Prospective, Comparative Assessment of Alveolar Ridge Preservation Using GUIDOR® Easy-graft® Classic in Atraumatic Extraction Socket
Phase: NA
Conditions: Dental Implants, Alveolar Ridge Preservation
Sponsor: Sunstar Americas

 
 
 
CLINICAL STUDY PROTOCOL 
VERSION 1.1 
 
 
 
 
 
NCT#: NCT02702609 
 
 
 
 
 
Study Product: 
GUIDOR® easy-graft® 
CLASSIC 
Study Code: 
CLP-2015-12-17-1 
Date: 
Jan. 22, 2016 
Version  
1.1 
PROSPECTIVE, COMPARATIVE ASSESSMENT OF 
ALVEOLAR RIDGE PRESERVATION USING GUIDOR® 
EASY-GRAFT® CLASSIC IN ATRAUMATIC 
EXTRACTION SOCKET  
 

 
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PROTOCOL SYNOPSIS 
 
Coordinating Investigator  
Dr. Hanae Saito, Assistant Professor at University of Maryland  
 
 
Study center(s) and number of subjects planned 
The study will include a total of 44 subjects equally distributed at two centers: 
Center 1: Professor Mark Reynolds, University of Maryland, USA 
Center 2: Professor Georgia K. Johnson, University of Iowa, USA 
 
Study timetable 
 
Estimated date of first subject 
enrolled 
April 2016 
Estimated date of last subject 
completed implant placement 
 
Estimated date of last subject 
completed follow-up period 
April 2017  
 
 
September 2018 
 
Objectives 
The primary objective of this study is to investigate linear and volumetric osseous 
changes at 4 months following ridge preservation by calculating horizontal and vertical 
bone changes via cone beam computed tomography (CBCT).   
 
The secondary objectives of the study are to evaluate:  
- 
New bone replacement/remaining graft residuals at re-entry 
(histomorphometric assessment). 
- 
Change in mesial and distal marginal bone loss on periapical 
radiographs from baseline to re-entry. 
- 
Change in mesial and distal marginal bone loss on periapical 
radiographs from crown delivery to 6 months and to 12 months after 
the crown delivery (follow-up observation). 
 
 
Study design 
The study is designed as a randomized controlled clinical trial.  Patients will be assigned 
for ridge preservation of a single extraction socket site to treatment group A (GUIDOR® 
easy-graft CLASSIC) or group B (Freeze-dried bone allograft (FDBA) with collagen 
plug).  

 
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The study will involve a ridge preservation procedure and the follow-up observation 
period in 12 months after delivery of implant-supported prosthesis. The study 
randomization key will be opened after completion of re-entry visit of all patients for 
analysis of the primary endpoint.  However, examiners and central reading centers will 
have to be masked until the end of study.  
 
Target subject population 
Patients in need of ridge preservation prior to dental implant therapy in a single 
extraction socket in premolars and molars except for third molar will be included. 
 
Investigational product 
GUIDOR® easy-graft CLASSIC is a bone graft substitute consisting of pure beta-
triphosphate calcium (β-TCP) coated by poly (lactic-co-glycolic acid) (PLGA) and 
BioLinker™.  BioLinker™ is comprised of N-methyl-2-pyrrolidone (NMP).  The particle 
size is 500– 1000 µm and is sterilized by gamma sterilization process.  The mixture of 
grafting material and BioLinker get hardening into a stable, porous immediately after the 
mixture contacts blood or body fluid in a defect. 
 
Comparator, dosage, and mode of administration 
Mineralized cortical freeze-dried particulate bone allograft (FDBA) has a particle size of 
250-1000 μm (Lifenet).  It is sterilized via Allowash XG® technology.   
 
Collagen plug (Zimmer Dental Inc.), is made from a bovine type I collagen. The 
resorption period is 10-14 days.     
 
Duration of treatment 
The study will be a five month follow up to re-entry for implant placement.  The 
treatment period includes ridge preservation followed by implant placement 5 months 
later.  Follow-up visits following the ridge preservation will occur at one week, two 
weeks, 4 weeks, 2 months, 4 months (CBCT) and 5 months (re-entry and implant 
placement). 
 
Follow-up observation after the implant placement will occur at the crown delivery, 6 
months and 12 months.   
 
Outcome variables 
Efficacy 
Primary outcome variable:  
- 
Linear and volumetric horizontal and vertical bone changes at 4 
months 
Secondary outcome variables:  
- 
Qualitative histology: new bone and residual graft particles  

 
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- 
Mesial and distal marginal bone loss on periapical radiographs at 
reentry and follow-up period after crown delivery. 
 
Safety 
- 
Complications 
- 
Adverse events 
 
Statistical methods 
The primary outcome variables of dimensional horizontal and vertical bone changes will 
be analyzed by Wilcoxon rank sum test.   
 
The secondary outcome variable assessing new bone formation and residual graft 
particles, and mesial/distal bone loss will be analyzed by Wilcoxon rank sum test. 
 
 
 
 

 
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1 INTRODUCTION 
1.1 Background 
A horizontal loss of some 15% of the original width of the alveolar ridge already occurs 
in the first 6–8 weeks after tooth loss. A broad systematic analysis of the relevant 
literature showed that vertical loss in the first 6 months equals about 1.2 mm which is 
about 11–22% of the original height (1). With physiological loss of hard and soft tissue 
following tooth extraction, the conditions deteriorate for proper axial alignment of the 
implant and aesthetically pleasing prosthetic treatment (2, 3).  
To minimize alveolar atrophy in the course of wound healing, method has been 
described that is summarized under the terms “ridge preservation”. This typically 
involves filling the extraction socket with bone or bone graft substitute and/or covering it 
with a membrane. When a tooth is extracted atraumatically without raising a flap the 
bone graft substitute can be plugged by a collagen plug. The primary objective of ridge 
preservation is preserving the alveolar ridge volume. A systematic literature analysis 
shows that ridge preservation procedures are effective. With ridge preservation 
procedures, alveolar atrophy in the first 6 months after tooth extraction is significantly 
lower than atrophy in non-treated control groups (4). 
Evidence-based reviews have shown positive outcomes using a broad range of grafting 
materials, including autogenous bone, allografts, and xenografts in ridge preservation 
procedures (5, 6). Synthetic bone grafting materials are made from mineral raw 
materials. The most-used materials are β -tricalcium phosphate (β -TCP), 
hydroxyapatitie (HA) and biphasic calcium phosphate. Human bone consists of 
approximately 60-70% of a modified hydroxyapatitie (HA) and 30-40% of organic 
constituents and water, this material can give bone its strength (7, 8).  
Easy-graft® CLASSIC, is commercially available alloplastic bone graft granules consists 
of pure β -TCP, which has been commonly used for the indication of ridge preservation 
(9). It has unique handling capacity based on an extremely thin coating of the graft 
granules with poly(lactic-co-glycolic acid) (PLGA). In medicine, PLGA is used to 
manufacture dental membranes, suture materials and resorbable screws. Before 
application, the granules are mixed with BioLinker™ which consists of water and N-
Methyl-2-pyrrolidone (NMP). It is non-volatile solvent which has been in used in various 
medical products for more than 10 years. Easy-graft remains moldable until it comes in 
contact with blood or tissue fluids. When the material is soaked in blood in bone defects 
it hardens in a few minutes to form stable porous scaffold for bone regeneration. This 
characteristic of graft material gives better handling for the clinician.  
The pilot case study aiming to evaluate the performance of easy-graft CLASSIC in 
extraction socket ridge preservation has been conducted by University of Maryland 
School of Dentistry (IRB# HP00063203).  The interim observation of the study indicates 
that the effectiveness of easy-graft CLASSIC is not inferior to those of other leading 
bone graft substitutes even when easy-graft is used without a membrane or a plug 

 
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covering the defect site.  It is beneficial to both dentists and patients to avoid additional 
treatment time and a cost of membrane or a plug.   
The purpose of study is to evaluate two different treatment approaches using easy-graft 
CLASSIC for comparative effectiveness to freeze-dried bone allograft (FDBA) with 
collagen plug (Collagen Plug, Zimmer Dental Inc.) in ridge preservation when the study 
tooth is extracted atraumatically. Furthermore, implant stability will be observed in the 
follow-up period.   
 
2 STUDY OBJECTIVES 
2.1 Primary objective 
The primary objective is to assess horizontal and vertical linear and volumetric osseous 
changes after single tooth extraction and the application of two different ridge 
preservation techniques, via DICOM data analysis. The changes from baseline to four 
months will be compared. Radiographic measurements will be obtained from DICOM data 
files acquired by CBCT imaging. 
 
Hypothesis: The treatment group with easy-graft CLASSIC is superior or at least not 
inferior to the control treatment group (FDBA with collagen plug). 
2.2 Secondary objectives 
Secondary objectives of the study are to evaluate and compare: 
- 
New bone replacement/remaining graft residuals at re-entry (histomorphometric 
assessment). 
- 
Change of mesial and distal marginal bone loss on periapical radiographs from 
baseline to re-entry. 
- 
Change of mesial and distal marginal bone loss on periapical radiographs from 
crown delivery to 6 months and to 12 months after the crown delivery (follow-up 
observation). 
 

 
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3 STUDY PLAN AND PROCEDURES 
3.1 Overall study design and flow chart 
The study is designed as a randomized control prospective study with two study 
centers. 
 
The study population will consist of individuals requiring ridge preservation prior to 
dental implant therapy in a single tooth extraction socket in premolars and molars 
except for third molars. 
 
A total of 44 subjects will be randomized to obtain at least 40 evaluable subjects in 
anticipation of a 10% dropout rate. 44 evaluable subjects will be enrolled at two centers. 
Each subject will be randomized into one of two groups: group A (GUIDOR® easy-graft 
CLASSIC) and group B (FDBA and collagen plug).  Each center will enroll 22 evaluable 
subjects, 11 per group ideally.  
 
The ridge preservation study will be a 5-month follow-up with 9 main clinic visits to re-
entry/implant placement.  Three additional clinic visits for the observation period will be 
scheduled after crown delivery to the study site.  
3.1.1 
Visit 1:  Screening 
Subjects in need of ridge preservation of a single tooth extraction socket in premolars or 
molars prior to dental implant surgery that are deemed eligible by meeting inclusion and 
exclusion criteria will be considered for treatment in this study.  Third molars will be 
excluded as a study site. 
 
Screening process will include evaluation of general dental and systemic health.  It will 
also include a clinical and radiographic assessment of the potential study site and the 
adjacent teeth.  Pre-existing intraoral (periapical) radiograph can be used but must not 
be older than 6 months. All women except for postmenopausal women will require a 
negative urine human chorionic gonadotropin (HCG) test result prior to inclusion in the 
study to rule out pregnancy. Postmenopausal is considered when the patient has not 
had her period for an entire year. Eligible subjects will immediately be scheduled for 
Visit 2 provided that they fulfill all inclusion and none of the exclusion criterion. 
3.1.2 
Visit 2:  Enrollment  
Visit 1 (Screening) and Visit 2 (Enrollment) may occur on the same day.  Individuals 
meeting all inclusion and none of the exclusion criteria and that have signed all 
appropriate consent forms will be further evaluated.  Before any assessment or 
examination is carried out for study purposes the subject must have been informed 
orally and in writing about the study, and have signed the appropriate consent forms.  
Informed consent for the research study will be given and signed on paper, as well as 

 
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HIPAA authorization, if not already obtained. Subjects will also be asked to sign 
informed consent documents.  
Subjects meeting all inclusion and none of the exclusion criteria will be randomly 
allocated to Group A or B.  Subjects with smoking habit will be stratified to be distributed 
equally to two treatment groups. 
Cone beam computed tomography (CBCT) imaging 
 
Small segmental cone beam computed tomography (CBCT) imaging will be obtained for 
all patients 4 months following the ridge preservation surgical procedure. Images will 
provide baseline data for horizontal and vertical bone locations.  
 
A CBCT scan will be obtained using i-CAT Next Generation (Imaging Sciences 
International Inc., Hatfield, PA, USA) or equivalent system. Only the arch that contains 
the site of interest will be scanned to minimize the radiation exposure. Based on 
previous investigations, the field of view will be approximately 6 cm and the machine 
settings will be fixed at 120 kVp and 18.66 mAs for all scans.    
 
Subject with intact ridge verified with CBCT scan is eligible to be enrolled to the study (If 
not, Screen failure).   
 
 
 

 
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Figure 1 Study flow chart 
 
 
 
3.1.3 
Visit 3:  Extraction Tooth and Socket Ridge Preservation 
Visit 2 (Enrollment) and Visit 3 (Surgery) may occur on the same day.  
 
Pre-Surgical, Surgical, and Post-Surgical Care (at surgical appointment) 
 
Pre-surgical, surgical and post-surgical care will be given at the discretion of the 
Investigator and recorded in appropriate sections in the CRF: 
 
• Antibiotics 
• Analgesics 
----- CBCT
----- PA radiograph
----- CBCT
----- PA radiograph 
       Histology
----- PA radiograph
----- PA radiograph
*after prosthesis delivery
Prosthesis Delivery
Follow-up (6 months*)
Follow-up (12 months*)
Post-op Follow-up (4 months)
Post-op Follow-up 
(1, 2, 4 Wks and 2 months)
Implant Placement (5 months)
Eligible patients
Baseline measurement
Extraction socket ridge preservation
Group B 
(FDBA + CollaPlug)
Group A 
(GUIDOR easy-graft)

 
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• Sedation 
• Anaesthesia 
 
Antibiotics: 
 
Post-surgical antibiotic coverage will be provided to patients.  The regimen is left up to 
the surgeon’s discretion.   
 
Analgesics: 
The regimen is left up to the surgeon’s discretion.   
 
Sedation: 
The regimen is left up to the surgeon’s discretion.   
 
Anesthesia: 
The regimen is left up to the surgeon’s discretion.   
 
Pre-Surgical Procedures 
 
Buccal and occlusal photographs of the planned surgical site will be obtained. Width of 
keratinized mucosa on the buccal and thickness of the buccal and lingual mucosa will 
be measured by a caliper. Standardized periapical radiograph of a target tooth will be 
taken.  
 
Surgical Procedure 
 
After administration of local anesthesia, the tooth will be extracted without raising a 
mucoperiosteal flap. A minimally invasive extraction procedure helps protection and 
preservation of the surrounding socket bone.  Horizontal bucco-lingual ridge width at crest 
will be measured intraoperatively and recorded in CRF.  The bucco-lingual width will be 
measured intraoperatively using a pointy caliper. The width will be measured 1mm apical 
to the alveolar crest level.   
 
If fenestration and/or dehiscence are present when the marginal bone is sounded by a 
perioodontal probe through the sulcus around the tooth or fracture of the buccal bone is 
noted upon extraction, the subject will be excluded from the study and treated as a 
normal patient of the clinic (Incorrect enrollment). 
 
After thorough debridement of granulated tissue and rinsing with sterile saline the 
prepared easy-graft® CLASSIC (Group A) or FDBA (Group B) will be grafted to the 
socket defect.  Easy-graft CLASSIC should be prepared according to manufacturer’s 
instruction.  FDBA will be rehydrated by sterile saline before grafting.   
The graft materials will be condensed to achieve a fill of the socket to level of crestal 
bone.   
 

 
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A bioabsorbable collagen wound dressing (Collagen Plug, Zimmer Dental Inc.) will be 
placed on the top of the graft (FDBA) and secured with sutures. (Group B).   
 
Post-Surgical Procedures 
 
Buccal and occlusal photographs of the surgical site will be obtained.  Post-operative 
medications will be prescribed. An intraoral PA radiograph will be taken in order to 
assess ridge preservation surgery. 
3.1.4 
Visit 4:  Post-Operative Visit (7 days ± 2 days) 
Buccal and occlusal photographs of the surgical site will be obtained. Gentle 
debridement and oral hygiene instruction will be provided.  AEs will be recorded.   
3.1.5 
Visit 5:  Post-Operative Visit (14 days ± 2 days) 
Remaining suture material will be removed (only Group B).  Buccal and occlusal 
photographs of the surgical site will be obtained.  AEs will be recorded. 
3.1.6 
Visit 6:  Post-Operative Visit (28 days ± 2 days) 
Buccal and occlusal photographs of the surgical site will be obtained. Gentle 
debridement and oral hygiene instruction will be provided.  AEs will be recorded.   
3.1.7 
Visit 7:  Post-Operative Visit (2 months ± 4 days) 
Buccal and occlusal photographs of the surgical site will be obtained. Gentle 
debridement and oral hygiene instruction will be provided.  AEs will be recorded.   
3.1.8 
Visit 8:  Post-Operative Visit (4 months ± 7 days) 
In this visit, a second segmental CBCT scan will be obtained for all patients, using the 
same settings employed at baseline, as detailed in above.  Images will provide post-
ridge preservation data for horizontal and vertical bone locations.  Buccal and occlusal 
photographs of the surgical site will be obtained.  AEs will be recorded. 
3.1.9 
Visit 9:  Re-entry and Dental Implant Placement (5 months ± 14 
days) 
 
Pre-Surgical, Surgical, and Post-Surgical Care  
 
See Section 3.1.3. 
 
Pre-Surgical Procedures 
 
Buccal and occlusal photographs of the surgical site will be obtained. Standardized 
periapical radiograph of a target tooth will be taken. 
 

 
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If the bucco-lingual ridge width is judged not enough for implant placement the subject 
will be terminated from the study and will receive an appropriate treatment and followed 
according to the clinic’s routines. 
 
Surgical Procedure 
 
Implant placement is made per standard procedure.  For patients in each treatment 
group, a trephine drill will be used to harvest a core of bone for descriptive histology.  A 
trephine drill will be used to harvest a core of bone corresponding with the planned 
implant length.  A trephine drill of 2.8 mm in diameter will be used as the first choice.  If 
another diameter has to be used a diameter of the trephine will be recorded in CRF.  A 
length of a trephine will be up to 8 mm.  Following harvesting, the trephined bone core 
will immediately be transferred to a solution of 10% neutral buffered formalin (NBF). 
These samples are to be used for histomorphometric assessment.  Bone Density 
Classification (Misch Classification)(10) will be evaluated and recorded in CRF. 
 
Selection of implant system will be left to the judgment of study sites; however the same 
system should be used in all the cases treated at the site.  Implant site preparation and 
placement will proceed according to the implant system manufacturer 
recommendations. 
 
When one-stage approach is chosen, a healing abutment will be placed to finger 
tightness.  Depending on the buccal soft tissue thickness, the crestal tissue will either 
be removed or deepithelialized and inverted to the buccal to increase the soft tissue 
thickness.  When two-stage procedure is chosen, a cover screw will be placed and stay 
buried and left to heal.  Once healed, a second surgery is performed to attach an 
abutment for securing the crown in place.  Selection of approach will be left up to the 
dentist’s discretion. 
 
Post-Surgical Procedures 
 
An intraoral periapical radiograph will be obtained immediately postoperatively to 
assess the depth and angulation of dental implant placement.  Buccal and occlusal 
photographs of the surgical site will be obtained. An intraoral PA will be taken in order to 
assessment of implant placement. Post-surgical AEs will be recorded. 
 
Post-operative medications will be prescribed.  
3.1.10 
Visit 10:  Prosthesis Delivery 
Visit 10 will be scheduled on the day of prosthesis delivery or at least 14 days after 
prosthesis delivery. Buccal and occlusal photographs of the surgical site will be 
obtained.  
 
Standardized periapical radiograph of a study site will be taken following prosthesis was 
delivered. Plaque Index (modified Quegley- Hein) of teeth adjacent to the study site and 

 
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bleeding on probing on the study site will be evaluated and recorded in CRF. AEs will 
be recorded. 
3.1.11 
Visit 11:  Follow-Up Visit (6 months ± 14 days after Prosthesis 
Delivery) 
Buccal and occlusal photographs of the surgical site will be obtained. Standardized 
periapical radiograph of a target tooth will be taken. Standardized periapical radiograph 
of a study site will be taken following prosthesis was delivered.  Plaque Index (modified 
Quegley- Hein, 1970) of teeth adjacent to the study site and bleeding on probing on the 
study site will be evaluated and recorded in CRF. AEs will be recorded. 
 
3.1.12 
Visit 12:  Follow-Up Visit (12 months ± 28 days after Prosthesis 
Delivery) 
Buccal and occlusal photographs of the surgical site will be obtained. Standardized 
periapical radiograph of a target tooth will be taken. Standardized periapical radiograph 
of a study site will be taken following prosthesis was delivered.  Plaque Index (modified 
Quegley- Hein, 1970) of teeth adjacent to the study site and bleeding on probing on the 
study site will be evaluated and recorded in CRF. AEs will be recorded. 
 
 
 
 
 

 
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Figure 2  Appointment flow chart 
 
 
Visit 1
Can be combined
Visit 2
t= -2 wks
Can be combined
Visit 3
t= 0
Visit 4 - 7
t= 1, 2, 4 wks & 2 mos
Visit 8
t= 4 mos
Visit 9
t= 5 mos
Visit 10
Visit 11
t'= 6 mos after Visit 10
Visit 12
t'= 12 mos after Visit 10
Prosthesis Delivery
Implant Stability Evaluation
Implant Stability Evaluation
Re-entry
Implant Placement
Screening
Informed Concent, CBCT, 
Enrollment, Randomization
Tooth Extraction
Ridge Rreservation
Post-Operative Evaluation
CBCT

 
 
 
VERSION 1.1 
 
1.Pre-existing CBCT taken for the treatment planning are available.
Table 1  Study plan 
 
 
 
 
 
 
 
 
 
   
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Visit Description 
Screeni
ng 
Enrolm
ent 
Ridge 
preserv
ation 
Post-op 
Post-op 
Post-op 
Post-op 
Post-op 
(CBCT) 
Implant 
placem
ent 
Prosthe
sis 
delivery 
Follow-
up 
Follow-
up 
Visit Window 
 
-2w> 
0 
1w±2d 
2w±2d 
4w±2d 
2m±4d 
4m±1w 
5m±2w 
0 
6m±2w 
1Y±4w 
Patient Information 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
Patient demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Oral examination 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
 
X 
 
 
 
 
 
 
 
 
 
 
Treatment 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical photography 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tooth extraction / Ridge preservation 
 
 
X 
 
 
 
 
 
 
 
 
 
Suture removal 
 
 
 
 
X 
 
 
 
 
 
 
 
Trephined bone sample 
 
 
 
 
 
 
 
 
X 
 
 
 
Implant placement 
 
 
 
 
 
 
 
 
X 
 
 
 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
CBCT (ridge dimensions) 
 
(X)1 
 
 
 
 
 
X 
 
 
 
 
Standardized PA radiograph 
 
 
X 
 
 
 
 
 
X 
X 
X 
X 
Bone density classification 
 
 
 
 
 
 
 
 
X 
 
 
 
Histology 
 
 
 
 
 
 
 
 
X 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Width of keratinized mucosa 
 
 
X 
 
 
 
 
 
 
 
 
 
Horizontal ridge width  
 
 
X 
 
 
 
 
 
 
 
 
 
Wound dehiscence 
 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Adverse events/Adverse device 
effects 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
VERSION 1.1 
 
3.2 Rationale and risk/benefit assessment  
It is necessary to further define the effects of different grafting materials on clinical 
outcomes following ridge preservation.  This study will employ gold standard 
methods of evaluation efficacy and safety conforming to that stipulated of the 
medical, clinical research, and regulatory communities to demonstrate clinical benefit 
of GUIDOR® easy-graft CLASSIC.  The study has been designed to treat a clinical 
scenario commonly encountered in clinical practice.   
 
The patients will benefit from a preserved alveolar ridge dimension to permit dental 
implant placement.  The public will benefit from the study results which will help to 
refine the knowledge of bone preservation and healing following ridge preservation 
with different grafting material.  This will help aid clinicians in the selection of 
materials to optimize their clinical outcomes of treatment.  The study also includes 
dental implant placement and acquisition of data that will help to define the effect 
that different grafting materials have on implant stability at time of placement and 
follow-up period for one year after the implant placement.  Data acquisition includes 
minimally invasive collection methods, both before and after the surgical procedures.   
3.2.1 
Study selection record 
Investigator(s) will keep a record of subjects who were considered for enrollment but 
were never enrolled (e.g., subject screening log).  This information is necessary to 
establish that the subject population was selected without bias. 
3.2.2 
Inclusion criteria 
For inclusion in the study subjects must fulfill all of the following criteria: 
 
1. 
Provision of informed consent 
2. 
At least 18 years old 
3. 
In need of one posterior tooth, excluding third molar molars, planned for 
extraction and replacement with a dental implant (If the subject requires two 
adjacent socket preservation, they can still be enrolled in the study but only one 
site will be used for the study) 
4. 
Intact ridge as verified with cone-beam CT scan 
5. 
At least one natural tooth adjacent to the study site present. 
3.2.3 
Exclusion criteria 
Any of the following is regarded as a criterion for exclusion from the study: 
 
1. 
Insufficient interocclusal space to allow for implant supported prosthesis 
2. 
Dehiscence or fenestration identified at the time of reviewing CBCT.  
3. 
No previous interventions performed involving soft and/or bone grafting 

 
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4. 
Non-treated caries or uncontrolled periodontal disease present affecting the 
teeth in adjacent to study site 
5. 
Any of natural teeth adjacent to the study site presents active periapical 
endodontic lesion (“active periapical endodontic lesion” will be determined per 
consultation by endodontics specialist). 
6. 
Adjacent tooth (mesial and distal) to study site was extracted within last 6 
months 
7. 
Smoker using more than 10 cigarettes or equivalent per day 
8. 
Smokeless tobacco use or e-cigarette use 
9. 
Current alcohol or drug abuser 
10. Systemic or local disease or condition that would compromise post-operative 
healing and/or osseointegration e.g. uncontrolled diabetes 
11. Need for systemic corticosteroids or any other medication that would influence 
post-operative healing and/or osseointegration 
12. Pregnancy, as indicated by positive urine human chorionic gonadotropin (HCG) 
test result. 
13. Unable or unwilling to return for follow-up visits for a period of 5 months 
14. Unlikely to be able to comply with study procedures according to Investigators 
judgement 
15. Subject in other clinical trials 
3.2.4 
Restrictions 
Subjects will be advised of the following restrictions during the study period: 
• Bridge or denture involving the study site is not allowed except for Essex type 
appliance as long as it does it does not touch the surgical site. 
• To avoid disruption of wound healing during the initial study period the subject 
should have a restricted diet for at least 14 days (printed instructions will be 
distributed to the subjects at Visit 3 per institutional standard of care). 
• For current smokers, no more than 10 cigarettes per day are allowed. 
3.2.5 
Discontinuation of subjects from treatment or assessment 
Criteria for discontinuation 
Subjects may be discontinued from study treatment and assessments at any time. 
Specific reasons for discontinuing a subject from this study are: 
 
• Voluntary discontinuation by the subject who is at any time free to discontinue 
his/her participation in the study, without prejudice to further treatment 
• Safety reasons as judged by the investigator and/or Sponsor 

 
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• Severe non-compliance to protocol as judged by the investigator and/or 
Sponsor 
• Incorrect enrolment (i.e., the subject does not meet the required 
inclusion/exclusion criteria for the study) 
- 
If a dehiscence and/or a fenestration are observed intraoperatively 
upon tooth extraction, the subject will be excluded. 
• Subject received further dental therapy on study site or adjacent teeth without 
consent of investigator (e.g. new crown, periodontal surgery, or orthodontics 
on adjacent teeth) 
• Subject lost to follow-up 
Procedures for discontinuation 
Subjects who discontinue should always be asked about the reason(s) for their 
discontinuation and the presence of any AEs or ADEs.  If possible, they should be 
seen and assessed by an investigator(s).  Ongoing AEs and ADEs should be 
followed up. 
 
A subject will be classified as lost to follow up only if, he/she has failed to return to 
the required study visits and his/her dental status remains unknown, despite multiple 
attempts to contact the subject via telephone, fax, email, certified letter and through 
subject locator agencies (if allowed per national regulation). 
Procedures for handling incorrect enrolled subjects 
Subjects not meeting the inclusion/exclusion criteria for a study should, under no 
circumstances, be enrolled into the study - there can be no exceptions to this rule. 
When subjects not meeting the study criteria are enrolled in error, or if subjects 
subsequently fail to meet the criteria for the study after enrollment, they will be 
excluded from the study and from the analyses.  
 
If subjects are excluded intraoperatively (e.g. dehiscence), the subjects will receive a 
standard grafting treatment at no cost. However, an implant placement at the site will 
be at the patient’s cost. 
3.3 Treatments 
3.3.1 
Identity of investigational product and comparators 
GUIDOR® easy-graft CLASSIC is bone grafting system contains: syringe containing 
beta-tricalcium phosphate (β-TCP) granules coated with poly (lactide-co-glycolide) 
(PLGA) and ampule containing BioLinker™ Activator (N-methyl-2-pyrrolidone and 
water). 
 
Easy-graft CLASSIC is a bioresorbable, synthetic, porous bone graft substitute. It 
consists of two components: granules (supplied in syringe) and BioLinker activator 
(supplied in ampule).  After mixing the components together, easy-graft CLASSIC 
forms a moldable mass that can be applied directly from the syringe into the bone 
defect. easy-graft CLASSIC hardens in contact with body fluids, allowing a working 
time of approximately one minute after application into the bone defect.  Easy-graft 
CLASSIC is provided in the particle size of 500 – 1000 μm.  Easy-graft CLASSIC is a 
biocompatible and osteoconductive material that allows for complete resorption by 

 
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the body.  β-TCP and PLGA are derived from synthetic raw materials.  Easy-graft 
CLASSIC comes sterilized via gamma irradiation.  
 
Collagen Plug, Zimmer Dental Inc. is made from type I bovine collagen.  Collagen 
Plug is a biocompatible, sterile resorbable highly porous collagen wound dressing for 
bleeding control, stabilizing the blood clot, and protecting the wound bed.  Its 
dimensions are 10mm X 20 mm and have a resorption period of 10-14 days.  
 
Lifenet Health® mineralized cortical freeze-dried particulate bone allograft (FDBA) 
has a particle size of 250-1000 μm.  It is sterilized via Allowash XG® technology, 
consisting of rigorous screening and assessment of donor tissues; cleaning with 
hypotonic solutions and antimicrobial reagents; decontamination, disinfection, and 
cleaning regimens with hydrogen peroxide and isopropanol alcohol solutions; and 
terminal sterilization with gamma irradiation.  The particulate material comes 
packaged in a sterile vial in a blister pack. 
3.3.2 
Labeling 
All grafting materials will be labelled as follows: 
• “Reference number” 
• “Lot number” 
• “Expiration date” 
 
All dental implant materials will be labeled as follows: 
• “Reference number” 
• “Lot number” 
• “Expiration date” 
• “Single use” 
• “Sterile” 
 
The reference number and lot numbers will be recorded in clinical records (source 
data) and CRF. 
3.3.3 
Storage 
All investigational products must be kept in a secure place under appropriate storage 
conditions.  Descriptions of the appropriate storage and shipment conditions are 
specified on the study product label and product information. 
3.3.4 
Accountability 
Distributed study products will be used for this study in accordance with the study 
protocol.  All product deliveries, distributions and dispositions will be confirmed by 
the investigator or delegate, and recorded in the log.   
3.4 Method of assigning subjects to treatment groups 
Screening numbers will be assigned at day of screening (Visit 1).  Subjects at center 
1 will receive numbers starting at S101 and subjects at center 2 will receive numbers 
starting at S201.  Subject numbers (subject ID) will be consecutively allocated in 
series at day of inclusion (Visit 2).  Subjects at center 1 will receive numbers starting 

 
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at 101 and subjects at center 2 will receive numbers starting at 201.  Enrollment will 
continue until 22 subjects at each center have been allocated a subject ID.  If a 
subject discontinues, the subject number will not be reused. 
 
Subjects will be randomized strictly sequentially at enrollment (Visit 2).  The 
randomization schedule will be generated using a validated system under the 
responsibility of the data management team.  The randomization procedure will be 
concealed.  Randomization will be stratified by center and smoking habit, i.e. each 
center will have 11 subjects in each group A and B, respectively with an equal 
number of subjects with current tobacco consumption per group.  The allocation will 
be revealed to the clinician only following tooth extraction for ridge preservation. 
3.5 Pre-study, concomitant and post-study treatment(s) 
Systemic corticosteroids or any other medication that would compromise post-
operative healing and/or bone healing are not allowed. 
 
After surgery, mouth rinsing with 0.12% non-alcohol chlorhexidine rinse will be 
subscribed according to local routines.  
 
Subjects will be given post-surgical instructions with regards to diet and oral hygiene. 
Oral hygiene instructions will be given to the subjects at all study visits. 
 
Other medication, which is considered necessary for the subject’s safety and well-
being, may be given at the discretion of the investigator(s). The administration of all 
medication must be recorded in the appropriate sections of the CRF. This includes 
all mediation administered pre-surgical, during surgery and post-surgical.  
 
 

 
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4 MEASUREMENTS OF STUDY VARIABLES AND 
DEFINITIONS OF OUTCOME VARIABLES 
4.1 Screening and demographic measurements 
The following data will be recorded via a standard CRF: 
• Date of birth 
• Sex 
• Race 
• Relevant medical and surgical history 
• Medication 
• Oral examination  
• Local condition of alveolus and adjacent teeth 
o Periodontal disease 
o Bone loss 
o Caries 
o Endodontic treatment 
o Existing periapical radiolucency 
• Tobacco use 
• Reason for tooth extraction 
• Previous bone graft, soft tissue graft, or apical surgery 
• Opposing tooth contact in maximum intercuspation 
4.2 Efficacy 
4.2.1 
Primary outcome variable 
4.2.1.1 Dimensional osseous changes 
The amount of horizontal and vertical bone changes will be calculated using data 
from DICOM images acquired by CBCT using 3D software. 
4.2.1.1.1 Methods of assessment 
CBCT scans will be obtained at baseline and 4 months following ridge 
preservation (Visit 8). Linear measurements will be done at the 
University of Iowa by a single, calibrated examiner. Volumetric 
assessments will be performed by an external reading center in 
Georgia that is associated with the University of Iowa. All examiners 
will be masked for the therapy applied in each case.  
For the horizontal and vertical measurements a plane of reference will 
be set to allow for reproducible and reliable assessments (in mm) 
between both baseline and 4-month datasets.  
Volumetric assessments will be performed using a specific software 
(Simplant 16 Pro) via selection of a region of interest (ROI) that 
includes only hard tissues. The same segmentation settings of the ROI 
selected in the baseline scan will be transferred to the 4-month 
reconstruction in order to generate comparable volumes. Volume 

 
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measurements will be expressed in cc, which allows for a calculation of 
the % of volumetric reduction that took place from baseline until one 
month prior to surgical re-entry.  
4.2.1.1.2 Derivation or calculation of variable 
The mid-alveolar point positioned on a tangent drawn from the mesial 
and distal adjacent tooth CEJs will be used as a reference point for 
assessment of dimensional bone changes in the Z-axis (bone width) 
and Y-axis (bone height).  The changes in the bone dimensions 
between baseline (Visit 2) and 4 months (Visit 8) will be measured.  
The change for each study site will be compared longitudinally and the 
average for each treatment group will be calculated and compared 
among treatment groups. 
4.2.2 
Secondary outcome variables 
4.2.2.1 Qualitative histological evaluation 
A core of bone from the defect sites will be harvested for qualitative histological 
assessment. 
4.2.2.1.1 Methods of assessment 
Trephined bone cores will be obtained from a subset of patients from 
each treatment group (Visit 9).   Tissues stored in 10% neutral buffered 
formalin (NBF) will be fixed for at least 7 days.  All bone core samples 
will be sent to University of Maryland. The samples will be 
subsequently rinsed in phosphate buffered solution (PBS) and 
demineralized by immersion in ethylenediaminetetraacetic acid (EDTA) 
for a minimum of 5 weeks.  Cores will be embedded in paraffin, 
sectioned along a transverse plane, and stained with conventional 
hematoxylin and eosin (H&E) technique, and coverslipped for 
qualitative histologic analysis. 
 
Images of sections will be taken with microscope and connected with 
digital camera.  Quantitative assessment of newly formed bone and, 
residual bone graft particles and non-mineralized tissue on histological 
section with H&E staining will be performed at least 5 images randomly 
chosen in the same section and analyzed with recommended software.  
The assessment will be performed by the central reader at University of 
Maryland.   
 
 
 
4.2.2.2 Mesial and distal marginal bone loss on standardized periapical 
radiographs 
The marginal bone loss of the study defect is the change on standardized periapical 
radiographs between baseline and re-entry (Visit 9), and between crown delivery 
(Visit 10) and at 12 months after the crown delivery (Visit 12).  
4.2.2.2.1 Methods of assessment 

 
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Intra-oral periapical radiographs will be obtained at baseline, at 5 
months (re-entry), at crown delivery and at 12 months after the crown 
delivery. These radiographs should be taken using device to 
standardize during course of the study and should image the target 
tooth and at least 2 mm on either side of the osseous defect. The 
following standardizing technique will produce repeatable diagnostic 
quality radiographs with close to identical geometry and image clarity. 
Once the exposure parameters are selected they should not be 
changed during the course of the study. Send the image files to the 
central reading center at each study site for analysis following the 
instructions. 
4.2.2.2.2  Derivation or calculation of variable 
Image processing software is used to capture measurements. First, 
the image of the penny will be used for the conversion of pixels to 
millimeters for every system. The number of pixels per millimeter is 
calculated by dividing the measurement of the penny in pixels by the 
known diameter of a penny of 19.2 mm. If all parameters of the 
system stay the same from radiograph to radiograph, the image of 
the penny should only be submitted once. However, if any parts of 
the system change (i.e. the sensor or capturing device, scanner or 
capturing software), a new penny radiograph should be submitted.  
 
The measurements are taken from a stationary landmark (e.g. the 
mesial and/or distal adjacent tooth CEJs) to the crest of and distal 
marginal bone, to the crest and bottom of osseous defect and to the 
apex of the longest root of mesial and/or distal adjacent tooth in 
millimeters. Ad0 is the root length of distal adjacent tooth at baseline; 
Bd0 is the measurement from the CEJ to the crest of distal marginal 
bone at baseline. All measurements are taken parallel to the long axis 
of the adjacent tooth.  
 
 
Subsequent images are logged in and saved to the file. Linear 
measurements of bone height along root surfaces are made using the 
same method as the original defect.  
 
Measurements to the root apex taken from baseline images (Ad0, 
Am0) are used to correct for any geometric distortion 
(elongation/foreshortening) of subsequent images. 
 
Linear bone change (distal) = Bd0 – Bd5m 
Linear bone change (mesial) = Bm0 – Bm5m 
 
4.3 Safety measurements and variables 
The methods for collecting safety data are described below. 

 
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4.3.1 
Adverse Events 
4.3.1.1 Definitions 
The definitions of AEs, ADEs and Serious Adverse Events (SAEs) are given below.  
It is of the utmost importance that all staff involved in the study are familiar with the 
content of this section.  The principal investigator is responsible for ensuring this. 
Adverse Event 
An AE is any untoward and unintended medical occurrence in a subject.  This 
definition does not imply that there is a relationship between the AE and the medical 
device under investigation.  An AE which is possibly related, is one that may have 
been caused by the medical device, or treatment, however there is insufficient 
information to determine the likelihood of this possibility.   
• Possibly related: temporal relationship of the onset of the event, relative to the 
use/administration of the medical device, is reasonable but the event could 
have been due to another, equally likely cause.  
• Non-related (unlikely): temporal relationship of the onset of the event, relative 
to the use/administration of the medical device, is not reasonable or another 
cause can itself explain the occurrence of the event. 
Ambiguous cases should be considered as possibly related. 
Adverse Device Effect 
An ADE is any untoward and unintended response to a medical device.  This 
definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use of the medical device or any event that is a result of a user error.  
This definition also includes treatment- or procedure-related events. ADEs can only 
occur from the time of medical device use/administration.  Here the event is related 
to the use of the medical device where there is a probable/definite relationship that 
the event may have been caused by the medical device, or treatment.  
• Probably related: temporal relationship of the onset of the event, relative to 
the use/administration of the medical device, is reasonable and the event is 
more likely explained by the medical device/treatment than by any other 
cause.  
• Definitely related: temporal relationship of the onset of the event, relative to 
the use/administration of the medical device, is reasonable and there is no 
other cause to explain the event. 
Expected post-surgical events (i.e.. pain, swelling, bleeding and edema) on the study 
site within 7 days following surgeries will be excluded from AE/ADE. 
Serious Adverse Event 
A SAE is an AE/ADE occurring during any study phase of the medical device that 
fulfills one or more of the following criteria: 
• Results in death 
• Is immediately life-threatening 
• Requires in-subject hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Is a congenital abnormality or birth defect 
• Is an important medical event that may jeopardize the subject or may require 
medical intervention to prevent one of the outcomes listed above 

 
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If a non-related AE becomes serious, i.e. fulfilling one or more of the above criteria, 
action should be taken as for any other SAE. 
4.3.1.2 Recording of Adverse Events and Adverse Device Effects 
At each visit, scheduled or unscheduled, the subject will be asked an open question; 
"Have you had any health problems since the previous visit?"  
 
All health problems, reported by the subject or found at the clinic visit, where the 
investigator believes the event "possibly" has been caused by the investigational 
medical device or treatment, must be recorded in the CRF as AEs, specifying time of 
onset, action taken, outcome and whether it constitutes a SAE or not.  Non-related 
AEs must be recorded in the CRF together with a short description and whether it 
constitutes a SAE or not. 
 
All health problems, reported by the subject or found at the clinic visit, where the 
investigator believes the event "probably/definitely" has been caused by the 
investigational medical device or treatment, must be recorded in the CRF as AEs 
and ADEs, specifying time of onset, action taken, outcome and whether it constitutes 
a SAE or not. 
 
Should a pregnancy occur, it must be reported in accordance with the procedures 
described in Section 8.2, Pregnancy.  Pregnancy in itself is not regarded as an AE 
unless there is a suspicion that a medical device under study may have interfered 
with the effectiveness of a contraceptive medication. 
4.3.1.3 Reporting of Serious Adverse Events 
Timelines for reporting of SAEs 
Investigators and other study site personnel must inform appropriate Sponsor 
representatives of any SAE that occurs during the course of the study within one day 
(i.e., immediately but no later than the end of the next business day) of when he or 
she becomes aware of it.  
 
The Sponsor representative will work with the Investigator to compile all the 
necessary information and ensure that the appropriate Sponsor personnel receives a 
report by day one for all fatal and life-threatening cases and by day five for all other 
SAEs. 
 
If an AE or ADE becomes a SAE, this and other relevant follow-up information must 
also be provided to Sponsor within one day for all fatal and life-threatening cases 
and by day five for all other SAEs. 
 
The Investigator is responsible for informing the ethics committee of SAEs as per 
local requirements.  
 
SUNSTAR is responsible for informing the regulatory authority of device related 
SAEs as per requirements. 

 
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5 DATA MANAGEMENT 
5.1 Data handling 
Sponsor or the designee will supply investigative sites with access to electronic case 
report forms (eCRF) via a web-based electronic data capture system. The eCRF will 
be completed for each included patient.  The completed eCRFs will not be made 
available in any form to third parties without written permission from Sponsor.  
 
All data from source documents will be entered into the eCRF database.  The data 
entry will be verified by means of double data entry or proofreading by each clinical 
site.  Before database lock, both manual and computerized validation tests will be 
performed and, if necessary, data queries will be sent to the investigator for 
clarification.  Should questionable data be detected during the validation process, 
written queries will be raised as result of this validation.  The study site personnel are 
required to resolve any such queries.  The eCRFs will be retained for 10 years. 
 
At the end of the study, Sponsor or the representative will perform final validation 
checks, including central consistency checks, after which Clean File will be declared 
and the database locked.  
5.2 Record retention 
To enable evaluations and/or audits from regulatory agencies or Sponsor and its 
representatives, the investigator agrees to keep records in the Investigator’s Study 
File (ISF), including the identification list of the participating patients, all original 
signed Informed Consent forms, and detailed records of medical device disposition.  
To comply with international regulations, the investigator should retain the records 
for 10 years. 
 
 

 
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6 STATISTICAL METHODS AND DETERMINATION OF 
SAMPLE SIZE 
6.1 Statistical evaluation – general aspects 
A comprehensive Statistical Analysis Plan (SAP) may be prepared before database 
lock. If prepared, the SAP will be kept as an appendix to the Data Management Plan. 
When using the terminology descriptive statistics it means that number of patients, 
mean, median, standard deviation, minimum and maximum values will be presented 
for continuous data and frequencies and percentages for categorical data. 
 
If nothing else is stated, descriptive statistics will be given for each variable in the 
study and p-values may be complemented by confidence intervals as appropriate. 
All p-values presented will be two-sided. A p-value less than 5% will be called 
“statistically significant” but all conclusions will be based on the primary objective and 
hence multiplicity is accounted for even though careful interpretations are necessary 
as multiple tests are performed. 
6.1.1 
Demographics and other baseline characteristics 
Demographics and other baseline characteristics will be presented by means of 
descriptive statistics (by group and in total).  Continuous variables will be presented 
by means of number of observations (N), minimum (min), median, maximum (max), 
mean, and standard deviation (std).  Discrete variables will be presented by 
frequency and percentage. 
6.1.2 
Covariates and prognostic variables 
No covariates are judged to influence the outcome of the primary or any of the 
secondary variables. 
6.1.3 
Handling of dropouts and missing data 
Patients dropping out from the trial prior to study end will not be replaced.  Data 
totally missing will not be estimated. 
6.1.4 
Multicenter 
This study is a multicenter study. However, there is not a priori reason to suspect 
that there will be any qualitative differences between the centers regarding any of the 
efficacy variables or regarding the safety variables. Therefore, the primary statistical 
analyses will not include center in the model. 
 
In order to harmonize the use and handling of the graft materials and dental implant 
systems, training will be conducted prior to study start at each center. 
6.1.5 
Subgroup analyses 
Subgroup analysis is not planned.  

 
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6.2 Method of statistical analysis 
6.2.1 
Primary objective 
The primary objective is to compare dimensional bone changes from baseline (Visit 
2) to 4 months (Visit 8) occurring in a single tooth extraction socket following ridge 
preservation using three different techniques.  
 
Assume the change (in the mid-buccal horizontal bone dimensions from baseline to 
five months) is denoted CA and CB, for group A and B. The null-hypotheses (two) is 
then to test if: 
H0 CA = CB 
can be rejected and hence 
H1 CA  CB  
accepted. 
  
H0 will be tested by means of the Wilcoxon rank sum test.  A p-value less than 5% 
will be regarded statistically significant. 
6.2.2 
Secondary objectives 
The data collected in the study were expressed as mean ± standard deviation (SD). 
The Wilcoxon rank sum test will be used for statistical analysis. 
6.3 Determination of sample size 
A sample size of 22 participants per treatment group was selected following power 
calculations and allowing for 10% patient dropout.  A sample size of 20 patients was 
calculated for the primary outcome variable (horizontal bone changes) with the 
assumption that the detectable difference would amount to 0.7 mm with a standard 
deviation of 0.8.  The type I error probability was set at 0.05 and the statistical power 
was set at 80%. 
 
 

 
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7 STUDY MANAGEMENT 
7.1 Monitoring 
Before first subject into the study, a representative of Sponsor will visit the 
investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) (and other personnel involved with the study) 
their responsibilities with regard to protocol adherence, and the 
responsibilities of Sponsor or its representatives.  This will be documented in 
a Clinical Study Agreement between Sponsor and the investigator. 
During the study, a monitor from Sponsor or a company representing sponsor will 
have regular contacts with the study site, including visits to: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are 
being accurately recorded in the eCRFs, and that investigational product 
accountability checks are being performed 
• Perform source data verification (a comparison of the data in the eCRFs with 
the subject’s medical records at the hospital or practice, and other records 
relevant to the study).  This will require direct access to all original records for 
each subject (e.g., clinic charts). 
The monitor or another Sponsor representative will be available between visits if the 
investigator(s) or other staff at the center needs information and advice. 
7.2 Audits and inspections 
Authorized representatives of Sponsor, and an Institutional Review Board (IRB) may 
visit the center to perform audits or inspections, including source data verification.  
The purpose of a Sponsor audit or inspection is to systematically and independently 
examine all study-related activities and documents to determine whether these 
activities were conducted, and data were recorded, analyzed, and accurately 
reported according to the protocol, ISO 14155, Good Clinical Practice (GCP), 
guidelines of the International Conference on Harmonization (ICH), and any 
applicable regulatory requirements.   
7.3 Training of staff 
The principal investigator will maintain a record of all individuals involved in the study 
(medical, nursing and other staff).  He or she will ensure that appropriate training 
relevant to the study is given to all of these staff, and that any new information of 
relevance to the performance of this study is forwarded to the staff involved. 
7.4 Changes to the protocol 
Study procedures will not be changed without the mutual agreement of the principal 
investigators and Sponsor. 

 
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If it is necessary for the study protocol to be amended, the amendment and/or a new 
version of the study protocol (Amended Protocol) must be notified to or approved by 
each IRB, and if applicable, also the local regulatory authority, before 
implementation.  Local requirements must be followed. 
 
If a protocol amendment requires a change to a particular center’s Informed Consent 
Form, then Sponsor and the center’s Ethics Committee must be notified. Approval of 
the revised Informed Consent Form by Sponsor and by the IRB is required before 
the revised form is used.   
 
Sponsor will distribute administrative changes, amendments and new versions of the 
protocol to each principal investigator. 
7.5 Study agreements 
The principal investigator at each center must comply with all the terms, conditions, 
and obligations of the Clinical Study Agreement for this study.  In the event of any 
inconsistency between this Clinical Study Protocol and the Clinical Study Agreement, 
the Clinical Study Protocol shall prevail. 
7.6 Study timetable 
Before a subject's enrollment in the study and any study-related procedures are 
undertaken the following should be fulfilled: 
• Signed Clinical Study Protocol and other agreements between Sponsor and 
the Principal Investigator/Study Site 
• Approval of the study by the IRB 
 
 

 
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8 PROCEDURES IN CASE OF EMERGENCY 
8.1 Medical emergency 
In the case of a medical emergency you may contact the Clinical Study Team 
Leader.  If the Clinical Study Team Leader is not available, contact the Senior 
Manager at SUNSTAR, see below:  
 
Role in the study 
Name 
Address & telephone number 
Scientific advisor 
Akane Takemura, PhD 
 
Senior Manager 
Technology & New 
Product Development 
SUNSTAR Americas, Inc. 
301 E. Central Rd. Schaumburg, 
IL 60195 
 
Tel: (847)-794-4276 
Fax: (773)-481-3595 
Principal Investigator 
Dr. Hanae Saito, DDS, 
MS, CCRC 
 
Assistant Professor, 
Department of 
Periodontics 
 
Dr. Gustavo Avila-Ortiz, 
DDS, MS, PhD  
 
Associate Professor 
Department of 
Periodontics  
 
University of Maryland School of 
Dentistry 
650 W. Baltimore Street Rm 4201 
Baltimore, MD 21201 
Tel: 410-706-7152  
Fax: 410-706-7201  
 
The University of Iowa College of    
Dentistry 
Dental Science Building - Room 
S462, 801 Newton Rd.  
Iowa City, IA 52242-1001  
Phone: (319) 335-7241 
Fax: (319) 335-7239 
Study Coordinator 
Dr. Hanae Saito 
 
Amber Marolf, BA 
Clinical Research 
Coordinator 
 
University of Maryland School of 
Dentistry 
 
Dows Institute for Dental 
Research 
The University of Iowa College of 
Dentistry & Clinics 
Iowa City, IA 52242 
Phone: (319) 335-7411 
Fax: (319) 335-8895 
 
Medical Research Manager 
(CRO) 
Sharon Herbert, PhD, 
MBA  
 
Senior Medical 
Research Manager 
NAMSA 
1307 S. Mary Avenue, Suite 280, 
Sunnyvale, CA  94087 
Phone: (415) 889-9254 
Fax: (408) 462-9132  
 
The principal investigator(s) is responsible for ensuring that procedures and 
expertise are available to handle medical emergencies during the study.  A medical 
emergency usually constitutes an SAE and should be reported as such. 

 
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8.2 Pregnancy 
Many physiologic changes can be observed in the pregnant patient and should be 
considered when planning dental treatment. It has been suggested to avoid elective 
dental procedures in the 1st and 3rd trimesters due to risk of spontaneous abortions, 
pre-term births, increased patient discomfort, and increased likelihood of 
intraoperative complications.  The ultimate goal in dental therapy during pregnancy 
should be to educate the patient on the importance of oral hygiene and plaque 
control, perform periodontal maintenance therapy and treat emergency situations.  
All women except for postmenopausal women will require a negative urine human 
chorionic gonadotropin (HCG) test result prior to inclusion in the study to rule out 
pregnancy. Postmenopausal is considered when the patient has not had her period 
for an entire year. 
 
Pregnancy itself is not regarded as an AE/ADE unless there is a suspicion that the 
medical device under study may have interfered with the effectiveness of a 
contraceptive medication.  
 
Congenital abnormalities/birth defects and spontaneous miscarriages should be 
reported as SAEs.  Elective abortions without complications should not be handled 
as AEs/ADEs. 
 
 

 
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