Clinical Evaluation of Class I and II Cavities Restored With the Combination of a New Flowable and a New Sculptable Universal Bulk-fill Composite: A Prospective Single Arm Study
Phase: NA
Conditions: Insufficient Dental Filling or Primary Caries (Class I or II Cavities in Premolars or Molars)
Sponsor: Ivoclar Vivadent AG

Clinical Study Protocol
Clinical evaluation of Class I and II cavities restored with the combination of a 
new flowable and a new sculptable universal bulk-fill composite: A prospective 
single arm study 
Type of investigation: 
Clinical investigation concerning medical devices (MD). 
Categorisation: 
Category according to Art 6 ClinO-MD: C2 
Registration: 
Registry at ClinicalTrials.gov of the U.S. National Library of Medicine 
(http://www.clinicaltrials.gov) 
The trial gets registered in the supplementary federal database 
(Portal 
for 
clinical 
trials 
in 
Switzerland 
– 
SNCTP, 
https://www.kofam.ch/en/snctp-portal/) upon its submission on 
BASEC (BASEC ID: 2024-D0004).  
Furthermore, as soon as the new electronic system EUDAMED is 
operational, the clinical investigation will be retrospectively 
registered, if required (CIV-24-02-046014) 
Identifier: 
OTCS 36392568 (Document ID: OTCS 36406866) 
Principal Investigator and 
Sponsor, or Sponsor-
Investigator: 
Principal Investigator (PI): 
Dr. med. dent. Carola Pentelescu 
Internal Clinic of Ivoclar Vivadent AG 
Bendererstrasse 2 
9494 Schaan 
Liechtenstein 
Tel. 
  
Mail: 
 
Sponsor: 
Ivoclar Vivadent AG 
Patrizia Elkuch-Hoch 
Team Leader Study Management 
Bendererstrasse 2 
9494 Schaan 
Liechtenstein 
Tel.: 
 
Mail: 
 
Sponsor representative (if the 
Sponsor is not located in 
Switzerland) 
n.a.
Medical Device: 
TM Fill and TM Flow (Ivoclar Vivadent AG) 
CIP Version and Date: 
Version 3.0, 10.04.2024 
CONFIDENTIAL 
The information contained in this document is confidential and the property of Ivoclar Vivadent AG (or 
“Sponsor”). The information may not – in full or in part – be transmitted, reproduced, published, or 
disclosed to others than the applicable Competent Ethics Committee(s) and Regulatory Authority(ies) 
without prior written authorisation from the Sponsor except to the extent necessary to obtain informed 
consent from those who will participate in the investigation. 

Signature Page
ID number of the
investigation:
OTCS 36392568
Registry at ClinicaITrials.gov of the U.S. National Library of
Medicine (http://www.clinicaltrials.qov)
The trial additionally registers in the supplementary federal
database (Portal for clinical trials in Switzerland - SNCTP,
https://www.kofam.ch/en/snctp-portal/) with its submission on
BASEC.
Furthermore, as soon as the new electronic system EUDAMED is
operational, the clinical investigation will be retrospectively
registered, if required
Title:
Clinical evaluation of Class 1 and 11 cavities restored with the
combination of a new flowable and a new sculptable universal
bulk-fill composite: A prospective single arm study
The Sponsor, the Principal Investigator and the Statistician have approved the CIP version 3.0 (dated
10.04.2024), and confirm hereby to conduct the investigation according to the CIP, the current version
of the World Medical Association Declaration of Helsinki, IS014155 norm, ICH-GCP as far as applicable,
and the local legally applicable requirements.
Sponsor: Patrizia Elkuch-Hoch
Place/Date
Signatu re
Principal Investigator: Dr. med. dent. Carola Pentelescu
Place/Date
Signature
OTCS 36392568, Version 3.0 of 10.04.2024
Page 2

OTCS 36392568, Version 3.0 of 10.04.2024 
Page 3 
Table of Contents 
SYNOPSIS .............................................................................................................................................. 4 
ABBREVIATIONS ................................................................................................................................... 8 
INVESTIGATION SCHEDULE ................................................................................................................ 9 
1.
BACKGROUND AND RATIONALE .............................................................................................. 10 
1.1 
Background and Rationale for the clinical investigation .............................................................. 10 
1.2 
Identification and description of the Investigational Medical Device ........................................... 11 
2.
CLINICAL INVESTIGATION OBJECTIVES ................................................................................. 12 
2.1 
Overall Objective ......................................................................................................................... 12 
2.2 
Primary Objective ........................................................................................................................ 12 
2.3 
Secondary Objectives ................................................................................................................. 12 
2.4 
Safety Objectives ........................................................................................................................ 12 
3.
CLINICAL INVESTIGATION OUTCOMES ................................................................................... 13 
3.1 
Primary Outcome ........................................................................................................................ 13 
3.2 
Secondary Outcomes .................................................................................................................. 14 
3.3 
Other Outcomes of Interest ......................................................................................................... 14 
3.4 
Safety Outcomes ......................................................................................................................... 14 
4.
CLINICAL INVESTIGATION DESIGN .......................................................................................... 15 
4.1 
General clinical investigation design and justification of design ................................................. 15 
4.2 
Methods for minimising bias ........................................................................................................ 15 
4.2.1 Randomisation .................................................................................................................... 15 
4.2.2 Blinding procedures ............................................................................................................ 15 
4.2.3 Other methods for minimising bias ..................................................................................... 15 
4.3 
Unblinding Procedures (Code break) .......................................................................................... 15 
5.
CLINICAL INVESTIGATION INTERVENTION ............................................................................. 16 
5.1 
Identity of the medical device under investigation ...................................................................... 16 
5.1.1 Experimental Intervention (medical device) ........................................................................ 16 
5.1.2 Control Intervention (standard/routine/comparator) ............................................................ 16 
6.
STATISTICAL METHODS ............................................................................................................. 17 
6.1 Hypothesis ..................................................................................................................................... 17 
6.2 Determination of Sample Size ....................................................................................................... 17 
6.3 Statistical criteria of termination of the investigation ..................................................................... 17 
6.4 Planned Analyses .......................................................................................................................... 17 
6.4.1 Datasets to be analysed, analysis populations ..................................................................... 17 
6.4.2 Primary Analysis ................................................................................................................... 18 
6.4.3 Secondary Analyses ............................................................................................................. 18 
6.4.4 Interim analyses .................................................................................................................... 18 
6.4.5 Deviation(s) from the original statistical plan ........................................................................ 18 
6.5 Handling of missing data and drop-outs........................................................................................ 18 
7.
REFERENCES ............................................................................................................................... 19 

OTCS 36392568, Version 3.0 of 10.04.2024 
Page 4 
SYNOPSIS 
Sponsor / Sponsor-
Investigator 
Ivoclar Vivadent AG 
Title: 
Clinical evaluation of Class I and II cavities restored with the combination of a 
new flowable and a new sculptable universal bulk-fill composite: A prospective 
single arm study 
Short title / 
Investigation ID: 
Clinical evaluation of a new flowable and a new sculptable universal bulk-fill 
composite for direct restorative treatment 
OTCS 36392568 
Clinical Investigation 
Plan, version and 
date: 
Version 3.0, 10.04.2024 
Registration: 
Registry at ClinicalTrials.gov of the U.S. National Library of Medicine 
(http://www.clinicaltrials.gov) 
The trial gets registered in the supplementary federal database (Portal for 
clinical trials in Switzerland – SNCTP, https://www.kofam.ch/en/snctp-portal/) 
upon its submission on BASEC.  
As soon as the new electronic system EUDAMED2 is operational, the clinical 
investigation will be retrospectively registered, if required. 
Category and its 
rationale: 
Category C2 (Art. 6 ClinO-MD)  
The medical device has no conformity marking. 
Name of the MD, 
Unique Device 
Identification (UDI), 
name of the 
manufacturer 
TM Flow 
UDI not available 
Shades: A2 plus (LOT: YM0209), A3 plus (LOT: YM0210), A3.5 plus (LOT: 
YM0211), Bleach plus (LOT: YM0212) 
TM Fill 
UDI not available 
Shades: A2 plus (LOT: YM0205), A3 plus (LOT: YM0206), A3.5 plus (LOT: 
YM0207), Bleach plus (LOT: YM0208) 
Manufacturer 
Ivoclar Vivadent AG 
Benderer Strasse 2 
9494 Schaan 
SRN-number: LI-MF-000000522 
Accessories: 
Cannulas Luer-Lock 
Stage of 
development: 
Pivotal stage  
The clinical investigation is conducted for a conformity assessment purpose. 

OTCS 36392568, Version 3.0 of 10.04.2024 
Page 5 
Background and 
rationale: 
Direct restorations in the oral cavity are placed when tooth tissue is partially 
lost due to caries, trauma, or tooth wear in order to restore the morphology, 
aesthetics and function of the teeth.  Nowadays resin composites used with 
adhesive systems that bond the restorative material to the tooth structure are 
most often the materials of choice.  
Resin composites can be classified by their viscosity in sculptable composites, 
and flowable composites that show a low viscosity. Resin composites are 
cured with a polymerization lamp which limits the thickness of material layers 
to 1-2 mm. Bulk-fill resin composites have been developed to facilitate 
clinicians’ work, reduce working time and simplify the restorative procedure. 
They can be placed in increments of up to 4-5 mm. 
If a sculptable (bulk-fill) composite is used in combination with a flowable bulk-
fill composite, a first layer of flowable composite can be applied in the cavity 
and light cured. The flowable composite has the advantage of an easy and fast 
application, so that the first 4 mm of the cavity are rapidly filled. Afterwards, a 
capping layer with a sculptable bulk-fill composite is applied and light cured. 
The newly developed bulk-fill composites TM Flow (flowable) and TM Fill 
(sculptable) can be light-cured in 3, 5 and 10 seconds (light intensity 3000, 
2000 and 1200 mW/cm2, respectively). The photons of the curing light activate 
the initiator for the polymerization reaction, but also create heat which could 
cause a pulp damage. Damage related to heat stress could lead to 
postoperative hypersensitivity with elevated pain to cold, heat or chewing. 
Class I and II cavities need to be filled most often in the daily practice since 
occlusal and approximal surfaces of molars and premolars are predominantly 
affected by caries. Class I and II restorations are in areas with the highest 
occlusal load, so that the material used for these types of restorations is 
challenged heavily by mechanical forces. I new resin composites TM Fill and 
TM Flow will be used for direct restorations of class I and II cavities (3 seconds 
light-curing mode) in premolars and molars in this clinical investigation to prove 
their clinical performance and safety. 
Objective(s): 
The overall objective of this clinical investigation is to evaluate the clinical 
safety and performance of the new resin composites TM Flow and TM Fill. 
The primary objective is to assess the rate of postoperative hypersensitivity 
after treatment of class I or II restorations with TM Flow in combination with TM 
Fill (3 seconds light-curing mode, 3000 mW/cm2). 
The secondary objective of this study is to assess the long-term clinical efficacy 
of the materials under investigation in terms of marginal quality 
retention/fracture rate of the restorations and vitality. The color match, surface 
lustre and texture, contour and form, occlusion and wear are also 
assessed. These outcomes provide information about the clinical performance 
of the material including the aesthetic performance. 
Outcome(s): 
The primary outcome of this clinical investigation is the rate of postoperative 
hypersensitivity (acceptance criterium < 10%).
The secondary outcomes focus on tooth vitality and clinical performance of the 
composites by evaluation of functional (e.g. fracture of the material and 
retention), biological (e.g. caries at restoration margins) and aesthetic (e.g. 
color match) properties of the restorations.  
The primary and the secondary outcomes are assessed using the FDI criteria 
(Hickel et al., 2022). 
Design: 
Prospective, single-arm study 

OTCS 36392568, Version 3.0 of 10.04.2024 
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Inclusion / exclusion 
criteria: 
Inclusion criteria: 
•
Informed Consent signed by the subject
•
Age: 18-65 years
•
Indication Class I or II direct restorations in premolars or molars
(Replacement of insufficient fillings due to secondary caries,
fractures, insufficient marginal adaptation, loss of filling or primary
caries)
•
Cavity width must be at least half of the cusp tip distance
•
Vital teeth, regular sensitivity
•
Sufficient language skills
•
No active periodontits
•
Preoperative VAS values < 3 regarding tooth sensitivity and biting
Exclusion criteria: 
•
Sufficient isolation of the cavity not possible
•
Not completed hygiene phase or poor oral hygiene
•
Missing antagonist, non-occlusion
•
Missing tooth adjacent to the tooth to be treated
•
Restorations replacing more than 1 cusp
•
Caries profunda or very deep cavity
•
Patients with a proven allergy to ingredients of the used materials
(methacrylates) or local anesthetics (Articain, sulfite)
•
Patients with severe systemic diseases
•
Pregnancy
•
Part of the development project team of TM Flow or TM Fill
•
Staff of the study management team
•
Staff of the internal clinic
Measurements and 
procedures: 
Each participant receives one filling in one tooth. The fillings are assessed 
according to selected FDI criteria at baseline (7-10 days after filling placement) 
and after 1, 6, 12, 24, 36 and 60 months. At the 1 and 6 month recall the 
sensitivity is recorded using a visual analogue scale and at all the other recalls 
the sensitivity is only recorded if necessary. The results are documented by 
intraoral images. 
Intervention: 
The newly developed resin composites TM Flow and TM Fill will be used for 
the restoration of class I and II cavities (3 seconds light-curing mode, 3000 
mW/cm2). The treatment workflow is very similar to other resin composites, for 
instance the predecessor products Tetric PowerFill and Tetric PowerFlow. 
Control intervention 
(if applicable): 
Not applicable 
Number of subjects 
with rationale: 
61 subjects were calculated for the single-arm study design. Considering a 
drop-out rate of 5%, 65 subjects will be included in this clinical investigation. 
Duration of the 
investigation: 
60 months for each patient (recruiting phase 4 months) 
Investigation 
schedule: 
May 2024 First-subject-In 
April 2030 Last-subject-Out 

OTCS 36392568, Version 3.0 of 10.04.2024 
Page 7 
Investigator(s): 
-
Dr. Enggist Lukas, Bendererstrasse 2, 9494 Schaan
-
Dr. Carola-Sonia Pentelescu, Bendererstrasse 2, 9494 Schaan
-
Dr. Peschke Arnd, Bendererstrasse 2, 9494 Schaan
-
Dr. Hu Ming, Bendererstrasse 2, 9494 Schaan
-
Dr. Ronny Watzke, Bendererstrasse 2, 9494 Schaan
-
Dr. Lydia Eberhard, Bendererstrasse 2, 9494 Schaan
-
Dr. Glebova Tatiana, Bendererstrasse 2, 9494 Schaan
Investigational 
Site(s): 
This is a single center study. 
R&D Clinic 
Ivoclar Vivadent AG 
Bendererstrasse 2 
9494 Schaan 
Liechtenstein 
Statistical 
considerations: 
The sample size was calculated for a single-arm study design with a one-sided  
hypothesis (target alpha 5%; power of at least 80%).  
A one-sided binomial exact test is used to calculate if the probability of 
postoperative hypersensitivities is lower than 10% (acceptance criterium). 
Compliance 
statement: 
This investigation will be conducted in compliance with the CIP, the current 
version of the Declaration of Helsinki, ISO14155, ICH-GCP (as far as 
applicable) as well as all national legal and regulatory requirements. 

OTCS 36392568, Version 3.0 of 10.04.2024 
Page 8 
H1 
HRA 
IB 
ICF 
ICH-GCP 
IFU 
ISF 
ISO 
ITT 
MedDO 
MD 
MDR 
PI 
SADE 
SAE 
SDV 
SNCTP 
SOP 
USADE 
VAS 
Alternative hypothesis 
Federal Act on Research involving Human Beings (in German: HFG, in French: 
LRH, in Italian: LRUm) 
Investigator’s Brochure 
Informed Consent Form 
International Council for Harmonisation – guidelines of Good Clinical Practice 
Instruction For Use 
Investigator Site File 
International Organisation for Standardisation 
Intention to treat 
Medical Devices Ordinance (in German: MepV, in French: Odim, in Italian: Odmed) 
Medical Device  
Medical Device Regulation (EU) 2017/745 of 5 April 2017 
Principal Investigator 
Serious Adverse Device Effect 
Serious Adverse Event 
Source Data Verification  
Swiss National Clinical Trials Portal 
Standard Operating Procedure 
Unanticipated Serious Adverse Device Effect 
Visual Analogue Scale 
ABBREVIATIONS 
AE 
ADE 
ASADE 
ASR 
CA 
CEC 
CIP 
ClinO 
ClinO-MD 
CRF 
DD 
DMC / DSMC 
FDI 
Ho 
Adverse Event  
Adverse Device Effect 
Anticipated Serious Adverse Device Effect 
Annual Safety Report 
Competent Authority (Amt für Gesundheit Liechtenstein) 
Competent Ethics Committee 
Clinical investigation plan 
Ordinance on Clinical Trials in Human Research (in German KlinV, in French Oclin, 
in Italian OSRUm) 
Ordinance on Clinical Trials with Medical Devices (in German: KlinV-Mep, in French: 
Oclin-Dim, in Italian: OSRUm-Dmed) 
Case Report Form (pCRF paper CRF; eCRF electronic CRF) 
Device Deficiency 
Data Monitoring Committee, Data Safety Monitoring Committee 
Fédération Dentaire Internationale 
Null hypothesis 

OTCS 36392568, Version 3.0 of 10.04.2024 
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INVESTIGATION SCHEDULE 
Study Periods 
Screening 
Treatment, 
Intervention 
Period 
Follow-up 
Visit 
0 
1 
2 
3 
4 
5 
6 
7 
8 
Time (hour, day, 
week) 
-3- (-30) d
0 d 
7-10 d
1 m 
6 m 
12 m 
24 m 
36 m 
60 m 
Patient 
Information 
and 
Informed Consent 
x 
Medical History 
x 
In- 
/Exclusion 
Criteria 
x 
Tooth 
Examination 
x 
Pregnancy Test 
x 
Vitality test 
x 
x 
x 
x 
x 
x 
x 
x 
x 
VAS 
for 
tooth 
sensitivity 
x 
x 
x 
x 
x* 
x* 
x* 
x* 
Preparation 
of 
tooth 
x 
Placement 
of 
restoration 
x 
Primary Variables 
x 
x 
x 
x 
x 
x 
x 
Secondary 
Variables 
x 
x** 
x 
x 
x 
x 
x 
Photographs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse 
events 
and 
device 
deficiendcies 
x 
x 
x 
x 
x 
x 
x 
x 
* Assessment will only be done if there is a patient complaint for paraesthesia or pain
** Not all variables will be assessed (only fracture of material, surface luster, color match)

OTCS 36392568, Version 3.0 of 10.04.2024 
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1.
BACKGROUND AND RATIONALE
1.1 Background and Rationale for the clinical investigation
Caries lesions are a chronic disease that is widely spread among the population all over the world 
affecting 60-90% of children and the vast majority of adults in industrialised countries. (Pitts et al., 2017). 
Caries in posterior teeth (molars or premolars) occurs mostly in fissures or on approximal surfaces below 
the contact point of two neighboring teeth. In order to treat the disease caries affected tissue is removed. 
This leads either to class I cavities which have just one outer surface on the occlusal aspect of a posterior 
tooth or class II fillings, which are characterized with two outer filling surfaces on the occlusal and 
approximal aspect.  
Over the last three decades, caries prevalence has decreased in all age groups in modern Western 
countries (Jordan et al., 2019). For example, in European, caries prevalence in adults has declined by 
about 20% between 1996 and 2016 (Kassebaum et al., 2017). In Germany the cumulative caries 
experience has decreased from 1.1 billion DMFT (decayed/missing/filled teeth) in 2000 to 867 million in 
2015 and is expected to further decrease to 740 million in 2030 (Jordan et al., 2019).  However, not all 
societal groups have benefitted equally from this decline (Jordan et al., 2019). There is evidence for an 
association between low socio-economic status and a higher risk of having dental caries. In addition, on 
an international le–el - associated with population growth and increased tooth retent–on - the number 
of people affected by dental caries has grown substantially, increasing the total burden globally by 37% 
for untreated caries (Kassebaum et al., 2017).  
The evolution of carious lesion can be fast (acute) or slow (chronic). Both evolution rates are leading to 
loss of tooth structure over time and the morphology and function of teeth is affected. The goal of 
therapeutic procedures is to restore the morphology, aesthetics, and function of teeth by replacing the 
missing tooth substance with restorative materials. The therapeutic procedures are of two types: direct 
restorative procedures, where the tooth structure is restored directly in the oral cavity and indirect 
procedures where the restorations are manufactured either in the dental laboratory or chairside in a 
digital workflow. 
Direct (in the oral cavity of the patient) dental restorations are placed when sound tooth tissue (enamel 
and/or dentin) is partially lost due to caries, trauma, or tooth wear. When carious lesions no longer can 
be remineralized or arrested with non-invasive methods such as fluoride applications, the defect needs 
to be restored. For the direct restorative procedures dental resin composites and amalgam are mostly 
used in the daily practice. Resin composites are tooth-colored materials.   Resin composites are used 
with adhesive systems that bond the restorative material to the tooth structure. This allows dentists to 
accomplish defect-oriented preparations, limiting the removal of tooth substance to the area of the defect 
that needs to be restored. Composite resins are delivered in various shades, opacities and 
translucencies which allows aesthetically pleasing restoration of the original tooth structure.  
Resin composites can be classified by their viscosity in sculptable composites, showing a high viscosity 
respectively flowable composites showing a low viscosity. Resin composites are cured with a 
polymerization lamp which limits the thickness of material layers to 1-2 mm. Therefore, resin composites 
must be placed in incremental layers. Bulk-fill resin composites have been developed to facilitate 
clinicians’ work, reduce working time and simplify the restorative procedure (Kruly et al., 2018). They 
can be placed in increments of up to 4-5 mm as they either contain special light initiators which 
polymerize the resin in thicker increments or as the material is more translucent which allows the light 
to penetrate into deeper areas of the resin. 
The sculptable (bulk fill) composites can be used either alone or in combination with flowable bulk-fill 
composites. If such a combination is used to restore cavities a first layer of up to 4 mm thickness of 
flowable composite is applied in the cavity and light cured. The flowable composite has the advantage 
of an easy and fast application, so that the first 4 mm of the cavity are rapidly filled. Afterwards a capping 
layer of sculptable bulk-fill composite is applied, modelled and light cured. In this manner the cavities 
are restored even more rapidly. 
The modern curing lights use LED technology whose photons activate the initiators within the resin 
composite. Lamps with different power density are available. They vary between 700 mW/cm2 and 5,700 
mW/cm2 (Christensen et al., 2019). The higher the power density the shorter the polymerization time. 
The polymerization time required for a lamp with 1.200 mw/cm2 is 10 seconds, with 2,000 mw/cm2 it is 
5 seconds and with 3,000 mW/cm2 it is 3 seconds. However, each increment must be cured separately 
which results in multiple curing shots. The photons of the curing light activate the initiator, but also create 
heat which has raised the concern that heat might be transmitted from the cavity to the pulp with the 
potential risk of pulp damage. In addition, the exothermal polymerization reaction of dental composites 
is delivering also heat to the tooth contributing to the increase of the pulpal temperature. The flowable 

OTCS 36392568, Version 3.0 of 10.04.2024 
Page 11 
composites show a higher exothermal polymerization reaction then sculptable composites due to the 
higher monomer content. Possible damage related to heat stress comprises (1) reversible pulpitis with 
elevated pain to cold, heat or chewing after the treatment (post-operative hypersensitivity), (2) 
irreversible pulpitis with or without pain which makes a root canal treatment necessary or (3) internal 
resorption in the pulp chamber.  
Post-operative hypersensitivity is reversible in most cases and lasts from one week to several months 
(Major et al., 2002). Besides heat stress generated by the curing lamp and by the exothermic reaction 
of the resin composite, many other factors may influence the occurrence of sensitivity such as the 
remaining dentin thickness that separates the cavity from the pulp chamber, the size of the cavity and 
previous damage of the tooth.  
In an attempt to clarify the relationship between radiant exposure values and pulp temperature, Arrais 
et al. (2019) evaluated the in-vivo pulp temperature rise in premolars with cervical cavities which were 
exposed to 10 seconds of 2,000 mW/cm2 or 2x3 seconds of 3,000 mW/cm2 (Arrais et al., 2019). The 
teeth were extracted 2 hours after light exposure and histologically and immunochemically examined 
for signs of early inflammatory indicators like IL-β and TNF-α. The results showed a similar histological 
and immunochemical expression in both groups. A prospective clinical study on 62 posterior resin 
composite bulk-fill restorations that had been cured with a 3,000 mW/cm2 curing lamp for 3 seconds 
found that after 12 months, none of the treated teeth had suffered loss of sensitivity (vitality). However, 
in two independent clinical trials the rate of post-operative hypersensitivity at baseline was slightly higher 
compared to restorations that had been cured with the conventional technique . Most cases of post-
operative sensitivity subsided without intervention within several weeks. There were a few restorations 
that had manageable remnant post-operative sensitivity for which the subjects did not want intervention 
(Lawson et al., 2020, 2022, Enggist, 2018). 
TM Fill (sculptable) and TM Flow (flowable) are dental bulk-fill composites that can be applied in up to 
4 mm layers and can be light cured in 10, 5 or 3 seconds. The products are not bearing a CE mark and 
are not yet available on the market, so no clinical studies are available with these two products regarding 
the incidence rate of postoperative hypersensitivity and clinical performance of the product. The aim of 
this study is to assess the incidence rate of postoperative hypersensitivity, when class I and II cavities 
are directly restored with TM Fill in combination with TM Flow, both being light cured in the 3 seconds 
curing mode (3,000 mW/cm2). The application of a first layer of up to 4 mm TM Flow is considered the 
worst-case scenario, due to the higher exotherm polymerization reaction of flowable composites. By this 
clinical study not only the pulp response of the teeth to the materials in combination with the 3 seconds-
curing mode is determined, but also the clinical performance of the material by the assessment of the 
secondary outcomes like tooth vitality, marginal quality, fracture of material and retention loss, surface 
quality and aesthetics.  
1.2 Identification and description of the Investigational Medical Device
This information is provided within the Investig’tor's Brochures (IB) and the Instructions for Use (IFU). 

OTCS 36392568, Version 3.0 of 10.04.2024 
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2.
CLINICAL INVESTIGATION OBJECTIVES
2.1 Overall Objective
The aim of this clinical trial is to assess the clinical performance and safety of the new medical devices 
TM Flow and TM Fill in direct restorative treatment (class I and II restorations) polymerized in 3 seconds 
(3000 mW/cm2) with Bluephase PowerCure. 
2.2 Primary Objective
The primary objective is to assess the rate of postoperative hypersensitivity after treatment of class I 
and II cavities with the new composites TM Flow and TM Fill and to compare to the acceptance level of 
10% (see chapter statistics).  
2.3 Secondary Objectives
The secondary objective of this study is to assess the long-term clinical efficacy of the materials under 
investigation in terms of functional (fracture of material and retention, marginal adaptation, proximal 
contact point, form and contour, occlusion and wear) biological (caries at the restoration margins, dental 
hard tissue defects at the restoration margin, pulpal status) and aesthetic properties (surface luster 
andsurface texture, marginal staining, colour match). These outcomes provide information about the 
clinical performance of the material including the aesthetic performance. 
2.4 Safety Objectives
This study aims to assess the long-term safety of TM Fill and TM Flow in terms of tooth vitality and 
failure rate of placed restorations. Tooth vitality is an indicator for the health status of the dental pulp.  A 
vitality test is performed to acquire information about the vitality of teeth. A healthy dental pulp offers a 
positive response to the vitality test. Once the dental pulp is severely injured an irreversible inflammatory 
reaction starts with the endpoint the necrosis of the dental pulp. Pulpal necrosis is followed by a negative 
response to the vitality test. 

OTCS 36392568, Version 3.0 of 10.04.2024 
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3.
CLINICAL INVESTIGATION OUTCOMES
3.1 Primary Outcome
The primary outcome in this clinical trial is the FDI criteria - B3 pulpal hypersensitivity and pulpal status 
(Hickel et al. 2022) 1 month after placing of the fillings. FDI grades 3-5 are considered as postoperative
hypersensitivity in this clinical investigation, since FDI grade 2 does not need any treatment, subsides 
spontaneously and does not have further clinical relevance. Postoperative hypersensitivity is considered 
an indicator of the response of a tooth (pulp) to the therapeutic procedure applied. Postoperative 
hypersensitivity can be observed within a short time after the treatment. Therefore, it is assessed for the 
first time at the baseline recall (after 7-10 days). The assessment of postoperative hypersensitivity 
includes questions about type and duration of pain, intensity of pain and on the stimulus inducing the 
pain. The subjective perception of the intensity of postoperative hypersensitivity caused by thermal
stimuli and caused by occlusal forces (during biting) will be determined by the aid of a Visual Analog 
Scale (VAS). The VAS values are brought into relationship to the preoperative values. In the table below 
a description of the correlation between FDI grade and VAS values and clinical signs and symptoms is 
shown. Not all signs need to be present at one stage. The exact VAS values vary widely from patient to 
patient, depending on each individual’s pain tolerance. Therefore, it is one of the factors influencing the 
FDI grade, but it is not directly correlated. Not all the described conditions have to be fulfilled to attribute 
an FDI score. Depending on the intensity and character of the pain, further therapy will be determined. 
Usually, postoperative hypersensitivity subsides spontaneously and no treatment is necessary. In case 
of very intense pain an immediate treatment is required. The application of a fluoride varnish is the first
procedure of choice. If no improvement is achieved by this method, then the replacement of the 
restoration would be the next step. In the worst case, the pulp is severely inflamed, requiring endodontic 
treatment. If the postoperative hypersensitivity does not subside spontaneously or worsens after the 
applied treatment, the highest assessed FDI value is used for the statistical analysis.  
For all participants a 1-month recall is planned to finally assess the postoperative hypersensitivity rate. 
The clinical experience of the evaluators is of major importance in the correct assessment of the FDI 
grade. In general, the rule applies, that in case of uncertainties the higher score is attributed. 
FDI grade 
1 
2 
3 
4 
5 
Intervention 
none 
no treatment 
necessary 
fluoride 
varnish if 
desired 
replacement 
of restoration 
or endodontic 
treatment with 
access cavity 
only 
endodontic 
treatment and 
replacement 
of restoration 
Patient’s view 
/ description 
of pain / 
discomfort 
no complaint 
minor pain 
distinct pain 
persistent 
pain for 
prolonged 
period of time, 
patient asks 
for treatment 
treatment 
unavoidable 
VAS score 
0-3
<5 
>5
Pulp status 
none 
reversible pulpitis 
reversible or 
irreversible 
pulpitis 
irreversible 
pulpitis or pulp 
necrosis, with 
or without 
periapical 
periodontitis 
Duration of 
symptoms 
no symptoms 
<1 week 
>1 week
>1 month
n.a.
Vitality test 
normal, short reaction 
normal or 
more intense 
intense 
negative, 
nonvital tooth 
(no response) 

OTCS 36392568, Version 3.0 of 10.04.2024 
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The assessment of the pulp status is done at all recalls following the 1-month recall because the pulp is 
exposed to lifelong stimuli and can react any time. The methods of assessment are as described above. 
VAS during the 1 year recall and later is only done if the patient feels any hypersensitivity.   
3.2 Secondary Outcomes
The FDI criteria are well established parameters to evaluate the long-term performance of dental 
restorations (Hickel et al., 2022). The following FDI criteria were selected for the evaluations of the 
fillings in this clinical investigation: 
Tooth vitality 
A1 - Surface lustre and texture  
A2 - Marginal staining  
A3 - Color match  
F1 - Fracture of material and retention  
F2 - Marginal adaptation 
F3 - Proximal contact point 
F4 - Form and contour   
F5 - Occlusion and wear  
B1- Caries at restoration margins  
B2 - Dental hard tissue defects at the restoration margins 
M1 - Patients view 
Colour match, surface lustre and texture are secondary outcomes that provide information about the 
aesthetic potential of the material. Surface lustre also proves information about the ability of the material 
to be polished to a level where plaque accumulation is reduced and the potential of the material to 
maintain its lustre over time. 
The retention/fracture rate of the restorations and the fracture rate of teeth (dental hard tissue defects 
at the restoration margins) are outcomes that provide information about the clinical performance of the 
bond of the restoration to the tooth structure and about the strength of the material and its ability to resist 
to the occlusal forces. 
The marginal quality including marginal staining, marginal adaptation, caries at the margins of the 
restorations provides information about the quality of the bond between tooth structure and the dental 
composites.  
Contact point, contour and form, occlusion and wearare secondary outcomes that provide information 
about the physical properties of the material and its ability to maintain its form when in clinical use. 
The secondary outcomes will be assessed at all recalls. 
3.3 Other Outcomes of Interest
Not applicable 
3.4 Safety Outcomes
No other specific safety outcomes than the previous described (postoperative hypersensitivity, loss of 
vitality, loss of restoration, tooth fracture, tooth loss) will be evaluated. 

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4.
CLINICAL INVESTIGATION DESIGN
4.1 General clinical investigation design and justification of design
A single arm, prospective clinical trial is planned with TM Fill in combination with TM Flow, cured in the 
3 seconds curing mode (3000mW/cm2). In this high energy curing mode the photons of the curing light 
activate the initiator, but also create heat which has raised the concern that heat might be transmitted 
from the cavity to the pulp with the potential risk of pulp damage. TM Flow will be applied as an initial 
layer of up to 4 mm thickness (A3.5 mm in case of the shade A3.5 plus). The materials also have an 
exothermic reaction during the light polymerization that adds to the energy output of the lamp, and since 
the flowable material have a higher exothermal reaction when compared to sculptable materials, the 
application of an initial layer of flowable material in the maximal layer thickness represents a worst-case 
with regard to the pulp response to the temperature increase. The materials will be used for the 
restoration of class I and II cavities in posterior teeth (molars, premolars) since class I and II cavities are 
the most frequent in the daily practice and are exposed to the highest occlusal forces. This allows the 
assessment of the performance of the material in its main field of application.   
The participants are recruited from the existing patient base of the internal practice of Ivoclar Vivadent 
AG and are thus employees of the company. No active recruiting measures are taken. Each participant 
has the right to refuse further participation in the clinical trial at any time.  
No participant will receive more than one restoration during the clinical trial. The recruited participants 
who meet all inclusion criteria will have a detailed medical anamnesis (signed by dentist and participant) 
to evaluate diseases and a detailed dental medical report. In addition, there is a therapy plan in the 
sense of the complex rehabilitation concept. These details are documented in the participant file 
independently of the clinical study. 
During the study each participant will receive one TM Filling. The restorations will consist of an initial 
layer TM Flow of up to 4 mm and a subsequential layer TM Fill.  
The procedure for the application of the adhesive Adhese Universal is the "Etch & Rinse (E&R)" 
technique (previous enamel/dentine etching with phosphoric acid). 
5 trained operators will insert 65 indirect restorations, so each operator will perform 13 restorations. 
2 trained evaluators will perform the baseline examination (7-10 days) after placement of the 
restorations, and the following recalls at 1, 6, 12, 24, 36 and 60 months. 
4.2 Methods for minimising bias
4.2.1 
Randomisation
Not applicable since it is a single arm study. 
4.2.2 
Blinding procedures
Not applicable since it is a single arm study. 
4.2.3 
Other methods for minimising bias
This section is not applicable 
4.3 Unblinding Procedures (Code break)
Not applicable since it is a single arm study. 

OTCS 36392568, Version 3.0 of 10.04.2024 
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5.
CLINICAL INVESTIGATION INTERVENTION
5.1 Identity of the medical device under investigation
TM Flow is a flowable, light-curing, radiopaque composite (200% Al) for the direct restorative treatment 
of anterior and posterior teeth. TM Fill is a sculptable, light-curing, radiopaque composite (200% Al) for 
the direct restorative treatment of anterior and posterior teeth. TM Fill is also suitable for restoring 
occlusal surfaces.TM Flow and TM Fill cure with light in the wavelength range of 400–500 nm and can 
be applied in layers of up to 4 mm. 
5.1.1 
Experimental Intervention (medical device)
The direct filling therapy of a class I or II with flowable and sculptable composites is an everyday 
procedure for most dentists. The placement of this kind of filling is part of the basic training during dental 
medicine study. It is described in textbooks and videos which are freely available.  
5.1.2 
Control Intervention (standard/routine/comparator)
Not applicable since it is a single arm study. 

Page 17 
6. STATISTICAL METHODS
6.1 Hypothesis
The Null Hypothesis (H0) is that the proportion of postoperative hypersensitivity occurrence after the 
treatment with the new composites (Ptreat) is higher than the clinically acceptable 10% (P0). The 
Alternative Hypothesis (H1) states that the proportion of occurring hypersensitivity in this study is less 
than 10%. 
Single-arm study with a one-sided hypothesis: 
H0: Ptreat ≥ 10% 
H1: Ptreat < 10%  
The frequency of postoperative sensitivities calculated in meta-analyses with class I and II cavities vary 
widely between 1% and 29% (Gordan et al., 2002, Hayashi et al., 2003, Heintze et al., 2012, Arbildo et 
al., 2020, Reis et al., 2015) because there are many influencing factors that are difficult to standardize 
between different studies. Factors that influence the development of postoperative hypersensitivites
include the depth and size of cavities, removal of the smear layer (adhesive strategy), type of tooth, 
polymerization technique, gap formation between filling material and dentin, inadequate sealing of 
dentinal tubules, residual caries, bacterial penetration, contractual stress and level of pain sensation. 
Based on their experience, the dentists of the internal clinic consider the occurrence of more than 10% 
postoperative hypersensitivity unacceptable.  This level was already chosen for previous studies, e.g. 
«Klinische Untersuchung des F-Composite 2 Systems in der direkten Füllungstherapie» (BASEC-ID
2017-00904).
6.2 Determination of Sample Size
The sample size calculation was performed by Dr. Nicole Graf (biostatistician) from the Clinical Trials 
Unit of the Kantonsspital St. Gallen. Her CV and calculations can be provided upon request. 
The power was calculated using PASS Version 21.0.5 (PASS 2021 Power Analysis and Sample Size 
Software (2021). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass.). 
Using the parameters listed in the table below, a sample size of 61 achieves 82% power to detect a 
difference (P1-P0) of -0.076 using a one-sided binomial exact test with a target significance level of 0.05. 
Considering a drop-out rate of 5%, it is planned to include 65 patients in this study. 
Parameters used for the sample size calculation: 
P0 
P1*
Difference P1-P0 
Target alpha 
Power 
Sample size 
0.10 
0.024 
-0.076
0.05 
0.82 
61 
*Proportion of patients that experienced postoperative hypersensitivity after a direct restorative treatment with
already established composites at the study site (internal clinic of Ivoclar Vivadent AG).
6.3 Statistical criteria of termination of the investigation
If 6 or more patients show a postoperative hypersensitivity of FDI grade 4 or 5, the study will be 
terminated.  
6.4 Planned Analyses
The IBM SPSS Version 25 software package will be used for data analysis. 
6.4.1 Datasets to be analysed, analysis populations
The data collected of all eligible participants will be used for the statistical data analysis. 
OTCS 36392568, Version 3.0 of 10.04.2024 

OTCS 36392568, Version 3.0 of 10.04.2024 
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6.4.2 Primary Analysis
Regarding the primary outcome, the interim analysis will be done at baseline. The final analysis of the 
primary outcome will be done after 1month. VAS values (biting and thermal stimuli) and the clinical signs 
and symptoms regarding tooth vitality, response to thermal tests, duration and intensity of pain are 
summarized in an FDI score as described by Hickel et al. (2022). It will be evaluated if the postoperative 
hypersensitivity rate (FDI criterium B3) is below 10% using a one-sided binomial exact test. Only FDI 
grades 3-5 will be considered as postoperative hypersensitivity, since FDI grade 2 does not need any
treatment, subsides spontaneously, and does not have further clinical relevance. The analysis will be 
done by the principal investigator within 3 months after the collection of the data. 
6.4.3 Secondary Analyses
Regarding the secondary outcomes, the analyses will be done after the 1, 6, 12, 24, 36 and 60 months 
recalls. A descriptive statistical analysis will be done by the principal investigator within 3 months after 
the collection of the data.  
6.4.4 Interim analyses
The interim analysis will be done after the collection of data at each recall. 
6.4.5 Deviation(s) from the original statistical plan
Deviations from the original statistical plan must be reported to the sponsor. 
6.5 Handling of missing data and drop-outs
After baseline drop-outs will not be replaced. In previous clinical trials, there were few drop-outs in the 
internal clinic of Ivoclar Vivadent AG. There had also been a small number of no-shows. 

OTCS 36392568, Version 3.0 of 10.04.2024 
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Arbildo-Vega H., Lapinska B., Panda S., Lamas-Lara C., Khan A., Lukomska-Szymanska M., Clinical E 
ectiveness of Bulk-Fill and Conventional Resin Composite Restorations: Systematic Review and Meta-
Analysis, Polymers 2020, 12, 1786 
Arrais, C., F. Rueggeberg, and P. Runnacles, Analysis of pulp temperature and inflammatory response 
to radiant exposure from an experimental Polywave LED light curing unit. Final Report - In vivo analysis 
of pulp temperature, 2019. Ponta Grossa, Brazil: p. 1-21. 
Boeckler A, Boeckler L, Eppendorf K, Schaller H-G, Gernhardt C R. A prospective, randomized clinical 
trial of a two-step self-etching vs two-step etch-and-rinse adhesive and SEM margin analysis: four-year 
results. J. Adhes. Dent. 2012;14:585–92.
Christensen, G.J., Are new innovations in curing lights more effective? Clinicians Report, 2019. 12(3). 
Enggist, L.; Baseline report of the study "Clinical investigation of the F-Composite 2 Systems in direct 
filling therapy". Internal Report 2018 (OTCS 3221260) 
Enggist, L.; 6 month recall of the study "Clinical investigation of the F-Composite 2 Systems in direct 
filling therapy". Internal Report 2018 (OTCS 3263577) 
7. REFERENCES
Heintze S D, Rousson V. Clinical effectiveness of direct class II restorations - a meta-analysis. J. Adhes. 
Dent. 2012;14:407–31. 
Hickel, R., J. F. Roulet, et al. (2007). "Recommendations for conducting controlled clinical studies of 
dental restorative materials. Science Committee Project 2/98--FDI World Dental Federation study 
design (Part I) and criteria for evaluation (Part II) of direct and indirect restorations including onlays and 
partial crowns." J Adhes Dent 9 Suppl 1: 121-147. 
Hickel, R., A. Peschke, et al. (2010). "FDI World Dental Federation: clinical criteria for the evaluation of 
direct and indirect restorations-update and clinical examples." Clin Oral Investig14(4): 349-366. 
Hickel, R.; Mesinger, S.; Opdam, N., Loomans, B.; Frankberger, R.; Cadenaro, M.; Burgess, J.; 
Peschke, A.; Heintze, S.D.; Kühnisch, J. Revised FDI criteria for evaluating direct and indirect dental 
restorations - recommendations for its clinical use, interpretation, and reporting. Clinical Oral 
Investigations 2022, 27, 2573-2592. 
Jordan, R.A., et al., Trends in caries experience in the permanent dentition in Germany 1997-2014, and 
projection to 2030: Morbidity shifts in an aging society. Sci Rep, 2019. 9(1): p. 5534. 
Kassebaum, N.J., et al., Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted 
Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global 
Burden of Diseases, Injuries, and Risk Factors. J Dent Res, 2017. 96(4): p. 380-387. 
Kruly, P.d.C., et al., Meta-analysis of the clinical behavior of posterior direct resin restorations: Low 
polymerization shrinkage resin in comparison to methacrylate composite resin. PLoS One, 2018. 13(2): 
p. e019194
Lawson, N., Twelve month clinical performance of an ultra-rapid polymerization bulk-fill composite. 2020 
IADR/AADR/CADR General Session, Abstract number 1381 

OTCS 36392568, Version 3.0 of 10.04.2024 
Page 20 
Lawson, N., 24-Month Clinical Performance of an Ultra-Rapid Polymerization Time Bulk-Fill Composite
2022 AADOCR/CADR Annual Meeting, Abstract number 0383 
Loguercio A D, Rezende M, Gutierrez M F, Costa T F, Armas-Vega A, Reis A. Randomized 36-month 
follow-up of posterior bulk-filled resin composite restorations. J. Dent. 2019;85:93–102.
Mjor, I.A. and M. Ferrari, Pulp-dentin biology in restorative dentistry. Part 6: Reactions to restorative 
materials, tooth-restoration interfaces, and adhesive techniques. Quintessence Int., 2002. 33(1): p. 
35-63.
Pintado-Palomino K, de Almeida C V V B, da Motta R J G, Fortes J H P, Tirapelli C. Clinical, double 
blind, randomized controlled trial of experimental adhesive protocols in caries-affected dentin. Clin. 
Oral. Investig. 2019;23:1855–1864.
Pitts, N.B. et al., Dental Caries, A.Nat Rev Dis Primers. 2017 May 25;3:17030. 
Reis A, Dourado Loguercio A, Schroeder M, Luque-Martinez I, Masterson D, Cople Maia L., Does the 
adhesive strategy influence the post-operative sensitivity in adult patients with posterior resin 
composite 
restorations?: 
A 
systematic 
review 
and 
meta-analysis, 
Dent 
Mater. 
2015 
Sep;31(9):1052-67. 
All internally available documents with "OTCS-Numbers" will be provided upon request.