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• Hand or foot braces to compensate for muscle weakness or to help relieve nerve 
compression. 
• Orthopedic shoes to improve gait (walking) problems to will prevent foot injuries.  
 
 
 
 

 
 
 
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THEORY OF MECHANISM OF OPERATION OF THE APPLICATION OF LOW-LEVEL 
LASER THERAPY TO REDUCING PAIN   
 
“Low-energy photon irradiation by low level laser light lasers or LED arrays has been 
found to modulate various biological processes in cell culture and animal models. This 
mechanism of photobiomodulation by LLLT lasers or LED arrays at the cellular level has 
been ascribed to the activation of mitochondrial respiratory chain components, resulting 
in initiation of a signaling cascade that promotes cellular proliferation and 
cytoprotection.”  
Source: Proc Natl Acad Sci U S A. 2003 Mar18; 100(6): 3439-44. 2003 Mar 07. 
 
When applied to injuries and lesions, low level laser light has been shown to stimulate 
healing and to reduce pain by accelerating the speed, quality and strength of tissue 
repair and the reduction of inflammation. Furthermore, laser therapy has been found to 
be particularly effective over other standard therapies in relieving pain and other 
symptoms associated with injuries as it impacts the complete system of targeted 
muscles, tendons, ligaments, connective tissue, bone, nerve, and dermal tissues.     
                       
Lasers can strengthen damaged cells. Using photochemical processes, laser light 
inserts bio-photons into damaged cells. The cells begin to produce energy (ATP), which 
improves their function, assists their division, strengthens the body's immune system, 
and causes the secretion of various hormones. The tissues are healed, and pain 
diminishes. If damaged cells have died, the bio-photons help the division of neighboring 
cells, generating new tissues, and thus bring about healing.  
 
Therefore, LLLT promotes healing, regeneration and pain reduction through the 
following mechanisms: 
 
1) increased cell membrane polarization and permeability 
2) increased ATP production and respiratory chain activity 
3) increased enzyme activity 
4) increased collagen and epithelial production 
5) increased capillary formation 
6) increased macrophage (immune) activity 
7) analgesic effects due to elevated endorphin production, electrolytic nerve blockage, 
and improved blood and lymph flow 
8) anti-inflammatory effect due to improved circulation and accelerated tissue 
regeneration; and 9) increased production of antioxidants. 
 
Of additional benefit is that light energy from low level lasers will only be absorbed by 
those cells and tissues that are not functioning normally and that need it. Soft laser light 
has no effect on healthy cells. 
 
The progressive process by which low level laser light aids in the production of ATP, 
consequently providing cells with more energy which in turn optimizes the cells’ 
condition to play their part in a natural healing and pain reduction process, is as follows: 
 
 

 
 
 
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The effects of low-level laser light are photo-chemical (not thermal), 
triggering normal cellular function. 
 
PHOTONS 
 
 
 
ABSORBED IN CYTOCHROMES & PORPHYRINS  
WITHIN THE MITOCHONDRIA  
AND AT THE CELL MEMBRANE 
 
 
 
SINGLET OXYGEN PRODUCTON 
 
 
 
FORMATION OF PROTOC GRADIENTS ACROSS CELL MEMBRANE  
AND ACROSS MEMBRANE OF MITOCHODRIA 
 
 
  
  CHANGES IN         INCREASED                 DNA 
                                    CELL MEMBRANE     ATP LEVELS           PRODUCTION 
                                        PERMEABILITY 
 
 
PHYSIOLOGICAL CHANGES 
 
 
THEORY OF MECHANISM OF OPERATION OF THE APPLICATION OF LOW-LEVEL 
LASER THERAPY TO REDUCING CHRONIC DIABETIC PERIPHERAL 
NEUROPATHY PAIN   
 
Considering the general mechanism of operation of LLLT as explained above, it follows 
that LLLT provides relief from the foot pain from chronic diabetic peripheral neuropathy 
by: 
 
• penetrating the skin of the foot and the ligaments and tendons to increase the 
production of 
ATP and activate enzymes in the targeted cells of the tissue to promote healing of the 
tendons and ligaments 
   • cultivating a growth factor response within the cells and tissue of the foot as a result of 
the increased ATP production to promote new, healthier cell and tissue growth to 
strengthen and support ligaments and tendons, to restore mechanical and sensory 
function, and to protect against further damage 
• The anti-inflammatory properties of low-level lasers reduce nerve irritation and 
inflammation in the foot to provide pain relief 
 
 
 
 

 
 
 
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ERCHONIA CORPORATION LLLT LASER DEVICES AND PAIN REDUCTION 
INDICATIONS 
 
Erchonia Corporation’s 635nm red diode low-level lasers have been shown through 
controlled clinical trials to be effective for pain reduction, as evidenced through the 
following FDA 510(k) approvals for various pain reduction indications based on the 
supportive outcome of those clinical trials. 
 
1. K180197: Erchonia® FX-635: is indicated for the following two indications: 
a. as an adjunct to provide relief of minor chronic low back pain of musculoskeletal 
origin. 
b. as an adjunct to reducing chronic heel pain arising from plantar fasciitis. 
 
2. K132940: Erchonia® Allay™: is indicated as an adjunct to reducing chronic heel pain 
arising from plantar fasciitis. 
 
3. K072206: Erchonia® EML Laser: is indicated for the temporary reduction in post-
surgery pain at 24 hours after surgery following bilateral breast augmentation surgery. 
 
4. K041139: Erchonia® EML Laser: is indicated as an adjunct to liposuction procedures 
of the thighs, hips and stomach for reduction of pain associated with the recovery 
process. 
 
5. K012580: Erchonia PL2000: is indicated for adjunctive use in providing temporary relief 
of minor chronic neck and shoulder pain of musculoskeletal origin. 
 
 
STUDY RATIONALE & JUSTIFICATION 
 
The chronic pain of diabetic peripheral neuropathy can be debilitating, impacting the 
individual’s day-to-day functionality that further leads to physical, cognitive, 
psychological, sleep and social impairments. Additionally, diabetic neuropathic pain 
patients are typically burdensome to the health care system, frequently seeking relief 
from the persistent pain. Many afflicted also suffer economically, as coping with the 
chronic pain of the condition may render them unemployable or under-employed. 
 
Current therapeutic approaches for managing the chronic pain of diabetic peripheral 
neuropathy are primarily over-the-counter and prescription medications. However, in 
addition to their general limited effectiveness, many have harmful side effects with 
prolonged use such as stomach irritation and bleeding, kidney and liver damage, 
prevention of wound healing, elevated blood pressure and heart rate problems which 
can be both more likely to occur and more likely to pose serious implications for 
individuals with diabetes. Additional potential side effects include dizziness, drowsiness, 
weight gain, dry mouth, and dry eyes, as well as the potential for addiction with certain 
prescription medications. Non-medication alternatives are also of limited effectiveness 
and most, including injections of local anesthetics, surgical destruction of nerves, device 
implantation and transcutaneous electrotherapy and percutaneous electrical nerve 
stimulation are costly, invasive and carry their owns set of potentially harmful and lasing 
side effects.    
 
Low level laser light therapy, such as that provided through application of the Erchonia® 
FX-635™ Laser as proposed in this study protocol, offers a simple, quick, non-invasive, 

 
 
 
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safe, effective and side-effect free option to reduce diabetic peripheral neuropathy pain. 
Prior trials with Erchonia low level lasers have demonstrated their efficacy in reducing 
chronic pain in various clinically diagnosed chronic pain conditions, and in post-surgical 
pain, in a clinically meaningful and statistically significant manner, as is the treatment 
goal being evaluated in the current clinical study.  
 
Specific Justification for the assertion of anticipated safety and effectiveness of the 
Erchonia® FX-635™ for application to reducing chronic pain arising from diabetic 
peripheral neuropathy is found through the following FDA clearances for Erchonia® low 
level laser devices for chronic pain reduction and post-surgical pain reduction 
indications, each device of whose technical specifications and outputs are comparable to 
those of the Erchonia® FX-635™ as presented in the current clinical study protocol:  
For all of the respective 510(k) clearances, the assigned Product Code is NHN, defined 
as follows:  
 Device: Powered Light Based Non-Laser Non-Thermal Instrument With Non-Heating 
Effect For Adjunctive Use In Pain Therapy 
 Regulation Description: Infrared lamp 
 Definition: A light based non-laser device that emits energy in infrared or other 
wavelengths, provides non-heating and non-thermal effect, and is indicated for 
adjunctive use in pain therapy or related indication. It does not provide therapeutic 
topical heating. The classification regulation for infrared lamps describes a device 
that emits energy in the infrared wavelength to provide topical heating and that is not 
limited to adjunctive use. 
 Device Class: 2 
 
The above-referenced 510(k) clearances are the following: 
 
1. K180197: Erchonia® FX-635: is indicated for the following two indications: 
a. as an adjunct to provide relief of minor chronic low back pain of musculoskeletal 
origin. 
b. as an adjunct to reducing chronic heel pain arising from plantar fasciitis. 
 
2. K132940: Erchonia® Allay™: is indicated as an adjunct to reducing chronic heel pain 
arising from plantar fasciitis. 
 
3. K072206: Erchonia® EML Laser: is indicated for the temporary reduction in post-
surgery pain at 24 hours after surgery following bilateral breast augmentation surgery. 
 
4. K041139: Erchonia® EML Laser: is indicated as an adjunct to liposuction procedures 
of the thighs, hips and stomach for reduction of pain associated with the recovery 
process. 
 
5. K012580: Erchonia PL2000: is indicated for adjunctive use in providing temporary relief 
of minor chronic neck and shoulder pain of musculoskeletal origin. 
 
Therefore, Erchonia® low level lasers of comparable configuration, technical 
specification and application as proposed in this current clinical study protocol have 
been determined to be safe and effective by the FDA for various pain reduction 
indications, including an indication for reducing chronic heel pain arising from plantar 
fasciitis, such that evaluation of application of the Erchonia® low level laser to reducing 

 
 
 
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chronic diabetic peripheral neuropathy foot pain is a natural extension of its proven and 
accepted application for chronic pain reduction purposes.  
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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DEVICE INFORMATION: ERCHONIA® FX-635™ 
 
REGULATORY BACKGROUND 
 
The Erchonia® FX-635™ Laser being evaluated in this clinical study for use as an 
adjunct to reduction of chronic diabetic peripheral neuropathy foot pain is identical to the 
laser devices that received FDA 510(k) clearance for market for the following pain 
reduction indications. 
 
1. K180197: Erchonia® FX-635: is indicated for the following two indications: 
a. as an adjunct to provide relief of minor chronic low back pain of musculoskeletal 
origin. 
b. as an adjunct to reducing chronic heel pain arising from plantar fasciitis. 
 
2. K132940: The Erchonia® Allay™ laser is indicated as an adjunct to reducing chronic 
heel pain arising from plantar fasciitis. 
 
The Erchonia® FX-635™ laser device to be used in this clinical study is identical in 
design, configuration and technical specifications including dosage output and energy 
delivered to the skin as the above Erchonia laser devices whose FDA clearance was 
attained following review of the outcome of a controlled clinical trial that supported the 
respective indications.   
 
DEVICE DESCRIPTION & DETAILS 
 
The Erchonia® FX-635™ used in this study is made up of 3 independent 17 mW, 635 
nm red laser diodes mounted in scanner devices with flexible arms positioned 
equidistant from each other.  
 
The Erchonia® FX-635™ is a variable hertz device. The variable hertz feature of the 
Erchonia® FX-635™ is a pulsed wave, defined as containing a selected series of 
breaks, variances that are preprogrammed. 
   
The Erchonia® FX-635™ utilizes internal mechanics that collects the light emitted from 
each of the laser diodes and processes each through a proprietary patented lens which 
redirects the beam with a line refractor. The refracted light is then bent into a spiraling 
circle pattern that is totally random and independent of the other diodes.  
 
The Erchonia® FX-635™ has the following specifications:   
 
 Configuration: Class 2 Line Generated Laser Diode Modules 
 Wavelength: 635 nm  
 Power Output (Mean): 17 mW 
 Modulation: Pulsed Wave (50% duty Cycle 
 Display: Full Color TFT Touch Screen Control Center 
 Adjustments: 
• 44” Vertical Arm Height Adjustment. 
• Three Independent Adjustable Arms 
 Power Source: 100-240 VAC 50-60 Hz 
 Chassis: 
• Metal Frame Powder Coated for Ease of Cleaning 

 
 
 
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• 4 Anti-Static Casters (4 Locking) 
 Housing: Black Carbon Fiber Finish Thermoformed from Non-Allergen 
Material/Plastic 
 Weight: 70 lbs. 
Dosage calculations for the Erchonia® FX-635™ 
 
Equations:  
1) Intensity = W/cm2  
2) Dosage = (J/cm2)=(W/cm2) x τ(s)  
3) Oval Surface area = π x (r1/2) x (r2/2)  
MW = miliwatts  
W= Watts 
 
Intensity:  
Intensity ÷ oval surface area = intensity at tissue  
1) 17.5 mW / 1000 = 0.0175 W (Intensity conversion from mW to W)  
2) π x (9cm/2) x (9.5cm/2) = 21.375 cm2 (surface area of treated region at single diode 
at 3.5”  above the skin surface.  
3) 0.0175 / 21.375 cm2 = 8.2 x10-4 W/cm2 (intensity for single diode at skin)  
4) 8.2 x 10-4 W/cm2 x (3 diodes) = 2.46 x10-3 W/cm2 (intensity for all 3 diodes 
combined at the skin)  
 
Dosage delivered to the skin:  
Intensity x τ(s) = dosage at specific area  
1) 2.46 x 10-3 W/cm2 x (900 seconds) = .0865 J/cm2 (total dosage delivered to the skin) 
 
 
The Erchonia® FX-635™ used in this study is shown in Figures 1 and 2 below. 
 
 

 
 
 
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Figure 1: Erchonia® FX-635™ 
Figure 2: Erchonia® FX-635™ 

 
 
 
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The Erchonia® FX-635™ System Components is shown in Figures 3 and 4 below. 
 
 
 
 
Figure 3: Erchonia® FX-635™ System Components 
 
1. Power Safety Lockout Key 
2. Touch Screen 
3. Main Upright of Base 
4. Power Inlet/Fuse Holder 
5. Arm Lock (Fig. 2) 
6. Wheel Lock 
7. Boom Arm 
  8. Center Head Adjustment Knob 
  9. Laser Head Assembly 
10. Upper Arms 
11. Upper/Lower Pivots 
12. Laser Output Heads 
13. Locking Knob – not shown 
14. Power Cord – not shown 
15. Electrical Connector – not shown 
 
POWER SAFETY LOCKOUT KEY (1) 
The Power Safety Lockout Key is the outwardly visible portion of an internal locking 
mechanism on top of the touch screen [2] 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. 
 
TOUCH SCREEN (2) 
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. 
 
MAIN UPRIGHT OF BASE (3) 
The main upright of base supports the boom arm and contains the electrical connector 
(See Setup) and the Locking Knob [13]. 
 

 
 
 
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POWER INLET/FUSE HOLDER (4) 
The device contains an appliance coupler (power inlet) and a flexible detachable power 
cord [14].  This is the location on the device where the power cord is connected. 
 
ARM LOCK (5) 
The Arm Lock is the black lever attached to the side of the Boom Arm.  This is a 
secondary locking mechanism for the boom arm.  The arm tension can be adjusted or 
locked into position with the arm lock lever.   
 
WHEEL LOCKS (6) 
The device includes four antistatic wheels that enable ease for maneuverability.  Once 
the device is transported to the desired location the wheel locks can be engaged to 
eliminate excessive movement of the device. 
 
BOOM ARM (7) 
The Boom Arm serves to position the Laser Head Assembly [9] vertically only.  It is 
designed to adjust by intentional force from the end user.  This allows the end user to 
lower and raise the Laser Output Heads for proper positioning to patient for accurate 
treatment distance. 
 
CENTER HEAD ADJUSTMENT KNOB (8) 
The Center Head Adjustment Knob [8] serves to adjust the treatment height of the center 
head.  This also acts as the locking mechanism for the center head.   
 
LASER HEAD ASSEMBLY (9) 
This three head assembly located on the end of the laser arm (boom arm) 
accommodates the laser output heads, pivots, arms and center head adjustment knob.  
This assembly can be rotated 120 degrees for proper positioning to patient for accurate 
treatment. 
 
UPPER ARMS (10) 
The upper arms serve as a positioning support for Laser Output Heads [12].  It is 
designed to adjust by intentional force from the end user.  This allows the end user to 
lower and raise the Laser Output Heads for proper positioning to patient for accurate 
treatment distance. 
 
UPPER/LOWER PIVOTS (11) 
The upper and lower pivots serve as a positioning support for Laser Output Heads [12].  
It is designed to adjust by intentional force from the end user.  This allows the end user 
to move the laser output heads in and out, as well as side to side for proper positioning 
to patient for accurate treatment distance. 
 
LASER OUTPUT HEADS (12) 
The three plastic housings located on the end of the Lower Pivots [11] as well as the 
center of laser head assembly [9], accommodates the lens, laser diodes, motors, and 
their associated electronics.  The side heads are designed to adjust by intentional force 
from the end user; this allows the end user to change the angle of the laser output heads 
for proper positioning to patient for accurate treatment distance.  The center head is 
designed to be adjusted by center head adjustment knob [8]. 
 

 
 
 
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LOCKING KNOB (13) 
The locking Knob is utilized to secure the two-piece assembly [3 & 7], also preventing 
the boom arm assembly from unwanted rotation during use. 
 
POWER CORD (14) 
The device contains a flexible detachable power cord.   
 
ELECTRICAL CONNECTOR (15) 
The electrical connector is a two-piece assembly.  The electrical connector connects the 
main head assembly to the base assembly in order to transfer data and power. 
 
This pictorial shows the simple 2-piece 
assembly of the scanner.  This assembly 
is best done with 2 people. 
 
The 2 major components are the arm [7] 
and base [3]. 
 
Figure 4: Erchonia® FX-635™ Assembly 
 
 
 
 

 
 
 
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DEVICE SAFETY 
 
RISK AND PREVENTION OF EYE INJURY 
The Erchonia® FX-635™ 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 
subject. 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, eye protection is implemented 
for both the investigator administering the study procedures with the Erchonia® FX-
635™ Laser and for the subject receiving the laser procedure administrations. 
 
A pair of specialty safety glasses is provided for use during all procedure applications. 
These safety glasses are Laser Safety Industries PN: 100-40-240 light blue safety 
glasses. These safety glasses have the following specifications: 
 
 OD 4+ @ 630-690 nm 
 OD 7+ @ 690-970 nm 
 OD 5+ @ 970-1100 nm 
 VLT 36% 
 
The Laser Safety Industries PN: 100-40-240 light blue safety glasses are shown in 
Figures 5 & 6 below. 
 
 
 
Figure 5: Laser Safety Industries PN: 100-40-240 Safety Glasses* 
 
*The block out glasses are specifically for the clinical trial 
 
 
 

 
 
 
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Figure 6: Laser Safety Industries PN: 100-40-240 Safety Glasses Specifications

 
 
 
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FOOD AND DRUG ADMINISTRATION (FDA) DETERMINATION OF NON-
SIGNIFICANT RISK (NSR) STATUS 
 
(i) Regulatory Clearances: The Food and Drug Administration (FDA) has determined the 
family of Erchonia® low level laser devices, including those employing 635 nm red 
diodes, to be non-significant risk (NSR) through numerous 510(k) clearances, 
including several for pain relief indications, as follows. 
 
1. K180197: Erchonia® FX-635: is indicated for the following two indications: 
a. as an adjunct to provide relief of minor chronic low back pain of musculoskeletal 
origin. 
b. as an adjunct to reducing chronic heel pain arising from plantar fasciitis. 
 
2. K132940: Erchonia® Allay™: is indicated as an adjunct to reducing chronic heel pain 
arising from plantar fasciitis. 
 
3. K072206: Erchonia® EML Laser: is indicated for the temporary reduction in post-
surgery pain at 24 hours after surgery following bilateral breast augmentation surgery. 
 
4. K050672: Erchonia® EVRL Laser: The Erchonia EVRL Laser is generally indicated: 
 
a. while using the red diode, for adjunctive use in providing temporary relief of minor 
chronic neck and shoulder pain of musculoskeletal origin, and 
b. while using the blue diode, to treat dermatological conditions, and specifically 
indicated to treat moderate inflammatory Acne Vulgaris. 
 
5. K041139: Erchonia® EML Laser: is indicated as an adjunct to liposuction procedures 
of the thighs, hips and stomach for reduction of pain associated with the recovery 
process. 
 
6. K100509 & K130741: Erchonia® THL1 Laser & Erchonia® PL5000: is indicated for 
adjunctive use in providing temporary relief of minor chronic neck and shoulder pain 
of musculoskeletal origin. 
 
7. K130996: Erchonia® XLR8™: The Erchonia XLR8™ is indicated for the following 
three indications: 
 
a. adjunctive use in providing temporary relief of minor chronic neck and shoulder 
pain of musculoskeletal origin 
b. as an adjunct to liposuction procedures of the thighs, hips and stomach for 
reduction of pain associated with the recovery process 
c. temporary reduction in post-surgery pain at 24 hours after surgery following 
bilateral breast augmentation surgery 
 
8. K142042: Erchonia® SHL Laser: is indicated for use as a non-invasive dermatological 
aesthetic treatment for reduction of circumference of hips, waist and upper abdomen when 
applied to individuals with a Body Mass Index (BMI) between 30 kg/m² and 40 kg/m². 
 
9. K130922: Erchonia® Verju Laser System with Massager: is indicated for use as a 
non-invasive dermatological aesthetic treatment as an adjunct for individuals 
intending to undergo liposuction procedures for the reduction of circumference of 

 
 
 
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hips, waist and thighs. The Massager component is indicated for the temporary 
reduction in the appearance of cellulite. 
 
10. K123237 & K133718: Erchonia® Zerona™ 2.0 Laser & Zerona®-Z6: is indicated for 
use as a non-invasive dermatological aesthetic treatment as an adjunct for 
individuals intending to undergo liposuction procedures for the reduction of 
circumference of hips, waist, and thighs. 
 
11. K121695 & K082609: Erchonia® ML Scanner (MLS) & Erchonia® Zerona: is 
indicated for use as a non-invasive dermatological aesthetic treatment as an adjunct 
for individuals intending to undergo liposuction procedures for the reduction of 
circumference of hips, waist, and thighs. 
 
12. K21690 & K120257: Erchonia® MLS, Zerona, Zerona-AD: is indicated for use as a 
non-invasive dermatological aesthetic treatment as an adjunct for individuals 
intending to undergo liposuction procedures for the reduction of circumference of the 
upper arms. 
 
13. K101430: MLS-AC Derma Scanner™: is indicated while using the red diodes for 
adjunctive use in providing temporary relief of minor chronic neck and shoulder pain 
of musculoskeletal origin, and while using the blue diode, to treat moderate 
inflammatory Acne Vulgaris. 
 
14. K082609: Erchonia® ML Scanner (MLS): is indicated for use as a non-invasive 
dermatological aesthetic treatment for the reduction of circumference of hips, waist 
and thighs. 
 
(ii) Pre-IDE Reviews: FDA has previously reviewed numerous clinical study protocols 
employing various Erchonia® Corporation low level laser devices, including all of the 
clinical studies conducted in support of the above 510(k) clearances and those 
employing 635 nm red diodes. For all of the FDA’s pre-IDE reviews of Erchonia low 
level laser clinical study protocols, there was concurrence from FDA that the clinical 
study protocols and application of the Erchonia laser devices therein were 
considered non-significant risk (NSR). 
 
INSTITUTIONAL REVIEW BOARD (IRB) DETERMINATION OF NON-SIGNIFICANT 
RISK (NSR) STATUS 
 
Erchonia® Corporation low level laser devices have been determined to be non-
significant risk (NSR) when applied in various clinical studies through several IRBs, 
including those involving application of 635 nm red diode energy and application for pain 
reduction indications, as follows: 
 
 Western Institutional Review Board (WIRB®) has previously determined Erchonia 
low level laser devices to be non-significant risk (NSR) when applied in the following 
clinical studies: 
 
1. WIRB PRO NUM: 20141594: Erchonia® Verju™: An evaluation of the effect of 
the Erchonia® Verju™ laser with Suprenza™ to reduce central adiposity in 
overweight and obese individuals  
 

 
 
 
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2. WIRB PRO NUM: 20140748: Erchonia® ZERONA® Z6: Evaluation of efficacy, 
usability and labeling comprehension for over-the-counter use of the Erchonia 
Corporation ZERONA® Z6 for body contouring of the waist, hips and thighs  
 
3. WIRB PRO NUM: 20140535: Erchonia® EML Laser: A randomized evaluation of 
the effect of the Erchonia® EML laser on the autologous transfer of fat to the 
hands from fat harvested during laser-assisted liposuction of the thighs and/or 
hips and/or stomach pilot study 
 
4. WIRB PRO NUM: 20131165: Erchonia® ZERONA 6 Headed Scanner (EZ6): An 
evaluation of the effect of the Erchonia® ZERONA 6 Headed Scanner (EZ6) six-
week treatment protocol on circumference reduction of the waist, hips, highs and 
upper abdomen clinical study  
 
5. WIRB PRO NUM: 20130851: Erchonia® ML Scanner (MLS): An evaluation of the 
effect of the Erchonia® ML Scanner (MLS) laser on increasing blood circulation in 
individuals with chronic heel pain clinical study   
 
6. WIRB PRO NUM: 20130488: Erchonia® TMJ laser: A pilot evaluation of the effect 
of the Erchonia® TMJ Laser on reducing jaw pain and improving jaw function for 
individuals with temporomandibular joint (TMJ) disorder   
 
7. WIRB PRO NUM: 20130343: Erchonia® Obesity Laser: A double-blind, placebo-
controlled randomized evaluation of the Erchonia® Obesity Laser on the reduction 
of the circumference of the hips, waist and upper abdomen for individuals with 
Body Mass Index (BMI) of 40 to 40 kg/m²  
 
8. WIRB PRO NUM: 20121548: Erchonia® MLS: A double-blind, placebo-controlled 
randomized evaluation of the effect of the Erchonia® ML Scanner (MLS) laser on 
reducing pain associated with degenerative arthritis (osteoarthritis) of the midfoot 
clinical study protocol 
 
9. WIRB PRO NUM: 20120787: Erchonia® MLS: A double-blind, placebo-controlled 
randomized evaluation of the effect of the Erchonia® ML Scanner (MLS) on low 
back pain clinical study protocol 
 
10. WIRB PRO NUM: 20111793: Erchonia® MLS: A double-blind, placebo-
controlled randomized evaluation of the effect of the Erchonia® ML Scanner 
(MLS) laser on chronic heel pain clinical study protocol 
 
11. WIRB PRO NUM: 20110331: Erchonia® MLS: An evaluation of the effectiveness 
of the Erchonia® ML Scanner (MLS) as a non-invasive dermatological aesthetic 
treatment for the reduction of circumference of the upper arms clinical study 
protocol  
 
12. WIRB PRO NUM: 20120911: Erchonia® MLS: A double-blind, placebo-
controlled randomized evaluation of the effect of the Erchonia® ML Scanner 
(MLS) on body contouring of the waist, hips and thighs five-day treatment 
protocol clinical study protocol 
 
13. WIRB PRO NUM: 20110758: Erchonia® MLS: A pilot evaluation of the effect of 
the Erchonia® ML Scanner (MLS) laser device on enhancing body weight loss, 

 
 
 
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fat loss and circumference reduction of the waist, hips and thighs clinical study 
protocol  
 
14. WIRB PRO NUM: 20121330: Erchonia LUNULA™: An Evaluation of the Effect 
of the  Erchonia LUNULA™ on Treating Toenail Onychomycosis Clinical Study 
Protocol; Version 6.0 August 7, 2012  
 
15. WIRB PRO NUM: 20110461: Erchonia FX-405™: An Evaluation of the Effect of 
the  Erchonia FX-405™ on Treating Toenail Onychomycosis Clinical Study 
Protocol; Version 3.0 March 19, 2011  
 
16. WIRB PRO NUM: 20120489: Erchonia® MLS: A double-blind, placebo-
controlled randomized evaluation of the effect of the Erchonia® ML Scanner 
(MLS) on lipid panel levels clinical study protocol 
 Independent Review Consulting, Inc.’s/Ethical and Independent Review Services has 
previously determined Erchonia low level laser devices to be non-significant risk 
(NSR) when applied in the following clinical studies: 
 
1. IRC# 07150, NSR# DER-006: Erchonia® MLS: A double blind, placebo-controlled 
randomied evaluation of the effect of the Erchonia® ML Scanner (MLS) on body 
contouring  of the waist, hips and thighs clinical study protocol.  
 
2. IRC# 09120, NSR# DER-015: Erchonia® MLS: A double-blind, placebo-controlled 
randomized evaluation of the effect of the Erchonia® ML Scanner (MLS) on 
reducing the appearance of cellulite clinical study protocol.  
 
3. IRC# 08167, NSR# DER-009: Erchonia® MLS: A double blind, placebo-controlled 
randomized evaluation of the effect of the Erchonia® ML Scanner (MLS) on 
capsular contracture clinical study protocol.  
 
4. IRC# 09059, NSR# DER-010: Erchonia® MLS: A double blind, placebo-controlled 
randomized evaluation of the effect of the Erchonia® ML Scanner (MLS) in 
combination with silicone sheets on cellulite pilot study protocol.  
 
 Chesapeake Research Review, Inc. determined the Erchonia® ML Scanner (MLS) 
laser device to be a non-significant risk (NSR) device when applied in the following 
study: 
 
1. Pro. # 00006393: Erchonia® MLS: A pilot evaluation of the effect of the  
Erchonia® ML Scanner (MLS) as applied to the abdomen on reducing visceral 
abdominal fat in patients with HIV-associated lipodystrophy.  
 
 
OTHER POTENTIAL RISKS 
 
Other potential risks and their mitigation include:  
 
(i) 
Electric shock: operator risk only: mitigated through electrical safety testing. 
(ii) Electromagnetic interference: mitigated through EMC/EMI testing. 
(iii) User error: mitigated through instructions for use documentation. 
 
 

 
 
 
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In accordance with ISO 14971 and Erchonia published SOPs, any risks associated with 
this device has been reduced to as far as possible. 
 
 
 
 
 
 
 
 
 
 
 
STUDY DESIGN 
 
This clinical study is a double-blind, placebo-controlled randomized parallel group design 
multi-site evaluation of the effect of the Erchonia® FX-635™ on providing relief of 
chronic foot pain arising from diabetic peripheral neuropathy. 
 
SUBJECT GROUPS  
 
Each subject will be randomized to the test procedure group or to the placebo procedure 
group, as follows: 
 
Test procedure group: Subjects randomized to the test procedure group will receive the 
study procedures with the active (true) Erchonia® FX-635™ laser.  
 
Control procedure group: Subjects randomized to the control procedure group will 
receive the study procedures with a ‘fake’ (placebo) Erchonia® FX-635™ laser.   
 
The ‘fake’ (placebo) laser device will appear to the subject to be an active device but will 
not produce any therapeutic light output. The placebo laser device is designed to have 
the same physical appearance as the actual (active test) laser device, including the 
appearance of any visible light output. Therefore, both the test and control devices emit 
light when activated that is indistinguishable to the subject. As the laser light does not 
put out any notable degree of heat or noise, these are not distinguishing factors for 
subjects between the active and control devices.  
 
Apart from the distinction of whether the subject receives the study procedures with the 
actual or the fake laser device, all subjects and investigative parties will adhere to all 
phases of the entire protocol design.   
 
DOUBLE BLIND DESIGN  
 
This clinical study will be a double-blind design, such that neither the subject nor the 
investigator will be aware of whether a subject is receiving the study procedures with the 
active (test procedure group assignment) or the ‘fake’ (placebo procedure group 
assignment) Erchonia® FX-635™ until after the study is completed.  
 
Maintenance of study double-blind throughout the entire course of the study will be 
achieved through the following means: 

 
 
 
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1) Each subject will be randomly assigned to Procedure Group A or to Procedure 
Group B by the independent study Monitor. Subjects assigned to Procedure Group A 
will be treated with the Erchonia® FX-635™ A and subjects assigned to Procedure 
Group B will be treated with Erchonia® FX-635™ B. Only the study Sponsor will 
know which label (‘A’ or ‘B’) corresponds to the actual (test) FX-635™ device and 
which label corresponds to the ‘fake’ device until the final study data analysis is 
complete. The Sponsor will ensure that this information is stored and maintained 
confidentially at the Sponsor’s work site. This knowledge will not be shared with the 
investigators, the subjects, or the study Monitor until the final data analysis is 
complete. 
 
2) The fake (placebo) Erchonia® FX-635™ is designed to have the same physical 
appearance as the actual Erchonia® FX-635™, including the appearance of any 
visible light output, with the placebo device employing a 635 nm LED rather than a 
635 nm laser diode in the active device. Therefore, both the test and sham devices 
emit light when activated that is indistinguishable to both the subject and to the 
investigator. As the laser light does not put out any notable degree of heat or noise, 
these are not distinguishing factors for subjects between the two groups.  
 
3) There will be two independent investigators interacting with subjects: (i) 
administration investigator: who will be responsible for administrating the study 
treatments; (ii) assessment investigator: who will be responsible for recording the 
study outcome measures. Only the administration investigator will be aware of 
whether a subject is assigned to Procedure Group A or B, although he or she will not 
be made aware of whether A or B corresponds to the true or fake laser. Neither the 
assessment investigator nor the subject will be aware of the subject’s A/B Group 
assignment. In this way, the assessment investigator will not be able to form an 
association between A/B Procedure Group and active/sham device over the course 
of the study if a treatment effect is observed. 
 
4) During the laser procedures, both the subject and the administration investigator will 
wear safety glasses that filter out the laser light spectrum. 
 
RANDOMIZATION 
 
Subject allocation to procedure group will be via variable block randomization with 
varying block sizes of two, four and six used at random to minimize the likelihood of 
predicting the next procedure group assignment. In addition, randomization will be 
stratified by test site. 
 
Randomization will be attained using computer generation sequence methodology, 
insuring that the randomization methodology and the generated allocation sequence is 
concealed from the investigator and subjects.  
 
Concealment will be insured as follows: 
 
(ii) Each computer-generated randomization sequence is unique and will therefore not 
be able to be replicated. 
(iii) Randomization will occur to either ‘Procedure Group A’ or to ‘Procedure Group B’ 
rather than to a test or placebo group, and only the Investigational Device Engineer 
will know which assignment (A or B) corresponds to the active device and which 

 
 
 
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corresponds to the fake device. The Engineer will not reveal this information to any 
source (investigators, subjects, CRO, or Sponsor) until the final study data analysis 
is complete and the Post-Study Open-Label phase begins. 
 
Once a subject has signed the informed consent form, the Principal Investigator will 
contact the Sponsor (via email or phone) who will act as the central source for providing 
sequential subject procedure group assignment.  
 
SUBJECTS  
 
Subject Sample 
Subjects will be males and females aged 18 years or older who have diagnosed diabetic 
peripheral neuropathy with pain persisting over at least the past three months.  
 
Sample size  
There will be 64 qualified subjects enrolled in this clinical study: 
 
32 subjects in the active procedure group 
32 subjects in the control procedure group 
 

 
 
 
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Rationale for sample size 
Based on the following parameters established for the purposes of assessing efficacy of 
the Erchonia® FX-635™ in this clinical study …: 
 
 Individual subject success criteria defined as a 30% or greater reduction in self-
reported Degree of Pain rating on the 0-100 VAS from baseline to study endpoint 
evaluation.  
 
N.B.: The clinical relevance of a 30% change in VAS score is explained and 
supported in the STATISTICAL ANALYSIS PLAN section further along in this 
protocol document. 
 
 Overall study success criteria of at least a 35% difference between the test device 
group and the placebo group, comparing the proportion of individual successes in 
each group.  
 It is anticipated that about 55% of subjects in the test device group and about 20% of 
subjects in the placebo group will meet the individual success criteria, and 
 intended application of a two-tailed test with an alpha value of 0.05 and Power of 0.8 
 
…the sample size of 29 subjects per group (test group and the control group, 
separately) has been determined using the following reference calculator: 
Hypothesis Testing: Categorical Data - Estimation of Sample Size and Power for 
Comparing Two Binomial Proportions in Bernard Rosner's Fundamentals of 
Biostatistics. 
 
For the purposes of sample size calculation, it is anticipated that about one-twentieth of 
subjects overall may withdraw 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 group: 
 
Final sample size = sample size X 1/(1-d); where d = # expected dropouts/# subjects 
enrolled. 
Final sample size = 29 X 1/(1-0.083) 
Final sample size = 29 X 1/0.917 = 29 X 1.0905 = 31.62, rounded to 32 subjects per 
procedure group. 
 
Therefore, a minimum starting sample size of 32 subjects in each group is needed to 
ensure that sufficient numbers remains at the end of the trial (29 subjects per group) for 
any significant differences found between groups to be considered statistically valid and 
representative of the general population being sampled. This results in a total of 64 
subjects being enrolled in this study across both study procedure groups.  
 
 

 
 
 
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Recruitment 
Subjects will be recruited from among the Principal Investigator’s/test site’s pool of 
patients who are currently being treated for, or who are seeking treatment for, diagnosed 
diabetic peripheral neuropathy, or from response to the following recruitment materials.   
 
a) Flyer 
 
WANTED 
 
ADULTS WITH DIABETES WITH FOOT PAIN 
ONGOING OVER THE LAST 3 MONTHS FOR 
A  
CLINICAL STUDY OF THE EFFECTS OF  
LOW LEVEL LASER LIGHT ON  
REDUCING FOOT PAIN  
 
 
THIS STUDY INVOLVES TWELVE  
LASER LIGHT PROCEDURES  
WITH THE ERCHONIA® FX-635™ LASER  
OVER SIX WEEKS AT THE TEST SITE.  
 
THERE ARE THREE MORE VISITS TO THE TEST SITE  
TWO WEEKS, FOUR WEEKS AND THREE MONTHS  
AFTER THE LAST LASER LIGHT PROCEDURE. 
 
  
FOR MORE INFORMATION PLEASE 
CONTACT: 
 

 
 
 
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<PI name> 
<test site name & location> 
<phone # and/or e-mail> 
b) Newspaper Ad 
 
Diabetic Foot Pain 
Research Study 
 
This study is to see if the 
Erchonia® FX-635™, a non-
invasive, investigational device 
that uses low-level laser light, can 
help to relieve foot pain in people 
with diabetes that has been 
ongoing for at least 3 months. 
 
The study involves fifteen visits to 
a test site and recording some 
information at home. 
 
 
Please contact <PI name> at 
<test site name & location> at  
<phone and/or e-mail> for details. 
 
Compensation 
A subject will not receive financial or any other form of compensation to participate in this 
clinical study. However, he or she will also not be charged for the cost of the study 
procedures with the Erchonia® FX-635™ Laser 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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STUDY PROCEDURE 
 
          STUDY TEST BATTERY 
 
The following is a list of the study outcome assessment tools that will be used in this 
clinical study. For each study phase, the precise tools from this list that will be employed 
will be specified.  
 
BASELINE FOOT VARIABLES: The following is recorded at baseline evaluation: 
(i) Duration of Pain: years/months since foot pain began 
(ii) Number of Months/Years Since Diabetes Diagnosis 
(iii) Insulin Dependency: Insulin dependent diabetes or non-insulin dependent diabetes 
 
BASELINE CONCOMITANT MEDICATION AND THERAPY USE: The following is 
recorded at baseline evaluation:     
 
(i) Over-the-counter and prescription medications that have been used specifically to 
relieve the subject’s diabetic peripheral neuropathy foot pain, presently or in the past.   
(ii) Non-drug treatments/therapies (conventional, alternative, experimental and 
recreational/medicinal) that have been used specifically to relieve the subject’s 
diabetic peripheral neuropathy foot pain, presently or in the past.   
(iii) Over-the-counter and prescription medications currently used, and therapies 
currently engaged in by the subject for any non-pain relief indication, including 
dosages, frequency of use and indication for use. 
 
SUBJECT DEMOGRAPHICS: The subject’s age and gender are recorded. 
 
VISUAL ANALOG SCALE (VAS) DEGREE OF PAIN RATING: Subjects will be asked 
to rate the overall degree of pain experienced in their feet on the following 0-100 mm (0 -
10 cm) Visual Analog Pain Scale, by responding to the following question: 
 
“Using the scale below, please mark with a cross (X) the spot along the 0 to 100 line 
below that best shows how much pain you feel in your feet right now. ‘0’ means you 
feel no pain at all and ‘100’ means you feel the worst pain imaginable. Please mark 
only one spot. Do not think of or write in a number.”   
 
                     no pain  
                                              worst pain 
imaginable 
 
 
The Visual Analog Pain Scale (VAS) is one of the three most commonly used scales for 
assessing chronic pain. It is a simple scale that consists of a line anchored at one end by 
a label such as "NO PAIN" and at the other end "WORST POSSIBLE PAIN". The subject 
marks on the line the spot for the pain intensity, which is then measured.  
 
Standard guidelines for effective use of the VAS that are followed in this clinical study 
are: 
 
i. The line should be 10, 15 or 20cm long, as other lengths are less reliable.  
ii. There should be a small vertical mark at each end, with numbers 0 and 100, and a 
verbal description.  
iii. The verbal description must be in absolute terms (e.g. worst pain imaginable); 

 
 
 
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iv. The line itself should be clear of any markings and should be horizontal rather than 
vertical, for more reliable measurements.  
 
Used in the above way, it has been shown that the VAS is a proper ratio scale. Like a 
thermometer, this means that its two ends are rooted, and a doubling of the score does 
accurately reflect a doubling of the pain. Consequently, sensitive t-tests and ANOVA 
methods can be used in the analysis, so that significant differences can be identified with 
relatively small sample sizes or small differences between groups.  
Source: Measuring Pain by Adrian White, Acupuncture in Medicine, November 1998 – Vol 16 No. 
2 
 
The subject is instructed to refrain from consuming any pain relief medication within 4 
hours of recording a required VAS Degree of Pain Rating to ensure that the effect of the 
pain relief medication does not influence any potential treatment effect of the study 
procedure with the Erchonia® FX-635™ as evidenced through the VAS ratings. The 
subject may take a dosage of his or her study rescue pain relief medication immediately 
after recording a VAS rating, if needed.  
 
The study Principal Investigator will have the sole responsibility of measuring and 
recording the subject’s VAS markings according to the guidance document titled: 
“Instructions for Principal Investigators for Measuring and Recording Visual 
Analog Scale (Vas) Ratings in an Erchonia Corporation Sponsored Clinical Study” 
as contained in Appendix B of this protocol. 
 
NEUROPATHIC PAIN SYMPTOM INVENTORY (NPSI): The NPSI was developed in 
2004 by Bouhassira Didier to evaluate the different symptoms of neuropathic pain in 
adults. It is a 12-item self-administered patient-reported outcome (PRO) assessment tool 
with a recall/ observation period of over the past 24 hours. It contains 10 descriptors 
representing 5 distinct dimensions on the basis of factor analysis: burning pain, deep 
pain, paroxysmal pain, evoked pain, paresthesia/dysesthesia, and 2 temporal items 
designed to assess pain duration and the number of pain paroxysms. The NPSI has 
been validated in patients with definite neuropathic pain of peripheral or central origin.  
 
The development and validation of the NPSI is contained in the abstract below: 
 
Development and validation of the Neuropathic Pain Symptom Inventory. 
Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing 
S, Lanteri-Minet M, Collin E, Grisart J, Boureau F. 
Pain. 2004 Apr;108(3):248-57. 
 
This study describes the development and validation of the Neuropathic Pain Symptom 
Inventory (NPSI), a new self-questionnaire specifically designed to evaluate the different 
symptoms of neuropathic pain. Following a development phase and a pilot study, we 
generated a list of descriptors reflecting spontaneous ongoing or paroxysmal pain, 
evoked pain (i.e. mechanical and thermal allodynia/hyperalgesia) and 
dysesthesia/paresthesia. Each of these items was quantified on a (0-10) numerical 
scale. The validation procedure was performed in 176 consecutive patients with 
neuropathic pain of peripheral (n = 120) or central (n = 56) origin, recruited in five pain 
centers in France and Belgium. It included: (i) assessment of the test-retest reliability of 
each item, (ii) determination of the factorial structure of the questionnaire and analysis of 
convergent and divergent validities (i.e. construct validity), and (iii) evaluation of the 

 
 
 
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ability of the NPSI to detect the effects of treatment (i.e. sensitivity to change). The final 
version of the NPSI includes 10 descriptors (plus two temporal items) that allow 
discrimination and quantification of five distinct clinically relevant dimensions of 
neuropathic pain syndromes and that are sensitive to treatment. The psychometric 
properties of the NPSI suggest that it might be used to characterize subgroups of 
neuropathic pain patients and verify whether they respond differentially to various 
pharmacological agents or other therapeutic interventions. 
PMID: 15030944 
The full article and the NPSI Assessment tool are contained in Appendix C of this 
clinical study protocol.  
 
SUBJECT DAILY DIARY: Commencing upon administration of the first Erchonia® FX-
635™ laser procedure through to completion of the 4-week post-procedure evaluation 
phase, for a total of 10 consecutive weeks, the subject will be required to complete a 
Subject Daily Diary at home, recording the following information, as applicable: 
 
 Rescue Pain Medication Use: The subject will record each time a dose of the study 
rescue pain medication is taken as needed to manage foot pain. 
 Confirmation of Abstinence from Other Pain Medication Use: The subject will confirm 
at the end of each day that he or she refrained from consuming any OTC and/or 
prescription medication(s) for the indication of pain relief other than the study pain 
relief rescue medication during that day  
 ‘Other’ Medication Use: The subject will record at the end of each day any 
medication(s) he or she consumed that day that was different from that reported 
during Baseline evaluation. 
 Adverse Events recording, as applicable. 
 
SUBJECT SATISFACTION WITH FOOT PAIN LEVEL: The subject is asked to rate 
how satisfied he or she is with the level of foot pain experienced at the relevant 
evaluation points following completion of the laser administration procedures with the 
Erchonia® FX-635™, by using the 5-point Likert scale presented below to respond to the 
following question: “Overall, how satisfied or dissatisfied are you with any change in the 
pain in your feet following the study procedures with the study laser device?”  
 
• Very Satisfied 
• Somewhat Satisfied 
• Neither Satisfied nor Dissatisfied 
• Not Very Satisfied 
• Not at All Satisfied   
 
SUBJECT PERCEIVED GROUP ALLOCATION AND RATIONALE: The subject 
records whether he or she believes to have received the study procedures with the true 
or fake Erchonia® FX-635™ and records verbatim his or her reasoning or rationale for 
this perceived determination. 
 
ASSESSMENT INVESTIGATOR PERCEIVED GROUP ALLOCATION AND 
RATIONALE: The Assessment Investigator records whether he or she believes the 
subject to have received the study procedures with the true or fake Erchonia® FX-635™ 
and records verbatim his or her reasoning or rationale for this perceived determination. 
 

 
 
 
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RESCUE PAIN MEDICATION USE: As subjects in this study are those that present with 
a chronic pain level of 50 or greater on the 0 to 100 VAS pain scale, it is unethical to 
require subjects in this clinical study to refrain from consuming any and all medication(s) 
indicated for the relief of pain, particularly for subjects assigned to the placebo group. 
Therefore, this clinical study will incorporate the use of rescue pain medication, to be 
taken as needed throughout the subject’s participation in the clinical study.  
 
The rescue medication to be used in this study will be over-the-counter Regular Strength 
Tylenol® tablets. Subjects will be instructed to take a dosage of Tylenol as needed to 
control any foot pain he or she may be experiencing, ensuring that the directions for use 
are followed.  
Subjects will be instructed to record each time a dosage of the pain medication is taken 
during the study procedure administration and evaluation phase in the Subject Daily 
Diary. 
Subjects will be instructed not to take a dose of any other over-the-counter or 
prescription medications for the indication of pain relief, including NSAIDs, over the 
course of study participation.   
 
Subjects will be instructed not to record a VAS pain rating (whenever indicated) any 
sooner than six hours after they have consumed a dosage of the study pain relief rescue 
medication. This is to ensure that the effect of the pain relief medication does not 
influence the effect of the study procedures with the Erchonia® FX-635™ Laser device. 
That is, a VAS rating is only to be recorded once the effect of any previously-consumed 
rescue pain medication has dissipated. The subject will be able to take another dosage 
of the study pain relief rescue medication immediately after recording the VAS rating, if 
needed.  
 
Throughout the course of his or her study participation, a subject can continue to take 
any other over-the-counter and/or prescription medication(s) that he or she usually takes 
for any other (non-pain relief) indication(s), as he or she usually takes them, as reported 
at Baseline evaluation and approved by the study investigator. Subjects will be required 
to record any deviations from Baseline reported medication use throughout the course of 
study participation. 
 

 
 
 
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STUDY PROCEDURE PROTOCOL 
 
PRE-PROCEDURE ACTIVITIES 
 
The pre-procedure activities will be conducted at the test site prior to administration of 
the initial study procedure with the Erchonia® FX-635™. 
 
STUDY QUALIFICATION 
 
SIGNING OF INFORMED CONSENT FORM 
The PI will commence by presenting and reviewing in detail the items in the informed 
consent form with the individual and answer any questions he or she may have. To 
proceed, the individual must willingly sign the informed consent form. 
 
It is important the subject is aware of the level of commitment they will need in order to 
partake in this study. This information is detailed in the Informed Consent Form, but the 
PI should also stress to the subject the number, frequency and length of the visits to 
minimize future Protocol Deviations due to scheduling conflicts. The PI should also 
stress the importance of completing the At Home Measures and maintaining the Daily 
Diaries as completely as possible to reduce questions regarding authenticity.    
 
ASSIGNMENT OF SUBJECT IDENTIFICATION NUMBER 
The subject will be 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.” 
 
SUBJECT GROUP RANDOMIZATION  
 
A fully qualified subject will be randomly assigned to Procedure Group A or to Procedure 
Group B, following the methodology outlined above in the STUDY DESIGN section of 
the protocol. 
 
STUDY QUALIFICATION EVALUATION: INCLUSION/EXCLUSION CRITERIA  
 
INCLUSION CRITERIA 
 
To be eligible for study participation, a subject must satisfy each of the following criteria. 
 
1. Significant spontaneous pain of 50 or greater on the 0-100 VAS for the feet overall. 
2. Existing clinical diagnosis of diabetes induced Peripheral Neuropathy documented by 
a suitably qualified and licensed medical professional. 
3. Significant spontaneous foot pain that occurs approximately equally (comparably) 
bilaterally 
4. Foot pain is chronic, defined as having been ongoing for at least 3 months, 
bilaterally. 
5. Subject has been on a stable anti-diabetic medication regimen for the prior 30 days 
or on no anti-diabetic medication regimen for the prior 30 days. 

 
 
 
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6. Subject has not used or is willing to abstain from using any one or more of the 
following analgesics, or an equivalent, within 7 days prior to initiation of the study 
procedure administration with the Erchonia® FX-635™:  
 OTC NSAIDs (nonsteroidal anti-inflammatory drugs) such as aspirin, ibuprofen 
(Advil, Motrin) and naproxen (Aleve), 
 prescription NSAIDs such as Celebrex, Lodine and Relafen 
7. Subject has been on a stable dosage of any of the following antidepressants or 
any equivalent agent for at least 90 days prior to initiation of the study procedure 
administration with the Erchonia® FX-635™ and is willing and able to maintain 
that stable dosage throughout study participation OR subject has not used or is 
willing to abstain from using any of the following antidepressants or any 
equivalent agent for 30 days prior to initiation of the study procedure 
administration with the Erchonia FX-635™:  
 Tricyclic antidepressants (TCAs) such as Elavil, Pamelor and Norpramin; 
amitriptyline 
 Selective serotonin reuptake inhibitors (SSRIs) such as Paxil, paroxetine, 
fluoxetine (Prozac) 
 clomipramine (Anafranil) 
 desipramine (Norpramin) 
 
8. Subject has been on a stable dosage of any of the following prescription medications 
or any equivalent agents for at least 90 days prior to initiation of the study procedure 
administration with the Erchonia FX-635™ and is willing and able to maintain that 
stable dosage throughout study participation OR subject has not used or is willing to 
abstain from using any of the following prescription medications or any equivalent 
agents for 30 days prior to initiation of the study procedure administration with the 
Erchonia FX-635™: 
 Neurontin 
 Lyrica 
 Tramadol 
 Opioid medicines such as Ultram and Ultracet 
 
9. Subject has not received or is willing to abstain from receiving any injections of local 
anesthetics such as lidocaine within 30 days prior to initiation of the study procedure 
administration with the Erchonia FX-635™. 
10. Subject is able and willing to take over-the-counter Regular Strength Tylenol® 
tablets to manage his or her pain, as needed, throughout the course of study 
participation. 
11. Subject is willing and able to refrain from consuming any over-the-counter and/or 
prescription medications including muscle relaxants and/or herbal supplements 
and/or recreational and medical drugs including cannabis intended for the relief of 
pain and/or inflammation throughout the course of study participation, except for the 
study-specific pain relief medication of over-the-counter Tylenol.  
12. Subject is willing and able to refrain from engaging in any non-study procedure 
therapies for the management of his or her foot pain throughout the course of study 
participation, including conventional therapies such as physical therapy, occupational 
therapy and hot or cold packs, as well as alternative therapies such as chiropractic 
care and acupuncture. 
13. Subject agrees to refrain from taking a dosage of the study rescue pain medication of 
over-the-counter Regular Strength Tylenol® tablets for at least 6 hours before a 
scheduled VAS foot pain rating is to be recorded. The subject understands that he 

 
 
 
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may take a dosage of the over-the-counter Regular Strength Tylenol® tablets right 
after the VAS rating has been recorded, if needed to manage foot pain.  
14. Subject agrees and is able to complete the Subject Diary, as applicable.  
15. 18 years of age or older. 
16. Subject is able to communicate fluently in English with the investigator and is able to 
read and write English sufficiently to comply with the study procedures and complete 
the information in the Subject Diary. 
 
 
 

 
 
 
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EXCLUSION CRITERIA 
 
A subject who satisfies any of the following criteria will be excluded from study 
participation: 
 
1. Subject’s foot pain is undiagnosed, or has been diagnosed by a qualified medical 
professional, as being other than, or in addition to, diabetes induced Peripheral 
Neuropathy (such as due to drugs, poisoning, cancer or genetic conditions). 
2. Subject’s foot pain is unilateral or notably different between the two feet (such that 
the pain in one foot is notably lesser/greater than in the other). 
3. Serious organ disease or other serious primary disease merger. 
4. Diabetes ketosis, ketoacidosis or severe infection within the past two weeks. 
5. Current, active chronic pain disease: chronic fatigue syndrome, fibromyalgia, 
endometriosis, inflammatory bowel disease, interstitial cystitis, peripheral vascular 
disease. 
6. Cancer or treatment for cancer in the past 6 months. 
7. Surgical intervention to treat diabetic peripheral neuropathy foot pain, including 
implantation of a pain relief device. 
8. Active infection, wound, or other external trauma to the areas to be treated with the 
laser. 
9. Medical, physical, or other contraindications for, or sensitivity to, light therapy. 
10. Pregnant, breast feeding, or planning pregnancy prior to the end of study 
participation. 
11. Serious mental health illness such as dementia or schizophrenia; psychiatric 
hospitalization in past two years. 
12. Developmental disability or cognitive impairment that in the opinion of the 
investigator would preclude adequate comprehension of the informed consent form 
and/or ability to record the necessary study measurements. 
13. Any condition or other variable that in the opinion of the investigator may confound or 
interfere with the evaluation of the effectiveness of the investigational treatment or 
otherwise render the subject unable to comply with the requirements of the study 
protocol.  
14. Involvement in litigation and/or receiving disability benefits related in any way to the 
parameters of the study. 
15. Participation in a clinical study or other type of research in the past 30 days. 
 
 
 
 

 
 
 
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DAYS -2 AND -1: PRE-PROCEDURE WASHOUT PHASE: THE 48-HOUR PERIOD 
PRIOR TO COMMENCEMENT OF THE PRE-PROCEDURE EVALUATION PHASE 
 
The pre-procedure washout phase comprises the 48-hour (2 day) period immediately 
preceding the pre-procedure evaluation phase, beginning upon waking on the first 24-
hour period.  
 
On each of the two consecutive days of the washout phase, the subject is required to 
record the specified measures on the washout phase subject record sheets provided by 
the test site in his or her home and to bring the completed forms to the test site on their 
pre-procedure evaluation visit.  
 
The investigator will record the dates of the 48-hour washout phase on the subject’s 
take-home record sheets based upon the timeframe required to satisfy the pre-
procedure medication abstinence criteria, as applicable.   
 
At the start of the pre-procedure washout phase, the subject commences his or her 
required abstinence from use of non-study related medications and therapies for the 
relief of foot pain and simultaneously commences the as-needed consumption of the 
study rescue medication – OTC Tylenol – for his or her foot pain, that will continue 
through to the end of the post-procedure evaluation phase. 
 
PRE-PROCEDURE WASHOUT PHASE MEASURES 
 
On each day of the two-day Pre-Procedure Washout Phase, the subject records the 
following measures on the supplied record sheets, as outlined in the STUDY TEST 
BATTERY section above. 
 
 Visual Analog Scale (VAS) Foot Pain Rating 
 Use of Study Rescue Medication (Tylenol) 
 Use of Other Medications  
 
DAY 1: PRE-PROCEDURE EVALUATIONS 
 
The pre-procedure evaluation visit occurs on the day following successful completion of 
the two-day pre-procedure washout phase and comprises the following activities: 
 
CONFIRMATION OF QUALIFYING VAS RATING 
 
The investigator measures and records the 2 individual VAS foot pain ratings and 
calculates the average of the 2 VAS foot pain ratings recorded during the 48-hour pre-
procedure washout phase. The 2-day average washout phase VAS foot pain rating must 
be 50 or greater for the subject to proceed with study participation. If the 2-day average 
washout phase VAS foot pain rating is less than 50, the subject’s participation in the 
study ends at this time. 
 
CONFIRMATION OF STUDY QUALIFICATION  
 
If more than 7 days has passed since initial study qualification evaluation and the pre-
procedure evaluation phase, the investigator will confirm with the subject that the 
information attained during study qualification evaluation has not since changed. If any 

 
 
 
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changes are reported, the investigator will review the change(s) to determine if the 
subject continues to qualify for study participation.  
 
 
 
PRE-PROCEDURE VARIABLES 
 
The following pre-procedure variables will be recorded prior to commencement of the 
procedure administration phase (prior to procedure administration #1), as listed and 
described in the STUDY TEST BATTERY section above.  
 
 Baseline Foot Variables 
 Baseline Concomitant Medication and Therapy Use 
 Subject Demographics 
 
PRE-PROCEDURE MEASURES 
 
The following pre-procedure measures will be recorded prior to commencement of the 
procedure administration phase (prior to procedure administration #1), as listed and 
described, and according to the methodology outlined, in the STUDY TEST BATTERY 
section above.  
 
 Visual Analog Scale (VAS) Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 
 
 

 
 
 
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PROCEDURE ADMINISTRATION PHASE 
 
PROCEDURE ADMINISTRATION PROTOCOL   
 
 The procedure administration phase of the study commences within one hour 
subsequent to recording of the pre-procedure measures and variables, on the same 
day.    
 The procedure administration phase extends over 6 consecutive weeks.  
 Each subject receives 12 total procedure administrations with the Erchonia® FX-
635™ across the consecutive 6-week procedure administration phase, 2 procedure 
administrations per week, each procedure administration approximately evenly 
spaced. That is, each procedure administration will be 3 or 4 days apart with a 
treatment window of ±1 day. 
 Each procedure administration lasts a total of 15 minutes per foot, for a total 
combined procedure administration time of 30 minutes per session. 
 Each procedure administration with the Erchonia® FX-635™ is administered at the 
investigator’s test site. 
 The procedure administration protocol for each session is as follows: 
 
1. The subject enters the procedure administration room and is seated on a chair with 
the right foot elevated. 
2. The subject is correctly fitted with the laser safety glasses. 
3. The procedure administrator puts on the laser safety glasses and selects the 
Erchonia® FX-635™ Laser A or B according to the subject’s procedure group 
assignment.  
4. The FX-635™ Laser is positioned around the foot such that each of the 3 laser 
lights is positioned between 3 and 4 inches away from, but directed toward, a) the 
top of the foot (dorsal aspect); b) the bottom of the foot (plantar aspect); and c) the 
posterior tibial nerve within the tarsal tunnel. 
5. The FX-635™ Laser is activated 
6. The laser diodes laze each of these 3 areas for 15 minutes simultaneously.  
7. The procedures listed in 4. through 6. above is repeated for the left foot.  
8. The investigator and the subject remove the safety glasses. 
9. The subject rises and leaves the procedure administration room. 
 
At each of the procedure administration test site visits, the investigator performs an 
adverse events evaluation.  
 
PROCEDURE ADMINISTRATION PHASE MEASURES 
 
DAILY MEASURES 
 
Commencing on the same day as the first study procedure administration with the 
Erchonia® FX-635™ is administered, the subject will begin to record the required 
information in the Subject Daily Diary, as applicable, at home. 
 
FOLLOWING EACH PROCEDURE ADMINISTRATION  
 
Within 10 minutes following administration of each of the first 11 study procedure 
administrations with the Erchonia® FX-635™, the subject will record the following at the 
test site: 
 

 
 
 
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 Visual Analog Scale (VAS) Degree of Foot Pain Rating 
 Adverse Events Evaluation  
 
 
 

 
 
 
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POST-PROCEDURE ACTIVITIES 
    
POST-PROCEDURE EVALUATION PHASE  
 
The post-procedure administration evaluation phase of this study will commence 
immediately following completion of the procedure administration phase and will last 3 
months (about 12 weeks).  
 
POST-PROCEDURE EVALUATION VISITS AND MEASURES 
 
There will be 4 post-procedure evaluation visits. The first post-procedure evaluation visit 
will occur at the test site, and the remaining three post-procedure evaluation visits will 
take place at the subject’s home. The subject will be provided with pre-dated case report 
forms on which to record the required information on each of those three post-procedure 
days, and a staff member at the investigator’s test site will contact the individual on the 
designated day to remind him or her to record the required information. These visits, and 
the associated measures to be recorded at each visit, as listed and described, and 
according to the methodology outlined, in the STUDY TEST BATTERY section above 
are as follows:  
 
DAILY MEASURES: AT HOME 
 
The subject will continue to record the required information in the Subject Daily Diary, as 
applicable, at home, through to the 4 weeks post-procedure evaluation visit. 
 
STUDY ENDPOINT EVALUATION: FOLLOWING COMPLETION OF THE 
PROCEDURE ADMINISTRATION PHASE: AT THE TEST SITE  
 
The study endpoint evaluation visit will occur at the test site within ten minutes following 
completion of the procedure administration phase, after administration of the 12th and 
final procedure administration with the Erchonia® FX-635™.  
 
The following measures will be recorded at this visit:  
 
 Visual Analog Scale (VAS) Degree of Foot Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 Subject Satisfaction With Foot Pain Level 
 Subject Perceived Group Allocation and Rationale 
 Assessment Investigator Perceived Group Allocation and Rationale 
 Adverse Events Evaluation  
 
TWO WEEKS POST-PROCEDURE EVALUATION: AT HOME  
 
Two weeks following completion of the procedure administration phase, the following 
measures will be recorded:  
 
 Visual Analog Scale (VAS) Degree of Pain Rating 
 Adverse Events Evaluation  
 
 
 

 
 
 
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FOUR WEEKS POST-PROCEDURE EVALUATION: AT HOME  
 
Four weeks following completion of the procedure administration phase, the following 
measures will be recorded:  
 
 Visual Analog Scale (VAS) Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 Subject Satisfaction With Foot Pain Level 
 Adverse Events Evaluation  
 
THREE MONTHS POST-PROCEDURE EVALUATION: AT HOME  
 
Three months following completion of the procedure administration phase, the following 
measures will be recorded:  
 
 Visual Analog Scale (VAS) Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 Subject Satisfaction With Foot Pain Level 
 Adverse Events Evaluation  
 
 
OPEN-LABEL PLACEBO SUBJECT PROCEDURE ADMINISTRATION PERIOD  
 
Following completion of the 3-month post-procedure administration phase, individual 
subject blinding will be broken. Subjects who had been randomized to the placebo 
(sham) procedure group will then be offered participation in an additional 6-week post-
study open-label procedure administration period during which time they will knowingly 
receive the active 6-week 12-procedure administration protocol with the Erchonia® FX-
635™ Laser as did the subjects initially assigned to the active test procedure group at 
the time of study enrollment.     
 
Participation in the 6-week post-study open–label procedure administration period is 
voluntary for subjects who had been assigned to the placebo (sham) procedure group. 
Participation in the 6-week post-study open–label procedure administration period will 
not be offered to subjects who had initially been randomized to the active test laser 
procedure group.  
 
A subject participating in the post-study open-label placebo subject procedure 
administration period will be required to: 
 
 continue his or her required abstinence from use of non-study related medications 
and therapies for the relief of foot pain and the as-needed consumption of the study 
rescue medication (OTC Tylenol) for his or her foot pain, through to the end of the 
open-label placebo subject procedure administration period; 
 record the same measures as during the initial procedure administration phase, as 
follows: 
 
DAILY MEASURES 
 
The subject will record the required information in the Subject Daily Diary, as applicable, 
at home. 

 
 
 
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FOLLOWING EACH PROCEDURE ADMINISTRATION  
 
Within 10 minutes following administration of each of the post-study open-label 
procedure administration period 12 study procedure administrations with the Erchonia® 
FX-635™, the subject will record the following at the test site: 
 
 Visual Analog Scale (VAS) Degree of Pain Rating 
 Adverse Events Evaluation  
 
FOLLOWING COMPLETION OF THE PROCEDURE ADMINISTRATION PHASE: AT 
THE TEST SITE  
 
The post-study open-label procedure administration period final evaluation visit will occur 
at the test site within one hour following completion of the 12th and final open-label 
procedure administration with the Erchonia® FX-635™.  
 
The following measures will be recorded at this visit:  
 
 Visual Analog Scale (VAS) Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 Subject Satisfaction With Foot Pain Level 
 Adverse Events Evaluation  
 
Following completion of the final post-study open-label test site evaluation visit, a 
subject’s participation in the post-study open-label placebo subject procedure 
administration period will be complete. Subjects participating in the post-study open-
label procedure administration phase will not be required to enter a post-procedure 
evaluation phase. 
 
 
 
 
   
 

 
 
 
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TABLE OF SUBJECT EVENTS 
 
The following table provides a progressive summary of subject events throughout this 
study.  
 
PRE-PROCEDURE ACTIVITIES  
 
 A potentially well-suited and interested candidate for participation in the study attends the 
investigator’s office. 
 The investigator reviews the informed consent form with the candidate.  
 A candidate who voluntarily signs the informed consent form will be randomly assigned to 
procedure group and enter the study qualification evaluation phase of the study. 
 
PRE-PROCEDURE WASHOUT PHASE: 48 HOURS 
 VAS Degree of Pain Rating (Daily) 
PRE-PROCEDURE EVALUATION PHASE 
 
 Confirmation of Continued Study Qualification.  
 
PRE-PROCEDURE VARIABLES 
 
 Baseline Foot Variables 
 Baseline Concomitant Medication and Therapy Use 
 Subject Demographics 
 
PRE-PROCEDURE MEASURES 
 
 VAS Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 
PROCEDURE ADMINISTRATION PHASE 
 
PROCEDURE ADMINISTRATION PROTOCOL  
 
Twelve 30-minute (15 minutes per foot) study procedure administrations with the Erchonia® 
FX-635™ over 6 consecutive weeks, 2 procedure administrations per week, administered at 
the test site. 
 
PROCEDURE ADMINISTRATION PHASE MEASURES 
 
 Subject Daily Diary 
 VAS Degree of Pain Rating  
 Adverse Events Evaluation  
 
 
 

 
 
 
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POST-PROCEDURE ACTIVITIES 
 
DAILY MEASURES: AT HOME 
 
 
 Subject Daily Diary through to Week 4 Post-Procedure  
 
   STUDY ENDPOINT EVALUATION: AT TEST SITE 
 
 VAS Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 Subject Satisfaction With Foot Pain Level 
 Subject Perceived Group Allocation and Rationale 
 Assessment Investigator Perceived Group Allocation and Rationale 
 Adverse Events Evaluation  
 
 TWO WEEKS POST-PROCEDURE EVALUATION: AT HOME 
 
 VAS Degree of Pain Rating 
 Adverse Events Evaluation  
 
 FOUR WEEKS POST-PROCEDURE EVALUATION: AT HOME 
 
 VAS Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 Subject Satisfaction With Foot Pain Level 
 Adverse Events Evaluation  
 
 THREE MONTHS POST-PROCEDURE EVALUATION: AT HOME 
 
 VAS Degree of Pain Rating 
 Neuropathic Pain Symptom Inventory (NPSI) 
 Subject Satisfaction With Foot Pain Level 
 Adverse Events Evaluation   
 
POST-STUDY OPEN-LABEL PLACEBO SUBJECT PROCEDURE ADMINISTRATION PERIOD 
 
OPEN-LABEL PLACEBO SUBJECT PROCEDURE ADMINISTRATION PROTOCOL  
 
Twelve 30-minute (15 minutes per foot) study procedure administrations with the Erchonia® 
FX-635™ over 6 consecutive weeks, 2 procedure administrations per week, administered at 
the test site. 
 
OPEN-LABEL PROCEDURE ADMINISTRATION PHASE MEASURES 
 
 Subject Daily Diary 
 VAS Degree of Pain Rating  
 Neuropathic Pain Symptom Inventory (NPSI) 

 
 
 
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 Subject Satisfaction With Foot Pain Level 
 Adverse Events Evaluation  

 
 
 
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ADVERSE EVENTS  
 
ADVERSE EVENTS DEFINITION 
 
An adverse event (AE) is defined as any unfavorable and unanticipated sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of 
a study procedure(s), whether or not it is related to the study procedure(s). The intensity 
of all AEs is classified as follows:  
 
• 
Mild: A mild AE is defined as an event characterized by "awareness of symptoms 
which are easily tolerated." 
• 
Moderate: A moderate AE is defined as an event in which "sufficient discomfort is 
present to cause interference with usual activity." 
• 
Severe: A severe AE is defined as an event characterized by "extreme distress 
causing significant impairment of function or incapacitation. 
• 
A Serious Adverse Event (SAE) is any AE occurring at any dose that results in: 
 
− 
Death. 
− 
A life-threatening event. 
− 
Inpatient hospitalization or prolongation of existing hospitalization. 
− 
Persistent or significant disability/incapacity. 
− 
Congenital anomaly/birth defect. 
 
In addition, an important medical event that may not result in death, be life-threatening, or 
require hospitalization may be considered a SAE when, based on appropriate medical 
judgment, it may jeopardize the individual and/or may require medical or surgical 
intervention to prevent one of the outcomes listed above. 
 
An Unexpected AE is any AE of which the specificity or severity is not consistent with that 
expected or anticipated as possible from administration of the study procedure.  
 
A Reasonably Related AE is one that is possibly probably or definitely related to the study 
procedure (as determined by the study investigator). 
 
REASONABLY ANTICIPATED AND POTENTIAL ADVERSE EVENTS 
 
SAEs are not anticipated to occur in this clinical study.  
 
Reasonably anticipated and potential AEs that may occur in this clinical study include the 
following: 
  
• Anticipated Adverse Event: None observed or reported to date in prior clinical trials.  
 
• Potential Adverse Events: include skin irritation, itching, discoloring, rash, indentations, 
pain/discomfort and infection. 
 
EVALUATION OF ADVERSE EVENTS 
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At each evaluation and procedure administration test site visit throughout the clinical 
study, and at any other time throughout the duration of the clinical trial that is necessary, 
evaluation for the occurrence of any potential adverse event will occur. This includes any 
observations made by the study investigator or other study staff or any reports made by 
the subject. Subjects will be instructed as to what constitutes an adverse event and how 
to report any potential adverse event(s) he or she may identify during study participation 
to the test site. The subject will be instructed to formally evaluate for potential adverse 
events through their recordings in their Subject Daily Diary completed at home.  
 
RECORDING OF ADVERSE EVENTS 
 
AEs that occur after randomization are recorded by the Principal Investigator on the AE 
page of the CRF. Recording is done in a concise manner using standard, acceptable 
medical terms. Any clinically significant changes in pre-existing conditions (based on 
medical history/physical examination results) are recorded on the CRF AE pages.  
 
REPORTING OF ADVERSE EVENTS 
 
The investigator will notify the Sponsor right away of any identified or reported adverse 
event, whether determined by the investigator to be related or unrelated to the study 
treatment or device or whether it is an anticipated or unanticipated AE. The investigator 
and the Sponsor will determine if the AE is a promptly reportable event to the governing 
IRB. The investigator will formally report any serious, life-threatening, or unexpected 
adverse experiences, including death that occurs within the duration of this study 
regardless of the relationship to the study procedure.  
  
 
PROTOCOL DEVIATIONS AND VIOLATIONS 
 
Both protocol deviations and protocol violations are accidental or unintentional changes 
to, or non-compliances with, the IRB-approved research protocol without prior sponsor 
and IRB approval. The difference between the two lies in the level of risk introduced by 
the change. 
 
Protocol Deviation: Protocol deviations do not increase risk or decrease benefit; or have 
a significant effect on the subject’s rights, safety, or welfare, and/or on the integrity of the 
data. Deviations may result from the action of the subject, investigator, or research staff, 
but do not result from willful or knowing misconduct on the part of the investigator or 
research staff. A protocol deviation may be due to the research subject’s nonadherence; 
or an unintentional change to, or noncompliance with, the research protocol on the part of 
a researcher.  
 
Examples of a protocol deviation include:  
• a rescheduled study visit that falls outside the acceptable timeframe for the visit;  
• failure to collect a scheduled outcome measure;   
• subject’s refusal to complete scheduled research activities; and 
• mechanical equipment failure or malfunctioning that affects the protocol.  
 
Protocol Violation: Protocol violations generally increase risk or decrease benefit, and 
affect the subject’s rights, safety, or welfare, or the integrity of the data. There may be 
evidence of willful or knowing misconduct on the part of the investigator(s).  The 

 
 
 
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investigator may demonstrate other serious or continuing noncompliance with federal, 
state, or local research regulations. 
 
Examples of protocol violations include:  
• 
failure to obtain valid informed consent (e.g., obtained informed consent on a non-date 
stamped form); 
• 
not following the inclusion/exclusion criteria such that non-qualifying subjects are 
enrolled in the study; 
• 
adding or modifying a research tool; 
• 
accidental application of incorrect study treatment (e.g. treatment not completed per 
protocol, placebo subject given active treatment); and 
• 
loss of laptop computer, paper files, or any other documentation or hardware that 
contains identifiable, private information about subjects such that subject privacy and 
confidentiality may be compromised. 
 
The investigator will not intentionally deviate from the study protocol procedures except in 
medical emergencies. Any protocol deviations that do occur will be recorded on the 
protocol deviation CRF and the IRB will be informed of the deviation, if applicable.  
 
 
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 maintained in the subject’s file at all times other than when 
information is being recorded on them.   
 
Copies of all 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 
 
Monitoring of the clinical study will be according to the applicable protocols and 
procedures contained within the Erchonia Corporation Clinical Trials Monitoring Plan, CT-
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STATISTICAL ANALYSIS 
 
PRIMARY EFFICACY OUTCOME MEASURE: CHANGE IN SUBJECT SELF-
REPORTED VAS PAIN RATING FROM BASELINE TO STUDY ENDPOINT   
 
Primary efficacy outcome measure for this clinical study will be a statistically significant 
difference in the proportion of subjects between test and control groups who achieve a 
clinically meaningful and statistically significant decrease in self-reported VAS pain rating 
from baseline to study endpoint.    
 
The primary efficacy outcome evaluation will be performed on the blinded data attained 
from subjects who were initially enrolled in either the test or placebo procedure group 
and will not include active procedure test data attained from placebo subjects who 
partook in the post-study open-label procedure administration period after blinding was 
broken. 
 
Subjects meeting Individual Success Criteria 
The individual subject success criteria defined as a 30% or greater decrease in self-
reported VAS pain rating at study endpoint relative to baseline. 
 
Overall Study Success Criteria.  
Overall study success criteria defined as at least a 35% difference between procedure 
groups, comparing the proportion of individual successes in each group. It is anticipated 
that about 55% of subjects in the test group will meet the individual success criteria and 
about 20% of subjects in the control group will meet the individual success criteria.  
 
The clinical relevance of a 30% change in VAS score has been well previously 
established by FDA’s Division of Surgical, Orthopedic and Restorative Devices through 
numerous pre-IDE reviews, the results of said studies that were subsequently used to 
successfully support various pain-reduction related indications for various Erchonia 
Corporation light therapy devices under Product Code NHN for the 510(k)s listed below 
over the past 8 years: 
 
1. K180197: Erchonia® FX-635: is indicated for the following two indications: 
a. as an adjunct to provide relief of minor chronic low back pain of musculoskeletal 
origin. 
b. as an adjunct to reducing chronic heel pain arising from plantar fasciitis. 
 
2. K101430; 06/22/10: “The MLS-AC DermaScanner™ is indicated, while using the red 
diodes, for adjunctive use in providing temporary relief of minor chronic neck and 
shoulder pain of musculoskeletal origin.” 
 
3. K100509; 06/08/10: “The Erchonia THL1 is indicated for use in providing temporary 
relief of minor chronic neck and shoulder pain of musculoskeletal origin.” 
 
4. K072206; 04/24/08: “The Erchonia EML Laser is indicated for the temporary reduction 
in post -surgery pain at 24 hours after surgery following breast augmentation surgery.” 
 

 
 
 
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5. K050672; 06/02/05: “The Erchonia EVRL Laser is generally indicated while using the 
red diode for adjunctive use in providing temporary relief of minor chronic neck and 
shoulder pain of musculoskeletal origin.” 
 
6. K041139; 09/30/04: “The Erchonia EML Laser is indicated as an adjunct to liposuction 
procedures of the thighs, hips and stomach for reduction of pain associated with the 
recovery process.” 
 
Evaluation Time Point 
The study end evaluation time point at which primary study success will be analyzed is 
at six weeks post-baseline, following completion of the 12th and final study procedure 
administration with the Erchonia® FX-635™.   
 
Null Hypothesis: There will be no statistically significant difference in the proportion of 
individual successes, as defined, between the test and control groups. 
 
Alternative Hypothesis: There will be a statistically significant difference in the 
proportion of individual successes, as defined, between the test and control groups, to 
the effect of 35% or greater. 
 
SECONDARY EFFICACY OUTCOME MEASURES  
 
Secondary efficacy outcome measures will be evaluated for the following four data sets: 
 
1. The blinded data set only attained from subjects who were initially enrolled in either 
the test or placebo procedure group and will not include active procedure test data 
attained from placebo subjects who partook in the post-study open-label procedure 
administration period after blinding was broken. 
 
For this group, the following secondary efficacy outcome measure will be evaluated: 
 
a) Change in VAS rating across and between all study evaluation time points within and 
between treatment groups 
b) Change in scores on the Neuropathic Pain Symptom Inventory (NPSI) across and 
between all evaluation points within and between treatment groups 
c) Differences in the use of rescue pain medication between procedure groups across 
study duration 
 
2. The combined data set comprising the blinded data set attained from subjects who 
were initially enrolled in either the test or placebo procedure group, and the active 
procedure test data attained from placebo subjects who partook in the post-study 
open-label procedure administration period after blinding was broken, comparing 
combined test (blinded and non-blinded) to placebo data 
 
For this group, the following secondary efficacy outcome measure will be evaluated: 
 
a) Change in VAS rating across and between all study evaluation time points to study 
endpoint evaluation within and between treatment groups 
b) Changes in scores on the Neuropathic Pain Symptom Inventory (NPSI) across and 
between all evaluation points to study endpoint evaluation within and between 
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c) 
Differences in the use of rescue pain medication between procedure groups across 
study duration to study endpoint evaluation. 
 
3. The data set comprising the blinded data set attained from subjects who were initially 
enrolled in the test procedure group, and the active procedure test data attained from 
placebo subjects who partook in the post-study open-label procedure administration 
period after blinding was broken, comparing combined blinded to non-blinded test 
group data 
 
For this group, the following secondary efficacy outcome measure will be evaluated: 
 
a) Change in VAS rating across and between all study evaluation time points to study 
endpoint evaluation within and between treatment groups 
b) Changes in scores on the Neuropathic Pain Symptom Inventory (NPSI) across and 
between all evaluation points to study endpoint evaluation within and between 
treatment groups 
c) 
Differences in the use of rescue pain medication between procedure groups across 
study duration to study endpoint evaluation. 
 
4. The data set comprising the blinded data set attained from subjects who were initially 
enrolled in the placebo procedure group, and the active procedure test data attained 
from placebo subjects who partook in the post-study open-label procedure 
administration period after blinding was broken, comparing combined blinded 
placebo to non-blinded test group data 
 
For this group, the following secondary efficacy outcome measure will be evaluated: 
 
a) Change in VAS rating across and between all study evaluation time points to study 
endpoint evaluation within and between treatment groups 
b) Changes in scores on the Neuropathic Pain Symptom Inventory (NPSI) across and 
between all evaluation points to study endpoint evaluation within and between 
treatment groups 
c) 
Differences in the use of rescue pain medication between procedure groups across 
study duration to study endpoint evaluation. 
 
In addition, the following will be explored: 
 
 Any deviations in compliance with study required abstinences between procedure 
groups  
 Comments provided by subjects 
 Adverse events 
 
5. The data set comprising the blinded data set attained from subjects who were initially 
enrolled in the test procedure group, and the active procedure test data attained from 
placebo subjects who partook in the post-study open-label procedure administration 
period after blinding was broken, comparing combined blinded to non-blinded test 
group data 
 
For this group, the following secondary efficacy outcome measure will be evaluated: 
 
d) Change in VAS rating across and between all study evaluation time points to study 
endpoint evaluation within and between treatment groups 

 
 
 
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e) Changes in scores on the Neuropathic Pain Symptom Inventory (NPSI) across and 
between all evaluation points to study endpoint evaluation within and between 
treatment groups 
f) 
Differences in the use of rescue pain medication between procedure groups across 
study duration to study endpoint evaluation. 
 
 
 
 
 
 
 
STATISTICAL METHODS 
 
Efficacy analysis will be according to the intent to treat (ITT) principle by last observation 
carried forward (LOCF). 
 
Intent to Treat: Subjects will be included in the analysis if they were randomized to study 
procedure group, had a valid baseline visit including the required Low Back Pain VAS 
recordings; and received the first study procedure administration.  
 
Last observation carried forward: Missing data will be handled by carrying forward the 
last observation.  
 
Per-protocol analysis will also be performed for the set of all subjects who were 
randomized to procedure group and completed the study according to the full protocol.  
 
STATISTICAL ANALYSIS 
 
The primary analysis of efficacy will be through the application of: 
 
1) Fisher's exact test to compare the proportion of success between the test and the 
control groups, considering that randomization has been diligently conducted and 
important covariates between the two groups are well balanced. 
 
2) Parametric ANCOVA model analysis with the mean change from baseline to study 
endpoint in foot pain ratings on the VAS as the dependent variable, procedure group 
as the independent variable of interest and baseline average foot pain VAS rating as 
a covariate. A two-tailed significance level of 5% will be considered to be statistically 
significant.  
 
Covariates: The following potential covariate baseline variables will be adjusted, as 
applicable, through application of an ANCOVA analysis for the continuous variables and 
linear regression analysis for categorical variables. 
 
 Baseline VAS rating 
 Baseline NPSI total score  
 Duration of foot pain 
 Time since Diabetes diagnosis 
 Insulin dependent versus non-insulin dependent Diabetes 
 Age   
 Gender 
 

 
 
 
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Secondary Measures Analysis 
 The secondary measures that are continuous variables will be analyzed through 
parametric analysis using ANCOVA. A two-way significance level of 5% will be 
considered to be statistically significant.  
 The secondary measures that are categorical will be evaluated through linear 
regression analysis. 
 
Satisfaction with Study Outcome Ratings: will be tabulated according to category and 
reported as percentages. Satisfaction levels will be correlated with subject individual 
study success and recorded changes in foot pain VAS ratings from Baseline to post-
procedure evaluations.  
 
 
BLINDING EFFICACY EVALUATION  
 
Statistical evaluation of blinding efficacy will be performed as follows: 
 
(i) The percentage of subjects who correctly perceived their procedure group allocation 
and the percentage of subjects who did not correctly perceive their procedure group 
allocation will be calculated. 
(ii) The percentage of times the assessment investigator correctly perceived subjects’ 
procedure group allocation and the percentage of times the assessment investigator 
did not correctly perceive subjects’ procedure group allocation will be calculated. 
(iii) The Fischer’s Exact categorical analysis technique for comparison of proportion of 
successes (accurate procedure group allocation determination) between actual 
active and placebo subject groups will be performed. 
 
It is anticipated that the results of the Fischer’s Exact analysis will not be statistically 
significant; that is, it is anticipated that both subjects assigned to the active procedure 
group and subjects assigned to the placebo procedure group will demonstrate a high 
percentage of accuracy of group allocation determination if the study treatment proves 
efficacious. Similarly, it is anticipated that assessment investigators will demonstrate a 
high percentage of accuracy of group allocation determination for both subjects assigned 
to the active procedure group and subjects assigned to the placebo procedure group, if 
the study treatment proves efficacious. Therefore, it should be noted that lack of a 
statistically significant Fischer’s Exact analysis result will be considered an indicator of 
study blinding efficacy, providing additional support to study outcome efficacy, 
particularly if appropriately supported by the reasoning statements, as explained below.     
 
Positive blinding efficacy will be supported by comments provided to support perceived 
group allocation that pertain to the determination being made based on treatment 
efficacy or lack thereof; e.g.: ‘My foot pain is much less than it used to be, so I believe I 
got the real treatment’ or ‘My foot pain hasn’t really changed, so I believe I got the fake 
treatment.’ 
 
Blinding will be determined to have failed if comments provided to support perceived 
group allocation pertain to factors such as sensation/visual clues (e.g. I saw/didn’t see a 
light go on the laser, etc.) or other factors that pertain to blinding having been 
compromised such as ‘I overheard the doctor saying I wasn’t getting the real treatment.’ 
 
SAFETY ANALYSES  

 
 
 
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Safety analyses will be based on all subjects who were randomized to test or placebo 
procedure group. Safety will be assessed by evaluating and comparing frequency and 
incidence of observed and/or reported adverse events between test and placebo 
procedure groups related to administration of the Erchonia® FX-635™ laser procedures. 
A chi-square test with a continuity correction will be performed to compare the 
percentage of subjects who experienced adverse events between test and placebo 
procedure group subjects.  
 
INDIVIDUAL SITE ANALYSIS 
 
Analysis of results will be performed by individual test site and pooled across test sites. 
Application of a balanced test-control group study design incorporating a varied block by 
test site randomization procedure will contribute to statistical justification of pooling data 
across the different test sites.  
 
INFORMED CONSENT 
 
• 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. 
• 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.   
• 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.   
• Each subject will also be made aware of alternative treatments available to him or her.   
• 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.   
• 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. 
• 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. 
 
CASE REPORT FORMS 
 
The case report forms that will be used to collect the data from each subject in this 
clinical study can be found in Appendix