A Prospective, Multicenter Study Comparing Healing After Treatment With the Sonendo GentleWave™ System as Compared to a Traditional Root Canal Therapy Literature Control
Phase: NA
Conditions: Root Canal Therapy
Sponsor: Sonendo, Inc.

 
 
Proprietary and Confidential 
 
  
  
 
A Prospective, Multicenter Study Comparing Healing After 
Treatment with the Sonendo GentleWave™ System as 
Compared to a Traditional Root Canal Therapy Literature 
Control  
 
The SUPREME Study 
 
Protocol Number: CS-06 
Revision: B 
Date 23 March 2015 
NCT02285595 
 
Study Sponsor 
SONENDO INC. 
26061 Merit Circle, Suite 101 
Laguna Hills, California 92653 
Phone:   (949) 766-3636 
Fax:   (949) 305-5201 
  
 
 
 

The Sonendo GentleWave System 
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Study Protocol# CS-06 Revision B 
23 March 2015 
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Table of contents 
1.0 STUDY SYNOPSIS ..............................................................................................................11 
2.0 INTRODUCTION AND RATIONALE ....................................................................................18 
2.1 General Background ..................................................................................................... 18 
2.2 Drawbacks of Current Methods in Root Canal Therapy ............................................... 18 
2.2.1 Leaving Uninstrumented Recesses ................................................................................18 
2.2.2 Root Weakening ............................................................................................................18 
2.2.3 Ledge Formation ...........................................................................................................19 
2.2.4 Perforation ....................................................................................................................19 
2.2.5 Penetration of Instruments into the Periapical Tissue ..................................................19 
2.2.6 Instrument Separation ..................................................................................................20 
2.2.7 Extrusion of Debris into the Periapical Tissue ...............................................................20 
2.2.8 Extrusion of Sodium Hypochlorite into the Periodontal Tissues ...................................21 
2.3 Healing Rates for Traditional Root Canal Therapy ........................................................ 21 
2.4 Sonendo GentleWave Technology Overview ............................................................... 22 
2.5 Device Description ........................................................................................................ 23 
2.5.1  Console .........................................................................................................................23 
2.5.2 Molar Handpiece ...........................................................................................................24 
2.5.3 Treatment Fluids ...........................................................................................................26 
2.6 Sonendo System Technology: Previous Clinical Experience ......................................... 26 
3.0 STUDY PURPOSE AND OBJECTIVES ..................................................................................27 
4.0 STUDY DESIGN ................................................................................................................ 28  
5.0 STUDY POPULATION ........................................................................................................28 
5.1 Pre-Procedure Inclusion Criteria ...................................................................................28 
5.2 Pre-Procedure Exclusion Criteria ..................................................................................28 
24. Patients with any medical condition causing chronic pain (e.g. spinal injury) ............. 29 

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5.3 Intra-Procedure Inclusion Criteria ................................................................................30 
5.4 Intra-Procedure Exclusion Criteria ................................................................................30 
6.0 DENTAL CONE BEAM CT SUB-SET ....................................................................................30 
7.0 STUDY PROCEDURES ........................................................................................................30 
7.1 Pre-Screening Visit by Screening Dentist ...................................................................... 30 
7.1.1 Screening Code ..............................................................................................................32 
7.2 Pre-Screening Review and Notification ........................................................................ 33 
7.2.1 Pre-Screening by the PI .................................................................................................33 
7.2.2 Pre-Screening by the Screening Dentist ........................................................................33 
7.2.3 Notification of Pre-Screening Outcome to the Screening Dentist .................................33 
7.2.4 Pre-Screen Failures ........................................................................................................33 
7.4.1 Informed Consent ..........................................................................................................33 
7.4.3 Screening .......................................................................................................................34 
7.4.4 Baseline Exam ...............................................................................................................34 
7.4.5 Baseline Exam Re-Assessment ......................................................................................38 
7.5 Procedure Visit .............................................................................................................. 39 
7.5.1 Sonendo GentleWave System Preparation ...................................................................39 
7.5.2 Root Canal Therapy Procedure Preparation .................................................................39 
7.5.3 Orifice Negotiation ........................................................................................................ 40 
7.6 Enrollment .................................................................................................................... 41 
7.6.1 Screen Failures ..............................................................................................................41 
7.6.2 Subject Identification ....................................................................................................41 
7.7 Sonendo GentleWave System Treatment .................................................................... 42 
7.7.1 Sonendo GentleWave System Treatment Process ........................................................42 
7.7.2 Leakage .........................................................................................................................42 
7.8 Control of Bleeding ....................................................................................................... 43 
7.9 Second Procedure Visit ................................................................................................. 43 
7.10 Inability to Complete Treatment .................................................................................. 43 

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7.11 Obturation..................................................................................................................... 43 
7.12 Coronal Seal .................................................................................................................. 44 
7.13 Intra-Procedure Assessments and Evaluations ............................................................ 44 
7.14 Post Procedure Assessments and Evaluations ............................................................. 45 
7.15 Out-Patient Questionnaires .......................................................................................... 45 
7.15.1 McGill Short Form Pain Questionnaire ....................................................................... 45 
7.16 Crown Placement .......................................................................................................... 46 
7.17 Follow-Up Study Visits .................................................................................................. 46 
7.17.1 Follow-Up Study Visit Windows ..................................................................................46 
7.17.2 Follow-Up Visit Evaluations and Assessments ............................................................46 
7.18 Unscheduled Visits ........................................................................................................ 49 
7.19 Mail, Telephone and Dentist Contact ........................................................................... 50 
7.20 Subject Completion ....................................................................................................... 50 
8.0 SCHEDULE OF VISITS ........................................................................................................51 
9.0 PATIENT AND SUBJECT STATUS .......................................................................................52 
9.1 Pre-Screen Failure ......................................................................................................... 52 
9.2 Pre-Screen Closure ........................................................................................................ 52 
9.3 Screen Failure................................................................................................................ 52 
9.4 Subject versus Patient ................................................................................................... 52 
9.5 Enrolled……. .................................................................................................................. 52 
9.7 Termination ................................................................................................................... 52 
9.8 Withdrawal ................................................................................................................... 53 
9.9 Discontinuation ............................................................................................................. 53 
9.10 Lost to Follow-up .......................................................................................................... 53 
10.0 ADVERSE EVENTS .............................................................................................................53 
10.1 Definition of Adverse Events ........................................................................................ 53 
10.2 Definition of Serious Adverse Events (SAE) .................................................................. 54 

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10.3 Adverse Event Assessments .......................................................................................... 54 
10.4 Unresolved Adverse Events .......................................................................................... 55 
10.5 Assessment of Causality ................................................................................................ 55 
10.5.1 Definition of Sonendo GentleWave System Treatment ............................................... 56 
10.6 Serious Adverse Event Reporting.................................................................................. 56 
10.7 Unanticipated Adverse Device Effect ........................................................................... 57 
10.8    Anticipated Adverse Events ....................................................................................... 57 
10.8.1 Risks generally associated with any dental procedure include, but are not limited to, the 
following: ...............................................................................................................................57 
10.8.2   Potential risks for root canal therapy include, but are not limited to, the following:58 
10.9    Other Potential Risks ................................................................................................. 59 
10.9.1   Radiation Risks ..........................................................................................................59 
10.9.2   Cone Beam Computed Tomography (CBCT) Radiation Risks ....................................59 
10.10    Definitions of Adverse Events .................................................................................. 59 
11.0 BENEFITS……….. ................................................................................................................60 
12.0 PROTOCOL DEVIATIONS ...................................................................................................60 
12.1.1 
Protocol Deviation Types ........................................................................................60 
13.0 STATISTICAL METHODS ....................................................................................................61 
13.1 Sample Size ................................................................................................................... 61 
13.2 Analysis Populations and Handling of Dropouts ........................................................... 61 
13.3 Demographics and Baseline Characteristics ................................................................. 62 
13.4 Method for the Analysis of Primary Effectiveness Parameter ..................................... 62 
13.5 Secondary Analysis ........................................................................................................ 62 
13.6 Safety Analyses ............................................................................................................. 62 
13.7 Handling Missing Effectiveness and Safety Data .......................................................... 62 
13.8 Handling Post-Market Analysis ..................................................................................... 62 
14.0 DATA REPORTING.............................................................................................................62 

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15.0 STUDY MONITORING .......................................................................................................63 
16.0 ETHICAL AND REGULATORY CONSIDERATIONS ...............................................................64 
17.0 SPONSOR RESPONSIBILITIES ............................................................................................64 
18.0 INVESTIGATOR’S RESPONSIBILITIES .................................................................................64 
18.1 Retention of Records .................................................................................................... 65 
18.2 Study Documents .......................................................................................................... 65 
18.3 Subject Selection ........................................................................................................... 66 
18.4 Subject Informed Consent ............................................................................................ 66 
18.5 Confidentiality ............................................................................................................... 66 
19.0 INVESTIGATOR TRAINING ................................................................................................66 
19.1 Roll-In Subjects .............................................................................................................. 67 
APPENDIX I. HEALING LITERATURE REPORT .............................................................................68 
APPENDIX II. INFORMED CONSENT FORM ...............................................................................69 
APPENDIX III. SCREENING PROTOCOL .......................................................................................70 
APPENDIX IV. CONFIDENTIALITY ...............................................................................................71 
APPENDIX V. REFERENCES ........................................................................................................72 
 
 
 
 
 
 

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SPONSOR APPROVAL PAGE 
 
Sonendo Sponsored Study 
A Prospective, Multicenter Study Comparing Healing After Treatment with the 
Sonendo GentleWave™ System as Compared to a Traditional Root Canal Therapy 
Literature Control (SUPREME) 
Clinical Protocol Number: CS-06 Revision B 
 
Date: 23 March 2015 
 
I have read this protocol and I approve the design of this study. 
 
 
__________________________________ 
                             
Printed Name of V.P., Regulatory/Clinical Affairs & Quality       
 
 
 
__________________________________ 
 
 
________________________ 
Signature of V.P., Regulatory/Clinical Affairs & Quality             Date (DD/MMM/YYYY) 
 
 

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Study Protocol# CS-06 Revision B 
23 March 2015 
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Study Protocol# CS-06 Revision B 
23 March 2015 
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INVESTIGATOR APPROVAL PAGE 
 
Sonendo Sponsored Study 
A Prospective, Multicenter Study Comparing Healing After Treatment with the 
Sonendo GentleWave™ System as Compared to a Traditional Root Canal Therapy 
Literature Control (SUPREME) 
Clinical Protocol Number: CS-06, Revision B 
 
Date: 23 March 2015 
 
I have read this protocol and agree to adhere to the requirements. I will provide 
copies of this protocol and all pertinent information to the study personnel under 
my supervision. I will discuss this material with them and ensure they are fully 
informed regarding the use of the device. I will ensure that the study is conducted 
in compliance with the protocol, Good Clinical Practices and all applicable 
regulatory requirements. 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
Investigator’s Signature 
 
Date 
 

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PERSONNEL AND FACILITIES 
STUDY SPONSOR: 
SONENDO INC. 
SARA TISH RODRIGUEZ, DIRECTOR OF CLINICAL AFFAIRS 
26061 MERIT CIRCLE, SUITE 102 
LAGUNA HILLS, CALIFORNIA 92653 
PHONE:   (949) 766-3636 
FAX:   (949) 305-5201 
EMAIL: CLINICAL@SONENDO.COM 
 
 
 
 

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1.0 STUDY SYNOPSIS 
Study Title 
A Prospective, Multicenter Study Comparing Healing After 
Treatment with the Sonendo GentleWave™ System as Compared to 
a Traditional Root Canal Therapy Literature Control (SUPREME) 
Study Short Title  
The SUPREME Study 
Purpose 
The purpose of this study is to assess healing rates following root 
canal therapy with the Sonendo GentleWave System as compared 
to a literature control.  
Objective 
The objective of this study is to evaluate healing and post procedure 
pain following root canal therapy (RCT) of 1st and 2nd molars treated 
with the Sonendo GentleWave System and to compare it to data 
presented in a traditional RCT literature control.   
Sites 
Up to 8 clinical sites in the United States 
Study Design 
A prospective, non-significant risk device, literature controlled, 
study evaluating healing rates for the Sonendo GentleWave System 
in the treatment of 1st and 2nd molars indicated for root canal 
therapy. 
 All patients will receive root canal therapy with the Sonendo 
GentleWave System. All patients will be followed for 24 months 
post procedure.   
Study Population 
Up to 120 subjects, aged 18 to 75 years, who have a 1st or 2nd molar 
tooth indicated for root canal therapy, will be enrolled in the study.  
Study Duration 
Duration of  24 months 
Study Visits: Screening, Baseline, Treatment (within 7 days of 
Baseline) and  6, 12, 18, and 24 months.  
Expected Enrollment Commencement: August 2014 
Expected Enrollment Period: January 2016   
Expected Study Completion: March 2018 
Sample Size  
86 subjects 
Roll-in patients: Up to 5 per site 
Lost- to Follow-up 20%: 18 Subjects 
Total: Up to 120 patients 
Roll-In Subjects 
Roll-in subjects, up to 5 per clinical site, will be included in the 
study. The Sponsor will determine the required number of Roll-In 
cases depending on the Investigator’s experience with the Sonendo 

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GentleWave System and training. Roll-in cases may not be included 
in the final data analysis. 
Study Cohorts 
There will be two cohorts within the study. The two cohorts are 
defined as follows: 
• All subjects meeting the Treatment Complete criteria 
• All subjects meeting the Treatment Incomplete criteria 
Only subjects in the Treatment Complete Cohort will be followed 
for 24 months according to the study visit schedule. Only subjects in 
the Treatment Complete cohort will be included in the primary 
effectiveness and safety endpoint analyses.  
Treatment Complete 
Treatment Complete is defined as any subject that received 100% of 
the Sonendo GentleWave Treatment (Treatment) over the course of 
no more than two visits. 
Definition of Sonendo 
GentleWave System 
Treatment  
The Sonendo GentleWave System Treatment is defined as beginning 
when LuxaBite® (DMG) or a Sonendo Tooth Cap is placed until 100% 
completion of the Sonendo GentleWave System. All other 
procedures will be categorized as traditional RCT procedures. 
Indication 
The Sonendo GentleWave System is intended to prepare, clean, and 
irrigate 1st and 2nd molar teeth indicated for root canal therapy.  
Primary Effectiveness 
Endpoint 
Subject teeth in the Treatment Complete cohort that are healed or 
are healing at the twenty-four month follow-up visit.  
Healed is defined by absence of a radiographic indication of apical 
periodontitis (PAI <3) and absence of clinical signs and symptoms.  
Healing is defined by a reduction of radiolucency (if radiolucency is 
present at Baseline) and/or reduction of clinical signs and symptoms 
(if clinical signs and symptoms are present at Baseline)  
Secondary analysis will be completed after all Treatment Complete 
subjects complete the 12 month follow-up.  Additional analysis may 
occur.  
Primary Safety Endpoint 
Incidence of device related adverse events as defined by 
perforation, instrument separation, root fracture, sodium 
hypochlorite accident, or Gutta Percha extrusion, as related to the 
device for the Treatment Complete cohort.   

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Secondary Endpoint(s) 
The following outcomes will be assessed: 
1. McGill Short Form Pain Questionnaire 
2. Gracely Descriptor Differential Scale (DDS) 
3. Patient Satisfaction Survey  
4. AAE Case Difficulty Assessment 
5. Soft Tissue Lesions  
6. Swelling  
7. Root Canal Therapy Retreatment 
8. Treatment Time 
9. Procedure Time 
10. Periapical Index (PAI) analyzed utilizing 
radiographic analysis by independent reviewer 
11. Cone Beam Computed Tomography (CBCT) Sub-Set 
Evaluation 
12. Additional Radiographic Analysis may be completed 
Pre-Procedure Inclusion 
Criteria 
1. The patient is 18 to 75 years of age  
2. The subject tooth is indicated for root canal therapy 
3. The subject tooth is a 1st  or 2nd  molar  
4. The patient is mentally and physically able and willing to fully 
comply with this protocol, including adhering to the follow-up 
schedule and completing forms and questionnaires 
5. Signed Informed Consent Form 
Pre-Procedure Exclusion 
Criteria 
1. Poor oral hygiene according to a Poor, Fair, Good Scale 
 
Poor:  There is evidence of: generalized inflammation and        
             swelling of gingival tissue, generalized bleeding on probing    
             and/or generalized plaque/calculus accumulation     
          
2. Subject tooth with ≥ Class II Mobility  
3. Subject tooth with Periodontal Pocket Depth ≥ 6 
4. Periodontal probe reaches the apex  of the subject tooth 
5. Furcation involvement originating from periodontal disease, on 
the subject tooth, one or two adjacent teeth in direct contact 
with the subject tooth 

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6. Subject tooth with ≥ Class III endodontic furcation involvement  
7. Subject tooth with open or incompletely formed root apices 
8. Vertical fracture, horizontal fracture, or perforation extending 
below the Cemento-Enamel Junction (CEJ) of the subject tooth 
9. Caries or another condition of the subject tooth that  
a. prevents adequate seal of the device 
b. requires a separate procedure for crown lengthening  
c. requires a post 
d. provides inadequate biological width for crown 
retention  
10. Any dental treatment on the subject tooth completed with the 
known use of devitalizers or formocresol  
11. Subject tooth having previous or attempted pulpectomy or root 
canal therapy 
12. One or two adjacent teeth in direct contact with the subject 
tooth requiring root canal therapy, pulpectomy or pulpotomy 
13. Any tooth on the same side of the oral cavity as the subject 
tooth with a source of pain 
14. Extraoral swelling on or around the subject tooth that has not 
undergone antibiotic treatment or a procedure to treat the 
swelling prior to RCT 
15. Any condition that would preclude tolerance of a root canal 
therapy including but not limited to being in a reclined and 
prolonged position in a dental chair, use of a dental dam, or 
ability to  have an open mouth for extended periods of time 
(>15 minutes) (e.g. history of seizure within the last 5 years, 
severe asthma, or extreme gag reflex) 
16. Any other condition that the Investigator determines is 
unacceptable for enrollment into the study 
17. Nonodontogenic facial pain 
18. History of cancer within the oro-maxillofacial region  
19. History of any cancer within the last two years, including skin 
cancer 
20. History of head and/or neck radiation therapy 

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21. Immunocompromised patients (i.e. corticosteroid usage) 
22. Any medical history that affects blood coagulation (e.g. bleeding 
disorders) 
23. Long-term or current usage of medication that affects blood 
coagulation. This includes herbal or other over the counter 
medications. Exception: Patients taking daily low dose Aspirin 
(81mg) or patients that can stop Aspirin or Ibuprofen products 
three (3) days prior to procedure, should not be excluded from 
the study.  
24. Patients with any medical condition causing chronic pain (e.g. 
spinal injury)  
25. Patients on long-term (i.e. more than three months) narcotic, 
opioid, or other similar analgesic (e.g. daily narcotic pain 
medication for spinal disease) 
26. Any infectious diseases (e.g. HIV, Hepatitis B, Hepatitis C, 
Tuberculosis, BCE, or Prion diseases) 
27. Uncontrolled diabetes or diabetics with unknown hemoglobin  
A1c levels 
28. A known allergy to local anesthetics, titanium carbon-nitride or 
stainless steel 
29. A pacemaker, implantable cardiac defibrillator (ICD), or other 
implanted electronic medical device 
30. Patient is institutionalized, a prisoner, homeless, or on active 
military duty  
31. Patients with documented current alcohol and/or drug abuse 
32. Patient is pregnant or planning to become pregnant within the 
duration of the study 
33. Participated in any clinical study in the past 30 days 
Intra-Procedure Inclusion 
Criteria 
1. Successful removal of caries on the subject tooth  
2. Successful completion of build-up to restore the subject tooth 
crown when used in combination with the Occlusal Plate. 
Exception: This does not apply when the Tooth Cap is utilized. 
Intra-Procedure Exclusion 
Criteria 
1. Use of laser devices 
2. Subject tooth that requires crown lengthening 

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3. Subject tooth that requires a post 
4. Subject tooth that provides inadequate biological width for 
crown retention  
5. Perforation of the subject tooth  
6. Vertical fracture or horizontal fracture below the Cemento-
Enamel Junction (CEJ) of the subject tooth  
7. Internal or external root resorption that affects the use of 
Sonendo GentleWave System 
Assessments Completed 
for the Study 
Data will be collected on the following Standard of Care 
Assessments: 
• Medical and Dental History and Exam 
• Medication Regime 
• Periapical Radiographs: PA Parallel Periapical Index (PAI) Scoring 
by an independent reviewer  
• General Dental Assessments including Tooth Number, Oral 
Hygiene, Probing Pocket Depth, Mobility Assessment, Swelling, 
Soft Tissue Lesions and Furcation Involvement 
• Endodontic Assessments including Periradicular Tests 
(Percussion and Palpation), Cold Test, Root Resorption, Pulp 
Diagnosis, and Periradicular Diagnosis 
• Procedural details including Calcification Assessment, Irrigation, 
and Material Utilization 
• Sonendo GentleWave System Devices Utilized 
• Traditional Root Canal Therapy Devices and Instruments Utilized 
• Procedure Time (dental dam placement to removal) 
• Sonendo GentleWave Treatment Time (Treatment Time) 
• Cone Beam Computed Tomography (CBCT) Sub-Set Evaluation 
• Radiographic Evaluation of Obturation  
• Adverse Events 
Questionnaires 
Completed for the Study 
The following questionnaires will be completed for the study:  
• McGill Short Form Pain Questionnaire at Baseline, 1, 2, 3, 7 and 
14 days post-procedure, at all Follow-up Visits and at 
Unscheduled Visits, as necessary  

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• Gracely Descriptor Differential Scale (DDS) at Baseline, 
immediately post procedure and 1 day post procedure 
• Patient Satisfaction Survey immediately post procedure 
• 
AAE Case Difficulty Assessment post procedure  
 
 

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2.0   INTRODUCTION AND RATIONALE  
2.1   General Background 
Over 15 million cases of root canal therapy (RCT) are performed each year in the United States1. 
If performed effectively, RCT can be the best treatment for a necrotic or irreversibly inflamed 
pulp. However, the current methodologies rely on technologies invented over 200 years ago and 
which are not only inefficient, but also are associated with several procedural and safety issues, 
such as leaving uninstrumented recesses, root weakening, ledge formation, perforations, over-
instrumentation, instrument separation, extrusion of debris into the periapical tissue, and 
periapical extrusion of sodium hypochlorite. The introduction of the Sonendo GentleWave 
device may substantially reduce and, in some cases, eliminate the risks associated with a 
traditional root canal procedure.  
2.2   Drawbacks of Current Methods in Root Canal Therapy 
After more than two centuries, modern endodontics still suffers from a number of procedural 
and safety issues that diminish the achievement of consistently successful outcomes in RCT. 
Some of these issues are briefly discussed below. 
2.2.1 Leaving Uninstrumented Recesses 
The conventional method of RCT does not uniformly and completely clean canals. Although 
metallic files (e.g nickel titanium) are flexible and conform to the curvature of a canal, they still 
do not touch all root canal surfaces as they are fundamentally rigid, round pieces of metal. 
Therefore, it is typical for at least 35% (and as high as 50%) of the canal surface to be passed 
over during instrumentation2, 3. This bypass, combined with the inefficiency of current irrigation 
methods, results in 40% to 60% of canals still yielding positive cultures after instrumentation 
and irrigation with different sodium hypochlorite (NaOCl) concentrations4, 5. 
Another factor increasing the chance of leaving uninstrumented recesses is the canal curvature. 
This issue is specifically the case for long and narrow oval canals (ratio of major/minor canal 
diameters is greater than 2.0). Hulsmann et al.6 studied the RCTs performed on mandibular 
molars using two different rotary instruments. They found that 81-88% of the canals will be left 
with some degree of uninstrumented recesses. Vaudt et al.7 compared the performance of the 
Alpha System and ProTaper Universal with manual techniques and found that in 80% of the 
manually treated curved mesial canals of mandibular molars more than 25% of the canal surface 
remained uninstrumented.  
2.2.2 Root Weakening 
Instrumentation increases the diameter of the root canals to allow for proper flow of irrigant 
and obturation. This filing also removes dentin from canal walls, which weakens the root8. From 
a strength and materials perspective, it is straightforward that removing the natural dentinal 
structure reduces the tooth strength. Consequently, RCT may be associated with some level of 
root weakening. A high price is paid solely due to the inability of the current methodology to 
remove the pulp and the bacteria without damaging and weakening the natural structure of the 

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tooth. This adverse treatment effect becomes even more pronounced when the canal cross-
sectional shape deviates from a circular shape and when canals are curved. For instance, long 
oval shapes are generally impossible to completely instrument without perforating or severely 
weakening the roots9. While nature is elegant, it rarely forms perfectly straight and wide canals 
that are well-situated to the equipment and technical limitations of the current standard of care. 
2.2.3 Ledge Formation 
Ledge formation is among the most commonly observed procedural errors during root canal 
instrumentation10. It is defined as a deviation from the original canal curvature, where 
communication with the apical constriction is lost. The presence of a ledge might exclude the 
possibility of achieving an adequately shaped canal that reaches the ideal working length, which 
may result in incomplete instrumentation and disinfection of the root canal system, as well as 
incomplete filling of the canal. The root canal space apical to the ledge is difficult to adequately 
clean and shape; therefore, ledges frequently result in persistent periapical pathosis after the 
endodontic treatment. Consequently, there is a causal relationship between ledge formation and 
unfavorable endodontic treatment outcomes11, 12, 13, 14, 15, 16. Some of the reported frequencies 
of ledge formation include: 11% by Bergenholtz et al.17, 10% by Stadler et al.18, 46% by Greene 
and Krell15, 52% by Kapalas and Lambrianidis12, and 25% by Eleftheriadis and Lambrianidis19. In 
one study12, endodontists performed RCTs and reportedly created ledges in 33% of previously 
untreated canals and 41% of endodontic retreatment cases. 
2.2.4 Perforation 
Root perforations are shown to be one of the eminent causes of endodontic failures20. They are 
artificial openings in root walls created by boring, piercing, or filing that result in a communication 
between the pulp space and periodontal tissues21. These openings may cause secondary 
periodontal involvement and eventual loss of the tooth22. Iatrogenic perforations are often due 
to insufficient attention to the details of internal anatomy and a failure to consider anatomic 
variations. They may also be due to lack of information on the canal anatomy and morphology, 
as the dental radiographs only provide a buccolingual view of the tooth. Accidental root 
perforations, which may have serious implications, occur in approximately 2–12% of 
endodontically treated teeth20, 21, 22, 23. Bacterial infection emanating either from the root canal 
or the periodontal tissues, or both, prevents healing and promotes inflammatory sequels where 
the supporting tissues have been exposed. This bacterial exposure may be followed by painful 
conditions, abscesses, and fistulae, including bone resorption processes. Once an infectious 
process has established itself at the perforation site, prognosis for treatment is precarious and 
the complication may prompt extraction of the affected tooth23. 
2.2.5 Penetration of Instruments into the Periapical Tissue 
Another commonly occurring iatrogenic error is the penetration of the endodontic instruments 
beyond the apical foramen, which results in damage to the periapical tissue and triggers foreign 
body immunological response (Figure 1). It is well accepted and proven that instrumentation 
beyond the apical foramen should be avoided as it reduces the success rate24, 25, 26, 27. In clinical 

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practice, one of the major difficulties is that the apical constriction cannot be detected 
radiographically29. According to ElAyouti et al.28, the endodontic instruments penetrate beyond 
the apical foramen in 25% of cases. In 10% of cases, the file penetration is greater than 1mm. 
They argued that this penetration is mainly due to the fact that the apical foramen is located 
laterally in 78% to 93% of the cases. ElAyouti et al.28 determined that a seemingly accurate 
working length (ending radiographically 0 to 2mm short of the radiographic apex) frequently 
resulted in instrumentation beyond the apical foramen. Even the advent of apex locators has not 
been able to resolve the issue as the function of apex locators is consistent in only 85% of 
patients29. 
 
 
Figure 1: The photograph of the extracted tooth illustrates the file beyond the apical foramen. Examiners indicated that the file was 
at the correct radiographic working length. This penetration error is an example of an underestimation of the actual working length 
distance, causing the file to be too long30. 
2.2.6 Instrument Separation 
After decades of research and development, intracanal breakage of root canal instruments 
continually causes endodontists and patients considerable anxiety. Removal of separated 
instruments requires additional dentin removal and irrigation which generally results in 
perforated or severely weakened roots. An 18-month study involving 7,159 discarded rotary NiTi 
instruments from 14 endodontists worldwide reported a frequency of 5% instrument 
separation31. A review of the literature reveals that the mean prevalence of retained fractured 
endodontic hand instruments (mostly stainless steel files) is approximately 1.6%, with a range of 
0.7% to 7.4%32. However, it bears mentioning that much of the published literature is comprised 
of outcome studies that do not specifically evaluate prevalence of instrument fracture. The mean 
clinical fracture frequency of rotary NiTi instruments is approximately 1.0% with a range of 0.4 to 
3.7%32. Suter et al.33 analyzed the probability of removing fractured instruments from root canals. 
During an 18-month study, they found that a fractured instrument was left inside 1% of all the 
root canals treated.  
2.2.7 Extrusion of Debris into the Periapical Tissue 
During preparation, irrigant (i.e. sodium hypochlorite) and debris (e.g. bacteria, dentin debris, 
and necrotic tissue) are often extruded into the periradicular region, leading to periapical 
inflammation and postoperative flare-ups34. It is known that inflammatory reactions can cause 

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bone resorption, edema, and pain35. All preparation techniques and instruments have been 
reported to be associated with extrusion of infected debris, even when preparation is maintained 
short of the apical terminus36, 37, 38, 39, 40, 41, 42, 43, 44. There are several studies analyzing the apical 
debris extrusion resulting from different instrument types and instrumentation techniques38, 39, 
45, 46. Various conclusions have been drawn, but all studies agree that, regardless of the 
instrument type or the technique, currently practiced RCT is associated with some level of apical 
debris extrusion, which affects the healing process significantly.  
2.2.8 Extrusion of Sodium Hypochlorite into the Periodontal Tissues 
Root canal irrigation with sodium hypochlorite (NaOCl) plays an important role in the 
debridement and disinfection of the root canal system and is an integral part of traditional root 
canal procedures. However, sodium hypochlorite has a pH of approximately 11 to 12, causing 
injury upon entering the body. If the irrigating solution permeates the periodontal tissues, it can 
result in inflammation, postoperative pain, and extended healing. Other commonly reported 
responses include severe pain, a rapidly developing edema, hematomas, necrosis, and abscesses. 
Several reports of the effects of sodium hypochlorite accidentally spreading beyond the interior 
regions of the tooth can be found in the literature47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57. Additionally, 
instrumentation and the enlargement of canals have a significant effect on the penetration of 
sodium hypochlorite through the apical foramen. Salzgeber and Brilliant46 showed that 
instrumentation beyond a size 35 may allow penetration of irrigant beyond the apex and into 
periapical tissue. 
2.3   Healing Rates for Traditional Root Canal Therapy 
While the literature presents many different definitions of healing, any future endodontic 
clinical studies should utilize a healing endpoint based upon both clinical and radiographic 
findings.  The radiographic finding should be based upon the periapical index score, with PAI 1 
or 2 indicating success.  Additionally, no clinical signs or symptoms should be present.  
Separating complete healing and incomplete healing will also more clearly present study results. 
Success rates over time varied widely across the literature.  Generally, most healing had 
occurred 1 year following root canal treatment, though healing was shown to take up to 4 years 
or more.  Thus, success rates should also be presented at each time-point studied and not just 
a cumulative number over a range of follow-up periods. An approximate success rate for 1 year 
follow-up would be 68-70% while that success rate would increase to 80-85% after four years.   
While effective chemomechanical canal preparation is extremely important, the literature 
indicated other factors significantly affected long-term prognosis for the patient.  If a patient 
presented with apical periodontitis and had a periapical lesion, the long-term success was 
significantly lower.  Thus, including a large number of patients with a pre-operative periapical 
radiolucency could result in lower long-term success rates. Effective obturation to within 2 mm 
within the radiographic apex and effective coronal restorations also improved long-term 
success.  The number of roots treated and mid-treatment complications could also impact 
success rates.  These facts highlight the importance of choosing the appropriate patient 

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population and standardizing the treatment regimen in clinical studies so that the variable being 
studied can be reliably assessed. 
While a number of studies have been published regarding the healing and success rates 
following root canal treatment, the quality of this literature is generally less than other medical 
disciplines.  A dearth of randomized, controlled trials exists in endodontic research, and a large 
number of retrospective studies are published.  Finally, the lack of standardization of study 
design and clinical endpoints across studies makes the comparison of results between studies 
difficult at best. (See Appendix I. Healing Literature Report) 
2.4 Sonendo GentleWave Technology Overview 
The Sonendo GentleWave System (System) introduces a novel method of cleaning root canals 
that may be safer, less invasive, and more efficient. It has been designed to conserve more of 
the natural structure of the tooth and to minimize procedural and safety issues. The System, 
when used in combination with the Molar Handpiece (Figure 2), has been designed to clean root 
canals of molar teeth without requiring excessive enlargement of root canals. Traditional root 
canal therapy devices enter into the root canal of the tooth, whereas the System’s treatment 
tube (guide tube) is designed to enter only to the pulpal chamber. It has been designed to clean 
the root canals remotely and simultaneously in a matter of minutes.  
 
Figure 2: Illustrations of the Molar Handpiece applied to a molar tooth. The Handpiece delivers a stream of treatment fluid in such a way as 
to generate a set of physicochemical phenomena that effectively, yet safely, clean the pulpal space of the tooth. 
The Sonendo GentleWave treatment is designed for use with minimal instrumentation of the 
root canals in order to facilitate obturation of the root canal system. It is also thought that by 
minimizing the shaping process, a large amount of tooth structure may be saved, as opposed to 
traditional practice, which typically removes this structure. In addition, the System may reduce 
the risks associated with instrumentation, i.e. ledge formation, instrument separation, and 
perforation. Unlike conventional root canal treatment, irrigation solutions are delivered into the 
root canal system without requiring the irrigation component (i.e. the needle) to be inserted 
inside each individual canal. With the System, the solution enters the tooth at about 1 mm above 

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the pulpal chamber floor. This alteration from traditional root canal therapy may minimize the 
risk of irrigant extrusion into the periapical tissues. 
2.5 Device Description 
The Sonendo GentleWave System (System) is comprised of two units: the Sonendo 
GentleWaveTM Console (Console) and the Molar Handpiece (Handpiece). The Console prepares 
and delivers treatment fluid to the Handpiece. The Handpiece comes with additional accessories 
needed to interface the Handpiece to the Console and tooth.  
The System delivers treatment fluid into the axis cavity of the tooth in such a way that it creates 
hydroacoustic waves within the treatment fluid accumulated inside the tooth. The treatment 
fluid delivered into the tooth removes organic tissues and smear layer from the root canal 
system. The Console aspirates the treatment fluid and organic/inorganic matter from the tooth 
into the Console waste canister. The Console is designed for use with a treatment fluid of 8-10% 
sodium 
hypochlorite 
(NaOCl) 
without 
surfactants, 
17% 
neutral 
pH 
buffered 
ethylenediaminetetraacetic acid (EDTA), and distilled water. 
All of the materials coming into contact with the patient and/or the treatment fluid have known 
biocompatibility and a history of acceptable use in medical device applications.  
2.5.1  Console 
The Console (Figure 3) is a semi-stationary unit designed to prepare and deliver treatment fluid 
to the Handpiece. It is comprised of a treatment fluid Delivery Hose, a Suction Hose, a Purge 
Port, Evacuation Tubing, a User Interface Screen, a distilled water Reservoir, an NaOCl Reservoir, 
an EDTA Reservoir, a Waste Canister, and a Foot Pedal. Similar to the dental handpieces 
currently used in dentistry, the System is activated by a foot pedal, which must remain 
depressed in order to operate the System.  
The Console is made up of five functional subgroups of components: 
1. 
Delivery System  
The Delivery System is composed primarily of a pump. This pump operates in 
two cycles: a delivery cycle and a retraction cycle. During the delivery cycle, the 
piston moves forward in order to pump the treatment fluid through the outlet. 
The pump operates with two cylinders/pistons (continuous flow). During the 
retraction cycle, more water is drawn into the cylinder, readying the System for 
the upcoming cycle. 
2. 
Mixing System  
The Mixing System is designed to mix and prepare the treatment fluids NaOCl, 
water and EDTA at the prescribed concentrations. 
3. 
Degassing System 
The Degassing System is configured to reduce dissolved gasses from treatment 
fluids as they are passed through the degassing cartridge.  

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4. 
User Interface 
A touch-panel screen is mounted on the outside of the Console and provides 
the operator with real-time feedback relating to the treatment progress. 
5. 
Evacuation System 
The Evacuation System is designed to prevent waste and treatment fluid from 
spraying or spilling from the Handpiece or tooth during normal operation. In 
addition, the fluid that passes through the System and into the Handpiece is 
then returned to the Console through the Evacuation System.  
 
Figure 3. Example image of the Sonendo GentleWave System 
The treatment fluid containers are connected to the System using standard quick-connects that 
are included in Food and Drug Administration’s (FDA) U.S. Pharmacopeia (USP) Class VI list of 
established materials. The System is designed to comply with applicable electrical safety 
standards for medical electrical equipment. The user will activate and maintain operation of the 
System by depressing the foot pedal. 
2.5.2 Molar Handpiece 
The Molar Handpiece comes with the following accessory items which are needed, in addition 
to items commonly used in standard dental practice, in order to successfully carry out the 
Sonendo GentleWave treatment: 
1. Molar Handpiece 
The Handpiece consists of a quick-connect fitting to the delivery hose, fluid 
conduit, distal fluid chamber, nozzle, delivery tube, and clamshell plastic grip. 

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The Handpiece is designed to be a single use, disposable component. The 
Handpiece may be sterilized by a steam autoclave or gamma irradiation.  
The Handpiece, containing proprietary features such as a nozzle and a 
treatment tube (also called a guide tube), delivers a stream of treatment fluid 
into the pulp chamber of the tooth. This is completed in such a way that it 
creates hydroacoustic waves within the treatment fluid accumulated inside the 
tooth. The treatment fluid is a low concentration sodium hypochlorite (NaOCl) 
solution, which is the most commonly used irrigant in traditional endodontic 
procedures for dissolution of organic matter and for added sterility. The stream 
of solution delivered into the tooth is designed to be dispersed and deflected 
by proprietary features at the distal end of the treatment tube. This is designed 
to create a safe yet effective circulation (irrigation) of the solution within the 
tooth. These physicochemical phenomena occurring inside the pulpal space 
may be powerful enough to remove all of the organic tissues and 
microorganisms from the root canals in just a few minutes, yet gentle enough 
not to affect the hard structure of the tooth or the periodontal tissues enclosing 
the roots. The used treatment fluid flows from the tooth into a Waste Canister 
rendering the procedure dry and contained.  
The Handpieces are produced by approved suppliers based on Sonendo 
drawings and are inspected upon receipt. They are checked for dimensional 
accuracy, performance, production, and inclusion of appropriate material 
certifications in the shipment documentation.  
2. Single Use Suction Hose 
The single use Suction Hose is designed to suction air and fluids during the 
procedure. The Suction Hose is made from Tigon tubing and Policarbonate 
fittings.  
3.  Occlusal Plate 
The Occlusal Plate features a handle, a circular area, and a pin protruding from 
the middle of the circular area. This pin helps locate the center of the tooth 
surface in order to facilitate locating the pulp chamber. The Occlusal Plate is 
used to form a flat surface, called an Occlusal Platform, so that the Handpiece 
can create a seal against it. The Occlusal Plate is made from polycarbonate.  
4. Molar Tooth Caps 
The Molar Tooth Caps are designed to provide the interface, the Occlusal 
Platform that is required for use with the Molar Handpiece when a substantial 
amount of the tooth's original structure is missing. In these situations, it is 
difficult to prepare the tooth for treatment with the Sonendo GentleWave 
System using the Occlusal Plate and impression material, so the Molar Tooth 

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Caps may be used instead. The main components of the Molar Tooth Cap 
consist of polypropylene. 
5.  Set of Depth Gauges 
The Depth Gauges are utilized to determine the depth of the pulp chamber. 
This is done to ensure the correct selection of the Sealing Cap size and correct 
positioning of the Treatment Tube (guide tube) within the pulp chamber. The 
Depth Gauges are made from polycarbonate.  
6.  Set of Sealing Caps  
The Sealing Caps are designed to adapt the Molar Handpiece to different sized 
teeth. Each Sealing Cap is designed to properly position the Handpiece with 
respect to the floor of the pulp chamber. The Sealing Caps are made from 
polycarbonate, medical grade adhesives, silicone and/or polycarbonate. 
2.5.3 Treatment Fluids 
The three treatment fluids utilized during the System operation are sodium hypochlorite 
(NaOCl), ethylenediaminetetraacetic acid (EDTA) and distilled water. All fluids are introduced for 
treatment through the Console and Handpieces.  
The first treatment fluid is a NaOCl solution. NaOCl is the most commonly utilized irrigation fluid 
during traditional root canal therapy, which is typically introduced via a dental syringe. This 
solution is prepared by the Console, which mixes distilled water and regular 8-10% NaOCl.  
In addition, the root canals will be irrigated with EDTA solution. This solution is prepared by the 
Console, which mixes distilled water and 17% EDTA. The System automatically introduces EDTA 
into the tooth, while standard dental practice uses a dental syringe to release EDTA.  
2.6  Sonendo System Technology: Previous Clinical Experience 
Five clinical studies have used the Sonendo System Technology. The first two studies are closed. 
The CS-01 dose feasibility clinical study included twenty-nine (29) patients. The CS-02 system 
feasibility clinical study enrolled twenty (20) patients that were treated with the Sonendo 
System Technology prior to tooth extraction.  
Three studies are currently enrolling patients. Clinical study CS-02.1 has enrolled twenty (20) 
patients that were treated with the Sonendo GentleWave System prior to tooth extraction. In 
the CS-03 PURE study, molar teeth treated with the Sonendo System are evaluated for long-
term performance of the System. A total of hundred and twenty two (122) patients have been 
enrolled to date in this study.  
A fifth clinical study is CS-05, which is a randomized extraction study that will compare cleaning 
results in teeth treated with Sonendo GentleWave System and in teeth treated with traditional 
RCT. A total of seven (7) patients have been enrolled to date in this study.  
A total of 198 patients have been treated with the Sonendo System. 
 

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3.0 STUDY PURPOSE AND OBJECTIVES  
The purpose of this study is to assess healing rates and post-procedure pain following root canal 
therapy with the Sonendo GentleWave System as compared to a literature control.  
3.1  Primary Effectiveness Endpoints  
Subject teeth in the Treatment Complete cohort that are healed or are healing at the twenty-
four month Follow-up Visit.  
Healed is defined by absence of a radiographic indication of apical periodontitis (PAI <3) and 
absence of clinical signs and symptoms. 
Healing is defined by a reduction of radiolucency (if radiolucency is present at Baseline) and/or 
reduction of clinical signs and symptoms (if clinical signs and symptoms are present at Baseline)  
Secondary analysis will be performed after all Treatment Complete subjects have completed the 
12 month Follow-up Visit. 
3.2  Primary Safety Endpoints 
Incidence of device related adverse events as defined by perforation, instrument separation, 
root fracture, sodium hypochlorite accident, or Gutta Percha extrusion, as related to the device 
for the Treatment Complete cohort.   
3.3  Secondary Endpoints 
The following outcomes will be assessed: 
1. McGill Short Form Pain Questionnaire58 
 
2. Gracely Descriptor Differential Scale (DDS) 59 
3. Patient Satisfaction Survey  
4. AAE Case Difficulty Assessment 
5. Soft Tissue Lesions  
6. Swelling  
 
7. Root Canal Therapy Retreatment 
8. Treatment Time 
9. Procedure Time 
10. Periapical Index (PAI) analyzed utilizing radiographic analysis by 
independent reviewer 
11. Cone Beam Computed Tomography (CBCT) Sub-Set Evaluation 
 
12. Additional Radiographic Analysis may be completed  

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4.0    STUDY DESIGN     
A prospective, non-significant risk device, literature controlled, study evaluating healing rates 
for the Sonendo GentleWave System in the treatment of 1st and 2nd molars indicated for root 
canal therapy.  
All patients will receive root canal therapy with the Sonendo GentleWave System. All patients 
will be followed for 24 months post procedure.   
5.0 STUDY POPULATION 
Up to 120 subjects, aged 18 to 75 years, who have a 1st or 2nd molar tooth indicated for root 
canal therapy, will be enrolled in the study.  
5.1   Pre-Procedure Inclusion Criteria 
1. The patient is 18 to 75 years of age  
2. The subject tooth is indicated for root canal therapy 
3. The subject tooth is a 1st  or 2nd  molar  
4. The patient is mentally and physically able and willing to fully comply with this 
protocol, including adhering to the follow-up schedule and completing forms and 
questionnaires 
5.  Signed Informed Consent Form 
5.2    Pre-Procedure Exclusion Criteria 
1. Poor oral hygiene according to a Poor, Fair, Good Scale 
 
2. Subject tooth with ≥ Class II Mobility 
 
3. Subject tooth with Periodontal Pocket Depth ≥ 6 
 
 
4. Periodontal probe reaches the apex  of the subject tooth 
5. Furcation involvement originating from periodontal disease, on the subject tooth, 
one and/or two adjacent teeth in direct contact with the subject tooth 
6. Subject tooth with ≥ Class III endodontic furcation involvement  
7. Subject tooth with open or incompletely formed root apices 
8. Vertical fracture, horizontal fracture, or perforation extending below the Cemento-
Enamel Junction (CEJ) of the subject tooth 
9. Caries or another condition of the subject tooth that  
a. prevents adequate seal of the device 
b. requires a separate procedure for crown lengthening  
c. requires a post 

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d. provides inadequate biological width for crown retention  
10. Any dental treatment on the subject tooth completed with the known use of 
devitalizers or formocresol  
11. Subject tooth having previous or attempted pulpectomy or root canal therapy 
12. One or two adjacent teeth in direct contact with the subject tooth requiring root 
canal therapy, pulpectomy or pulpotomy 
13. Any tooth on the same side of the oral cavity as the subject tooth with a source of 
pain 
14. Extraoral swelling on or around the subject tooth that has not undergone antibiotic 
treatment or a procedure to treat the swelling prior to RCT 
15. Any condition that would preclude tolerance of a root canal therapy including but 
not limited to being in a reclined and prolonged position in a dental chair, use of a 
dental dam, or ability to  have an open mouth for extended periods of time (>15 
minutes) (e.g. history of seizure within the last 5 years, severe asthma, or extreme 
gag reflex) 
16. Any other condition that the Investigator determines is unacceptable for enrollment 
into the study 
17. Nonodontogenic facial pain 
18. History of cancer within the oro-maxillofacial region  
19. History of any cancer within the last two years, including skin cancer 
20. History of head and/or neck radiation therapy 
21. Immunocompromised patients (i.e. corticosteroid usage) 
22. Any medical history that affects blood coagulation (e.g. bleeding disorders) 
23. Long-term or current usage of medication that affects blood coagulation. This 
includes herbal or other over the counter medications. Exception: Patients taking 
daily low dose Aspirin (81mg) or patients that can stop Aspirin or Ibuprofen products 
three (3) days prior to procedure, should not be excluded from the study.  
24. Patients with any medical condition causing chronic pain (e.g. spinal injury)  
25. Patients on long-term (i.e. more than three months) narcotic, opioid, or other similar 
analgesic (e.g. daily narcotic pain medication for spinal disease) 
26. Any infectious diseases (e.g. HIV, Hepatitis B, Hepatitis C, Tuberculosis, BCE, or Prion 
diseases) 
27. Uncontrolled diabetes or diabetics with unknown hemoglobin A1c levels 
28. A known allergy to local anesthetics, titanium carbon-nitride or stainless steel 

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29. A pacemaker, implantable cardiac defibrillator (ICD), or other implanted electronic 
medical device 
30. Patient is institutionalized, a prisoner, homeless, or on active military duty  
31. Patients with documented current alcohol and/or drug abuse 
32. Patient is pregnant or planning to become pregnant within the duration of the study 
33. Participated in any clinical study in the past 30 days 
5.3    Intra-Procedure Inclusion Criteria 
1. Successful removal of caries on the subject tooth  
2. Successful completion of build-up to restore the subject tooth crown when used in 
combination with the Occlusal Plate.  
Exception: This does not apply when the Tooth Cap is utilized. 
5.4    Intra-Procedure Exclusion Criteria 
1. Use of laser devices 
 
2. Subject tooth that requires crown lengthening 
3. Subject tooth that requires a post 
4. Subject tooth that provides inadequate biological width for crown retention  
5. Perforation of the subject tooth  
6. Vertical fracture or horizontal fracture below the Cemento-Enamel Junction (CEJ) of 
the subject tooth  
7. Internal or external root resorption that affects the use of Sonendo GentleWave 
System 
6.0   DENTAL CONE BEAM CT SUB-SET  
Dental cone beam computed tomography (CBCT) systems are a variation of traditional cone 
beam systems. The CBCT systems used by dental professionals rotate around the patient, 
capturing data using a cone-shaped X-ray beam. These data are used to reconstruct three-
dimensional (3D) images of the patient’s dental anatomy (teeth)60. 
Subjects enrolled in the study may be included in a CBCT subset.  All subjects that have access 
to the clinical sites with CBCT scanners may be included in the subset. 
7.0    STUDY PROCEDURES 
7.1    Pre-Screening Visit by Screening Dentist 
Pre-Screening Visits can be conducted by a Screening Dentist (SD). Screening Dentists are 
general dental practitioners that normally refer patients for endodontic treatment to an 
endodontist.  For the purpose of the study, Screening Dentists are the dentists who are part of 

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the study and are trained on the screening aspect of the study. Patients that appear to be eligible 
will be initially contacted through the Screening Dentist’s own patient pool. 
A patient will visit the Screening Dentist, according to standard of care, to be evaluated for root 
canal therapy. 
The Screening Dentist will, according to standard of care, use a Screening Protocol and Screening 
Form (see Appendix III. Screening Protocol) to evaluate:  
1. The patient’s medical and dental health 
2. The patient’s eligibility as a study candidate 
In addition, the GP or the SD should have completed the following: 
1. Caries removal on the subject tooth and restoration, if applicable.  
 
2. If caries are present underneath a crown, inlay or onlay then removal of the crown, inlay or 
onlay should occur in addition to caries removal and resin based restorative material 
restoration.  
 
3. Caries removal on any tooth on the same side of the oral cavity as the subject tooth. 
 
4. Extraction of partially erupted, malposed, carious, impacted wisdom tooth; and/or 
extraction of retained roots that may affect the outcome of root canal therapy on the subject 
tooth.  
 
5. Treatment of any tooth on the same side of the oral cavity that has a source of pain. 
 
6. Dental cleaning (full mouth) if not completed within six (6) months of Pre-Screening. In the 
case of patients who have heavy calculus and plaque accumulation tendencies, a full mouth 
dental cleaning should be completed even if the last dental cleaning was performed within 
six (6) months of Pre-Screening. 
These above mentioned items should have been completed, as necessary, prior to screening the  
patient for the study according to standard of care dental procedures.  
These screening candidates will be responsible for any standard of care costs associated with 
any of the above treatments or visits.  
No Protected Health Information (PHI) will be collected on the Screening Form. The patient will 
be identified by a screening code on the Screening Form (see Section 7.1.1 Screening Code). 
If the patient is successfully pre-screened, the SD will send the following to the Sponsor: 
• One (1) Periapical (PA) digital and/or hard copy redacted radiograph taken within two 
(2) months of Pre-Screening. 
 
• One (1) Bitewing (BW) digital and/or hard copy redacted radiograph taken within two 
(2) months of Pre-Screening. 
 
• PA radiograph has to show the periradicular tissue surrounding the subject tooth roots.  
 

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• BW radiograph has to show interproximal aspects of the coronal portion of the subject 
tooth, teeth adjacent to the subject tooth, and the opposing teeth in that quadrant. 
 
• Redacted camera images of the patient’s smile using retractors and the occlusal surface 
of the subject tooth are requested.  If camera images are not available, then full mouth 
radiographs are requested for screening.  
 
• Completed and signed Screening Form.  
In addition, the SD should send the following to the PI’s clinical site designee: 
• The last dental visit notes for the patient. At a minimum, this should include information 
on the patient’s dental treatment on the subject tooth and any assessments performed 
at the screening visit.  
 
• Contact information for the patient. At a minimum, this includes phone number, address, 
and email, if applicable. 
 
• Any other pertinent information required for treatment. 
For a particular patient the SD may submit all eligible teeth for review. This Pre-Screening 
submission will include separate Screening Forms, as well as pertinent radiographs and camera 
images for all eligible subject teeth.  
The Sponsor will not accept incomplete or inaccurate submissions and will not process study 
payments until required items are received and verified.  
Both Screening Dentists and PIs conduct a medical and dental review and assessments on a 
patient. The Screening Dentist performs this review only as part the pre-screening process. 
Information collected by a Screening Dentist will not be included as study data (i.e. Screening 
Form, pre-screening radiographs, and dental notes). Only information collected by a PI will be 
used as study data. The data collected or assessments performed by a PI supersede those 
completed by a Screening Dentist. Source data verification will occur using the subject’s dental 
file.  
7.1.1 Screening Code 
The patient will be identified by a screening code. The Sponsor will generate a Screening Code 
for each subject tooth that is sent in for a patient on the Screening Form. (If more than one 
subject tooth is submitted for the same patient, each tooth will receive a unique screening 
code.) The screening code should be six (6) alphanumeric characters: FML-XXX. The first set of 
three (3) characters (FML) is the initials of the PI or Screening Dentist. If there is no middle initial, 
a dash will be used. The second set of three (3) characters (XXX) is a sequential number starting 
at 001; each screening site will start at 001. Therefore, the first patient screened by a PI or 
Screening Dentist with the initials ABC will have the screening code ABC-001.  

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7.2    Pre-Screening Review and Notification 
7.2.1 Pre-Screening by the PI 
For patients pre-screened and approved by a PI, the PI will send the Screening Information to 
the Sponsor along with any required radiographs and camera images. The PI or a clinical site 
designee will schedule the patient for a Baseline Visit if the Screening Visit and Baseline Visit are 
not on the same day.  
7.2.2 Pre-Screening by the Screening Dentist 
For patients pre-screened by a Screening Dentist, the Sponsor will review the information 
provided to ensure completeness and eligibility, and, if eligible, will then forward the completed 
documentation to a PI for review.  
7.2.3 Notification of Pre-Screening Outcome to the Screening Dentist 
After the PI and the Sponsor determine patient eligibility for the study, the Screening Dentist 
will be notified. If the patient is eligible, the PI or clinical site designee will schedule the patient 
for a Baseline Visit at the clinical site; at this visit; the patient will complete the screening process 
for the study. 
7.2.4 Pre-Screen Failures 
If, during the Pre-Screening Process, the PI and/or the Sponsor determine that the patient is not 
eligible for the study, the patient will be considered a Pre-Screen Failure. Pre-Screen Failures will 
be treated and followed according to standard of care by their Screening Dentist or Endodontist, 
but will not be documented or followed for study purposes.  
7.3 Prior to Baseline Visit 
 
Patients who have a tooth approved for inclusion in the study and have had sinusitis or 
symptoms of sinusitis within the last 3 months may be required to receive a CBCT scan prior to 
the Baseline Visit. If the patient is included into the study, this CBCT may be used for the Baseline 
CBCT scan. 
 
7.4  Baseline Visit 
7.4.1 Informed Consent 
Once the patient arrives for the Baseline Visit, the informed consent process may begin. The PI 
or clinical site designee will review the Informed Consent Form (ICF) with the patient (see 
Appendix II. Informed Consent). The patient will be given the opportunity to ask questions and 
will be allowed sufficient time to consider the information provided. The PI will confirm the 
patient’s understanding and consent for the study. Written consent will be obtained, which will 
occur prior to any data collection for the study.  
In addition, the patient is informed within the ICF of possible attendance by the Sponsor and/or 
Sponsor representative during the Procedure Visit. 

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The ICF will be signed and dated by the PI, patient and clinical site designee executing the 
consent process. The patient shall be given a copy of the signed ICF. 
7.4.1.1 Consent for Audio-Video Recordings and Photographs Release 
In addition to the ICF, all patients will be provided with an Audio-Video Recording and 
Photograph Release Form.  If the patient agrees and signs the ICF, the Sponsor will be able to 
obtain audio-video recordings and/or photographs of the patient’s oral cavity and root canal 
treatment performed during the patient’s participation in the study. The patient’s participation 
in the study is not contingent upon agreeing to this consent. 
7.4.2 Cone Beam Computed Tomography (CBCT) Consent 
All patients will be provided with information regarding dental CBCT scanning for the study. If 
the patient agrees, they may be included in a study subset where dental CBCT scans will be 
obtained for the study. 
7.4.3 Screening 
After the ICF has been signed, additional screening may occur to determine if the patient meets 
the inclusion and none of the exclusion criteria. The patient will undergo standard of care 
endodontic and dental assessments necessary to determine the patient’s eligibility according to 
the Pre-Procedure Inclusion and Exclusion Criteria.  
7.4.4 Baseline Exam 
The PI will perform the following standard of care assessments and evaluations prior to the 
procedure, if they were not already completed: 
1. Medical and Dental History and Exam 
a. Medical History: Only those histories related to endocrine/metabolic, 
hematologic, musculoskeletal, and immunological will be collected for the study. 
2. Medication Regime: Only prescribed herbal or over the counter systemic antibiotics, 
analgesics, and anti-inflammatory medications taken during the duration of the study (24 
months post procedure) and the prior three months will be documented for this study.  
• Any antibiotics, analgesics or anti-inflammatory medications provided intra-
procedure by the PI during the Baseline and Procedure Visits will be collected for 
the study and will be documented on the Concomitant Medication Log.   
 
• Any antibiotics, analgesics and anti-inflammatory medications should be 
collected if prescribed or provided post Procedure Visit, and at all Follow-ups.  
 
3. McGill Short Form Pain Questionnaire: The McGill Pain Questionnaire (MPQ) is one of the 
most widely used tests for the measurement of pain. It provides information on sensory, 
affective, and evaluative dimensions of pain experience and is capable of discriminating 
among different pain problems. 
 

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4. Gracely Descriptor Differential Scale (DDS): This scale is an intensity and unpleasantness 
scale. The scale includes both verbal and numeric characteristics. 
 
5. Diagnostic Radiographic Analysis: Periapical (PA) Parallel Radiograph, showing the 
periapical region surrounding the subject tooth should be collected for each visit. 
Additional radiographs completed as necessary by the PI will be collected for the study.  
 
6. Periapical Index (PAI) Score61 analyzed by independent reviewer 
Up to three (3) independent reviewers will be provided radiographs in order to complete the 
PAI scoring. Independent reviewers will be blinded to the site, subject, and visit when 
completing the PAI score. This is being done to eliminate bias.  
• Score of 1: Normal  
• Score of 2: Small changes in bone structure  
• Score of 3: Changes in bone structure with some mineral loss (bone loss)  
• Score of 4: Periodontitis with well-defined radiolucent area (apical 
periodontitis)  
• Score of 5: Severe Periodontitis with exacerbating features (apical 
periodontitis) 
 
      Note: A Protocol Deviation CRF will not be completed if PAI score was not completed by an    
      independent reviewer for a particular visit. In addition there is no defined study window   
      for completion of PAI scoring by an independent reviewer.  
 
7. Dental Cone Beam Computed Tomography (CBCT) X-rays, as applicable    
 
8. Intra-Oral Examination including, but not limited to: 
 
a. Tooth Number: Based on the Universal Tooth Numbering System (1-32) 
b. Oral Hygiene: Oral hygiene should be graded on a score of Poor, Fair, or Good. 
• Poor:  
There is evidence of: generalized inflammation and swelling of gingival 
tissue, generalized bleeding on probing and/or generalized plaque/ 
calculus accumulation 
 
• Fair:  
There is evidence of: localized mild to moderate inflammation of the 
gingival tissue, mild localized swelling of the gingival tissue, localized 
plaque/calculus accumulation and/or localized bleeding on probing 
 
 
• Good:  
There is evidence of: healthy gums and Minimal plaque. No evidence of 
gingival inflammation and no bleeding on probing.  
 
c. Subject Tooth Assessments including: 

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i. Probing Pocket Depth62: The distance between the height of the free 
gingival margin and the height of attachment apparatuses below (bone, 
cementum, and periodontal ligament). Using a calibrated periodontal 
probe, the periodontal pocket depth should be recorded on the mesial, 
middle, and distal aspects of both the buccal and lingual  sides of the 
tooth 
ii. Mobility63  
• None: No distinguishable sign of movement. 
• Class I: The first distinguishable sign of movement greater than 
normal. 
• Class II: Horizontal tooth movement no greater than 1 mm. 
• Class III: Horizontal tooth movement greater than 1 mm, with or 
without the visualization of rotation or vertical depressability.  
• Any mobility other than none should be considered abnormal. 
iii. Swelling: This assessment includes the type and location of swelling.  
iv. Soft Tissue Lesions: This assessment includes the lesion presence, color 
and size where applicable. This assessment shall also include ulcerations 
and fistula/sinus tract. 
v. Cold Test63  
• Normal: A sensation is felt, but disappears immediately upon 
removal of the stimulus 
• Negative: Lack of response to stimulus 
• Lingering: Lingering or intensification of a painful sensation after 
the stimulus is removed 
• Immediate: Excruciating, painful sensation as soon as the stimulus 
is placed on the tooth 
• Delayed: A painful sensation is felt after an initial delay 
vi. Root Resorption 
vii. Furcation Involvement/Furcation Defect64, 65 
• Class I: The furcation can be probed, but not to a significant depth.  
• Class II: The furcation can be entered into but cannot be probed 
completely through to the opposite side. 
• Class III: The furcation can be probed completely through and 
through.  
• Class IV: The furcation can be probed through and through, and 
recession reveals a visible furcation. 
9. Endodontic Assessments including: 

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a. Pulp Diagnosis66:  
• Normal Pulp: A clinical diagnostic category in which the pulp is symptom-
free and normally responsible to pulp testing. 
• Reversible Pulpitis: A clinical diagnosis based on subjective and objective 
findings indicating that the inflammation should resolve and the pulp 
return to normal. 
• Symptomatic Irreversible Pulpitis: A clinical diagnosis based on subjective 
and objective findings indicating that the vital inflamed pulp is incapable 
of healing. Additional descriptors: lingering thermal pain, spontaneous 
pain, referred pain. 
• Asymptomatic Irreversible Pulpitis: A clinical diagnosis based on 
subjective and objective findings indicating that the vital inflamed pulp is 
incapable of healing. Additional descriptors: no clinical symptoms but 
inflammation produced by caries, caries excavation, trauma. 
• Pulp Necrosis: A clinical diagnostic category indicating death of the dental 
pulp. The pulp is usually nonresponsive to pulp testing. 
 
b. Periradicular Tests63 (Percussion and Palpation):  
• None (-): No discomfort at all.  
• Mild (+): Little discomfort, but may be noticeable by the patient.  
• Moderate (++): Some noticeable discomfort.  
• Severe (+++): Definitive discomfort.  
 
c. Periradicular Diagnosis:66  
• Normal Apical Tissue: Teeth with normal periradicular tissues that are not 
sensitive to percussion or palpation testing. The lamina dura surrounding 
the root is intact, and the periodontal ligament space is uniform. 
• Symptomatic Apical Periodontitis: Inflammation, usually of the apical 
periodontium, producing clinical symptoms including a painful response 
to biting and/or percussion or palpation. It might or might not be 
associated with an apical radiolucent area. 
• Asymptomatic Apical Periodontitis: Inflammation and destruction of 
apical periodontium that is of pulpal origin, appears as an apical 
radiolucent area, and does not produce clinical symptoms. 
• Acute Apical Abscess: An inflammatory reaction to pulpal infection and 
necrosis characterized by rapid onset, spontaneous pain, tenderness of 
the tooth to pressure, pus formation, and swelling of associated tissues. 
• Chronic Apical Abscess: An inflammatory reaction to pulpal infection and 
necrosis characterized by gradual onset, little or no discomfort, and the 
intermittent discharge of pus through an associated sinus tract. 

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• Condensing Osteitis: Diffuse radiopaque lesion representing a localized 
bony reaction to a low-grade inflammatory stimulus, usually seen at apex 
of tooth. 
After assessments are completed, the patient may be prescribed medication(s) for pain 
management according to standard of care procedures. If analgesic medications need to be 
provided to the patient in order to complete one or more of the assessments, the assessments 
that require a pain response (i.e. cold test, percussion and palpation) should be completed prior 
to providing these medications.  
Upon determining that the patient meets all the Pre-Procedure Inclusion and none of the Pre-
Procedure Exclusion Criteria, the patient may proceed to the Procedure Visit.   
If the patient does not meet all of the Pre-Procedure Inclusion and/or meets any of the Pre-
Procedure Exclusion Criteria, the patient will be considered a Screen Failure (see Section 7.6.1 
Screen Failures).  
All redacted source documentation with PI signature should be provided to the Sponsor for 
filing after each study visit. If changes are made to the source documents after PI signature, 
the updated source documents should be provided to the Sponsor for filing.   
Both Screening Dentists and PIs conduct a medical and dental review and assessments on a 
patient. The Screening Dentist performs this review only as part the pre-screening process. 
Information collected by a Screening Dentist will not be included as study data (i.e. Screening 
Form, pre-screening radiographs, and dental notes). Only information collected by a PI will be 
used as study data. The data collected or assessments performed by a PI supersede those 
completed by a Screening Dentist. Source data verification will occur using the subject’s dental 
file.  
7.4.5 Baseline Exam Re-Assessment 
For most patients, the Baseline and Procedure Visits will be on the same day. The patient and/or 
PI may choose to have the Procedure Visit occur on a day separate than that of the Baseline 
Visit. 
If the Procedure Visit is not on the same day as the Baseline Visit, the Procedure must occur 
within seven (7) days. If the Procedure Visit is not completed within seven (7) days of the 
Baseline Visit, the Baseline Exam results are no longer valid and must therefore be repeated and 
captured on a new source document. Only data captured on the final Baseline Visit will be used 
for data analysis and will be monitored. All assessments listed under Section 7.4.4 Baseline Exam 
need to be repeated if the Procedure Visit is not completed within seven (7) days of the Baseline 
Visit.  

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7.5    Procedure Visit 
7.5.1 Sonendo GentleWave System Preparation 
Prior to use of the Sonendo GentleWave System, the System and auxiliary equipment need to 
be prepared for treatment. Follow the Manufacturer’s Operator’s Manual and IFU for set-up of 
the System. 
After the Sonendo GentleWave System is prepared, prepare for root canal therapy. 
7.5.2 Root Canal Therapy Procedure Preparation  
During RCT preparation, the PI should assess the subject tooth to determine if the tooth meets 
all of the Intra-Procedure Inclusion and none of the Intra-Procedure Exclusion Criteria. The RCT 
preparation is to be performed using standard endodontic practices.   
1. 
Use of a dental bib is recommended. 
2. 
Protective safety eyewear is required.  
3. 
Anesthetize the subject tooth and surrounding area. 
 
Note: If at any stage throughout RCT preparation, the subject expresses pain, 
sensitivity or discomfort, the PI may provide more anesthetic per standard practice.  
4. 
Isolate the subject tooth by placing a rubber dam.  
5. 
If using an Occlusal Plate, it is recommended to clamp the distal adjacent tooth, if a 
distal adjacent tooth is present. If using a Tooth Cap, it is recommended to clamp the 
subject tooth.  
6. 
Use of a putty or caulking (i.e. OraSeal® (Ultradent) or equivalent) along the subject 
tooth and rubber dam interface for optimum isolation of the subject tooth is 
recommended.  
7. 
The subject tooth may be disinfected (e.g. using chlorhexidine or betadine). 
8. 
Any caries and/or dental fillings (e.g. amalgam) on the subject tooth must be removed. 
If a crown, inlay or onlay is present, it does not require removal unless necessary for 
treatment or if caries and/or leakage are present below the crown, inlay or onlay. 
 
Note: If there is tissue present that may affect caries removal and/or crown 
restoration, sear off the tissue according to standard dental practice.  
9. 
Use of caries detector to ensure that all caries are removed even if caries are not    
visibly present or cannot be detected with a dental probe is recommended.  
 
Note: Ensure that the tooth is restorable without a post and has adequate biological 
width for restoration after caries removal. If not, the patient will be considered a 
Screen Failure (see Section 7.6.1 Screen Failures).  

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10. When necessary, restore/build-up the missing subject tooth structure with 
permanent restorative and bonding materials.  Ensure the permanent restorative 
material is fully cured prior to treatment with the GentleWave System.  
Note: If there are any caries left, they will be removed by the Sonendo GentleWave 
System, and this can cause leakage. This leakage will require any build-up material to 
be removed and replaced.  If a crown, inlay or onlay comes off prior to or during 
treatment, it is recommend that the entire tooth structure be re-built or the crown or 
inlay or onlay be re-cemented unless an adequate seal can be created.  
11. Prepare a conservative endodontic access opening defined as a straight line path from 
the coronal orifice to the full working length per standard endodontic procedure. If a 
crown, inlay or onlay is present, the access opening may be performed through it as 
long as a caries detector is used post access. 
Note: Make sure the endodontic access is performed properly (per standard practice, 
i.e. pulp horns are removed and there is sufficient exposure of the pulpal cavity and 
floor).  
7.5.3 Orifice Negotiation  
Orifice negotiation for the study is defined as locating, accessing, finding or negotiating 
through the orifice of each canal.  
1. 
Locate the orifices of each canal of the subject tooth. 
a. Ultra-sonic and sonic devices may be used for removal of calcification and/or 
orifices negotiation.  
b. Use of lasers is not permitted for the study. 
          Note: Use of orifice openers or Gates Glidden are allowed for tortuous or heavily calcified  
          canals.  
 
          Note: If laser devices are used the patient will be considered a Screen Failure as this meets   
          Intra-Procedure Exclusion for the study.  
7.5.4 Minimal Shaping 
1. 
Prior to starting the minimal instrumentation process, it is recommended to utilize PA 
radiographs or cone beam to estimate the length of each root. 
2. 
A syringe of ≥ 0.5% NaOCl along with lubrication during the minimal shaping process 
is required according to standard of care.   
3. 
Gain patency. Use of a 6, 8, or 10 hand file to gain patency along with an apex locator 
is required per standard of care. Patency for use with the Sonendo GentleWave 
System is defined as 0.5mm from the apical foramen. 
4. 
Use of an endodontic ruler to ensure no apical penetration throughout the 
instrumentation process is required per standard of care.  

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  Note: There should be no apical penetration of any subject  teeth. If apical penetration   
  occurs on an upper subject tooth, the patient will be considered as a Screen Fail (see    
  Section 7.6.1 Screen Failures). 
5. 
Removal of calcification is recommended. Ultra-sonic and sonic devices may be used 
for removal of calcification 
 Radiographic verification of the working length for each canal using a Gutta Percha or    
                  size 10 or 15 file is recommended.  
 
 Note: There should be no apical penetration of any subject  teeth. If apical penetration 
occurs on an upper subject tooth, the patient will be considered as a Screen Fail (see 
Section 7.6.1 Screen Failures). 
6. 
Minimal shaping the canals to a maximum hand files size 25.02 is required.  
 Note: There should be no apical penetration of any subject  teeth. If apical penetration 
occurs on an upper subject tooth, the patient will be considered as a Screen Fail (see 
Section 7.6.1 Screen Failures). 
7. 
Minimal shaping of all canals using rotary file size to a maximum of 25.08 is required. 
The  Master Apical File (MAF) is defined for the study as the final apical file. 
 Note: There should be no apical penetration of any subject  teeth. If apical penetration 
occurs on an upper subject tooth, the patient will be considered as a Screen Fail (see 
Section 7.6.1 Screen Failures). 
8. 
Continue with Sonendo GentleWave System preparation (see Section 7.7 Sonendo 
GentleWave System Treatment). 
7.6  Enrollment 
Patients are considered to be enrolled after all Pre- and Intra-Procedure Inclusion Criteria and 
none of the Pre- and Intra-Procedure Exclusion Criteria are met and beginning of Luxabite 
material or Tooth Cap. Once patients are enrolled in the study, they are considered subjects.  
7.6.1 Screen Failures 
Patients that were consented but that did not meet all Pre- and Intra-Procedure Inclusion 
Criteria and/or met any Pre- and Intra-Procedure Exclusion Criteria are considered Screen 
Failures. Screen Failures will be treated and followed according to standard of care by their 
Screening Dentist or endodontist, but will not be documented or followed for study purposes.  
A Screen Failure patient will be counseled by the endodontist on any treatment they require. 
The patient will be responsible for any standard of care treatments.  
7.6.2 Subject Identification 
Once a subject is enrolled in the study, they will be assigned a Subject Identification (ID) code. A 
Subject ID is a numeric six (6) digit code: XXX-XXX. The first set of three (3) numbers is the clinical 
site number. The second set of three (3) numbers is a sequential number starting at 001; each 

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clinical site will start at 001. Therefore, the first subject enrolled at site 101 is 101-001, the 
second is 101-002, and so forth.  
If the subject is a Roll-In subject (as defined in Section 19.1 Roll-In Subjects), then the second 
three (3) digit code begins with an R to designate the subject as a Roll-In. The R is followed by a 
sequential two digit number for that site. Therefore, the first Roll-In subject enrolled at site 101 
is 101-R01, the second is 101-R02, and so forth.  
7.7  Sonendo GentleWave System Treatment  
After a subject has been enrolled in the study, the PI will begin the Sonendo GentleWave System 
treatment.  
The Sonendo GentleWave System Treatment is defined as beginning when LuxaBite or a Tooth 
Cap is placed (start of placement) until 100% completion of the Sonendo GentleWave System. 
All other procedures will be categorized as traditional RCT procedures. 
7.7.1 Sonendo GentleWave System Treatment Process 
Use the Manufacturer’s Operator’s Manual and IFU for the treatment process.  
To ensure optimal performance of the Sonendo GentleWave System, please ensure that the 
following has occurred prior to start of the Sonendo GentleWave System:  
• Ensure that the occlusal platform is placed and formed correctly.  
 
• Ensure that the cotton pellet is removed from the pulp chamber. 
 
• Utlize Depth Gauge to size Sealing Cap for pulp chamber. 
 
• If Sealing Cap size is incorrect, change the size. It is recommended to choose the 
next smaller Depth Gauge (larger Sealing Cap). 
 
• Ensure that the guide tube is placed in the center of the pulp chamber.  
If the sealing cap and/or handpiece must be changed during the treatment, a new handpiece 
should be obtained. Once the new handpiece has been attached according to the IFU, the 
treatment should recommence where it was stopped and treatment should continue.  
7.7.2 Leakage 
If fluid or air leaks in and/or out of the Sealing Cap and/or the subject tooth, stop the Sonendo 
GentleWave treatment and determine the cause. Leakage may be caused by: 
• 
Presence of caries 
 
• 
Fracture 
 
• 
Break in the build-up or leakage from LuxaBite or Tooth Cap 
Note: There are certain circumstances that will require build-up to be removed 
and then replaced in order to perform a successful treatment after a leak 
• 
Hand position of the PI 
 
• 
Other items such as an issue with the irrigants 

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To avoid leakage, the following precautions should be taken: 
• Do not tilt rock, rotate or move the handpiece. 
 
• If the PI needs to adjust their hand or position, or if the patient wants to move, 
the treatment should be paused prior to movement.  
Once a leak has been corrected, restart the Sonendo GentleWave System treatment. Treatment 
will commence from the point where it was stopped (exception: during leak test). 
7.8  Control of Bleeding 
Bleeding and control of bleeding during any RCT is expected and is considered standard of care. 
Bleeding is typically controlled through a combination of paper point usage, waiting for the 
bleeding to stop, starting the cone fit process and usage of intra-canal medications. If bleeding 
cannot be controlled and prevents the System from treating the tooth, the PI should pack the 
tooth with calcium hydroxide (Ca(OH)2) and restore the tooth with temporary material until the 
patient can be scheduled for a Second Procedure Visit according to standard of care.   
 
7.9  Second Procedure Visit 
The Sonendo GentleWave treatment may be completed on a subsequent visit, a Second 
Procedure Visit. The Second Procedure Visit can be scheduled according to standard of care.   
At this visit, the PI should remove the Ca(OH)2 with the Sonendo GentleWave System. Use of 
files or irrigation to remove Ca(OH)2 is not allowed for the study.  
7.10 
Inability to Complete Treatment 
If, for any reason, Sonendo GentleWave treatment cannot be completed over the course of no 
more than two visits, the subject will be considered as a Treatment Incomplete Subject. Subjects 
in the Treatment Incomplete Cohort will be documented as such but will not be followed for the 
study. No additional data will be collected on the Treatment Incomplete Cohort. Reasons for 
incomplete treatment may include, but are not limited to, periodontal issues, uncontrolled 
bleeding, root fracture, patient reported pain, etc.  
These subjects will be counseled by the PI on any treatment they require. Subjects in the 
Treatment Incomplete Cohort will be responsible for any standard of care treatment.   
7.11 
Obturation 
After the Sonendo GentleWave System treatment is completed; obturation, and coronal seal 
are required according to standard endodontic practices.  
1. 
Dry the pulp chamber and the root canals in preparation for obturation.  
2. 
Obturate the subject tooth using standard endodontic techniques. A warm vertical 
compaction method should be utilized as the obturation technique for this study. 
3. A cone fit radiograph is recommended prior to completion of obturation.  
4.  Complete obturation to the full working length leaving the coronal 1-2mm for    

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 extension of the restorative materials of each canal is recommended.  
 
7.12 
Coronal Seal  
1. 
 It is recommended to use a cotton ball dipped in alcohol to wipe the pulpal chamber   
         floor and prepare for coronal seal and build-up.  
 
2. 
Seal the pulp chamber floor and canal orifices with using a permanent restorative   
         material (approx. 3mm thick), according to standard of care.  
 
3.       Complete the case according to standard endodontic procedure.  
   
7.13 
Intra-Procedure Assessments and Evaluations 
The following information, among others, will be collected during traditional root canal therapy 
and the Sonendo GentleWave Treatment. 
1. 
Procedure Time: Defined for this protocol as the time from dental dam placement 
until dental dam removal.   
2. 
Procedural Details: Working Length, Master Apical File size, Irrigation, Calcification 
Assessment, additional therapies or procedures utilized and Material Utilization. 
3. 
Enrollment Time: Study Enrollment time is equivalent to Sonendo GentleWave 
System Treatment Start Time.  
4. 
Sonendo GentleWave Treatment Start Time: Defined for this protocol as starting 
when the LuxaBite or Tooth Cap is placed (start of placement) on the subject tooth.  
5. 
 Traditional Root Canal Therapy devices and instruments utilized. 
6. 
Sonendo GentleWave System devices utilized. 
7. 
Sonendo GentleWave Treatment End Time: Defined for this protocol as when the 
Sonendo GentleWave System user interface screen indicates 100% completion.  
        a.  If the subject is required to return for a Second Procedure Visit, then the   
             Sonendo GentleWave Treatment End Time for the first visit is defined as the   
             time when the Investigator determines the subject tooth needs to be packed  
             with calcium hydroxide.  
 
        b.  Sonendo GentleWave Treatment End Time for the First visit:  Defined for this     
             protocol as the last time when Sonendo GentleWave Treatment is stopped.  
 
8. 
  Medications: Any antibiotics, analgesics and/or anti-inflammatory medications    
  provided intra-procedure by the PI will be collected for the study and will be   
  documented on the Concomitant Medication Log.  
9. 
Radiographic Assessment: Working Length and Cone Fit radiographs, if applicable. 
10. Adverse Events (SEE SECTION 10.0 Adverse Event) 

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7.14 
Post Procedure Assessments and Evaluations 
The following information will be collected post procedure; 
1. Diagnostic Radiographic Analysis: Periapical (PA) Parallel Radiograph, showing the 
periapical region surrounding the subject tooth should be collected for each visit. 
Additional radiographs completed as necessary by the PI will be collected for the 
study.  
 
2. Cone Beam Computed Tomography (CBCT) radiograph post procedure is 
recommended.  
 
3. Radiographic Evaluation of Obturation67:  
a. The PI will evaluate the radiographs to determine the level of obturation.  
i. Short Fill: Sealer or obturation material <2mm above the apex. 
ii. Flush Fill: Sealer or obturation material within 2mm of the apex. 
iii. Overfill: Sealer or obturation material >2mm below the apex. 
iv. Presence and size of sealer puff 
 
4. 
AAE Case Difficulty Assessment68: This form will be utilized by the PI after every 
Procedure Visit to assign a level of difficulty to a particular case.  
5. 
Gracely Descriptor Differential Scale 
6. 
Patient Satisfaction Survey: This is a questionnaire that asks the patient to rate their 
experience of the root canal procedure they had and compare it with their previous 
root canal procedure experience, if applicable. The questionnaire also asks the 
patient to indicate any sensations or pain felt during the procedure.  
If the PI prescribes any antibiotics, analgesics and/or anti-inflammatory medications post 
procedure; these medications will be documented at subject’s next study visit if the medications 
were taken by the subject. If the prescribed medications were not taken by the subject, the 
clinical site designee should make a note of this on the source document.  
All subjects are instructed to contact the PI and/or clinical site designee in case of increased pain 
or discomfort after the procedure. If during the wait period between the Procedure Visit and 
next study visit, the subject has increased pain or discomfort, the PI will provide the subject with 
standard post-operative care and guidance.  
All redacted source documentation with PI signature should be provided to the Sponsor for 
filing after each study visit. If changes are made to the source documents after PI signature, 
the updated source documents should be provided to the Sponsor for filing.   
7.15 
Out-Patient Questionnaires 
7.15.1 McGill Short Form Pain Questionnaire 
Subjects will be asked to complete a McGill Short Form Pain Questionnaire for their physical 
mouth and tooth pain at 1, 2, 3, 7 and 14 days post-procedure and at all Follow-up Visits . This 

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form should be completed and returned to the clinical site designee at the next study visit or 
using certified mail or using a pre-paid FedEx envelope.  
If the subject is unable to complete one or more outpatient McGill Short Form Pain 
Questionnaire(s) then the clinical site designee may call the subject and complete the 
questionnaire(s) themselves based upon responses provided by the subject.   
7.15.2 Gracely Descriptor Differential Scale (DDS) 
Subjects will be asked to complete a Gracely Descriptor Differential Scale Questionnaire wherein 
they will be asked to rate the sensation felt in the tooth treated with Sonendo GentleWave 
System at 1 day post-procedure. This form should be completed and returned to the clinical site 
designee at the next study visit or using certified mail or using a pre-paid FedEx envelope.  
If the subject is unable to complete the outpatient Gracely Descriptor Differential Scale 
Questionnaire then the clinical site designee may call the subject and complete the 
questionnaire themselves based upon responses provided by the subject.   
7.16 
Crown Placement  
Subjects enrolled in the study should obtain a permanent crown per standard of care.    It is 
recommended that crown placement should occur within six weeks of the root canal therapy 
procedure per standard of care.   For the protocol, final crown placement date will be the date 
CRC obtains from the subject and/or GP and/or the Investigator.   
Pain and tenderness to percussion, palpation, ill-fitting margins, open margins, high occlusal 
contact points with the opposing teeth  or any other restoration related issues after crown 
placement experienced by the patient or reported by the PI and/or SD and/or Crown Placement 
dentist, will not be considered an adverse event but will be documented.  
7.17 
Follow-Up Study Visits 
The study follow-up visits will occur 6, 12, 18, and 24 months post-procedure. In addition, 
subjects may be requested to attend Follow-up Visits once a year after the twenty-four month 
follow-up for up to ten years.  
7.17.1 Follow-Up Study Visit Windows 
The visit windows are as follows: 
• Treatment: Within seven (+7) days of the baseline visit 
• 6 Month Visit: Plus or minus fourteen (±14) days. 
• 12 Month Visit: Plus or minus thirty (±30) days 
• 18 Month Visit: Plus or minus thirty (±30) days 
• 24 Month Visit: Plus or minus forty-five (±45) days 
7.17.2 Follow-Up Visit Evaluations and Assessments  
These study follow-up visits will occur at the clinical site and the following assessments will occur 
according to standard of care at each visit: 

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1. Medication Regime: Only prescribed herbal or over the counter systemic antibiotics, 
analgesics, and anti-inflammatory medications taken during the duration of the study (24 
months post procedure) and the prior three months will be documented for this study.  
 
2. McGill Short Form Pain Questionnaire: The McGill Pain Questionnaire (MPQ) is one of the most 
widely used tests for the measurement of pain. It provides information on sensory, affective, and 
evaluative dimensions of pain experience and is capable of discriminating among different pain 
problems. 
 
3. Diagnostic Radiographic Analysis: Periapical (PA) Parallel Radiograph, showing the periapical 
region surrounding the subject tooth should be collected for each visit. Additional 
radiographs completed as necessary by the PI will be collected for the study. 
4.     Periapical Index (PAI) Score analyzed by independent reviewer 
Up to three (3) independent reviews will be provided radiographs in order to complete the 
PAI scoring. Independent reviewers will be blinded to the site, subject, and visit when 
completing the PAI score. This is being done to eliminate bias.  
• Score of 1: Normal  
• Score of 2: Small changes in bone structure  
• Score of 3: Changes in bone structure with some mineral loss (bone loss)  
• Score of 4: Periodontitis with well-defined radiolucent area (apical 
periodontitis)  
• Score of 5: Severe Periodontitis with exacerbating features (apical 
periodontitis) 
 
      Note: A Protocol Deviation CRF will not be completed if PAI score was not completed by    
      independent reviewer for a particular visit. In addition there is no defined study window   
      for completion of PAI scoring by independent reviewer.  
 
5.  Dental Cone Beam Computed Tomography (CBCT) at 12 and 24 months and additional as   
     required by the PI.     
6.  Intra-Oral Examination including, but not limited to: 
a. Tooth Number: Based on the Universal Tooth Numbering System (1-32) 
 
b. Subject Tooth Assessments including: 
i. Probing Pocket Depth: The distance between the height  of the free 
gingival margin and the height of attachment apparatuses below (bone, 
cementum, and periodontal ligament). Using a calibrated periodontal 
probe, the periodontal pocket depth should be recorded on the mesial, 
middle, and distal aspects of both the buccal and lingual  sides of the 
tooth 
ii. Mobility  

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• None: No distinguishable sign of movement. 
• Class I: The first distinguishable sign of movement greater than 
normal. 
• Class II: Horizontal tooth movement no greater than 1 mm. 
• Class III: Horizontal tooth movement greater than 1 mm, with or 
without the visualization of rotation or vertical depressability.  
• Any mobility other than none should be considered abnormal. 
iii. Swelling: This assessment includes the type and location of swelling.  
iv. Soft Tissue Lesions: This assessment includes the lesion presence, color 
and size where applicable. This assessment shall also include ulcerations 
and fistula/sinus tract. 
 
v. Root Resorption 
vi. Furcation Involvement/Furcation Defect 
• Class I: The furcation can be probed, but not to a significant depth.  
• Class II: The furcation can be entered into but cannot be probed 
completely through to the opposite side. 
• Class III: The furcation can be probed completely through and 
through.  
• Class IV: The furcation can be probed through and through, and 
recession reveals a visible furcation. 
7. Endodontic Assessments including: 
a. Periradicular Tests (Percussion and Palpation)  
• None (-): No discomfort at all.  
• Mild (+): Little discomfort, but may be noticeable by the patient.  
• Moderate (++): Some noticeable discomfort.  
• Severe (+++): Definitive discomfort.  
 
b. Periradicular Diagnosis:  
• Normal Apical Tissue: Teeth with normal periradicular tissues that are not 
sensitive to percussion or palpation testing. The lamina dura surrounding 
the root is intact, and the periodontal ligament space is uniform. 
• Symptomatic Apical Periodontitis: Inflammation, usually of the apical 
periodontium, producing clinical symptoms including a painful response 
to biting and/or percussion or palpation. It might or might not be 
associated with an apical radiolucent area. 
• Asymptomatic Apical Periodontitis: Inflammation and destruction of 
apical periodontium that is of pulpal origin, appears as an apical 
radiolucent area, and does not produce clinical symptoms. 

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• Acute Apical Abscess: An inflammatory reaction to pulpal infection and 
necrosis characterized by rapid onset, spontaneous pain, tenderness of 
the tooth to pressure, pus formation, and swelling of associated tissues. 
• Chronic Apical Abscess: An inflammatory reaction to pulpal infection and 
necrosis characterized by gradual onset, little or no discomfort, and the 
intermittent discharge of pus through an associated sinus tract. 
• Condensing Osteitis: Diffuse radiopaque lesion representing a localized 
bony reaction to a low-grade inflammatory stimulus, usually seen at apex 
of tooth 
 
8.  Adverse Events (see Section 10.0 Adverse Event).  
After assessments are completed, the patient may be prescribed medication(s) for pain 
management according to standard of care procedures. If analgesic medications need to be 
provided to the patient in order to complete one or more of the assessments, the assessments 
that require a pain response (i.e. cold test, percussion and palpation) should be completed prior 
to providing this medication.  
All redacted source documentation with PI signature should be provided to the Sponsor for 
filing after each study visit. If changes are made to the source documents after PI signature, 
the updated source documents should be provided to the Sponsor for filing.   
In addition, the clinical site designee will report all significant findings at Follow-Up Visits to the 
Sponsor either via email or by sending redacted source documentation.  
Subjects should be evaluated to determine if the subject tooth remains functional. If the subject 
tooth is or still requires healing, the subject should be evaluated closely. If the subject has clinical 
symptoms or signs after the twelve month follow-up, the PI should follow standard endodontic 
care, as applicable. All such care should be documented accordingly for the study.  
7.18 
Unscheduled Visits 
Apart from the scheduled study visits, if the subject returns to the PI for a suspected adverse 
event (AE), the PI may perform tests and request additional information about what the subject 
is experiencing. Only those assessments that the PI deems as necessary for assessment of a 
possible AE will be collected. Assessments that are not completed during the Unscheduled Visit 
will not be considered as Protocol Deviations.  The information collected at this visit will be 
recorded on appropriate Case Report Forms. An Unscheduled Visit will not be completed unless 
an AE is suspected.   
All redacted source documentation with PI signature should be provided to the Sponsor for 
filing after each study visit. If changes are made to the source documents after PI signature, 
the updated source documents should be provided to the Sponsor for filing.   

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7.19 
Mail, Telephone and Dentist Contact 
If the subject is unable or unwilling to attend all study visits, the subject consents to be called or 
sent mail by the PI or clinical site designee to provide information about their dental status.  
The data provided via telephone contact or mail may include the following: 
1. Medical and Dental History and Exam 
2. Medication Regime 
3. McGill Short Form and/or Numeric Rating Scale  
The clinical site designee will follow the Numeric Rating Scale mentioned below or 
verbally ask questions on the McGill Short Form Pain Questionnaire. When asking the 
patient to rate their pain per the Numeric Rating Scale, the following question should 
be asked: 
“On a scale of 0 to 10, with 0 being ‘no pain’ and 10 being the ‘most intense pain 
imaginable’, what would you rate the severity of your tooth pain right now”?  
4. Adverse Events 
7.20 
Subject Completion 
Subjects are considered to have completed the study when they have completed the twenty-
four (24) month follow-up examination.  Subjects may be requested to have an in person or 
telephone follow-up visit every year after the twenty-four (24) month visit for up to ten (10) 
years. 

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8.0 SCHEDULE OF VISITS 
 
 
 
 
 
 
1. 
The procedure must be completed within seven days (7) of the baseline visit. For any treatment not completed within seven days of the baseline, the baseline assessments must be completed 
again within the time frame indicated. In addition, if a subject must return to the clinical site for completion of a procedure, as indicated in Section 7.9  Second Procedure Visit, this must also 
occur within seven days of the baseline.  
2. 
Subjects may be asked to have a follow-up visit every year after the twenty-four (24) month visit for up to ten (10) years. 
3. 
Only PA Parallel radiographs will be obtained.   
Description 
Screening 
Baseline 
Procedure1 
(+7 ds) 
Post-
Operative 
 
1 day  
 
2 days 
 
 
3 days 
 
 
7 days 
 
 
14 days 
 
6 mo. 
(± 14ds) 
12 mo. 
(± 30ds) 
18 mo. 
(± 30ds) 
24 mo.2 
(± 45ds) 
 
Unsched
uled 
Visits 
Screening Form by Screening 
Dentist or PI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Images of Smile & Oclussal 
Surface 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X-Rays (Periapical)3 
X 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
As 
 needed 
Medical and Dental History 
X 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
As  
needed 
Medication Regimen Review 
X 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
As  
needed 
Informed Consent 
 
X 
 
 
 
 
 
 
 
As 
needed 
As  
needed 
As 
needed 
As  
needed 
As          
needed 
CBCT  
 
X, if 
applicable 
 
X, if 
applicable 
 
 
 
 
 
 
X, if 
applicable 
 
X, if 
applicab
le 
As  
needed 
McGill Short Form 
 
X 
 
 
X  
X 
X 
X 
X 
X 
X 
X 
X 
As  
needed 
Gracely DDS 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
Periapical Index Score 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
As  
needed 
General Dental and 
Endodontic Assessments 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
As  
needed 
Sonendo GentleWave 
Treatment  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Root Canal Therapy 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Intra Assessments and 
Evaluations 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Post Operative Assessments 
and Evaluations 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Patient Satisfaction Survey 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
AAE Case Difficulty 
Assessment 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Adverse Event Assessment 
 
 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
As  
needed 

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9.0 PATIENT AND SUBJECT STATUS 
9.1   Pre-Screen Failure 
During the Pre-Screening Process, if the PI and/or the Sponsor determine that the patient is not 
eligible for the study, the patient will be considered a Pre-Screen Failure. Pre-Screen Failures will 
be treated and followed according to standard of care by their Screening Dentist or endodontist, 
but will not be documented or followed for study purposes.  
9.2   Pre-Screen Closure 
If a patient is eligible and approved for the screening process, but does not complete a Baseline 
Visit, the patient will be considered a Pre-Screen Closure. Patients that fall into this category may 
have been lost or missed a scheduled Baseline Visit. In order for a patient to be considered lost, 
the clinical site should attempt contact with the patient at least three times. The first two 
attempts may be by phone call and must be documented. The third attempt must be made via 
certified letter.   
9.3   Screen Failure 
Patients who were consented but did not meet all Pre-Procedure and Intra-Procedure Inclusion 
Criteria and/or met any Pre-Procedure or Intra-Procedure Exclusion Criteria are considered 
Screen Failures. Screen Failures will be documented as such for the study but will be followed 
according to standard of care. Screen Failures will not be followed for the study. 
9.4   Subject versus Patient 
Once a patient is enrolled in the study, they are considered a subject. 
9.5   Enrolled  
Eligible patients will be considered enrolled after all Pre-and Intra-Procedure Inclusion Criteria 
are met and none of the Pre- and Intra-Procedure Exclusion Criteria are met.  
9.6   Treatment Complete and Treatment Incomplete 
Treatment Complete is defined by any subject that received 100% of the Sonendo GentleWave 
Treatment (Treatment).  
Subjects that do not meet the Treatment Complete definition above are considered Treatment 
Incomplete.   
9.7   Termination 
Subjects may be terminated from the study at the discretion of the PI for reasons related to the 
study treatment that would jeopardize a subject’s health and/or welfare if they were to continue 
in the study.  Terminated subjects may be replaced. Terminated subjects may not be included in 
final data analysis. Notification of a subject termination should be made immediately to the 
Sponsor. 

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9.8   Withdrawal 
Subjects may be withdrawn from the study for non-treatment-related reasons only when no 
other option is possible.  Reasons for withdrawal include, but are not necessarily limited to, 
voluntary withdrawal from the study by the subject. 
The reason for withdrawal will be recorded on the appropriate Case Report Form.  Withdrawn 
subjects may be replaced in the study. Notification of a subject withdrawal should be made 
immediately to the Sponsor. 
9.9   Discontinuation 
Subjects may be discontinued from the study for non-treatment-related reasons only when no 
other option is possible.  Reasons for discontinuation include, but are not necessarily limited to, 
a subject that is unwilling or unable to cooperate with study requirements (medication regimen, 
follow-up visits, etc.). The reason for discontinuation will be recorded on the appropriate Case 
Report Form.  Discontinued subjects may be replaced in the study. Notification of a subject 
discontinuation should be made immediately to the Sponsor. 
9.10 
Lost to Follow-up 
A subject that is consented but does not attend the study required visits and/or does not respond 
to contact attempts will be considered lost to follow-up. The clinical site should attempt contact 
with the subject at least three times. The first two attempts may be by phone call and must be 
documented. The third attempt must be made via certified letter.  
If the subject is unable or unwilling to come in for a study visit, the process for mail, telephone 
call or general dentist contact should be attempted and documented (see Section 7.19 Mail, 
Telephone and Dentist Contact).  Lost to follow-up subjects may be replaced in the study. 
10.0 
ADVERSE EVENTS    
10.1 
Definition of Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence in a subject. An AE can 
therefore be any unfavorable and unintended sign or symptom, intercurrent illness, injury, or 
disease temporally associated with treatment whether or not related to the procedure or device.  
• Mild:  The AE is transient and easily tolerated by the subject. 
• Moderate:  The AE causes the subject discomfort and interrupts the subject’s usual 
activities. 
• Severe:  The AE causes considerable interference with the subject’s usual activities, may 
be incapacitating and may require hospitalization. 
 

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10.2 
Definition of Serious Adverse Events (SAE) 
A serious adverse event (SAE) is defined as an adverse event that results in any of the following 
outcomes: 
• Results in death 
• Is life-threatening (defined as any AE that places a person, in the view of the Investigator, 
at immediate risk of death from the reaction as it occurred, i.e., it does not include an AE 
that, had it occurred in a more severe form, might have caused death) 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity (defined as a substantial disruption 
of a person’s ability to conduct normal life functions) 
• Is a congenital anomaly or birth defect. 
10.3 
Adverse Event Assessments 
Adverse Events (AEs) that occur during the Baseline, Treatment Visit(s) and all the other Follow-
up Visits including the Unscheduled Visits will be assessed by PI, recorded in the patient’s study 
chart and then transcribed onto the Adverse Event Form Case Report Form (CRF).  
Pain, inflammation, swelling, or other reactions that are expected and associated with standard 
traditional root canal or dental procedures will not be considered adverse events for the study.  
Those events that may be exacerbated intra-procedure or post-procedure will be considered 
adverse events if the PI determines that these expected reactions are exacerbated or different 
from those experienced with the standard traditional root canal or dental procedures. 
AEs include, but are not limited to, the following:   
• Observed or volunteered problems 
• Complaints 
• Physical signs and symptoms 
• Medical condition which occurs during the study, having been absent at baseline 
• Medical condition present at baseline, which appears to worsen during the study. 
AEs related to only dental and endodontic procedures will be collected for the study.  
In addition to recording the AE on the Adverse Event CRF, the PI should also prepare an AE 
narrative (a complete written summary of the event and its outcome). Each AE must be described 
as follows: 
• Describe the event by stating the underlying cause (the diagnosis), coexisting disease, or 
other.  In order to avoid vague, ambiguous or colloquial expressions, the AE should be 
recorded in standard medical terminology rather than the subject’s own words when 

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possible 
• Note the duration by entering the date of onset, and date of resolution.  If the event is 
present at the final study visit, the ongoing box must be marked 
• Note the worst severity of the event as mild, moderate, or severe using the definitions 
provided in the protocol 
• Note the outcome of the event 
• Note the action taken as none, medical and/or surgical 
• Note the relationship to surgical procedure and device 
• Note any seriousness criteria 
Any medication necessary for the treatment of an AE must be recorded on the Concomitant 
Medication CRF.  If more than one distinct adverse event occurs, each event should be recorded 
separately. 
In addition, PIs must report all AEs to their Institutional Review Board (IRB) and regulatory bodies 
according to applicable guidelines and regulations. A copy of the notification must also be 
submitted to the Sponsor. 
10.4 
Unresolved Adverse Events 
Any subject terminated from the study due to an AE will be followed until the outcome of the 
event is determined.   
Any subject that is discontinued, withdrawn, or lost to follow-up will have this information 
documented on the End of Study CRF. This is considered the End of Study for the patient and all 
unresolved AEs must be marked as ongoing on the AE or AE Resolution CRF. 
All other AEs will be followed through to the end of the study.  Any unresolved AE at the subject’s 
final visit must be marked as ongoing on the AE CRF.   
10.5 
Assessment of Causality 
Due to the temporal proximity of an AE to the procedure under investigation, there is a 
reasonable possibility that the procedure may have caused an AE or may have contributed to the 
severity or duration of an event caused by other means. Causality to the study procedure or 
device will be assessed by the PI and relationship will be classified in one of the following 
categories:  
 

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Definitely Not Related 
Evidence exists that the adverse event definitely has a cause other 
than the procedure/device under investigation (e.g. pre-existing 
condition or underlying disease, intercurrent illness, or concomitant 
medication) and does not meet any other criteria listed. 
Probably Not Related 
An adverse event has little or no temporal relationship to the study 
device/study procedure and/or a more likely alternative etiology 
exists. 
Possibly Related 
A temporal relationship exists between the event onset and procedure 
under investigation, and appears with some degree of certainty to be 
related based on known therapeutic actions of the procedure/device 
under investigation.  It cannot be readily explained by the patient’s 
clinical state or concomitant therapies. 
Probably Related 
 
 
 
 
Definitely Related 
 
 
 
 
 
A temporal relationship exists between the event onset and procedure 
under investigation, and appears with some degree of certainty to be 
related based on known therapeutic actions of the procedure/device 
under investigation. It cannot be readily explained by the patient’s 
clinical state or concomitant therapies. 
 
Strong evidence exists that the procedure/device under investigation 
caused the adverse event.  There is a temporal relationship between 
the event onset and the procedure under investigation.  There is 
strong therapeutic evidence that the event was caused by the 
procedure/device under investigation.  The patient’s clinical state and 
concomitant therapies have been ruled out as a cause.  
10.5.1 Definition of Sonendo GentleWave System Treatment 
The Sonendo GentleWave System Treatment is defined as beginning when LuxaBite or a Tooth 
Cap is placed until 100% completion of the Sonendo GentleWave System. All other procedures 
will be categorized as traditional RCT procedures. 
10.6 
Serious Adverse Event Reporting 
PIs must report all Serious Adverse Events (SAEs) to the Sponsor within a timely manner of 
observing or learning of the event. For initial SAE reports, Investigators should record all case 
details that can be gathered within a timely manner on the SAE CRF and fax this information 
immediately upon completion to the Sponsor.  The fax number is (949) 305-5201.  
Each SAE must be followed with appropriate medical management until it’s resolved or assessed 
as chronic or stable regardless of whether or not, in the opinion of the Investigator, the event is 

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thought to be related to the procedure. The Investigator will be required to provide complete 
information concerning each SAE to the sponsor within in a timely manner. This information must 
be recorded in the subject’s medical record and then transcribed onto the Adverse Event CRF. 
The completed Serious Adverse Event Report (SAE) (including the Investigator’s opinion of the 
relationship of the SAE to the procedure/device under investigation), copies of related 
results/reports, consultant report(s), and other relevant information will be faxed and/or mailed 
to the Sponsor. 
All SAEs as described above, covering the period from a subject’s enrollment in the study through 
seven (7) days following a subject’s completion as per protocol or premature discontinuation 
from the trial will be managed and reported. The decision to report potential SAEs beyond the 
seven (7) day post-study period will be at the discretion of the Sponsor, unless otherwise advised 
by the IRB. 
In addition, Investigators must report all SAEs to their Institutional Review Board (IRB) and 
regulatory bodies according to applicable guidelines and regulations. A copy of the notification 
must also be submitted to the Sponsor. 
10.7 
Unanticipated Adverse Device Effect 
Pursuant to Part 812.3(s) of Title 21 of the Code of Federal Regulations, the definition of an 
Unanticipated Adverse Device Effect (UADE) means any serious adverse effect (as defined above) 
on health or safety or any life-threatening problem or death caused by, or associated with a 
device, if that effect, problem, or death was not previously identified in nature, severity or degree 
of incidence in the clinical protocol or application (including a supplementary plan or application), 
or any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
Any UADE must be reported to the Sponsor either by telephone (949) 766-3636 or fax (949) 305-
5201 within 24 hours of knowledge of that event. In addition, Investigators must report all UADEs 
to the IRB and regulatory bodies according to applicable guidelines and regulations.  
The Sponsor will be responsible for informing Regulatory Authorities, all other IRBs, and 
Investigators participating in the study of the UADE according to the applicable guidelines and 
regulations.    
10.8 
Anticipated Adverse Events 
10.8.1 Risks generally associated with any dental procedure include, but are not limited to, the 
following:  
• Pain and/or discomfort 
• Swelling or inflammation 
• Pressure 
• Numbness  
• Paresthesia (tingling) 
• Post-treatment infection 

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• Abscessed tooth 
• Bleeding 
• Tooth color changes 
• Potential for re-treatment 
• Reoccurring decay 
• Reaction to medications or 
anesthesia  
• Reaction to materials or chemicals 
used  
• Sensitivity to hot and/or cold air 
pressure or sweets 
• Breakdown of the inner filling 
causing infection and/or damage 
• Weakening of the tooth 
• Instrument breakage within the 
canal 
• Perforating (creating a small hole) 
the side of the root 
• Tissue damage 
• Tooth crown fracture or breakage 
10.8.2 Potential risks for root canal therapy include, but are not limited to, the following: 
• Post-treatment pain and/or 
discomfort 
• Post-treatment swelling or 
inflammation 
• Pressure 
• Numbness  
• Paresthesia (tingling) 
• Post-treatment infection 
• Abscessed tooth 
• Bleeding 
• Tooth color changes 
• Potential for re-treatment 
• Reoccurring decay 
• Reaction to medications or 
anesthesia  
• Reaction to materials or chemicals 
used  
• Extrusion of debris into the 
periapical tissue 
• Sensitivity to hot and/or cold, air 
pressure or sweets 
• Breakdown of the inner filling 
causing infection and/or damage 
• Defective or inadequate restoration 
of the tooth which could lead to  
infection, leakage, loosening, 
detachment, or breakage 
• Uninstrumented recesses of the 
tooth (i.e. missed canals or 
uncleaned areas) 
• Instrument separation (i.e. breakage 
within the canal) 
• Perforating (creating a small hole)  
the side of the root 
• Damage to sinus floor or sinus 
infection 
• Tissue damage 
• Root weakening 
• Ledge formation 

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• Weakening of the tooth 
• Jaw bone infection or damage 
• Worn out filling 
• Broken or cracked filling 
• Tooth root fracture or breakage 
• Tooth crown fracture or breakage 
10.9 Other Potential Risks 
10.9.1 Radiation Risks 
Radiation exposure will occur during radiograph examinations. Exposure to ionizing radiation 
while a low risk, has the potential to cause cancer and other risks.  
There are also additional fetal risks associated with ionizing radiation exposure. Ionizing radiation 
is utilized in diagnostic procedures, such as radiographs, because without these procedures 
diagnostics on pulp diseases and other conditions would not occur.  
 
10.9.2 Cone Beam Computed Tomography (CBCT) Radiation Risks 
Although the radiation doses from dental CBCT exams are generally lower than other cone beam 
exams, dental CBCT exams typically deliver more radiation than conventional dental radiographic 
exams. 
10.9.3  Pregnancy (risks for the fetus) 
As dental procedures are associated with risks for pregnant women and the fetus, pregnant 
women will not be included in this research study. It will be recommended for subjects to avoid 
becoming pregnant during the study.  
If a subject becomes pregnant during the duration of the study, the clinical site will document 
the pregnancy with a Memo to File.  Study required radiographs or cone beam will not be 
collected for pregnant subjects but these subjects will still be followed for the duration of the 
study. The clinical site designee will not complete a Protocol deviation CRF for study required 
radiograph assessment not completed due to pregnancy.  A Memo to File documenting this 
deviation will suffice.  
10.10  Definitions of Adverse Events 
Sodium Hypochlorite Accident is defined as follows: 69, 70 
Inadvertent extrusion of sodium hypochlorite past the protective apical constriction or through 
a lateral canal or root perforation which results in bleach injury as characterized by severe 
intermittent and/or constant pain, profuse bleeding combined with extraoral or facial swelling, 
edema, ecchymosis, and/or oral or facial parasthesia.  
Extrusion of Filling Materials is defined as follows: 71, 72 

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Gross overextension of the filling materials beyond the confines of the root canal and into the 
surrounding vital structures resulting in post operative discomfort, pain, parasthesia and/or 
anesthesia. 
11.0 
BENEFITS 
The potential benefits of the Sonendo GentleWave treatment include the following: 
• Significantly reduced pain 
• Provide long-term pain relief 
• Improved quality of life 
These benefits are consistent with the effectiveness criteria studied in similar devices. 
12.0 
PROTOCOL DEVIATIONS 
A protocol deviation is defined as an event where the PI or clinical site designee did not conduct 
the study according to the Clinical Protocol. 
A clinical designee should notify the Sponsor of any protocol deviation(s), preferably via email. 
Deviations must be reported to the Sponsor regardless of whether medically justifiable, pre-
approved by the Sponsor, or taken to protect the subject in an emergency.  PIs must also adhere 
to procedures for reporting protocol deviations to the IRB in accordance with their specific IRB’s 
reporting policies and procedures. 
Regulations require that PIs maintain accurate, complete and current records, including 
documents showing the dates of and reasons for each deviation from the protocol.  For reporting 
purposes, the Sponsor classifies study deviations as major and minor: 
• Major deviation:  Any deviation from subject’s Inclusion and Exclusion Criteria, subject’s 
informed consent procedures or unauthorized device use. This also includes enrollment 
in another clinical study within 30 days of enrollment. 
• Minor deviation:  Deviation from a protocol requirement such as incomplete/inadequate 
subject testing procedures, follow-ups performed outside specified time windows, etc.  
It is untimely the PI’s responsibility to determine the protocol deviation classification.   
12.1.1 Protocol Deviation Types 
The Sponsor has designated the following protocol deviation types for reporting purposes: 
• Deviation from Informed Consent Process 
• Patient did not meet Inclusion and/or met Exclusion Criteria  
• Patient study visit out of study window 
• Patient missed a study visit 

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• Assessment/Questionnaire was not completed 
• Assessment/Questionnaire was completed out of study window 
• Other 
13.0 
 STATISTICAL METHODS    
All required data for this study will be collected on paper or electronic Case Report Forms (CRFs). 
The Investigator (or designated study staff) will assure primary data collection based on source 
documented dental chart reviews. Independent monitoring will be performed to ensure that the 
investigator and his/her study team conducted the clinical investigation in accordance with 
contract specifications, study protocol, Declaration of Helsinki73, and applicable local or national 
regulations, to ensure adequate protection of the rights and safety of subjects and the quality 
and integrity of the resulting data. 
In general, quantitative variables will be summarized to indicate the population sample size (N), 
number of patients with available data (n), mean, standard deviation, median, minimum, and 
maximum values. Qualitative variables will be summarized by the population size (N), number of 
patients with available data (n), number of patients in each category, and the percentage of 
patients in each category. Analyses will be based on the Safety Population defined as all patients 
who receive the Sonendo GentleWave System procedure. Details of analysis methods will be 
described in the statistical analysis plan. 
13.1 
Sample Size  
All patients will receive root canal therapy with the Sonendo GentleWave System and will be 
subsequently followed for 24 months post procedure. A sample size of 108 subjects, assuming a 
20% lost to follow-up or Treatment Incomplete Cohort rate, will result in approximately 86 
subjects who would be evaluable for the primary efficacy endpoint.  A sample size of 86 evauable 
subjects provides approximately 90% power to detect a difference between a 85% response rate 
for subjects using the Sonendo GentleWave System against a null hypothesis of a 70% response 
rate based on data presented in literature for traditional root canal therapy, using a two-sided 
binomial test at the 5% level of significance.   
13.2 
Analysis Populations and Handling of Dropouts 
The Safety Population is defined as all patients who receive the Sonendo GentleWave System 
procedure.  
The Efficacy Evaluable population is defined as all subjects who enroll in the study and who 
receive 100% of the Sonendo GentleWave Treatment (Treatment Complete Cohort) over the 
course of no more than two visits.  Analysis of efficacy data will be performed using the Efficacy 
Evaluable population.  Efficacy analyses will be based on observed data only; no imputation 
methods will be used. Dropout subjects will not be replaced. 

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13.3 
Demographics and Baseline Characteristics 
Age, sex, height, weight medical history and other baseline characteristics will be collected at 
Screening. Continuous variables will be summarized using descriptive statistics; categorical 
variables will be summarized using counts and percentages. 
13.4 
Method for the Analysis of Primary Effectiveness Parameter 
The primary effectiveness analysis will be based on Healing at twenty-four (24) months for 
Treatment Complete Cohort.  
The proportion of subjects with healing, along with the exact 95% confidence interval, will be 
provided for healing at 24 months. 
13.5 
Secondary Analysis  
Secondary analysis will be completed after all Treatment Complete subjects complete the 24 
month follow-up.   
13.6 
Safety Analyses 
Incidence of device related adverse events as defined by perforation, instrument separation, root 
fracture, sodium hypochlorite accident or Gutta Percha extrusion, as related to the device will be 
summarized for the Safety Population.   
13.7 
Handling Missing Effectiveness and Safety Data  
Missing data will be reported as a protocol deviation. The data will be interpreted and noted as 
incomplete. The Sponsor has the discretion to disqualify a patient due to a protocol deviation.  
For incomplete assessments or missing data, analysis will utilize the last observation carried 
forward method.  
All data analyses will be conducted on data from subjects with the necessary observed endpoint 
data (complete case analysis).  
13.8 
Handling Post-Market Analysis 
With the addition of Post Market enrollment subjects the sponsor may elect to provide separate 
subset analysis of pre and post market enrollment. 
14.0 
DATA REPORTING 
A CRF casebook will be used for each subject enrolled in the study. All clinical data generated in 
the study will be reviewed for quality assurance review, data entry, and statistical analysis. All 
forms will be reviewed for completeness; evident recording errors will be rectified by contact with 
the appropriate clinical site. 
The appropriate CRF will be completed by the PI or a clinical site designee after each visit. The PI 
will sign the CRFs to indicate verification and approval. All CRFs will be completed in a legible 

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manner in blue or black ink. Any corrections will be made by drawing a single line through the 
incorrect entry, entering the correct information, and initialing and dating the change. 
 If there is a discrepancy between a CRF and the source document and any significant data within 
the CRF is changed, the PI should re-sign the form to indicate verification and approval of the 
change(s).  
If no Second Day Procedure, Protocol Deviation, AE, or AE Resolution occurred, then the 
associated CRF does not need to be completed or collected. 
CRFs should be completed within two (2) weeks of a subject’s study visit. The original signed 
forms, not copies, will be returned to the Sponsor.  
All redacted source documentation with PI signature should be provided to the Sponsor for 
filing after each study visit. If changes are made to the source documents after PI signature, the 
updated source documents should be provided to the Sponsor for filing.   
Both Screening Dentists and PIs conduct a medical and dental review and assessments on a 
patient. The Screening Dentist performs this review only as part the pre-screening process. 
Information collected by a Screening Dentist will not be included as study data (i.e. Screening 
Form, pre-screening radiographs, and dental notes). Only information collected by a PI will be 
used as study data. The data collected or assessments performed by a PI supersede those 
completed by a Screening Dentist. Source data verification will occur using the subject’s dental 
file.  
15.0 
STUDY MONITORING 
In accordance with applicable regulations and Good Clinical Practice74 (GCP), the PI and/or 
Sponsor will check and assess the progress of the study, review the data collected, conduct 
source document verification, and identify any issues and address resolutions. These activities 
are conducted to verify that the data are authentic, accurate, complete, that the safety and rights 
of subjects are being protected, and that the study is conducted in accordance with the currently 
approved protocol (with amendments), and all applicable regulatory requirements. 
If a clinical monitor becomes aware that a PI is not complying with the requirements mentioned 
above, the monitor will notify the Sponsor. The Sponsor will evaluate the noncompliance.  
Monitoring visits will be performed at regular intervals and according to the study monitoring 
plan to ensure appropriate study conduct and integrity of the data being recorded. Any 
discrepancies in the data will be noted and data clarifications or queries will be issued by the 
monitor to correct these discrepancies or obtain additional information. Following completion of 
a monitoring visit, monitoring reports will be generated and will be sent to the Sponsor for review 
and approval. 

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The PI agrees to allow the monitor direct access to all relevant documents and agrees to allocate 
his/her time and the time of his/her staff to the monitor to discuss findings and any relevant 
issues. 
Information collected by a Screening Dentist is considered part of the pre-screening process and 
none of this information will be monitored or utilized as study data (i.e. Screening Form, pre-
screening radiographs, dental notes, and correspondence). 
The monitoring will be performed by a Sonendo representative, who will also assess the progress 
of the study and identify any concerns that result from device performance, review of the PI’s 
study records, study management documents, and subject informed consent documents. This 
review includes adherence to the study protocol, IRB review of the study and its progress, and 
maintenance of records and reports.  
16.0 
 ETHICAL AND REGULATORY CONSIDERATIONS 
This protocol was designed and will be conducted, recorded, and reported in compliance with 
the principles of Good Clinical Practice (GCP) regulations.  These requirements are stated in global 
regulations as well as “Guidance for Good Clinical Practice,” International Conference on 
Harmonization (ICH), and the most recent guidelines of the Declaration of Helsinki of Technical 
Requirements for Registration of Pharmaceuticals for Human Use.  
17.0 
SPONSOR RESPONSIBILITIES  
The Sponsor agrees to comply with the FDA 21 CFR Part 812 for all applicable regulations for non-
significant risk devices.   
18.0 
 INVESTIGATOR’S RESPONSIBILITIES 
It is understood that the term “Investigator” as used in this protocol and on Case Report Forms 
refers to the Principal Investigator or a member of the staff that the Principal Investigator has 
trained and designates to perform a certain duty. The Principal Investigator is ultimately 
responsible for the conduct of all aspects of the study.  
The PI must have prior knowledge and training on GCP and Human Subjects Protection. 
The PI must receive training for the Sonendo GentleWave System prior to commencement of the 
study.  
The PI must have written approval from the Institutional Review Board prior to enrolling a patient 
into the study. The Sponsor must be informed about the approval by receipt of written 
confirmation.  
The PI will ensure that this study is conducted in full accordance with the Declaration of Helsinki. 
It is the responsibility of the PI to obtain written informed consent from each individual 
participating in the study, after adequate explanation of the aims, methods, objectives, and 

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potential hazards of the study. The PI or designee must also explain to subjects that they are 
completely free to refuse to enter the study or to withdraw from it at any time.  
The PI should ensure the accuracy, completeness, legibility and timely reporting of the study 
required data.  
The PI is required to sign an Investigator’s Agreement or Investigator’s Contract. This document 
includes information on the Investigator’s obligations with respect to the use of the device, 
informed consent, and reporting of AEs. By signing the Investigator’s Agreement, the PI 
acknowledges assurance to the Sponsor and compliance with the protocol and study obligations.  
No changes to this protocol can be made without the Sponsor’s written approval.  
18.1 
Retention of Records 
The PI is responsible for maintaining the following study records and for providing access to these 
records by the Sponsor, IRB, and FDA for audit and inspection: 
• Source documents (e.g., medical and dental records) including subject’s case history, 
documentation that informed consent was obtained prior to study participation, and a 
description of circumstances if no informed consent was obtained  
• Case Report Forms 
• Signed and dated Informed Consent Forms 
• Patient’s Audio-Video Recording and Photograph Release Form 
• Electronically saved audio-video recordings and photographs of individual study cases  
• Correspondence with the Sponsor, Medical Monitor, IRB, FDA and other Investigators 
including required reports 
• Study protocol and any amendments 
• Continuing review reports to IRB and Sponsor annually or as required by IRB 
• Any other records required by the IRB 
The PI is required to maintain the records for at least two (2) years following the latter of either 
the date when the study is terminated or completed, or the date that the records are no longer 
required for purposes of supporting a marketing application.  
18.2 
Study Documents  
This protocol, the subject Informed Consent Form (ICF) and amendments to the ICF, if applicable, 
must be reviewed and approved by an IRB that is operating in accordance with local procedures 
and the abbreviated requirements for 21 CFR Parts 812, before enrollment of subjects.  In 
developing a site-specific Informed Consent Form, the PI must comply with the guidelines for the 

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content of Informed Consent Forms.  Any site-specific Informed Consent Form and ICF 
amendments must be reviewed and approved by the Sponsor prior to submission to the IRB.  
It is the responsibility of the PI to obtain and maintain approval for the Study Protocol, ICF and 
ICF amendments and to keep the IRB informed of serious adverse events and any amendments 
to the protocol.  It is also the PI’s responsibility to maintain a file of all correspondence with the 
IRB and to forward copies of that correspondence to the Sponsor, or the Sponsor’s 
representative. 
18.3 
Subject Selection   
The PI is responsible for ensuring that all subjects entering the study conform to the subject 
Inclusion and Exclusion Criteria and are willing and able to complete the required study visits. 
18.4 
Subject Informed Consent 
Before any study related procedures are completed or a patient is enrolled into the study, each 
potential subject will be given appropriate explanation of the study.  Once the essential 
information has been provided and the Investigator is assured that the candidate understands 
the implications of participating in the study, the subject will be asked to give his/her consent to 
participate in the study by signing the Informed Consent Form.  The person performing the 
consent process and the Investigator must sign the ICF. The subject will be given a copy of the 
executed ICF. 
18.5 
Confidentiality 
The PI will ensure that patient names and data will be kept confidential.  The Investigator and 
study staff agree to comply with the HIPAA Privacy Rule75. In case of adverse and serious adverse 
event reporting, only the subject initials and subject ID shall be employed and the patient’s 
identity will not be disclosed. 
Subject identity will only be revealed in the case that patient confidentiality would compromise 
patient or study safety. 
19.0 
INVESTIGATOR TRAINING  
All PIs must participate in a training program conducted by the Sponsor or designated 
representative.  
There will be up to five (5) Roll-In cases per PI. The number of cases is dependent on the training 
and Sonendo experience level of the PI. The Sponsor may elect to disregard one (1) to five (5) of 
the Roll-In cases for a particular PI. PIs who will be performing root canal therapy (RCT) with the 
Sonendo GentleWave System must receive a Certification of Training from Sonendo prior to their 
first Non-Roll-In subject enrollment.  
Requirements for certification of an Investigator include: 

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1. Completion of didactic instruction on the function, theory and application of the Sonendo 
GentleWave System. 
2. Training on the protocols for access, treatment, and obturation, review of patient 
eligibility, Inclusion and Exclusion Criteria, and the rationale for the criteria, as well as 
details on all study methods. 
3. Completion of a comprehensive laboratory training on the procedure employed for 
Sonendo GentleWave treatment.  Practice cases with ex-vivo extracted teeth will be 
performed onsite in the Sonendo, Inc. laboratory and tooth treatment facility.  
4. Completion of up to five (5) successful Roll-In cases in an in-vivo environment.  
19.1 
Roll-In Subjects 
There will be up to five (5) Roll-In cases per PI. The number of the Roll-In subjects will be 
determined by Sonendo during training and will depend on the PI’s level of experience with the 
Sonendo GentleWave System. The Sponsor may elect to disregard one (1) to five (5) of the Roll-
In cases for a particular PI.  
Roll-in subjects will be provided Subject IDs different from that of Non Roll-In subjects. The 
second three (3) digit code begins with an R to designate the subject as a Roll-In. The R is followed 
by a sequential two digit number for that site. Therefore, the first Roll-In subject enrolled at site 
101 is 101-R01, the second is 101-R02, and so forth. The data obtained from Roll-In cases will be 
collected, but may not be included in the final data analysis.  
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX I. HEALING LITERATURE REPORT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX II. INFORMED CONSENT FORM 
 
 

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APPENDIX III. SCREENING PROTOCOL 
 
 

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APPENDIX IV. CONFIDENTIALITY  
CONFIDENTIAL - DO NOT COPY 
Information contained herein is confidential and proprietary with respect to Sonendo Inc. 
products and clinical trials. I agree to hold this information in confidence and not to disclose it to 
any third parties for a period of three years from the date of this Protocol, or until this information 
becomes a matter of public knowledge or until a formal agreement for that purpose has been 
entered into by the parties. 
 
 

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APPENDIX V. REFERENCES 
 
 
1  
American Association of Endodontists: http://www.aae.org/News_Room/Endodontic_Facts.aspx 
2  
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canal geometry assessed by micro computed tomography: Int. Endo. J., 2001, Vol. 34. 
3  
Peters O. A., Peters C. I., Schönenberger K., Barbakow F. ProTaper Rotary Root Canal 
Preparation: Effects of Canal Anatomy on Final Shape Analyzed by Micro CT. Int. Endo J., 
2003, Vol. 36. 
4  
Shuping G. B., Orstavik D., Sigurdsson A., Trope M. Reduction of intracanal bacteria using nickel-
titanium rotary instrumentation and various medications. J Endod 2000, Vol 26. 
5 
McGurkin-Smith R., Trope M., Caplan D., Sigurdsson A. Reduction of intracanal bacteria using GT 
rotary instrumentation, 5.25% NaOCl, EDTA, and Ca(OH)2. J Endod 2005, Vol. 31. 
6  
Hülsmann M., Schade M., Schäfers F. A comparative study of root canal preparation with HERO 642 
and Quantec SC rotary Ni–Ti instruments. Int. Endo. J., 2001, Vol. 34. 
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8  
Wilcox L. R., Roskelley C., Sutton T. The relationship of the rootcanal enlargement to finger-spreader 
induced verticle root fracture, J Endod 23(8):533, 1997. 
9  
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Third. Oral Surg. Oral Med. Oral Path., 2000, Vol. 89. 
10  Jafarzadeh H., Abbott P. V. Ledge Formation: Review of a Great Challenge in Endodontics. JOE, 2007, 
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11 Cohen S., Burns R. C. Pathways of the pulp. 8th ed. St Louis: Mosby, 2002. 
12  Kapalas A., Lambrianidis T. Factors Associated with Root Canal Ledging During Instrumentation. 
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16  Gutmann J. L., Dumsha T. C., Lovdahl P. E., Hovland E. J. Problem Solving in Endodontics (3rd ed.). St. 
Louis: Mosby, 1997. 

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17  Bergenholtz G., Lekholm U., Milthon R., Heden G., Odesjo B., Engström B. Retreatment of Endodontic 
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Iatrogenic Errors in an Undergraduate Dental Clinic. Int. Endo. J., 2005, Vol. 38. 
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Clinical, Roentgenographic, and Histologic Findings. Oral Surg. Oral Med. Oral Path., 1967, Vol. 23. 
21  Alhadainy, H. A.  Root Perforations. A Review of Literature. Oral Surg. Oral Med. Oral Pathol., 1994, 
Vol. 78. 
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Adjacent to Root Perforations Filled with Cavit. Oral Surg. Oral Med. Oral Path., 1982, Vol. 54. 
23  Ingle J. I., Bakland L. K. Endodontics. 5th ed. London: BC Decker Inc., 2002. 
24  Swartz D. B., Skidmore A. E., Grieffin J. A. Twenty Years of Endodontic Success and Failure. JOE, 1983, 
Vol. 9. 
25  Sjörgen U., Hagglund B., Sundqvist G., Wing K. Factors Affecting the Long-term Results of Endodontic 
Treatment.  JOE, 1990, Vol. 16. 
26  Smith C. S., Setchell D. J., Harty F. J.  Factors Influencing the Success of Conventional Root Canal 
Therapy - A Five Year Retrospective Study.Int. Endo. J., 1993, Vol. 26. 
27  Friedman S., Löst C., Zarrabian M., Trope M. Evaluation of Success and Failure After Endodontic 
Therapy Using a Glass Ionomer Cement Sealer.  JOE, 1995, Vol. 21. 
28  ElAyouti A., Weiger R., Löst C. Frequency of Over-instrumentation with an Acceptable Radiographic 
Working Length. 1, JOE, 2001, Vol. 27. 
29  ElAyouti A., Dima E., Ohmer J., Sperl K., von Ohle C., Lösta C. Consistency of Apex Locator Function: 
A Clinical Study. 2,  JOE, 2009, Vol. 35. 
30  Williams C. B., Joyce A. P., Roberts S. A Comparison between In Vivo Radiographic Working Length 
Determination and Measurement after Extraction. JOE, 2006, Vol. 32. 
31  Parashos P., Gordon I., Messer H. H. Factors Influencing Defects of Rotary Nickel-Titanium Endodontic 
Instruments After Clinical Use. JOE, 2004, Vol. 30. 
32  Parashos P., Messer H. H. Rotary NiTi Instrument Fracture and its Consequences. JOE, 2006, Vol. 32. 
33  Suter B., Lussi A., Sequeira P. Probability of Removing Fractured Instruments from Root Canals. Int. 
Endo. J., 2005, Vol. 38. 
34  Seltzer S., Naidorf I. J. Flare-ups in Endodontics: I. Etiological Factors. JOE, 1985, Vol. 11. 
35  Naidorf I. J. Endodontic Flare-ups: Bacteriological and Immunological Mechanisms. JOE, 1985, Vol. 11. 

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36  Vande-Visse J. E., Brilliant J. D.  Effect of the Irrigation on the Production of Extruded Material at the 
Root Apex During Instrumentation. JOE, 1975, Vol. 1. 
37  Martin H., Cunningham W. T. The Effect of Endosonic and Hand Manuplation on the Amount of Root 
Canal Material Extruded. Oral Surg. Oral Med. Oral Pathol., 1982, Vol. 53. 
38  Al-Omari M. A. O, Dummer P. M. H. Canal Blockage and Debris Extrusion with Eight Preparation 
Techniques.  JOE, 1995, Vol. 21. 
39  Reddy S. A., Hicks M. L.  Apical Extrusion of Debris Using Two Hand and Two Rotary Instrumentation 
Technique. JOE, 1998, Vol. 24. 
40  Ferraz C. C. R., Gomes N. V., Gomes B. P. F. A., Zaia A. A., Teixeira F. B., Souza-Filho F. J.  Apical 
extrusion of debris and irrigants using two hand three engine-driven instrumentation techniques. Int. 
Endo. J., 2001, Vol. 34. 
41  Azar N. G., Ebrahimi G.  Apically-Extruded Debris Using the Pro-Taper System.Aust. Endod. J., 2005, 
Vol. 31. 
42  Tinaz A. C., Alacam T., Uzun O., Maden M., Kayaoglu G. The Effect of Disruption of Apical Constriction 
on Periapical Extrusion. JOE, 2005, Vol. 31. 
43  Tanalp J., Kaptan F., Sert S., Kayahan B., Bayirli G.  Quantitative Evaluation of the Amount of Apically 
Extruded Debris Using 3 Different Rotary Instrumentation Systems. Oral Surg. Oral Med. Oral Pathol. 
Oral Radiol. Endo., 2006, Vol. 101. 
44  Kuştarcı A., Akpınar K. E., Er K. Apical Extrusion of Intracanal Debris and Irrigant Following Use of 
Various Instrumentation Techniques. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endo., 2008, Vol. 
105. 
45  Logani A., Shah N. Apically Extruded Debris with Three Contemporary Ni-Ti Instrumentation Systems: 
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