Multi-Center Phase 3 Trial of Chlorhexidine Gluconate Chip for the Use in Subjects With Peri-Implantitis.
Phase: PHASE3
Conditions: Peri-Implantitis
Sponsor: Dexcel Pharma Technologies Ltd.

 
 
Dexcel Pharma Technologies Ltd. 
 
The Efficacy and Safety of Chlorhexidine Gluconate 
Chip (PerioChip®) in Therapy of Peri-implantitis 
 
Summary of Protocol Changes 
 
 
 
Protocol Number: 
CLI/016P 
 
 
NCT Number 
NCT02080403 
 
 
EudraCT Number:  
2013-000383-28 
 
 
Sponsor: 
 
Dexcel Pharma Technologies Ltd. 
Date: 
13/April/2021 
 
 
 
 

TABLE OF CONTENTS
Summary of changes from version 1 dated 02 Nov. 2013 to version 2 dated 22 Jan. 2014
Summary of changes from version 2 dated 22 Jan. 2014 to version 3 dated 13 July 2014
Summary of changes from version 3 dated 13 July2014 to version 4 dated 16 Nov. 2014
Summary of changes from version 4 dated 16 Nov. 2014 to version 6 dated 07 Oct. 2015
Summary of changes from version 5 dated 07 Oct. 2015 to version 7 dated 20 July 2017
Summary of changes from version 6 dated 07 Oct. 2015 to version 8 dated 29 Aug. 2017

- CONFIDENTIAL –
 
1 
Protocol No.: CLI/016P 
Protocol Title: The Efficacy and Safety of Chlorhexidine Gluconate Chip (PerioChip®) in Therapy of Peri-Implantitis  
Clinicaltrial.gov Identifier: NCT02080403 
EudraCT Number: 2013-00038-28 
Summary of changes from version 1 dated 02 Nov. 2013 to version 2 dated 22 Jan. 2014 
Page/Section 
Original Text (version 1) 
Amended Text (version 2) 
All through the 
protocol 
Number of subjects that are expected to be randomized to the study 230 
(115 at each study group) 
Number of subjects that are expected to be randomized to the study 246 
(123 at each study group) 
All through the 
protocol 
Number of subjects that are expected to be screened to the study 288 
Number of subjects that are expected to be screened to the study 336 
All through the 
protocol 
Study expected power 80% and statistical significance level 4% for all 
statistical analysis and comparisons 
Study expected power 85% and statistical significance level 5% for all 
statistical analysis and comparisons 
Page 22 - Study 
Design and 
Duration 
The duration of patient follow-up will be 25-28 weeks (including 
Screening), with interim visits at 0, 2, 4, 6, 8, 10, 12, 16 and 24 weeks 
The duration of patient follow-up will be 25-28 weeks (including 
Screening and hygienic phase visits), with interim visits at 0, 2, 4, 6, 8, 
10, 12, 16 and 24 weeks 
Page 40 - 
Randomization 
Code 
The randomization will be performed with stratification to study sites 
smoking habits and Baseline PD measurement in balanced blocks, each 
block containing 6 subjects. A total number of 48 blocks will be 
prepared for a total of 288 Each site will receive 4 types of lists by the 
defined stratification (smokers with PD 5 mm, smokers with PD 6-8 
mm, non-smokers with PD 5 mm and non-smokers with PD 6-8 mm). 
This number already includes 10 blocks for spare. 
The randomization will be performed with stratification to study sites 
smoking habits and Baseline PD measurement in balanced blocks, each 
block containing 6 subjects (3 per treatment Subgingival debridement + 
PerioChip® and 3 per treatment Subgingival debridement alone). A total 
number of 56 blocks will be prepared for a total of 336 subjects. 
Randomization blocks will be sent to the sites by the study data 
management Statistician. Each site will receive 4 types of lists by the 
defined stratification (smokers with PD 5 mm, smokers with PD 6-8 
mm, non-smokers with PD 5 mm and non-smokers with PD 6-8 mm). 
Additional blocks will be provided to the sites according to the 
recruitment rate. This number already includes 10 blocks for spare. 
Page 41 – Sample 
size 
Statistical significance level was set to 4% since an Interim Analysis, 
that will use 1% of the total significance level, is planned. 
Statistical significance level for all statistical analysis was set to 4% 
since an Interim Analysis that will use 1% of the total significance level, 
is planned 5. 
Page 42 - Analysis 
population 
Intent-to-treat (ITT) population – all patients randomized for one of the 
treatment arms and treated with at least one chip of study treatment or 
underwent Subgingival debridement will be used for all safety 
evaluations 
Intent-to-treat (ITT) population – all patients randomized for one of the 
treatment arms and treated with at least one chip of study treatment or 
underwent Subgingival debridement will be used for assessments related 
to efficacy and all safety evaluations 
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Page 44 - Efficacy 
analysis and 
statistical models 
Analysis for the number of pockets with at least 1 mm reduction in PD, 
and analysis for BOP for the target implant/s measured at each visit will 
be analysed by a Chi-square test or Fisher's exact test as is appropriate 
Analysis for the number of pockets with at least 1 mm and at least 2 mm 
reduction in PD, and analysis for BOP for the target implant/s measured 
at each visit will be analysed by a Chi-square test or Fisher's exact test 
as is appropriate 
Page 11- Protocol 
synopsis  and 
Page 46 - Interim 
Analysis 
An interim analysis is planned when 30 patients in each group have 
completed 24 weeks of therapy. Interim analysis will include primary 
efficacy endpoint and safety assessment. The purpose of the interim 
analysis is to achieve a primary assessment for the study safety and 
efficacy endpoints. The primary efficacy endpoint will be tested using a 
0.01 significance level. 1% (0.01) of the overall type 1 error for this 
study of 5% will be used in the interim analysis. The final analyses will 
be tested with statistical significance level of 4% (0.04). The levels of 
significance will maintain an overall P value of 0.05 (Peto, Pike, 
Armitage, Breslow, Cox, Howard, et al. 1976 
An interim analysis is planned when 30 patients in each group have 
completed 24 weeks of therapy. Interim analysis will include primary 
efficacy endpoint and safety assessment. The purpose of the interim 
analysis is to achieve a primary assessment for the study safety and 
efficacy endpoints. The primary efficacy endpoint will be tested using a 
0.01 significance level. 1% (0.01) of the overall type 1 error for this 
study of 5% will be used in the interim analysis. The final analyses will 
be tested with statistical significance level of 4% (0.04). The levels of 
significance will maintain an overall P value of 0.05 (Peto, Pike, 
Armitage, Breslow, Cox, Howard, et al. 1976 
Summary of changes from version 2 dated 22 Jan. 2014 to version 3 dated 13 July 2014 
Page/Section 
Original Text (version 2) 
Amended Text (version 3) 
Page 20 - Study 
Design and 
Duration 
 
The reason for preferring the above design over the Double-blind, 
Placebo-controlled design is that in previous clinical studies with 
PerioChip® it was evident that when used Placebo chips have worse 
clinical outcome compare to No-chip. Namely, periodontal pockets 
treated with Placebo chips showed less improvement in PD and 
attachment levels compare to No-chip treated pockets. It was also noted 
that at six months following the use of Placebo chips fewer incidences 
of patients were considered to have healthy pockets. The results of these 
studies suggest, that placing of the Placebo chip acting as a mechanical 
barrier preventing environmental/outside improvement in the pockets 
(Perio Products-I; Perio products-II). Due to the above mentioned 
findings the use of Placebo treatment arm is less adequate. In this case 
excluding the Placebo arm from the study design ultimately prevents the 
establishment of Double-blind procedure. 
Page 39 - 
Statistical 
methods  
 
It is worth noting that although parameters used in the above calculation 
are derived from a placebo-controlled design, it is reasonable to assume 
this calculation is more conservative than if the parameter used were 
taken from previous studies where the study design included a treatment 
arm with no chip assigned, in Periodontitis patients. 
In other words, the sample size calculation is based on sound data 
derived from a study design which used the same indication 
(periimplantitis) and treatment regimen (frequent chip insertion) as 
appear in the current protocol 
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Page 58 - 
Reference List 
 
23. Perio Products.I. Clinical effects following subgingival 
administration of Chlorhexidine gluconate (2.5 mg) in a cross-linked 
gelatin matrix (PerioChip) in patients with periodontal disease (study 
91-011). Clinical Study Report  
24. Perio Products. II. Clinical effects following subgingival 
administration of Chlorhexidine gluconate (2.5 mg) in a cross-linked 
gelatin matrix (PerioChip) in patients with periodontal disease (study 
91-013). Clinical Study Report 
Summary of changes from version 3 dated 13 July2014 to version 4 dated 16 Nov. 2014 
Page/Section 
Original Text (version 3) 
Amended Text (version 4) 
Page 7 -  Protocol 
Synopsis; Page 22 
- Inclusion 
Criteria 
Inclusion Criteria 1 "Signed and dated informed consent"  
Inclusion Criteria 1 "Signed and dated informed consent. The patient is 
of age and is capable of understanding the nature, significance and 
implications of the clinical trial and to form a rational intention in the 
light of the facts." 
Page 8 – Protocol 
synopsis; Page 24 
- Exclusion 
Criteria 
Exclusion Criteria 9: "Patients treated with systemic antibiotic therapy 
or periodontal/mechanical/local delivery therapy within 6 weeks prior to 
study entry and throughout the study duration." 
Exclusion Criteria 9: "Patients treated with systemic antibiotic therapy 
or periodontal/mechanical/local delivery therapy within 6 weeks prior to 
study entry and throughout the study duration. In case the investigator 
advises the patient that antibiotic therapy is required during the course 
of the study, the patient should be excluded from further participation." 
Page 25 - Patient 
Discontinuation/ 
Withdrawal 
Criteria 
"Patient receives emergency dental treatment which may interfere with 
the assessment of study endpoints."  
"Patient receives emergency dental treatment including target implant 
explanation which may interfere with the assessment of study endpoints. 
Paragraph was added: "Despite participating in the study, patient, who 
in the opinion of the investigator displays an inadequate response to 
subgingival debridement and chemical disinfection during the study 
period, may be entitled to surgical therapy of peri-implantitis." 
Page 26 - 
Concomitant 
Medication 
Treatment 
 
Patients will be instructed to refrain from: 
"Any use of Chlorhexidine oral rinses/mouthwashes during the study"  
Patients will be instructed to refrain from: 
"Any use of Chlorhexidine oral rinses/mouthwashes during the study 
without consulting the Investigator in advance." 
Summary of changes from version 3 dated 13 July2014 to version 5 dated 07 Oct. 2015 
Page/Section 
Original Text (version 3) 
Amended Text (version 5) 
Page 7 - Protocol 
Synopsis 
Number of clinical sites "5 clinical sites" to "at least 5 clinical sites" 
Number of clinical sites "at least 7 clinical sites" 
Page 13; Page 28; 
Page 37 - Study 
Schedule 
Last visit number "visit 9"  
The allowance (window)of final visit “90 ±10 days from previous visit” 
Last visit number "visit 10"  
The allowance (window)of final visit “56±10 days from previous visit (8 
weeks)” 
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Summary of changes from version 4 dated 16 Nov. 2014 to version 6 dated 07 Oct. 2015 
Page/Section 
Original Text (version 4) 
Amended Text (version 6) 
Page 7 - Protocol 
Synopsis 
Number of clinical sites "5 clinical sites" to "at least 5 clinical sites" 
Number of clinical sites "at least 7 clinical sites" 
Page 13;Page 29; 
Page 38 -Study 
Schedule 
Last visit number "visit 9"  
The allowance (window)of final visit “90 ±10 days from previous visit” 
Last visit number "visit 10"  
The allowance (window)of final visit “56±10 days from previous visit (8 
weeks)” 
Summary of changes from version 5 dated 07 Oct. 2015 to version 7 dated 20 July 2017 
Lines 
Original Text (version 5) 
Amended Text (version 7) 
Headline (First Page) 
8 - 9 
Date : 07 October 2015 
Date : 02 August 2017 
8 - 9 
Version : 5 
Version : 7 
19 
Footer date: 07 October 2015 
Footer version: Protocol # CLI/016P – version 5 
Footer date: 02 August 2017 
Footer version: Protocol # CLI/016P – version 7 
Table of Contents 
39-41 
5.3 page 24;  
5.3 page 25;  
42 - 44 
5.4 page 25;  
5.4 page 26;  
45 - 80 
6. Page 26; 6.1 page 28; 6.2 page 29; 6.2.1 page 29; 6.2.2 page 32; 6.2.3 
page 34; 6.2.4 page 36; 6.2.5 page 36; 6.2.5 page 36; 6.3 page 37; 6.3.1 
page 37; 6.3.2 page 37; 6.3.3 page 37;  
6. Page 27; 6.1 page 29; 6.2 page 30; 6.2.1 page 31; 6.2.2 page 33; 6.2.3 
page 35; 6.2.4 page 37; 6.2.5 page 37; 6.2.5 page 37; 6.3 page 38; 6.3.1 
page 38; 6.3.2 page 38; 6.3.3 page 38;  
81-95 
7. Page 37; 7.1 page 37; 7.2 page 37; 7.3 page 38; 7.4 page 39;  
7. Page 38; 7.1 page 38; 7.2 page 39; 7.3 page 40; 7.4 page 40;  
96-125 
8. Page 39; 8.1 page 39; 8.2 page 40; 8.3 page 40; 8.3.1 page 40; 8.3.2 
page 40; 8.3.3 page 41; 8.4 page 41; 8.5 page 44; 8.6 page 44; 
8. Page 46; 8.1 page 40; 8.2 page 41; 8.3 page 42; 8.3.1 page 42; 8.3.2 
page 42; 8.3.3 page 42; 8.4 page 42; 8.5 page 45; 8.6 page 46; 
126-140 
9. page 45; 9.1 page 45; 9.2 page 46; 9.3 page 46; 9.4page 47;   
9. page 46; 9.1 page 46; 9.2 page 47; 9.3 page 48; 9.4 page 48;   
141-146 
10. page 48; 10.1 page 48; 
10. page 49; 10.1 page 49; 
Clinical Study Protocol - Overview 
203 
Date : 07 October 2015 
Date : 02 August 2017 
Protocol Synopsis - Number of patients 
221-224 
A total of 246 patients in at least five clinical sites will be randomized. 
123 patients for the Subgingival debridement + PerioChip® arm, and 
123 patients for Subgingival debridement alone arm 
A total of 290 patients in at least nine clinical sites will be randomized. 
At least 123 patients for the Subgingival debridement + PerioChip® arm, 
and at least 123 patients for Subgingival debridement alone arm will 
complete all required study visits, considering withdrawal rate 
estimation of between 12%-15% 
Protocol Synopsis - Inclusion Criteria #5 
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248-254 
The patient has at least one implant in the oral cavity with clinical and 
radiographical signs of peri-implantitis. In the affected implant, at least 
one of the four aspect measured (mesio-buccal, mid-buccal, disto-buccal 
and mid-lingual) must show radiographic evidence of bone loss of at 
least 3 mm from implant shoulder, and at least 2 mm distal and mesial 
supporting bone left from the apex to the coronal direction, in 
combination with bleeding and/or suppuration on probing and a peri-
implant Probing Depth (PD) of 5-8 mm. 
 
The patient has at least one implant in the oral cavity with clinical and 
radiographical signs of peri-implantitis. In the affected implant, at least 
one of the four aspects measured  [mesio-buccal (MB), mid-buccal 
(MiB), disto-buccal (DB) and mid-lingual (MiL)] must show 
radiographic evidence of bone loss of at least 3 mm from implant 
shoulder, and at least 2 mm distal and mesial supporting bone left from 
the apex to the coronal direction, in combination with bleeding and/or 
suppuration on probing and a peri-implant Probing Depth (PD) of 5-8 
mm. 
Protocol Synopsis - Exclusion Criteria #10 
273-276 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs) or any medications know to affect 
soft tissue condition (excluding treatment of Acetylsalicylic acid ≤ 100 
mg/day). 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs),or any medications known to affect 
soft tissue condition (excluding treatment of Acetylsalicylic acid ≤ 100 
mg/day). A comprehensive list can be found in the Patient information 
sheet – list of prohibited medications.  
Protocol Synopsis - Exclusion Criteria #11 (New) 
277-283 
 
11. Patients with any history of use of Medications known to cause 
Medication related osteonecrosis of the jaw:  Bisphosphonates, RANKL 
inhibitors, Antiangiogenic agents and m-TOR inhibitors administered 
Intravenously (IV), Intramuscularly (IM) or Subcutaneously (SC). 
Patients with  a history of a one year or more of Per-Os (PO) use of the 
medications known to cause Medication related osteonecrosis of the jaw  
, with  last dose being under 3 months prior to the screening visit, and a 
CTX test value of < 150 ng/ml. 
Protocol Synopsis - Exclusion Criterias 12 - 16 
284-285 
11. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
12. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
286-287 
12. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
13. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
288-289 
13. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
14. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
290 
14. Drug and alcohol abuse. 
15. Drug and alcohol abuse. 
291-292 
15. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
16. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
Protocol Synopsis – Statistical Methods – Sample Size 
315-321 
A total of 246 patients will be randomized, 123 patients for the 
A total of up to 290 patients will be randomized. At least 123 patients 
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Subgingival Debridement + PerioChip® arm and 123 patients for the 
Subgingival Debridement alone arm. 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 336 patients will be screened in order to randomize 246 
patients. 
for the Subgingival Debridement + PerioChip® arm and 123 patients for 
the Subgingival Debridement alone arm to complete all required study 
visits. 
Based on the current drop-out rate (after randomization) of 9%, the 
expected drop-out rate (after randomization) should be between 12%-
15% 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 375 patients will be screened in order to randomize up to 
290 patients that complete all required study visits. 
Abbreviations 
401-402 
4 abbreviations regarding pocket aspects were not listed 
MB - Mesio-Buccal; MiB - Mid-Buccal; DB -Disto-Buccal; MiL-Mid-
Lingual 
Study Schedule 
404-413 
Evaluations/Activity Column: "dental Radiography 
SuperScript #1: Dental Radiography evaluation dated within 1 (one) 
year prior the Screening visit 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 5 and 
7 a pocket examination will be conducted by the designated examiner to 
verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip and which pocket depth at those visits is 
≥ 5 mm and which pocket depth at those visits is ≥5 mm" was removed 
Evaluations/Activity Column: "Periapical dental Radiography 
SuperScript #1: "Periapical Dental Radiography evaluation dated 
within 1 (one) year prior the Screening visit. 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 4, 5 
and 7 a pocket examination will be conducted by the designated 
examiner to verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip and which pocket depth at those visits is 
≥ 5 mm 
Study Design and Duration 
621 
The same examiner will perform all the measurements during the study. 
Calibrated examiners will perform all the measurements during the 
study. 
5.1 Number of Patients 
649-657 
A total of 246 patients, with symptoms of peri-implantitis, will be 
randomized, into one of the study arms; 123 patients for the Subgingival 
debridement + PerioChip® arm and 123 patients for the Subgingival 
debridement arm alone. 
 
A total of 290 patients, with symptoms of peri-implantitis, will be 
randomized into one of the study arms; At least 123 patients for the 
Subgingival debridement + PerioChip® arm, and at least 123 patients for 
Subgingival debridement alone arm will complete all required study 
visits, considering withdrawal rate estimation of between 12%-15% 
658-663 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 336 patients will be screened in order to randomize 246 
patients. 
 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Based on updated current study data 
the expected rate of patients that are randomized and later drop out will 
be between 12%-15%. Thus, it is estimated that approximately 375 
patients will be screened in order to randomize up to 290 patients, of 
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which 246 patients will complete all required study visits. 
5.2.2 Exclusion Criteria – Exclusion Criteria #10 
708-713 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs), and/or any medications known to 
affect soft tissue condition (excluding treatment of Acetylsalicylic acid 
≤ 100 mg/day). 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs), and/or any medications known to 
affect soft tissue condition (excluding treatment of Acetylsalicylic acid 
≤ 100 mg/day). A comprehensive list can be found in the Patient 
information sheet – list of prohibited concomitant medications 
Protocol Exclusion Criteria #11 (New)  
714-721 
 
11. Patients with any history of use of Medications known to cause 
Medication related osteonecrosis of the jaw:  Bisphosphonates, 
RANKL inhibitors, Antiangiogenic agents and m-TOR inhibitors 
administered Intravenously (IV), Intramuscularly (IM) or 
Subcutaneously (SC). 
Patients with  a history of a one year or more of Per-Os (PO) use of the 
medications known to cause Medication related osteonecrosis of the 
jaw  , with  last dose being under 3 months prior to the screening visit, 
and a CTX test value of < 150 ng/ml. 
Protocol Synopsis - Exclusion Criterias 12 - 16 
722-724 
11. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
12. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
725-726 
12. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
13. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
727-729 
13. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
14. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
730 
14. Drug and alcohol abuse. 
15. Drug and alcohol abuse. 
731-732 
15. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
16. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
5.3 Patient Discontinuation/ Withdrawal Criteria 
744 
Serious Adverse Events (SAEs) which are still ongoing at the end of the 
study period must be followed up to determine the final outcome. 
Serious Adverse Events (SAEs) which are still on-going at the end of 
the study period must be followed up to determine the final outcome. 
5.4 Concomitant Medication Treatment 
782-785 
Any use of toothpicks and/or floss around the treated implant/s in the 24 
hours following the chip insertion. 
Any use of toothpicks and/or floss around the treated implant/s in the 24 
hours following the chip insertion and advised to use such interproximal 
cleaning devices only to negotiate food impaction for the following 6 
days. 
6. Study Plan - Treatment 1: (PerioChip®) 
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804-807 
Subgingival debridement will be carried out for each one of the target 
implant which its probing pockets depth (PD of 5-8 mm) were selected 
as target pockets (The Subgingival debridement procedure will be 
employ twice: at baseline (visit 2) and after 3 months, at visit 8). 
Subgingival debridement will be carried out for each one of the target 
implant which its probing pockets depth (PD of 5-8 mm) were selected 
as target pockets (the Subgingival debridement procedure will be 
employed twice: at baseline (visit 2) and after 3 months, at visit 8). 
6.1 Study Schedule 
826-834 
Evaluations/Activity Column: "dental Radiography 
SuperScript #1: Dental Radiography evaluation dated within 1 (one) 
year prior the Screening visit 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 5 and 
7 a pocket examination will be conducted by the designated examiner to 
verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip and which pocket depth at those visits is 
≥ 5 mm  
Evaluations/Activity Column: "Periapical dental Radiography. 
SuperScript #1: "Periapical Dental Radiography evaluation dated 
within 1 (one) year prior the Screening visit. 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 4, 5 
and 7 a pocket examination will be conducted by the designated 
examiner to verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip 
6.2.1 Screening Visit and Hygienic Phase Therapy (Weeks (-3 to -1)) 
850-860 
radiographic evaluation dated within 1 (one) year prior the Screening 
visit 
periapical radiographic evaluation dated within 1 (one) year prior the 
Screening visit 
6.2.2 Baseline Visit (Week 0) 
955-961 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization. The Subgingival 
debridement is the removal of all local irritants from the periodontal 
pockets and implant surface including the inflammatory tissue. The 
procedure will be carried out using metal based curettes and ultrasonic 
management and irrigation with Chlorhexidine ("blasting" cleaning is 
prohibited). 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization. The Subgingival 
debridement is the removal of all local irritants from the periodontal 
pockets and implant surface including the inflammatory tissue. The 
procedure will be carried out using metal based curettes and possibly 
ultrasonic management and/or irrigation with Saline ("blasting" cleaning 
is prohibited). 
980-987 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or in the 24 hours following the chip insertion. 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or floss at least for the 24 hours following the chip 
insertion, and advised to use such interproximal cleaning devices only to 
negotiate food impaction for the following 6 days. 
990-991 
 
The period between Baseline visit and Visit 3 should not exceed 14 ± 4 
days 
6.2.3 Visits 3, 4, 5, 6, 7 and 8 (Weeks 2, 4, 6, 8, 10 and 12) 
1010 
Supragingival Scaling (at week 12 only) 
Supragingival Scaling (at week 12 (Visit 8) only). 
1012-1013 
Pocket examination and measurements (i.e. PD, R and BOP) only for 
Pocket examination and measurements (i.e. PD, R and BOP) only for 
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the target implant/s (only at weeks: 8 and 12) 
the target implant/s (only at weeks: 8 and 12 (visits 6 and 8)). 
1015-1017 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization, (at week 12 only). 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization, (at week 12 (Visit 
8) only). 
1018-1029 
Chip/s insertion only in those target pockets which had previously 
received a chip and which pocket depth is ≥ 5 mm. 
 
 In case chips are pop-out recurrently in visits 3, 4, 5 and 7 a pocket 
examination will conducted by the designated examiner to verify PD ≥ 
5 mm. The examiner will then declare "please try to restore again" if 
PD≥ 5 mm or "do not proceed with the insertion". 
Chip/s insertion only in those target pockets which had previously 
received a chip. 
For visits 6 and 8, chip insertion will follow pocket depth verification of 
≥ 5 mm as measured during the visit. 
For visits 3, 4, 5 and 7, in case chips pop-out recurrently a pocket 
examination will be conducted by the designated examiner to verify PD 
≥ 5 mm. The examiner will then declare "please try to insert again" if 
PD≥ 5 mm or "do not proceed with the insertion". 
1030-1037 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or in the 24 hours following the chip insertion. 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or floss at least for the 24 hours following the chip 
insertion, and advised to use such interproximal cleaning devices only to 
negotiate food impaction for the following 6 days. 
6.2.4 Visits 9 (Week 16) 
1058-1059 
 
The allowed window for visit 9 should not exceed 28 ± 4 days from the 
previous visit. 
6.3.1 Calibration of Examiners 
1076-1078 
PD and R measurement procedures will be standardized between 
medical centres and investigators prior to study initiation, consistent 
with Good Clinical Practice (GCP). 
PD and R measurement procedures will be standardized between 
investigators within each medical centre prior to study initiation, 
consistent with Good Clinical Practice (GCP). 
7.2 Randomization Codes 
1107-1108 
A total number of 56 blocks will be prepared for a total of 336 subjects. 
Line removed 
1113 
This number already includes 10 blocks for spare 
Line removed 
7.3 Blinding 
1118-1122 
Subgingival debridement only 
Subgingival debridement alone 
8.1 Sample Size 
1133-1140 
A total of 246 patients will be randomized, 123 patients for the 
Subgingival debridement + PerioChip® arm and 123 patients for the 
Subgingival debridement alone arm. 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
A total of up to 290 patients will be randomized, in order to analyse at 
least 123 patients in the Subgingival debridement + PerioChip® arm and 
at least 123 patients in the Subgingival debridement alone arm, 
considering expected patient drop-out rate estimation of between 12%-
15%. 
DeY~el Pharma Technologies Ltd 

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approximately 336 patients will be screened in order to randomize 246 
patients. 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 375 patients will be screened in order to randomize up to 
290 patients, of which 246 patients will complete all required study 
visits. 
Summary of changes from version 6 dated 07 Oct. 2015 to version 8 dated 29 Aug. 2017 
Lines 
Original Text (version 6) 
Amended Text (version 8) 
Headline (First Page) 
8 - 9 
Date : 07 October 2015 
Date : 29 August 2017 
8 - 9 
Version : 6 
Version : 8 
18 
Footer date: 07 October 2015 
Footer version: Protocol # CLI/016P – version 6 
Footer date: 29 August 2017 
Footer version: Protocol # CLI/016P – version 8 
Table of Contents 
38 
5.3 page 24;  
5.3 page 25;  
45 - 47 
6.2.3 page 35 6.2.5 page 37;  
6.2.3 page 36; 6.2.5 page 38; 
52-55 
7. Page 38; 7.1 page 38; 7.2 page 38; 7.3 page 39; 
7. Page 39; 7.1 page 39; 7.2 page 40; 7.3 page 40; 
60-66 
8.3 page 40; 8.3.1 page 40; 8.3.2 page 40;  8.4 page 41; 8.6 page 44; 
8.3 page 42; 8.3.1 page 42; 8.3.2 page 42; 8.4 page 44;  8.6 page 46; 
69-73 
9.2 page 47; 9.3 page 47; 9.4page 48;   
9.2 page 48; 9.3 page 48; 9.4 page 49;   
Clinical Study Protocol – Overview 
130 
Date : October 7th 2015 
Date : August 29th 2017 
Protocol Synopsis - Number of patients 
148-151 
A total of 246 patients in at least five clinical sites will be randomized. 
123 patients for the Subgingival debridement + PerioChip® arm, and 
123 patients for Subgingival debridement alone arm 
A total of 290 patients in at least nine clinical sites will be randomized. 
At least 123 patients for the Subgingival debridement + PerioChip® arm, 
and at least 123 patients for Subgingival debridement alone arm will 
complete all required study visits, considering withdrawal rate 
estimation of between 12%-15% 
Protocol Synopsis - Inclusion Criteria #5 
177-183 
The patient has at least one implant in the oral cavity with clinical and 
radiographical signs of peri-implantitis. In the affected implant, at least 
one of the four aspect measured (mesio-buccal, mid-buccal, disto-buccal 
and mid-lingual) must show radiographic evidence of bone loss of at 
least 3 mm from implant shoulder, and at least 2 mm distal and mesial 
supporting bone left from the apex to the coronal direction, in 
combination with bleeding and/or suppuration on probing and a peri-
implant Probing Depth (PD) of 5-8 mm. 
 
The patient has at least one implant in the oral cavity with clinical and 
radiographical signs of peri-implantitis. In the affected implant, at least 
one of the four aspects measured  [mesio-buccal (MB), mid-buccal 
(MiB), disto-buccal (DB) and mid-lingual (MiL)] must show 
radiographic evidence of bone loss of at least 3 mm from implant 
shoulder, and at least 2 mm distal and mesial supporting bone left from 
the apex to the coronal direction, in combination with bleeding and/or 
suppuration on probing and a peri-implant Probing Depth (PD) of 5-8 
mm. 
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Protocol Synopsis - Exclusion Criteria #10 
204-207 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs)or any medications know to affect 
soft tissue condition (excluding treatment of Acetylsalicylic acid ≤ 100 
mg/day). 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs) or any medications known to affect 
soft tissue condition (excluding treatment of Acetylsalicylic acid ≤ 100 
mg/day). A comprehensive list can be found in the Patient information 
sheet – list of prohibited medications.  
Protocol Synopsis - Exclusion Criteria #11 (New) 
208-213 
 
11. Patients with any history of use of Medications known to cause 
Medication related osteonecrosis of the jaw:  Bisphosphonates, RANKL 
inhibitors, Antiangiogenic agents and m-TOR inhibitors administered 
Intravenously (IV), Intramuscularly (IM) or Subcutaneously (SC). 
Patients with  a history of a one year or more of Per-Os (PO) use of the 
medications known to cause Medication related osteonecrosis of the 
jaw, with  last dose being under 3 months prior to the screening visit, 
and a CTX test value of < 150 ng/ml. 
Protocol Synopsis - Exclusion Criterias 12 – 16 
214-215 
11. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
12. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
216-217 
12. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
13. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
218-219 
13. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
14. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
220 
14. Drug and alcohol abuse. 
15. Drug and alcohol abuse. 
221-222 
15. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
16. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
Protocol Synopsis – Statistical Methods – Sample Size 
245-252 
A total of 246 patients will be randomized, 123 patients for the 
Subgingival Debridement + PerioChip® arm and 123 patients for the 
Subgingival Debridement alone arm. 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 336 patients will be screened in order to randomize 246 
patients. 
A total of up to 290 patients will be randomized. At least 123 patients 
for the Subgingival Debridement + PerioChip® arm and 123 patients for 
the Subgingival Debridement alone arm to complete all required study 
visits. 
Based on the current drop-out rate (after randomization) of 9%, the 
expected drop-out rate (after randomization) should be between 12%-
15% 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 375 patients will be screened in order to randomize up to 
DeY~el Pharma Technologies Ltd 

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290 patients that complete all required study visits. 
Abbreviations 
332-333 
4 abbreviations regarding pocket aspects were not listed 
MB - Mesio-Buccal; MiB - Mid-Buccal; DB -Disto-Buccal; MiL-Mid-
Lingual 
Study Schedule 
336-344 
Evaluations/Activity Column: "dental Radiography 
SuperScript #1: Dental Radiography evaluation dated within 1 (one) 
year prior the Screening visit 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 5 and 
7 a pocket examination will be conducted by the designated examiner to 
verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip and which pocket depth at those visits is 
≥ 5 mm 
Evaluations/Activity Column: "Periapical dental Radiography 
SuperScript #1: "Periapical Dental Radiography evaluation dated 
within 1 (one) year prior the Screening visit. 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 4, 5 
and 7 a pocket examination will be conducted by the designated 
examiner to verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip and which pocket depth at those visits is 
≥ 5 mm 
Study Design and Duration 
522 
The same examiner will perform all the measurements during the study. 
Calibrated examiners will perform all the measurements during the 
study. 
5.1 Number of Patients 
580-584 
A total of 246 patients, with symptoms of peri-implantitis, will be 
randomized, into one of the study arms; 123 patients for the Subgingival 
debridement + PerioChip® arm and 123 patients for the Subgingival 
debridement arm alone. 
 
A total of 290 patients, with symptoms of peri-implantitis, will be 
randomized into one of the study arms; At least 123 patients for the 
Subgingival debridement + PerioChip® arm, and at least 123 patients for 
Subgingival debridement alone arm will complete all required study 
visits, considering withdrawal rate estimation of between 12%-15% 
585-590 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 336 patients will be screened in order to randomize 246 
patients. 
 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Based on updated current study data 
the expected rate of patients that are randomized and later drop out will 
be between 12%-15%. Thus, it is estimated that approximately 375 
patients will be screened in order to randomize up to 290 patients, of 
which 246 patients will complete all required study visits. 
5.2.2 Exclusion Criteria – Exclusion Criteria #10 
640-645 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs), and/or any medications known to 
affect soft tissue condition (excluding treatment of Acetylsalicylic acid 
≤ 100 mg/day). 
Patients chronically (i.e. two weeks or more) treated with non-steroidal 
anti-inflammatory drugs (NSAIDs), and/or any medications known to 
affect soft tissue condition (excluding treatment of Acetylsalicylic acid 
≤ 100 mg/day). A comprehensive list can be found in the Patient 
information sheet – list of prohibited concomitant medications 
Protocol Exclusion Criteria #11 (New) 
646-654 
 
11. Patients with any history of use of Medications known to cause 
DeY~el Pharma Technologies Ltd 

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13 
 
Medication related osteonecrosis of the jaw:  Bisphosphonates, RANKL 
inhibitors, Antiangiogenic agents and m-TOR inhibitors administered 
Intravenously (IV), Intramuscularly (IM) or Subcutaneously (SC). 
Patients with  a history of a one year or more of Per-Os (PO) use of the 
medications known to cause Medication related osteonecrosis of the 
jaw, with  last dose being under 3 months prior to the screening visit, 
and a CTX test value of < 150 ng/ml. 
Protocol Synopsis - Exclusion Criterias 12 – 16 
655-657 
11. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
12. Patients with uncontrolled diabetes, of any type, and/or patients with 
HbA1c test value >7.5% dated 3 months prior to the screening visit. 
658-659 
12. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
13. Patients receiving radiation therapy to the head and neck area and/or 
receiving immunosuppressive therapy. 
660-662 
13. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
14. The presence of any medical or psychiatric condition or any other 
condition that, in the opinion of the Investigator, could affect the 
successful participation of the patient in the study. 
663 
14. Drug and alcohol abuse. 
15. Drug and alcohol abuse. 
664-665 
15. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
16. Patient participates in any other clinical study 30 days prior to the 
start of the study and throughout the study duration. 
5.3 Patient Discontinuation/ Withdrawal Criteria 
677 
Serious Adverse Events (SAEs) which are still ongoing at the end of the 
study period must be followed up to determine the final outcome. 
Serious Adverse Events (SAEs) which are still on-going at the end of 
the study period must be followed up to determine the final outcome. 
5.4 Concomitant Medication Treatment 
721-723 
Any use of toothpicks and/or floss around the treated implant/s in the 24 
hours following the chip insertion. 
Any use of toothpicks and/or floss around the treated implant/s in the 24 
hours following the chip insertion and advised to use such interproximal 
cleaning devices only to negotiate food impaction for the following 6 
days. 
6. Study Plan - Treatment 1: (PerioChip®) 
742-745 
Subgingival debridement will be carried out for each one of the target 
implant which its probing pockets depth (PD of 5-8 mm) were selected 
as target pockets (The Subgingival debridement procedure will be 
employ twice: at baseline (visit 2) and after 3 months, at visit 8). 
Subgingival debridement will be carried out for each one of the target 
implant which its probing pockets depth (PD of 5-8 mm) were selected 
as target pockets (the Subgingival debridement procedure will be 
employed twice: at baseline (visit 2) and after 3 months, at visit 8). 
6.1 Study Schedule 
764-772 
Evaluations/Activity Column: "dental Radiography 
SuperScript #1: Dental Radiography evaluation dated within 1 (one) 
year prior the Screening visit 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 5 and 
7 a pocket examination will be conducted by the designated examiner to 
Evaluations/Activity Column: "Periapical dental Radiography. 
SuperScript #1: "Periapical Dental Radiography evaluation dated 
within 1 (one) year prior the Screening visit. 
SuperScript #2: In case chips are pop-out recurrently in visits 3, 4, 5 
and 7 a pocket examination will be conducted by the designated 
DeY~el Pharma Technologies Ltd 

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verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip and which pocket depth at those visits is 
≥ 5 mm  
examiner to verify PD ≥ 5 mm 
SuperScript #6: Chip/s will be inserted only in target implant/s which 
had previously received a chip 
6.2.1 Screening Visit and Hygienic Phase Therapy (Weeks (-3 to -1)) 
788-798 
radiographic evaluation dated within 1 (one) year prior the Screening 
visit 
periapical radiographic evaluation dated within 1 (one) year prior the 
Screening visit 
6.2.2 Baseline Visit (Week 0) 
893-899 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization. The Subgingival 
debridement is the removal of all local irritants from the periodontal 
pockets and implant surface including the inflammatory tissue. The 
procedure will be carried out using metal based curettes and ultrasonic 
management and irrigation with Chlorhexidine ("blasting" cleaning is 
prohibited). 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization. The Subgingival 
debridement is the removal of all local irritants from the periodontal 
pockets and implant surface including the inflammatory tissue. The 
procedure will be carried out using metal based curettes and possibly 
ultrasonic management and/or irrigation with Saline ("blasting" cleaning 
is prohibited). 
918-925 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or in the 24 hours following the chip insertion. 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or floss at least for the 24 hours following the chip 
insertion, and advised to use such interproximal cleaning devices only to 
negotiate food impaction for the following 6 days. 
928-929 
 
The period between Baseline visit and Visit 3 should not exceed 14 ± 4 
days 
6.2.3 Visits 3, 4, 5, 6, 7 and 8 (Weeks 2, 4, 6, 8, 10 and 12) 
949 
Supragingival Scaling (at week 12 only) 
Supragingival Scaling (at week 12 (Visit 8) only). 
951-952 
Pocket examination and measurements (i.e. PD, R and BOP) only for 
the target implant/s (only at weeks: 8 and 12) 
Pocket examination and measurements (i.e. PD, R and BOP) only for 
the target implant/s (only at weeks: 8 and 12 (visits 6 and 8)). 
954-956 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization, (at week 12 only). 
Subgingival debridement will be carried out for all the chosen target 
implant/s, regardless of the study arm randomization, (at week 12 (Visit 
8) only). 
957-966 
Chip/s insertion only in those target pockets which had previously 
received a chip and which pocket depth is ≥ 5 mm. 
 In case chips are pop-out recurrently in visits 3, 4, 5 and 7 a pocket 
examination will conducted by the designated examiner to verify PD ≥ 
5 mm. The examiner will then declare "please try to restore again" if 
PD≥ 5 mm or "do not proceed with the insertion". 
Chip/s insertion only in those target pockets which had previously 
received a chip. 
For visits 6 and 8, chip insertion will follow pocket depth verification of 
≥ 5 mm as measured during the visit. 
For visits 3, 4, 5 and 7, in case chips pop-out recurrently a pocket 
examination will be conducted by the designated examiner to verify PD 
DeY~el Pharma Technologies Ltd 

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15 
 
≥ 5 mm. The examiner will then declare "please try to insert again" if 
PD≥ 5 mm or "do not proceed with the insertion". 
967-974 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or in the 24 hours following the chip insertion. 
Oral Hygiene instructions - The Investigator or designee will remind the 
patient of the importance of good hygiene of the mouth (if necessary) 
and of the restriction of use of Chlorhexidine oral rinses/mouthwashes. 
In addition the patient will be instructed to refrain from use of 
toothpicks and/ or floss at least for the 24 hours following the chip 
insertion, and advised to use such interproximal cleaning devices only to 
negotiate food impaction for the following 6 days. 
6.2.4 Visits 9 (Week 16) 
995-996 
 
The allowed window for visit 9 should not exceed 28 ± 4 days from the 
previous visit. 
6.3.1 Calibration of Examiners 
1013-1015 
PD and R measurement procedures will be standardized between 
medical centres and investigators prior to study initiation, consistent 
with Good Clinical Practice (GCP). 
PD and R measurement procedures will be standardized between 
investigators within each medical centre prior to study initiation, 
consistent with Good Clinical Practice (GCP). 
7.2 Randomization Codes 
1044-1045 
A total number of 56 blocks will be prepared for a total of 336 subjects. 
Line removed 
1050 
This number already includes 10 blocks for spare 
Line removed 
7.3 Blinding 
1055-1059 
Subgingival debridement only 
Subgingival debridement alone 
8.1 Sample Size 
1070-11077 
A total of 246 patients will be randomized, 123 patients for the 
Subgingival debridement + PerioChip® arm and 123 patients for the 
Subgingival debridement alone arm. 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 336 patients will be screened in order to randomize 246 
patients. 
A total of up to 290 patients will be randomized, in order to analyse at 
least 123 patients in the Subgingival debridement + PerioChip® arm and 
at least 123 patients in the Subgingival debridement alone arm, 
considering expected patient drop-out rate estimation of between 12%-
15%. 
Based on previous phase IIa studies, the expected drop-out rate in this 
study will be between 20%-25%. Thus, it is estimated that 
approximately 375 patients will be screened in order to randomize up to 
290 patients, of which 246 patients will complete all required study 
visits. 
 
DeY~el Pharma Technologies Ltd