clinical evaluation of the whitening effect of a toothpaste … · 2019-01-06 · subject have...

FINAL REPORT

CLINICAL EVALUATION OF THE WHITENING EFFECT

OF A TOOTHPASTE PRODUCT

STUDY UNDER DENTIST CONTROL

Report : DA14A050-1, November 20, 2014

Product: Sparkle Coffee & Tea Drinkers’

Whitening Toothpaste

Form: White paste

Application zone: Teeth

Sponsor: Kuron Corporation Limited.

193,195,197 Krungthepkreetha Rd.,

Sapansoong, Bangkok 10250

THAILAND

Investigation site: Dermscan Asia Co., Ltd.

3300/46-47 29th

Floor, Tower A

Elephant Tower, Phaholyothin Rd.

Chomphon, Chatujak, Bangkok 10900

THAILAND

Investigator (Dentist): Dr. Salunya TANCHAROEN

Document: 1/1

(Document including 33 pages)

Kuron Corporation Limited DA14A050-1 2/33

Report_V1.0_November 20, 2014

TABLE OF CONTENTS

SUMMARY OF THE STUDY ........................................................................................................... 5 1. STUDY OBJECTIVES ............................................................................................................. 6

1.1. Primary objective .......................................................................................................... 6 1.2. Secondary objectives ................................................................................................... 6

2. METHOD ................................................................................................................................. 6 2.1. Trial period ..................................................................................................................... 6 2.2. Experimental plan ......................................................................................................... 6 2.3. Assessment criteria ...................................................................................................... 6

2.3.1. Primary criterion .......................................................................................................... 6 2.3.2. Secondary criteria ....................................................................................................... 6 2.3.3. Principle(s) .................................................................................................................. 7

2.3.3.1. Whitening effect (clinical score) ......................................................................... 7 2.3.3.2. Tolerance ........................................................................................................... 8 2.3.3.3. Subjective evaluation questionnaire ................................................................... 9 2.3.3.4. Macrophotographs ............................................................................................. 9

2.4. Subject selection ........................................................................................................... 9 2.4.1. Number of subjects ..................................................................................................... 9 2.4.2. Inclusion criterion ........................................................................................................ 9

2.4.2.1. General criteria ................................................................................................... 9 2.4.2.2. Specific criteria ................................................................................................... 9

2.4.3. Non-inclusion criteria .................................................................................................. 9 2.4.4. Compliance assessment .......................................................................................... 10 2.4.5. Associated treatment during the study ..................................................................... 10

2.5. Operational aspect ...................................................................................................... 10 2.5.1. Trial organization: schedule ...................................................................................... 10 2.5.2. Study flow chart ........................................................................................................ 11 2.5.3. Adverse Events/Serious Adverse Events ................................................................. 11

2.5.3.1. Definitions ........................................................................................................ 11 2.5.3.2. Documentation ................................................................................................. 11 2.5.3.3. Notification ....................................................................................................... 12 2.5.3.4. Follow-up .......................................................................................................... 12 2.5.3.5. Occurrence of pregnancy ................................................................................. 12 2.5.3.6. Premature termination of the study .................................................................. 12

2.5.4. Collection and validation of data ............................................................................... 13 2.5.5. Audit and trial monitoring visit ................................................................................... 13 2.5.6. Quality management ................................................................................................. 13

2.6. Studied product ........................................................................................................... 13 2.6.1. Confidentiality procedure .......................................................................................... 13 2.6.2. Storage ..................................................................................................................... 13 2.6.3. Reference ................................................................................................................. 13 2.6.4. Aspect ....................................................................................................................... 14 2.6.5. Labelling .................................................................................................................... 14 2.6.6. Dosage...................................................................................................................... 14 2.6.7. Application site(s) and method(s) ............................................................................. 14 2.6.8. Product(s) issue ........................................................................................................ 14 2.6.9. Product(s) future ....................................................................................................... 14

2.7. Method of product's) attribution to the subjects ..................................................... 14 2.7.1. Randomization method ............................................................................................. 14 2.7.2. Product allocation ..................................................................................................... 15

2.8. Data analysis ............................................................................................................... 15 2.8.1. Calculation formulas ................................................................................................. 15 2.8.2. Statistical method(s) ................................................................................................. 15 2.8.3. Software used ........................................................................................................... 16

2.9. Archives ....................................................................................................................... 16 3. TEST FOLLOW-UP ............................................................................................................... 17

3.1. Population .................................................................................................................... 17

Kuron Corporation Limited. DA14A050-1 3/33


3.2. Protocol non-adherences ........................................................................................... 17 3.3. Audit / Trial monitoring visit ...................................................................................... 17

4. SUBJECTS' CHARACTERISTICS........................................................................................ 18 4.1. Demographic data ....................................................................................................... 18 4.2. Concomitant treatments ............................................................................................. 18

5. RESULTS .............................................................................................................................. 19 5.1. Whitening effect (clinical score) ................................................................................ 19 5.2. Tolerance ..................................................................................................................... 20 5.3. Subjective evaluation questionnaire ......................................................................... 21

6. CONCLUSION AND SIGNATURE ........................................................................................ 23 7. CERTIFICATION ................................................................................................................... 26 8. BIBLIOGRAPHY ................................................................................................................... 27

8.1. Regulatory ................................................................................................................... 27 8.2. Data analysis ............................................................................................................... 27

9. APPENDIX ............................................................................................................................. 28 9.1. Clinical scoring ........................................................................................................... 28 9.2. Clinical examination ................................................................................................... 30 9.3. Subjective evaluation questionnaire ......................................................................... 31



QUALITY CONTROL STATEMENT

Clinical study number : DA14A050-1

Study start date : September 25, 2014

Study completion date : October 9, 2014

The study listed above was conducted in conformance with Good Clinical Practice (GCP-ICH) and DERMSCAN ASIA standard operating procedures. The study has been conduct according to the study protocol defined with the sponsor. All the case report forms and the data were checked. The Quality inspection Auditor testifies to the respect of the rules, the standards and procedures listed above.

Last name :

First name :

Date :

Signature :



SUMMARY OF THE STUDY

Sponsor: Kuron Corporation Limited.

Address: 193,195,197

Krungthepkreetha Rd.,

Sapansoong, Bangkok, 10250

THAILAND

Investigator : Dermscan Asia Co., Ltd

Address: 3300/46-47 29

th Flr., Tower A

Elephant Tower, Phaholyothin Rd.,

Chomphon, Chatujak,

Bangkok,10900 THAILAND

Study Title

CLINICAL EVALUATION OF THE WHITENING EFFECT

OF A TOOTHPASTE PRODUCT

STUDY UNDER DENTIST CONTROL

Product(s) Reference: Sparkle Coffee & Tea Drinkers’ Whitening Toothpaste

Type: White paste

Study date(s) 25/09/2014 - 09/10/2014

Objective(s)

- To evaluate the whitening effect of the product. - To evaluate the tolerance of the product. - To evaluate the efficacy, tolerance and organoleptic properties of the toothpaste - To visualize its expected effect by macrophotographs

Methodology - Open and intra-individual study.

Assessment

Criteria

- Whitening effect (clinical scoring ) Kinetics D0, D14

Methodology Before / After

- Tolerance (clinical examination), - Subjective evaluation (questionnaire). - Macrophotographs

Zone Teeth.

Application

frequency

Twice-daily (morning and evening)

Studied

population

Number of analysed subjects: 20 subjects

Age: 25± 1 (average ± SEM) 18 to 37 years old.

Main inclusion criteria:

Sex: Asian male or female.

Age: between 18 years old and more.

Subject have yellow teeth grade 2-3 with VITA Toothguide 3D-MASTER

®

Subject regularly drinks coffee or tea.

Results -

Conclusion

Under these study conditions, after 14 days of use product " Sparkle Coffee & Tea

Drinkers’ Whitening Toothpaste":

presented a significant whitening effect of upper and lower teeth as

evidenced by the clinical scoring carried by the dentist

was very well tolerated

was appreciated by the subjects its organoleptic characteristic and for its

efficacy. 90% of the subjects would like to continue its use and might buy the

product at the end of the study.

Investigator:

Dr. Salunya TANCHAROEN

Dentist

Date

Signature



1. STUDY OBJECTIVES

1.1. Primary objective

The primary objective of this study was to evaluate, the whitening effect, on subjects, of product “Sparkle Coffee & Tea Drinkers’ Whitening Toothpaste" after 14 days of use.

1.2. Secondary objectives

The secondary objectives of this study were to evaluate, for the tested product:

its tolerance

the subjective appreciation, its organoleptic characteristics, its efficacy and its future use.

its visual effect by illustrative macrophotographs.

2. METHOD

2.1. Trial period

Product reception : September 18, 2014

Beginning of the test September 25, 2014

End of the test October 9, 2014

2.2. Experimental plan

This was an open and intra-individual study; each subject was his/her own control.

2.3. Assessment criteria

2.3.1. Primary criterion

Evaluation of the teeth color by the dentist by using a specific color scale (VITA Toothguide 3D-MASTER

®).

2.3.2. Secondary criteria

Evaluation of the tolerance by clinical examination under dentist control.

Analysis of the subjects' answers to a subjective evaluation questionnaire.

Illustration of the visual expected effect by realization of macrophotographs



2.3.3. Principle(s)

2.3.3.1. Whitening effect (clinical score)

The dentist in charge of the study assesses the initial color of the upper and lower incisors and canines using the selected Shade System (VITA Toothguide 3D-MASTER

®).

This instrument is composed different colors to which a score was attributed according to the table below:

Color Score

1M1 1

1M2 2

2M1 3

2L1.5 4

2R1.5 5

2M2 6

2L2.5 7

2R2.5 8

2M3 9

3M1 10

3L1.5 11

3R1.5 12

3M2 13

3L2.5 14

3R2.5 15

3M3 16

4M1 17

4L1.5 18

4R1.5 19

4M2 20

4L2.5 21

4R2.5 22

4M3 23

5M1 24

5M2 25

5M3 26

After product use, the dentist assesses the final color of the same teeth. For each subject, evaluation of the color is done on 12 teeth (upper teeth: n° 11, 12, 13, 21, 22 and 23 and lower teeth: n° 31, 32, 33, 41, 42 and 43) then the average score is calculated. See the diagram below:



The whitening effect is calculated by comparing the average score before and after product use. The variations (Di-D0) in the teeth color are calculated. Descriptive statistics are done and a Student t-test is done on purpose to determine the significance of the variation.

The product is considered effective if it induces any significant decrease in the mean clinical

scores obtained for both upper and lower teeth.

2.3.3.2. Tolerance

Before and after product use, the tolerance of the product is assessed by clinical examination under dentist control. The dentist assesses the following parameters: Examination of the tissues: Evaluation of the oral hygiene: none very slight slight moderate severe Redness Bleeding Swelling Pain Others: Please specify:..................................................................................... This evaluation takes into account the relevant elements reported by the subject (functional and physical signs (T1)) as well as those noted by the dentist (clinical signs (T2)). The confrontation of these signs is used to conclude the final tolerance of the tested product. The global tolerance of the tested product is defined as the least favourable result (T1 or T2). The relevance of a sign is defined as follows:

- lasting more than five minutes and,

- possible or certain imputability with the tested product and,

- length of time superior or equal to a quarter of the total duration of the study.



This leads to the exclusion of null or doubtful signs of imputability as well as signs that last only a few days during the study (notably at the beginning of the study). All possible or certain signs of imputability that appear during the final days of the study are retained, providing there is no ulterior follow-up.

2.3.3.3. Subjective evaluation questionnaire

A subjective evaluation questionnaire was prepared by the clinical trial center and submitted to the sponsor, was filled in by the subjects on D14 to subjectively evaluate the characteristics of the studied product, its global efficacy, its tolerance and its future use.

2.3.3.4. Macrophotographs

Standardized macrophotographs are taken before and after product use according the same settings. Repositioning occurs directly on the computer screen due to simultaneous image visualization at different acquisition times.

2.4. Subject selection

2.4.1. Number of subjects

The study was done on 20 subjects minimum, at the sponsor’s request.

2.4.2. Inclusion criterion

2.4.2.1. General criteria

Healthy subject.

Type: Asian.

Subject having given their informed, written consent.

Cooperative subject, aware of the necessity and duration of controls so that perfect adhesion to the protocol established by the clinical trial center could have been expected.

2.4.2.2. Specific criteria

Asian female and male with aged 18 years old and more.

Subject have yellow teeth grade 2-3 with VITA Toothguide 3D-MASTER®

Subject regularly drink coffee or tea

2.4.3. Non-inclusion criteria

For women: pregnant or nursing woman or woman planning to get pregnant during the study.

Pathology on studies zone.

Subject having a known allergy to one of constituents of the product being tested.

Use of topical or systemic treatment during the previous weeks liable to interfere with the assessment of the investigational product

Any dental treatment during the study period

Subjects wear denture, dental crown or dental braces which interfere the assessment on studies zone

Excessive users of alcohol or tobacco.

Subjects enrolled in another clinical trial during the study period.



Subject who has been deemed by the screener as potentially unable or unwilling to comply with the protocol.

2.4.4. Compliance assessment

If the protocol was not respected and if the deviation was minor, the technician or investigator in charge of the study warned the subject of the importance of respecting the instructions. If the subject persisted or if the deviation was major, the subject was declared no-compliant. In this case, the subject was removed from the test for non-compliance.

Under normal conditions of use (application of the product at home), no compliance control could be carried out during the study. However, the subject filled in every day the daily log and noticed the number of use.

2.4.5. Associated treatment during the study

No use of oral hygiene products other than the investigational product was authorized on the teeth during the study. Only the usual personal care product(s) were authorized and their toothbrush during the study.

2.5. Operational aspect

2.5.1. Trial organization: schedule

On t0:

Subjects came to the laboratory having brushed their teeth in the morning before the visit.

Subjects read, signed and dated the information sheet (instructions on the product use and restrictions related to the study) and informed consent forms in duplicate. These documents were also signed and dated by the person who conducted the informed consent discussion. The subjects received a copy.

Verification of inclusion and non-inclusion criteria by the dentist.

Clinical examination of the mouth by the dentist (teeth, gums, soft tissues ...).

Evaluation of the color of the teeth (upper and lower incisors and canines) using VITA Toothguide 3D-MASTER

®.

Take photography of teeth.

Distribution of the daily log and the product to the subjects who use it twice – daily during 14 days.

On D14

The subjects came back to the laboratory without having applied any cosmetic product to their face and lips since the previous evening (except the morning wash).

They brought the daily log and the studied product back.

New clinical examination of the mouth by the dentist (teeth, gums, soft tissues... ) and interrogation of the subjects regarding to potential intolerance sensations.

New evaluation of the teeth color (upper and lower incisors and canines) using VITA Toothguide 3D-MASTER

®.

Take photography of teeth.

Collection of intolerance reactions felt during the study.

The subjects filled in the subjective evaluation questionnaire.



2.5.2. Study flow chart

D0 D0 to D13 D14

Information of the subject about study conditions and collection of his informed consent.

Verification of inclusion and non-inclusion criteria.

Clinical examination by the dentist.

Take a photography

Distribution of product and daily log.

Application of the product by the subjects at home.

Collection of product and daily log.

Record of possible adverse events and intolerance sensations.

Subjective evaluation questionnaire.

2.5.3. Adverse Events/Serious Adverse Events

During the study, the following rules were applied:

2.5.3.1. Definitions

An Adverse Event (AE) is defined as any noxious symptom, temporarily linked to the use of a study product, occurring in a subject taking part in a clinical trial, whether or not this symptom is related to the studied product(s). An adverse reaction is defined as any noxious and unexpected reaction that might be related to the studied product(s). All adverse events judged, by the investigator, as being possibly, probably or certainly related to the studied product are considered as adverse reactions. A Serious Adverse Event (SAE) is defined as an adverse event or effect that:

results in death (note: death is the outcome, not the event),

is life threatening,

requires in-patient hospitalization (at least one night) or prolongation of existing hospitalization (does not include hospitalization scheduled before the inclusion),

results in persistent or significant disability or incapacity,

is a congenital anomaly/birth defect,

is considered like by the investigator. The severity/intensity of adverse events can be graded on a three-point scale:

Mild or Grade 1: discomfort noted, but does not disturb normal daily activities.

Moderate or Grade 2: discomfort sufficient to reduce or affect normal daily activities.

Severe or Grade 3: inability to work or have normal daily activities.

2.5.3.2. Documentation

All concomitant treatments are reported in the CRF and the study report. All Adverse Events likely to be related to the studied product (adverse reactions) are reported in the CRF and the study report. All Serious Adverse Events are reported in the CRF and the study report.



2.5.3.3. Notification

The investigator declares to the sponsor, by fax or e-mail, the occurrence of adverse reactions according to their severity and their unexpectedness (according to the investigator's advice). All Serious Adverse Events are transmitted by e-mail to the sponsor without delay, at the latest 24 hours after knowledge of their occurrence. A SAE declaration form signed by a physician is sent, within 48 hours, by fax or e-mail with acknowledgement of receipt.

2.5.3.4. Follow-up

When an adverse event linked to the studied product or the protocol persists at the end of the study, the Investigator ensures that the subject is followed up until total resolution of the event or stabilization of the symptoms without releasing the Sponsor of any obligation or responsibility.

2.5.3.5. Occurrence of pregnancy

The occurrence of a pregnancy (reported or diagnosed) after inclusion in the study is considered as an intercurrent event not related to the studied product(s) nor the protocol and induces the immediate dropping out of the subject. A follow-up will be done according to the current internal procedures up to the end of the pregnancy or to its interruption.

2.5.3.6. Premature termination of the study

Study exit conditions * In compliance with the Helsinki Declaration (1964) and its successive updates, subjects have the right to exit from the study at any time and for any motive. * The investigator can also interrupt the subject participation in the study prematurely in the case of a disease occurrence, a pregnancy or the occurrence of an adverse reaction. * The sponsor can demand that any subject be excluded from the study for major infringements to the protocol, for administrative reasons or any other motive. Nevertheless, premature removal of a high percentage of subjects from the study can make the study difficult or impossible to interpret. Consequently, any premature exit without valid motives should be avoided as much as possible and is carefully documented in the case report form, the final report and, if necessary, in the Adverse Event form. Every premature exit must be classified under one of the following headings:

presence of a non-inclusion criteria,

Adverse Event occurrence,

Serious Adverse Event occurrence,

withdrawal of consent,

untraceable panelist,

appearance of non-inclusion criteria,

non-adherence to the protocol,

other reason.

Replacement conditions

No replacement is foreseen as 10% additional subjects are planned to be included in the study.



2.5.4. Collection and validation of data An identification code was attributed to each subject for the purpose to keep her identity confidential. This code consists of: the first three letters of the subject's name and the first two letters of her first name. The personnel in charge of the study (technician, physician, …) added data to subject case report form and to a computerized data base. The simple data entry was done from the case report forms by the designed technician(s) or operator(s), without any interpretation, in specific MS EXCEL databases. Then the Trial Manager or assistant checked at least 10% of data to insure the coherence between computed data and information in the case report forms. He/She also checked formulas used in the EXCEL tables (calculation formulas, selected data…). The coherence of data coming directly from measurement software(s) was also checked and validated by the Trial Manager or assistant, taking into account the potential acquisition errors. When all CRF were computed and all controls done, the databases were frozen.

2.5.5. Audit and trial monitoring visit An audit and/or trial monitoring visit might be carried out at the sponsor's request or by the appropriate regulatory authority. The aim of the monitoring visit is to verify that the study is conducted according to the determined protocol and current regulations.

2.5.6. Quality management

In order to ensure that the clinical trials are in compliance with the sponsor’s requirement, DERMSCAN Asia has implemented quality procedures including Good Clinical Practices (GCP) and regulation requirements.

Each study report is subjected to a quality inspection by a member of the DERMSCAN Proofreading Committee. The proofreader is chosen because he(she) is not involved in the audited study. The inspection of the study report allows us to confirm that the results reflect exactly the study raw data. A certificate of quality inspection, signed by the person who checked the report is enclosed in each study report to certify that the study report reflects the study raw data and fulfils any standard and regulatory requirements.

2.6. Studied product

2.6.1. Confidentiality procedure

The product supplied by the sponsor was encoded.

2.6.2. Storage Before the beginning of the study, products were kept at room temperature in a dedicated air-conditioned room. This room is locked and access controlled.

2.6.3. Reference

Sparkle Coffee & Tea Drinkers’ Whitening Toothpaste



2.6.4. Aspect

White paste

2.6.5. Labelling

Example of labeling of each product by the clinical trial center and translation:

หมายเลขการวิจัย #

ช่ือผลิตภณัฑ์.:…………………….

เบอร์โทรติดต่อกรณีฉกุเฉิน: …………………

วิธีใช้: …………………….....................

เก็บรักษาท่ีอณุหภมูิห้อง กรุณาเก็บให้พ้นมือเดก็

ส าหรับใช้ในการวิจยัภายใต้การดแูลอย่างใกล้ชิดของทนัตแพทย์ผู้ เชี่ยวชาญเท่านัน้

DERMSCAN Study #

Product: …………………… Emergency telephone number: …………………….. Dermscan ref.:…………………….

Conservation: room temperature

Keep out of reach and sight of children.

To be used only under strict dentist supervision for clinical trial.

2.6.6. Dosage

At home: twice a day (in the morning and in the evening) during 14 days.

2.6.7. Application site(s) and method(s)

Application site: teeth and gums. Application method: use the toothpaste under normal condition and brush the teeth during two minutes.

Rinse abundantly.

2.6.8. Product(s) issue

The product was delivered to the subjects by the technician with an explanation of the application conditions.

2.6.9. Product(s) future

As far as possible, one sample of the studied product was kept by the laboratory for a period of one year after its receipt. By default, the products (used and not used) were destroyed at the end of the study according to the current internal procedures.

2.7. Method of product's) attribution to the subjects

2.7.1. Randomization method

Not applicable



2.7.2. Product allocation

Not applicable. All the subjects tested the same product

2.8. Data analysis

2.8.1. Calculation formulas

The raw variations () and in percentage (%) of the different studied parameters were calculated according to the following formulas:

= (TZti - TZt0)

% = (TZti - TZt0)x 100

TZt0 with: TZ: value obtained on the treated zone, t0: before application,

ti: at each measurement time after application.

Remarks:

The percentage of the variation (%) is expressed in percentage of the variation on the measurement's zone (TZti - TZt0). These variations are balanced at the initial value TZt0 (before application).

This expression (%), therefore, gives the variation, in percentage, on the measurement’s zone compared to the initial conditions (TZt0). Measured values are presented in raw value tables. These tables also show the descriptive statistics: means, medians, minima, maxima, standard errors of the means (SEM) and confidence intervals of 95% (95% CI). Also, raw variations, percentage variations, descriptive statistics and the results of the statistical analysis (p) are presented in the variation tables.

2.8.2. Statistical method(s)

The statistical analysis determined the significance of the measurement variations obtained under the effect of the studied product. The comparison was on the values obtained before and at the different times of kinetics after treatment.

Data were analyzed with a paired t-test. This method tests whether the mean of sample differences between pairs of data is significantly different from the hypothetical mean, zero under the null hypothesis (H0). The alternative hypothesis (H1) was that the average difference was either greater or less than 0 (two-tailed test). Before carrying out a test, a type I error of 5% was chosen (which corresponds to the risk of rejecting a true null hypothesis).

If p0.05, H0 was rejected. There was a significant difference between before and after the

treatment.

If p>0.05, H0 was accepted, the mean was not different from 0. Data did not show a significant

difference between before and after the treatment.



2.8.3. Software used

The software used was EXCEL version 2010.

2.9. Archives

Data will be securely archived digitally and on paper for ten years from the date of dispatch of the final report. DERMSCAN Asia Paper documents relating to this study are stored maximum during one year at Dermscan before being transmitted for archiving to the ASIA WAREHOUSE COMPANY LIMITED (office located at 49, 6

th fl. Asia

Sermkij Tower Building, Silom Road soi 3, Silom, Bangrak District, Bangkok). The warehouse is at 1019/1 Chong Nonsri, Klongtoey, Klongkoey District, Bangkok. At the end of this period of ten years, the study archives will be destroyed unless otherwise stipulated in writing by the sponsor.



3. TEST FOLLOW-UP

3.1. Population

Method

Number of subjects Reason(s)

include

subjects

Subjects

who

completed

the study

Analyzed

subjects

Subjects who did

not complete the

study

Subjects excluded

from the data

analysis

Clinical scoring

21 20 20 Subject#4

untraceable on D14

- Macrophotograph

Questionnaire

3.2. Protocol non-adherences None protocol non-adherence was observed during the study

3.3. Audit / Trial monitoring visit

No monitoring visit took place



4. SUBJECTS' CHARACTERISTICS

4.1. Demographic data The table below presents the observations concerning the subjects included in the study.

SubjectLast

name

First

nameAge Comments Inclusion date End date

1 PAN KE 29 None September 25, 2014 October 9, 2014

2 KUM CH 33 None September 25, 2014 October 9, 2014

3 BOO NA 22 None September 25, 2014 October 9, 2014

(4)* (TOC)* (PI)* (33)* (Untraceable on D14)* (September 25, 2014)* (October 9, 2014)*

5 PAK NA 28 None September 25, 2014 October 9, 2014

6 CHA PO 23 None September 25, 2014 October 9, 2014

7 OUM WA 25 None September 25, 2014 October 9, 2014

8 AON SU 18 None September 25, 2014 October 9, 2014

9 LAD SA 37 Missing the tooth n° 42 September 25, 2014 October 9, 2014

10 JAN NA 20 None September 25, 2014 October 9, 2014

11 MUN KA 20 None September 25, 2014 October 9, 2014

12 SAN PI 20 None September 25, 2014 October 9, 2014

13 ANU BO 18 None September 25, 2014 October 9, 2014

14 OJA SI 18 None September 25, 2014 October 9, 2014

15 NIY CH 21 None September 25, 2014 October 9, 2014

16 BUN PA 34 None September 25, 2014 October 9, 2014

17 THA WA 29 None September 25, 2014 October 9, 2014

18 CHA PO 30 None September 25, 2014 October 9, 2014

19 KAE MU 20 None September 25, 2014 October 9, 2014

20 SIN PO 28 None September 25, 2014 October 9, 2014

21 NOI SO 24 None September 25, 2014 October 9, 2014

25 F 17 N 3 I 0

24 M 3 D 2 II 0

18 C 6 III 8

37 G 9 IV 12

1 V 0

3 VI 0

Legend: Un: untraceable

DO: subject dropped out during the study

()*: values not included in data analysis

F: female

M: male

D: dry skin

N: normal skin

C: combination skin

G: greasy skin

Maximum

SEM

CI 95%

Mean

Median

Minimum

F G IV

F N III

F C IV

F G III

F C III

F G IV

F G III

F D III

F G IV

F G IV

M G IV

F G III

F N III

F C IV

M C III

M C IV

(F)* (N)* (IV)*

F G IV

F D IV

F C IV

SexSkin

typePhototype

F N IV

4.2. Concomitant treatments

SubjectMedication

(trades name)Indication

Chlorpheniramine Allegy relief D 2 D 2

Dimenhydrinate Dizziness D 4 D 4

Chlorpheniramine Allegy relief D 11 D 11

Dimenhydrinate Dizziness D 13 D 13

5 Paracetamol Headache D 8 D 8

13 Paracetamol Headache D 2 D 2

Beginning of

treatment

End of treatment

compared to the

1



5. RESULTS

5.1. Whitening effect (clinical score)

The scoring of teeth was realized immediately after product application, individual results are presented in the Appendix 9.1.

Upper teeth -3.2 ± 0.6 -30% <0.001 Yes 90%

Lower teeth -3.5 ± 0.6 -36% <0.001 Yes 90%

(D14-D0)

% of subjects with

positive effectZone

Statistical analysis

Kinetic

(mean ± SEM)

% on the

averagep Significant

Under these study conditions, after 14 days of use product "Sparkle Coffee & Tea Drinkers’

Whitening Toothpaste", a significant whitening effect was observed on the upper teeth in 90% of

subjects (-30% on average; p <0.001) and lower teeth in 90% of subjects (-36% on average; p

<0.001).



5.2. Tolerance

The individual results of cutaneous tolerance are presented, below (relevant signs are presented in bold types):

Functional signs Physical signs

1 None None None

2 None None None

3 None None None

(4)*

5 None None None

6

Moderate burning sensation

more than 5 minutes at lower lip

after using product on D8-D11

(doubtful imputability)

None None

7 None None None

8 None None None

9 None None None

10 None None None

11 None None None

12 None None None

13 None None None

14 None None None

15 None None None

16 None None None

17 None None None

18 None None

Slight redness at gingiva between

#11 and #12 (Traumatic from hard

type of toothbrush), (without

imputability)

19 None None None

20 None None None

21 None None None

Legend: DO: dropped-out

( )*: values not included in data analysis

Subject

Signs reported by the subjects D14Clinical signs observed by the

dentist on D14

DO

According to these results, the product "Sparkle Coffee & Tea Drinkers’ Whitening Toothpaste"

was very well tolerated after 14 days of use.



5.3. Subjective evaluation questionnaire

The subjects' answers (in percentage) to the subjective evaluation questionnaire are presented in the Appendix 9.3. To be easier to read, the percentages were rounded off. The sum of these percentages may be different from 100%. In this study on D14 (n=20), one subject represents 5%. A synthesis of the answers is presented in the table below.

% of subjects

(very pleasant /

pleasant)

very

ple

asant

ple

asant

General appreciation 100% 55% 45%

Aspect 85% 35% 50%

Odor 90% 50% 40%

Taste 90% 60% 30%

Color 100% 50% 50%

Texture 95% 50% 45%

% of subjects

(very easily /

rather easily)

very

easily

rath

er

easily

Easy to used 100% 70% 30%

Easy to rinsed 100% 40% 60%

AFTER 14 DAYS OF USE

GENERAL APPRECIATION OF THE PRODUCT AND ITS PROPERTIES

% of subjects

( totally agree/

agree somewhat)

tota

lly a

gre

e

agre

e

som

ew

hat

it helps clean teeth 100% 45% 55%

it decreases bad breath 95% 45% 50%

it brings fresh breath 85% 50% 35%

it helps sparkling teeth 75% 15% 60%

your teeth look whiter 85% 35% 50%

PRODUCT EFFICACY



% of subjects (yes)

During use product,intolerance sensations 0%

Stop the treatment 0%

Stop because of an intolerance reaction 0%

% of subjects (yes)

Would like to continue use the product 90%

Would like to buy the product 90%

TOLERANCE

FUTURE USE OF THE PRODUCT



6. CONCLUSION AND SIGNATURE The primary objective of this study was to evaluate, the whitening effect, on subjects, of product “Sparkle Coffee & Tea Drinkers’ Whitening Toothpaste" after 14 days of use.

The secondary objectives of this study were to evaluate for the studied product:

its tolerance

the subjective appreciation, its organoleptic characteristics, its efficacy and its future use.

its visual effect by illustrative macrophotographs. Study condition:

Product(s) Reference: Sparkle Coffee & Tea Drinkers’ Whitening Toothpaste

Type: White paste

Study date(s) 25/09/2014 - 09/10/2014

Objective(s)

- To evaluate the whitening effect of the product. - To evaluate the tolerance of the product. - To evaluate the efficacy, tolerance and organoleptic properties of the toothpaste - To visualize its expected effect by macrophotographs

Methodology - Open and intra-individual study.

Assessment

Criteria

- Whitening effect (clinical scoring ) Kinetics D0, D14

Methodology Before / After

- Tolerance (clinical examination), - Subjective evaluation (questionnaire). - Macrophotographs

Zone Teeth.

Application

frequency

Twice-daily (morning and evening)

Studied

population

Number of analysed subjects: 20 subjects

Age: 25± 1 (average ± SEM) 18 to 37 years old.

Main inclusion criteria:

Sex: Asian male or female.

Age: between 18 years old and more.

Subject have yellow teeth grade 2-3 with VITA Toothguide 3D-MASTER

®

Subject regularly drinks coffee or tea.



Under these study conditions, after 14 days of used product "Sparkle Coffee & Tea Drinkers’

Whitening Toothpaste"

presented a significant whitening effect of upper and lower teeth as evidenced by the clinical

scoring carried by the dentist.

was very well tolerated.

a satisfaction from the majority of the subjects for :

its organoleptic properties

60%

80%

100%

Generalappreciation

Aspect Odor Taste Color Texture

100%

85%

90% 90%

100%

95%

% o

f subje

cts

GENERAL APPRECIATION AND ORGANOLEPTIC CHARACTERISTICS(very pleasant / pleasant)

0%

20%

40%

60%

80%

100%

Easy to used Easy to rinsed

100% 100%

% o

f subje

cts

ORGANOLEPTIC CHARACTERISTICS(very easily / rather easily)



its efficacy

0%

20%

40%

60%

80%

100%

it helps cleanteeth

it decreases badbreath

it brings freshbreath

it helpssparkling teeth

your teeth lookwhiter

100%95%

85%75% 85%

% o

f subje

cts

PRODUCT EFFICACY (totally agree,/ agree somewhat)

its future of use

0%

20%

40%

60%

80%

100%

Would like to continueuse the product

Would like to buy theproduct

90% 90%

% o

f subje

cts


Bangkok

November 20, 2014



7. CERTIFICATION

The study was conducted according to Helsinki Declaration (1964) and its successive updates. Data were obtained using the study protocol, current internal procedures and in the spirit of the note for guidance on Good Clinical Practice CPMP / ICH / 135 / 95, January 1997

(ref: 1 to 4 in §9.1).

Only the hard copy of the protocol transmitted by Groupe Dermscan can be considered an attestation and official. Digitally-produced or electronic documents transmitted by Groupe Dermscan are not protected by an electronic signature, according to Law n°2000-230 dates March 13, 2000 and its applicable decrees. The contents of digitally-produced or electronic documents in no means engage the responsibility of Groupe Dermscan. Any modifications are the sole responsibility of the author of the modification, whether he/she is acting for the sponsor or independently. Any partial or total reproduction of this study report requires prior written agreement from Groupe Dermscan. The quality system of the Groupe Dermscan is certified ISO 9001: 2000.

Date and signature:

Name Aeumporn SRIGRITSANAPOL, Ph.D. Function Scientific Director



8. BIBLIOGRAPHY

8.1. Regulatory

1 - ICH TOPIC E6 Note for guidance on Good Clinical Practice, CPMP / ICH / 135 / 95 January 1997. 2 - WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI Ethical Principles for Medical Research Involving Human Subjects Helsinky Declaraion (1964) and its successive updates 3 - LOI HURIET SERUSCLAT CSP Titre II – Recherches Biomédicales n°88-138 du 20 décembre 1988 modifié par la loi française 2004-806 du 9 août 2004, concernant la santé publique 4 - LOI « INFORMATIQUE ET LIBERTES » Loi n°78-17 du 6 janvier 1978 relative à l’informatique, aux fichiers et aux libertés mise à jour par la loi n°2004-801 du 6 août 2004 concernant la protection des personnes pour la déclaration à la CNIL

8.2. Data analysis

1 - Robert R. SOKAL and F. James ROHLF Biometry : the principles and practice of statistics in biological research , 3

nd edn.W.H. Freeman and company, New York (1995).



9. APPENDIX

9.1. Clinical scoring

Subjects D0 D14 D0 D14 (D14-D0)

1 72.0 66.0 12.0 11.0

2 69.0 62.0 11.5 10.3

3 88.0 85.0 14.7 14.2

4 (56.0)* DO (9.3)* DO

5 66.0 66.0 11.0 11.0

6 52.0 26.0 8.7 4.3

7 84.0 69.0 14.0 11.5

8 60.0 32.0 10.0 5.3

9 66.0 30.0 11.0 5.0

10 66.0 16.0 11.0 2.7

11 36.0 33.0 6.0 5.5

12 42.0 30.0 7.0 5.0

13 60.0 36.0 10.0 6.0

14 69.0 31.0 11.5 5.2

15 66.0 39.0 11.0 6.5

16 78.0 36.0 13.0 6.0

17 72.0 30.0 12.0 5.0

18 84.0 84.0 14.0 14.0

19 36.0 30.0 6.0 5.0

20 24.0 22.0 4.0 3.7

21 66.0 50.0 11.0 8.3

Mean 62.8 43.7 10.5 7.3

Median 66.0 34.5 11.0 5.8

Minimum 24.0 16.0 4.0 2.7

Maximum 88.0 85.0 14.7 14.2

SEM 3.8 4.6 0.6 0.8

IC 95% 7.5 9.1 1.3 1.5%p

Legend : DO: Dropped out

( )* : value not taken in the data analysis

AV: aberrante value

% of subjects show a positive effect

Upper teeth

Average of Score

-30%

90%

-3.2

-2.6

-8.3

0.0

0.6

1.2

-6.3

-4.5

-7.0

-7.0

0.0

-1.0

-0.3

-2.7

-4.7

-6.0

-8.3

-0.5

-2.0

-4.0

<0.001

Sum of Score

-1.0

-1.2

-0.5

DO

0.0

-4.3

-2.5



Subjects D0 D14 D0 D14 (D14-D0)

1 42.0 36.0 7.0 6.0

2 51.0 30.0 8.5 5.0

3 76.0 62.0 12.7 10.3

4 (36)* DO (6)* DO

5 66.0 39.0 11.0 6.5

6 64.0 44.0 10.7 7.3

7 78.0 30.0 13.0 5.0

8 42.0 39.0 7.0 6.5

9 65.0 30.0 13.0 6.0

10 66.0 27.0 11.0 4.5

11 58.0 32.0 9.7 5.3

12 42.0 30.0 7.0 5.0

13 52.0 52.0 8.7 8.7

14 84.0 39.0 14.0 6.5

15 72.0 34.0 12.0 5.7

16 78.0 55.0 13.0 9.2

17 24.0 6.0 4.0 1.0

18 84.0 81.0 14.0 13.5

19 36.0 30.0 6.0 5.0

20 24.0 24.0 4.0 4.0

21 75.0 42.0 12.5 7.0

Mean 59.0 38.1 9.9 6.4

Median 64.5 35.0 10.8 6.0

Minimum 24.0 6.0 4.0 1.0

Maximum 84.0 81.0 14.0 13.5

SEM 4.2 3.5 0.7 0.6

IC 95% 8.3 6.9 1.4 1.1%p

Legend : DO: Dropped out

( )* : value not taken in the data analysis

AV: aberrante value

Lower teeth

Average of Score

DO

-2.3

-3.5

-1.0

-6.5

-7.0

-0.5

-8.0

-3.3

-3.0

-4.5

-3.8

-6.3

-7.5

0.0

-2.0

-4.3

-5.5

0.0

-1.0

-0.5

0.6

-3.5

0.0

-8.0

-3.4

% of subjects show a positive effect 90%

<0.001

-36%

1.1

Sum of Score



9.2. Clinical examination

Pathology specify Pathology specify

1 No - satisfactory No - satisfactory

2 Presence

White lesion at

dorsal of tongue

(right side)

satisfactory No - satisfactory


(4)* (No)* (-)* (satisfactory)* DO DO DO

5 No - poor No - poor


7 Presence

Aphthous ulcer at

the lower anterior

mucosa

satisfactory No - satisfactory


9 Presence

Yellowish color at

#12 around 3 mm

diameter

satisfactory Presence

Yellowish color at

#12 around 3 mm

diameter

satisfactory







16 No - average No - average

17 No - poor No - poor

18 No - average No - average


20 No - very good No - very good

21 Presence

#21 mesial;

composite filling

discoloration

satisfactory Presence

#21 mesial;

composite filling

discoloration

satisfactory

Subjects

D0 D14

Examination of tissue

Oral hygiene

Examination of tissue

Oral hygiene

Legend : DO : Dropped out

(..)* : value not taken in the data AV: aberrant value



9.3. Subjective evaluation questionnaire

1 How many time per day, do you usually brush your teeth?

once 0%

twice 95%

three times 5%

over three times: precise……………… 0%

2 Which toothpaste do you usually use ? (if you change often or usually use more than 1 brands,

please notice the last use)

Subject Brand

1 Thipniyom

2 Sensodyne

3 Salz

(4)* DO

5 Systema

6 Glister

7 Twin Lotus

8 Colgate

9 Glister

10 Colgate

11 Glister

12 Sparkle White

13 Darlie

14 Colgate

15 Colgate

16 Parodontax

17 Darlie

18 Colgate

19 Darlie

20 Close-Up

21 Colgate

3 Do you usually use complementary oral care product or dental / oral hygiene products ?

(example: mouthwash, dental floss…..)

yes no

30% 70%

Subject Product type Brand

5 Mouthwash Listerine


9 Mouthwash Colgate

15 Mouthwash Colgate


21 Dental Floss Oral-B

USUAL ORAL HYGIENE



4 Have you ever use the tooth whitening ?

yes no

5% 95%

Subject

20

5 After use the tooth whitening, did you appreciation with this method? Why?

yes no

5% 0%

Subject Reason

20 Natural White

Method

Laser at Dental clinic

What do you think about this product?

very pleasant pleasant

neither

pleasant nor

unpleasant unpleasant

very

unpleasant

6 General appreciation 55% 45% 0% 0% 0%

7 aspect 35% 50% 15% 0% 0%

8 odor 50% 40% 10% 0% 0%

9 taste 60% 30% 10% 0% 0%

10 color 50% 50% 0% 0% 0%

11 texture 50% 45% 5% 0% 0%

12

very easily rather easily rather difficult very difficult

70% 30% 0% 0%

13

very easily rather easily rather difficult very difficult

40% 60% 0% 0%

AFTER 14 DAYS OF USE

GENERAL APPRECIATION OF THE PRODUCT AND ITS PROPERTIES

Particularly, do you find that the product used easily ?

Particularly, do you find that the product was rinsed easily ?

After use the product, what is your opinion about product efficacy?

totally agree agree somewhatdisagree totally

disagree

14 it helps clean teeth 45% 55% 0% 0%

15 it decreases bad breath 45% 50% 5% 0%

16 it brings fresh breath 50% 35% 15% 0%

17 it helps sparkling teeth 15% 60% 25% 0%

18 your teeth look whiter 35% 50% 15% 0%

PRODUCT EFFICACY



19 During use the product, did you feel any intolerance sensations (gum, soft tissue...)?

yes no

0% 100%

20 Did you stop using this product?

yes no

0% 100%

If yes, how long did you stop for?

If you stopped, what was the reason?

21 Because of an intolerance reaction?

yes no

0% 0%

22 For other reasons?

yes no

0% 0%

TOLERANCE

23 Would you like to continue to use this product?

yes no

90% 10%

24 Would you like to buy this product (regardless of the price)?

yes no

90% 10%

Subject

16 Product should have more beads.


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