Clinical trial NCT06354270
Conditions: Dentin Sensitivity
Sponsor: HALEON
Start date: 2024-04-11; Completion date: 2024-06-23
Enrollment: 115 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of this study is to confirm the clinical Dentin Hypersensitivity (DH) efficacy of a 0.454 percent (%) Stannous Fluoride (SnF2) toothpaste.

Detailed description:
This will be a single center, 8-week, randomized, controlled, examiner-blind, 2-treatment arm, parallel design, stratified (by maximum baseline Schiff sensitivity score of the two selected 'test teeth') clinical study to evaluate the anti-sensitivity efficacy of a 0.454% SnF2 toothpaste in healthy participants with DH. The clinical efficacy of the 0.454% SnF2 toothpaste (test toothpaste) will be compared with that of a reference toothpaste, a commercially available, regular fluoride toothpaste with no known anti-sensitivity properties (negative control). Sufficient participants will be screened to randomize approximately 110 participants to investigational product (approximately 55 per treatment group) and to ensure approximately 100 evaluable participants complete the entire study (approximately 50 per treatment group).

Arms: arm 1: Participants will dose the toothbrush with a ribbon of toothpaste, across the full brush head and will brush the entire dentition thoroughly for at least 1-timed minute, twice daily (morning and evening), for approximately 56 days making sure to brush the sensitive areas of the two 'test teeth' carefully first. Participants who wish to rinse after brushing will be instructed to rinse with 10 milliliter (ml) water using graduated rinsing cup provided. arm 2: Participants will dose the toothbrush with a ribbon of toothpaste, across the full brush head and will brush the entire dentition thoroughly for at least 1-timed minute, twice daily (morning and evening) for approximately 56 days. Participants who wish to rinse after brushing will be instructed to rinse with 10 ml water using graduated rinsing cup provided.
Interventions: intervention 1: Stannous fluoride toothpaste intervention 2: Regular fluoride toothpaste (Crest Cavity Protection)
Intervention descriptions: intervention 1: Toothpaste containing 0.454 % weight/weight (w/w) SnF2. intervention 2: Regular fluoride toothpaste containing 1100 parts per million (ppm) fluoride.

Protocol documents:
Prot_000.pdf: 
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C LI NI C A L P R O T O C O L  
A N  8 -W E E K, R A N D O MI Z E D, C O N T R O L L E D, E X A MI N E R -B LI N D, 
C LI NI C A L S T U D Y T O E V A L U A T E T H E E F FI C A C Y O F A S T A N N O U S 
F L U O RI D E  T O O T H P A S T E F O R T H E R E LI E F O F D E N TI N 
H Y P E R S E N SI TI VI T Y I N A P O P U L A TI O N  O F D E N TI N 
H Y P E R S E N SI TI VI T Y  S U F F E R E R S  
Pr ot o c ol N u m b er:  
3 0 0 1 0 4  
Pr o d u ct N a m e:  
0. 4 5 4  p er c e nt ( % ) w ei g ht/ w ei g ht ( w/ w ) 
st a n n o u s fl u ori d e  (S n F 2 ) t o ot h p a st e 
U nit e d St at e s ( U S) I n v e sti g ati o n al 
N e w Dr u g (I N D) N u m b er:  
N/ A  
E ur o p e a n Cli ni c al Tri al s D at a b a s e 
( E u dr a C T) N u m b er: 
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Ot h er R e g ul at or y A g e n c y 
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P h a s e:  
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p u blicl y a vaila ble versi o n
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S p o n s or I nf or m ati o n  
 
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H al e o n ( U K)  
T h e H ei g ht s ,  
B uil di n g 5 , Fir st Fl o or ,  
W e y bri d g e ,  
S urr e y ,  
K T 1 3 0 N Y ,  
U nit e d Ki n g d o m  ( U K) 
S p o n s or C o nt a ct D et ail s  
 
H al e o n  
St G e or g e s A v e n u e,  
W e y bri d g e,  
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D o c u m e nt Hi st or y  
 
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C orr e cti o n of a n a d mi ni str ati v e err or r el ati n g t o t h e D H E Q 
e n d p oi nt s a n d a n al y si s.  
S e cti o n 1. 1. S y n o p si s , O bj e cti v e s a n d E n d p oi nt s a n d S e cti o n 
3. St u d y O bj e cti v e s a n d E n d p oi nt s:  D H E Q -r el at e d e n d p oi nt s.  
S e cti o n 1 I m p a ct o n E v er y d a y Lif e ( Q 1 -3) c orr e ct e d t o  S e cti o n 1 
I m p a ct o n E v er y d a y Lif e ( Q 7-9).  
1 2. 3. 2. S e c o n d ar y E n d p oi nt A n al y s e s, D H E Q -4 8:   
S e cti o n  1 - I m p a ct o n E v er y d a y Lif e: Q 1, Q 2 & Q 3 ( s e p ar at e 
s c or e s) c orr e ct e d t o  S e cti o n  1 - I m p a ct o n E v er y d a y Lif e: Q 7, Q 8 
& Q 9 ( s e p ar at e s c or e s)  
 
 
 
 
 
 
 
A me n d me nts i nc or p orate all re visi o ns t o d ate, i ncl u di n g a me n d me nts ma de at t he re q uest of t he 
c o u ntr y healt h a ut h orit y , i nstit uti o nal re vie w b oar d (I R B), etc.   
 
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I n v e sti g at or Pr ot o c ol A gr e e m e nt P a g e 
•  I c o nfir m a gree m e nt t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol a n d a n y 
a me n d me nts acc or di n g t o t he c urre nt I nter n ati o nal C o nfere nce o n Har m o nisati o n G o o d 
Cli nical Practice (I C H G C P) g ui deli nes , a n d a p plica ble me dical de vice  re g ulati o ns. 
•  I ac k n o wle d g e t hat I a m res p o nsi ble f or o verall st u d y c o n d uct. I agree t o p ers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.  
•  I a gree t o e ns ure t hat all ass ociates, c ollea g ues a n d e m pl o yees assisti n g i n t he c o n d uct of 
t he st u d y are i nf or m e d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n place t o e ns ure site staff 
recei v e all a p pr o priate i nf or mati o n t hr o u g h o ut t he st u d y. 
•  I a gree t o c o n d uct t his st u d y i n f ull c o nf or ma nce wit h t he la ws a n d re g ul ati o ns of t he 
c o u ntr y i n w hic h t he researc h is c o n d u cte d a n d t he Declarati o n of Helsi n ki.  
 
I n v e sti g at or N a m e: 
I n v e sti g at or Q u alifi c ati o n s: 
I n v e sti g at or Si g n at ur e: 
D at e of Si g n at ur e/ A gr e e m e nt:  
D D -M m m -Y Y Y Y  
 
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E xcl usi o n Criteria  .................................................................................................. 3 0  
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Lifest yle C o nsi derati o ns  ........................................................................................ 3 2  
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Oral H y gie ne R estricti o ns  ..................................................................... 3 3  
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Dietar y a n d Al c o h ol Restr icti o ns .......................................................... 3 3  
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C o ntrace pti o n  ........................................................................................ 3 3  
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Scree n Fail ures ....................................................................................................... 3 3  
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S p o ns or’s Q ualifie d Me dical Pers o n nel  ................................................................ 3 3  
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I n cl usi o n/ E xcl usi o n Criteria ................................................................. 4 5  
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S u bject Eli gi bilit y  ................................................................................. 4 5  
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F oll o w -U p C o ntact  ................................................................................................ 5 2  
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Scree ni n g Tactile Se nsiti vit y Assess me nt  ............................................. 5 4  
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De nti ne H y perse nsiti vit y E x perie nce Q uesti o n nair e ( D H E Q -4 8)  ........ 5 6  
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Oral S oft Tiss ue ( O S T) E xa mi nati o n  .................................................... 5 9  
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Oral Har d Tiss ue ( O H T) E xa mi nati o n  .................................................. 5 9  
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E x pl orat or y A nal yses  ............................................................................ 7 5  
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Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
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Ha n dli n g of Dr o p o uts a n d Missi n g Data  .............................................. 7 7  
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I nteri m A nal ysis .................................................................................... 7 8  
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Re g ulat or y a n d Et hical C o nsi derati o ns  ................................................................. 7 9  
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Re p orti n g of Safet y Iss ues a n d Seri o us Breac hes of t he Pr ot oc ol or 
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P osti n g of I nf or m ati o n o n P u blicl y A vaila ble Cli nical Trial Re gisters  ................. 8 0  
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Pr o visi o n of St u d y Res ults t o I n vesti gat ors  ........................................................... 8 0  
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Rec or ds Rete nti o n  .................................................................................................. 8 1  
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C o n diti o ns f or Ter mi nati n g t he St u d y  ................................................................... 8 1  
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A b bre viati o ns  ......................................................................................................... 8 9  
1 5. 2  
De nti ne H y perse nsiti vit y E x perie nce Q uesti o n nair e ( E xa m ple D H E Q-4 8)  ......... 9 1  
1 5. 3  
La belle d Ma g nit u de Scales: I nt e nsit y, D urati o n, T olera bilit y & Descri pti o n 
( E xa m ple L M Ss) .................................................................................................... 9 8  
1 5. 4  
L M S Trai ni n g E xercise ( E xa m ple)  ...................................................................... 1 0 0  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9  of 1 1 3  
Li st of In -T e xt T a bl e s  
Ta ble 1 -1  
Sc he d ule of Acti vities  ........................................................................... 1 5  
Ta ble 6 -1  
Accli matizati o n/I n vesti g ati o nal T o ot h pastes  ........................................ 3 4  
Ta ble 6 -2  
S u n dr y Ite ms  ......................................................................................... 3 5  
Ta ble 1 5 -1  
A b bre viati o ns  ........................................................................................ 8 9  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0  of 1 1 3  
1  
P R O T O C O L S U M M A R Y  
1. 1  
S y n o p si s  
S u m m ar y Titl e:  
Cli nical  st u d y t o eval u ate t he a nti-se nsiti vit y effi cac y of a sta n n o us fl u ori de to ot h paste i n a 
p o p ulati o n of de nti n h y perse nsiti vit y s ufferers . 
B a c k gr o u n d a n d R ati o n al e  f or t h e St u d y: 
Sta n n o us fl u ori de ( S n F 2) has bee n i nc or p orate d i nt o oral h y gie ne pr o d ucts i n dicate d f or t h e 
relief of de nti n h y p erse nsiti vit y ( D H ) si nce t he 1 99 0s ; it pr o vi des relief fr o m D H b y t he p h ysical 
occl usi o n of de nti n t u b ules t hr o u g h c he mical preci pitati o n of sta n n o us o xi des a n d h y dr o xi des.  
Ra n d o mize d  c o ntr olle d cli nical trials  (ma n y  of  8  wee ks treat me nt d urati o n) s u p p ort t he l o n ger-
ter m a nti-se nsiti vit y effic ac y of 0. 4 5 4 % S n F 2-c o ntai ni n g  t o ot h pastes wit h t wice dail y use. T h e 
ai m of t he c urre nt 8 -w ee k st u d y is t o c o nfir m t he cli nical D H efficac y of a 0. 4 5 4 % S n F 2 
t o ot h paste. C ha n ges t o t he f or m ulati o n, c o m pare d t o t h ose pre vi o usl y i n vesti gate d  b y t he 
s p o ns or, i ncl u de re m o v al of t he o pacifi er , a d diti o n of a bl ue pi g me nt, i ntr o d ucti o n of a ne w 
fla v or f or i m pr o ve d i n-use e x perie n ce, a n d m o dificati o n of t he de ntal a brasi ve s yste m f or 
i m pr o ve d stai n re m o val a n d e n a mel p olis hi n g be nefits. N o ne of t hes e c h a n ges are e x p ecte d t o 
i m pact t he occl usi o n m o de of acti o n  ( M o A) of S n F 2 or  t he a nti-se nsiti vit y efficac y of a 0. 4 5 4 % 
S n F 2 t o ot h paste. I n a d diti o n t o de m o nstrat i n g t he efficac y of t he T est T o ot h paste , t his st u d y 
will m o nit or  t he i m pact of dail y use of a 0. 4 5 4 % S n F 2 t o ot h paste o n t he n u m ber of ‘ Se nsiti ve 
Teet h’ , a n d s u bject perce pti o n of pr o d uct be nefits .  
D H will be  assesse d at Baseli ne, a n d after 4 - a n d 8-wee ks treat me nt. At eac h p ost -Baseli ne ti me 
p oi nt, t he efficac y of t he 0. 4 5 4 %  S n F 2 t o ot h paste will be c o m pare d wit h t hat of a re g ular 
fl u ori de t o ot h paste wit h n o k n o w n a nti-se nsiti vit y efficac y ( ne gati ve c o ntr ol).  
O bj e cti v e s a n d E n d p oi nt s : 
O bj e cti v e s  
E n d p oi nt s  
Effi c a c y  
Pri m ar y  
T o de m o nstrate  t he cli nic al efficac y of a 
0. 4 5 4 %  w/ w S n F 2 t o ot h paste i n re d uci n g D H 
t o a n e va p orati ve  (air ) sti m ul us (as meas ure d 
b y Sc hiff se nsiti vit y sc ore) , c o m pare d t o  a 
ne gati ve c o ntr ol t o ot h paste, after 8  wee ks  
t wice dail y use . 
C ha n ge fr o m Baseli ne i n Sc hiff se nsiti vit y 
sc ore at Da y 5 6 ( Wee k 8 ). 
S e c o n d ar y  
T o de m o nstrate  t he cli nic al efficac y of a 
0. 4 5 4 % w/ w S n F 2 t o ot h paste i n re d uci n g D H  
t o a tactile sti m ul us (as meas ure d b y tactile 
t hres h ol d i n gra ms [ g] ), c o m pare d t o a 
ne gati ve c o ntr ol t o ot h paste, after 8  wee ks  
t wice dail y use. 
C ha n ge fr o m Baseli ne i n tactile t hres h ol d 
( g) at Da y 5 6 ( Wee k 8) . 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 1  of 1 1 3  
T o de m o nstrate  t he cli nic al efficac y of a 
0. 4 5 4 % w/ w S n F 2 t o ot h paste i n re d uci n g D H 
t o e va p orati ve (air) a n d t actile sti m uli  (as 
meas ure d b y Sc hiff se nsiti vit y sc ore  a n d 
tactile t hres h ol d (g ), res p ecti vel y), c o m pare d 
t o a ne gati ve c o ntr ol t o ot h paste, after 4 wee ks  
t wice dail y use. 
C ha n ge fr o m Baseli ne i n Sc hiff se nsiti vit y 
sc ore at Da y 2 8 ( Wee k 4 ). 
C ha n ge fr o m Baseli ne i n tactile t hres h ol d 
( g) at Da y 2 8  ( Wee k 4 ). 
T o descri be s u bject-percei ve d c ha n g es i n oral 
healt h -rel ate d q ualit y of life (O Hr Q o L ), as 
meas ure d b y t he De nti n H y perse nsiti vit y 
E x perie nce Q uesti o n nair e ( D H E Q -4 8 ), after 
4 - a n d 8 -w ee ks  t wic e dail y use of t heir 
assi g ne d i n vesti gati o nal  t o ot h paste. 
At D ay 2 8  ( Week 4) & D ay 5 6 ( Week 8): 
C ha n ge fr o m Baseli ne i n  D H E Q -4 8 
e n d p oi nts . 
Secti o n 1  
•  I m pact o n E ver y da y L ife ( Q7 -9 )  
Secti o n 2  
•  T otal S c ore ( Q 1 -3 4)  
•  I n di vi d ual D o mai n S c ores  
- Restricti o ns ( Q 1 -4)  
- A da ptati o n ( Q 5 -1 6)   
- S ocial I m pact ( Q 1 7 -2 1)   
- E m oti o nal I m pact ( Q 2 2 -2 9)   
- I d e ntit y ( Q 3 0-3 4)   
•  Gl o bal Oral H ealt h Sc ore ( Q 3 5)  
•  Effect o n Life O verall Sc ore ( Q 3 6 -3 9)  
E x pl or at or y  
T o deter mi ne  t he n u m ber of ‘ Se nsiti ve Teet h’ 
(e va p orati ve (air) se nsiti vit y o nl y ) i n t he p o ol 
of ‘ Eli gi ble Teet h’ i de ntifie d at Scree ni n g , at 
Scree ni n g, Baseli ne, a n d  after 4 a n d 8 wee ks 
t wice dail y use of assi g ne d i n vesti gati o nal 
t o ot h paste. 
At Scree ni n g, B aseli ne, D ay 2 8 ( Week 4) & 
D ay 5 6 ( Week 8): 
N u m ber of ‘ Se nsiti ve Teet h’  
Defi ne d as t he n u m ber of ‘ Eli gi ble Teet h’ 
(i de ntifie d at Scree ni n g) wit h a Sc hiff Se nsiti vit y 
Sc ore ≥ 2 .  
T o i n vesti gate s u bject-percei ve d c ha n ges i n 
D H t o a n e va p orati ve (air) sti m ul us , as 
meas ure d b y  L a belle d M a g nit u de Scales 
( L M Ss), after 4  a n d 8 wee ks  t wice dail y use 
of t heir assi g ne d i n vesti g ati o nal t o ot h paste. 
At D ay 2 8  ( Week 4) & D ay 5 6 ( Week 8): 
C ha n ge fr o m Baseli ne i n  L M S e n d p oi nts.  
•  I nte nsit y 
•  D urati o n  
•  T olera bilit y  
•  Descri pti o n  
T o i n vesti gate t he relati o ns hi p bet wee n 
s u bject res p o nses t o t he D H E Q-4 8 a n d t h e 
L M Ss at Baseli ne , a n d after 4  a n d 8 wee ks  
t wice dail y use of assi g ne d i n vesti gati o nal  
t o ot h paste. 
At B aseli ne, D ay 2 8  ( Week 4) & D ay 5 6 
( Week 8): 
•  D H E Q -4 8 e n d p oi nts, as liste d a b o ve.  
•  L M S e n d p oi nts, as liste d a b o ve.  
T o i n vesti gate t he relati o ns hi p bet wee n t he 
Sc hiff se nsiti vit y scale a n d t he L M Ss at 
Baseli ne , a n d aft er 4  a n d 8 wee ks  t wice dail y 
use of assi g ne d i n vesti gati o nal  t o ot h paste. 
At B aseli ne, D ay 2 8  ( Week 4) & D ay 5 6 
( Week 8): 
•  Mea n Sc hiff se nsiti vit y sc ore  of t he t w o 
‘ Test Teet h’. 
•  L M S e n d p oi nts, as liste d a b o ve.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 2  of 1 1 3  
T o i n vesti gate s u bject satisfacti o n wit h t heir 
assi g ne d i n vesti gati o nal  t o ot h paste f or t he 
o verall ma na g e me nt of D H, as meas ure d b y a 
N u meric Rati n g Scale ( N R S), after 8 wee ks 
treat me nt. 
At D ay 5 6  ( Week 8): 
Satisfacti o n N R S sc ore   
S af et y  
T o m o nit or  t he safet y a n d oral t olera bilit y of 
t he i n vesti gati o nal t o ot h pastes o ver 8 wee ks  
t wice dail y use . 
Treat me nt e mer ge nt a d verse e ve nts 
( T E A Es). 
 
St u d y D e si g n : 
T his will be a si n gle ce nt er, 8 -wee k, ra n d o mi ze d, c o ntr olle d, e x a mi ner -bli n d, 2 -treat me nt ar m, 
parallel desi g n, stratifie d ( b y ma xi m u m B aseli ne Sc hiff se nsiti vit y sc ore of t he t w o selecte d 
‘Test Teet h ’) cli nical st u d y t o e val uate t he a nti-se nsiti vit y efficac y of a 0. 4 5 4 %  S n F 2 t o ot h paste 
i n a D H  p o p ulati o n. T he cli nical efficac y of t he 0. 4 5 4 %  S n F 2 t o ot h paste (Test T o ot h paste ) will 
be c o m pare d wit h  t hat of a Refere nce T o ot h paste, a c o m merciall y a vaila ble, re g ular fl u ori d e 
t o ot h paste wit h n o k n o w n a nti-se nsiti vit y pr o perties ( ne gati ve c o ntr ol). 
At Scree ni n g ( Visit 1), f oll o wi n g pr o visi o n  of writte n i nf or m e d c o nse nt , suita bilit y t o 
partici pate will be re vie we d a g ai nst t he pr ot oc ol i ncl usi o n/e xcl usi o n criteria . Eli gi ble s u bjects 
will e nter a n accli matizati o n peri o d ( 1 4 -2 8 da ys ) pri or t o Baseli ne assess me nts  d uri n g w hic h 
t he y will br us h t wice d ail y ( m or ni n g a n d e ve ni n g) wit h t he accli matizati o n t o ot h paste ( a 
differe nt c o m merciall y a vaila ble, re g ular fl u ori de t o ot h paste fr o m t he Refere nce T o ot h paste ). 
At Baseli ne  ( Visit 2), eli gi bilit y t o c o nti n ue will be assesse d.  S u bjects w h o de m o nstrate t h e 
re q uire d q ualif yi n g le vels of D H at Scree ni n g ( Visit 1) a n d Baseli ne ( Visit 2) will b e  
ra n d o mize d t o st u d y treat me nt a n d i nstr ucte d t o br us h wit h t heir assi g ne d i n vesti gati o nal 
t o ot h paste t wice dail y ( m or ni n g a n d e ve ni n g) f or t he d urati o n of t he 8 -wee k treat me nt peri o d.  
D H will be assesse d at Scree ni n g  ( Visit 1) a n d Baseli ne  ( Visit 2), a n d after 2 8 - a n d 5 6 -da ys 
treat me nt ( Visits 3 a n d 4 , res pecti vel y) usi n g t w o i n de pe n de nt cli nical meas ure s: (i) tactile 
t hres h ol d ( g) f oll o wi n g a tactile sti m ul us a n d (ii) Sc hiff s e nsiti vit y sc ore f oll o wi n g a n 
e va p orati ve (air) sti m ul us .  
O ral h ealt h-rel ate d q u alit y of life ( O H R Q o L) will be m o nit ore d  o v er t h e treat me nt peri o d usi n g 
t he De nti n H y p erse nsiti vit y E x perie nce Q uesti o n naire ( D H E Q -4 8 ), c o m plete d b y st u d y 
s u bjects at Baseli ne  ( Visit 2), a n d after 2 8- a n d 5 6 -da ys treat me n t ( Visits 3 a n d 4, res pecti vel y). 
S u bject -percei ve d D H  will als o be i n v esti gate d acr oss t he 8-wee k treat me nt p eri o d usi n g f o ur 
La belle d 
Ma g nit u de Scales ( L M S s) t o ca pt ur e t he I nte nsity, D ur ati o n , T oler a bility  a n d 
Descri pti o n  of t heir res p o nse t o t he e va p orati ve (air) sti m ul us . At t he fi nal visit  ( Da y 5 6), 
s u bjects will rate t heir le vel of satisfacti o n wit h t heir assi g ne d i n vesti gati o nal t o ot h p aste f or t he 
o verall ma na g e me nt of t heir D H , usi n g a N u meri c Rati n g Scale ( N R S) .  
S afet y a n d oral t olera bilit y of t he i n vesti gati o nal t o ot h pastes will be m o nit or e d o ver t he 8 -wee k 
usa ge peri o d b y re vie w of treat me nt e mer ge nt a d v erse e v e nts ( T E A Es) . 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 3  of 1 1 3  
I n v e sti g ati o n al Pr o d u ct s : 
Descri pti o n  
Test  
T o ot h p aste  
Refere nce T o ot h p aste  
( Ne g ati ve C o ntr ol) 
N a me  
0. 4 5 4 % w/ w S n F 2 t o ot h paste 
Re g ular fl u ori de t o ot h paste 
( Crest Ca vit y Pr otecti o n *)  
M aster 
F or m ul ati o n C o de  
 
N/ A  
Fl u ori de Le vel  
1 1 0 0  parts per milli o n ( p p m ) fl u ori de†  
1 1 0 0  p p m fl u ori de ¥ 
R o ute of 
A d mi nistr ati o n  
T o pical Oral Use  
T o ot h p aste Us a ge 
I nstr ucti o ns 
D ose t he t o ot h br us h wit h a ri b b o n of t o ot h paste, acr oss t he f ull br us h hea d.  
Br us h t he e ntire de ntiti o n t h or o u g hl y 
f or at least 1-ti me d mi n ute, t wice dail y 
( m or ni n g & e ve ni n g), ma ki n g s ure t o 
br us h t he se nsiti ve areas of t he t w o 
' Test teet h' caref ull y first.   
B r us h t he e ntire de ntiti o n 
t h or o u g hl y f or at least 1 -ti me d 
mi n ute, t wice dail y ( m or ni n g & 
e ve ni n g). 
S u bjects w h o wis h t o ri nse after br us hi n g will be i nstr ucte d t o ri nse wit h 1 0 
milliliter ( ml ) water usi n g gra d uate d ri nsi n g  c u p pr o vi de d. 
*  C o m merciall y a vaila ble dail y use t o ot h paste, U S  mar ket .   
†  As S n F 2   
¥ As s o di u m fl u ori de ( Na F) 
T y p e a n d Pl a n n e d N u m b er of S u bj e ct s : 
Male a n d fe male s u bjects a ge d 1 8 -6 5  y ears (i ncl usi ve), i n g o o d ge neral a n d oral healt h , wit h a 
mi ni m u m of 2 0 nat ural teet h , a self-re p orte d hist or y of t o ot h se nsiti vit y a n d cli nicall y c o nfir me d 
D H will be e nr olle d . Q ualif yi n g  s u bjects wit h  at least t w o teet h wit h cli nical l y c o nfir me d D H , 
(tactile t hres h ol d ≤ 2 0 g a n d Sc hiff se nsiti vit y sc ore ≥ 2  at b ot h Scree ni n g a n d Baseli ne  visits ) 
will be ra n d o mize d t o treat me nt .  
S ufficie nt s u bjects  will b e scree ne d a n d e nt ere d i nt o t he accli matizati o n peri o d  t o ra n d o miz e 
a p pr o xi matel y 1 1 0  s u bjects t o i n vesti gati o nal pr o d uct  (a p pr o xi matel y 5 5  p er treat me nt gr o u p ) 
a n d so e ns ure a p pr o xi matel y 1 0 0  e val ua ble s u bjects c o m plete t he e ntire st u d y (a p pr o xi matel y 
5 0  per treat me nt gr o u p ), all o wi n g f or a p pr o xi matel y 1 0 % dr o p o uts.  
St ati sti c al A n al y si s S u m m ar y:  
A m o difie d I nte nt -T o -Treat ( mI T T) p o p ulati o n ( all ra n d o mize d s u bjects w h o recei ve at least 
o ne d ose of i n vesti gati o nal pr o d uct  a n d c o m plete at le ast o n e-p ost Baseli ne D H efficac y 
assess me nt ) will be use d f or t he efficac y a n al yses . Si g nifica nce testi n g will be c o n d u cte d at t he 
t w o-si de d 5 % si g nifica nce le vel. 
Sc hiff se nsiti vit y sc ore  a n d tactile t hres h ol d ( g) will be deri ve d as t he mea n  sc ore/val u e  of  t he 
t w o ‘ Test Teet h’ (selecte d at Baseli ne). C ha n ge fr o m Baseli ne will be deri ve d f or eac h  
i n di vi d ual to o t h first bef ore cal c ulati n g mea n  c h a n ge f or t he t w o ‘ Test Teet h’. 
T he pri mar y e n d p oi n t, cha n ge fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore at Da y 5 6 , will be 
a nal yze d usi n g a Mi xe d M o del wit h Re peate d Meas ures ( M M R M) wit h i n vesti gati o nal pr o d uct, 
visit a n d [i n vesti gati o nal pr o d uct x visit] i nteracti o n as fi xe d effects, a n d Baseli ne Sc hiff 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 4  of 1 1 3  
sensiti vit y sc ore as c o variate. S u bject will be i ncl u de d as a re peate d meas ure wit h u nstr uct ur e d 
c o varia n ce matri x. Ke n war d R o gers de grees  of free d o m a p pr oac h will be a p plie d . T he 
differe n ce bet w ee n t he least s q uare mea n c ha n ges fr o m B aseli ne f or t he Test T o ot h paste 
c o m pare d t o R efere nce T o ot h paste ( ne g ati ve c o ntr ol) at Da y 5 6  fr o m t he M M R M wi ll be 
prese nte d , al o n g wit h  t he t w o-si de d p-val ue a n d 9 5 % c o n fi de n ce i nter vals ( CIs). 
T he k e y sec o n dar y  e n d p oi nt, c ha n ge fr o m Baseli ne i n tactile t hres h ol d ( g) at Da y 5 6, will be 
a nal yse d usi n g t he sa me M M R M as t he pri mar y e n d p oi nt b ut wit h Baseli ne tactile t hres h ol d ( g) 
as c o variate . I n a d diti o n, t he ma xi m u m B aseline S c hiff se nsiti vit y sc ore of t he t w o  ‘ Test T eet h’ 
( 2 or 3) will be fitte d as a fi xe d effect. T he differe nce bet w ee n t he least s q uare mea n c ha n ges 
fr o m Baseli ne f or t he Test T o ot h paste c o m pare d t o Refere n ce T o ot h paste ( ne gati ve c o ntr ol) at 
Da y 5 6 fr o m t he M M R M will be prese nte d, al o n g wit h t he t w o -si de d p-val ue a n d 9 5 %  CIs .  
S u m mar y statistics ( mea n, me dia n, sta n dar d err or (S E ), sta n dar d de viati o n ( S D), mi ni m u m, 
ma xi m u m) will be prese nte d f or eac h  Sc hiff s e nsiti vit y sc ore a n d tactile t hres h ol d ( g) o utc o me 
varia ble at eac h assess me nt ti me p oi nt. Ra w mea ns ( ± S E) of Sc hiff se nsiti vit y sc ore  a n d tactile 
t hres h ol d ( g) at e ac h assess me nt ti me p oi nt will be pl otte d b y treat me nt gr o u p. 
1. 2  
S c h e d ul e of A cti viti e s  
T h e Sc he d ule of A cti vities  (Ta ble 1 -1 ) pr o vi des a n o ver vie w of t he s u bject visits , st u d y 
pr oce d ures  a n d assess m e nts . T he i n vesti gat or m a y sc he d ule a d diti o nal ( u n pla n ne d) visits  t o 
co n d uct a d diti o nal e val u ati o ns or assess me nts re q uire d t o pr otect t h e well -bei n g of t he s u bject.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 5  of 1 1 3  
T a bl e 1 -1  
S c h e d ul e of A cti viti e s  
 
Pr oce d ure/ Assess me nt  
St u d y Visits  
Visit 1  
Scree ni n g  
 
Visit 2  
D a y 0  
B aseli ne  
Visit 3  
D a y 2 8  
( ± 2 da ys)  
Visit 4  
D a y 5 6  
( ± 3  da y s)   
I nf or me d C o nse nt 
X  
Accli matizati o n Peri o d ( 1 4 -2 8 da ys ) 
 
 
 
De m o gra p hics  
X  
 
 
 
Re vie w S u bject’s Oral Care Pr o d ucts  
X  
 
 
 
Re vie w Me dical Hist or y & C urre nt/ Pri or C o nc o mita nt Me dicati o n/ Treat me nt  1 
X  
 
 
 
Re vie w C ha n ges i n Healt h & Me dicati o ns/ Treat me nts  1 
 
X  
X  
X  
Ret ur n Accli matizati o n T o ot h paste, T o ot h br us h & Diar y  2 
 
X  
 
 
Ret ur n I n vesti gati o nal T o ot h paste, T o ot h br us h & Diar y  2 
 
 
 
X  
C o m plia nce C hec ks 2 
 
X  
X  
X  
S u bject -C o m plete d D H E Q 3 
 
X  
X  
X  
S u bject -C o m plete d L M S Trai ni n g E xercise  
X  
 
 
 
Oral S oft Tiss ue ( O S T) E xa mi nati o n  
X  
X  
X  
X  
Oral Har d Tiss ue ( O H T) E xa mi nati o n  
X  
 
 
X  
Eli gi ble Teet h Assess me nts ( De ntiti o n E xcl usi o ns, E r osi o n/ A brasi o n/ Recessi o n [ E A R], 
M o difie d Gi n gi val I n de x [ M GI], T o ot h M o bilit y)  
X  
 
 
 
Q ualif yi n g Cli nical Assess me nt of Tactile Se nsiti vit y 4 
X  
X  
 
 
Q ualif yi n g Cli nical Assess me nt of E va p orati ve ( Air) Se nsiti vit y  ( Sc hiff se nsiti vit y sc ore) 5   
X  
X  
 
 
S u bject -Percei ve d E va p orati ve ( Air) Se nsiti vit y ( L M Ss) 6 
 
X  
 
 
Cli nical Assess me nt of E va p orati ve ( Air) Se nsiti vit y of  t he Re mai ni n g ‘ Eli gi ble  Teet h’  
I de ntifie d at Scree ni n g 5  
 
X  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 6  of 1 1 3  
Pr oce d ure/ Assess me nt  
St u d y Visits  
Visit 1  
Scree ni n g  
 
Visit 2  
D a y 0  
B aseli ne  
Visit 3  
D a y 2 8  
( ± 2 da ys)  
Visit 4  
D a y 5 6  
( ± 3  da y s)   
Cli nical E xa mi ner Selects T w o ‘ Test Teet h’ ( Q ualif yi n g S u bjects O nl y) 7 
 
X  
 
 
Re vie w I ncl usi o n/ E xcl usi o n Criteria  
X  
X  
 
 
C o nfir m S u bject Eli gi bilit y / Q ualificati o n 
X  
X  
 
 
Dis pe nse Accli matizati o n T o ot h paste, T o ot h br us h, Ti mer , Ri nsi n g C u ps & Diar y  
X  
 
 
 
S u per vi se d Br us hi n g wit h Accli matizati o n T o ot h paste  
X  
 
 
 
Stratificati o n/ Ra n d o mizati o n  
 
X  
 
 
Dis pe nse I n vesti gati o nal T o ot h paste, T o ot h br us h , Ri nsi n g C u ps & Diar y  
 
X  
X 8 
 
S u per vi se d Br us hi n g wit h I n vesti gati o nal T o ot h paste  
 
X  
 
 
Cli nical Assess me nt of Tactile Se nsiti vit y: T w o ‘ Test Teet h’ O nl y  4  
 
 
X  
X  
Cli nical Assess me nt of E va p orati ve ( Air) Se nsiti vit y  ( Sc hiff se nsiti vit y sc ore): Assess t he 
T w o ‘ Test Teet h’ First,  the n t he Re mai ni n g ‘ Eli gi ble  Teet h’  Ide ntifie d at Scree ni n g  5 
 
 
X  
X  
S u bject -Percei ve d E va p orati ve ( Air) Se nsiti vit y ( L M Ss): T w o ‘ Test Teet h’ O nl y 6 
 
 
X  
X  
S u per vise d Br us hi n g wit h I n vesti gati o nal T o ot h paste  
 
 
 
X  
 
Satisfacti o n wit h Treat me nt: S u bject -C o m plete d N R S  
 
 
 
 
X  
St u d y C o ncl usi o n  
 
 
 
 
X  
M o nit or A d verse E ve nts ( A Es)  a n d Me dical De vice I nci de nts 9 
X  
 
X  
X  
X  
F O O T N O T E S :  
1.  Fe male s u bjects of c hil d -beari n g p ote ntial s h o ul d be as ke d t o c o nfir m pre g na nc y stat us at eac h visit. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 7  of 1 1 3  
2.  S u bjects will be re q uire d t o bri n g t heir st u d y s u p plies ( mi n us ti mer & ri nsi n g c u ps) t o e ver y visit .  
Perf or m vis ual c hec k of ret ur ne d st u d y s u p plies, re vie w diar y & e val uate c o m plia nce .  
Visit 2:  C hec k c o m plia nce wit h use of accli matizati o n t o ot h paste .  
Visit 3 & Visit 4:  C hec k c o m plia nce wit h use of i n vesti gati o nal t o ot h paste .  
Visits 2 -4:  C hec k c o m plia nce wit h Lifest yle G ui deli nes/ Me dicati o n re q uire me nts.  
3.  D H E Q -4 8  m ust be c o m plete d  pri or t o t he O S T e xa mi nati o n  a n d cli nical assess me nts .  
Visit 2: C o m plete all q uesti o ns .  
Visits 3  & 4 : C o m plete Secti o n 1 , Q uesti o ns 7 -9  & Secti o n 2 , all q uesti o ns .  
4.  T actile T hres h ol d Assess me nt s: Visits 1 -2:  Ma xi m u m f orce 2 0 g ( Scree ni n g a n d Baseli ne); Visits 3 -7:  Ma xi m u m f orce 8 0 g.  
5.  E v a p or ati ve ( air) se nsiti vit y ( Sc hiff se nsiti vit y sc ore) s h o ul d be assesse d after  tactile se nsiti vit y, e ns ure  mi ni m u m 5 -mi n ute  dela y  after  t he last tactile 
assess me nt bef ore t he first e va p orati ve (air) assess me nt f or t o ot h rec o ver y.  
Visit 1  (Scree ni n g) : A ssess e va p orati ve (air) se nsiti vit y f or all teet h wit h a Scree ni n g  tactile t hres h ol d ≤ 2 0 g.  
Visit 2  ( Baseli ne): First  assess e va p orati ve (air) se nsiti vit y f or all ‘Eli gi ble Teet h ’ i de ntifie d at Scree ni n g wit h  a Baseli ne  tactile t hres h ol d of ≤ 2 0 g , t he n 
assess  t he re mai ni n g ‘Eli gi ble Teet h ’ (i.e., t he re mai ni n g teet h fr o m t he p o ol of ‘Eli gi ble Teet h ’ i de ntifie d at Scree ni n g, wit h a  Baseli ne  tactile 
t hres h ol d > 2 0 g ).  
Visit 3 ( Da y 2 8) & Visit 4 ( Da y 5 6): First  assess e va p orati ve (air) se nsiti vit y f or t he t w o ‘Test Teet h ’ first, t he n assess  t he re mai ni n g ‘Eli gi ble Teet h ’ 
i de ntifie d at Scree ni n g (e xcl u di n g t he t w o ‘ Test Teet h’). 
‘ Eli gi ble Teet h’ = T eet h wit h  n o de ntiti o n excl usi o ns w hic h met E A R, M GI & m o bility  criteri a, wit h  Scree ni n g t actile t hres h ol d ≤ 2 0 g &  Scree ni n g Sc hiff se nsitivity sc ore ≥ 2.  
6.  Visit 2 ( Baseli ne): C o m plete 4 L M Ss (I nte nsity, D ur ati o n, T oler a bility & Descri pti o n) f or eac h t o ot h wit h a Baseli ne  Sc hiff se nsiti vit y sc ore ≥ 2  o nl y , 
i m me di atel y after  t he Baseli ne Sc hiff se nsiti vit y sc ore has bee n rec or de d  f or t hat t o ot h. 
Visit 3 ( Da y 2 8) & Visit 4 ( Da y 5 6): C o m plete 4 L M Ss  f or eac h ‘ Test To o t h’, i m me di atel y after  its Sc hiff se nsiti vit y sc ore has bee n rec or de d. 
7.  Selecte d ‘ Test Teet h’ s h o ul d be i n differe nt  q ua dra nts , wit h t he re q uisite q ualif yi n g le vels of D H  at b ot h Scree ni n g ( Visit 1) a n d  Baseli ne ( Visit 2) , i.e., tactile 
t hres h ol d ≤ 2 0 g a n d  Sc hiff se nsiti vit y sc ore ≥ 2.  
8.  Visit 3:  S u p pl y ne w diar y o nl y . 
9.  A Es , a n d t heref ore all seri o us a d verse e ve nts ( S A Es) will be rec or de d  fr o m i m me diatel y after si g ni n g t he i nf or me d c o nse nt f or m (I C F) u ntil 5 da ys after  t he 
last use of i n vesti gati o nal t o ot h paste. I nci de nts will be rec or de d fr o m first t o last use of t he me dical de vice (t he ma n ual t o ot h br us h use d t o a p pl y t he 
accli matizati o n a n d i n vesti gati o nal t o ot h pastes).
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 8  of 1 1 3  
2  
I N T R O D U C TI O N 
De nti n h y perse nsiti vit y  ( D H) is a c o m m o n de ntal c o n diti o n; pre vale nce is re p orte d t o ra n g e 
fr o m 3 % t o 5 7 % i n t he ge neral p o p ulati o n ( A d d y, 2 0 0 2 ). It is t y picall y ass ociate d wit h t h e 
e na mel w ear a n d/ or gi n gi val recessi o n e x perie n ce d i n a d ult h o o d ( b ot h of w hic h l ea d t o 
e x p osure of  t he u n derl yi n g de nti n) (West, 2 0 2 2 ) a n d has b ee n descri be d as a ‘s h ort, s har p pai n 
arisi n g fr o m e x p ose d de nti ne i n res p o nse t o sti m uli t y picall y t her mal, e va p orati ve, t actile, 
os m otic or c he mical a n d w hic h ca n n ot be ascri b e d t o a n y ot her f or m of d e nt al defect or diseas e ’ 
(A d d y, 1 9 8 5 ; Ca n a dia n A d vis or y B oar d o n De nti n H y perse nsiti vit y, 2 0 0 3 ). Cli nicall y, t h e 
pri mar y dia g n osis of t o ot h h y perse nsiti vit y is ma de w he n a p atie nt c o m pl ai n s of brief, well -
l ocalize d p ai n res ulti n g fr o m t her mal (t y picall y c ol d), tactile, or os m otic sti m ulati o n of e x p os e d 
de nti n i n t he a bse nce of a n y ot her de ntal  pat h ol o g y ( A d d y, 2 0 0 2 ).   
T he m ost wi del y acce pte d t he or y t o e x plai n  D H  is t he h y dr o d y na mic t he or y, first descri be d i n 
t he literat ure b y G ysi (G ysi, 1 9 0 0 ) a n d e x p a n de d o n later b y Brä n nstr ö m (Brä n nstr ö m, 1 9 6 3 ). 
T he h y dr o d y n a mic t he or y pr o p oses t hat a n e xter nal s ti m ul us, s uc h as a te m perat ur e (c ol d or  
h ot ) or os m otic differe nti al , or tactile press ur e , a p plie d t o e x p ose d de nti n disr u pts t he m o ve me nt 
of fl ui d wit hi n de nti n t u b ules. T his disr u pti o n is t h o u g ht t o sti m ulate mec ha n orece pt ors 
ass ociate d wit h o d o nt o blast pr ocesses a n d ner ve fi bers l ocate d near t he cer vical p ul p-de nti n 
c o m ple x, tri g geri n g t he s h ort, s har p pai n c haract eristic of D H  (A bsi, 1 9 8 7; Pas hle y, 1 9 9 4 ). 
Ot her me c ha nis ms f or D H  ha v e b ee n pr o p ose d, h o we ver o nl y t he h y dr o d y na mic t he or y 
e x plai ns t he para d o xical fi n di n g t hat t he de nti n -e na mel j u ncti o n is se nsiti ve  t o e xter nal sti m uli, 
e ve n t h o u g h t he de nti n itself a p pears n ot t o be hi g hl y i n ner vate d ( Da ba b n e h, 1 9 9 9 ). T he t he or y 
is als o c o nsiste nt wit h t h e o bser vati o n t hat tr eat me nt of h y p erse nsiti ve d e nti n wit h a ge nts t hat 
eit her occl u de t he e x p ose d de nti n t u b ules or re d uce mec ha n orece pt or/ ner ve acti vit y , res ults i n 
a re d ucti o n i n t he disc o mf ort or  pai n o bser ve d cli nicall y ( West, 2 0 1 4 ).  
T wice dail y use of a n a nti -h y perse nsiti vit y  t o ot h paste is ge nerall y rec o m me n de d as t he first li ne 
treat me nt f or D H ; treat me nt m o dalities are base d o n eit her de nti n t u b ule occl usi o n or i ntra-
de ntal ner ve d ese nsitizati o n ( A d d y, 2 0 0 2 ; Pereira, 2 0 1 5 ). S n F 2 is o ne of t he m ost c o m m o nl y 
e m pl o ye d t u b ule occl u di n g a ge nts use d i n O ver -t he-C o u nter ( O T C)  t o ot h pastes a n d has bee n 
wi del y mar kete d as a t o ot h dese nsitizer i n O T C  dail y use t o ot h pastes ( 0. 4 5 4 % w/ w  S n F 2) i n t he 
U S f or ma n y years. T he sta n n o us (ti n [II]) i o n reacts wit h water a n d p h os p hate mi nerals f o u n d 
i n t he sali va a n d de nti n t u b ule fl ui d t o ra pi dl y f or m i ns ol u ble de p osits o ver t he s urface of t he 
de nti n ( Ma ki n, 2 0 1 3 ; Miller, 1 9 9 4 ). T hese  d e p o sits act as barriers t o e xter nal sti m uli f or D H, 
p h ysicall y bl oc ki n g or narr o wi n g t he o pe ni n gs of e x p ose d t u b ules, t here b y re d uci n g de nti n fl ui d 
m o ve me nt a n d decreasi n g t he a bilit y of t he sti m ul us t o acti vate t he i ntra-de ntal ner ves a n d 
e v o ke a p ai n res p o n se (A d d y M, 2 0 0 2; B ur nett G R, 2 0 1 3 ; Miller S, 1 9 9 4 ; Par ki ns o n , 2 0 1 1 ).  
T he use of S n F 2 as a t hera pe utic a ge nt i n oral care pr o d ucts dates bac k t o t he 1 9 5 0s w he n it was 
first use d as a n a nti-caries a ge nt i n de ntifrices ( Ma ki n, 2 0 1 3 ). N u mer o us cli nical st u dies 
re p orte d i n t he scie ntific literat ure si nc e t he n ha v e esta blis he d t he safet y a n d cli nical efficac y 
of S n F 2, n ot o nl y as a n a nti-caries acti ve, b ut als o as a n  a nti-D H a n d a nti -pla q ue/ gi n gi vitis a ge nt.  
Citize ns Petiti o ns were s u b mitte d b y Pr octer & Ga m ble i n 2 0 0 6 , a n d Gla x o S mit h Kli ne 
C o ns u mer Healt hcare ( G S K C H n o w Hal e o n ) i n 2 0 1 2 , re q u esti n g t he F D A t o re o p e n t he Oral 
Healt h Care Dr u g Pr o d ucts T F M a d mi nistrati ve  rec or d a n d re vie w ne w effi cac y d ata s u p p orti n g 
t he recl assificati o n of S n F 2 ( 0. 4 5 4 % w/ w ) as a Cate g or y I s afe a n d effecti ve t o ot h se nsitizer, i n 
a d diti o n t o its rec o g niz e d a nti -caries G R A S E stat us. T he o utc o me of t h e F D A re vi e w of t hese 
citize ns petiti o ns a n d t h e fi nalizati o n of t he Oral Healt h Care Dr u g Pr o d uct m o n o gra p h is 
pe n di n g.     
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 9  of 1 1 3  
2. 1  
B a c k gr o u n d  a n d R ati o n al e  f or St u d y  
Sta n n o us fl u ori de ( S n F 2) has bee n i nc or p orate d i nt o oral h y gie ne pr o d ucts i n dicate d f or t h e 
relief of D H si nce t he 1 9 9 0s (Sc hiff, 2 0 0 6 ); it pr o vi des relief fr o m D H b y t he occl usi o n of t he 
de nti n t u b ules via t he  c he mical preci pitati o n of i ns ol u ble ti n salts o n t o t he s urface of e x p ose d 
de nti n  (Ma ki n, 2 0 1 3 ; Miller, 1 9 9 4 ). Hale o n  (t he s p o ns or of t his st u d y) h as mar kete d  0. 4 5 4 % 
S n F 2 t o ot h pastes i n dicate d f or D H relief i n t he U S si nce 2 0 1 3 . 
N u mer o us cli nical st u dies of 4 -2 4  wee ks treat me nt d urati o n  (t y pically 8 wee ks ) d e m o nstrat e 
t he l o n git u di nal a nti-se nsiti vit y efficac y of S n F 2-c o ntai ni n g f or m ulati o ns  (e. g., A mi ni, 2 0 1 9 ; 
C ha k nis, 2 0 1 1 ; Creet h, 2 0 2 1 ; Da y, 2 0 1 0 ; D u, 2 0 1 1 ; Gall o b, 2 0 1 7 ; Haze n, 1 9 6 8 ; He, 2 0 1 4 [a]; 
He, 2 0 1 9 ; Hi nes, 2 0 1 9 ; Ki m, 2 0 2 1 ; Mas o n, 2 0 1 9 ; Ni, 2 0 1 0 ; Ni, 2 0 1 1 ; Par ki ns o n, 2 0 1 3 ; 
Par ki ns o n, 2 0 1 5 [a]; Sc hiff, 2 0 0 5 ; Sc hiff, 2 0 0 6 ; S har ma, 2 0 1 0 ; Vi na y a, 2 0 1 0 ). Re vie ws  a n d 
p o ole d/ meta -a nal ys es of ra n d o mize d c o ntr olle d trials als o re p ort S n F2-c o n tai ni n g t o ot h pastes 
t o be cli nicall y effecti ve i n t he treat me nt of D H (Ba da d he, 2 0 2 3 ; Bae, 2 0 1 5 ; Creet h, 2 0 1 9 [a]; 
Creet h, 2 0 1 9 [b ]; E xter kate 2 0 2 2 ; Gerlac h, 2 0 1 7 ; Ka n o uté, 2 0 2 2 ; K o nra dss o n, 2 0 2 0 ; Marti ns, 
2 0 2 0 ; Marti ns, 2 0 2 2 ; Mart o, 2 0 2 0 ; P ollar d, 2 0 2 3 ; West, 2 0 1 5 ; West, 2 0 1 9 ; West, 2 0 2 1 ; Ya n g, 
2 0 1 6 ). T he  l o n g er-ter m cli nical efficac y of t he s p o ns or’s mar k ete d  0. 4 5 4 % S n F 2 t o ot h pastes is 
s u p p orte d b y t w o 8-wee k D H st u dies (Par ki ns o n, 2 0 1 3; Par ki ns o n, 2 0 1 5 [a]).  
T he  ai m of t his 8 -w ee k  cli nical st u d y is t o c o nfir m t he l o n git u di nal a nti-se nsiti vit y efficac y  of 
a 0. 4 5 4 % S n F 2 t o ot h paste. C ha n ges t o t he f or m ulati o n, c o m pare d t o t h ose pre vi o usl y 
i n vesti gate d, i ncl u de re m o val of t he o p acifier, a d diti o n of a bl ue pi g me nt, a n e w fl a v or f or 
i m pr o ve d i n-us e e x perie n ce, a n d m o dificati o n of t he de ntal a brasi ve s yste m f or i m pr o ve d stai n 
re m o val a n d e n a mel p olis hi n g be nefits. N o ne of t hese c ha n g es are e x p ecte d t o i m pact t he M o A  
of S n F 2 ( de nti n t u b ule occl usi o n) or  t he a nti-se nsiti vit y efficac y of a 0. 4 5 4 % S n F 2 t o ot h paste. 
Cli nical D H assess me nts will be c o m plete d at Baseli ne, a n d after 2 8 - a n d 5 6 -da ys treat me nt. At 
eac h p ost -Bas eli ne assess me nt  ti me p oi nt, t he efficac y of t h e 0. 4 5 4 % S n F2 t o ot h paste will be 
c o m pare d wit h t hat of a re g ular fl u ori de t o ot h paste wit h  n o k n o w n a nti -se nsiti vit y efficac y 
( ne gati ve c o ntr ol). 
2. 2  
B e n efit/ Ri s k A s s e s s m e nt  
S n F 2 ha s bee n i ncl u de d as a t hera p e utic a ge nt (a nti-caries) i n dail y use t o ot h pastes si nce t he 
1 9 5 0s  (Ma ki n, 2 0 1 3 ). N u mer o us cli nical st u dies re p orte d i n t he s cie ntific literat ure si nc e t he n 
ha ve esta blis he d t he safet y a n d cli nical efficac y of S n F 2, n ot o nl y f or a nti-caries, b ut als o f or 
a nti-h y perse nsiti vit y  a n d a nti -pla q ue/ a nti -gi n gi vitis i n dicati o ns.  
S n F 2 is i ncl u de d i n t he i n vesti gati o nal t o ot h paste at 0. 4 5 4 % w/ w t o pr o vi de relief fr o m t he p ai n 
a n d disc o mf ort of D H.  T he f or m ulati o n  c o ntai ns o nl y i n gre die nts wit h a hist or y of safe use i n 
oral healt hcare pr o d ucts  a n d is desi g ne d f or d ail y use b y D H s ufferers . C o m plete safet y 
i nf or mati o n f or t his 0. 4 5 4 % S n F 2 t o ot h paste ca n be f o u n d i n t he si n gle refere n ce safet y 
d oc u me nt  f or t his pr o d uct, w hic h f or t his st u d y is t he I n vesti gat or’s Br oc h ure  (I B).  
N u mer o us c li nic al st u dies s u p p ort t he l o n ger-ter m cli nical efficac y a n d safet y of 0. 4 5 4 % S n F 2 
t o ot h pastes i n re d uci n g t he pai n a n d disc o mf ort  ass ociate d wit h D H f oll o wi n g e x p os ure t o a 
ra n ge of acce pt e d sti m uli (t her mal a n d tactile  (H olla n d, 1 9 9 7 )), s ee Secti o n 2. 1 . I n these st u dies , 
0. 4 5 4 % S n F 2 t o ot h pastes w ere a p plie d t wice d ail y  b y t o ot h br us hi n g f or 4 t o 2 4 wee ks (t ypicall y 
8 wee ks)  a n d were w ell t olerate d .  
Re vie w of t he s p o ns or’s i nter ve nti o nal cli nical st u dies i n v ol vi n g 0. 4 5 4 % S n F2 t o ot h pastes has 
n ot i de ntifie d a n y si g nifi ca nt safet y iss ues.  As p er t he s p o ns or's Gl o b al Data S heet ( G D S) f or 
0. 4 5 4 % S n F 2 t o ot h paste, w hic h is c o nti n u o usl y mai ntai ne d b y t he o n g oi n g p ost-mar keti n g 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 0  of 1 1 3  
s ur veilla nce acti vities, t he fre q ue n c y of a d verse reacti o ns is rare or ver y rare. T he s p o ns or 
c o nsi ders t he o v erall be n efit -ris k pr ofile of 0. 4 5 4 % S n F 2 t o ot h paste t o be fa v ora ble w he n us e d 
as directe d i n its i nte n de d tar get treat me nt p o p ulati o n.  
T he A ccli matizati o n a n d Refere n ce T o ot h pastes will be dail y use, re g ular fl u ori de t o ot h pastes  
(t w o differe nt pr o d ucts) ; eac h will be c o m merci all y a vaila ble i n t he U S. T h e i n gre die nts liste d 
o n b ot h c o m mercial pac ks ha ve a hist or y of safe use i n oral healt hcare pr o d ucts. T he usa g e 
i nstr ucti o ns gi ve n t o st u d y s u bjects will be c o nsiste nt wit h t he i nstr ucti o ns o n t he c o m mercial 
pac ks. N o s pecific cli nical be nefits, ris ks or a d verse effects are a ntici pat e d fr o m t heir use i n t his 
st u d y. 
T he ma n ual t o ot h br us h ( Oral B Se nsi-S oft t o ot h br us h) t o be use d t o a p pl y t he st u d y t o ot h pastes 
b y t o ot h br us hi n g is a me dical de vice i n t he U S. D e vice usa g e i nstr ucti o ns will be  c o nsiste nt 
wit h its c o m mercial pac k i nstr ucti o ns.  N o s pecific  cli nical be nefits , ris ks or a d verse de vice 
effects are a ntici pate d  fr o m its use i n t his cli nical st u d y. 
Base d o n c urre ntl y a vail a ble data, t he i n v esti gati o nal a nd  accli matizati o n t o ot h paste s, a n d t he 
ma n ual t o ot h br us h ( me dical de vice ) t o be use d t o a p pl y t he m, are c o nsi d ere d safe f or use u n der 
t he c o n diti o ns of t he pr o p ose d cli nical st u d y.  
2. 3  
 M e c h a ni s m of A cti o n/I n di c ati o n  
De nti n t u b ule occl u di n g a ge nts, s uc h as sta n n o us salts, are u n d erst o o d t o act b y p h ysicall y 
bl oc k i n g or narr o w i n g t he e x p ose d e n ds of de nti n t u b ules, t here b y re d u ci n g de nti nal fl ui d 
m o ve me nt  i n res p o nse t o a n e xter n al sti m ul us f or D H a n d  decreasi n g t he eff ect of t h at sti m ulus  
(Ma ki n, 2 0 1 3 ).  
•  I n t he pres e nce of water (sali va) a n d sali va-deri ve d i o ns , sta n n o us (S n  [II]) i o ns ra pi dl y 
o xi dize t o sta n nic ( S n  [I V]) i o ns a n d h y dr ol yze t o f or m i ns ol u ble ti n c o m p o u n ds 
( h y dr o xi des, o xi des, p hos p hates a n d fl u or o p h os p h ates) ( Ma ki n, 2 0 1 3 ).  
•  T he c he mical preci pitati o n of i ns ol u ble ti n salts o nt o t he s urface of e x p os e d de nti n  a n d 
wit hi n e x p ose d d e nti n t u b ules ser ves t o o ccl u de pate nt de nti n  t u b ules (B ur nett , 2 0 1 3; 
Earl, 2 0 1 3 ), t here b y pr o vi di n g relief fr o m D H.  
•  S n  [II] i o ns ha ve bee n s h o w n i n vitr o t o f or m i ns ol u ble preci pitates o n t he d e nti n s urfac e 
a n d wit hi n e x p ose d de nti n t u b ules (Elli n gse n, 1 9 8 7 ; Miller, 1 9 9 4 ; Par ki ns o n, 2 0 1 1 ; S hi,  
2 0 1 2 ; W hite, 2 0 0 7 ; Zsis ka, 2 0 1 2 ).  
T he s mear la yer is a n a m or p h o us de p osit of or g a nic ( h y dr o x ya p atite)  a n d i n or ga nic (e. g., fr o m 
t o ot h pastes/t o ot h br us hi n g or de ntal tr eat me nts s uc h as pr o p h yl a xis) matt er w hic h c o vers t he 
s urface of e x p ose d de nti n a n d pr o vi des a de gree of nat ural occl usi o n of  pate nt de nti n t u b ules. 
T he s mear la yer is v ul nera ble t o aci d c halle n ge ( e. g., fr o m di etar y aci ds). Sta n no us i o ns are 
k n o w n t o pr otect t he s mear la yer fr o m aci d diss ol uti o n b y i nteracti n g wit h h y dr o x ya patite t o 
preci pitate aci d -resista nt la yers of sta n n o us o xi d e, h y dr o xi de, p h os p hate or fl u or o p h os p hate 
(B ur nett, 2 0 1 3 ).  
T o ma xi mise deli ver y of bi oa vaila ble sta n n o us (ti n [II]) i o ns t o t he oral ca vit y, S n F2 t o ot h pastes 
are oft e n ‘sta bilize d’ b y re d uc i n g t he p H  of t he f or m ulati o n , b y t he a d diti o n of c o m ple xi n g 
a ge nts , a n d/ or b y de vel o p i n g l o w water c o nte nt/a n h y dr o us f or m ulati o ns. T he i n vesti gati o nal 
0. 4 5 4 % S n F 2 t o ot h paste is a n a n h y dr o us f or m ulati o n. 
T he l o n git u di nal e x p os ure of ra dic ular or c or o nal pri mar y de nti n  (d ue t o  e na mel er osi o n, e na mel 
a brasi o n a n d/or g u m recessi o n ) res ults i n t he s y nt hesis of tertiar y or re p arati ve d e nti n ; t he 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 1  of 1 1 3  
pri mar y p ur p ose of re p arati ve de nti n is t o pr otect t he p ul p tiss ue w here t he t o ot h’s n or mal 
pr otecti ve tiss ues (e na mel a n d g u m) ha ve bee n irre versi bl y l ost ( Li n de, 1 9 9 3 ).  T h e re parati ve 
pr ocess ca n be i nitiate d i n  res p o nse t o t he effect of e xter n al sti m uli at t he de nti n s urface , as 
e x perie n ce d b y D H s ufferers  (C o x, 1 9 9 2; D’ S o u za, 1 9 9 5; Ma gl oire, 1 9 9 2; Mj or, 2 0 0 2 ). T he 
occl u di n g la yer  f or me d o ver  t he de nti n s urface, a n d wit hi n de nti n t u b ules , wit h dail y use of a 
0. 4 5 4 % S n F 2 t o ot h paste f u ncti o ns i n a si milar wa y t o t his nat ural  re pair pr ocess . It t o o is 
re parati ve i n n at ure, acti n g t o pr otect t h e de nti n a n d t he u n d erl yi n g p ul p tiss ue fr o m e xter nal 
pai n -i n d uci n g sti m uli w here e n a mel a n d/or gi n gi v al  tiss ue has bee n l ost. 
3  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S  
 
O bj e cti v e s  
E n d p oi nt s  
Effi c a c y  
Pri m ar y  
T o de m o nstrate t he cli nic al efficac y of a 
0. 4 5 4 % w/ w S n F 2 t o ot h paste i n re d uci n g D H 
t o a n e va p orati ve (air ) sti m ul us (as meas ure d 
b y Sc hiff se nsiti vit y sc ore) , c o m pare d t o  a 
ne gati ve c o ntr ol t o ot h paste, after 8 wee ks  
t wice dail y use . 
C ha n ge fr o m Baseli ne i n Sc hiff se nsiti vit y 
sc ore at Da y 5 6 ( Wee k 8) . 
S e c o n d ar y  
T o de m o nstrate  t he cli nic al efficac y of a 
0. 4 5 4 % w/ w S n F 2 t o ot h paste i n re d uci n g D H  
t o a tactile sti m ul us (as meas ure d b y tactile 
t hres h ol d i n gra ms [ g] ), c o m pare d t o a 
ne gati ve c o ntr ol t o ot h paste, after 8  wee ks  
t wice dail y use. 
C ha n ge fr o m Baseli ne i n tactile t hres h ol d 
( g) at Da y 5 6 ( Wee k 8) . 
T o de m o nstrate  t he cli nic al efficac y of a 
0. 4 5 4 % w/ w S n F 2 t o ot h paste i n re d uci n g D H 
t o e va p orati ve (air) a n d t actile sti m uli  (as 
meas ure d b y Sc hiff se nsiti vit y sc ore  a n d 
tactile t hres h ol d ( g), res p ecti vel y), c o m pare d 
t o a ne gati ve c o ntr ol t o ot h paste, after 4 wee ks  
t wice dail y use. 
C ha n ge fr o m Baseli ne i n Sc hiff se nsiti vit y 
sc ore at Da y 2 8 ( Wee k 4) . 
C ha n ge fr o m Baseli ne i n tactile t hres h ol d 
( g) at Da y 2 8 ( Wee k 4) . 
T o descri be s u bject -percei ve d c ha n g es i n oral 
healt h -rel ate d q ualit y of life ( O Hr Q o L), as 
meas ure d b y t he De nti n H y perse nsiti vit y 
E x perie nce Q uesti o n nair e ( D H E Q -4 8 ), after 
4 - a n d 8 -w ee ks  t wic e dail y use of t heir 
assi g ne d i n vesti gati o nal  t o ot h paste. 
At D ay 2 8  ( Week 4) & D ay 5 6 ( Week 8): 
C ha n ge fr o m Baseli ne i n  D H E Q -4 8 
e n d p oi nts.  
Secti o n 1  
•  I m pact o n E ver y da y L ife ( Q7 -9 )   
Secti o n 2  
•  T otal S c ore ( Q 1 -3 4)  
•  I n di vi d ual D o mai n S c ores  
- Restricti o ns ( Q 1 -4)  
- A da ptati o n ( Q 5 -1 6)   
- S ocial I m pact ( Q 1 7 -2 1)   
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 2  of 1 1 3  
- E m oti o nal I m pact ( Q 2 2 -2 9)   
- I d e ntit y ( Q 3 0-3 4)   
•  Gl o bal Oral H ealt h Sc ore ( Q 3 5)  
•  Effect o n Life O verall Sc ore ( Q 3 6 -3 9)  
E x pl or at or y  
T o deter mi ne t he n u m ber of ‘ Se nsiti ve Teet h’ 
(e va p orati ve (air) se nsiti vit y o nl y) i n t he p o ol 
of ‘ Eli gi ble Teet h’ i de ntifie d at Scree ni n g, at 
Scree ni n g, Baseli ne, a n d after 4 a n d 8 wee ks 
t wice dail y use of assi g ne d i n vesti gati o nal 
t o ot h paste. 
At Scree ni n g,  B aseli ne, D ay 2 8 ( Week 4) & 
D ay 5 6 ( Week 8):  
N u m ber of ‘ Se nsiti ve Teet h’  
Defi ne d as t he n u m ber of ‘ Eli gi ble Teet h’ 
(i de ntifie d at Scree ni n g) wit h a Sc hiff Se nsiti vit y 
Sc ore ≥ 2.   
T o i n vesti gate s u bject-percei ve d c ha n ges i n 
D H t o a n e va p orati ve (air) sti m ul us , as 
meas ure d b y  L a belle d M a g nit u de Scales 
( L M Ss), after 4 a n d 8 wee ks  t wice dail y use 
of t heir assi g ne d i n vesti g ati o nal  t o ot h paste. 
At D ay 2 8  ( Week 4) & D ay 5 6 ( Week 8): 
C ha n ge fr o m Baseli ne i n  L M S e n d p oi nts.  
•  I nte nsity 
•  D ur ati o n  
•  T oler a bility  
•  Descri pti o n  
T o i n vesti gate t he relati o ns hi p bet wee n 
s u bject res p o nses t o t he D H E Q-4 8 a n d t h e 
L M Ss at Baseli ne a n d aft er 4  a n d 8 wee ks  
t wice dail y use of assi g ne d i n vesti gati o nal  
t o ot h paste. 
At B aseli ne, D ay 2 8  ( Week 4) & D ay 5 6 
( Week 8): 
•  D H E Q -4 8 e n d p oi nts, as liste d a b o ve.  
•  L M S e n d p oi nts, as liste d a b o ve.  
T o i n vesti gate t he relati o ns hi p bet wee n t he 
Sc hiff se nsiti vit y scale  a n d t he L M Ss at 
Baseli ne , a n d aft er 4  a n d 8 wee ks  t wice dail y 
use of assi g ne d i n vesti gati o nal  t o ot h paste. 
At B aseli ne, D ay 2 8  ( Week 4) & D ay 5 6 
( Week 8): 
•  Mea n Sc hiff se nsiti vit y sc ore of t he t w o 
‘ Test Teet h’. 
•  L M S e n d p oi nts, as liste d a b o ve.  
T o i n vesti gate s u bject satisfacti o n wit h t heir 
assi g ne d i n vesti gati o nal  t o ot h paste f or t he 
o verall ma na g e me nt of D H, as meas ure d b y a 
N u meric Rati n g Scale ( N R S), after 8 wee ks 
treat me nt. 
At D ay 5 6  ( Week 8): 
Satisfacti o n N R S sc ore   
S af et y  
T o m o nit or  t he safet y a n d oral t olera bilit y of 
t he i n vesti gati o nal t o ot h pastes o ver 8 wee ks  
t wice dail y use . 
Treat me nt e mer ge nt a d verse e ve nts 
( T E A Es). 
T his st u d y will be c o nsi dere d s uccessf ul if t he 0. 4 5 4 % S n F 2 t o ot h paste de m o nstrates 
statisticall y si g nifica nt, s u peri or a nti-h y perse nsiti vit y efficac y, c o m pare d t o t he ne gati ve c o ntr ol  
t o ot h paste, as meas ur e d b y Sc hiff se nsiti vit y sc ore at Da y 5 6 ( Wee k 8 ). 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 3  of 1 1 3  
4  
S T U D Y D E SI G N  
4. 1  
O v er all D e si g n  
T his will be a si n gle ce nt er, 8 -wee k, ra n d o mize d, c o ntr olle d, e x a mi ner-bli n d, 2 -treat me nt ar m, 
parallel gr o u p, stratifie d  st u d y i n healt h y s u bjects wit h D H . S u bjects w h o meet t he re q uire d 
st u d y criteria at Scree ni n g a n d Baseli ne will be ra n d o mize d t o o ne of t w o st u d y treat me nts: 
0. 4 5 4 % S n F 2 t o ot h paste ( Test T o ot h paste ) or a re g ular fl u ori de t o ot h paste  (Refere n ce  
T o ot h paste ) 
T w o i n de pe n d e nt sti m ul us -base d cli nical meas ures will be e m pl o ye d t o assess t he efficac y of 
t he i n vesti gati o nal t o ot h pastes.  
•  A tactile sti m ul us will be a d mi nistere d usi n g a c o nsta nt press ure pr o be - Yea ple Pr o be 
(P ols o n, 1 9 8 0 ); s u bject res p o nse t o t he sti m ul us deter mi nes t he tactile t hres h ol d i n 
gra ms ( g).  
•  A n e va p orati ve (air) sti m ul us (i.e., a t her mal sti m ul us) will be a d mi nistere d usi n g a 
de ntal air s yri n ge; s u bject res p o nse t o t he sti m ul us will be e xa mi ner-e val uat e d usi n g t he 
Sc hiff se nsiti vit y scale ( Sc hiff, 1 9 9 4 ). 
D H  will be assesse d at S cree ni n g, Da y 0 ( Bas eli ne), Da y 2 8  ( Wee k 4) a n d Da y 5 6  ( Wee k 8). 
O n c o m pleti o n of t he Baseli ne assess me nts , the cli nical e xa mi ner will select t w o ‘ Test T eet h ’ 
f or assess me nt of tactile a n d e va p orati ve (air) s e nsiti vit y at all s u bse q ue nt visits. T o q ualif y f or 
selecti o n as a ‘ Test T o ot h’, t he t o ot h m ust meet t he pr ot oc ol -s pecific i ncl usi o n/e xcl usi o n 
criteria (Secti o n  5 . 2 Incl usi o n Criteria 6 & 7 ; Secti o n 5 . 3 E xcl usi o n Criteri o n 2 6) , s pecificall y 
tactile t hres h ol d ≤ 2 0 g a n d  Sc hiff se nsiti vit y sc ore ≥ 2 at b ot h  Scree ni n g a n d  Baseli ne visits.  
I n a d diti o n, the n u m ber of ‘ Se nsiti ve Teet h’ will be deter mi ne d at eac h st u d y visit ( Sc hiff 
se nsiti vit y sc ore ≥ 2 ) as d escri be d i n Secti o ns 8. 1. 5 , 8. 2. 1. 5 , 8. 2. 2. 5  a n d 8. 2. 3. 5 . 
A p pr o xi matel y 1 1 0  q ualif yi n g s u bjects will be stratifie d acc or di n g t o t he ma xi m u m Baseli ne 
Sc hiff se nsiti vit y sc ore of t heir t w o ‘ Test Teet h’ a n d ra n d o mize d t o tr eat me nt  (a p pr o xi matel y 
5 5  s u bjects per treat me nt gr o u p). Ra n d o mize d s u bjects will be i nstr ucte d t o br us h t wice da il y 
( m or ni n g a n d e v e ni n g) wit h t heir assi g ne d i n vesti gati o nal t o ot h paste f or t he ne xt 5 6 da ys 
(8  wee ks ) a n d rec or d eac h br us hi n g i n t he diar y pr o vi de d . First use  will be perf or me d u n der 
s u per visi o n at t he i n vesti gat or site; to facilitate c o m plia nce a n a d diti o nal  s u per vise d o n -site 
br us hi n g will be c o m plete d at t he e n d of Visit 3 . 
C ha n ges i n O H R Q o L will be m o nit ore d o ver t he treat me nt peri o d usi n g t he vali date d De nti n 
H y perse nsiti vit y E x perie nce Q uesti o n nair e ( D H E Q -4 8) . T he D H E Q -4 8 will be  c o m plete d b y 
st u d y s u bjects at Baseli ne, a n d after 2 8- a n d 5 6-d a ys treat me nt. S u bject -percei ve d D H will als o 
be i n vesti gate d  f or t he t w o selecte d ‘ Test Teet h’ usi n g La belle d Ma g nit u de Scales ( L M Ss ). 
S u bjects will c o m plete f o ur L M Ss  t o ca pt ure t he I nte nsity, D ur ati o n , T oler a bility  a n d 
Descri pti o n  of t heir res p o nse t o t he e va p orati ve (air) sti m ul us  a d mi nistere d  at Baseli ne, Da y 2 8 
a n d Da y 5 6 . At t he fi nal visit ( Da y 5 6), after all cli nical pr oce d ures ha v e bee n c o m plete d, 
s u bjects will rate t heir le vel of satisfacti o n wit h t heir assi g ne d i n vesti gati o nal t o ot h paste f or t he 
o verall ma na g e me nt of D H usi n g a N R S.  
T o sta n dar dize oral h y gi e ne practic e i n t he st u d y p o p ulati o n  pri or t o treat me nt a n d t o hel p 
mi ni mize t he p ote ntial i m pact of ‘ place b o’/‘ n o treat me nt’ effects , eli gi ble s u bjects will 
c o m plete a n accli matizati o n peri o d ( 1 4 -2 8 da ys d urati o n) bet wee n t he Scree ni n g a n d Baseli n e 
visits  d uri n g w hi c h t he y will br us h t wice dail y ( m or ni n g a n d e ve ni n g) wit h a re g ular fl u ori de 
t o ot h paste (a differe nt c o m merciall y a vaila ble pr o d uct  fr o m t he Refere nce T o ot h paste). First 
use of accli matizati o n t o ot h paste will be perf or me d u n der s u per visi o n at t he i n vesti gat or site. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 4  of 1 1 3  
Safet y a n d oral t olera bilit y of t he i n vesti gati o nal t o ot h pastes will be m o nit ore d o ver t he 
treat me nt peri o d b y re vie w of T E A Es.  
4. 2  
S ci e ntifi c R ati o n al e f or St u d y D e si g n  
T he ra n d o mize d, c o ntr olle d, e xa mi ner -bli n d, parallel gr o u p desi g n selecte d f or t his D H st u d y 
f oll o ws p u blis he d g ui da nce  f or t h e desi g n a n d c o n d uct of st u dies i n vesti gati n g t he cli nical 
effic ac y of a nti-se nsiti vit y pr o d uct s (H olla n d, 1 9 9 7 ). In li ne wit h t hes e sa m e rec o m me n dati o ns, 
t w o i n de pe n de nt, c o ntr olla ble D H sti m uli (tactile a n d t her mal) will be e m pl o ye d t o assess t he 
perf or ma n ce  of t h e  0. 4 5 4 % S n F 2 t o ot h paste, wit h t he least s e vere sti m ul us (t actile) a p plie d first 
(H olla n d, 1 9 9 7 ). T o  a v oi d i nter-e xa mi ner varia bilit y, t he sa me cli nical e xa mi ner will  a d mi nist er 
a gi ve n sti m ul us (tactile a n d/or e va p orati ve (air)) a n d assess its ass ociate d D H  meas ure  (tactil e 
t hres h ol d ( g) or Sc hiff se nsitivit y sc ore) t hr o u g h o ut t he st u d y.  
D H will be cli nicall y assesse d at Scree ni n g  a n d B aseli ne ( pre -tr eat me nt) t o deter mi ne  s uita bilit y 
t o partici pate a n d c o nfir m s u bject q ualificati o n , a n d a gai n after 2 8 - a n d 5 6-da ys treat me nt t o 
e val uate t he efficac y  of t he Test  T o ot h paste  wit h t wice -dail y use . At all p ost -Baseli ne ti me 
p oi nts, t he a nti -se nsiti vit y efficac y of t he Test  T o ot h paste  will be c o m pare d wit h  t hat of a 
Refere n ce T o ot h paste - a c o n v e nti o nal , dail y us e fl u ori de t o ot h paste wit h n o k n o w n a nti-
se nsiti vit y efficac y (i.e., a n o n-dese nsitisi n g t o ot h paste  will act as t he ne gati ve c o ntr ol ). 
Q ualif yi n g s u bjects will be ra n d o mi ze d t o o n e of t he t w o i n vesti gati o nal treat me nts usi n g a 1: 1 
all ocati o n rati o.  
•  Da y 5 6 has bee n s elect e d as t he pri mar y ti me p oi nt t o c o nfir m  t he a nti -se nsiti vit y 
effic ac y  of t he i n vesti gati o nal 0. 4 5 4 % S n F 2 t o ot h paste; 5 6 -da y ( 8 -wee k) st u d y d urati o n 
is acce pt e d as a p pr o priat e t o e val uat e t he l o n g-ter m efficac y of m ost a nti-se nsiti vit y 
pr o d ucts (H olla n d, 1 9 9 7 ). 
•  E va p orati ve (air) is a t her mal sti m ul us re prese ntati ve of t he i m pact of c hille d f o o d s a n d 
dri n ks , or  a n i nta ke of c ol d air , o n se nsiti ve teet h . ‘C ol d’ is  re p orte d t o be t he m ost 
c o m m o n  sti m uli f or D H  pai n ( Fisc h er, 1 9 9 2 ; Fl y n n, 1 9 8 5 ; Gilla m, 2 0 0 2 ). T h us, cha n ge 
fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore at Da y 5 6 has b ee n select e d as t he pri mar y 
e n d p oi nt , 
wit h st u d y s uccess defi n e d as statisticall y si g nifica nt, s u peri or a nti-
h y perse nsiti vit y effic ac y  f or t he 0. 4 5 4 % S n F 2 t o ot h paste, vs.  ne gati ve c o ntr ol, as 
meas ure d b y Sc hiff se nsiti vit y sc ore at Da y 5 6 ( Wee k 8 ).  
O n c o m pleti o n of t he Baseli ne assess me nts, t he cli nical e xa mi ner will select t w o ‘ Test T eet h’ 
fr o m t h ose t hat q ualify  at b ot h Scree ni n g ( Visit 1) a n d Baseli ne ( Visit 2) f or ass ess me nt of 
tactile a n d e va p orati ve (air) se nsiti vit y at all s u bse q ue nt visits. Q ualif yi n g s u bjects will be 
stratifie d acc or di n g t o t he ma xi m u m Sc hiff se nsiti vit y sc ore of t heir t w o selecte d ‘Test Teet h ’ 
t o e ns ure treat me nt gr o u ps are bala nce d f or D H se verit y. Re peate d  sti m ulati o n of m ulti ple 
se nsiti ve teet h ma y  alt er t he pai n  res p o nse as testi n g c o nti n ues ar o u n d t he m o ut h ; t he 
antici pati o n of pai n or disc o mf ort  wit h pr otracte d testi n g, al o n g wit h t he disc o mf ort of h a vi n g 
t o kee p t he m o ut h o p e n f or a n e xt e n de d p eri o d of ti me, ma y  als o affect  s u bject perce pti o n of 
pai n  (H olla n d, 1 9 9 7 ). T h us, t he sele cti o n of t w o re prese ntati ve ‘ Test T eet h’ t o e val uate c ha n g es 
i n D H wit h treat me nt is c o m m o n practice i n D H effi cac y st u dies. T o b e  re prese nt ati ve of 
differe nt areas of t he m o ut h , wit h i n de pe n de nt i n ner vati o n, t he ‘ Test Teet h’  s h o ul d be n o n -
a djace nt a n d  i n differe nt q ua dra nts .  
T he n u m ber of teet h se nsiti ve t o a n e va p orati ve (air) sti m ul us i n t he p o ol of ‘ Eli gi ble Teet h’ 
i de ntifie d at Scree ni n g will be m o nit ore d  acr oss t he st u d y p eri o d . T h e e va p orati ve (air) 
se nsiti vit y of a ll ‘Eli gi ble Teet h ’ i de ntifie d at Scree ni n g (i.e., teet h wit h n o de ntiti o n e xcl usi o ns 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 5  of 1 1 3  
w hic h meet t he E A R, 
M GI a n d m o bilit y i ncl usi o n criteria, a n d h a ve a Scree ni n g tactile 
t hres h ol d ≤ 2 0 g a n d a Scree ni n g Sc hiff s e nsitivit y sc ore ≥ 2 ) will b e ass esse d at Baseli ne, a n d 
after 2 8 - a n d 5 6 -da ys treat me nt . F or t his p ur p ose, a ‘ Se nsiti ve T o ot h’ will be defi ne d as ha vi n g 
a mar ke d res p o nse t o t he e va p orati ve (air) sti m ul us ( Sc hiff se nsiti vit y sc ore  ≥ 2).  
T o hel p mi ni mize e x p os ure t o e n vir o n me ntal  tri g gers f or se nsiti vit y pri or t o cli nical D H  
assess me nt , s u bjects will be i nstr uct e d t o refrai n fr o m oral h y gi e ne, c he wi n g g u m , eati n g a n d 
dri n ki n g f or a peri o d of ti me pri or t o t heir arri val at t he i n vesti gat or site. 
Cli nical trials e val uati n g pai n -relat e d e n d p oi nts ca n be pr o ne t o ‘ place b o effects’ (A d d y, 1 9 8 5 ; 
West, 1 9 9 7 ); su c h effects are fre q ue ntl y o bs er ve d i n D H st u dies. A st u d y c o n d ucte d t o e val uate 
t he nat ural hist or y of t he D H  c o n diti o n als o hi g hli g hte d t he e xiste nce of a ‘ n o treat me nt’ effect , 
c haracteri ze d b y a n i m pr o ve me nt i n se nsiti vit y si m pl y as a res ult of st u d y partici pati o n (Lei g ht, 
2 0 0 8 ). T o hel p mi ni mi ze t he p ote ntial i m pact of s uc h effects , an accli mati zati o n peri o d (1 4 -2 8 
da y s d urati o n) will prece de t he Baseli ne visit . D uri n g t his peri o d, st u d y s u bjects will br us h 
t wice dail y wit h t h e re g ular flu ori de t o ot h paste a n d t o ot h br us h pr o vi de d ( i n place of t h eir o w n  
oral h y gie ne pr o d ucts ) a n d rec or d eac h br us hi n g occasi o n i n a diar y. T he accli mati zati o n peri o d 
will als o ser ve t o s ta n dar dize oral h y gie ne practice  acr oss t he st u d y p o p ulati o n a n d fa miliariz e 
partici pa nts wit h  s e veral i m p orta nt st u d y pr oce d ures (e. g., t o ot h paste d osa g e, ti me d br us hi n gs, 
diar y c o m pleti o n) pri or t o treat me nt.  
D H is a n e pis o dic c o n diti o n; s y m pt o ms are k n o w n t o var y s p o nta ne o usl y ( West, 2 0 0 8, West, 
2 0 1 3) . Baseli ne cli nical val ues t hat w o ul d s u p p ort e nr ol me nt ma y re prese nt ra n d o m hi g hs t hat 
c o ul d be f oll o we d b y re gressi o n t o t he mea n, lea vi n g t he s u bject or select e d test t o ot h wit h o ut 
t he c o n diti o n u n der i n vesti gati o n (i.e., D H) d uri n g t he treat me nt peri o d. T o hel p mi ni mize  t he 
p ote ntial f or t his t o occ ur in t he c urre nt st u d y, ra n d o mize d s u bjects will be re q uire d t o 
de m o nstrate c o nsiste nc y  i n res p o nse t o b ot h D H sti m uli at b ot h t he Scree ni n g a n d Baseli ne 
visits. Q ualif yi n g s u bjects will ha ve a mi ni m u m of t w o q ualif yi n g  teet h wit h a tactile t hr es h ol d 
≤ 2 0 g  a n d a Sc hiff se nsiti vit y sc ore ≥ 2 at b ot h Scree ni n g a n d Baseli ne.  I n li ne wit h p u blis he d 
g ui deli nes f or t he desi g n a n d c o n d uct of st u dies i n vesti gati n g t he cli nical efficac y of a nti-
se nsiti vit y pr o d uct s, inc o nsiste nt res p o n ders will be e xcl u de d  (H olla n d, 1 9 9 7 ). 
T he eti ol o g y of D H  re q uires t o ot h wear (l oss of e n a mel) a n d/ or gi n gi val recessi o n (wit h l oss of 
ce me nt u m) t o e x p ose t he u n derl yi n g de nti n ( A d d y, 1 98 7) . In t he a bse nce of a n u n derl yi n g 
c o n diti o n  or pat h ol o g y, t hese  pr ocess es are sl o w a n d pr o gressi ve , lea di n g t o de nti n e x p os ure i n 
earl y a d ult h o o d ; t h us, D H  is rarel y s ee n i n c hil dre n (West, 2 0 2 2 ). W hile t he  a ge ra n ge o v er  
w hic h a n i n di vi d ual ca n e x perie n ce D H is wi de (earl y tee ns t o 7 0s), p ea k i nci de nce is k n o w n 
t o occ ur bet wee n t he a ges of 2 0-4 0 years  a n d d ecli n e t hereafter (B art ol d, 2 0 0 6 ; Da ba b ne h, 1 9 9 9; 
Fisc her, 1 9 9 2 ; Fl y n n, 1 9 8 5 ; West, 2 0 1 4 ). T he fall i n pre vale nce  o bser ve d i n later deca d es 
reflects a ge-relate d c ha n ges i n t he de nti n a n d p ul p of t he t o ot h w hic h act t o re d uce b ot h de nti n 
per mea bilit y a n d t he t o ot h’s res p o nse t o e xter nal tri g gers of D H (Seltzer, 1 9 7 5 ; S pliet h, 2 0 1 3 ). 
D e ntal pai n e x p erie n ce d b y  ol der me m bers of t he p o p ulati o n is less li kel y t o be dia g n ose d as  
D H (Rees, 2 0 0 0 ), t h us a n a ge ra n g e of 1 8 -6 5  years has bee n sel ecte d f or t his st u d y t o tar g et 
i n di vi d uals wit h  t o ot h se nsiti vit y d ue t o D H. 
C urre ntl y, t here is n o p u blis he d e vi de nce t o i n dicate t hat ge n der , race or et h nicit y i m pacts t he 
pat h o p h ysi ol o g y of D H . T h us, t he i n vesti gat or site will ma ke e ver y eff ort t o e nr oll s u bjects 
re pres e ntati ve of t he a d ult p o p ulati o n w h o w o ul d be nefit fr o m use of a n a nti-se nsiti vit y 
t o ot h paste. T he st u d y p o p ulati o n will c o m prise male a n d fe male s u bjects  a n d t he pr ot oc ol 
i ncl usi o n/e xcl usi o n criteria will n ot u n necessaril y precl u de  a n y s u bject fr o m partici pati o n . T o 
f urt her i ncreas e t he di versit y of e nr olle d s u bjects : (i) t he i n vesti gat or site will be e nc o ura g e d t o 
e m pl o y a ra n ge of a d vertisi n g met h o ds (e. g., p osters i n l ocal c o m m u nit y ce nters, retail o utlets 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 6  of 1 1 3  
a n d healt hcare facilities, l ocal ra di o, s ocial me dia) t o ma xi mize  t heir a bilit y t o reac h a di verse 
p o p ulati o n wit hi n t heir g e o gra p hic l ocati o n; (ii) w here v er p ossi ble, t h e i n vesti gat or site will 
e ns ure accessi bilit y t o cli nical areas f or s u bjects wit h m o bilit y iss ues; (iii) fle xi bilit y will  be 
a d de d t o V isit 3 a n d Visit 4  ti mi n gs t o facilitate s u bject atte n da nce at site (Da y 2 8 ± 2 da ys; 
Da y 5 6 ± 3  da ys ); (i v) st u d y pa y me nt will a p pr o priatel y c o m pe nsate p ot e ntial s u bjects f or t he 
a ntici pate d c osts of partici pati o n (e. g., tra vel t o t he i n vesti gat or site f or sc he d ule d visits) t o 
e ns ure fi na n cial c o nsi derati o ns d o n ot i m pe de partici pati o n . 
Fe male s u bjects w h o are pre g na nt  (or i nte n di n g t o bec o me pre g n a nt d uri n g t he st u d y ) or breast -
fee di n g will be e xcl u d e d fr o m partici pati o n i n t he st u d y. T he st u d y t o ot h pastes are n ot c o ntr a -
i n dicate d f or pre g na nc y or  breastfee di n g (t heir us e w o ul d n ot b e e x p ecte d t o ca use har m t o t he 
m ot her, t he f oet us or a b a b y), h o we ver, pre g na nt a n d la ctati n g fe m ales will be e xcl u d e d d ue t o 
t he i ncrease d pre vale n ce/se verit y of gi n gi vitis a n d peri o d o ntal disease re p orte d d uri n g 
pre g na nc y a n d breastfee di n g w hic h, t o get her wit h t he i ncreas e d a m o u nts of calc ul us a n d pla q ue 
o bser ve d o n t h e teet h d uri n g pre g n a n c y, c o ul d affect  D H assess me nt  (A g haza d e h, 2 0 1 9 ; 
Sa ma nt, 1 9 7 6 ).  
P ote ntial st u d y s u bjects  will  be  as ke d t o bri n g t heir c urre nt oral h y gie ne pr o d ucts t o Scree ni n g 
( Visit 1)  w h ere t he y will be c h ec ke d f or pres e nce of k n o w n a nti -se nsiti vit y i n gre die nts. 
I n di vi d uals alr ea d y usi n g a nti -se nsiti vit y pr o d uct (s) as part of t heir n or m al  oral h y gie ne r o uti ne 
will be e xcl u de d . If t he y are usi n g s uc h pr o d ucts a n d c o nti n ui n g t o e x perie nce D H , t he y w o ul d  
be  u nli kel y t o res p o n d t o f urt her use of a nti-se nsiti vit y t o ot h paste i n t his st u d y a n d will be 
a d vise d t o see k hel p fr o m t heir de ntal healt hcare pr o vi der.  
‘P atie nt-re p ort e d o utc o mes’ ( P R Os) ca n pr o vi de val ua ble i nf or mati o n a b o ut t he effect of a 
c o n diti o n , a n d its treat me nt , o n da y -t o-da y life  fr o m t he pers pecti ve of t he p ers o n s ufferi n g wit h 
t he c o n diti o n . T he i ncl usi o n of well -defi ne d , relia ble ‘P R O s’ i n cli nical st u dies is i ncreasi n gl y 
e nc o ura g e d t o e ns ure t he i m pact of tr eat me nt o n q ualit y of life  a n d s u bject-re p orte d s y m pt o ms 
is assesse d al o n gsi de c o n ve nti o nal cli nical o utc o mes . I n dee d, p u blis he d g ui d eli nes  f or t he 
desi g n a n d c o n d uct of st u dies  i n vesti gati n g t he cli nical efficac y of a nti-se nsiti vit y pr o d uct s 
(H olla n d, 1 9 9 7 ), rec o m me n d t hat treat me nt e val uati o ns i ncl u de s u bject-assess me nt of o verall 
c ha n ge t o e v er y  da y tri g gers f or D H. T h re e ‘P R O ’ meas ures will be i ncl u de d i n t his st u d y : 
(i) t he De nti ne H y perse nsiti vit y E x perie nce Q uesti o n naire ( D H E Q) ; (ii) a series of  La belle d 
Ma g nit u de Scales ( L M S s); (iii) a Treat me nt Satisfacti o n N R S . Gi ve n st u d y partici pa nts  will n ot 
be patie nts, f or t he p ur p oses of t his st u d y, t hes e m eas ures will be d escri b e d  as ‘s u bject -re p orte d 
o utc o mes’ . 
T he D H E Q a n d t he L M Ss  were de vel o p e d wit h D H s ufferers a n d ca n be  use d t o assess t he 
i m pact of D H o n d ail y life , t o meas ure D H pai n  a n d/ or assess  s u bject res p o nse t o D H  treat me nt.  
St u d y s u bjects will c o m plete a D H E Q -4 8 ( A p pe n di x 1 5. 2 ) at Baseli ne ( Visit 1), a n d after 2 8- 
a n d 5 6-da ys treat me nt ( Visits 6 a n d 7), pri or t o a n y cli nical e xa mi nati o ns or assess me nts.  
•  T he D H E Q is a v ali date d, c o n diti o n -s pecific meas ure of O H R Q o L use d t o i n vesti gate 
t he i m pacts of t o ot h se nsiti vit y o n e ver y da y life . It was d e vel o pe d b y t h e s p o ns or i n 
c olla b orati o n wit h S heffi el d U ni versit y t hr o u g h a r o b ust t he oretical fra me w or k, ( Ba k er, 
2 0 1 4 ; B oi k o, 2 0 1 0 ; R o bi ns o n, 2 0 1 4 ) a n d has s h o w n relia bilit y a n d vali dit y i n b ot h a 
ge neral p o p ulati o n ( P orritt, 2 0 1 6 ) a n d i n cli nical st u dies (B oi k o 2 0 1 0 ; Gi bs o n, 2 0 1 5 ).  
It has b ee n  vali dat e d as b ot h l o n g - a n d s h ort-f or m versi o ns (D H E Q -4 8 a n d D H E Q -1 5 ), 
co m prisi n g 4 8 ( Ba ker, 2 0 1 4; B oi k o, 2 0 1 0 ) a n d 1 5 (Mac h u ca, 2 0 1 4 ) q uesti o ns, 
res pecti vel y, a n d has bee n tra nslate d i nt o m ulti ple la n g ua ges (e. g., C hi nese, T ur kis h, 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 7  of 1 1 3  
P ort u g uese), c o nfir mi n g its gl o bal rele va n ce ( B aşara n, 2 0 1 8 ; D o u glas -De -Oli veira ; 
2 0 1 8 ; He, 2 0 1 5 [a]; H e, 2 0 1 5 [b ]).  
S t u d y s u bjects will c o m plete f o ur L M Ss  (A p pe n di x 1 5 . 3) relati n g t o c o n diti o n -s pecifi c 
c haracteristics of t h e D H pai n res p o ns e ( i nte nsity, d ur ati o n , t oler a bility a n d descri pti o n ) at 
Baseli ne ( f or eac h t o ot h w hic h q ualifies f or e va p orati ve (air) ass ess me nt ), a n d after 2 8 - a n d 5 6-
da ys treat me nt  (f or t he t w o selecte d ‘ Test Teet h’ o nl y ). L M Ss will be c o m plete d s h ortl y after 
t he e va p orati ve (air) sti m ul us has bee n a d mi nistere d , a n d after t he cli nical e xa mi ner has 
rec or de d t heir Sc hiff se nsiti vit y sc ore. To a v oi d bi as , t he e xa mi ner a n d  t he s u bject will ha v e n o 
visi bilit y of  t heir res pecti ve ‘sc ores’.  
•  Vis ual A nal o g ue Scales ( V A Ss) wit h t w o a nc h or p oi nts  at 0 milli meters ( m m) a n d 1 0 0 
m m  (t y picall y la belle d ‘ n o pai n’ a n d ‘ w orst i ma gi na ble p ain’ ) are fre q ue ntl y e m pl o ye d 
i n t he cli nical st u d y  of  pai n . W hile are effecti ve f or meas uri n g  c ha n g e i n hi g h i nte nsit y 
pai n (e. g., p ost -o perati ve pai n  Ga gliese, 2 0 0 5 ), t h e y ca n be less  us ef ul  f or l o w-le vel, 
e pis o d ic pai n , s u c h as t hat ass ociate d wit h D H . T h e L M Ss  t o be use d i n t his st u d y were 
de vel o pe d b y t he s p o ns or i n c olla b orati o n wit h t he U ni versit y  of Was hi n gt o n  (Seattle , 
U S) , s pecificall y t o discri mi nate bet wee n differe nt le vels of D H pai n , a n d ha ve bee n 
pil ote d, vali date d, a n d utilize d i n o bser vati o nal a n d i nter ve nti o nal cli nical D H st u dies 
(C u n ha -Cr uz, 2 0 1 3; Heat o n, 2 0 1 3; Mas o n, 2 0 1 7; Mas o n, 2 0 1 9 ). Rec urri n g , c o nsiste nt 
d escri pt ors of D H p ain  (fr o m t he mil dest t o t he m ost se vere ) were i de ntifie d d uri n g  
f oc us gr o u ps wit h  cli nicall y c o nfir me d  D H  s ufferers. P s yc h o p h ysical pr oce d ures 
( ma g nit u de esti mati o n a n d cr oss-m o dalit y ma g nit u de matc hi n g) were t he n a p plie d t o 
ali g n t hese c o n diti o n -s p ecific des cri pt ors  al o n g V A S s at dista nces reflect i n g t he 
ps yc h ol o gical dista nces b et wee n t he d escri pti ve ter ms.  
T o i n vesti gate satisfacti o n wit h t heir assi g ne d i n vesti gati o nal t o ot h paste f or t h e o verall 
ma na ge me nt of D H, s u bjects will be as ke d t o c o m plete a N R S  (a n 1 1-p oi nt or di nal scale) at t he 
e n d of t he treat me nt peri o d . T he y will rec or d t he n u meric val ue (fr o m 0 t o 1 0) that best descri bes 
t heir le vel of satisfacti o n a n d descri b e w h y t he y ga ve t he pr o d uct t hat r ati n g (free te xt) . 
Per I nter n ati o nal C o nfere nce o n Har m o nizati o n (I C H) G C P g ui da nce  (I C H E 6 ( R 2) G o o d 
C li nical P ractice), f or a st u d y t o be cl assifie d as d o u ble bli n d , t he s u bjects, i n vesti gat or(s) a n d 
staff i n v ol ve d i n t he treat me nt or cli nical e val uati o n of s u bjects s h o ul d be u na ware of treat me nt 
recei v e d; t his i ncl u des staff i n v ol ve d i n t he deter mi n ati o n of s u bject eli gi bilit y, e val uatio n  of  
e n d p oi nts  (cli nical e xa mi ners), or assessme nts of pr ot oc ol  c o m plia nce (e. g., m o ni t ors, data 
a nal yst s). I n s u m mar y, n eit her t he s u bject n or t he researc her s s h o ul d k n o w  if t he s u bject has 
bee n assi g ne d t o Test  or Refere n ce  treat me nt. I n a d diti o n, t he pr o d ucts u n der test s h o ul d ha ve 
t he sa me a p peara nce, s mell a n d taste (i.e., st u d y ar ms s h o ul d n ot be disti n g uis ha ble fr o m eac h 
ot her ). Gi ve n t his will n ot be p ossi ble f or t he i n vesti gati o nal pr o d ucts e val uate d i n t his st u d y 
(a n e x p eri me nt al t o ot h paste a n d c o m merciall y a vaila ble re g ular fl u ori de t o ot h paste), t he st u d y 
is descri be d as ‘e xa mi ner bli n d’. H o we ver , gi v e n desi g n of t he st u d y a n d t he pr oce d ures i n 
place at t he i n vesti gat or site to mai ntai n t he bli n d d uri n g st u d y c o n d uct , it is hi g hl y u nli kel y 
t hat t he s u bjects, i n vesti gat or, cli nical e xa mi ner(s)  or a n y me m ber of t h e site staff i n v ol ve d i n 
effic ac y a n d s afet y assess me nts  will be a ware of treat me nt all ocati o n.  
•  
In t his parallel -desi g n st u d y , st u d y s u bjects will see a n d use o nl y o ne of t he t w o 
i n vesti gati o nal t o ot h pastes f or t he d urati o n of t he treat me nt peri o d. T h e y will be 
i nstr ucte d n ot t o disc uss t he a p peara nce, usa ge or percei ve d perf or ma nce of t heir 
assi g ne d i n vestigati o nal  t o ot h paste wit h t he cli nical e xa mi ner (s), wit h staff i n v ol ve d i n 
cli nical assess me nts or wit h ot her st u d y s u bjects.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 8  of 1 1 3  
•  
B ot h  i n vesti gati o nal pr o d ucts are bl ue  t o ot h pastes. T he y will be pr o vi de d  t o t he 
i n vesti gat or site o ver wra p pe d i n w hite vi n yl t o mas k t heir i de ntit y , a n d t o o bsc ure a n y 
bra n di n g  o n t he Refere n ce T o ot h paste , wit h a st u d y la bel affi x e d.  
•  
T he i n vesti gati o nal  t o ot h pastes will be s u p plie d i n c art o ns, eac h cart o n will c o ntai n 4  
o ver -wra p pe d t u bes of t o ot h paste. T he c art o n a n d its 4 t u bes will be la belle d wit h t he 
sa me u ni q ue ra n d o mizati o n n u m ber . S u bjects will be ce ntrall y ra n d o mi ze d t o treat me nt 
i n or der of q ualificati o n usi n g a n I nteracti ve Res p o nse Tec h n ol o g y (I R T) ; pr o d uct c o des 
will n ot be use d . 
•  
T he cli nical e x a mi ner(s) a n d site staff i n v ol ve d i n efficac y a n d safet y assess me nts will 
n ot be p er mitte d i n a n y area w here t h e i n vesti gati o nal t o ot h pastes or diari es  are st ore d, 
dis pe nse d  or i n use. 
•  
Site  staff i n v ol ve d i n t he dis pe nsi n g  of i n vesti gati o nal t o ot h pastes, pr o vi di n g br us hi n g 
a n d diar y c o m pleti o n i nstr ucti o n, s u per visi o n of o n-site br us hi n gs , treat me nt 
c o m plia nce c hec ks a n d pr o d uct acc o u nta bilit y  will n ot be  i n v ol ve d i n cli nical efficac y 
a n d safet y ass ess me nts  a n d will w or k i n a se parate area fr o m t h e cli nical e xa mi ner(s) 
a n d site staff i n v ol ve d i n efficac y a n d s afet y assess me nts. 
•  
S u bjects  will be i nstr ucte d n ot t o re m o ve t heir assi g ne d i n vesti gati o nal t o ot h paste or 
diar y  fr o m t he o pa q ue carrier ba g pr o vi de d o utsi de of t he dis pe nsi n g/s u per vi se d 
br us hi n g r o o m, w hile at t he i n vesti gat or site. 
•  
W here  cert ai n staff will  be u n bli n de d t o carr y o ut t heir res p o nsi bilities (e. g., staff 
i n v ol ve d i n S A E  re p orti n g, m o nit ors), t he i n vesti g at or a n d s p o ns or are re q uire d t o p ut  
a de q uate pr oce d ures i n place t o pre ve nt i na p pr o priate disse mi nati o n of treat me nt 
i de ntificati o n.  
4. 3  
J u stifi c ati o n f or D o s e  
T he i n vesti gati o nal pr o d ucts are t o ot h pastes ; the y are i nte n de d f or t o pical oral use a n d will be 
a p plie d b y t o ot h br us hi n g usi n g a ma n u al t o ot h br us h.  
I n li ne wit h wi del y r ec o m me n de d oral h y gie ne practice a n d t y pical c o ns u mer ha bit, q u alif yi n g 
s u bjects will be i nstr ucte d t o br us h t wice dail y ( m or ni n g a n d e ve ni n g) wit h t heir assi g ne d 
i n vesti gati o nal t o ot h paste, c o veri n g t he t o ot h br us h hea d wit h f ull ri b b o n of t o ot h paste 
(a p pr o xi matel y 1. 5 g) o n eac h br us hi n g o ccasi o n.  
•  S u bjects ra n d o mize d t o T est T o ot h paste will b e i nstr ucte d t o br us h t heir e ntire de ntiti o n 
t h or o u g hl y f or at least 1-ti me d mi n ute, ma ki n g s ure t o br us h t he se nsiti ve areas of t heir 
t w o ' Test teet h' caref ull y first. 
•  S u bjects ra n d o mize d t o Refere n ce T o ot h paste will be i nstr ucte d t o br us h t heir e ntire 
de ntiti o n t h or o u g hl y f or at least 1 -ti me d mi n ute. 
U sa ge i nstr ucti o ns are c o nsiste nt wit h t he pr o p ose d la belli n g f or t he T est T o ot h paste a n d wit h 
t he c o m mercial pac k i nstr ucti o ns of  t he Refere n ce T o ot h paste . A t l east 1 -m i n ute br us hi n g is  i n 
li ne wit h  t he br us hi n g ti mes s pecifie d i n si milar D H efficac y st u dies (D oci m o, 2 0 0 9 ; Hall, 2 0 1 7 ; 
He, 2 0 1 4[ b]);  Par ki ns o n, 2 0 1 3; Par ki ns o n, 2 0 1 5 [a]).  
After 8 wee ks ( i.e., 5 6 ±  3  da ys) t wice dail y usa ge, eac h s u bj ect s h o ul d c o m plete bet wee n 1 0 6 -
1 1 8  br us hi n gs.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 2 9  of 1 1 3  
4. 4  
E n d of St u d y D efi niti o n  
A s u bject will be c o nsi dere d t o ha v e c o m plet e d  t h e st u d y if t he y h a ve  c o m plete d all p hases of 
t he st u d y, i ncl u di n g t he last visit or t he last sc he d ule d pr oce d ure s h o w n i n t he Sc he d ule of 
Acti vities  (Ta ble 1 -1 ). T he e n d of t his st u d y is defi ne d as t he date of t he last sc he d ule d 
pr oce d ure  f or t h e last s u bject, as descri be d i n t he Sc he d ule of Acti vities (Ta ble 1 -1 ). 
5  
S T U D Y P O P U L A TI O N  
5. 1  
T y p e a n d Pl a n n e d N u m b er of S u bj e ct s  
T he st u d y will be c o n d u cte d i n male a n d fe male s u bjects i n g o o d ge neral /oral  healt h , wit h pr e-
e xisti n g self -re p orte d t o ot h se nsiti vit y, a n d at least t w o se nsiti ve teet h ( wit h cli nicall y c o nfir me d 
D H ) t hat meet st u d y eli gi bilit y  criteria at b ot h Scree ni n g ( Visit 1) a n d Baseli ne ( Visit 2).  
S ufficie nt s u bjects will be scree ne d a n d e ntere d i nt o t he accli matizati o n  p hase  t o e ns ure 
a p pr o xi matel y 1 1 0  s u bjects are ra n d o mize d t o i n vesti gati o nal pr o d uct (a p pr o xi matel y 5 5  
s u bjects per tr eat me nt gr o u p ) a n d a p pr o xi matel y 1 0 0  s u bjects c o m plete t he st u d y 
(a p pr o xi matel y 5 0  s u bjects per tr eat me nt gr o u p ), all o wi n g f or 1 0 %  dr o p o uts . S u bjects will be 
recr uite d pri maril y fr o m t he i n vesti gat or site data base. 
F or t his st u d y, a n e nr olle d s u bject is defi ne d as a s u bject  w h o has a gree d t o partici pate i n t he 
st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d s uc cessf ull y met t he st u d y 
eli gi bilit y criteria t o pr ocee d be y o n d t he s cree ni n g visit .  
T he i n vesti gat or site will ma ke e v er y eff ort t o e nr oll s u bjects re prese ntati ve of t he a d ult 
p o p ulati o n w h o w o ul d be nefit fr o m use of a n a nti -se nsiti vit y t o ot h paste; t he rati o nale f or st u d y 
p o p ulati o n selecti o n is pr o vi de d i n t he Scie ntific Rati o nale f or St u d y Desi g n  (Secti o n 4 . 2). 
A cli nical  st u d y ca n o nl y f ulfill its o bjecti ves if a p pr o priate s u bjects are e nr olle d. T he f oll o wi n g 
eli gi bilit y criteria ha ve b ee n  d esi g ne d t o sel ect s u bjects f or w h o m partici pati o n i n t he st u d y is 
c o nsi dere d a p pr o priate  w hile n ot u n necessaril y precl u d i n g a n y s u bject fr o m st u d y part ici pati o n. 
All rele va nt me dical a n d n o n -me dical c o n diti o ns s h o ul d be ta ke n i nt o c o nsi derati o n w he n 
deci di n g w het h er or n ot a s u bject is s uita ble.  Eli gi bilit y t o partici pate will  be re vie we d a n d 
d oc u me nte d b y t he i n vesti gat or (or m e dicall y q ualifie d desi g ne e) b ef ore eac h s u bject is 
i ncl u de d i n t he st u d y. 
5. 2  
I n cl u si o n Crit eri a 
Eac h  i n di vi d ual s u bject m ust meet all t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble t o partici pate  
i n t he st u d y. 
1.  S u bject p r o visi o n of si g ne d a n d date d i nf or me d c o nse nt bef ore a n y st u d y pr oce d ures are 
perf or me d.  
2.  S u bject is male or fe male .  
3.  S u bject is 1 8 t o  6 5  years  of a ge , i ncl usi ve, at t he ti me of si g ni n g t he i nf or me d c o nse nt. 
4.  S u bject is willi n g a n d a ble t o c o m pl y wit h t he stu d y visit  sc he d ule, pr o d uct usa ge 
i nstr ucti o ns, lifest yle restricti o ns a n d ot her st u d y pr oce d ures . 
5.  S u bject  is i n g o o d ge neral, oral a n d me nt al healt h wit h, i n t he o pi ni o n of t he i n vesti gat or or 
me dicall y q ualifie d  d esi g nee, n o cli nicall y si g nifica nt or rele va nt a b n or malities i n self-
re p orte d me dical hist or y , or u p o n oral e xa mi nati o n, t hat w o ul d i m pact t he ir safet y or  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 0  of 1 1 3  
well bei n g , or t he  o utc o m e s of t he st u d y, if t he y were t o partici p ate i n t he st u d y, or affect 
t heir a bilit y t o u n dersta n d a n d f oll o w st u d y re q uir e me nts . 
6.  S C R E E NI N G (Visit 1)  
S u bject m ust ha ve : 
a)  H ist or y of t o ot h se nsiti vit y lasti n g m ore t ha n si x m o nt hs b ut n ot m ore t ha n 1 0 years  
(self-re p orte d). 
b)  G o o d ge neral oral he alt h , wit h a mi ni m u m of 2 0 nat ural teet h. 
c)  M i ni m u m of 2 accessi ble, n o n-a djace nt teet h (i ncis ors, ca ni nes, pre m olars), i n differe nt 
q ua dra nts, w hic h  me et all of t he f oll o wi n g criteria: 
•  E x p ose d de nti n d ue t o facial/cer vical er osi o n, a brasi o n or gi n gi val recessi o n ( E A R). 
•  M GI = 0 dir ectl y a djace nt t o t he e x p ose d d e nti n  (i.e., t he test area o nl y ) (L o be ne, 
1 9 8 6 ). 
•  C li nical m o bilit y = 0 (Laster, 1 9 7 5 ).   
•  Cli nicall y c o nfir me d D H t o b ot h  tactile a n d  e va p orati ve (air) sti m uli:  
- 
Q ualif yi n g tactile t hres h ol d ≤ 2 0 g   
- 
Q ualif yi n g Sc hiff se nsiti vit y sc ore ≥ 2.  
7.  B A S E LI N E (Visit 2 , Pre-Tre at me nt ) 
S u bject m ust ha ve a mi ni m u m of t w o, n o n -a djace nt accessi ble teet h (i ncis ors, ca ni nes, 
pre m olars ), i n differe nt q ua drants,  wit h cli nicall y c o nfir me d D H t o b ot h tactile a n d 
e va p orati ve (air) sti m uli at b ot h  Scree ni n g  ( Visit 1) a n d  Baseli ne  (Visit 2) . 
•  Q ualif yi n g tactile t hres h ol d ≤ 2 0 g  at Scree ni n g &  Baseli ne  
•  Q ualif yi n g Sc hiff se nsiti vit y sc ore ≥ 2 at Scree ni n g &  B aseli ne 
T he cli nical e xa mi ner will select t w o ‘Test T eet h ’ fr o m t h ose w hic h meet t he tactile 
t hres h ol d a n d Sc hiff se nsiti vit y sc ore i ncl usi o n criteria at b ot h Scree ni n g a n d Baseli ne. 
N ote s: All teet h wit h cli nic ally c o nfir me d , q u alifyi n g levels of D H at Scree ni n g ( i.e., a 
Scree ni n g t a ctile t hres h ol d ≤ 2 0 g a n d a S cree ni n g Sc hiff se nsitivity sc ore ≥ 2 ) will be 
assesse d f or t actile se nsitivity  at B aseli ne . T eet h wit h a B aseli ne t actile t hres h ol d ≤ 2 0 g will 
t he n be assesse d f or B aseli ne ev a p or ative ( air) s e nsitivity.   
5. 3  
E x cl u si o n Crit eri a  
A n i n di vi d ual w h o me ets a n y of t h e f oll o wi n g e xcl usi o n criteria will be  e xcl u d e d fr o m 
partici pati o n  i n t he st u d y. 
1.  S u bject is a n e m pl o yee of t he i n vesti gat or  site directl y i n v ol ve d i n t he c o n d uct of t he st u d y, 
or a n e m pl o yee of t he i n vesti gat or  site ot her wise s u per vise d  b y t he i n vesti gat or , or a 
me m ber of t heir i m me diate fa mil y . 
2.  S u bject is a n e m pl o yee of t he  s p o ns or dir ectl y i n v ol ve d i n t he c o n d u ct of t he st u d y or a 
me m ber of t heir i m me diate fa mil y.  
3.  Fe male s u bject w h o is pre g na nt or i nte n di n g t o bec o me pre g na nt d uri n g  t he st u d y (self-
re p orte d).  
4.  Fe male s u bje ct  w h o is br eastfee di n g  (self-re p ort e d). 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 1  of 1 1 3  
5.  S u bject wit h k n o w n or s us pecte d i nt olera nce or h y perse nsiti vit y t o t he st u d y pr o d ucts , a n y 
of t heir state d i n gre di e nts  or cl osel y relat e d c o m p o u n ds  (self-re p orte d).  
6.  S u bject wit h a rece nt hist or y ( wit hi n t he last year) of alc o h ol or ot her s u bsta nce a b use  (self-
re p orte d). 
7.  S u bject is partici pati n g i n or has partici pate d i n ot her st u dies (i ncl u di n g n o n -me dici nal 
st u dies) i n v ol vi n g i n vesti gati o nal pr o d uct(s) wit hi n  3 0 da ys of Scree ni n g ( Visit 1)  or pla ns 
t o partici pate i n ot her st u dies (i ncl u di n g n o n-me dici nal s t u dies) d uri n g t his st u d y. 
8.  S u bject has partici pate d i n a t o ot h se nsiti vit y st u d y wit hi n 8 wee ks of Scree ni n g ( Visit 1). 
9.  S u bject is c urre ntl y usi n g a n oral care pr o d uct i n dicate d f or D H  relief or care of se nsiti ve 
teet h or has use d  a n a nti -se nsiti vit y pr o d uct wit hi n 8 wee ks of Scree ni n g ( Visit 1) 
S u bject s will be re q uire d t o bri n g t heir c urre nt or al c are pr o d ucts t o Scr ee ni n g ( Visit 1 ) f or 
st aff t o verify t he a bse nce of k n o w n a nti-se nsitivity i n gre die nts a n d se nsitivity-rel ate d cl ai ms  
o n  t he pr o d uct p ack a gi n g/ l a bel text. 
1 0.  S u bject ta kes d ail y d oses of me dicati o n s/treat me nts w hic h, i n t h e o pi ni o n of t he i n vesti gat or 
or me dicall y q ualifie d d esi g nee, c o ul d i nterfere wit h t heir perce pti o n of t o ot h se nsiti vit y 
(e. g., a nal g esics, a ntic o n v ulsa nts, a nti hista mi nes t hat ca use mar ke d or m o derate se d ati o n, 
se dati ves, tra n q uilizers, a nti de pressa nts, m o o d-alteri n g a n d a nti -i nfla m mat or y dr u gs). 
1 1.  S C R E E NI N G ( Visit 1)  
S u bject has ta ke n a nti bi otics i n t he 2 wee ks pri or t o Scree ni n g ( Visit 1). 
1 2.  B A S E LI N E (Visit 2 , Pre-Tre at me nt ) 
S u bject has ta ke n a nti bi otics i n t he 2 wee ks pri or t o Baseli ne ( Visit 2 ), i.e., d uri n g t he 
accli mati zati o n peri o d.  
1 3.  S u bject ta kes dail y d oses of a me dicati o n w hic h, i n t he o pi ni o n of t he i n vesti gat or or 
me dicall y  q ualifie d desi g nee, is ca usi n g xer ost o mia.  
1 4.  S u bject re q uires a nti bi otic pr o p h yla xis f or d e ntal pr oce d ures.  
1 5.  S u bject ha s ha d pr ofessi o nal t o ot h de -se nsitisi n g treat me nt wit hi n 8 wee ks of Scree ni n g 
( Visit 1). 
1 6.  S u bject has ha d a to ot h  bleac hi n g pr oce d ure wit hi n 8 wee ks of Scree ni n g  ( Visit 1). 
1 7.  S u bject has ha d de ntal pr o p h yla xis wit hi n 4 wee ks of Scree ni n g  ( Visit 1). 
1 8.  S u bject has ha d treat me nt f or peri o d o n tal disease (i ncl u di n g s ur ger y) wit hi n 1 2 m o nt hs of 
Scree ni n g  ( Visit 1). 
1 9.  S u bject has ha d scali n g or r o ot pla n ni n g wit hi n 3 m o nt hs of Scree ni n g  ( Visit 1). 
2 0.  S u bject wit h gr oss peri o d o ntal disease . 
2 1.  S u bject wit h a t o n g ue or li p pierci n g .  
2 2.  S u bject wit h e vi de nce of gr oss i ntra -oral n e glect or t he nee d f or e xte nsi v e d e ntal t hera p y.  
2 3.  S u bject wit h a fi xe d or re m o va ble partial pr ost hesis w hic h, i n t he o pi ni o n of t he i n vesti gat or 
or de ntall y  q ualifie d  desi g nee , co ul d i m pact st u d y o utc o mes . 
2 4.  S u bject wit h m ulti ple de ntal i m pla nts  w hic h,  i n t he o pi ni o n of t he i n vesti gat or or de nt all y  
q ualifie d  desi g nee , co ul d i m pact st u d y o utc o mes.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 2  of 1 1 3  
2 5.  S u bject wit h fi xe d or re m o va ble ort h o d o ntic braces/ ba n ds or a fi xe d ort h o d o ntic retai ner.  
2 6.  S P E CI FI C D E N TI TI O N E X C L U SI O N S F O R ‘ T E S T T E E T H’:  
a)  T o ot h wit h e vi de nce of c urre nt /rece nt caries 
b)  T o ot h wit h  (self-re p ort e d) treat me nt f or deca y wit hi n 1 2 m o nt hs of Scree ni n g  ( Visit 1). 
c)  T o ot h wit h e x p ose d de nti n a n d dee p, d efecti ve or facial rest or ati o ns.  
d)  T o ot h wit h a f ull cr o w n or ve neer. 
e)  T o ot h a djace nt t o a bri d g e a b ut me nt or cr o w n w hi c h, i n t he o pi ni o n of t he i n vesti gat or  
or de ntall y  q ualifie d  desi g nee , co ul d i m pact st u d y o utc o mes.  
f) Se nsiti ve t o ot h wit h c o ntri b uti n g eti ol o gies ot her t ha n E A R  t o e x p ose d de nti n. 
g)  Se nsiti ve t o ot h n ot e x pecte d t o be nefit fr o m use of a n a nti -se nsiti vit y t o ot h paste, i n t he 
o pi ni o n of t he i n vesti gat or  or de ntall y  q ualifie d  d esi g nee . 
2 7.  S u bject w h o, i n t he o pi ni o n of t he i n vesti gat or or desi g nee , is u na ble t o pr o vi de a p pr o pri ate  
res p o nses t o t he L M S trai ni n g questi o ns  (A p pe n di x 1 5. 4 ).  
2 8.  S u bject has pre vi o usl y bee n e nr olle d i n t his st u d y.  
2 9.  S u bject w h o, i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d d esi g nee , s h o ul d n ot 
partici pate i n t he st u d y.  
5. 4  
R a n d o mi z at i o n Crit eri a 
S u bjects will be ra n d o mize d i nt o t he st u d y pr o vi de d t he y ha ve satisfie d all s u bject selecti o n 
criteria. E ac h eli gi ble su bject will be stratifie d b y t he ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore 
of t heir t w o select e d ‘ Test Teet h’. T he str atificati o n fact or will gi ve rise t o t w o strata. 
•  Str at u m 1:  M a xi m u m Sc hiff se nsiti vit y sc ore = 2.  
•  Str at u m 2:  M a xi m u m Sc hiff se nsiti vit y sc ore = 3.  
5. 5  
Lif e st yl e C o n si d er ati o n s  
T he i n vesti gat or site ma y c o ntact s u bjects t o re mi n d t he m of a n a p pr oac hi n g sc he d ule d visit 
a n d a n y a p plica ble lifest yle restricti o ns.  
If, i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d desi g nee, a s u bject has n ot c o m plie d 
wit h a lifest yle restricti o n ( oral h y gie ne, dietar y or alc o h ol-relat e d) pri or t o a st u d y visit, e ver y 
eff ort will be ma de t o re -a p p oi nt t he m wit hi n t he per mitte d visit t olera nces , as defi ne d i n t he 
Sc he d ule of A cti vities  (Ta ble 1 -1 )). T he reas o n f or re-a p p oi nt me nt will be d oc u me nte d i n t h e 
electr o nic case re p ort f or m  (e C R F).  
If re-a p p oi nt me nt is n ot p ossi ble, t he f oll o wi n g visit s pecific acti o ns s h o ul d be ta ke n. 
•  B aseli ne ( Visit 2):  t h e s u bject will be wit h dr a w n fr o m t he st u d y (Secti o n 7. 1 ). N o 
cli nical assess me nts will be perf or me d. T he s u bject ma y  be re place d.  
•  D a y  2 8 ( Visit  3) : t he s u bject will c o nti n ue i n t he st u d y. N o cli nical assess m e nts will be 
perf or me d.  
•  D a y 5 6  ( Visit 4 ): if t h e s u bject ca n n ot b e rea p p oi nte d, t he y will be wit h dr a w n fr o m t he 
st u d y (Secti o n 7. 1 ). N o cli nical assess me nts will b e perf or me d. T he s u bject will n ot be 
re place d. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 3  of 1 1 3  
5. 5. 1  
Or al H y gi e n e  R e stri cti o n s  
F or t he D ur ati o n of t he St u d y:  Fr o m Scree ni n g ( Visit 1) t o t he S u bject’s L ast Visit   
•  S u bjects s h o ul d n ot use a n y ot her oral care pr o d ucts (e. g., t o ot h pastes, t o ot h br us hes, 
oral ri nses, t o n g ue cle a ners, 
w hite ni n g/ bleac hi n g pr o d ucts, i nter -de nt al clea ni n g 
pr o d ucts) t ha n t h ose pr o vi de d d uri n g t he st u d y.  
N ote:  Use of d e nt al fl oss is per mitte d t o re m ove i m p acte d f o o d o nly .  
•  S u bjects s h o ul d n ot use a n y ot her pr o d ucts i nte n de d f or treati n g or cari n g f or se nsiti ve 
teet h (i ncl u di n g her bal re me dies) t ha n t h ose pr o vi de d d uri n g t he st u d y. 
•  S u bjects s h o ul d n ot c he w g u m.  
Bef ore a Cli nic al Assess me nt Vis it: Fr o m B aseli ne ( Visit 2)  t o t he S u bject’s L ast Visit    
•  S u bjects will refrai n fr o m all oral h y gie ne pr oce d ures f or at least 8 h o urs bef ore  a st u d y 
visit . 
5. 5. 2  
Di et ar y a n d Al c o h ol R e stri cti o n s  
Bef ore a Cli nic al Assess me nt Visit : B aseli ne ( Visit 2)  t o t he S u bject’s L ast Visit  
•  S u bjects m ust n ot eat or dri n k f or at least 2 h o urs bef ore a cli nical ass ess me nt visit.  
N ote:  S m all si ps of r o o m -te m per at ure w ater ar e per mitte d t o t a ke me di c ati o ns or t o 
relieve a dry m o ut h u p t o 1 h o ur bef ore t heir a p p oi nt me nt ti me 
•  S u bjects s h o ul d refrai n fr o m e xcessi ve alc o h ol c o ns u m pti o n f or 2 4 h o urs bef ore a 
cli nical assess me nt visit . 
5. 5. 3  
C o ntr a c e pti o n  
T he st u d y t o ot h pastes are n ot c o ntra -i n dicate d f or pre g na nc y or  breastf ee di n g (t heir use w o ul d 
n ot be e x pect e d t o ca use h ar m t o t he m o t her, t he f oet us or a ba b y) a n d there will be  n o pre g na nc y 
war ni n g s o n t he la belli n g of a n y of t he st u d y pr o d ucts . T h us, st u d y-s pecific c o ntrace pti v e 
re q uire me nts are n ot de e me d necess ar y f or st u d y s u bjects (fe mal e or male).  
5. 6  
S cr e e n F ail ur e s  
Scree n fail ures are defi n e d as s u bjects w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y  ra n d o mize d. T o e ns ure tra ns p are nt re p orti n g of s cree n fail ure s u bjects, a 
mi ni mal set o f scree n fail ure i nf or mati o n will i ncl u de de m o gra p h y, scree n fail ure reas o n (e. g., 
wit h dra wal of c o nse nt), eli gi bilit y criteria, a n y pr ot oc ol de viati o ns a n d a n y A Es , as a p plica ble.  
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) will n ot 
be re -s cree ne d. 
5. 7  
S p o n s or’ s Q u alifi e d M e di c al P er s o n n el  
C o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y q ualifie d a n d e x peri e n ce d me dical/ de ntal 
pers o n nel or Cli nical Researc h Scie ntist ( C R S) f or t his st u d y is d oc u me nte d i n t he S t u d y 
C o ntact List l ocate d i n t he i n vesti gat or site file hel d at t he i n vesti gat or site. 
T he c o ntact n u m ber  is o nl y t o be use d b y i n vesti gator  staff see ki n g a d vice o n me dical/ de ntal 
q uesti o ns or pr o ble ms i n t he e v e nt t hat t he esta blis he d c o m m u nicati o n pat h wa ys bet w ee n t h e 
i n vesti gator  site a n d t he s p o ns or’s st u d y tea m are n ot a vaila ble.   
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 4  of 1 1 3  
T he c o nta ct n u m ber is n ot i nte n de d f or direct us e b y st u d y s u bjects. T o facilitate access t o 
a p pr o priatel y q u alifie d a n d e x peri e nce d i n vesti gat or site or s p o ns or pers o n nel o n st u d y -rel ate d 
me dical/ de ntal q u esti o ns or pr o ble ms, s u bjects will be pr o vi de d wit h a c o ntact car d.   T h e 
c o ntact car d will pr o vi de, as a mi ni m u m, pr ot oc ol i de ntifiers, t he s u bj ect’s st u d y i de ntificati o n 
n u m ber, c o nta ct i nf or mati o n f or t he i n vesti gat or  site, a n d c o ntact d etails i n t he e ve nt t hat t h e 
i n vesti gator  site ca n n ot be reac he d t o pr o vi de a d vice o n a me dical q uesti o n or pr o ble m 
i de ntifie d b y a healt hcare pr ofessi o nal ot her t ha n t he i n vesti gat or.    
5. 8  
R at er/ Cli ni c al A s s e s s or Q u alifi c ati o n s  
T he e xa mi ner res p o nsi ble f or t he cli nical efficac y meas ures will be a q ualifie d de ntal h y gie nist  
trai ne d i n t he cli nical ass ess me nt of D H (tactile a n d / or e va p orati ve (air) se nsiti vit y).  
T he oral ( O S T  a n d O H T ) e xa mi nati o ns  will be c o m plete d b y a q ualifie d de ntist , or  a de ntal 
h y gie nist , as nee de d.   
6  
I N V E S TI G A TI O N A L/ S T U D Y P R O D U C T S 
F or t he p ur p os es of t his st u d y, per I C H g ui deli nes a n d s p o ns or p olic y, st u d y i nter ve nti o n is 
defi ne d as a n y i n vesti g ati o nal i nter ve nti o n(s), mar kete d pr o d uct(s), place b o, or me dical 
de vice(s) i nte n d e d t o be a d mi nistere d t o a st u d y s u bject acc or di n g t o t he st u d y pr ot oc ol. T his 
i ncl u des a pr o d uct wit h a mar keti n g a ut h orizati o n w he n use d or ass e m ble d (f or m ulate d or 
pac ka g e d) i n a wa y differe nt fr o m t he a p pr o ve d f or m, or w he n use d f or a n u na p pr o ve d 
i n dicati o n, or w he n use d t o gai n f urt her i nf or m ati o n a b o ut a n ap pr o ve d use.  
6. 1  
St u d y Pr o d u ct  S u p pli e s  
Eac h  s u bject will recei ve s ufficie nt t u bes of t he accli matizati o n t o ot h paste a n d t heir assi g ne d 
i n vesti gati o nal t o ot h paste t o c o ver usa g e d uri n g t he accli matizati o n a n d treat me nt peri o ds, 
res pecti vel y. T he f oll o wi n g st u d y pr o d ucts (accli matizati o n a n d i n vesti gati o nal t o ot h pastes) 
will be s u p plie d b y t he s p o ns or’s Cli nical S u p plies d e part me nt  (T a ble 6 -1 ).  
T he t o ot h paste u sa ge i nstr ucti o ns are c o nsiste nt wit h t he pr o p ose d la belli n g f or t he Test 
T o ot h paste , w he n mar k et e d,  a n d wit h t he c o m mercial pac k i nstr ucti o ns f or t he R efere nce a n d 
Accli matizati o n T o ot h paste s.  
T a bl e 6 -1  
A c cli m ati z ati o n/ I nv e sti g ati o n al  T o ot h p a st e s  
Descri pti o n  
Accli m atiz ati o n  
T o ot h p aste  
Test  
T o ot h p aste  
Refere nce T o ot h p aste 
( Ne g ati ve C o ntr ol) 
Pr o d uct N a me  
Re g ular fl u ori de 
t o ot h paste 
(C ol g ate Ca vit y 
Pr otecti o n *)  
0. 4 5 4  % w/ w S n F 2 
t o ot h paste 
Re g ular fl u ori de 
t o ot h paste 
(Crest Ca vit y Pr otecti o n *)  
Fl u ori de Le vel  
1 0 0 0  p p m fl u ori de †  
1 1 0 0 p p m fl u ori de¥ 
1 1 0 0  p p m fl u ori de ≠ 
M aster 
F or m ul ati o n C o de  
N/ A  
  
N/ A  
Dis pe nsi n g Det ails  
O ne cart o n c o ntai ni n g 
2  t u bes of t o ot h paste at 
Scree ni n g ( Visit 1)  
O ne cart o n c o ntai ni n g 4  o ver -wra p pe d t u bes of 
t o ot h paste at Baseli ne ( Visit 2)  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 5  of 1 1 3  
R o ute of 
A d mi nistr ati o n  
T o pical Oral Use  
T o ot h p aste Us a ge 
I nstr ucti o ns 
D ose t he t o ot h br us h wit h a ri b b o n of t o ot h paste, acr oss t he f ull br us h hea d . 
Start t he ti mer ( pre -set f or 1-mi n ute).  
Br us h t he e ntire 
de ntiti o n t h or o u g hl y 
f or at least 1-ti me d 
mi n ute, t wice dail y 
( m or ni n g & e ve ni n g). 
Br us h t he e ntire 
de ntiti o n t h or o u g hl y f or 
at least 1 -ti me d mi n ute, 
t wice dail y ( m or ni n g & 
e ve ni n g), ma ki n g s ure t o 
br us h t he se nsiti ve areas 
of t he t w o ' Test teet h' 
caref ull y first.  
Br us h t he e ntire 
de ntiti o n t h or o u g hl y 
f or at least 1-ti me d 
mi n ute, t wice dail y 
( m or ni n g & e ve ni n g). 
S u bjects w h o wis h t o ri nse after  br us hi n g will be i nstr ucte d t o ri nse wit h  
1 0 ml water usi n g gra d uate d ri nsi n g c u p pr o vi de d. 
D ur ati o n of 
Tre at me nt  
A p pr o xi matel y 8 wee ks ( 5 6 ± 3 da ys)  
Ret ur n 
Re q uire me nts  
All use d/ u n use d t u bes t o be ret ur ne d t o t he s p o ns or 
*  C o m merciall y  a vaila ble dail y use , re g ular fl u ori de t o ot h paste, U S  mar ket .   
†   As s o di u m m o n ofl u or o p h os p hate    ¥ As S n F 2     ≠ As Na F   
S ufficie nt s u p plies of t h e f oll o wi n g s u n dr y ite ms (Ta ble 6 -2 ) will b e s u p plie d t o c o m plete t h e 
st u d y b y t he s p o ns or’s Cli nical S u p plies d e part me nt  (t o be dis pe ns e d b y site staff, as re q uire d ). 
T a bl e 6 -2  
S u n dr y It e m s  
Ite m 
P ac k Desi g n  
Dis pe nsi n g Det ails  
Ret ur n/ Dis p os al Det ails  
Use d S a m ples  
U n use d 
S a m ples  
Oral B Se nsi -S oft  
(U S  mar ket)  
M a n u al, fl at tri m, 
me di u m t o ot h br us hes  
O ne t o ot h br us h i n 
its c o m mercial 
pac k  
Scree ni n g ( Visit 1):  
O ne t o ot h br us h  
B aseli ne ( Visit 2):  
O ne t o ot h br us h  
 
Destr o y at site 
usi n g site dis p osal 
pr oce d ures.   
 
Ret ur n t o 
s p o ns or 
C o u nt d o w n 
Ti mers  
O ne ti mer i n its 
c o m mercial pac k  
Scree ni n g ( Visit 1):  
O ne ti mer  
 
S u bject t o kee p or 
destr o y at site 
usi n g site dis p osal 
pr oce d ures .  
 
Gra d uate d 
Ri nsi n g  C u ps  
N/ A  
Scree ni n g ( Visit 1):  
4 c u ps  
B aseli ne ( Visit 2):  
8 c u ps  
S u bject t o kee p or 
destr o y at site 
usi n g site dis p osal 
pr oce d ures . 
O pa q ue Carrier 
Ba gs  
N/ A  
Scree ni n g ( Visit 1):  
O ne ba g  
B aseli ne ( Visit 2):  
O ne ba g  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 6  of 1 1 3  
Detaile d i nstr ucti o ns f or t he ret ur n of st u d y pr o d uct s a n d s u n dr y s u p plies f or acc o u nt a bilit y 
c hec ks a n d s u bse q ue nt d estr ucti o n will be pr o vi d e d b y t he s p o ns or at Site I nitiati o n a n d pri or 
t o st u d y cl ose o ut. 
6. 1. 1  
M e di c al D e vi c e s    
T he me dical de vi ce pr o vi de d b y t he s p o ns or f or us e i n t his st u d y is t he ma n ual t o ot h br us h  ( Oral 
B Se nsi -S oft t o ot h br us h , U S  mar ket) t o be use d t o a p pl y t he st u d y pr o d ucts  b y t wice dail y 
t o ot h br us hi n g. The de vice  will be s u p plie d t o st u d y s u bjects  i n its c o m mercial pac k; u sa ge 
i nstr ucti o ns will be  c o nsiste nt wit h t he c o m mercial pac k i nstr ucti o ns.   
D e vice d eficie n cies, (i n cl u di n g malf u ncti o n, use err or a n d i na de q u ate la belli n g) will  be 
d oc u me nte d a n d re p orte d b y t he i n vesti gat or t hr o u g h o ut t he st u d y a n d a p pr o priatel y ma na ge d 
b y t he s p o ns or  (see Secti o n 1 0 . 1 0). T he de vice d oes n ot i ncl u de a n y me dici nal, h u ma n or a ni mal 
or bi ol o gicall y acti ve materials .  
6. 1. 2  
D o s a g e F or m a n d P a c k a gi n g  
T he st u d y pr o d ucts  are t o ot h pastes . T he y are i nte n de d f or t o pical oral use a n d will be a p plie d 
usi n g a ma n ual t o ot h br us h.  
T he i n vesti gati o nal t o ot h pastes  will be pr o vi de d t o t he i n vesti gat or site i n la mi nate t u bes, 
o ver wra p pe d i n w hite vi n yl  (t o mas k t heir i de ntit y, a n d t o o bsc ure a n y bra n di n g , i mages  a n d 
te xt o n t he c o m mercial pac k of t he  Refere n ce T o ot h paste ) wit h a st u d y la bel affi xe d. T he 
accli matizati o n t o ot h paste will be s u p plie d i n its c o m mercial pac k, wit h o ut o ver wra p pi n g , wit h 
a st u d y la bel affi xe d . T he c o nte nt  of t he pr o d uct la bels will be i n acc or da nce wit h all a p plica ble 
re g ulat or y re q uire me nts a n d will be t he res p o nsi bilit y of t he s p o ns or’s Cli nical S u p plies 
d e part me nt. E ac h st u d y la bel will c o ntai n  (b ut n ot be li mite d t o ) t h e pr ot oc ol n u m ber  a n d 
st ora ge re q uire me nts.  
Care s h o ul d b e t a ke n t o e ns ure all  s u p plie d st u d y pr o d uct  is mai ntai ne d i n g o o d c o n diti o n.  It is 
i m p orta nt t hat all pr o d uct la bels re m ai n i ntact a n d l e gi ble f or t h e d urati o n of t he st u d y. S u bjects 
s h o ul d be i nstr ucte d t o n ot re m o ve or deface a n y part of t he st u d y la bel. 
St u d y pr o d uct s will be recei ve d at site b y me m b ers of t he i n vesti gat or tea m res p o nsi ble f or 
pr o d uct a d mi nistrati o n. T hese i n di vi d uals will n ot be i n v ol ve d i n a n y safet y  or  efficac y 
assess me nts or a n y ot her as pect of t he  st u d y t hat c o ul d be i nfl ue nce d b y k n o wle d ge of t he 
i n vesti gati o nal t o ot h paste a s u bject has b ee n assi g ne d t o.  
St u d y  pr o d ucts s u p plie d are f or use i n t his cli nical st u d y o nl y a n d s h o ul d n ot be use d f or a n y 
ot her p ur p ose.  
6. 1. 3  
Pr o d u ct  Di s p e n si n g  
S u bjects will be assi g ne d t o i n vesti gati o nal t o ot h paste i n acc or da n ce wit h t he ra n d o mizati o n 
sc he d ule g e nerate d b y a s p o ns or-a p pr o ve d  ve n d or, pri or t o t he start of t he st u d y, usi n g vali date d 
s oft ware. 
T he pr o d uct dis pe nsi n g area (s) will be se parate fr o m t h e cli nical e xa mi nati o n area (s). 
I n v esti gati o nal t o ot h pastes will be dis pe ns e d t o t h e s u bject, p er pr ot oc ol , i n bli n de d fas hi o n b y 
trai ne d st u d y pers o n nel. T hese staff me m bers will n ot be i n v ol ve d i n a n y safet y or cli nical 
effic ac y assess me nts or a n y ot her as pect of t h e st u d y t hat c o ul d b e i nfl ue n ce d b y k n o wi n g w hic h 
pr o d uct a s u bject has bee n assi g ne d t o. A n a d diti o nal me m ber of t he dis pe nsi n g  staff will verif y 
t he dis pe nsi n g pr oce d ure has bee n c o m plet e d c orrectl y  f or eac h s u bject.   
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 7  of 1 1 3  
A rec or d of pr o d uct dis pe nsi n g t o eac h s u bject will be mai ntai ne d i n t he dis pe nsi n g l o g; 
c o m pleti o n of t he dis pe nsi n g pr oce d ure will be rec or de d i n t he eC R F.  
6. 2  
A d mi ni str ati o n  
O nl y s u bjects e nr olle d i n t he st u d y ma y recei ve st u d y pr o d ucts  a n d o nl y a ut h orize d site staff 
ma y s u p pl y a n d a d mi nister st u d y pr o d ucts . All st u d y i nter ve nti o ns m ust be st ore d i n a sec ure, 
e n vir o n me ntall y c o ntr oll e d, a n d m o nit ore d ( ma n u al or a ut o mat e d) area i n acc or da nce wit h t he 
pr o d uct la bel st ora g e c o n diti o ns wit h access  li mite d t o t he a ut h orize d site st aff o nl y . 
S u bjects will self -a d mi nister t he accli matizati o n t o ot h paste (fr o m Visit 1 t o Visit 2) a n d t heir 
assi g ne d i n vesti gati o nal t o ot h paste (fr o m Visit 2 t o Visit 4 ) acc or di n g t o t he usa ge i nstr ucti o ns 
pr o vi de d b y  t he dis pe nsi n g staff at t he i n vesti gat or site a n d as descri be d  i n t heir diar y. S u bjects 
will be i nstr ucte d t o rec or d eac h br us hi n g wit h st u d y pr o d uct i n t heir diar y.  
T o hel p e ns ur e s u bjects f ull y u n dersta n d t h e a m o u nt of t o ot h paste t o use, t he br us hi n g 
instr ucti o ns a n d h o w t o c o m plete t he diar y:  
•  Scree ni n g ( Visit 1):  Staff will de m o nstrate dis pe nsi n g a f ull ri b b o n of t o ot h paste al o n g 
t he le n gt h of t he t o ot h br us h hea d t o eac h e nr olle d s u bject a n d s u per vise t heir first ti me d 
br us hi n g wit h t he accli matizati o n t o ot h paste  a n d diar y c o m pleti o n at t he e n d of t he visit, 
after all cli nical assess me nts ha ve bee n c o m plete d.  
•  B aseli ne ( Visit 2):  Staff will s u per vise t he dis pe nsi n g of a f ull ri b b o n of t o ot h paste b y 
eac h ra n d o mize d s u bject a n d s u per vise t he first ti me d br us hi n g wit h t heir assi g ne d 
i n vesti gati o nal t o ot h paste a n d diar y c o m pleti o n. Staff 
will s h o w eac h s u bject 
ra n d o mize d t o T est T o ot h paste t he l ocati o n of t heir ‘ Test T eet h’ a n d c o nfir m t he s u bject 
ca n c orrectl y l ocate t h e t w o ‘ Test T eet h’ t he ms el ves, pri or t o starti n g t heir o n -site ti me d 
br us hi n g .  
•  D a y 2 8 ( Visit 3 ): Staff will s u per vise eac h s u bject br us hi n g wit h t heir assi g ne d 
i n vesti gati o nal t o ot h paste an d c o m pleti n g t heir diar y at t he e n d of t he visit, after all 
cli nical assess me nts ha ve bee n c o m plete d. Staff will c hec k  t hat s u bjects ra n d o mize d t o 
Test T o ot h paste ca n c orrectl y i de ntif y t heir ‘ Test Teet h’ pri or t o starti n g t heir o n -site 
ti me d br us hi n g.  If a s u bject  ca n n ot c orrectl y i de ntif y t heir t w o ‘ Test Teet h’, t he y will 
be re -i nstr ucte d i n t heir l ocati o n a n d a d e viati o n will be rec or de d. 
O n -site a d mi nistrati o n of st u d y pr o d ucts will be rec or de d i n t he dis pe nsi n g l o g a n d t he e C R F . 
6. 2. 1  
M e di c ati o n/ D o si n g Err or s  
I n t his st u d y, d osi n g err ors ma y res ult fr o m t he a d mi nistrati o n or use  of  t he wr o n g st u d y pr o d uct,  
b y t he wr o n g s u bject, at t he wr o n g ti me, i n t he wr o n g wa y . S uc h d osi n g err ors s h o ul d be 
ca pt ure d i n t he eC R F.   
D osi n g err ors are re p orta ble irres pecti ve of t he prese nce of a n ass oci ate d A E, i ncl u di n g:  
•  D osi n g err ors i n v ol vi n g s u bject e x p os ure t o a n y of t he st u d y pr o d ucts.  
•  P ote ntial d osi n g err ors or uses o utsi de of w hat is f oresee n i n t he p r ot oc ol t hat d o or d o 
n ot i n v ol ve t he partici pati n g s u bject.  
If a d osi n g err or is acc o m pa nie d b y a n A E, as d eter mi ne d b y t he i n vesti gat or or me dicall y 
q ualifie d desi g nee , t h e d osi n g err or a n d a n y ass ociate d A Es  are t o be rec or de d i n t he eC R F.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 8  of 1 1 3  
6. 2. 2  
O v er d o s e  
A n o ver d ose is a deli berate or i na d verte nt a d mi nistrati o n of a st u d y pr o d uct at a n a m o u nt hi g her 
t ha n s pecifie d i n t he pr ot oc ol. O ver d ose is n ot li kel y t o occ ur i n t his st u d y.  
O ver d ose p er se is n ot a n A E. H o we v er, a n y cli nical se q uelae of a n o v er d ose s h o ul d  be re p ort e d 
as a n A E (or  seri o us a d v erse e v e nt ( S A E), as a p pr o priate)  p er pr ot oc ol  f oll o wi n g t he A E a n d 
S A E re p orti n g i nstr ucti o ns.  
6. 3  
St u d y Pr o d u ct St or a g e   
T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ur e c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all st u d y pr o d ucts  recei ve d a n d t hat a n y discre pa ncies are re p orte d 
a n d res ol ve d b ef ore use , acc or di n g t o t he s u p plie d s hi p pi n g d oc u me ntati o n . 
T he i n vesti gat or or desi g nee will e ns ure t hat all st u d y pr o d ucts are st ore d i n a sec ure d area wit h 
c o ntr olle d access u n der t he re q uire d st ora ge c o n diti o ns, i n acc or da n ce wit h a p plica bl e 
re g ulat or y re q uire me nts a n d t he pr o d uct la b el.   
In v esti gat or site s yste ms m ust be ca pa bl e of meas uri n g a n d d oc u me nti n g ( e. g., via a l o g), as a 
mi ni m u m, dail y mi ni m u m a n d ma xi m u m te m perat ures f or all st u d y pr o d uct st ora ge l ocati o ns 
(i ncl u di n g fr oze n, refri gerate d, a n d/ or r o o m-te m perat ur e pr o d ucts).  T his s h o ul d be ca pt ure d 
fr o m t he ti me of first pr o d uct recei pt t hr o u g h o ut t he st u d y.  F or c o nti n u o us m o nit ori n g s yste ms, 
a l o g or site pr oce d ure t hat e ns ures acti ve d ail y e val uati o n f or e xc ursi o ns s h o ul d be i n place.  
T he o perati o n of te m perat ure -m o nit ori n g de vice s a n d te m perat ure-c o ntr olle d st ora ge u nits 
(e. g., refri gerat ors) s h o ul d be re g ularl y i ns pecte d t o e ns ure t he y are mai ntai ne d i n w or ki n g 
or der.  
A n y e xc ursi o ns fr o m t he pr o d uct -la bel st ora ge c o n diti o ns s h o ul d be re p orte d t o a p pr o priate sit e 
staff u p o n disc o ver y a n d c o m mu nicate d t o s p o ns or as s o o n as p ossi ble.  T he i n vesti gat or site 
s h o ul d acti vel y p urs ue o pti o ns f or ret ur ni n g t he st u d y pr o d uct t o t he st ora ge c o n diti o ns 
descri be d o n  its la bel as s o o n as p ossi ble.  E xc ursi o ns fr o m st ora ge re q uire me nts, i ncl u di n g a n y 
acti o ns ta ke n, m ust be d o c u me nte d as a pr ot oc ol d e viati o n a n d re p orte d t o t he sp o ns or.   
O nce a n e x c ursi o n is i de ntifie d, t he affecte d st u d y pr o d uct ( or pr o d ucts) m ust be q uara nti ne d 
a n d n ot use d u ntil t he s p o ns or pr o vi des d oc u me ntati o n of per missi o n t o use. Use  of a n y of t he 
affecte d st u d y pr o d uct(s) pri or t o s p o ns or a p pr o val will be c o nsi dere d a pr ot oc ol de viati o n.   
Site staff will i nstr uct s u bjects o n t he pr o per st ora ge re q uir e me nts f or all ta ke -h o me st u d y 
pr o d ucts , i n acc or da nce  wit h  t he la bel re q uir e me nts.  
6. 4  
St u d y Pr o d u ct A c c o u nt a bilit y  
S t u d y pr o d ucts are s u p plie d f or use i n t his cli nical st u d y o nl y a n d s h o ul d n ot be use d f or a n y 
ot her p ur p ose.  T he i n v esti gat or is res p o nsi ble f or st u d y pr o d uct acc o u nta bilit y, rec o nciliati o n, 
a n d rec or d mai nte na n ce.  
S t u d y pr o d ucts m ust be recei ve d b y desi g nate d pers o nnel  at t he i n vesti gat or site, ha n dle d a n d 
st ore d safel y a n d pr o perl y, a n d ke pt i n a sec ure d l ocati o n t o w hic h o nl y a ut h orize d  staff ha v e 
access. U p o n recei pt, eac h st u d y pr o d uct s h o ul d b e st ore d i n acc or da n ce wi t h t he i nstr ucti o ns 
s pecifie d o n t he pr o d u ct la bel.  
St u d y pr o d ucts will  be dis pe nse d t o e nr olle d /ra n d o mize d s u bjects o nl y , i n acc or da nce wit h t h e 
pr ot oc ol, b y a ut h orize d site staff.  S u bjects will ret ur n all use d / u n use d t u bes of  accli mati zati o n 
t o ot h paste t o t he i n vesti gat or site at t heir Bas eli ne  visit  ( Visit 2). S u bjects will bri n g all  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 3 9  of 1 1 3  
use d /u n use d t u bes of t heir assi g ne d i n vesti gati o nal t o ot h paste t o eac h of t heir sc he d ule d visits 
t o t he i n vesti gat or site (per Sc he d ule of Acti vities , Ta ble 1 -1 ) a n d ret ur n  all use d/ u n use d st u d y 
pr o d uct t o t he i n vesti gat or site at st u d y c o ncl usi o n. Ret ur ne d st u d y pr o d ucts s h o ul d n ot be re -
dis pe nse d t o a n y s u bject.  
T he i n vesti gator  site m ust mai ntai n a de q uat e rec or ds (e. g., pr o d uct acc o u nta bilit y f or m s) 
d oc u me nti n g t he recei pt, use, l oss, ret ur n or ot her dis p ositi o n of all st u d y pr o d uct a n d s u p plies. 
A cc o u nta bilit y rec or ds m ust be a vaila ble f or i ns pe cti o n b y t he st u d y m o nit or d uri n g t he st u d y. 
P r o d uct acc o u nta bilit y will be m o nit ore d  d uri n g i n vesti gat or site visits a n d o n  t he c o m pleti o n 
of t he st u d y , as re q uir e d b y t he st u d y m o nit ori n g pla n.  
6. 4. 1  
D e str u cti o n of St u d y Pr o d u ct S u p pli e s  
At t he e n d of  t h e st u d y, t he in vesti gat or or a n a p pr o priate desi g ne e a n d t he s p o ns or’s 
re pres e ntati ve (st u d y m o nit or) will i n ve nt or y all use d a n d u n us e d st u d y pr o d ucts a n d t h e st u d y 
pr o d uct acc o u nta bilit y rec or d f or ret ur ne d st u d y pr o d ucts will be c o m plete d.  
All st u d y pr o d uct ( use d a n d u n use d) f or t his cli nical st u d y will be ret ur ne d t o t he s p o ns or or 
desi g nate d ve n d or f or d estr ucti o n usi n g t he ret ur n i nstr ucti o ns pr o vi de d  b y t he s p o ns or’s 
Cli nical S u p plies De part me nt .  
U n use d s u n dr y ite ms will be ret ur ne d t o t he s p o ns or; use d ite ms will be  dis p ose d of at t he 
i n vesti gat or site as descri be d i n Secti o n 6 .1  (Ta ble 6 . 2). Doc u me nte d a p pr o val f or dis p osal of 
use d s u n dr y ite ms m ust be recei ve d fr o m t he s p o ns or’s Cli nical S u p plies De part me nt  pri or t o 
des tr ucti o n. 
Detaile d i nstr ucti o ns f or t he ret ur n of st u d y pr o d uct s a n d t he destr u cti o n of s u n dr y ite ms, will 
be pr o vi de d b y t he s p o ns or pri or t o t he st u d y cl ose o ut visit. 
6. 5  
Bli n di n g a n d All o c ati o n/ R a n d o mi z ati o n  
Q ualif yi n g s u bjects will be ce ntrall y ra n d o mize d t o o ne of t w o i n vesti gati o nal t o ot h pastes usi n g 
a n I nteracti ve Res p o nse Tec h n ol o g y (I R T). Bef ore t h e st u d y is i nitiat e d, trai ni n g, l o gi n 
i nf or mati o n a n d directi o ns f or t he I R T will be pr o vi de d t o t he i n vesti gat or site. In v esti gati o nal 
t o ot h paste will be dis pe nse d acc or di n g t o t he i nstr ucti o n recei ve d t hr o u g h t he I R T at t he 
Baseli ne visit ( Visit 2). Ret ur ne d st u d y pr o d ucts s h o ul d n ot be re -dis pe nse d t o a n y s u bject.  
O nl y s u bjects w h o meet t he st u d y  selecti o n criteria will  be ra n d o mize d t o treat me nt. Q ualif yi n g 
su bjects will be stratifie d b y t he ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore of t heir t w o select e d 
‘ Test Teet h’; th is stratificati o n fact or will gi ve rise t o t w o strata. 
•  Str at u m 1:  M a xi m u m Sc hiff se nsiti vit y sc ore = 2. 
•  Str at u m  2:  M a xi m u m Sc hiff se nsiti vit y sc ore = 3.  
T his st u d y is descri be d as e xa mi ner -bli n d ( t h e cli nical e xa mi ner (s) will be bli n de d t o treat me nt 
recei v e d). H o we ver, s t u d y su bjects, i n vesti gat or site staff i n v ol ve d i n safet y or efficac y 
assess me nts , st u d y statisticia n(s), d ata ma na ge m e nt staff, ot her e m pl o yees of t he S p o ns or 
(i ncl u di n g t he C R S ) a n d ve n d ors acti n g o n be h alf of t he s p o ns or w h o m a y i nfl ue nce st u d y 
o utc o mes will als o be bli n de d t o treat me nt allocati o n.  M o nit ors a n d t he s p o ns or’s Cli nical St u d y 
Ma na ger ( C S M) ca n n ot be f ull y bli n de d as t he y ma y  o bser ve s u bjects br us hi n g wit h t heir 
all ocate d treat me nt w hile at t he i n vesti gat or site. 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 0  of 1 1 3  
As descri be d i n Secti o n 4 . 2, to mai ntai n t he bli n d  t hr o u g h o ut t he st u d y: 
•  S t u d y s u bjects will see a n d use o nl y o ne of t he t w o i n vesti gati o nal t o ot h pastes f or t he 
d urati o n of t he treat me nt peri o d . T he y will be i nstr ucte d n ot t o disc uss t he a p peara n ce, 
usa ge  or percei ve d p erf or ma nce of t h eir assi g ne d i n vestigat i o nal t o ot h paste wit h t he 
cli nical e xa mi ner (s), wit h staff i n v ol ve d i n cli ni cal  ass ess me nts or wit h ot her st u d y 
s u bjects.  
•  T he i n vesti gati o nal  t o ot h pastes will be pr o vi de d  t o t he i n vesti gat or site o ver wra p pe d i n 
w hite vi n yl t o mas k t heir i de ntit y , a n d t o o bsc ure a n y bra n di n g  o n t he Refere nce 
T o ot h paste , wit h a st u d y la bel affi x e d.  
•  T he i n vesti gati o nal  t o ot h pastes will be s u p plie d i n c art o ns; eac h cart o n will  c o ntai n 4 
o ver -wra p pe d t u bes of t o ot h paste. T he c art o n a n d its 4 t u bes will be la belle d wit h t he 
sa me u ni q ue ra n d o mizati o n n u m ber . S u bjects will be ce ntrall y ra n d o mi ze d t o treat me nt 
i n or der of q u alificati o n usi n g a n I R T ; pr o d u ct c o des will n ot be use d. 
•  T he c li nical e x a mi ner(s) a n d site staff i n v ol ve d i n efficac y a n d safet y assess me nts will 
n ot be p er mitte d i n a n y area w here t h e i n vesti gati o nal t o ot h pastes or diari es are st ore d, 
dis pe nse d  or i n use. 
•  Site s taff i n v ol ve d i n t he dis pe nsi n g  of i n vesti gati o nal t o oth pastes , pr o vi di n g br us hi n g 
a n d diar y c o m pleti o n i nstr ucti o n, s u per visi o n of o n-site br us hi n gs , treat me nt 
c o m plia nce c hec ks a n d pr o d uct acc o u nta bilit y  will n ot be  i n v ol ve d i n cli nical efficac y 
a n d safet y ass ess me nts  a n d will w or k i n a s e parate area fr o m t h e cli nical e xa mi ner(s) 
a n d i n vesti gat or staff i n v ol ve d i n efficac y a n d s afet y assess me nts. 
•  S u bjects will be i nstr ucte d n ot t o re m o ve t heir assi g ne d i n vesti gati o nal t o ot h paste or 
diar y fr o m t he o pa q ue carrier ba g pr o vi de d o utsi de of t he dis pe nsi n g/ s u per vise d 
br us hi n g r o o m, w hile at t he i n vesti gat or site. 
•  W here  cert ai n staff will  be u n bli n de d t o carr y o ut t heir res p o nsi bilities (e. g., staff 
i n v ol ve d i n S A E  re p orti n g, m o nit ors), t he i n vesti g at or a n d s p o ns or are re q uire d t o  p ut  
a de q uate pr oce d ures i n place t o pre ve nt i na p pr o priate disse mi nati o n of treat me nt 
i de ntificati o n.  
6. 6  
Br e a ki n g t h e Bli n d  
At st u d y i nitiati o n, t he i n vesti gat or site will be i nstr ucte d o n t he met h o d f or brea ki n g t he bli n d; 
t his will be a n electr o nic pr ocess.  
T h e ele ctr o nic s yste m will be pr o gra m me d wit h bli n d -brea ki n g i nstr ucti o ns. I n case of a n 
e mer ge n c y, t he i n vesti gat or has s ole res p o nsi bilit y f or deter mi ni n g if t he u n bli n di n g of t he 
s u bject’s treat me nt assi g n me nt is 
warra nte d. S u bject safet y 
m ust al wa ys be t he first 
c o nsi derati o n i n m a ki n g s uc h a det er mi nati o n. If t he i n v esti gat or deci des t hat u n bli n di n g is 
warra nte d, t he y  s h o ul d ma ke e ver y eff ort t o c o ntact t he s p o ns or pri or t o u n bli n di n g t he s u bject’s 
treat me nt assi g n me nt u nless t his w o ul d dela y e mer ge nc y tr eat me nt of t he s u bject.  
O nce  tr eat me nt assi g n m e nt is u n bli n de d, t he s p o ns or m ust be n otifie d wit hi n 2 4 h o urs of  
brea ki n g t he bli n d. T he date a n d reas o n f or brea ki n g t he bli n d m ust be rec or de d i n s o urce 
d oc u me ntati o n a n d t h e e C R F, as a p plica ble. T h e i n vesti gat or site m a y als o be re q uire d be 
re q uire d t o i nf or m t he I R B if t he bli n d is br o ke n.  
A n y A E ass ociat e d wit h brea ki n g t he bli n d m ust be rec or de d a n d re p orte d p er  pr ot oc ol.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 1  of 1 1 3  
6. 7  
C o m pli a n c e  
D iaries will be s u p plie d t o pr o m ote c o m plia nce a n d t o ca pt u re details of st u d y pr o d uct use 
t hr o u g h o ut t he st u d y peri o d. Eac h s u bject will be pr o vi de d wit h t hree diar i es, o ne at Scree ni n g 
( Visit 1), o ne at Baseli ne ( Visit 2) a n d o ne at Da y 2 8 ( Visit 3) , t o rec or d eac h br us hi n g wit h t he 
accli matizati o n a n d i n vesti gati o nal t o ot h pastes. T he diaries will als o pr o vi de  pr o d uct  usa g e 
i nstr ucti o ns f or t he s u bject t o refer t o t hr o u g h o ut t heir partici pati o n i n t he st u d y. 
•  S u bjects will be i nstr uct e d t o n ote a n y misse d/a d diti o nal br us hi n gs  a n d t he reas o ns f or 
misse d/a d diti o nal br us hi n gs  i n t he diar y. 
•  S u bjects will als o be i nstr ucte d t o rec or d a d diti o nal i nf or mati o n i n t he diar y s uc h as 
c ha n ges i n healt h, oral pr o ble ms, c ha n ges i n me dicati o ns/treat me nts , ne w me dicati o ns/  
treat me nts a n d a n y iss ues wit h t he t o ot h paste t he y are us i n g i n t he diary .  
S u bjects will be i nstr ucte d t o bri n g t heir c o m plete d diar y  t o eac h sc h e d ule d st u d y visit. 
C o m plete d diaries will be re vie we d b y i n vesti gat or staff at t he start of eac h st u d y visit (t o 
mai ntai n t he bli n d, staff perf or mi n g diar y re vie ws s h o ul d n ot be i n v ol ve d i n a n y safet y or 
effic ac y ass ess me nts) . A n y misse d or a d diti o nal br us hi n gs  will be rec or de d i n t he e C R F as 
pr ot oc ol de viati o ns  a n d s u bjects will be re -i nstr uct e d i n c orrect pr o d uct usa ge re q uir e me nts a n d 
diar y c o m pleti o n , as nee de d .  
I nf or mati o n rec or de d i n t he diar y relati n g t o c ha n g es i n healt h , me dicati o ns  a n d treat me nts will 
be re vie we d b y t he i n vesti gat or , or me dicall y  q ualifie d desi g nee , wit h t he s u bject a n d 
tra nscri be d i nt o t he eC R F , as a p pr o priate  (e. g., as a n A E). I nf or mati o n relat e d t o pr o d uct use or 
iss ues s h o ul d als o tra nscri be d i nt o t he eC R F , as nee de d , ta ki n g care t o mai ntai n t he bli n d. 
S u bjects will be i nstr uct e d t o bri n g all t u bes of st u d y pr o d uct ( use d a n d u n use d) a n d t heir  
t o ot h br us h t o eac h sc he d ule d st u d y visit. St u d y staff will perf or m a vis ual c hec k of pr o d uct 
usa ge  a n d t o ot h br us h c o n diti o n . A n y s us pecte d o ver or u n der us e will be d oc u me nte d i n t he 
e C R F a n d t he s u bject will be re -i nstr uct e d i n t he c orrect usa g e re q uire me nts.  
T o  c o nfir m  t he s u bject u n dersta n d s t he usa ge i nstr ucti o ns pr o vi de d at Scree ni n g ( Visit 1)  a n d 
Baseli ne ( V isit 2) , t heir first use of st u d y pr o d uct (accli matizati o n t o ot h paste a n d i n vesti gati o nal  
t o ot h paste, res pecti vel y) will be s u p er vise d o n -site. T o facilitate c o m plia nce, a furt her 
su per vi se d br us hi n g will be c o m plete d  o n -site at t he e n d of V isit 3 ( Da y 2 8) . Su bjects dee m e d 
n o n -c o m plia nt wit h a n y as pect of t he usa g e re q uire me nts or diar y c o m pleti o n  will be re-
i nstr ucte d i n c orrect pr oce d u re. A n y de viati o n fr o m pr ot oc ol re q uir e me nts will be rec or de d i n 
t he e C R F.  
6. 8  
C o n c o mit a nt M e di c ati o n/ Tr e at m e nt  
A n y me dicati o ns, treat me nts or vacci ne s (i n cl u di n g o ver-t he-c o u nter or pres cri pti o n me dici nes, 
vita mi ns a n d/ or her bal s u p ple me nts) ta ke n  or recei ve d  d uri n g t he st u d y, fr o m t he si g ni n g of  
i nf or me d c o nse nt, m ust be rec or de d i n t he eC R F wit h i n dicati o n, reas o n f or use, u nit d ose, dail y 
d ose a n d st art/st o p dates of a d mi nistrati o n. S u bjects will be q uesti o ne d a b o ut c ha n ges i n t heir 
me dicati o ns/treat me nts at t he start of eac h st u d y visit.  
Me dicati o n s a n d treat me nts ta ke n or recei v e d i n t he 3 0 da ys pri or t o  si g ni n g t he i nf or me d 
c o nse nt will be d oc u me nt e d as pri or me dicati o n/treat me nt. Me dicati o ns  a n d treat me nts ta ke n 
or recei ve d aft er si g ni n g t he i nf or m e d c o ns e nt 
will be d o c u me nte d as c o nc o mita nt 
me dicati o n/treat me nts .  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 2  of 1 1 3  
F or t he D ur ati o n of t he St u d y: Scree ni n g ( Visit 1) t o t he S u bject’s L ast St u d y Vis it  
•  S u bjects s h o ul d dela y a n y n o n -e mer ge n c y,  electi ve de ntal treat me nt s u ntil after st u d y 
c o m pleti o n (i ncl u di n g de ntal pr o p h yla xis).  
•  S h o ul d a n e nr olle d/ ra n d o mize d s u bject start a c o urse of treat me nt w hic h i n cl u des dail y , 
re g ular or i nter mitte nt use of a n y me dicati o n , details of t hat treat me nt will be rec or de d 
i n t he e C R F. T h e i n vesti gat or or t h eir me dicall y q ualifie d desi g ne e will d eci de if t he 
s u bject s h o ul d c o nti n ue i n t he st u d y or be wit h dra w n.  
•  S h o ul d a s u bject ta ke a me dicat i o n w hic h, i n t he o pi ni o n of t he i n vesti gat or or t heir 
me dicall y q ualifie d desi g nee, c o ul d i m pact t he  s u bject’s perce pti o n of pai n  (e. g., a n 
a nal gesic) wit hi n 8 h o urs of a sc h e d ule d st u d y visit, e ver y eff ort will be ma de t o 
rea p p oi nt t he m wit hi n per mitte d visit t olera nces  (s ee Sc h e d ule of Acti vities, Ta ble 1 -1 ). 
T he reas o n f or re -a p p oi nt me nt will be d oc u me nte d i n t he e C R F. T he m e dicati o n a n d 
a n y ass ociate d A E s h o ul d be rec or de d i n t he e C R F.   
If re-a p p oi nt m e nt is n ot p ossi ble, t he f oll o wi n g visit s pecific acti o ns s h o ul d be ta ke n : 
- 
Scree ni n g ( Visit 1):  T h e s u bject will be wit h dra w n fr o m t he st u d y. N o t o ot h 
se nsiti vit y assess me nts will be perf or me d. T h e s u bject ma y be re place d.  
- 
B aseli ne ( Visit 2):  T he s u bject w ill b e wit h dra w n fr o m t h e st u d y. N o t o ot h 
se nsiti vit y assess me nts will be perf or me d. T h e s u bject will n ot be re place d.  
- 
D a y 2 8 ( Visit 3 ) & D a y 5 6 ( Visit 4): T he s u bject will c o nti n ue i n t he st u d y. T o ot h 
se nsiti vit y assess me nts will be perf or me d. 
S u bjects s h o ul d n ot partici pate i n a n y ot her cli nical st u d y (i ncl u di n g c os metic st u dies) or be i n 
recei pt of a n ot her i n vesti gati o nal pr o d uct f or t he d urati o n of t his st u d y. 
7  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
S U B J E C T DI S C O N TI N U A TI O N/ WI T H D R A W A L  
7. 1  
S u bj e ct Di s c o nti n u ati o n/ Wit h dr a w al  
A s u bject ma y wit h dra w fr o m t he st u d y at a n y ti me at t heir o w n re q u est or ma y be wit h dra w n 
fr o m t he st u d y at a n y ti me at t he discreti o n of t he i n vesti gat or or t he s p o ns or f or safet y or  
be ha vi or al reas o ns, or d u e t o t he i n a bilit y of t he s u bject t o c o m pl y wit h t h e pr ot oc ol-re q uire d 
sc he d ule of st u d y visits or pr oce d ures.   
T he f oll o wi n g cir c u msta nces will re q uire disc o nti n uati o n of st u d y pr o d uct a n d/ or pre m at ure 
s u bject wit h dra wal. 
•  Pr ot oc ol vi olat i o n t hat c o ul d i m pact t he s u bject’s s afet y 
•  Wit h dra wal of i nf or me d c o nse nt  
•  S u bject l ost t o f oll o w -u p  
•  U n bli n di n g of t he s u bject  
•  Pre g na nc y  
If a s u bj ect is disc o nti n ue d or pre mat urel y wit h dra ws fr o m t he st u d y, t he reas o n(s) f or 
disc o nti n uati o n or wit h dra wal , a n d t he ass ociate d date , m ust be d oc u me nte d i n t he eC R F.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 3  of 1 1 3  
7. 2  
L o st t o F oll o w U p  
If a s u bject fails t o ret ur n t o t he i n vesti gat or site f or a re q uire d st u d y visit, t he i n vesti gat or staff 
m ust atte m pt t o c o ntact t he s u bject , resc h e d ule t h e misse d visit as s o o n as p ossi ble, c o u nsel t he 
s u bject o n t he i m p orta nce of mai ntai ni n g t he assi g ne d visit sc he d ule, a n d as certai n w het her  t he 
s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he st u d y. 
A s u bject will be c o nsi dere d l ost t o f oll o w u p if t he y re peate dl y fail t o atte n d sc he d ule d visits 
a n d ca n n ot  be c o ntacte d b y t he st u d y staff. Bef ore t he s u bject is dee me d l ost t o f oll o w u p, t he 
i n vesti gat or or desi g nee m ust ma ke e ver y eff ort t o re gai n c o ntact wit h t hem  ( w here p ossi ble 
t hree tele p h o ne calls a n d, if necessar y, a certifi e d letter t o t he s u bject’s last k n o w n maili n g 
a d dress or e q ui vale nt l oc al met h o ds). Eac h  c o ntact atte m pt s h o ul d be d oc u me nte d. If c o ntact is 
ma de, t he i n vesti gat or or desi g nee s h o ul d i n q uire a b o ut t he reas o n f or t heir wit h dra wal, re q u est 
t hat t he s u bject ret ur n all pr o d ucts pr o vi d e d  a n d, if a p pr o priate, re q uest t hat t he s u bject ret ur n 
f or a fi nal visit a n d f oll o w-u p a n y u nres ol ve d A Es.  Fi nal safet y assess me nts ma y be carrie d o ut 
w he n t he s u bject ret ur ns t o t he i nv esti gat or site, at t he i n v esti gat or’s discreti o n, w hic h ma y 
i ncl u de a n oral e xa mi nati o n. 
S h o ul d t he s u bject c o nti n ue t o be u nreac h a ble, t he y will be c o nsi dere d t o ha ve wit h dra w n fr o m 
t he st u d y a n d l ost t o f oll o w u p. T his will be d oc u me nte d i n t he eC R F . La c k of c o m pleti o n of 
all or a n y of t he earl y ter mi nati o n pr oce d ures will n ot be vie we d as pr ot oc ol de viati o ns pr o vi de d  
s u bject safet y w as pres er ve d. 
If t he s u bject wit h dra ws fr o m t he st u d y a n d wit h dra ws c o ns e nt f or discl os ure of f ut ure 
i nf or mati o n, n o f urt her e val uati o ns s h o ul d be p erf or me d,  a n d n o a d diti o nal data s h o ul d be 
c ollecte d.  T h e s p o ns or m a y retai n a n d c o nti n ue t o use a n y d ata c ollecte d bef ore t he wit h dra wal 
of c o nse nt.  
8  
S T U D Y P R O C E D U R E S  
T his secti o n lists t he pr oce d ures t o be c o m plete d at eac h sc h ed ule d  st u d y visit.  T he ti mi n g of 
eac h pr oce d ure is liste d i n t he Sc he d ule of Acti vities  (Ta ble 1 -1 ). A d here n ce t o t he st u d y desi g n 
re q uire me nts, i ncl u di n g all pr oce d ures is ess e ntial a n d re q uir e d f or st u d y c o n d uct.  
8. 1  
Vi sit 1  / S cr e e ni n g  
Scree ni n g pr oce d ures will be c o n d ucte d b y t he in vesti gat or , t he cli nical e xa mi ner(s) or s uita bl y 
q ualifie d /e x perie n ce d a n d trai ne d desi g nee s, 1 4 -2 8 da ys pri or t o t he Baseli ne visit (Visit 2) . 
W here practicall y feasi ble, t he y s h o ul d be c o m plete d i n t he or der liste d bel o w. Data c ollecte d 
will be rec or de d i n t he e C R F . 
8. 1. 1. 1  
I nf or m e d C o n s e nt 
T he i n vesti gat or or desi g nee m ust o btai n i nf or me d c o nse nt fr o m eac h s u bj ect partici pati n g i n 
t his st u d y after a de q uate e x pla nati o n of t he ai ms, met h o ds, o bjecti ves a n d p ote ntial hazar ds of 
t he st u d y. T he i n vesti gat or or desi g nee m ust als o e x plai n t o t he s u bjects t hat t he y are c o m pletel y 
free t o ref use t o e nter t he st u d y or t o wit h dr a w fr o m it at a n y ti me.  S u bjects will be pr o vi de d 
wit h a n i n gre die nts list f or t he pr o d ucts t o be use d i n t he st u d y t o e na ble t he m t o c o nfir m t he y 
are n ot a ware of a n y aller g y or h y perse nsiti vit y t o a n y of t he i n gre di e nts liste d. 
T w o c o pies of t he i nf or me d c o nse nt f or m (I C F) will be si g ne d a n d date d b y t he s u bject . T he 
i n vesti gat or or d esi g nee will als o  si g n a n d date eac h c o p y of t he I C F, after t he s u bject has 
si g ne d, t o c o nfir m t hat t he c o nse nt pr ocess was c o m plete d c orrectl y. T he s u bject will retai n o ne 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 4  of 1 1 3  
c o p y a n d t he ot her will be ke pt at t he i n vesti gat or  site. T he ti me of c o nse nt will als o be ca pt ure d 
o n t he I C F ; A Es will be ca pt ure d fr o m t his p oi nt.  T he date a n d ti me of c o nse nt will be rec or de d 
i n t he eC R F.  A p pr o priat e f or ms f or d o c u me nti n g i nf or me d c o nse nt will be pr o vi de d b y t he 
i n vesti gat or or b y t he s p o ns or. 
If ne w i nf or mati o n be c o mes a vaila ble d uri n g t he c o n d uct of t he st u d y t hat mi g ht  affect s u bject 
willi n g ness t o partici pate i n t he st u d y, eac h o n g oi n g s u bject s h o ul d recei v e a  ver bal  e x pla nati o n 
a n d writte n s u m mar y  of t h e ne w i nf or mati o n a n d be re -c o nse nte d i nt o t he st u d y. Eac h s u bject 
will  be pr o vi de d wit h a c o p y of t he ir si g ne d/dat e d  a me n de d I C F. D at e of re-c o ns e nt will be 
rec or de d in t he eC R F.  
After si g ni n g t he I C F, eac h s u bject will u n der g o a series of scree ni n g pr oce d ures a n d cli nical 
assess me nts t o c o nfir m t hat t he y meet t he pr ot oc ol re q uire d i ncl usi o n criteria a n d n o ne of t he 
e xcl usi o n criteria.  
8. 1. 2  
D e m o gr a p hi c s  
T he f oll o wi n g de m o gr a p hic i nf or mati o n will be rec or de d i n t he eC R F: year of birt h, ge n der , 
race a n d et h nicit y .  
8. 1. 3  
R e vi e w of Or al C ar e Pr o d u ct s   
S u bjects will be re q u ire d t o bri n g t heir c urre nt oral care pr o d ucts t o Scree ni n g ( Visit 1)  f or 
i n vesti gat or staff t o c o nfir m t he a bse nce of k n o w n a nti -se nsiti vit y i n gre die nts a n d se nsiti vit y-
relate d clai ms o n t he pr o d uct pac k a gi n g/la bel te xt. S u bjects w h o are c urre ntl y usi n g a nti -
se nsiti vit y oral care pr o d uct(s) will be e xcl u d e d .  
S u bjects will als o be as ke d a b o ut t he oral care pr o d ucts t he y ha ve bee n usi n g i n t he last 8 wee ks; 
t h ose w h o re p ort usi n g a nti-se nsiti vit y pr o d uct(s) i n t he 8 wee ks pri or t o Scree ni n g will be 
e xcl u de d.  
8. 1. 4  
M e di c al Hi st or y a n d Pri or M e di c ati o n s / Tr e at m e nts  
T he f oll o wi n g will be d oc u me nte d i n t he e C R F:  
•  Details of rele va nt me dical hist or y a n d rece nt s ur ger y ( wit hi n t he last year), i ncl u di n g 
aller gies a n d dr u g s e nsiti vities.  
•  Fe male s u bjects: p re g na n c y stat us (self-re p orte d). 
•  Pri or me dicati o ns/treat m e nts, i ncl u di n g prescri pti o n a n d n o n -pres cri pti o n dr u gs, dietar y 
s u p ple me nts a n d her bal re me dies, ta ke n i n t he 3 0 da ys pri or t o Scree ni n g . 
8. 1. 5  
Cli ni c al E x a mi n ati o n s a n d A s s e s s m e nt s  
I n pre parati o n f or L M S c o m pleti o n  at Visit s 2-4 , eac h s u bject will c o m plete t he L M S Trai ni n g 
E xercise (s o urce ), see A p pe n di x 1 5. 4  (trai ni n g e x ercise res p o nses will n ot  be tra nscri be d i n t o 
t he e C R F). A n y s u bject w h o, i n t he o pi ni o n of t he i n vesti gat or or desi g nee, is u na ble t o pr o vi de 
a p pr o priate res p o nses t o t he L M S trai ni n g q uesti o ns, will be e xcl u de d fr o m partici pati o n i n t he 
st u d y (Secti o n 5. 3 E xcl usi o n Criteri o n 2 7 ). 
T he f oll o wi n g cli nical e xa mi nati o ns a n d D H assess me nts will be c o m ple te d as descri be d i n 
St u d y Assess me nts  (Secti o n 9 ) a n d t he fi n di n gs rec or de d i n t he e C R F. T o facilitate s u bject fl o w, 
s o urce d oc u me nts ca n b e use d t o rec or d cli nical  data f or later tr a nscripti o n i nt o t he eC R F . 
T ra nscripti o n i nt o t he e C R F m ust be c o m plet e d wit hi n 5 da ys of rec or di n g t he data f or eac h 
s u bject. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 5  of 1 1 3  
•  Oral s oft tiss ue ( O S T ) e x a mi nati o n  
•  Oral har d tiss ue ( O H T ) e xa mi nati o n  
•  Cli nical assess me nt of i n cis ors, ca ni n es a n d pre -m olars f or de ntiti o n e xcl usi o ns, er osi o n 
a brasi o n a n d attriti o n ( E A R ), M o difie d Gi n gi val I n d e x ( M GI ), a djace nt t o t he test area 
o nl y , a n d cli nical m o bilit y t o i de ntif y a p pr o priate t eet h f or D H assess me nt. 
•  Cli nic al assess me nt of t actile se nsiti vit y  (t actile t hres h ol d ( g); m a xi m u m f orce 2 0 g ):  
Assess  all teet h wit h  n o d e ntiti o n e xcl usi o ns ( Secti o n 5. 3 E xcl usi o n Criteri o n 2 6 ) w hic h  
meet E A R, M GI a n d t o ot h m o bilit y re q uire me nts (Secti o n 5. 2  I n cl usi o n Criteria 6(c )). 
E ns ure at le ast a 5 -mi n ute bre ak bet wee n c o m pleti n g t he t actile assess me nts a n d 
starti n g t he ev a p or ative ( air) assess me nts.  
•  Cli nic al assess me nt of e v a p or ati ve ( air) s e nsiti vit y ( Sc hiff se nsiti vit y sc ore): 
Assess  eac h t o ot h wit h a Scree ni n g tactile t hres h ol d of ≤ 2 0 g. 
S u bjects m ust h a ve  a mi ni m u m of t w o ‘Eli gi ble Teet h ’ i n differe nt q u a dr a nts  t o c o nti n ue 
i n t he st u d y (Secti o n 5. 2 I ncl usi o n Criteri o n 6 c); ‘Eli gi ble Teet h ’ m ust h a ve a Scree ni n g 
t actile t hres h ol d ≤ 2 0 g a n d  a Scree ni n g Sc hiff se nsiti vit y sc ore ≥ 2   
S u bjects wit h fe wer t ha n t w o ‘Eli gi ble  Teet h ’ will be disc o nti n ue d . 
8. 1. 6  
I n cl u si o n/ E x cl u si o n Crit eri a 
I nf or mati o n rel ati n g t o i ncl usi o n/e xcl usi o n criteria will be c o m plete d  i n t he eC R F . 
8. 1. 7  
S u bj e ct Eli gi bilit y  
T he i n vesti gat or or me dicall y q ualifie d desi g nee will re vie w t he me dical hist or y, pri or 
me dicati o ns /treat me nts, cli nical e xa mi nati o n/ass ess me nt data a n d t h e i ncl usi o n/e xcl usi o n 
criteria f or eac h s u bject t o deter mi ne  t heir eli gi bilit y t o partici pate i n t he st u d y. T he e li gi bilit y 
decisi o n will be d oc u me nte d i n t he eC R F.   
If c o nfir m e d as eli gi ble t o partici pate , t he s u bject will be c o nsi dere d e nr olle d i n t he st u d y.  
T o pre pare f or st u d y partici pati o n, e nr olle d s u bjects will be i nstr ucte d i n t he Lifest yle 
G ui deli nes  (Secti o n 5. 5 ) a n d C o nc o mita nt Me dicati o ns/ Treat me nts  (Secti o n 6. 8 ) re q uire me nts 
of t he st u d y (as alrea d y detaile d i n t h e I C F a n d descri b e d d uri n g t h e c o nse nt pr ocess). 
A d here n ce t o t he re q uire me nts of t he st u d y pr ot oc ol is esse ntial f or s uccess f ul st u d y c o n d uct. 
8. 1. 7. 1  
S u p er vi s e d  Br u s hi n g wit h A c cli m ati z ati o n T o ot h p a st e  
E nr olle d s u bjects will b e pr o vi de d wit h t h e accli matizati o n t o ot h paste, a t o ot h br us h, a ti mer, 
ri nsi n g c u ps a n d a diar y t o use d uri n g t he accli matizati o n peri o d.  
Dis pe nsi n g s taff will descri be t he t o ot h paste us a ge i nstr ucti o ns t o t he s u bject, de m o nstrate 
c o veri n g t he f ull br us h h ea d wit h a ri b b o n of t o ot h paste  a n d h o w t o use t h e ti mer . Staff will 
t he n s u per vise t he s u bject carr yi n g o ut t heir first ti me d br us hi n g wit h t he accli matizati o n 
t o ot h paste a n d rec or di n g first use i n t heir diar y. A n y de viati o n fr o m t he pr o d uct usa g e 
i nstr ucti o ns will be ca pt ure d as a pr ot oc ol d e viati o n i n t he e C R F a n d t h e s u bject will be re-
i nstr ucte d i n t he c orrect directi o ns f or us e. Dis pe nsi n g of t he accli matizati o n t o ot h paste a n d 
c o m pleti o n of t he s u per vise d first br us hi n g will be d oc u me nte d i n t he e C R F.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 6  of 1 1 3  
S p o nta ne o usl y re p orte d A Es a n d a n y A Es elicite d b y as ki n g t he s u bject t o res p o n d t o n o n-
lea di n g q uesti o ns (s uc h as ‘h o w d o y o u feel?’ ) o n c o m pleti o n of t he s u per vise d br us hi n g will 
be rec or de d i n t he e C R F.  
Dis pe nsi n g staff will re mi n d s u bjects t o n ote a n y c ha n ges i n t heir healt h , me dicati o ns or 
treat me nts i n t he diar y (or re p ort s uc h c ha n ges t o t he i n vesti gat or staff bet wee n visits  usi n g t he 
c o ntact n u m bers pr o vi de d or  i nf or m staff at t heir ne xt visit , if preferre d) a n d t o bri n g t heir 
accli mati zati o n t o ot h past e, t o ot h br us h a n d c o m plete d diar y t o t heir ne xt st u d y visit . 
8. 2  
St u d y P eri o d  
8. 2. 1  
Vi sit 2  / B a s eli n e  (D a y  0)  
T he f oll o wi n g pr oce d ures a n d assess me nts will be c o m plete d  b y t he i n vesti ga t or, t he cli nical 
e xa mi ner(s) or a s uita bl y q ualifie d/e x perie nce d a n d trai ne d desi g nee . 
Where practicall y 
feasi ble, t he pr oce d ures a n d assess me nts s h o ul d be c o m plete d i n t he or der liste d bel o w. All data 
c ollecte d will  be rec or de d i n t he e C R F.  
8. 2. 1. 1  
C o m pli a n c e C h e c k s  
Dis pe nsi n g  staff will co m plete vis ual c hec ks of t he ret ur ne d accli matizati o n t o ot h paste a n d t he 
t o ot h br us h a n d re vie w t h e c o m plete d diar y t o assess  c o m plia nce .  
S us pecte d o ver or u n der use a n d t he n u m b er of misse d or a d diti o nal br us hi n gs will be rec or de d 
i n t he e C R F. A n y  de viati o n fr o m t he re q uire d usa ge i nstr ucti o ns will be ca pt ure d as a pr ot oc ol 
de viati o n i n t he e C R F a n d s u bjects will be re -i nstr ucte d i n t he c orrect us a g e . 
D o n ot  ret ur n t he accli m atizati o n t o ot h p aste, t o ot h br us h or  c o m plete d di ary t o t he s u bject.  
8. 2. 1. 2  
C h a n g e s i n M e di c al Hi st or y a n d C o n c o mit a nt M e di c ati o n s / Tr e at m e nt s 
In v esti gat or staff will as k s u bjects if t here ha ve b ee n a n y c ha n g es i n t heir healt h, c o nc o mita nt 
me dicati o ns a n d n o n -dr u g treat me nts; fe male s u bj ects of c hil d -beari n g p ote ntial will self -re p ort 
pre g na nc y st at us. All c ha n ges w ill be d oc u me nte d i n t he e C R F.  
S p o nta ne o usl y re p ort e d A Es a n d a n y A Es elicite d d uri n g q uesti o ni n g a b o ut c ha n ges i n healt h 
or b y as ki n g s u bjects t o res p o n d t o n o n -lea di n g q uesti o ns (s uc h as ‘h o w d o y o u feel?’ ) will 
rec or de d i n t he e C R F. A Es a n d/ or c ha n ges i n me dicati o ns/treat me nts i de ntifie d d uri n g re vie w 
of t he diar y will be rec or de d i n t he e C R F.   
8. 2. 1. 3  
S u bj e ct A d h er e n c e a n d C o nti n u a n c e  
In v esti gat or staff will q ues ti o n su bject s a b o ut a d here nce t o t he  re q uire me nts of t he pr ot oc ol; 
an y de viati o ns fr o m st u d y re q uire me nts  will be rec or de d i n t he eC R F . S u bject c o nti n ua nce will 
be c o nfir me d.  
8. 2. 1. 4  
S u bj e ct -R e p ort e d O ut c o m e s  
Pri or t o c o m me nci n g t he O S T  e xa mi nati o n  a n d 
D H assess me nts , eac h s u bject 
will 
i n de pe n de ntl y ( wit h o ut s u per visi o n) c o m plete a h ar d c o p y of t he D H E Q -4 8  (s o urce), Secti o ns 
1 a n d 2  (i.e., all q uesti o n s i n b ot h secti o ns), see A p pe n di x  1 5. 2 . S u bject res p o nses will be 
tra nscri be d i n t o t he e C R F. 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 7  of 1 1 3  
8. 2. 1. 5  
Cli ni c al E x a mi n ati o n s a n d A s s e s s m e nt s  
T he f oll o wi n g cli nical e xa mi nati o n  a n d D H ass ess me nt s will be c o m plete d as des cri be d i n 
St u d y Assess me nts  (Secti o n 9 ). T o facilitate s u bj ect fl o w, s o urce d oc u me nts ca n be use d t o 
rec or d cli nical data f or later tra nscri pti o n i nt o t he e C R F. 
•  O S T e xa mi nati o n  
•  Cli nic al assess me nt of t actile se nsiti vit y (t actile t hres h ol d ( g); m a xi m u m f orce 2 0 g) :  
Assess  eac h ‘eli gi ble t o ot h’ i de ntifie d at Scree ni n g (Scree ni n g  tactile t hres h ol d of ≤ 2 0 g 
a n d  a Scree ni n g  Sc hiff s e nsiti vit y sc ore ≥ 2 ). 
E ns ure at le ast a 5 -mi n ute bre ak bet wee n c o m pleti n g t he t actile  se nsitivity assess me nts 
a n d st arti n g t he ev a p or ative ( air) se nsitivity assess me nts.  
•  Cli nic al assess me nt of e v a p or ati ve ( air) se nsiti vit y  ( Sc hiff se nsiti vit y sc ore):  
- 
First  assess eac h t o ot h wit h a Baseli ne  tactile t hres h ol d of ≤ 2 0 g. 
- 
S u bject will  co m plete  t he f o ur L M Ss (I nte nsity, 
D ur ati o n, T oler a bility &  
Descri pti o n ) f or eac h t o ot h wit h a Baseli ne  Sc hiff se nsiti vit y sc ore ≥ 2  i m me di atel y 
after t h e Sc hiff se nsiti vit y sc ore f or t hat t o ot h is rec or de d. 
- 
W he n Sc hiff se nsiti vit y sc ore s ha ve  bee n rec or de d , a n d L M Ss c o m plete d , f or all 
teet h wit h a Baseli ne  tactile t hres h ol d of ≤ 2 0 g, t h e n assess Sc hiff s e nsiti vit y sc ore 
f or a n y re mai ni n g ‘Eli gi ble Teet h ’ i de ntifie d at Scree ni n g (i. e., t he ‘Eli gi ble Teet h ’ 
wit h a Baseli ne  tactile t hres h ol d > 2 0 g). 
‘ Eli gi ble Teet h’ = Teet h wit h n o de ntiti o n excl usi o ns w hic h met E A R, M GI a n d m o bility i ncl usi o n 
criteri a, wit h a Scree ni n g  t actile t hres h ol d ≤ 2 0 g a n d a Scree ni n g  Sc hiff se nsitivity sc ore ≥ 2.  
N ote: L M Ss s h o ul d n ot  be c o m plete d f or t he  re m ai ni n g ‘Eli gi ble  Teet h ’. 
S u bjects m ust h a ve  at le ast t w o ‘ q u alif yi n g teet h’, i n differe nt q u a dr a nts, wit h a  t actile 
t hres h ol d ≤ 2 0 g a n d  a Sc hiff se nsiti vit y sc ore ≥ 2 at b ot h Scree ni n g a n d  B aseli ne  t o 
c o nti n ue i n t he st u d y Secti o n 5. 2 I n cl usi o n Criteri o n 7 .  
S u bjects wit h fe wer t ha n t w o ‘ q ualif yi n g teet h’ will be disc o nti n ue d .  
T ra nscripti o n of data fr o m s o urce d oc u me nts i nt o t he e C R F m ust be c o m plete d wit hi n 5 da ys 
of rec or di n g t he data f or eac h s u bject.  
8. 2. 1. 6  
S el e cti o n of  T e st T e et h  
T he cli nical e xa mi ner res p o nsi ble f or e va p orati ve (air) assess me nts will sel ect t w o ‘T est T eet h’ 
f or assess me nt of b ot h tactile a n d e va p orati ve (air) se nsiti vit y at all s u bse q ue nt st u d y visits.  
‘Test T eet h’ s h o ul d o nl y be selecte d fr o m  teet h w hic h met t he E A R, M GI a n d t o ot h m o bilit y 
re q uire me nts a n d had  n o de ntiti o n e xcl usi o ns  at Scree ni n g , wit h t he re q uir e d q ualif yi n g le vels 
of D H  at b ot h  Scree ni n g ( Visit 1) a n d  Baseli ne ( Visit 2) : 
•  Tactile t hres h ol d ≤ 2 0 g at Scree ni n g a n d Baseli ne.  
•  Sc hiff se nsiti vit y sc ore ≥ 2 at Scree ni n g a n d B aseli ne.  
T o be re prese ntati ve of differe nt areas of t he m o ut h wit h i n de pe n de nt i n ner vati o n, ‘Test Teet h ’ 
s h o ul d be n o n-a dj ace nt a n d i n differe nt q ua dra nts.  T he i de ntit y of t h e t w o ‘Test Teet h’  will be 
rec or de d i n t he e C R F. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 8  of 1 1 3  
8. 2. 1. 7  
S u bj e ct Eli gi bilit y  
T he i n vesti gat or, or me dicall y q ualifie d d esi g nee, will re vie w t he i ncl usi o n/e xc l usi o n criteri a 
a n d verif y t he prese nce of t w o q u alif yi n g  ‘T est Teet h’  w hic h  m eet all st u d y criteri a b ef ore 
c o nfir m i n g eac h s u bject’s s uita bilit y t o c o nti n ue i n t he st u d y; t he eli gi bilit y decisi o n will be 
d oc u me nte d i n t he eC R F . 
8. 2. 1. 8  
Str atifi c ati o n a n d R a n d o mi z ati o n  
E ac h q ualif yi n g  su bje ct will be stratifie d t o o ne of t w o strata as des cri be d i n Secti o n 6 .5  a n d 
ra n d o mize d t o treat me nt. S u bject strat u m will be e ntere d directl y i nt o t he eC R F.  
Eac h s u bject will be assi g ne d a ra n d o mi zati o n n u m ber fr o m t heir desi g nate d strat u m i n 
asce n di n g n u meric al or der, a n d as eac h s u bject is deter mi ne d t o be f ull y eli gi ble. T he 
ra n d o mize d t o ot h paste c o de will be e ntere d directl y i nt o t he eC R F . 
8. 2. 1. 9  
S u p er vi s e d Br u s hi n g wit h I n v e sti g ati o n al T o ot h p a st e  
R a n d o mi ze d s u bjects will be pr o vi de d wit h t heir all ocate d i n vesti gati o nal t o ot h paste, a ne w 
t o ot h br us h, a d diti o nal  ri nsi n g c u ps a n d a ne w di ar y .  
Dis pe nsi n g staff will descri be t he t o ot h paste usa g e i nstr ucti o ns t o eac h s u bject, re mi n di n g t he m 
t o c o ver t he f ull br us h hea d wit h a ri b b o n of t o ot h paste a n d use t he ti mer  eac h ti me t he y br us h .  
•  S u bjects ra n d o mize d t o t he Test T o ot h paste will be s h o w n t he l ocati o n of t h eir  t w o ‘ Test 
Teet h’ wit hi n t he m o ut h ( usi n g a t o ot h dia gra m/ m o del a n d a mirr or, as nee de d) . 
T he y will be t h e n i nstr ucte d t o start t h eir ti mer ( pre -set f or 1-mi n ute) a n d br us h t heir 
e ntire de ntiti o n t h or o u g hl y f or at least 1 -ti me d mi n ute, ma ki n g s ure t o br us h t he 
se nsiti ve areas of t heir t w o selecte d ' Test teet h' caref ull y first.  
•  S u bjects ra n d o mi ze d t o t he Refere nce T o ot h paste will be i nstr ucte d t o start t heir ti mer 
( pre-s et f or 1-mi n ute) a n d br us h t heir e ntire de ntiti o n t h or o u g hl y f or at least 1-ti me d 
mi n ute.  
Dis pe nsi n g staff will s u p er vise eac h s u bj ect carr yi n g o ut t he first br us hi n g wit h t heir all ocate d 
i n vesti gati o nal t o ot h paste a n d rec or di n g t he first use i n t heir diar y. A n y de viati o n fr o m t he 
re q uire d pr o d uct usa ge i nstr ucti o ns will be ca pt ure d as a pr ot oc ol de viati o n  i n t he e C R F a n d t he 
s u bject will be re-i nstr uct e d i n t he c orrect directi o ns f or use.  
Dis pe nsi n g of t he i n vesti gati o nal t o ot h paste a n d c o m pleti o n of t he s u per vise d first br us hi n g 
will be d oc u me nte d i n t he e C R F.  
S p o nta ne o usl y re p orte d A Es a n d a n y A Es elicite d b y as ki n g t he s u bject t o res p o n d t o n o n -
lea di n g q uesti o ns (s uc h as ‘ h ow d o y o u feel?’) o n c o m pleti o n of t he s u per vise d br us hi n g will 
be rec or de d i n t he e C R F.  
Dis pe nsi n g staff will re mi n d s u bjects t o n ote a n y c ha n ges i n t heir healt h , me dicati o ns or 
treat me nts i n t he diar y (or re p ort s uc h c ha n ges t o t he i n vesti gat or staff bet wee n visits  usi n g t he 
c o ntact n u m bers pr o vi de d or  i nf or m staff at t heir ne xt visit , if preferre d) a n d t o bri n g t heir 
i n vesti gati o nal t o ot h paste, t o ot h br us h a n d c o m plete d dair y t o t heir ne xt st u d y visit . 
Ra n d o mize d s u bjects will als o be re-i nstr ucte d i n t he Lifest yle G ui deli nes  (Secti o n 5. 5 ) a n d 
C o nc o mita nt Me dicati o ns/ Treat me nts  (Secti o n 6. 8 ) re q uire m e nts of t he st u d y.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 4 9  of 1 1 3  
8. 2. 2  
Vi sit 3  / D a y  2 8  ( ± 2 d a y s) 
T he f oll o wi n g pr oce d ures a n d assess me nts will be c o m plete d  b y t he i n vesti gat or, t he cli nical 
e xa mi ner(s) or a s uita bl y q ualifie d/e x perie nce d a n d trai ne d desi g nee . 
Where practicall y 
feasi ble, t he pr oce d ures a n d assess me nts s h o ul d be c o m plete d i n t he or der liste d bel o w . All data 
c ollecte d will be rec or de d i n t he e C R F.  
8. 2. 2. 1  
C o m pli a n c e C h e c k s  
Dis pe nsi n g  staff will c o m plete vis ual c hec ks of t he ret ur n e d i n vesti gati o nal t o ot h paste a n d 
t o ot h br us h a n d re vie w t h e c o m plete d diar y t o assess c o m plia nce.  
S us pecte d o ver or u n der use a n d t he n u m b er of misse d or a d diti o nal br us hi n gs will be rec or de d 
i n t he e C R F. A n y  de viati o n fr o m t he re q uire d usa ge i nstr ucti o ns will be ca pt ure d as pr ot oc ol 
de viati o n s i n t he e C R F a n d s u bjects will b e re-i nstr ucte d i n t he c orrect us a ge . 
R et ur n t he i nvesti g ati o n al t o ot h p aste a n d  t o ot h br us h t o t he s u bject. Ret ai n t he c o m plete d 
di ary . 
8. 2. 2. 2  
C h a n g e s i n M e di c al Hi st or y a n d C o n c o mit a nt M e di c ati o n s / Tr e at m e nt s 
In v esti gat or staff will as k s u bjects if t here ha ve b ee n a n y c ha n g es i n t heir healt h, c o nc o mita nt 
me dicati o ns a n d n o n -dr u g treat me nts; f e male s u bj ects of c hil d -beari n g p ote ntial will  self-re p ort 
pre g na nc y st at us. All c ha n ges will be d oc u me nte d i n t he e C R F.  
S p o nta ne o usl y re p ort e d A Es a n d a n y A Es elicite d d u ri n g q uesti o ni n g a b o ut c ha n ges i n healt h 
or b y as ki n g s u bjects t o res p o n d t o n o n -lea di n g q uesti o ns (s uc h as ‘ h o w d o y o u feel?’) will 
rec or de d i n t he e C R F.  
A Es a n d/ or c ha n ges i n me dicati o ns/treat me nts i de ntifie d d uri n g re vie w of t he diar y will be 
rec or de d i n t he e C R F.  
8. 2. 2. 3  
S u bj e ct A d h er e n c e a n d C o nti n u a n c e  
I n v esti gat or staff will q uesti o n su bject s a b o ut a d here nce t o t he  re q uire me nts of t he pr ot oc ol; 
a n y de viati o ns fr o m st u d y re q uire me nts will be rec or de d i n t he eC R F.  S u bject c o nti n ua nce will 
be c o nfir me d.  
8. 2. 2. 4  
S u bj e ct -R e p ort e d O ut c o m e s  
Pri or t o c o m me nci n g t he cli nical e xa mi nati o ns a n d D H assess me nts, eac h s u bject will 
i n de pe n de ntl y ( wit h o ut s u per visi o n) c o m plete a har d c o p y of t he D H E Q -4 8  (s o urce), Secti o n 1 
Q uesti o ns 7 -9 o nl y  a n d Secti o n 2 all q uesti o ns  (see A p pe n di x  1 5. 2 ). S u bject res p o nses will be 
later tra nscri be d i nt o t he e C R F.  
8. 2. 2. 5  
Cli ni c al E x a mi n ati o n s a n d A s s e s s m e nt s  
T he f oll o wi n g cli nical e xa mi nati o n a n d D H ass ess me nts will be c o m plete d as des cri be d i n 
St u d y Assess me nts  (Secti o n 9 ). T o facilitate s u bj ect fl o w, s o urce d oc u me nts ca n be use d t o 
rec or d cli nical data f or later tra nscripti o n i nt o t he eC R F . 
•  O S T e xa mi nati o n  
•  Cli nic al assess me nt of t actile se nsiti vit y (t actile t hres h ol d ( g); m a xi m u m f orce 8 0 g) : 
Assess  t he t w o ‘ Test Te et h’ o nl y . 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 0  of 1 1 3  
E ns ure at le ast a 5 -mi n ute bre ak bet wee n c o m pleti n g t he t actile se nsitivity assess me nts 
a n d st arti n g t he ev a p or ative ( air) se nsitivity assess me nts.  
•  Cli nic al assess me nt of e v a p or ati ve ( air) se nsiti vit y ( Sc hiff se nsiti vit y sc ore):   
- 
First  assess t he t w o ‘ Test Teet h’ . 
- 
S u bject 
will c o m plete t he f o ur L M Ss ( I nte nsity, 
D ur ati o n, T oler a bility &  
Descri pti o n ) f or eac h ‘ Test T o ot h’ i m me di atel y after t h e Sc hiff se nsiti vit y sc ore 
f or t hat t o ot h is rec or de d. 
- 
W he n Sc hiff se nsiti vit y s c ores h a ve bee n rec or de d, a n d L M Ss c o m plete d, f or b ot h 
‘ Test Teet h’, t he n assess Sc hiff se nsiti vit y sc ore f or a n y re mai ni n g ‘Eli gi ble Teet h ’, 
as i de ntifie d at Scree ni n g  (d o n ot re -ass ess  t he t w o ‘ Test Teet h’). 
‘ Eli gi ble Teet h’ = Te et h wit h n o de ntiti o n excl usi o ns w hic h met E A R, M GI a n d m o bility i ncl usi o n 
criteri a, wit h a Scree ni n g  t actile t hres h ol d ≤ 2 0 g a n d a Scree ni n g  Sc hiff se nsitivity sc ore ≥ 2.  
N ote: L M Ss s h o ul d n ot  be c o m plete d f or t he re m ai ni n g ‘Eli gi ble Teet h ’. 
Tra nscri pti o n of data fr o m s o urce d oc u me nts i nt o t he e C R F m ust be c o m plete d wit hi n 5 da ys 
of rec or di n g t he data f or eac h s u bject.  
8. 2. 2. 6  
S u p er vi s e d Br u s hi n g wit h I n v e sti g ati o n al T o ot h p a st e  
Dis pe nsi n g staff will vis uall y c hec k t he c o n diti o n of t he s u bject’s t o ot h br us h. If it is da ma ge d, 
a ne w t o ot hbr us h s h o ul d be pr o vi de d; s u p pl y of a re place me nt t o ot h br us h will  be d oc u me nte d 
i n t he e C R F. Eac h s u bje ct  will be pr o vi de d wit h a ne w diar y.  
Dis pe nsi n g staff will re-descri be t he t o ot h paste usa ge i nstr ucti o ns t o eac h s u bj ect (re mi n di n g 
t he m t o c o ver t he f ull br us h hea d wit h a ri b b o n of t o ot h paste a n d use t he ti mer eac h ti me t he y 
br us h ) a n d t he n s u per vise eac h s u bj ect c o m pleti n g a n o n -site br us hi n g wit h t heir all ocate d 
i n vesti gati o nal t o ot h paste a n d rec or di n g t his use  i n t heir diar y.  
Dis pe nsi n g staff will as k s u bjects ra n d o mize d t o t h e Test T o ot h paste t o i n dicate t he l ocati o n of 
t heir t w o ‘ Test Teet h’ i n t he m o ut h  (bef ore  t he y start br us hi n g) a n d co nfir m  t he s u bject b r us hes  
t hese teet h first, pri or t o br us hi n g t heir e ntire de ntiti o n. 
A n y de viati o n fr o m t h e re q uire d pr o d uct us a ge i nstr ucti o ns will be ca pt ure d as a pr ot oc ol 
de viati o n  i n t he e C R F a n d t he s u bject will be re-i nstr ucte d i n t he c orrect directi o ns f or us e.  
C o m pleti o n of eac h s u per vise d o n -site br us hi n g will be d oc u me nte d i n t he e C R F.  
S p o nta ne o usl y re p orte d A Es a n d a n y A Es elicite d b y as ki n g t he s u bject t o res p o n d t o n o n -
lea di n g q uesti o ns (s uc h as ‘ h o w d o y o u feel?’) o n c o m pleti o n of t he s u per vise d br us hi n g will 
be rec or de d i n t he e C R F.  
Dis pe nsi n g staff will re mi n d s u bjects t o n ote a n y c ha n ges i n t heir healt h , me dicati o ns or 
treat me nts i n t he diar y (or re p ort s uc h c ha n ges t o t he i n vesti gat or staff bet wee n visits  usi n g t he 
c o ntact n u m bers p r o vi de d or i nf or m staff at t heir ne xt visit , if preferre d) a n d t o bri n g t heir 
i n vesti gati o nal t o ot h paste, t o ot h br us h a n d c o m plete d diar y t o t heir ne xt st u d y visit . 
Ra n d o mize d s u bjects will als o be re-i nstr ucte d i n t he Lifest yle G ui deli nes  (Secti o n 5. 5 ) a n d 
C o nc o mita nt Me dicati o ns/ Treat me nts  (Secti o n 6. 8 ) re q uire m e nts of t he st u d y.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 1  of 1 1 3  
8. 2. 3  
Vi sit 4  / D a y 5 6  ( ± 3 d a y s) 
T he f oll o wi n g pr oce d ures a n d assess me nts will be c o m plete d  b y t he i n vesti gat or, t he cli nical 
e xa mi ner(s) or a s uita bl y q ualifie d/e x perie nce d a n d trai ne d desi g nee . 
Where practicall y 
feasi ble, t he pr oce d ures a n d assess me nts s h o ul d be c o m plete d i n t he or der liste d bel o w . All data 
c ollecte d will be rec or de d i n t he e C R F.  
8. 2. 3. 1  
C o m pli a n c e C h e c k s  
Dis pe nsi n g staff will c o m plete vis ual c hec ks of t he ret ur n e d i n vesti gati o nal t o ot h paste a n d 
t o ot h br us h a n d re vie w t he c o m plete d diar y t o assess c o m plia nce. S us pecte d o ver or u n der use 
a n d t he n u m ber of mis se d or a d diti o nal br us hi n gs will be rec or de d i n t he e C R F. A n y  de viati o n 
fr o m t he re q uir e d usa ge i nstr ucti o ns will be ca pt ur e d as pr ot oc ol de vi ati o n s i n t he e C R F.  
D o n ot  ret ur n t he i nvesti g ati o n al t o ot h p aste, t o ot h br us h or  c o m plete d di ary t o t he s u bject.  
8. 2. 3. 2  
C h a n g e s i n M e di c al Hi st or y a n d C o n c o mit a nt M e di c ati o n s / Tr e at m e nt s 
In v esti gat or staff will as k s u bjects if t here ha ve b ee n a n y c ha n g es i n t heir healt h, c o nc o mita nt 
me dicati o ns a n d n o n -dr u g treat me nts; f e male s u bj ects of c hil d -beari n g p ote ntial will  self-re p ort 
pre g na nc y st at us. All c ha n ges will be d oc u me nte d i n t he e C R F.  
S p o nta ne o usl y re p ort e d A Es a n d a n y A Es elicite d d uri n g q uesti o ni n g a b o ut c ha n ges i n healt h 
or b y as ki n g s u bjects t o res p o n d t o n o n -lea di n g q uesti o ns (s uc h as ‘ h o w d o y o u feel?’) will 
rec or de d i n t he e C R F.  
A Es a n d/ or c ha n ges i n me dicati o ns/treat me nts i de ntifie d d uri n g re vie w of t he diar y will be 
rec or de d i n t he e C R F.  
8. 2. 3. 3  
S u bj e ct A d h er e n c e a n d C o nti n u a n c e  
I n v esti gat or staff will q uesti o n su bject s a b o ut a d here nce t o t he re q uire me nts of t he pr ot oc ol; 
a n y de viati o ns fr o m st u d y re q uire me nts will be rec or de d i n t he eC R F.  
8. 2. 3. 4  
S u bj e ct -R e p ort e d O ut c o m e s  
Pri or t o c o m me nci n g t he O S T/ O H T  e xa mi nati o ns a n d D H assess me nts, eac h s u bject will 
i n de pe n de ntl y ( wit h o ut s u per visi o n) c o m pl ete a har d c o p y of t he D H E Q -4 8  (s o urce), Secti o n 1 
Q uesti o ns 7 -9 o nl y,  a n d Secti o n 2 all q uesti o ns  (see A p pe n di x  1 5. 2 ). S u bject res p o nses will be 
later tra nscri be d i nt o t he e C R F.  
8. 2. 3. 5  
Cli ni c al E x a mi n ati o n s a n d A s s e s s m e nt s  
T he f oll o wi n g cli nical e xa mi nati o n s a n d D H assess me nts will be c o m plete d as descri be d i n 
St u d y Assess me nts  (Secti o n 9 ). T o facilitate s u bj ect fl o w, s o urce d oc u me nts ca n be use d t o 
rec or d cli nical data f or later tra nscripti o n i nt o t he eC R F . 
•  O S T e xa mi nati o n  
•  O H T e xa mi nati o n  
•  Cli nic al assess me nt of t actile se nsiti vit y (t actile t hres h ol d ( g); m a xi m u m f orce 8 0 g):  
Assess  t he t w o ‘ Test Te et h’ o nl y . 
E ns ure at le ast a 5 -mi n ute bre ak bet wee n c o m pleti n g t he t actile se nsitivity assess me nts 
a n d st arti n g t he ev a p or ative ( air) se nsitivity assess me nts.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 2  of 1 1 3  
•  Cli nic al assess me nt of e v a p or ati ve ( air) se nsiti vit y ( Sc hiff se nsiti vit y sc ore):   
- 
First  assess t he t w o ‘ Test Teet h’.  
- 
S u bject 
will c o m plete t he f o ur L M Ss ( I nte nsity, 
D ur ati o n, T oler a bility &  
Descri pti o n ) f or eac h ‘ Test T o ot h’ i m me di atel y after t h e Sc hiff se nsiti vit y sc ore 
f or t hat t o ot h is rec or de d. 
- 
W he n Sc hiff se nsiti vit y s c ores h a ve bee n re c or de d, a n d L M Ss c o m plete d, f or b ot h 
‘ Test Teet h’, t he n assess Sc hiff se nsiti vit y sc ore f or a n y re mai ni n g ‘Eli gi ble Teet h’ , 
as i de ntifie d at Scree ni n g ( d o n ot re -ass ess t he t w o ‘ Test Teet h’).  
‘ Eli gi ble Teet h’ = Teet h wit h n o de ntiti o n excl usi o ns w hic h met E A R, M GI a n d m o bility i ncl usi o n 
criteri a, wit h a Scree ni n g  t actile t hres h ol d ≤ 2 0 g a n d a Scree ni n g  Sc hiff se nsitivity sc ore ≥ 2.  
N ote: L M Ss s h o ul d n ot  be c o m plete d f or t he re m ai ni n g ‘Eli gi ble Teet h’ . 
After  t he cli nical e xa mi nati o ns/assess me nts ha ve bee n  c o m plete d , s u bjects will c o m plete a 
Satisfacti o n wit h Treat me nt N R S a n d descri be (free te xt) w h y t he y ga ve t heir rati n g (Secti o n 
9. 3. 4 ). 
T ra nscripti o n of data fr o m s o urce d oc u me nts i nt o t he e C R F m ust be c o m plete d wit hi n 5 da ys 
of rec or di n g t he data f or eac h s u bject.  
8. 3  
St u d y C o n cl u si o n  
T he St u d y C o ncl usi o n pa ge  of t he eC R F will be c o m plete d f or all s u bjects w het her or n ot t he y 
c o m plete all st u d y pr oce d ures (i.e., e ve n if t h e y are disc o nti n ue d earl y  at a n y p o i nt d uri n g t he 
st u d y). If t he s u bject is disc o nti n ue d earl y, t he pri mar y reas o n f or wit h dra wal s h o ul d be 
rec or de d o n t he St u d y C o ncl usi o n pa ge. F or s u bjects w h o atte n d all sc he d ule d st u d y visits, t he 
St u d y C o ncl usi o n pa ge of t he eC R F will be c o m pl ete d at V isit 4 .  
I n v esti gat or staff will i nstr uct eac h s u bject t o i nf or m t he site if t he y e x p eri e nce a n y c ha n ge i n 
healt h , me dicati o ns or treat me nts i n t he 5 da ys f oll o wi n g t heir last use of st u d y pr o d uct.  
If a s u bject has a n y cli nicall y si g nifica nt, st u d y-relate d a b n or malities or A Es at t h e e n d of  t he 
st u d y, t he s p o ns or’s me dical m o nit or ( or desi g nate d re prese ntati ve) s h o ul d  be n otifie d . The 
s u bject ma y be as ke d t o ret ur n t o t he i n vesti gat or site f or a f oll o w-u p visit t o e ns ure a n y iss ue 
is res ol ve d or dee me d n ot cli nicall y si g nifica nt.  
8. 4  
F oll o w -U p C o nt a ct  
T he i n vesti gat or site ma y c o ntact a s u bject t o f oll o w u p a n A E p ost-st ud y c o m pleti o n  or 
wit h dra wal a n d, i n s o me circ u msta nces, ma y re q uest t he y ret ur n t o t he site f or a d diti o nal f oll o w-
u p visits (fi nal safet y assess me nts). At t he discreti o n of t he i n vesti gat or or me dicall y q ualifie d 
desi g nee , a d diti o nal oral e xa mi nati o ns ma y be carrie d o ut at s uc h visits . 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 3  of 1 1 3  
9  
S T U D Y A S S E S S M E N T S  
E ver y eff ort s h o ul d b e ma de t o e ns ure st u d y-re q uire d e x a mi nati o ns a n d assess me nts  are 
c o m plete d as d escri b e d  a n d sc he d ul e d i n t his pr ot oc ol.  H o we v er, it is a ntici pate d t hat fr o m 
ti me t o ti me t here m a y b e cir c u msta nces, o utsi de t he c o ntr ol of t he i n v esti gat or t hat ma ke it 
u nfeasi ble t o c o m plete a n e xa mi nati o n or assess me nt.  I n t hes e cas es, t he i n v esti gat or m ust ta ke 
all ste ps necessar y t o e ns ure t he safet y a n d well -bei n g of t he s u bject.  W he n a pr ot oc ol -req uire d 
e xa mi nati o n or assess me nt ca n n ot be perf or me d, t he i n vesti gat or or desi g ne e will d oc u me nt t he 
reas o n f or t h e misse d pr oce d ure  as a pr ot oc ol de viati o n a n d a n y c orrecti ve a n d pre v e ntati ve 
acti o ns t he y ha ve ta ke n t o e ns ure t he re q uir e d pr oce d ure s are ad here d t o as s o o n as p ossi ble. 
T he sp o ns or s h o ul d be i nf or me d of a n y misse d e x a mi nati o ns  or assess me nts i n a ti mel y ma n ner.  
9. 1  
S cr e e ni n g E x a mi n ati o n s/ D H A s s e s s m e nt s  
Scree ni n g e xa mi nati o ns a n d assess me nts will be perf or me d b y a p pr o priatel y trai ne d a n d 
e x perie n ce d cli nical e x a mi ners /staff at t he ti mes a n d i n t he or der d efi ne d i n t he St u d y 
Pr oce d ures  s ecti o n of t his pr ot oc ol  (Secti o n 9 ).  
T he eli gi bilit y  of eac h t o ot h will be assesse d  a gai nst t he pr ot oc ol i ncl usi o n/e xcl usi o n criteria 
(Secti o ns 5 . 2 a n d 5 . 3) a n d rec or de d i n t he eC R F.  If, i n t he o pi ni o n of t he cli nical e x a mi ner , t h e 
val ue/ sc ore f or a partic ular t o ot h/area of gi n gi va  lies b et wee n t w o v al ues /descri pti o ns , a 
c o nser vati ve a p pr oac h s h o ul d be a d o pte d, a n d the m ore c o ns er vati ve val ue/ sc ore rec or de d. T he 
sa me a p pr oac h s h o ul d be a p plie d t hr o u g h o ut t he st u d y t o e ns ure c o nsiste nc y of assess me nt  at 
all ti me p oi nts.  
9. 1. 1  
Er o si o n , A br a si o n a n d R e c e s si o n ( E A R)  
T he faci al s urfaces of all i ncis or, ca ni ne a n d pre -m olar teet h (Fi g ur e 9 -1 ) t hat d o n ot prese nt 
a n y of t he ge neral de ntiti o n e xcl usi o n criteria, or s pecific de ntiti o n e xcl usi o n criteria , f or 
‘Eli gi ble Teet h’  will be e xa mi ne d f or si g ns of faci al/cer vical E A R (A d d y, 2 0 0 0 ). 
 
Fi g ur e 9 -1  D e nt al N o m e n cl at ur e (De m pse y, 2 0 0 1 ) 
9. 1. 2  
M o difi e d Gi n gi v al I n d e x ( M GI)  
T he M GI is a n o n -i n vasi ve vis ual assess me nt  of gi n gi val healt h  (L o be n e, 1 9 8 6 ). M GI will be 
assesse d f or i n cis or, ca ni ne a n d pre -m olar teet h (Fi g ure 9 -1 ) e x hi biti n g n o ne of t he de ntiti o n 
e xcl usi o ns a n d prese nti n g wit h facial/cer vical E A R. M GI s h o ul d be sc ore d f or t he facial gi n gi va 
directl y a djace nt t o t he area of e x p os e d de nti n (i.e., t he test area o nl y ).  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 4  of 1 1 3  
‘Eli gi ble T eet h ’ will h a ve a M GI of zer o ( 0) directl y a dj ace nt t o t he a re a of e x p ose d de nti n . 
Sc ore  
Descri pti o n  
0  
A bse nce of i nfla m mati o n  
1  
Mil d i nfla m mati o n; sli g ht c ha n ge i n c ol o ur, little c ha n ge i n c ol o ur; little c ha n ge i n 
te xt ure of a n y p orti o n of t he mar gi nal or pa pillar y gi n gi val u nit.  
2  
Mil d i nfla m mati o n; criteria as a b o ve b ut i n v ol vi n g t he e ntire mar gi nal or pa pillar 
gi n gi val u nit.  
3  
M o derate i nfla m mati o n; glazi n g, re d ness, o e de ma, a n d/ or h y pertr o p h y of t he mar gi nal 
or pa pillar y gi n gi val u nit.  
4  
Se vere i nfla m mati o n; mar ke d re d ness, o e de ma a n d/ or h y pertr o p h y of t he mar gi nal or 
pa pillar y gi n gi val u nit, s p o nta ne o us blee di n g, c o n gesti o n, or ulcerati o n.  
9. 1. 3  
Cli ni c al  M o bilit y  
Cli nical m o bilit y will be assesse d f or i n cis or, ca ni ne a n d pre -m olar t eet h (Fi g ure 9 -1 ) e x hi biti n g 
n o ne of t he de ntiti o n e xcl usi o ns, wit h facial/cer vical E A R a n d a M GI = 0  a djace nt t o t he test 
area o nl y , usi n g a m o difi cati o n of t he Miller I n d e x (Laster, 1 9 7 5 ).  
‘Eli gi ble T eet h ’ will h a ve cli nic al  m o bilit y = 0.  
Sc ore  
Descri pti o n  
0  
N o m o ve me nt or m o bilit y of t he cr o w n of t he t o ot h < 0. 2 m m i n a h oriz o ntal directi o n  
1  
M o bilit y of t he cr o w n of t he t o ot h 0. 2 - 1 m m i n a h oriz o ntal directi o n  
2  
M o bilit y of t he cr o w n of t he t o ot h e xcee di n g 1 m m i n a h oriz o ntal directi o n  
3  
M o bilit y of t he cr o w n of t he t o ot h i n a vertical directi o n as well.  
9. 1. 4  
S cr e e ni n g T a ctil e S e n siti vit y  A s s e s s m e nt  
T he tactile se nsiti vit y of i ncis or, ca ni ne a n d pre -m olar teet h (Fi g ur e  9 -1 ) e x hi biti n g n o ne of t he 
de ntiti o n e xcl usi o ns, a n d meeti n g t he E A R, M GI a n d cli nical m o bilit y  criteria, will be assesse d 
usi n g a c o nsta nt press ure pr o be ( Y ea ple pr o be (P ols o n, 1 9 8 0 )). T he pr o be ti p will be place d 
per pe n dic ular t o t he faci al s urface of t he t o ot h a n d dra w n sl o wl y acr oss t h e  e x p ose d de nti n t o 
e ns ure a p plicati o n of t he sti m ul us acr oss t he p ote ntiall y ‘se nsiti ve’ area .  
After eac h a p plicati o n  of t he tactile sti m ul us , t he s u bject will be as ke d t o i n dicate w het h er t hey 
e x perie n ce d a n y pai n or disc o mf ort. T he e xa mi ner will tell t h e s u bject t o o nl y res p o n d ‘y es ’ if 
t he y feel P AI N or DI S C O M F O R T w he n t he pr o be is a p plie d t o t heir t o ot h. ‘ Yes’ a n d ‘ no ’ are 
t he o nl y acce pta bl e a ns w ers.  T he s u bject ma y res p o n d ‘yes ’ if t he y feel press ure. T he e x a mi ner 
will re mi n d t he m, if nee de d, t hat t he y will feel press ure eac h ti me t he pr o be is i n c o ntact wit h 
t he t o ot h b ut t he y s h o ul d o nl y res p o n d ‘yes ’ if t h e y feel pai n or disc o mf ort.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 5  of 1 1 3  
T he gra m setti n g w hic h elicits t w o c o nsec uti ve ‘ yes’ res p o nses will be rec or de d as t he tactile 
t hres h ol d ( g) f or t h at t o ot h. At Scree ni n g, t he u p per f orce setti n g will be 2 0 g.  
•  T o be dee me d  ‘eli gi ble’ f or B aseli ne D H  assess me nt , a  t o ot h m ust h a ve a Scree ni n g 
t actile t hres h ol d ≤ 2 0 g.  
•  If n o se nsiti vit y is o bser ve d  at t he u p per f orce s etti n g, Scree ni n g t actile t hres h ol d 
will be rec or de d as > 2 0 g a n d t he t o ot h will be dis q u alifie d fr o m f urt her testi n g.  
If a s u bject fails t o gi ve a defi nite a ns wer, t he e xa mi ner will  re-pr o m pt t he m t o pr o vi de a 
res p o nse (‘yes ’ or ‘n o ’). If t heir u ncert ai nt y c o nti n ues, t his s h o ul d be rec or de d in t he s o urce 
d oc u me nt . If t he s u bject c o nti n ues t o be u ns ure, or t he e xa mi ner is u ns ure of t he relia bilit y of 
t heir res p o nse, t he e xa mi ner ma y o pt t o re-pr o be at t he s a me f orce setti n g (i n dicate d t o t h e 
scri be b y a n o n-ver bal si g nal, e. g., a ha n d g est ure) or m o v e t o t he ne xt f or ce setti n g ( 1 0 g 
i ncreas e). If t he e xa mi ner c o nsi ders t he s u bject’s ‘ yes’ res p o nse ma y b e bet wee n gra m setti n gs , 
a c o nser vati ve a p pr oac h s h o ul d al wa ys b e a d o pte d, a n d t he l o wer ( m ore ‘se v ere’) tactile 
t hres h ol d ( g) rec or de d. 
T he e xa mi ner will ge nerall y ma ke  t he f orce setti n g a dj ust me nts (t his ca n als o be d o ne b y a n 
assista nt  or t he scri be); t he scri be will rec or d t he micr o-a m pera g e setti n g a n d s u bject’s 
res p o nses i n t he s o urce d oc u me nt. 
C ali br ati o n of t he Ye a ple Pr o be:  
T he Y ea ple pr o be will be cali brate d b y  a n a p pr o pri atel y trai ne d me m ber of t he i n vesti gat or st aff 
(t y picall y t he cli nical e x a mi ner, t heir assista nt or scri be) b ef ore use o n eac h da y s u bjects are 
assesse d. T he micr oa m p setti n gs ma y var y fr o m da y t o da y ( partl y d ue t o batter y p o wer 
c o ns u m pti o n), b ut t he differe nce s h o ul d n ot b e si g nifica nt. T h us, pre vi o us pr o be setti n gs ca n 
be use d  as a g ui d e. Cali brati o n s h o ul d start at t he l o west micr oa m p setti n g a n d t he n i ncrease.   
Eit her cali brati o n met h o d descri be d b el o w is acce pta ble.  
•  Met h o d 1 (‘ W ater C u p’):  T he Yea pl e pr o be is fi xe d t o a cla m p attac he d t o a ri n g sta n d 
s o t hat t he pr o be ti p is vertical. A s mall p a per c u p attac he d wit h c ott o n t hrea d is bala nce d 
o ver t he e n d of t he Yea pl e pr o be, wit h o ut t he pr o be tri p pi n g. T he pr o be dial is set t o t he 
micr oa m p setti n g a n d w at er is fe d i nt o t he p a per c u p usi n g a dr o p per u ntil t he pr o be 
tri ps. T he gra m setti n g is rec or de d, a n d t he Yea ple pr o be reset t o t he ne xt micr oa m p 
val ue. T he pr oce d ure is r e peate d u ntil data has bee n c ollecte d t o m or e t ha n 8 0 g.  
•  Met h o d 2:  T he Yea ple pr o be is fi xe d t o a cla m p attac he d t o a ri n g sta n d s o t hat t he t o p 
is per pe n dic ular t o t he p a n of a n o ha us di al -o -gra m ®  bala nce or e q ui v ale nt. T he pr o be 
ti p is p ositi o ne d t o j ust t o uc h t he p a n w he n t he b ala nce is set at zer o gra ms. T he pr o be 
dial is set t o t h e micr oa m p setti n g a n d t h e gra m  setti n g is i ncreas e d o n t he b ala nce u ntil 
the pr o be tri ps. T he gra m setti n g is rec or de d, a n d t he Yea ple pr o be reset t o t he ne xt 
micr oa m p val ue.  
T he data are pl otte d, a n d t he p oi nts c o n necte d wit h li ne se g me nts i n or der t o i nter p olate t he 
micr o -a m p val ues e q ui vale nt t o 1 0, 2 0, 3 0, 4 0, 5 0, 6 0, 7 0 a n d  8 0 g. T his cali brati o n s h o ul d be 
re peat e d t hr ee ti mes a n d t he mea n  of t h e t hr ee us e d f or t h at da y’s setti n gs. T he setti n gs will b e 
rec or de d o n t he Y ea ple pr o be cali brati o n rec or d (al o n g wit h t he pr o be’s serial n u m ber) w hic h 
will ser ve as t he f orce s etti n g g ui de f or t hat da y’s e xa mi nati o ns. 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 6  of 1 1 3  
9. 1. 5  
S cr e e ni n g E v a p or ati v e (Air ) S e n siti vit y  A s s e s s m e nt  
E va p orati ve (air ) se nsiti vit y will be assesse d o n t h e facial s urfaces of i ncis or, ca ni n e a n d pre -
m olar teet h (Fi g ur e 9 -1 ) w hic h e x hi bit n o ne of t h e de ntiti o n e xcl usi o ns, m eet t he E A R, M GI, 
cli nical m o bilit y criteria a n d ha ve a Scree ni n g tactile t hres h ol d ≤ 2 0 g . E va p orati ve (air) 
assess me nts will start  a mi ni m u m of 5 mi n utes after t he tactile assess me nts ha ve c o m plete d  
(t o ot h rec o ver y ti me).  
T he assess me nt will be ma de b y directi n g a 1 -sec o n d a p plicati o n of air fr o m a sta n dar d de ntal 
s yri n ge hel d p er pe n dic ular  t o t he t o ot h s urface, a p pr o xi matel y 1-2 m m c or o nal t o t he gi n gi val 
mar gi n, a n d fr o m a dista nce of a p pr o xi matel y 1 c m. T he de ntal e xa mi ner will ta ke a p pr o priate 
meas ures t o is olate t he t o ot h s urface t o pre ve nt sti m ulati o n of a djace nt teet h or s urr o u n di n g s oft 
tiss ue. 
S u bject res p o nse t o t he sti m ul us will be e val uate d usi n g t he Sc hiff se nsiti vit y scale ( Sc hiff, 
1 9 9 4 ). T his is a n e xa mi ner-bas e d i n de x, sc ore d i m me diatel y f oll o wi n g a d mi nistrati o n of t he 
e va p orati ve (air) sti m ul us. T he scale f oc uses o n a c o m bi nati o n of s pecific, o bser va ble, p h ysical, 
be ha vi oral  a n d v er bal res p o nses fr o m t he s u bject, w hi c h ma y facilitate discri mi nati o n.  
Sc ore  Descri pti o n  
0  
S u bject d oes n ot res p o n d t o air sti m ulati o n  
1  
S u bject res p o n ds t o air sti m ul us b ut d oes n ot re q uest disc o nti n uati o n of sti m ul us  
2  
S u bject res p o n ds t o air sti m ul us a n d re q uests disc o nti n uati o n or m o ves fr o m sti m ul us  
3  
S u bject res p o n ds t o sti m ul us, c o nsi ders sti m ul us t o be pai nf ul, a n d re q uests 
disc o nti n uati o n of t he sti m ul us  
•  T o be dee me d ‘eli gi ble’ f or B aseli ne  D H assess me nt s, a t o ot h m ust h a ve a Scree ni n g 
t actile t hres h ol d ≤ 2 0 g a n d a Scree ni n g Sc hiff se nsiti vit y sc ore ≥ 2 .  
•  Teet h wit h a Scree ni n g Sc hiff se nsiti vit y sc ore < 2 will be dis q u alifie d fr o m f urt her 
testi n g. 
9. 2  
D H Effi c a c y A s s e s s m e nt s  
T he f oll o wi n g D H effi cac y ass ess me nts will be perf or m e d b y a p pr o priatel y trai ne d a n d 
e x perie n ce d cli nical e x a mi ners /staff, at t h e ti mes a n d i n t he or der defi ne d i n t he St u d y 
Pr oce d ures  s ecti o n of t his pr ot oc ol (Secti o n 8 ).  
If, i n t he o pi nio n of t he cli nical e xa mi ner, t he val u e/ sc ore f or a partic ul ar t o ot h is bet wee n t w o 
val ues/ descri pti o ns , a c o nser vati ve a p pr oac h s h o ul d be a d o pte d, a n d t he m ore c o nser vati ve 
val ue/ sc ore rec or de d. T h e sa me a p pr oac h s h o ul d be a p plie d t hr o u g h o ut t he st u d y t o e ns ure 
c o nsiste nc y of ass ess me nt  at all ti me p oi nts.  
9. 2. 1  
D e nti n e H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e ( D H E Q -4 8 ) 
T he D H E Q -4 8  is a c o n diti o n-s pecific meas ure of O Hr Q o L in relati o n t o D H ( B oi k o, 2 0 1 0 ) t hat 
has bee n pre vi o usl y vali date d i n l o n git u di nal st u dies a n d s h o w n t o be res p o nsi ve t o treat me nt 
(Ba ker, 2 0 1 4 ). T he  D H E Q t otal sc ore ca n be br o ke n d o w n i nt o 5 se parate ‘d o mai n ’ sc ores t o 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 7  of 1 1 3  
pr o vi de  a m ore gra n ular u n dersta n di n g of t he s pecific areas of i m pr o ve me nt s u bjects e x perie n ce 
i n t heir O Hr Q O L. 
•  Restricti o ns : Deri ve d fr o m partici pa nt  res p o nses t o Secti o n 2, Q 1-4  (‘t he w ays i n w hic h 
a ny se ns ati o ns i n y o ur teet h affect y o u i n y o ur d aily life ’).  
•  A d a pt ati o n : Deri ve d fr o m partici pa nt  res p o nses t o Secti o n 2, Q5 -1 6 (‘ t he w ays i n 
w hic h t he se ns ati o ns i n y o ur teet h h ave f orce d y o u t o c h a n ge t hi n gs i n y o ur d aily life ’; 
‘t hi n gs y o u d o i n y o ur d aily life t o av oi d ex perie nci n g t he se ns ati o ns i n y o ur teet h’). 
•  S oci al I m p act : Deri ve d fr o m partici pa nt  res p o ns es t o Secti o n 2, Q 17 -2 1  (‘t he w ay t h e 
se ns ati o ns affect y o u w he n y o u are wit h ot her pe o ple or i n cert ai n sit u ati o ns ’).  
•  E m oti o n al I m p act : Deri ve d fr o m partici pa nt  res p o nses t o Secti o n 2, Q2 2 -2 9  (‘t he w ay 
t he se ns ati o ns i n y o ur teet h m ake y o u feel’).  
•  I de ntit y: Deri ve d fr o m p artici pa nt  res p o ns es t o Secti o n 2, Q3 0 -3 4  (‘w h at t h e se ns ati o ns 
i n y o ur teet h me a n f or y o u’).  
T he  D H E Q als o pr o vi des s pecific i nf or mati o n o n h o w m uc h t he se nsati o ns i n t he partici pa nt ’s 
teet h affect t heir life o v erall:  
•  Gl o b al Or al He alt h : Deri ve d fr o m partici p a nt  res p o nse t o Secti o n 2, Q3 5  (‘r ate t he 
he alt h of y o ur m o ut h, teet h a n d g u ms ’).  
•  Effect o n  Life O ver all : Deri ve d fr o m partici p a nt  res p o nses t o Secti o n 2, Q3 6 -3 9  
(i m pact of D H o n o v erall Q o L). 
S u bjects will i n de pe n de ntl y ( u ns u per vise d) c o m pl ete a  har d c o p y of t he D H E Q -4 8  (A p pe n di x 
1 5 . 2) at Bas eli ne ( Visit 2 ), D a y 2 8  (Visit 3 ) a n d Da y 5 6  (Visit 4 ), pri or t o a n y cli nical 
e xa mi nati o ns a n d assess me nts . 
•  B aseli ne : C o m plete Secti o n 1 a n d Secti o n 2 (i.e., all q uesti o ns  i n b ot h secti o ns).  
•  D a y 2 8 & D a y 5 6 : C o m plete Secti o n 1 Q uest io n s 7 -9  o nl y,  a n d  Secti o n 2 all q uesti o ns.  
9. 2. 2  
T a ctil e S e n siti vit y A s s e s s m e nt s  
Tactile  se nsiti vit y will be assesse d at Baseli ne ( Visit 2), Da y 2 8 ( Visit 3) a n d Da y 5 6 ( Visit 4) . 
T he tactile sti m ul us will be a d mi nistere d, a n d s u bj ect res p o nse rec or de d, as descri be d i n Secti o n 
9 . 1. 4. T he gra m setti n g w hic h elicits t w o c o nsec uti ve ‘ yes’ res p o ns es will be rec or de d as t h e 
tactile t hres h ol d ( g). 
•  B aseli ne : Assess t he tactile se nsiti vit y of all teet h w hic h e x hi bit n o ne of t he de ntiti o n 
e xcl usi o ns a n d meet t he E A R, M GI a n d cli nical m o bilit y criteria , wit h a Scree ni n g 
tactile t hres h ol d of ≤ 2 0 g a n d a Scree ni n g Sc hiff se nsiti vit y sc ore ≥ 2 (i.e., t he ‘eli gi ble 
teet h’ i de ntifie d at Scree ni n g).  
T he u p per f orce setti n g will be 2 0 g; if n o se nsiti vit y is f o u n d at t he u p per setti n g, rec or d 
tactile t hres h ol d as > 2 0 g.  
•  D a y 2 8 & D a y 5 6 : Assess t he tactile se nsiti vit y of t he t w o ‘T est T eet h’ o nl y  (i.e., t he 
t w o teet h selecte d b y t he cli nical e xa mi ner at Baseli ne, as descri be d i n Secti o n 8 . 2. 1. 5). 
T he u p per f orce setti n g will be 8 0 g; if n o se nsiti vit y is f o u n d at t he u p per setti n g, rec or d 
tactile t hres h ol d as > 8 0 g. 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 8  of 1 1 3  
9. 2. 3  
E v a p or ati v e ( Air) S e n siti vit y A s s e s s m e nt s  
E va p orati ve (air) se nsiti vit y will be assesse d at Baseli ne ( Visit 2), Da y 2 8 ( Visit 3) a n d D a y 5 6 
( Visit 4). T he e v a p orati v e (air) sti m ul us will be a d mi nister e d, a n d s u bject res p o nse rec or de d  
( Sc hiff Se nsiti vit y Sc ore), as d escri be d i n Secti o n 9 . 1. 5. E va p orati ve (air) assess me nt s will start  
a mi ni m u m of 5 mi n utes after t he t actile assess me nts ha ve c o m plete d (t o ot h rec o ver y ti me). 
•  B aseli ne :  
- 
First  assess e v a p orati ve (air) se nsiti vit y f or all ‘Eli gi ble Teet h ’ i de ntifie d at 
Scree ni n g  wit h a Baseli n e  tactile t hres h ol d of ≤ 2 0 g. 
- 
T he n  assess e va p orati v e (air) se nsiti vit y f or t he re mai ni n g ‘Eli gi ble Teet h ’ 
i de ntifie d at Scree ni n g wit h a Baseli ne  tactile t hres h ol d of > 2 0 g .  
•  D a ys 2 8 & 5 6 :  
- 
First  assess e va p orati ve (air) se nsiti vit y f or t he t w o ‘ Test Teet h’  (i. e., t he t w o teet h 
selecte d b y t he cli nical e xa mi ner at Baseli ne, as d escri be d i n Secti o n 8. 2. 1. 5 ). 
- 
T he n  assess e va p orati ve (air) se nsiti vit y f or all re mai ni n g ‘Eli gi ble Teet h ’ 
i de ntifie d at Scree ni n g. D o n ot  re-assess t he t w o ‘ Test Teet h’ . 
‘ Eli gi ble Teet h’ = Teet h wit h n o de ntiti o n excl usi o ns w hic h me et E A R, M GI a n d m o bility i ncl usi o n criteri a, 
a n d h a ve a Scree ni n g  t actile t hres h ol d ≤ 2 0 g a n d a Scree ni n g  Sc hiff se nsitivity sc ore ≥ 2.  
Sc ore  
Descri pti o n  
0  
S u bject d oes n ot res p o n d t o air sti m ulati o n  
1  
S u bject res p o n ds t o air sti m ul us b ut d oes n ot re q uest disc o nti n uati o n of sti m ul us 
2  
S u bject res p o n ds t o air sti m ul us a n d re q uests disc o nti n uati o n or m o ves fr o m sti m ul us  
3  
S u bject res p o n ds t o sti m ul us, c o nsi ders sti m ul us t o be pai nf ul, a n d re q uests 
disc o nti n uati o n of t he sti m ul us  
 
9. 2. 4  
L a b ell e d M a g nit u d e S c al e s  ( L M S s) 
S u bjects will rate t he (i) i nte nsity, (ii) d ur ati o n  a n d (iii) t oler a bility of t heir res p o nse t o t h e 
e va p orati ve (air) sti m ul us  a n d (i v) descri be  t heir res p o nse, usi n g f o ur 1 0 0 -milli metre ( m m) 
L M Ss ( A p pe n di x 1 5 .3 ), at Baseli ne ( Visit 2), Da y 2 8 ( Visit 3) a n d Da y 5 6 ( Visit 4) .  
L M Ss s h o ul d be c o m plete d i m me di atel y after  t he cli nical e xa mi ner has rec or de d t he Sc hiff 
se nsiti vit y sc ore f or a gi ve n t o ot h. T o a v oi d bias, t he s u bject s h o ul d be u na ware of t he 
e xa mi ner’s sc ore a n d t h e cli nical e xa mi ner s h o ul d n ot ha ve visi bilit y of t he s u bject’s L M S 
res p o nses. 
•  B aseli ne : C o m plete f o ur L M Ss f or eac h t o ot h wit h a Baseli ne  tactile t hres h ol d of ≤ 2 0 g 
a n d a Baseli ne  Sc hiff se nsiti vit y sc ore ≥ 2 . 
•  D a ys 2 8 & 5 6 : C o m plete f o ur L M Ss f or eac h ‘ Test To o t h’ (i.e., t he t w o teet h selecte d 
b y t he cli nical  e xa mi ner at Baseli ne , as des cri be d i n Secti o n 8 . 2. 1. 5). 
S t u d y staff will meas ure t he dista nce  t o t he s u bj ect’s mar k (‘ X’) fr o m left t o ri g ht al o n g t he 1 0 0 
m m li ne a n d rec or d t his val ue (i n m m) i n t he e C R F f or eac h L M S c o m plet e d.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 5 9  of 1 1 3  
N ote:  S u bjects will  c o m plete t he L M S trai ni n g e xercise (A p pe n di x 1 5 .4 ) at Scree ni n g  ( Visit 1 ), 
bef ore t heir cli nical e xa mi nati o ns/ D H assess me nts.  A n y s u bject w h o, i n t he o pi ni o n of t he 
i n vesti gat or or desi g ne e, is u na ble t o pr o vi de a p pr o priate res p o nses t o t he L M S trai ni n g 
q uesti o ns, will be e xcl u d e d fr o m p artici pati o n i n t he st u d y  (Secti o n 5. 3 E xcl usi o n Criter i o n 27 ).  
9. 3  
S af et y A s s e s s m e nt s  
T he f oll o wi n g safet y assess me nts will be perf or m e d b y a p pr o pri atel y trai ne d cli nical e xa mi ner s, 
at t he ti mes a n d i n t he or der defi ne d i n t he  St u d y Pr oce d ures  secti o n of t his pr ot oc ol (Secti o n  8 ).   
9. 3. 1  
Or al S oft Ti s s u e ( O S T) E x a mi n ati o n  
T he  O S T e xa mi nati o n will be acc o m plis he d b y direct vis ual o bser vati o n a n d pal pati o n , usi n g 
retracti o n ai ds as a p pr o priate, a n d will i ncl u de e xa mi nati o n of t he la bial m uc osa (i ncl u d i n g 
li ps), b uccal m uc osa, m uc o gi n gi val f ol ds, gi n gi val m uc osa, har d p alate, s oft palate, t o nsillar 
area, p h ar y n geal area, t o n g ue, s u bli n g ual area, s u b ma n di b ular area a n d s ali var y gla n ds.  
T he res ults of t he e x a mi nati o n will be rec or de d i n t he eC R F as eit he r ‘n or mal ’ or ‘a b n or m al ’; 
details of a n y a b n or malities  will be d oc u me nte d i n t he e C R F . A n y o bser vati o n t hat c ha n ges 
fr o m ‘n or mal ’ t o ‘a b n or mal ’, or w orse ns, fr o m t he O S T e xa mi nati o n c o m plete d at S cree ni n g  
will  be rec or de d as a n A E.  
9. 3. 2  
Or al H ar d Ti s s u e ( O H T) E x a mi n ati o n  
T he O H T e x a mi nati o n will be acc o m plis he d b y direct vis ual o bser vati o n , usi n g retracti o n ai ds 
as a p pr o priate , a n d 
will i de ntif y e na mel irre g ularities, t o ot h fract ur es, gr ossl y cari o us 
lesi o ns/ gr oss deca y, defecti ve/f a ult y rest orati o ns (b ot h direc t a n d i n direct rest or ati o ns, 
i ncl u di n g fi xe d/ re m o vable  pr ost heses), n o n -cari o us t o ot h s urface l oss (a brasi o n, attriti o n, 
a bfracti o n a n d er osi o n), a n y ot her h ar d tiss u e irre g ularities (e. g. , h y p o - a n d h y per -
mi nerali zati o n, decalcificati o n) a n d si g nifica nt t o ot h stai ni n g.  
O bser vati o ns will b e liste d as ‘abse nt ’ or ‘ pres e nt’; c o n diti o ns n ote d as ‘pres e nt ’ will b e 
descri be d  i n t he e C R F. A n y o bser vati o n t hat c ha n g es fr o m ‘abse nt ’ t o ‘ prese nt’ or w orse ns fr o m 
t he O H T e xa mi nati o n c o m plete d at S cree ni n g  will  be rec or de d as a n A E.  
T he pres e nce of a n y i m pla nts, fi xe d or re m o v a ble de nt ures, fi xe d or re m o va ble ort h o d o ntic 
braces/ b a n ds, fi xe d ort h o d o ntic retai ners, f ull cr o w ns or ve neers will be rec or de d, al o n g wit h 
e vi de nce of gr oss i ntra -oral ne glect or t he nee d f or e xte nsi ve de nt al t hera p y.  
T he O H T e x a mi nati o n will als o be  use d t o ass ess t he s u bject’s de ntiti o n a gai nst t he ge neral a n d 
s pecific de ntiti o n e xcl usi o ns descri be d i n Secti o n 5. 3  (E xcl usi o n Criteria 2 2, 2 3, 2 4, 2 5, 2 6a -g ). 
9. 3. 3  
Pr e g n a n c y  
T his cli nica l st u d y will utilize t o ot h pastes classifie d as O T C m o n o gra p h dr u gs i n t he U S. 
H o we ver, n o ne of t he st u d y t o ot h pastes are c o ntra-i n dicat e d f or pre g na n c y or breastf ee di n g 
(t heir use w o ul d n ot be e x pecte d t o ca use h ar m t o t he m ot her, t he f oet us or a ba b y) ; the U S 
c o m mercial pr o d ucts  (t he A ccli matizati o n a n d Refere n ce T o ot h pastes)  d o n ot  carr y pre g na nc y 
war ni n g s o n t he la b elli n g (e. g., i nstr ucti o ns t o s pea k t o a d oct or b ef ore use if pre g na nt); t he Test 
T o ot h paste will n ot carr y a pre g na n c y war ni n g w he n mar ket e d i n t he U S . Th us , pre g na nc y 
testi n g of  fe male s u bjects is n ot re q uire d pri or t o t heir e nr ol me nt . 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 0  of 1 1 3  
Fe male s u bjects will pr o vi de ver bal c o nfir mati o n of pre g na n c y stat us at Scree ni n g ( Visit 1) a n d 
at eac h s u bse q ue nt st u d y visit ; this will be rec or de d i n t he  e C R F. T he y will be i nstr ucte d t o 
i nf or m t he i n vesti gat or staff i m me diatel y s h o ul d t he y fi n d o ut t he y are pre g na nt at a n y p oi nt 
d uri n g t he st u d y.   
Fe male s u bjects w h o are pre g na nt or i nte n di n g t o bec o me pre g n a nt d uri n g t he st u d y (self-
re p orte d) will be e xcl u de d (t he rati o nale f or e x cl usi o n is pr o vi de d i n Secti o n 4 . 2). 
9. 3. 4  
S ati sf a cti o n wit h Tr e at m e nt  
At t he e n d of t he st u d y ( Visit 4 ), s u bjects will be as ke d t o rate t heir le vel of satisfacti o n wit h 
t heir all ocate d i n vesti gati o nal t o ot h paste usi n g a N u meric Rati n g Scale ( N R S).  
T he N R S is a n 1 1 -p oi nt or di nal scale use d t o assess t he s u bject’s satisfacti o n wit h t he pr o d uct’s 
o verall ma na g e me nt of t heir D H. T he scale ra n ges fr o m 0 (c o m pletel y dissatisfie d) t o 1 0 
(c o m pletel y satisfie d), wit h hi g her s c ores i n dicati v e of greater satisfacti o n ( va n Berc kel, 2 0 1 7 ): 
see e xa m ple b el o w.  
S u bjects will be as ke d t o rec or d t he n u meric v al u e o n t he se g me nte d s cale t hat best descri bes 
t heir le vel of satisfacti o n after 8 wee ks t wice d ail y use a n d i n dicate w h y t he y selecte d a 
partic ular s c ore i n a ns wer t o t he q uesti o n ‘ Pleas e gi ve m ore det ails o n w h y y o u are satisfie d or 
dissatisfie d wit h t he pr o d uct’ (free te xt res p o nse).  
 
E x a m ple N R S - N ot t o Sc ale  
1 0  
A D V E R S E E V E N T S  A N D S E RI O U S A D V E R S E E V E N T S  
T he i n vesti gat or a n d t heir me dicall y 
q ualifie d desi g nees are res p o nsi ble f or detecti n g, 
d oc u me nti n g a n d re p orti n g e ve nts t hat m eet t h e defi niti o n of a n A E or S A E a n d re mai n 
res p o nsi ble f or f oll o wi n g u p A Es t hat are seri o us, c o nsi dered relate d t o st u d y pr o d uct , a st u d y 
pr oce d ure  or st u d y  p artici pati o n , or t hat ca us e d t h e s u bject t o disc o nti n ue use of st u d y pr o d uct 
or  st u d y partici pati o n.  
1 0. 1  
D efi niti o n of a n A d v er s e E v e nt ( A E)  
A n A E is a n y u nt o war d me dical occ urre nce i n a cli nical st u d y s u bject, te m p orall y ass ociate d 
wit h t he use of a st u d y pr o d uct i ncl u di n g a n accli matizati o n  pr o d uct ( or me dical d e vice), 
w het her or n ot c o nsi dere d relate d t o t he st u d y pr o d uct, i ncl u di n g a n accli matizati o n  pr o d uct ( or 
me dical de vice).  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 1  of 1 1 3  
N ote : A n A E ca n t h eref o re be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he 
use of a st u d y pr o d uct i n cl u di n g a n accli matizati o n  pr o d uct ( or me dical de vice).  
E ve nts Meeti n g  t he A E Defi niti o n:   
•  A n y a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y  or uri nal ysis) or 
ot her safet y assess m e nts (e. g. , electr o car di o gra m, ra di ol o gical s ca ns, vital si g n 
meas ure me nts), i ncl u di n g t h ose t hat w ors e n fr o m 
B aseli ne, c o nsi dere d cli nicall y 
si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or (i.e., n ot relate d t o 
pr o gressi o n of u n derl yi n g disease).  
N ote:  A n y O S T o bser vati o n t hat c ha n ges fr o m ‘ n or mal’ t o ‘a b n or mal’, or w orse ns, fr o m t he O S T 
e x a mi nati o n c o m plete d at Scree ni n g s h o ul d be rec or de d as a n A E’ irres pecti ve of cli nical si g nifica n ce.  
•  E xacer bati o n  of a c hr o nic or i nter mitte nt pre -e xisti n g c o n diti o n i ncl u di n g eit her a n 
i ncreas e i n fre q u e nc y a n d/ or i nte nsit y of t he c o n diti o n. 
•  Ne w c o n diti o ns detecte d  or dia g n ose d aft er st u d y pr o d uct a d mi nistrati o n e ve n t h o u g h it 
ma y ha ve bee n pres e nt b ef ore t h e start of t he st u d y.  
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.  
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o v er d ose of eit her st u d y pr o d uct 
or a c o n c o mita nt me dicati o n. O ver d ose p er s e will n ot be re p orte d as a n A E/ S A E u nless 
it is a n i nte nti o nal o v er d ose ta ke n wit h p ossi bl e s uici dal/self-h ar mi n g i nte nt. S uc h 
o ver d oses s h o ul d be re p orte d re g ar dless of s e q uelae.  
•  ‘Lac k of efficac y ’ or ‘fail ure of e x pecte d p har m ac ol o gical acti o n’ per se will n ot be 
re p orte d as a n A E. S u c h i nsta nces will be ca pt ure d i n t he efficac y assess me nts. 
H o we ver, t he si g ns, s y m pt o ms a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y 
will be re p orte d as a n A E if t he y f ulfill t he defi niti o n of a n A E.  
E ve nts N O T  meeti n g t he A E defi niti o n:  
•  A n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs (if a p plica ble) or ot her a b n or mal 
safet y assess me nts w hic h are ass ociat e d wit h t he u n derl yi n g disease, u nless j u d ge d b y 
t he i n vesti gat or t o be m ore se vere t ha n e x pect e d f or t he s u bject’s c o n diti o n.  
•  T he diseas e/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of t he 
disease/ dis or der b ei n g st u die d, u nless m ore se v ere t ha n e x pecte d f or t he s u bject’s 
c o n diti o n.  
•  A  m e dical or s ur gical pr oce d ure (e. g. , e n d osc o p y, a p pe n dect o m y) is n ot a n A E. T he 
c o n diti o n t hat lea ds t o t he pr oce d ure is a n A E ( e. g., a p pe n dicitis).  
•  Sit uati o ns w here a n u nt o war d 
me dical occ urre nce di d n ot o cc ur (s ocial a n d/ or 
c on ve nie nce a d missi o n t o a h os pital).  
•  A ntici pate d da y -t o-da y fl uct uati o ns of pre -e xisti n g disease(s) or c o n diti o n(s) pres e nt or 
detecte d at t he start of t h e st u d y t hat d o n ot w orse n.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 2  of 1 1 3  
1 0. 2  
D efi niti o n of a S eri o u s A d v er s e E v e nt ( S A E)  
A  seri o us ad v erse eve nt ( S A E) is a p artic ular cate g or y of A E  w here t he a d verse o utc o me is 
seri o us. If a n e v e nt is n ot a n A E per defi niti o n a b o ve, t he n it ca n n ot be a n S A E, e ve n if seri o us 
c o n diti o ns are met (e. g. , h os pitalizati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y , d eat h 
d ue t o pr o gressi o n of dis ease).  
A seri o us a d verse e v e nt is a n y u nt o war d me dical occ urre nce at a n y d ose t h at:  
•  Res ults i n de at h  
•  Is life-t hre ate ni n g  
- 
T he ter m 'life -t hreate ni n g' i n t he defi niti o n of 'seri o us' refers t o a n e ve nt i n w hic h 
t he s u bject was at ris k of deat h at t he ti me of t he e ve nt. It d oes n ot refer t o a n e ve nt, 
w hic h h y p ot heticall y mi g ht ha ve ca us e d deat h, if it were m or e se vere . 
•  Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n   
- 
I n g e neral, h os pitalizati o n sig nifies t hat t he s u bject has bee n detai ne d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge n c y war d f or 
o bser vati o n a n d/ or treat me nt t hat 
w o ul d n ot ha ve bee n a p pr o priat e i n t he 
p h ysicia n’s office or o ut patie nt setti n g. 
C o m plicati o ns  t hat occ ur d uri n g 
h os pitalizati o n are A Es. If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y 
ot her seri o us criteria, t he e ve nt is s eri o us. 
W he n i n d o u bt as t o 
w het her 
‘h os pitalizati o n ’ occ urre d, or was necessar y, t he A E s h o ul d be c o nsi dere d seri o us.  
- 
H os pitalizati o n f or electi ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot w orse n 
fr o m B aseli ne is n ot c o nsi dere d a n A E.  
•  Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y  
- 
T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a b ilit y t o c o n d uct 
n or mal life f u ncti o ns.  
- 
T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea d ac h e, na usea, v o miti n g, diarr hea, 
i nfl ue nza, a n d acci de ntal tra u ma (e. g., s prai ne d a n kle) w hich ma y i nterfere wit h or 
pre ve nt e v er y da y life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n . 
•  Res ults i n c o n ge nit al a n o m al y/ birt h defect  
•  Ot her sit u ati o ns:  
- 
Me dical or s cie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g w het h er S A E 
re p orti n g is a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical e v e nts t hat 
ma y n ot be i m me diatel y life -t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut 
ma y je o par di ze t he s u bj ect or ma y re q uire me dical or s ur gical i nter ve nti o n t o 
pre ve nt o n e of t he ot her o utc o mes liste d i n t he a b o ve d efi niti o n. T hese e ve nts 
s h o ul d us uall y be c o nsi dere d seri o us. 
E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve tr eat me nt 
i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias or 
c o n v ul si o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of dr u g 
de pe n de n c y or dr u g a b us e.  
N ote:  Classificati o n of a n A E as ‘seri o us’ is base d o n t he o utc o me of t he e ve nt a n d is a fact or 
i n deter mi ni n g re p orti n g re q uire me nts. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 3  of 1 1 3  
1 0. 3  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n 
All A Es, a n d t heref ore all S A Es , will be c ollecte d fr o m i m me diatel y after a s u bject pr o vi des 
c o nse nt  t o partici pate i n t he st u d y b y t he c o m pleti o n (si g nat ure) of t he I C F u ntil 5 d a ys 
f oll o wi n g t he last a d mi nistrati o n of st u d y pr o d uct ( or t he last st u d y pr oce d ure).  
Me dical occ urre nces t hat be ga n bef ore o btai ni n g i nf or me d c o nse nt will be rec or de d i n t he 
Me dical Hist or y/ C urre nt Me dical C o n diti o ns  secti o n of t he eC R F , n ot t he A E secti o n . 
Details rec or de d b y t he s u bject in a diar y or si milar d oc u me nt t h at meet t h e defi niti o n of a n A E 
m ust be disc usse d wit h t he s u bjects a n d tra ns cri b e d i nt o t he A E secti o n of t he eC R F.  
All S A Es will be rec or de d a n d re p orte d t o t he s p o ns or or d esi g nee i m me dia tel y, a n d u n der n o 
circ u msta nce s h o ul d t his e xcee d 2 4 h o urs. T he i n vesti gat or will s u b mit u p date d S A E data t o 
t he s p o ns or wit hi n 2 4 h o urs of it bei n g a vaila ble . 
T he i n vesti gat or  a n d t heir me dicall y q ualifie d desi g nees are  n ot o bli gate d t o acti vel y see k A Es 
or S A Es  after t he c o ncl usi o n of st u d y p artici pati o n . H o we ver, if t he i n vesti gat or or t heir 
me dicall y q ualifie d desi g nee lear ns of a n S A E, i n cl u di n g a deat h, at a n y ti m e after a s u bject has 
bee n disc h ar ge d fr o m t h e st u d y, a n d t he y c o nsi d er t he e ve nt t o b e reas o n a bl y relate d t o st u d y 
pr o d uct  or st u d y partici p ati o n, t he y  m ust pr o m ptl y n otif y t he s p o ns or.  
1 0. 4  
R e p orti n g Pr o c e d ur e s  
T he i n vesti gat or a n d t heir me dicall y q ualifie d 
desi g nees are res p o nsi ble f or detecti n g, 
d oc u me nti n g a n d re p orti n g e ve nts t hat meet t he d efi niti o n of a n A E a n d re mai n res p o nsi ble f or 
f oll o wi n g u p A Es t hat are seri o us, c o nsi dere d rel ate d t o st u d y pr o d uct, a st u d y pr oce d ure  or 
st u d y partici pati o n , or t hat ca use d t he s u bject t o disc o nti n ue use of st u d y pr o d uct or st u d y 
partici pati o n . 
T he i n vesti gat or a n d t h eir me dicall y q ualifie d d esi g nee s are t o re p ort all A Es directl y o bser ve d 
at st u d y visits a n d all A Es s p o nta ne o usl y re p orte d b y st u d y s u bject s.  
St u d y s u bjects will be q ue sti o ne d a b o ut A Es. Care will be ta ke n n ot t o i ntr o d uce bias w he n 
q uesti o ni n g a s u bject a b o ut a n y c ha n g es i n t heir healt h. O pe n -e n d e d a n d n o n -lea di n g v er bal 
q uesti o ni n g s h o ul d be use d.  
A Es s p o nta ne o us l y re p orte d b y st u d y s u bjects  a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d 
t o n o n-lea di n g q uesti o ns ( s uc h as ‘ ho w d o y o u fee l?’) will be assess e d , rec or de d i n t he eC R F  
a n d re p ort e d , as a p pr o pri ate . 
Eac h A E is t o be ass esse d t o deter mi ne if it meets t he criteria f or a S A E. If a n S A E occ urs, 
e x pe dite d re p orti n g will f oll o w l ocal a n d i nter nati o nal re g ulati o ns, as a p pr o priate.  
W he n a n A E o cc urs, it is t he res p o nsi bilit y of t he i n vesti gat or 
or t heir  me dicall y q ualifie d 
desi g nee t o re vie w all d o c u me ntati o n (e. g. , h os pital pr o gress n otes,  la b orat or y a n d dia g n ostics 
re p orts) relate d t o t he e ve nt. T he i n v esti gat or or st u d y staff will t he n rec or d all rele va nt 
i nf or mati o n rel ati n g t o t h e e v e nt i n t he A E secti o n of t he eC R F . I n a d diti o n, all details relati n g 
t o a n S A E will be rec or de d on  t he paper S A E for m pr o vi de d.  
It is n ot  acce pta ble f or t he i n vesti gat or or t heir me dicall y q ualifie d desi g nee t o se n d p h ot oc o pies 
of a s u bject’s me dical rec or ds t o t he s p o ns or i n lie u of c o m pleti o n of t he A E secti o n of t he 
eC R F / pa per S A E f or m.  T here m a y be i nsta n ces w he n c o pies of m e dical rec or ds f or certai n 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 4  of 1 1 3  
cases are re q u este d b y t he s p o ns or.  I n t his i nsta nce, all s u bject i de ntifiers, e xce pt f or t he s u bject 
n u m ber, will be re dacte d o n t he c o pies of t he me dical rec or ds pri or t o s u b missi o n t o t he s p o ns or. 
T he i n vesti gat or or t heir me dicall y q ualifie d desi g nee will atte m pt t o esta blis h a dia g n osis base d 
o n si g ns, s y m pt o ms a n d/ or ot her cli nical i nf or mati o n  relate d t o t he e ve nt. T he dia g n osis will be 
t he d oc u me nte d as t he A E/ S A E, w here k n o w n , a n d n ot t he i n di vi d ual si g ns/s y m pt o ms (e. g. , 
u p per res pir at or y tract i nfecti o n  or  seas o nal aller g y, n ot  ‘r u n n y n ose’). 
1 0. 4. 1  
R e p orti n g a n A E  
A Es will be re p orte d b y t he  i n vesti gat or, t heir me dicall y q ualifie d desi g ne e or site staff  i n t he 
A E secti o n of t he eC R F .  T he pa per f or m use d f or c ollecti o n of S A E i nf or mati o n is n ot t he sa me 
as t he A E s ecti o n of t he eC R F . A Es / S A Es s h o ul d be re p orte d usi n g c o ncise me di cal 
ter mi n ol og y.  W here t he s a me dat a are c ollecte d, t h e A E secti o n of t he eC R F a n d t he S A E f or m 
m ust be c o m plete d i n a c o nsiste nt ma n ner  (e. g., t h e sa me A E ter m s h o ul d be use d f or b ot h ).   
1 0. 4. 2  
R e p orti n g a n  S A E  
I n a d diti o n t o rec or di n g t he details of eac h S A E i n t he A E secti o n of t he eC R F , a n S A E f or m 
s h o ul d be c o m plete d, as f ull y as p ossi ble. Har d c o pies of t he ‘ pa p er’ S A E f or m will be pr o vi de d 
i n t he i n vesti gat or site file. Ori gi nal, c o m plete d S A E f or ms will be  retai ne d i n t he i n vesti gat or 
site file. 
It is esse ntial t o rec or d t h e f oll o wi n g i nf or mati o n f or eac h S A E:  
•  Pr ot oc ol a n d s u bject i de ntifiers  
•  S u bject de m o gra p h y  
•  Descri pti o n of e v e nt wit h dia g n osis , if a vaila ble 
•  I n v esti gat or o pi ni o n of relati o ns hi p t o st u d y pr o d uct ( or st u d y pr oce d ure)  
•  Criteri o n f or seri o us ness.  
T he f oll o wi n g are desir a ble a n d are of partic ul ar rele va nce f or i n vesti gat or a n d s p o ns or 
assess me nt of t he S A E re p ort:  
•  Date of o nset of S A E  
•  Date S A E st o p pe d, if rele va nt  
•  St u d y pr o d uct start date  
•  St u d y pr o d uct e n d date , if rele va nt 
•  Acti o n ta ke n i n relati o n t o st u d y pr o d uct  
•  O utc o me , if k n o w n 
T he S A E f or m, c o m plete d as f ull y as p ossi ble, m ust be sca n n e d a n d e -mail e d t o t he s p o ns or’s 
Case 
Ma na ge me nt Gr o u p  mail b o x (
, wit h t he a p pr o priate 
s p o ns or St u d y Ma na ger  i n c o p y, wit h t he st u d y n u m ber a n d s u bject n u m ber i n t he s u bject li ne 
of t he e mail i m me di atel y after site st aff le ar n of t he e ve nt, a n d u n der n o circ u mst a nce s 
s h o ul d t his e xcee d 2 4 h o urs . T he i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or, 
i m me di atel y it bec o mes a v ail a ble, a n d  u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 h o urs 
of it bei n g a v ail a ble .  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI
P P D


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 5  of 1 1 3  
T he i nitial re p ort will be f oll o we d u p wit h m ore  i nf or mati o n as rele va nt, or as re q ueste d b y t he 
s p o ns or’s St u d y Ma na ger . T he s p o ns or’s St u d y Ma na ger  will be res p o nsi ble f or f or war di n g t he 
S A E f or m t o ot her s p o ns or pers o n nel as a p pr o pri ate.  
1 0. 5  
E v al u ati n g A E s  
1 0. 5. 1  
A s s e s s m e nt of I nt e n sit y  
T he i n vesti gat or or t heir me dicall y q ualifie d desi g nee will ma ke a n assess me nt of i nte nsit y f or 
eac h A E re p ort e d d uri n g t he st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories:  
•  Mil d:   A n e ve nt t hat is easil y t olerate d b y t he s u bject, ca usi n g mi ni mal disc o mf ort a n d 
n ot i n terferi n g wit h e ver y da y acti vities. 
•  M o der ate:   A n e ve nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or mal 
e ver y da y acti vities  
•  Se vere:   A n e ve nt t hat pre ve nts n or mal e ver y da y acti vities.  
N ote : A n A E assess e d as ‘se vere’ s h o ul d n ot be c o nf use d wit h a n S A E. ‘Se vere ’ is a cate g or y 
utilize d f or rati n g t he i nte nsit y of a n e v e nt . Bot h n o n -seri o us A Es a n d S A Es ca n b e assess e d as 
se vere, e. g., a hea dac he ma y be se vere ( si g nifica ntl y i nterferes wit h t he s u bject's us ual f u ncti o n) 
b ut w o ul d n ot be classifie d as seri o us u nless it met o ne of t he criteria f or S A Es liste d i n Secti o n 
1 0 . 2. A n e ve nt is defi ne d as ‘seri o us’ w he n it meets at least o ne  of t he pre -defi ne d o utc o mes  
descri be d i n t he d efi niti o n of a n S A E  (Secti o n 1 0 . 2), n ot  w he n  it is rate d as ‘se vere’. 
1 0. 5. 2  
A s s e s s m e nt of C a u s alit y  
F or eac h A E ( n o n -seri o us a n d seri o us), t he i n vesti gat or or t heir me dicall y q ualifie d desi g nee  
m ust  pr o vi de a n assess me nt of ca usalit y in t he A E secti o n of t he eC R F a n d o n t he S A E f or m 
(as a p pr o priat e, s u bject t o classificati o n of t he A E). C a usalit y is o ne of t he criteria use d t o 
deter mi n e re g ulat or y re p orti n g re q uire me nts.  
A ‘reas o na bl e p ossi bilit y’ of a relati o ns hi p c o n v e ys t here are facts  (e vi de nce) a n d/ or ar g u me nts 
t o s u g gest a ca usal rel ati o ns hi p, rat her t ha n a relati o ns hi p ca n n ot be r ule d o ut. Ge nerall y, t h e 
facts (e vi de n ce) or ar g u m e nts t o s u g gest a ca usal relati o ns hi p s h o ul d be pr o vi de d i n t he A E/ S A E 
re p ort. 
T he i n vesti gat or or t heir me dicall y q ualifie d desi g nee  will use cli nical j u d g me nt t o deter mi ne 
ca usalit y  a n d will als o c o ns ult t he I n vesti gat or Br oc h ure (I B), Safet y State me nt a n d/ or Pr o d uct 
I nf or mati o n, as a p pr o priate , w he n ma ki n g  t heir assess me nt.  Alter nati v e ca uses, s uc h as 
u n derl yi n g disease(s), c o nc o mita nt t hera p y , ot her r is k fact ors a n d t h e te m p oral relati o ns hi p of 
t he e ve nt t o st u d y pr o d uct use will be c o nsi dere d a n d i n vesti gate d.  
W here a p plica ble, t he i n vesti gat or or t heir me dicall y q ualifie d desi g nee  m ust d oc u me nt i n t he 
me dical n otes t h e y ha v e re vie we d t he A E/ S A E a n d pr o vi de d a n ass ess me nt of ca usalit y. 
T here ma y be sit uati o ns , w he n a n S A E has occ urre d, w here t h e i n vesti gat or or t h eir me dicall y 
q ualifie d desi g nee  has mi ni mal i nf or mati o n t o i ncl u de i n t he i nitial  S A E  re p ort. H o we ver, it is 
ver y i m p ort a nt t h at t he i n vesti g at or or t heir m e dic all y q u alifie d desi g nee al w a ys m a ke s 
a n assess me nt of c a us alit y f or e ver y e v e nt pri or t o i niti al tr a ns missi o n of t he S A E d at a t o  
t he s p o ns or. T he i n vesti gat or ma y c ha n ge t heir o pi ni o n of ca u salit y, i n li g ht of f oll o w-u p 
i nf or mati o n, a n d se n d a n S A E f oll o w -u p re p ort wit h a n u p date d ca usalit y assess me nt.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 6  of 1 1 3  
1 0. 6  
F oll o w -u p of A E s a n d S A E s   
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or or t heir me dicall y q ualifie d desi g nee  is re q uire d 
t o pr oacti vel y f oll o w u p wit h eac h s u bject a n d pr o vi de f urt her i nf or mati o n o n t he s u bject’s 
c o n diti o n , as a vaila ble. 
All A Es ( n o n -seri o us a n d seri o us) s h o ul d be f oll o we d u ntil res ol uti o n, u ntil t he c o n diti o n 
sta bilizes, u ntil t he e ve nt is ot her wise e x plai ne d or u ntil t he s u bject is l ost t o f oll o w -u p.   
T he i n vesti gat or or t heir me dicall y q ualifie d desi g nee  is o bli gate d t o perf or m or arra n ge f or t he 
c o n d uct of  s u p ple me ntal meas ure me nts a n d/ or e val uati o ns as ma y b e i n dicate d (or as re q uest e d 
b y t he s p o ns or) t o el uci date as f ull y as p ossi ble t he nat ure a n d/ or ca usalit y of t he A E/ S A E. 
T h ese ma y i ncl u de a d diti o nal la b orat or y tests or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, 
or c o ns ultati o n wit h ot her healt hcare pr ofessi o nals.  
Ne w or u p date d i nf or mati o n will be rec or de d in t he A E secti o n of t he eC R F a n d o n t he S A E 
f or m (as a p pr o priate, s u bject t o classificati o n of t he A E). T h e i n vesti gat or or t heir me dicall y 
q ualifie d desi g nee  will s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs of recei pt 
of t he i nf or mati o n.  
T he i n vesti gat or  a n d t heir me dicall y q ualifie d desi g nees are  n ot o bl i gate d t o acti vel y see k A Es 
or S A Es  after t he c o ncl usi o n of st u d y p artici pati o n . H o we ver, if t he i n vesti gat or or t heir 
me dicall y q ualifie d desi g nee  lear ns of a n S A E, i n cl u di n g a deat h, at a n y ti m e after a s u bject has 
bee n disc h ar ge d fr o m t h e st u d y, a n d t hey  c o nsi d er t he e ve nt t o b e reas o n a bl y relate d t o st u d y 
pr o d uct  or st u d y partici pati o n, t he y  m ust pr o m ptl y n otif y t he s p o ns or  b y e maili n g t he 
i nf or mati o n  
t o  
t he 
s p o ns or’s 
Case  
Ma na g e me nt  
Gr o u p  
mail b o x 
(
, wit h t he a p pr o priate s p o ns or St u d y Ma na ger  i n c o p y. 
T he i n vesti gat or or t heir me dicall y q ualifie d desi g nee  will s u b mit a n y u p date d S A E data t o t he 
s p o ns or wit hi n t he desi g nate d re p orti n g ti me fra mes.  
1 0. 7  
Wit h dr a w al D u e t o a n A d v er s e E v e nt  
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o ot her ca us es, acc or di n g 
t o t he defi niti o n of a n A E pr o vi de d  (Secti o n 1 0 . 1) a n d rec or de d in t he A E s ecti o n of t he eC R F .  
W he n a s u bject wit h dra ws d ue t o  a n S A E, t he S A E m ust be re p orte d i n  acc or da nce wit h t he 
re p orti n g re q uir e me nts d efi ne d i n t his pr ot oc ol. 
1 0. 8  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s 
T he s p o ns or  h as a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t h e l ocal re g ulat or y a ut h orit y 
a n d ot her re g ulat or y a ut h orities a b o ut t he saf et y of a pr o d uct u n d er cli nical i n vesti gati o n.  
Pr o m pt n otificati o n of S A Es b y t he i n vesti gat or t o t he s p o ns or is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of s u bjects are m et.  
T he s p o ns or will c o m pl y wit h c o u ntr y s pecific re g ulat or y re q uire m e nts relati n g t o safet y 
re p orti n g t o t he re g ulat or y a ut h orit y, t he I R B a n d t he i n vesti gat or. 
T he i n vesti gat or a n d t he s p o ns or will c o m pl y wit h l ocal me dical de vice re p orti n g re q uire me nts .  
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x p ecte d seri o us a d verse reacti o ns 
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire m e nts a n d s p o ns or p olic y, a n d f or war de d t o t he 
i n vesti gat or, as a p pr o pri ate . 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI
P P D


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 7  of 1 1 3  
If t he i n vesti gat or recei ves a n i n vesti gat or safet y re p ort descri bi n g a S AE or ot her s pecific safet y 
i nf or mati o n (e. g., a s u m mar y or listi n g of S A Es) fr o m t he s p o ns or, t he y will re vie w it, file it 
w it h ot her safet y i nf or m ati o n (e. g., t he I B)  i n t he i n vesti gat or site file a n d n otif y t he I R B, if 
a p pr o priate, acc or di n g t o l ocal re q uir e me nts.  
1 0. 9  
Pr e g n a n c y  
1 0. 9. 1  
Ti m e P eri o d f or C oll e cti n g Pr e g n a n c y I nf or m ati o n  
Pre g na nc y i nf or mati o n will be c ollecte d o n all pre g na nci es re p orte d w hile a fe male s u bject is 
partici pati n g i n t he st u d y fr o m t he date/ti me of si g ni n g t he i nf or me d c o nse nt u ntil 5 da ys a fter 
t he last a d mi nistrati o n of st u d y pr o d uct. 
1 0. 9. 2  
A cti o n t o b e T a k e n if Pr e g n a n c y O c c ur s  
T he i n vesti gat or or t heir me dicall y q ualifie d desi g nee  will rec or d pre g na n c y i nf or mati o n o n t h e 
a p pr o priate f or m sca n 
a n d 
e -mail it t o t he 
Case 
Ma n a ge me nt 
Gr o u p 
mail b o x 
(
, wit h t he a p pr o priate s p o ns or St u d y 
Ma na ger  i n c o p y. 
Ori gi nal c o m plete d pre g na nc y i nf or mati o n f or ms will be retai ne d i n t he i n vesti gat or site file.  
T he fe male s u bject will be f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y.  I nf or m ati o n 
o n t he stat us of t he m ot her a n d i nf a nt/ ne o nate (i ncl u di n g c o nc o mita nt me dicati o ns ta ke n b y t he 
m ot her d uri n g pre g na n c y) will be f or war de d b y t he i n vesti gat or  or t heir me dicall y q ualifie d 
desi g nee  
t o  
t he 
s p o ns or’s 
Case  
Ma na ge me nt  
Gr o u p 
mail b o x 
(
), wit h t he a p pr o priate s p o ns or St u d y 
Ma na ger  i n c o p y. 
Ge nerall y, f oll o w -u p will be f or n o l o n ger t ha n 6 t o 8 wee ks f oll o wi n g t he esti mate d d eli ver y 
date. T er mi nati o n of pre g na nc y will be re p orte d.  
W hile pre g na n c y itself  is n ot c o nsi dere d t o be a n A E, a b n or mal pre g na n c y o utc o mes (e. g., 
s p o nta ne o us a b orti o n, fet al deat h, still birt h, c o n ge nital a n o malies, ect o pic pre g na nc y) are, a n d 
s h o ul d be rec or de d as a n S A E. 
A n y fe male s u bject w h o bec o mes pre g na nt w hile partici pati n g wi ll be wit h dra w n.    
1 0. 1 0  
M e di c al D e vi c e I n ci d e nt s  
A m e dical d e vice  is b ei n g pr o vi de d b y t he s p o ns or f or us e i n t his st u d y; t he me dical d e vice i n 
t his st u d y is t he ma n u al t o ot h br us h ( Oral B Se nsi-S oft , U S  mar ket)  use d t o a p pl y t he st u d y 
t o ot h pastes.  
T he i n vesti gat or a n d t he s p o ns or will c o m pl y wit h l ocal me dical de vice re p orti n g re q uire me nts.  
1 0. 1 0. 1  D efi niti o n of a n I n ci d e nt  
A me dical de vic e i nci de nt is a n y malf u n cti o n or deteri or ati o n i n t he c haracteristics a n d/ or 
perf or ma n ce of a d e vice as well as a n y i na de q uac y i n t he la beli n g or t he i nstr ucti o ns f or use 
w hic h, directl y or i n directl y, mi g ht lea d t o or mi g ht ha ve le d t o t he deat h of a s u bject/ user/ ot her 
pers o n or t o a seri o us det eri orati o n i n t heir state of healt h. 
N ot all i nci de nts lea d t o deat h or seri o us deteri or at i o n i n healt h. T he n o n-occ urre nce of s uc h a 
res ult mi g ht ha ve bee n d ue t o ot her f ort u nat e cir c u msta nces or t o t he i nter ve nti o n of healt hcare 
pers o n nel.  
It is s ufficie nt t hat an i n ci de nt ass ociate d  wit h a de vice ha p p e ne d a n d  the i nci de nt was s uc h 
t hat, if it occ urre d a gai n, mi g ht lea d t o deat h or a s eri o us deteri or ati o n i n healt h. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI
P P D
P P D


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 8  of 1 1 3  
A seri o us deteri orati o n i n state of healt h ca n i ncl u de a n y of t he f oll o wi n g:  
•  Life -t hreate ni n g ill ness 
•  Per ma ne nt i m pair me nt of b o d y f u ncti o n or per ma n e nt da ma ge t o b o d y str uct ure  
•  C o n diti o n necessitati n g me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he a b o ve  
•  Fetal distress, f etal deat h, or a n y c o n ge nital a b n or malit y or birt h defects  
E x a m ples of i nci de nts:  
•  A s u bject, user, care gi ver, or healt hcare pr ofessi o nal is i nj ure d as a res ult of a me dical 
de vice fail ure or its mis use.  
•  A s u bject’s st u d y treat me nt is i nterr u pte d or c o m pr o mise d b y a me dical de vi ce fail ure.  
•  A mis dia g n osis d ue t o me dical de vice fail ure lea ds t o i na p pr o priate treat me nt.  
•  A s u b ject’s healt h deteri orates d ue t o me dical de vice fail ure. 
1 0. 1 0. 2  R e p orti n g of I n ci d e nt s a n d M alf u n cti o n s  
All i nci de nts m ust be re p orte d t o  t he s p o ns or i m me di atel y t he i n vesti gat or or t heir me dicall y 
q ualifie d desi g ne e bec o m es a ware of t he sit uati o n , a n d u n der n o circ u mst a nce s h o ul d t his 
e xcee d 2 4 h o urs  of t he i n vesti gat or or desi g ne e b ec o mi n g a ware of t h e sit uati o n.  
A n y me dical de vice i nci de nt occ urri n g d uri n g t he st u d y will be d oc u me nte d i n t he s u bject's 
me dical rec or ds, if i n acc or da nce wit h t he i n vesti gat or's n or mal cli nical practice, a n d o n t he 
a p pr o priate I nci d e nt Re p ort F or m.  I n a d diti o n, f or i nci de nts f ulfilli n g t he defi niti o n of a n A E 
( n o n-seri o us a n d s eri o us ), t he A E secti o n of t he eC R F /S A E f or m will be c o m plete d a n d re p orte d 
as per t he A E/S A E re p orti n g s ecti o ns  a b o ve. 
T he I nci de nt Re p ort F or m will be c o m plete d as t h or o u g hl y as p ossi ble a n d si g ne d b y t he 
i n vesti gat or bef ore tra ns mittal t o t he s p o ns or.  It is ver y i m p orta nt t hat t he i n vesti gat or descri bes 
a n y c orrecti ve or re me di al acti o ns ta ke n t o pr e ve nt rec urre nce of t he i nci de nt. 
T he c o m plet e d I n ci de nt Re p ort F or m s h o ul d be sca n ne d a n d e maile d t o  t he s p o ns or’s Case 
Ma na ge me nt Gr o u p  mail b o x 
), wit h t he a p pr o priate s p o ns or 
St u d y Ma na ger  i n c o p y, wit h t he st u d y n u m ber a n d s u bject n u m ber i n t he s u bject li ne of t he 
e mail i m me di atel y after site staff lear n of t he e ve nt a n d u n der n o circ u mst a nce s s h o ul d t his 
e xcee d 2 4 h o urs after site staff lear n of t he e ve nt. If t here is a n S A E, t he c o m plete d S A E f or m 
s h o ul d be se nt t o get her wit h t he I n ci de nt Re p ort F or m. T h e  c o p y of t he S A E re p ort se nt wit h 
t his I nci de nt Re p ort F or m d oes n ot re place t he pr oce d ure f or re p orti n g a n S A E.  T he ori gi nal 
c o m plete d I nci de nt Re p ort F or m will be ret ai ne d i n t he i n vesti gat or site file.  
T he i nitial me dical de vice i nci de nt re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, 
or as re q u este d b y t he s p o ns or’s st u d y ma na ger. 
T he i n vesti gat or will f oll o w t he f oll o wi n g directi o ns re gar di n g t h e re p orti n g of a de vi ce fail ure 
( malf u ncti o n):  
•  N otif y t he s p o ns or i m me diatel y (as descri be d a b o ve).  
•  Sc he d ule t he s u bject t o ret ur n t o site pr o m ptl y t o ret ur n t he faile d de vice.  
•  Rec or d a n y i nci de nts in t he eC R F a n d o n t he I nci d e nt Re p ort F or m (as des cri be d a b o ve). 
•  F or a n y i nci d e nt/ malf u ncti o n occ urri n g wit h a me dical de vice (i ncl u di n g t h ose t hat are 
part of c o m bi nati o n pr o d ucts) s u p plie d b y t he s p o ns or, ret ur n t he faile d d e vice t o t he 
s p o ns or as s o o n as p ossi ble, i ncl u di n g d oc u me ntati o n of t he details of t he fail ure . 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI
P P D


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 6 9  of 1 1 3  
•  F or a n y i nci d e nt /malf u ncti o n  occ urri n g wit h a me dical de vice  (i ncl u di n g t h ose t hat are 
part of c o m bi nati o n pr o d ucts)  s u p plie d b y t he in vesti gat or site, re p ort t he i nci de nt t o t he 
de vice ma n ufact ur er  a n d f oll o w t he ma n ufact urer i nstr ucti o ns f or t he ret ur n of t he faile d 
de vice  ( w hilst ke e pi n g t he s p o ns or i nf or me d). 
1 0. 1 0. 3  F oll o w -u p of M e di c al D e vi c e I n ci d e nt s  
Me dical d e vice i nci de nts i n v ol vi n g a n A E will be f oll o we d a n d re p orte d i n t he sa me ma n ner as 
ot her A Es. T his a p plies t o all s u bjects, i ncl u di n g t h ose w h o dis c o nti n ue st u d y pr o d uct or are 
wit h dra w n fr o m t he st u d y.  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat f oll o w -u p i ncl u des a n y s u p ple me ntal 
i n vesti gati o ns as i n dicate d t o el uci date t he nat ur e a n d/ or ca us alit y of t he i nci de nt. 
Ne w or u p date d i nf or mati o n w ill be rec or de d o n t h e ori gi nall y c o m plete d I n ci de nt Re p ort f or m, 
wit h all c ha n ges si g ne d a n d date d b y t he i n vesti gat or.  
1 0. 1 0. 4  R e g ul at or y R e p orti n g R e q uir e m e nt s f or M e di c al D e vi c e I n ci d e nt s 
T o f ulfill re g ulat or y re p orti n g o bli gati o ns w orl d wi de, t he i n vesti gat or is res p o nsi ble f or t he 
detecti o n a n d d oc u me ntati o n of e ve nts meeti n g t he defi niti o ns of i nci de nt or malf u ncti o n t hat 
occ ur d uri n g all peri o ds of t he st u d y i n w hic h a m e dical de vice is use d.  
T he i n vesti gat or will pr o m ptl y re p ort all i nci de nts occ urri n g wit h a n y me dical de vice pr o vi de d 
f or use i n t he st u d y i n or der f or t h e s p o ns or t o f ulfill t he le gal res p o nsi bilit y t o n otif y a p pr o priate 
re g ulat or y a ut h orities a n d ot her e ntities a b o ut certai n safet y i nf or mati o n relati n g t o me dical 
de vices bei n g use d i n cli nical st u dies.  
T he i n vesti gat or will c o m pl y wit h a p plica ble l ocal re g ulat or y re q uire me nts relati n g t o t he 
re p orti n g of i nci de nts t o t he I R B. 
1 1  
D A T A M A N A G E M E N T  
As use d i n t his pr ot oc ol, t he  ter m C R F refers t o eit her a pa per f or m or a n el ectr o nic data rec or d 
or b ot h, de p e n di n g o n t h e data c ollecti o n met h o d. F or t his st u d y, s u bject d ata will be e ntere d 
i nt o a n electr o ni c C R F (e C R F), usi n g a vali date d s yste m. Data relati n g t o S A Es, pre g na nc y a n d 
i nci de nts will als o be c ollecte d o n pa p er f or ms. 
S u bjects will c o m plete pa per c o p ies of t he D H E Q -4 8  (s o urce), t he L M Ss (s o urce) a n d t he 
Treat me nt Satisfacti o n N R S (s o urce) ; to facilitate s u bject fl o w, p a per f or ms (s o urce) ma y  als o 
be use d t o rec or d cli ni cal data f or later tra ns cripti o n i nt o t he eC R F . Tra nscripti o n of 
D H E Q / L M S/ N R S res p o nses a n d cli nical d ata i nt o t he e C R F m ust be c o m plete d wit hi n 5 da ys 
of t he data b ei n g rec or de d. T he eC R F a n d t h e s u bject -c o m plete d diar y ca n be use d as a s o urce 
d oc u me nt at t he discreti o n of D ata M a n a ge me nt.  
T he s o urce d o c u me nts t h at c o ntai n s o urce data rec or de d i n t he eC R F s h o ul d  be s pecifie d .  
T he i n vesti gat or is res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y 
p h ys icall y or electr o ni call y si g ni n g t he eC R F.   
Eac h s u bject will be assi g ne d a n d i d e ntifie d b y a u ni q ue Scree ni n g S u bject N u m ber. A n y 
refere nce ma de t o a n i n di vi d ual s u bject wit hi n t he st u d y m ust be d o ne usi n g t heir u ni q ue 
Scree ni n g S u bject N u m b er.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 0  of 1 1 3  
1 1. 1  
C a s e R e p or t F or m 
A C R F is a pri nte d, o ptical or electr o nic d oc u me nt desi g ne d t o rec or d pr ot oc ol -re q uire d 
i nf or mati o n t o be re p ort e d t o t he s p o ns or o n eac h st u d y s u bject. 
F or eac h s u bject w h o gi ves  i nf or me d c o nse nt, t h e C R F m ust be c o m plete d a n d si g ne d b y t he 
in vesti gat or ( or a ut h orize d desi g ne e) t o certif y t hat t he dat a are c o m plete a n d c orrect.  T h e 
i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce d ata) t o s u p p ort t he i nf or mati o n 
e ntere d i n t he C R F.  
Ma na ge me nt of cli nical data will be perf or me d i n acc or da nc e wit h T hir d Part y B D M Ve n d or 
a p plica ble sta n dar ds a n d data clea ni n g pr oce d ures , wit h o versi g ht b y t he s p o ns or t o e ns ure data 
i nte grit y (e. g., t o re m o ve err ors a n d i nc o nsiste ncies i n t he data).  
T o pr otect t he pri vac y of st u d y s u bjects, n o Pers o nal I nf or mati o n ( PI), i ncl u di n g s u bject na me, 
i nitials a n d birt h date , is t o be rec or de d i n t he C R F or as part of q u er y te xt. 
All C R F pa ges s h o ul d be c o m plete d d uri n g a s u bject assess me nt w he n t he C R F is t he desi g nate d 
s o urce.  Data rec or de d else w here s h o ul d be tra nscri be d fr o m t he s o urce d oc u me nt i nt o t he C R F 
wit hi n 5 da ys of t he data bei n g rec or de d .   
T he s p o ns or  will o btai n a n d retai n all C R Fs a n d ass ociate d st u d y data , as a p plica ble , o n  
c o m pleti o n of t he st u d y.  
1 1. 2  
D at a H a n dli n g  
D oc u me ntati o n of all d ata ma na g e me nt acti vities s h o ul d all o w ste p -b y -ste p retr os p ecti ve 
assess me nt of data q u alit y a n d st u d y perf or m a nce.  
C ha n ges a n d c orrecti o ns t o data will be perf or me d i n t he Electr o nic Data Ca pt ure ( E D C) S yste m 
w hic h  will i ncl u de a rati o nale f or t he c ha n g e or c orrecti o n . T h e E D C s yste m has a n a u dit trail 
t o pr o vi de a c o m plete rec or d of t he c h a n ges a n d c orrecti o ns e n d orse d b y t h e in ves ti gat or. 
A Es  will be c o de d usi n g 
Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) , a n d 
c o nc o mita nt me dicati o n t er ms (if a p plica ble) usi n g a n i nter nal vali date d m e dicati o n dicti o nar y  
( W H O Dr u g).   
1 1. 2. 1  
D at a Q u eri e s  
Pr o gra m me d e dit c hec ks will be ge nerate d a ut o maticall y as t he data are bei n g e ntere d i nt o t he 
s yste m. Re p orts a n d listi n gs o n t he C R F data will als o be r u n, i n a d diti o n t o t he q ueries alrea d y 
pr o gra m me d a n d ge nerat e d b y t he s yste m, t o raise ma n ual q ueries as nee de d f or i n vesti gat or 
site clarificati o n or c orrecti o n. T he Cli nical Dicti o nar y De v el o p me nt a n d Ma na ge me nt Gr o u p 
will raise q ueries as nee de d o n safet y data t o c o de t he ter ms ( A Es a n d Dr u gs or c o nc o mita nt 
me dicati o n) a p pr o priatel y.  
T he st u d y m o nit or will perf or m o n g oi n g re vie w of t he C R Fs , in acc or da nce wit h t he m o nit ori n g 
pla n, t o c o nfir m t hat data e ntere d i nt o t he C R F b y a ut h orize d i n vesti gat or site pers o n nel are 
acc urate, c o m plet e, a n d verifia ble fr o m s o urce d oc u me nts; t hat t he safet y a n d ri g hts of 
partici pa nts are bei n g pr otecte d; a n d t ha t t he st u d y is bei n g c o n d ucte d i n acc or da n ce wit h t he 
c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y a gree me nts, I C H G C P a n d all a p plica bl e 
re g ulat or y re q uire me nts. 
Q ueries g e nerate d i n t h e E D C S yste m will a ut o maticall y be se nt t o t h e i n vesti gat or site, 
ena bli n g err ors t o be a d dresse d i n parallel wit h Data Ma na g e me nt re vie w. T he st u d y m o nit or 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 1  of 1 1 3  
will  als o r u n re p orts a n d listi n gs o n t he C R Fs t o raise ma n ual q ueries , as nee de d , f or i n vesti gat or 
site clarificati o n or c orrecti o n. 
1 1. 3  
Pr o c e s si n g S u bj e ct  R e p ort e d O ut c o m e s   
S u bject re p orte d o utc o mes will be rec or de d i n p a per -base d  diar ies a n d i n q uesti o n naire s 
( D H E Q-4 8 ,  L M Ss  a n d N R S ) f or later tra nscri pti o n i nt o t he e C R F.   
S o urce d oc u me nts rec or di n g su bject -re p orte d o utc o me s will  be re vie we d b y t he i n vesti gat or 
staff a n d t he st u d y mo nit or t o e ns ure t he data , a n d a n y p ote ntial A Es or c o nc o mita nt me dicati o ns 
re p orte d in t hese d o c u me nts , are acc uratel y tra nscri be d i nt o t he eC R F.    
S u bject re p orte d o utc o mes classe d as s o urce data will be retai ne d b y t he i n vesti gat or; 
tr ue/certifie d c o pies ma y be se nt t o t he s p o ns or or a t hir d-part y ve n d or , as re q uire d.  T o pr otect 
s u bject pri vac y , n o PI (i ncl u di n g s u bject na me, i nitials or birt h date) is t o be rec or de d in a n y 
s u bject re p orte d o utc o me s o urce d oc u me nt t hat w ill be f or war de d t o t he s p o ns or or a t hir d-part y 
ve n d or . 
1 2  
S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A A N A L Y S E S  
1 2. 1  
S a m pl e Si z e D et er mi n ati o n  
S ufficie nt s u bjects will b e scree ne d a n d e nt ere d i nt o t he accli matizati o n peri o d t o ra n d o miz e 
a p pr o xi matel y 1 1 0  s u bjects t o i n vesti gati o nal pr o d uct (a p pr o xi matel y 5 5  s u bjects per treat me nt 
gr o u p ) t o e ns ur e a p pr o xi matel y 1 0 0  c o m plete t he st u d y (a p pr o xi matel y 5 0  s u bjects per 
treat me nt gr o u p), all o wi n g f or a p pr o xi matel y 1 0 % dr o p o ut s. 
T he st u d y will be s ufficie ntl y p o were d t o de m o nstrate statistical s u peri orit y of t he Test 
T o ot h paste c o m pare d t o t he Refere nce T o ot h paste ( ne gati ve  c o ntr ol) f or t he c ha n ge fr o m 
Baseli ne i n t he Sc hiff se nsiti vit y sc ore  ( pri mar y o bjecti ve) a n d tactile t hres h ol d ( ke y s ec o n dar y 
o bjecti ve) after 5 6 d a ys ( 8  w ee ks ) treat me nt. A sa m ple siz e of 5 0  e val ua ble s u bjects per 
treat me nt gr o u p will pr o vi de at least 9 0 % p o wer t o detect a mea n differe n ce of 0. 4  u nits ( S D = 
0. 6 ) i n c ha n g e fr o m Bas eli ne i n Sc hiff se nsiti vit y score after 5 6  da ys tr eat m e nt, usi n g a 2 -taile d 
2 -sa m ple t-test wit h a 5 % si g nifica nce le vel. T he sa m ple size calc ulati o n was perf or me d usi n g 
P A S S s oft ware versi o n 2 3. 0. 1.  
T he dr o p o ut rate a n d S D esti mates are b ase d o n t he res ults of D H efficac y st u dies of si milar 
desi g n a n d d urati o n e val uati n g 0. 4 5 4 % S n F 2 t o ot h pastes (Cli nical St u dies  2 0 5 7 9 4 , 2 0 8 1 5 3  a n d 
2 1 6 9 5 4 : s p o ns or data hel d o n file, a vaila ble o n re q uest).  
1 2. 2  
P o p ul ati o n s  for A n al y si s  
1 2. 2. 1  
D efi niti o n s of A n al y si s P o p ul ati o n s  
T he Safet y p o p ulati o n will c o m prise  all ra n d o mize d s u bjects w h o recei ve at least o ne d ose of 
i n vesti gati o nal pr o d uct. S u m maries a n d a nal yses of t his p o p ulati o n will be base d o n t h e 
i n vesti gati o nal pr o d uct t h e s u bject recei ve d .  
T he pri mar y p o p ulati o n f or t he assess me nt of efficac y will be  a m o difie d  i nte nti o n-t o-treat 
(m I T T) p o p ulati o n. T h e mI T T  p o p ul ati o n will c o m prise  all ra n d o mize d s u bjects w h o recei v e at 
least o ne d ose of i n vesti gati o nal pr o d uct  a n d c o m plete at least o ne -p ost B aseli ne D H effi cac y 
assess me nt . T his p o p ulati o n will be base d o n t he i n vesti gati o nal pr o d uct t he s u bject was 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 2  of 1 1 3  
ra n d o mize d t o. 
All s u bjects w h o re cei ve a ra n d o mizati o n n u m ber 
will be c o nsi dere d  
ra n d o mize d. 
T he P er-P r ot oc ol ( P P) p o p ulati o n will c o m prise  all s u bjects i n t he mI T T p o p ulati o n w h o ha ve 
at least o ne D H effic ac y assess me nt c o nsi dere d t o be u naffecte d b y p r ot oc ol de viati o ns. 
1 2. 2. 2  
E x cl u si o n s of D a t a fr o m A n al y si s 
E xcl usi o n of data fr o m a n y of t he pla n ne d a nal yses will be a gree d d uri n g Bli n de d Data Re vie w 
( B D R), pri or t o data bas e l oc k. T he  reas o n(s) f or e xcl usi o n of a s u bject fr o m a n a n al ysis 
p o p ulati o n or s pecifi c dat a fr o m a n a n al ysis will be d oc u me nte d  a n d, if a p plica ble, liste d  i n t he 
Cli nical St u d y Re p ort ( C S R) . 
A P P a nal ysis will be perf or me d f or t he pri mar y e n d p oi nt if ≥ 1 0 % s u bjects i n t he mIT T 
p o p ulati o n are e xcl u de d fr o m t he P P p o p ulati o n. E fficac y data det er mi ne d  t o ha ve bee n 
p ote ntiall y i m pacte d b y a pr ot oc ol de vi ati o n will be e xcl u de d fr o m t he P P a nal ysis.  T h e 
d ecisi o ns as t o w het h er  or n ot  a pr ot oc ol d e viati o n i m pacts effi cac y data  a n d whet her t o p erf or m 
a P P a nal ysis will be ma de d uri n g  B D R , pri or t o data base l oc k.   
1 2. 3  
St ati sti c al  A n al y s e s  
T his is a s u m mar y of t he pla n ne d st atistical a nal yses; t he detail of t h e pr o p ose d statistical 
a nal yses will be d oc u me nte d  i n t he Statistical A nal ysis Pla n (S A P), t o be writte n f oll o wi n g 
fi nalizati o n of t he pr ot oc ol a n d pri or t o st u d y u n bli n di n g.  
T he mI T T p o p ulati o n will be use d f or all efficac y a nal yses.   
All p -val ues prese nt e d will be t w o-si de d a n d assess e d  at t h e 5 % si g nifica nce l e vel. A s e q ue ntial 
testi n g strate g y will be use d t o a dj ust f or t he c o m paris o ns bet wee n t he Test a n d Refere nce 
T o o t h pastes i n c ha n g e fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore a n d tactile t hres h ol d ( g) at eac h 
assess me nt ti me p oi nt . 
At eac h ti me  p oi nt, c ha n g e fr o m Baseli ne i n tactile t hres h ol d ( g)  will o nl y be assesse d f or 
c o nfir mat or y e vi de nce if t he c ha n g e fr o m Baseli ne i n Sc hiff s e nsiti vit y sc ore ac hie ves a 
statisticall y si g nifica nt greater re d u cti o n f or t he Test T o ot h paste c o m pare d t o t he  Refere n ce 
T o ot h p aste ( ne gati ve c o ntr ol) . T his strate g y will be gi n at Da y 5 6, t he n m o ve t o Da y 2 8 , o nl y 
m o vi n g t o t he earlier ti me p oi nt f or c o nfir mat or y e vi de nce if t he Da y 5 6 ti me p oi nt ac hie ves  
statisticall y si g nifica nt greater re d ucti o ns f or t he Test T o ot h paste c o m pared t o t he  Refere nce 
T o ot h paste ( ne gati ve c o ntr ol) f or b ot h Sc hiff se nsiti vit y sc ore a n d tactile t hres h ol d ( g) . T here 
will be n o f urt her a dj ust me nts f or m ulti plicit y f or t he ot her sec o n d ar y e n d p oi nt s ( D H E Q-4 8).  
S u m mar y statistics ( mea n, me dia n, S E, S D, mi ni m u m, ma xi m u m) will be prese nt e d f or eac h  
Sc hiff se nsiti vit y sc ore a n d tactile t hr es h ol d ( g) o ut c o me varia ble at eac h ass ess me nt ti me p oi nt. 
Ra w mea ns ( ± S E) of Sc hiff s e nsiti vit y sc ore  a n d tactile t hr es h ol d ( g) at eac h assess me nt 
ti me p oi nt will be pl ot te d b y treat me nt gr o u p. 
T he res ults fr o m eac h Mi xe d M o del wit h Re p eate d Meas ures ( M M R M) will be ta b ulate d, 
prese nti n g t he f oll o wi n g i nf or mati o n, i n a d diti o n t o t he res ults s pecifie d f or t he pri mar y a n d 
sec o n dar y a nal yses b el o w: least s q uare mea n c h a n ge fr om Bas eli ne f or eac h i n vesti gati o nal 
pr o d uct at Da ys 2 8 a n d 5 6 ( base d o n t he o bser ve d stratificati o n mar gi ns f or t h ose M M R M wit h 
a ter m f or ra n d o mize d str ata) a n d use d t o test f or a n y c ha n ge fr o m Baseli ne, wit h t w o -si de d p-
val ues a n d 9 5 % CIs.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 3  of 1 1 3  
1 2. 3. 1  
Pri m ar y E n d p oi nt  A n al y si s  
T he pri mar y e n d p oi nt of t his st u d y is t he c ha n ge fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore at 
Da y 5 6 ( Wee k 8); t he  pri mar y h y p ot hesis test will be t he c o m paris o n bet wee n t he Test 
T o ot h paste a n d t he  Refere nce T o ot h past e ( ne g ati ve c o ntr ol ) i n t he mI T T p o p ulati o n.  
Sc hiff se nsiti vit y sc ore will be deri ve d as t he mea n sc ore f or t he t w o ‘ Test Teet h’ (select e d at 
Baseli ne). C ha n ge fr o m Baseli ne will be deri v e d f or eac h i n di vi d ual t o ot h first bef ore 
calc ulati n g me a n c h a n g e f or t he t w o ‘ Test Teet h’ w here c ha n ge fr o m Baseli ne i n Sc hiff 
se nsiti vit y sc ore at Da y X is defi ne d as [( Sc hiff se nsiti vit y sc ore at Da y X) mi n us ( Bas eli ne 
Sc hiff se nsiti vit y sc ore)] . 
C ha n ge fr o m Basel i ne i n Sc hiff se nsiti vit y sc ore at Da y 5 6 will be a nal yse d usi n g a Mi xe d 
M o del 
wit h 
Re peat e d 
Meas ur es ( M M R M) 
wit h 
i n vesti gati o nal pr o d uct, 
visit a n d 
[i n vesti gati o nal pr o d uct x visit] i nteracti o n as fi xe d effects, a n d Baseli ne Sc hiff se nsiti vit y sc ore 
as a c o variate. S u bject will be i ncl u de d as a re peate d m eas ure wit h u nstr uct ure d c o varia nce 
matri x. Ke n w ar d R o gers de grees  of free d o m a p pr oac h will be a p plie d  (Ke n war d, 1 9 9 7 ). T he 
differe n ce bet w ee n t he least s q uare mea n c ha n ges fr o m B aseli ne f or t he Test T o ot h paste 
c o m pare d t o R efere nce T o ot h paste ( ne g ati ve c o ntr ol) at Da y 5 6  fr o m t he M M R M wi ll be 
prese nte d , al o n g wit h  t he t w o-si de d p-val ue a n d 9 5 % CIs . 
T he ass u m pti o n s of n or malit y  a n d h o m o ge neit y of varia nce i n t he M M R M will be i n vesti gate d. 
I n case of vi olati o n of t hese ass u m pti o ns, a s uita ble n o n-para metric test (a dj uste d f or t h e 
ra n d o mizati o n stratifi cati o n) will be perf or me d t o assess t he c ha n g e fr o m B aseli ne c o m paris o n 
(Test T o ot h paste vs.  Refere nce T o ot h paste  at Da y 5 6 ); t he res ults will be pr o vi de d t o s u p p ort 
t he M M R M res ults. 
1 2. 3. 2  
S e c o n d ar y  E n d p oi nt  A n al y s e s  
T actile T hres h ol d  at D a y 5 6 : 
T actile t hres h ol d ( g) will be deri ve d as t he mea n val ue f or t he t w o ‘ Test Teet h’ (select e d at 
Baseli ne). C ha n ge fr o m Baseli ne will be deri v e d f or eac h i n di vi d ual t o ot h first bef ore 
calc ulati n g me a n c h a n g e f or t he t w o ‘ Test Teet h’ w here c ha n ge fr o m Baseli ne i n tactil e 
t hres h ol d ( g) at Da y X is defi ne d as [(tactile t hres h ol d at Da y X) mi n us ( Baseli ne tactile 
t hres h ol d)]. 
T his k e y sec o n dar y e n d p oi nt, c ha n ge fr o m Bas eli ne i n tactile t hres h ol d ( g) at Da y 5 6 , will b e 
a nal yse d usi n g t he sa me M M R M as t he pri mar y e n d p oi nt b ut wit h Baseli ne tactile t hres h ol d  ( g) 
as a c o v ariate  (rat her t ha n Baseli ne Sc hiff se nsiti vit y sc ore ). I n a d diti o n, t he ma xi m u m Baseli ne 
Sc hiff se nsiti vit y sc ore of t he t w o  ‘ Test Teet h’ ( 2 or 3) will be fitte d as a fi xe d effect. T he 
differe n ce bet w ee n t he least s q uare mea n c ha n ges fr o m Baseli ne f or t he Test T o ot h paste 
c o mpare d t o R efere nce T o ot h paste ( ne g ati ve c o ntr ol) at Da y 5 6 fr o m t he M M R M will be 
prese nte d, al o n g wit h t he t w o -si de d p-val ue a n d 9 5 % CIs.  
T actile T hres h ol d / Sc hiff Se nsiti vit y Sc ore at D a y 2 8 : 
T he o t her sec o n dar y e n d p oi nts: 
•  C ha n ge  fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore at Da y 2 8  
•  C ha n ge  fr o m Baseli ne i n tactile t hres h ol d ( g) at Da y 2 8  
will be  a nal yse d usi n g t he sa me M M R M m o dels descri be d a b o v e  f or Sc hiff se nsiti vit y sc ore 
a n d tactile t hres h ol d ( g), res pecti vel y.  D iffere nces bet wee n t he least s q uare mea n c ha n g es fr o m 
B aseli ne i n Sc hiff se nsiti vit y sc ore a n d tactile t hres h ol d ( g) will be prese nte d f or t he T est 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 4  of 1 1 3  
T o ot h paste c o m pare d t o Refere n ce T o ot h paste ( ne gati ve c o ntr ol) at Da y  2 8  fr om  t heir 
res pecti ve M M R Ms, al o n g wit h t w o -si de d p-val u es a n d 9 5 %  CIs .  
T he ass u m pti o n s of n or malit y a n d h o m o ge neit y of varia nce i n eac h  M M R M will be 
i n vesti gate d. I n case of vi olati o n of t hese ass u m pti o ns, a s uita ble n o n-para metric test (a dj uste d 
f or t he ra nd o mi zati o n stratificati o n  val ue ) will be perf or me d t o assess c ha n ge fr o m B aseli ne 
c o m paris o ns ( T est T o ot h paste vs.  Refere nce T o ot h paste at Da y  5 6  a n d  Da y 2 8 , as a p pr o priate); 
t he res ults will be p r o vi de d t o s u p p ort t he M M R M res ults.  
D H E Q -4 8 : 
C ha n ge fr o m B aseli ne will be calc ulate d at Da y 2 8 a n d Da y 5 6  f or all D H E Q e n d p oi nts .  
•  Secti o n  1  
- 
I m pa ct o n E ver y da y L ife: Q7 , Q8  &  Q 9  (se parate sc ores) 
•  Secti o n 2  
- 
D H E Q T otal S c ore (s u m of Q 1 -3 4)  
- 
D H E Q Restricti o ns D o m ai n sc ore (s u m of Q 1 -4)  
- 
D H E Q A da pt ati o n D o mai n sc ore (s u m of Q 5 -1 6)  
- 
D H E Q S ocial I m pa ct D o mai n sc ore (s u m of Q 1 7 -2 1)  
- 
D H E Q E m oti o nal I m pact D o mai n sc ore (s u m of Q 2 2 -2 9)  
- 
D H E Q I de ntit y D o mai n sc ore (s u m of Q 3 0 -3 4)  
- 
D H E Q Gl o bal Oral Healt h ( Q 3 5)  
- 
D H E Q  Effect o n  L if e O v erall (s u m of Q 3 6 -Q 3 9)  
C ha n ge fr o m Baseli ne will be calc ulate d at t he s u bject -le vel first t he n mea n c ha n ge fr o m 
Baseli ne will be calc ulat e d f or eac h D H E Q e n d p oi nt acr oss all s u bjects.  
C ha n ge fr o m B aseli ne f or eac h D H E Q  e n d p oi nt liste d a b o ve will be a nal yze d usi n g a M M R M 
wit h ti me p oi nt a n d ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore of t h e t w o ‘ Test Teet h’ ( 2 or 3) 
as fi xe d effect s, a n d t he res pecti ve Baseli ne D H E Q sc ore as c o vari ate. Su bject  will be i ncl u de d 
as a re peate d meas ur e wit h u nstr uct ure d c o varia nce matri x. Ke n w ar d-R o gers de grees of 
free d o m will be a p plie d. T he esti mates of t he a dj uste d mea n ( S E) c h a n ge fr o m Baseli ne will be 
prese nte d al o n g wit h 9 5 % C Is f or eac h treat me nt gr o u p. 
F or eac h D H E Q e n d p oi nt  liste d a b o ve, a n d eac h i n di vi d ual D H E Q q uesti o n, t he val ue  at eac h 
ti me p oi nt ( Baseli ne, Da y 2 8 a n d Da y 5 6) a n d t h e c orres p o n di n g c h a n ge fr o m Baseli ne will be 
s u m marize d des cri pti vel y f or eac h tr eat me nt gr o u p. Ra w mea ns ( ± S E) f or eac h D H E Q 
e n d p oi nt, a n d t he i n di vi d ual D H E Q q uesti o ns,  at eac h assess me nt ti me p oi nt will be pl otte d b y 
treat me nt gr o u p. 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 5  of 1 1 3  
1 2. 3. 3  
E x pl or at or y  A n al y s e s  
N u m ber of ‘Se nsiti ve Teet h ’: 
T he n u m ber of teet h se nsiti ve t o a n e va p orati ve (air) sti m ul us i n t he p o ol of ‘ Eli gi ble Teet h’ 
i de ntifie d at Scree ni n g will be m o nit ore d acr oss t he st u d y perio d. F or t his p ur p ose, a ‘ Se nsiti ve 
T o ot h’ will be defi ne d as ha vi n g a Sc hiff se nsiti vit y sc ore  ≥ 2.  
‘ Eli gi ble Teet h’ = Teet h wit h n o de ntiti o n excl usi o ns w hic h meet E A R, M GI a n d m o bility i ncl usi o n criteri a, a n d 
h ave a Scree ni n g  t actile t hres h ol d ≤ 2 0 g a n d a Scree ni n g  Sc hiff se nsitivity sc ore ≥ 2.  
T he n u m ber of ‘ Se nsiti ve Teet h’ (i.e., t he n u m ber of ‘ Eli gi ble Teet h’ wit h Sc hiff se nsiti vit y 
sc ore ≥ 2 ) will be calc ulate d at Scree ni n g, Bas eli ne, Da y 2 8 a n d Da y 5 6.  
•  At Scree ni n g, t he n u m ber of ‘ Se nsiti ve Teet h’ will be e q u al t o t he n u m b er of ‘Eli gi ble 
Teet h ’ (as descri be d i n Secti o n 8. 1. 5 ). 
‘ Eli gi ble Teet h’ = Teet h wit h Scree ni n g  t actile t hres h ol d ≤ 2 0 g a n d Scree ni n g  Sc hiff se nsitivity 
sc ore ≥2.  
•  At Baseli ne, Da y 2 8 a n d Da y 5 6, all ‘Eli gi ble Teet h ’ will be teste d f or e va p orati ve (air) 
se nsiti vit y. T he n u m ber of ‘ Se nsiti ve Teet h’ will be t he n u m ber of ‘Eli gi ble Teet h ’ wit h 
a Sc hiff se nsiti vit y sc ore ≥ 2  at t hat visit . 
S u m mar y statistics ( m ea n, me dia n, S E, S D, mi ni m u m, ma xi m u m ) will be pres e nte d at eac h 
assess me nt ti me p oi nt f or eac h treat me nt gr o u p. F or eac h s u bject, t he Sc hiff se nsiti vit y sc ore of 
eac h ‘eli gi ble t o ot h’ at eac h ti me p oi nt  will be liste d  b y  treat me nt gr o u p. Mea n ( ±  S E) n u m ber 
of ‘ Se nsiti ve Teet h’ will be pl otte d b y treat me nt gr o u p  
L a belle d M a g nit u de Sc ales ( L M Ss) : 
C ha n ge fr o m B aseli ne will be calc ulate d at Da y  2 8 a n d Da y 5 6 f or eac h L M S  e n d p oi nt.  
•  I nte nsity 
•  D ur ati o n  
•  T oler a bility  
•  Descri pti o n  
L M S data will be a nal yse d  f or t he t w o ‘ Test Teet h’ o nl y. Cha n ge fr o m Baseli ne will be deri ve d 
f or eac h ‘ Test To ot h ’ first bef ore calc ul ati n g mea n c ha n g e f or t he t w o ‘ Test Teet h’ f or eac h 
s u bject. 
C ha n ge fr o m Baseli ne f or eac h L M S e n d p oi nt liste d a b o ve will be a nal yze d usi n g a M M R M 
wit h ti me p oi nt a n d ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore of t he t w o test teet h ( 2 or 3) as 
fi xe d effects, t he res pecti ve Baseli ne L M S  val u e  as a c o v ariate a n d s u bjec t as a re peate d 
meas ure  wit h u nstr uct ur e d c o vari a nce m atri x. Ke n war d -R o gers de grees of free d o m will be 
a p plie d. T he esti mate s of t he a dj uste d mea n ( S E) c ha n ge fr o m Bas eli ne will be prese nt e d al o n g 
wit h 9 5 % C Is f or eac h tr eat me nt gr o u p. 
F or eac h L M S  e n d p oi n t liste d a b o ve, t h e v al ue  (i n m m)  at eac h ti me p oi nt ( Baseli ne, Da y 2 8 
a n d Da y 5 6 ) a n d t he c orres p o n di n g c h a n ge fr o m Baseli ne (i n m m) will be s u m marize d 
descri pti vel y  f or eac h tr eat me nt gr o u p. Ra w mea ns ( ± S E) f or eac h L M S  e n d p oi nt, at eac h 
assess me nt ti me p oi nt, will be pl otte d b y treat me nt gr o u p.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 6  of 1 1 3  
D H E Q -4 8 a n d L a belle d M a g nit u de Sc ales ( L M Ss) Rel ati o ns hi p : 
T he rel ati o ns hi p bet wee n s u bject res p o ns es t o t he D H E Q -4 8  a n d t h e f o ur L M S s will be 
i n vesti gate d. F or eac h D H E Q d o mai n  ( Restricti o ns, A daptati o n, S ocial I m pact, E m oti o nal 
I m pa ct, I de ntit y), eac h L M S e n d p oi nt (I nte nsit y, D urati o n, T olera bilit y, Descri pti o n) will be 
pl otte d a gai nst d o mai n sc ore at eac h ass ess me nt ti me p oi nt ( Baseli ne, 2 8 a n d 5 6 da ys). A matri x 
of c orrelati o n pl ots will be pres e nte d f or eac h d o mai n.  S pear ma n’s c orrel ati o n c oefficie nt will 
be calc ulate d al o n g wit h t he ass ociate d p -val ue a n d prese nte d wit h its res pecti ve c orrelati o n 
pl ot.  
Sc hiff Se nsiti vit y Sc ore a n d L a belle d M a g nit u de Sc ales ( L M Ss) Rel ati o ns hi p : 
T he rel ati o ns hi p bet wee n Sc hiff se nsiti vit y sc ore a n d t he f o ur L M Ss will be i n vesti gate d. Sc hiff 
se nsiti vit y sc ore (mea n sc ore of  t he t w o ‘ Test Teet h’) a n d t he f o ur L M S e n d p oi nts ( I nte nsity, 
D ur ati o n, T oler a bility, Descri pti o n ) will be pl otte d at eac h assess me nt ti m e p oi nt ( Baseli ne, 2 8 
a n d 5 6 da ys) i n a matri x of c orrelati o n pl ots. S pear ma n’s c orrel ati o n c oeffi cie nt will be 
calc ulate d al o n g wit h t he ass o ciate d p-v al ue a n d prese nte d wit h its res pecti ve c orrelati o n pl ot.  
S atisf acti o n wit h Tre at me nt N R S  
A s u m mar y  of t he n u m b er of s u bjects re p orti n g at eac h le vel of t he N R S a n d t he c u m ulati ve 
n u m ber of s u bjects re p orti n g at eac h l e vel or hi g h er at D a y 5 6 ( Wee k 8) will be prese nte d , a n d 
t he N R S sc ore at D a y 5 6 ( Wee k 8) will be s u m marize d descri pti vel y , b y treat me nt gr o u p .  
S u bject free t e xt c o m me nts will be liste d  b y treat me nt gr o u p . 
1 2. 3. 4  
S af et y A n al y s e s  
Safet y a nal yses will be perf or me d o n t he Safet y p o p ulati o n, acc or di n g t o i n vesti gati o nal pr o d uct 
recei v e d. A Es will be re g ar de d as ‘treat me nt e mer ge nt’ if t he y o cc ur o n or after t h e first use of 
i n vesti gati o nal pr o d uct at Baseli ne ( Visit 2 ). I n t he e ve nt of a missi n g start date, a n A E will be 
ass u me d t o be ‘treat me nt e mer g e nt’ u nless t he e n d date is pri or t o starti n g tr eat me nt . I n cas e of 
misall ocati o n, c o m pare d t o t he ra n d o mizati o n sc he d ule, T E A Es will be ass ociate d wit h t h e 
m ost rece nt st u d y i n vesti gati o nal recei ve d. 
Eac h A E will b e cate g orize d as oral or n o n -oral b y t he i n vesti gat or or me dicall y q ualifie d 
desi g nee. All will be re vie we d b y t he C R S  a n d c o de d usi n g t he Me d D R A  pri or t o data base l oc k 
a n d u n bli n di n g .  
A listi n g of all A Es will b e pres e nte d f or all s u bjects i n t he Safet y p o p ulati o n wit h t he f oll o wi n g 
A E s u m maries ( n u m ber of disti nct A Es a n d fre q ue nc y/ pr o p orti o n of s u bjects affect e d) 
prese nte d b y  tr eat me nt gr o u p  a n d o verall :  
•  T E A Es   
•  T E A Es  b y S yste m Or ga n Class ( S O C) a n d Preferre d Ter m ( P T)  
•  T E A Es  b y Oral/ N o n -Oral a n d P T  
•  Treat me nt e mer ge nt treat me nt relate d A Es b y Oral/ N o n -Oral a n d P T  
•  Treat me nt  e mer ge nt treat me nt relate d seri o us A Es b y  S O C  a n d P T 
Se parate listi n gs will be prese nte d f or:  
•  Dea t hs, S A Es a n d a n y A Es lea di n g t o pr o d uct or st u d y disc o nti n uati o n. 
•  O S T fi n di n gs ( wit h a s u m mar y of a b n or malities b y visit)  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 7  of 1 1 3  
•  O H T  fi n di n gs ( wit h a s u m mar y of c ha n g es b y visit) 
•  E x p os ure  t o st u d y pr o d u ct (Secti o n 1 2 .3. 6 . 1.) 
Me dical de vi ce i n ci de nts will be liste d; if t here are n o i nci de nts, a n ull listi n g will be pr o d uce d. 
W hile n o s pecific ris ks or a ntici pate d a d verse d e vice effects are e x p ect e d fr o m use of t he 
me dical de vice ( ma n u al t o ot h br us h) pr o vi de d , a ny  me dical de vice i nci de nts re p orte d d uri n g t he 
c o n d uct of t his st u d y will be assesse d t o e val uate t he safet y of t h e de vice . 
1 2. 3. 5  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
De m o gra p hic a n d Baseli ne c haracteristics will be s u m mari ze d b y treat me nt gr o u p f or t he Safet y 
a n d mI T T p o p ulati o ns  (a n d f or t he P P p o p ulati o n, if a P P a nal ysis is perf or m e d) usi n g 
descri pti ve statistics . 
Cate g orical v aria bles (s uc h as s e x, race, et h ni cit y a n d Baseli ne Sc hiff se nsiti vit y sc ore 
stratificati o n val ue ) will be s u m marize d b y t he n u m ber a n d p erce nta ge of s u bjects wit h eac h 
rele va nt c h aracteristic i n eac h treat me nt gr o u p. C o nti n u o us varia bles s uc h as (a ge) will be 
s u m marize d b y mea n, S D , me dia n, mi ni m u m a n d ma xi m u m val ues i n eac h treat me nt gr o u p . 
1 2. 3. 6  
St u d y Pr o d u ct C o m pli a n c e a n d U s e of Ot h er T h er a pi e s  
1 2. 3. 6. 1  St u d y Pr o d u ct C o m pli a n c e  
C o m plia nce wit h i n vesti gati o nal pr o d uct use ( n u m ber of br us hi n gs) will be liste d a n d 
s u m marize d f or t he mI T T p o p ulati o n at eac h visit, a n d c u m ulati vel y f or t he e ntire  treat me nt 
peri o d (f or m ost s u bjects t h is will be a p pr o xi matel y 8  wee ks) b y tr eat me nt gr o u p.  
N u m ber of e x p ecte d br us hi n gs =  
2 × N u m ber of da ys bet w ee n Visit  2  a n d Visit  X  
N u m ber of act ual br us hi n gs      =  
(N u m ber of e x pecte d br us hi n gs ) –  ( Nu m ber of miss e d 
br us hi n gs ) + ( Nu m ber of a d diti o nal b r us hi n gs) 
% C o m pli a nce at ‘ Visit X’ =  
 ( N u m ber of act ual br us hi n gs pri or t o Visit X )     x 1 0 0  
(N u m ber of e x pect e d br us hi n gs  pri or t o Visit X ) 
1 2. 3. 6. 2  Pri or a n d C o n c o mit a nt M e di c ati o n s  
Pri or 
me dicati o ns / n o n-dr u g t hera pies  a n d c o n c o mita nt 
me dicati o ns /si g nifica nt n o n-dr u g 
t hera pies ta k e n d uri n g t he st u d y will be liste d f or t he Safet y p o p ulati o n. 
1 2. 3. 7  
H a n dli n g of Dr o p o ut s a n d Mi s si n g D at a  
M M R M a nal yses acc o u nt f or missi n g data usi n g  ‘a missi n g at ra n d o m ’ ass u m pti o n, i.e., t here 
is a s yste matic relati o ns hi p bet wee n t he pr o pe nsit y f or missi n g val ues a n d t he o bser ve d data, 
b ut n ot t he missi n g data.  
U n der s uc h ass u m pti o ns, M M R M is s h o w n t o pr o vi de u n biase d esti mates of t he treat me nt effect 
w hilst a nal ysis of o nl y c o m plete cases usi n g a n al ysis of c o v aria nce ( A N C O V A) is bias e d 
(As h bec k,  2 0 1 6 ; Bar o n, 2 0 0 8 ).  
S uc h c o m plete case a nal ysis re q uires a ‘ missi n g c o m pletel y at ra n d o m’ ass u m pti o n t o re mai n 
u n biase d a n d t his is u nli kel y t o h ol d, i.e.,  t he fact t hat t he data are missi n g is i n de pe n de nt of t he 
o bser ve d a n d u n o bs er ve d data .  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 8  of 1 1 3  
Usi n g a n M M R M, i t will  t heref ore b e ass u me d t hat a s u bject wit h missi n g data at o ne p ost -
Baseli ne assess me nt visit w o ul d ha ve o btai ne d a si milar  efficac y res ult at t hat visit c o m pare d 
t o a s u bject usi n g t he sa me i n vesti gati o nal pr o d uct wit h si milar n o n -missi n g res ults at ot her 
ti me p oi nts (B aseli ne a n d t he ot her p ost -B aseli ne assess me nt visit s).  
1 2. 3. 8  
I nt eri m A n al y si s  
N o i nteri m a nal ysis is pla n ne d f or t his st u d y . 
1 3  
S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S  
1 3. 1  
Q u alit y C o ntr ol  
I n acc or da nce wit h a p plica ble re g ulati o ns (i ncl u di n g G C P) a n d s p o ns or pr oce d ures, t he s p o ns or 
or desi g nee (i.e. , t hir d-p art y ve n d or) m o nit ors will c o ntact t he i n vesti gat or site pri or t o t he start 
of t he st u d y t o re vie w t he pr ot oc ol, st u d y re q uire me nts  a n d site res p o nsi bilities t o satisf y 
re g ulat or y, et hical a n d s p o ns or re q uire m e nts wit h t he st u d y staff.  
W he n re vie w i n g data c ollecti o n pr oce d ures, t he disc ussi o n 
will i ncl u de i de ntificati o n, 
a gree m e nt a n d d oc u me ntati o n of data ite ms f or w hic h t he eC R F will ser ve as t he s o urce 
d oc u me nt.  
T he s p o ns or  or desi g ne e will m o nit or t he st u d y a n d site acti vit y t o verif y t hat:  
•  Dat a are a ut he ntic, acc urate, a n d c o m plete.  
•  T he s afet y a n d ri g hts of s u bjects are b ei n g pr otect e d.  
•  T he s t u d y is c o n d ucte d i n acc or da n ce wit h t he c urre ntl y a p pr o ve d pr ot oc ol, a n y ot her 
st u d y a gree me nts, G C P a n d all a p plica ble re g ulat or y re q uire m e nts.  
T he e xte n t a n d nat ur e of m o nit ori n g will be descri be d i n a writte n m o nit ori n g pla n hel d o n file 
b y t he s p o ns or . T he i n vesti gat or ( or desi g nee) a grees t o all o w t he m o nit or direct access t o all 
rele va nt d o c u me nts a n d a grees t o c o-o perate wit h t he m o nit or t o e ns ure t h at a n y pr o ble ms 
detecte d d uri n g  t hes e m o nit ori n g visits are res ol ve d. 
1 3. 2  
Q u alit y A s s ur a n c e  
T o e ns ure c o m plia nce wit h G C P a n d all a p plica ble re g ulat or y re q uir e me nts, t he s p o ns or ma y 
c o n d uct a q ualit y ass ura n ce assess me nt a n d/ or a u dit of t he i n vesti gat or site rec or ds; re g ul at or y 
a ge ncies ma y c o n d u ct a re g ulat or y i ns pe cti o n at a n y ti me d uri n g or aft er c o m pleti o n of t he 
st u d y. 
I n t he e v e nt of a n assess me nt, a u dit or i ns pe cti o n, t he i n vesti gat or m ust a gree t o gra nt a d vis ors, 
a u dit ors a n d i ns pe ct ors direct access t o  all rele va nt d oc u me nts a n d t o all ocat e t heir ti me a n d t h e 
ti me of t heir staff t o disc uss t he c o n d uct of t he st u d y, a n y fi n di n gs/rele va nt iss ues a n d t o 
i m ple me nt a n y c orrecti ve a n d/ or pre v e ntati ve acti o ns t o a d dress a n y fi n di n gs/iss ues i de ntifie d. 
T he i n ve sti gat or will n otif y t he s p o ns or or its a ge nts i m me diatel y of a n y re g ulat or y i ns pecti o n 
n otificati o n i n relati o n t o t he st u d y. F urt her m ore, t he i n vesti gat or will c o o perat e wit h t he 
s p o ns or or its a g e nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w t he s p o ns or 
or its a ge nt, w he n e ver feasi ble, t o b e prese nt d uri n g t he i ns pe cti o n. T h e i n vesti gat or will 
pr o m ptl y s up pl y c o pies of t he i ns pecti o n fi n di n g s t o t he s p o ns or or its a ge nt. Bef ore res p o ns e 
s u b missi o n t o t he re g ulat or y a ut h orit y, t he i n vesti gat or will pr o vi de t he s p o ns or or its a ge nts 
wit h o p p ort u nit y t o re vie w a n d c o m me nt o n res p o nses t o a n y s uc h fi n di n gs.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 7 9  of 1 1 3  
T he s p o ns or will be a vail a ble t o hel p t he i n vesti gat or pre pare f or a n i ns pecti o n. 
1 3. 3  
R e g ul at or y a n d Et hi c a l C o n si d er ati o n s 
1 3. 3. 1  
I n stit uti o n al R e vi e w B o ar d (I R B)  
It is t he res p o nsi bilit y of t he i n vesti gat or t o ha v e pr os pecti ve a p pr o val of t he st u d y pr ot o c ol, 
pr ot oc ol a me n d me nts, t h e I C F, t h e I B a n d/ or safet y state me nt (i ncl u di n g a n y u p dates), a n d ot her 
rele va nt d o cu me nts  (e. g., recr uit me nt a d vertise m e nts, diaries), as a p plica bl e, fr o m t he I R B.  All 
c orres p o n d e nce wit h t he I R B s h o ul d be ret ai ne d i n t he i n v esti gat or site file. C o pies of I R B 
a p pr o vals s h o ul d be f or war de d t o t he s p o ns or pri or t o t he i nitiati o n of t he st u d y, a n d 
s u bse q ue ntl y f or a n y pr ot oc ol  a me n d me nt s. 
T he o nl y circ u msta n ce i n w hic h a n a me n d me nt ma y be i nitiate d pri or t o I R B a p pr o val is w here 
t he c ha n g e is n ecess ar y t o eli mi nate a p p are nt i m me diate hazar ds t o t he s u bjects.  I n t hat e v e nt, 
t he i n vesti gat or m ust n otif y t he I R B a n d 
t he s p o ns or i n 
writi n g i m me diatel y after 
i m ple me ntati o n. 
1 3. 3. 2  
Et hi c al C o n d u ct of t h e St u d y  
T he st u d y will be c o n d u cte d i n acc or da n ce wit h t he pr ot oc ol a n d a p plica ble l ocal re g ul at or y 
re q uire me nts a n d la ws , as well as t he ge neral pri nci ples set f ort h i n t he I nter nati o nal Et hical 
G ui deli nes f or Bi o me dical Researc h I n v ol vi n g H u ma n S u bjects ( C o u ncil f or I nter nati o nal 
Or ga nizati o ns of Me di cal Scie nces 2 0 0 2), I nt er nati o nal Et hical G ui deli nes f or Healt h -Rel ate d 
Researc h I n v ol vi n g H u ma ns ( C o u ncil f or I nter nati o nal Or ga ni zati o ns of Me dical Scie nces, 
2 0 1 6) , G ui deli nes  f or G C P (I C H T o pic E 6 ( R 2) G ui deli ne f or G o o d Cli nical Practice, N o v 
2 0 1 6 ), a n d t he Declarati o n of Helsi n ki (W orl d Me dical Ass ociati o n, 6 4t h Ge neral Asse m bl y, 
F ortale za 2 0 1 3 ). I n a d diti o n, t he st u d y will be c o n d ucte d i n acc or da n ce wit h a p plica ble me dical 
de vice  re g ulati o ns. 
1 3. 3. 3  
S u bj e ct I nf or m ati o n a n d C o n s e nt  
All parties will e ns ure pr otecti o n of s u bj ect p ers o nal data a n d will n ot i ncl u de s u bject na mes or 
ot her i de ntifia ble data i n a n y re p orts, p u blicati o ns, or ot her discl os ures, e xce pt w here re q uire d 
b y la ws .  
W he n st u d y data are c o m pile d f or tra nsfer t o t he s p o ns or a n d ot her a ut h orize d parties, s u bject 
na mes, a d dresses a n d ot her i de ntifia ble dat a will be re place d b y n u merical c o des bas e d o n a 
n u m beri n g s yste m pr o vi de d b y t he s p o ns or i n or der t o de-i de ntif y st u d y s u bjects. U se of s u bject 
i nitials s h o ul d be a v oi de d.   
T he i n vesti gat or site will mai ntai n a c o nfi de ntial list of s u bjects w h o partici pate d i n t he st u d y, 
li n ki n g eac h s u bject’s n u merical c o de t o t heir act ual i de ntit y. I n case of data tra nsfer, t he 
s p o ns or will mai ntai n hi g h sta n dar ds of c o nfi de nti alit y a n d pr otecti o n of s u bjects’ pers o nal data 
c o nsiste nt wit h a p plica ble pri vac y la ws.  
I nf or me d c o nse nt d oc u me nts 
m ust be i n c o m plia n ce wit h I C H G C P , l ocal re g ulat or y 
re q uire me nts (i ncl u di n g a p plica ble l ocal me dical de vice re g ulati o ns) a n d le gal re q uire me nts  
(i ncl u di n g a p plica ble pri vac y la ws). All  d oc u m e nts use d d uri n g t he i nf or me d c o nse nt pr ocess 
m ust be re vie we d a n d a p pr o ve d b y t he s p o ns or, a p pr o ve d b y t he I R B bef ore use, a n d a vaila bl e 
f or i ns pecti o n. 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 0  of 1 1 3  
T he i n vesti gat or m ust e ns ure t hat eac h st u d y s u bject  is f ull y i nf or me d a b o ut t he nat ure a n d 
o bjecti ves of t he st u d y , a n d p ossi ble ris ks ass o ciate d wit h partici p ati o n. I nf or me d c o nse nt 
d oc u me nts  s h o ul d be c o m pre he nsi ve, c o ncise, clear, rele va nt a n d u n d ersta n d a ble t o a la y pers o n . 
T he i n vesti gat or, or a pers o n desi g nate d b y t he i n vesti gat or, will o btai n writte n i nf or me d 
c o nse nt fr o m eac h s u bject bef ore a n y st u d y -s pecifi c acti vit y is perf or me d.  T he i n vesti gat or will 
retai n t he ori gi nal of eac h s u bject's i nf or me d c o ns e nt si g ne d d oc u me nt(s). 
1 3. 3. 4  
S u bj e ct R e cr ui t m e nt  
A d vertis i n g materials a p pr o ve d b y t he I R B a n d t he i n vesti gat or’s data base ma y be use d t o 
recr uit st u d y s u bjects.  Use of a n I R B a p pr o ve d  pre -scree ni n g q uesti o n nair e t o assess ge neral 
s uita bilit y (basic s u bject c haracteristics ) f or t he st u d y is per mi tte d. T his  ge neric q uesti o n nair e 
ma y be use d as a p h o ne s cri pt a n d/ or t o re vi e w i nter nal data bases t o i de ntif y p ote ntial s u bjects.   
T he s p o ns or will ha ve a n o p p ort u nit y t o re vie w a n d a p pr o ve t he c o nt e nt of a n y recr uit me nt 
materials bef ore s uc h m aterials are s u b mitte d f or I R B re vie w a n d use d  t o i de ntif y p ote ntial 
st u d y s u bjects.  
1 3. 3. 5  
R e p orti n g of S af et y I s s u e s a n d S eri o u s Br e a c h e s of t h e Pr ot o c ol or 
I C H G C P  
Wit hi n t he s p o ns or, a seri o us breac h is defi ne d as a breac h li kel y t o affect t o a si g nifica nt de gree 
t he safet y a n d ri g hts of a s u bject or t he relia bilit y a n d r o b ust ness of t he data ge nerat e d i n Hale o n -
s p o ns ore d h u ma n s u bject researc h st u dies.  
I n t he e ve nt of a n y pr o hi biti o n or restricti o n i m p ose d (i.e., cli nical h ol d) b y a n a p plica bl e 
c o m pete nt a ut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be n efits a n d ris ks of t he i n vesti gati o nal 
pr o d uct (s), t he s p o ns or s h o ul d be i nf or me d i m me diatel y.  
I n a d diti o n, t he i n vesti gat or will i nf or m t he s p o ns or i m me diatel y of a n y ur ge nt safet y meas ures 
ta ke n b y t he i n vesti gat or t o pr otect t he st u d y s u bjects a gai nst a n y i m me diate hazar d, a n d of a n y 
seri o us breac hes of t his pr ot oc ol or of I C H G C P t hat t he i n vesti gat or bec o m es a ware of.  
1 3. 4  
P o sti n g of I nf or m ati o n o n P u bli cl y A v ail a bl e Cli ni c al Tri al 
R e gi st er s  
St u d y i nf or mati o n fr o m t his pr ot oc ol will be p oste d o n p u blicl y a vaila ble cli nical trial re gisters 
bef ore e nr oll me nt of s u bj ects be gi ns i n acc or da n ce wit h a p plica ble s p o ns or pr ocesses.  
T o  hel p e ns ure t he data pr o vi de d b y st u d y partici pa nts are use d t o ma xi m u m effect i n t he 
creati o n of k n o wle d g e a n d u n dersta n di n g , the s p o ns or  i nte n ds t o ma ke a n o n y mize d s u bject-
le vel data fr o m t his st u d y a vaila ble t o e xter nal res earc h ers f or scie ntific a n al yses or t o c o n d uct 
f urt her researc h t hat c o ul d hel p a d va nce me dical s cie nce or i m pr o ve patie nt care.  
1 3. 5  
Pr o vi si o n of St u d y R e s ult s t o I n v e sti g at or s  
W here re q uire d b y a p plica ble re g ulat or y re q uir e me nts, a n i n vesti gat or si g nat or y will be 
i de ntifie d f or t he a p pr o val of t he C S R . T he i n vesti gat or will be pr o vi de d reas o na ble access t o 
statistical ta bles, fi g ures a n d rele va nt re p orts a n d will ha ve t he o p p ort u nit y t o re vie w t he 
c o m plete st u d y res ults at a s p o ns or site or ot her m ut uall y a greea ble  l ocati o n. 
T he s p o ns or  will als o pr o vi de t he i n vesti gat or wit h a f ull s u m mar y of t he st u d y res ults. T he 
i n vesti gat or is e nc o ura ge d t o s hare t he s u m mar y res ults wit h t he st u d y s u bjects, as a p pr o priate.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 1  of 1 1 3  
A ma n uscri pt will be pr o gresse d f or p u blicati o n i n t he scie ntific literat ur e  if t he res ults pr o vi d e 
i m p orta nt scie ntific or me dical k n o wle d ge. T h e pr oce d ures a n d ti mi n g f or p u blic discl os ure of 
t he res ults s u m mar y a n d f or t h e de v el o p me nt of a m a n uscri pt f or p u blicati o n will be i n 
acc or da nce wit h c o u ntr y s pecific re g ulat or y re q uir e me nts f or discl os ure  a n d s p o ns or p olic y . 
1 3. 6  
R e c or d s R et e nti o n  
F oll o wi n g cl os ure of t he st u d y, t he i n vesti gat or m ust mai ntai n all site st u d y rec or ds (e x ce pt f or 
t h ose re q uire d b y l oc al re g ulati o ns t o be mai ntai ne d else w here) i n a s afe a n d sec ure l o cati o n.   
R ec or ds (i n vesti gat or site file) m ust be mai ntai ne d i n s uc h a wa y t o all o w eas y a n d ti mel y 
retrie val w h e n nee d e d (e. g., f or s p o ns or a u dit or re g ulat or y i ns pecti o n) a n d m ust be a vaila ble 
f or re vie w i n c o nj u ncti o n wit h assess me nt of t he facilit y, s u p p orti n g s yste ms a n d rele va nt 
i n vesti gat or site staff. 
W here per mitte d b y l ocal la ws/re g ulati o ns or i nstit uti o nal p olic y, s o me or all of t hes e rec or ds 
ca n be mai ntai ne d i n a f or mat ot her t ha n har d c o p y (e. g. , micr ofic he, sca n ne d, electr o nic); 
h o we ver, ca uti o n n ee ds t o be e x ercise d bef ore s u c h acti o n is ta ke n. T he i n v esti gat or m ust e ns ure 
t hat all re pr o d ucti o ns are le gi ble, are a tr u e a n d acc ura te c o p y of t he ori gi nal a n d meet 
accessi bilit y a n d retri e v al sta n dar ds, i ncl u di n g re -ge n erati o n  of  a h ar d c o p y, if re q uire d.  
F urt her m ore, t he i n v esti gat or m ust e ns ure t here is a n acce pta bl e bac k -u p of t hese re pr o d ucti o ns 
a n d t hat a n acce pta bl e q u alit y c o n tr ol pr ocess e xists f or ma ki n g t hese re pr o d ucti o ns. 
T he i n vesti gat or m ust ass ure t he s u bject’s a n o n y mit y will be mai ntai ne d. In C R Fs or ot her 
d oc u me nts s u b mitte d t o t he s p o ns or, s u bjects s h o ul d n ot be i de ntifie d b y t heir na mes or i nitials, 
b ut b y a n i de nti ficati o n c o de. T he i n vesti gat or s h o ul d kee p a se parate l o g of s u bjects’ c o des, 
na mes a n d a d dresses.  D oc u me nts n ot f or s u b missi o n t o t he s p o ns or (e. g., s u bject si g ne d c o nse nt 
f or ms) s h o ul d be mai ntai ne d b y t he i n vesti gat or i n strict c o nfi de nce. 
Rec or ds a n d  d oc u me nts, i ncl u di n g si g ne d I C F s, p ertai ni n g t o t he c o n d uct of t his st u d y m ust b e 
retai ne d b y t he i n vesti gat or as per t he si g ne d c o ntract ual a gree me nt, fr o m t he iss ue of t he fi nal 
C S R or e q ui vale nt s u m mar y,  u nless l ocal re g ulati o ns or i nstit uti o nal p olici es re q uire a l o n ger 
rete nti o n peri o d. T he mi ni m u m rete nti o n ti me will meet t he strictest sta n dar d a p plica ble t o t hat 
i n vesti gat or site f or t his st u d y, as dictate d b y a n y i nstit uti o nal re q uire me nts or l ocal la ws or 
re g ulati o ns, s p o ns or sta n dar ds/ pr oce d ures, a n d/ or i nstit uti o nal re q uire me nts.   
N o st u d y d oc u me nt s h o ul d be d estr o ye d wit h o ut a pri or writte n a gree me nt b et wee n t he s p o ns or 
a n d t he i n vesti gat or. T h e i n vesti gat or m ust n otif y t he s p o ns or of a n y c ha n ges i n t he arc hi val 
arra n g e me nts i ncl u di n g, b ut n ot li mite d t o, arc hi val at a n off-site facilit y or tra nsfer of 
o w ners hi p of t he rec or ds i n t he e ve nt t he i n vesti gat or is n o l o n ger ass ociate d wit h t he 
i n vesti gat or site. 
1 3. 7  
C o n diti o n s f or T er mi n ati n g t h e St u d y  
Pre mat ure ter mi nati o n of t his st u d y ma y occ ur b eca u se of a re g ulat or y a ut h orit y decisi o n, a 
c ha n ge i n I R B o pi ni o n , st u d y pr o d uct safet y pr o ble ms, or at t he discreti o n of t he s p o ns or. I n 
a d diti o n, t he s p o ns or retai ns t he ri g ht t o disc o nti n ue de vel o p me nt of t he i n v esti gati o nal pr o d uct 
at a n y ti me.  
If a st u dy is pre m at urel y ter mi nate d, t he s p o ns or will pr o m ptl y n otif y t he i n vesti gat or. After 
n otificati o n, t he i n vesti gat or m ust pr o m ptl y c o ntact all partici pati n g s u bjects  a n d s h o ul d ass ur e 
a p pr o priate t hera p y/f oll o w -u p f or t he s u bjects.  As directe d b y t he s p o ns or, all st u d y materials 
m ust be c ollecte d a n d all C R Fs  c o m plete d t o t he greatest e xte nt p ossi ble. W here re q uire d b y 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 2  of 1 1 3  
t he a p plica ble re g ulat or y re q uire me nts, t he s p o ns or s h o ul d i nf or m t he re g ul at or y a ut h orit y(ies) 
a n d t he i n vesti gat or s h o ul d pr o m ptl y i nf or m t he I R B a n d pr o vi d e t he I R B a det aile d writte n 
e x pla nati o n f or t he t er mi nati o n or s us pe nsi o n.  
If t he I R B ter mi nates or s us pe n ds its a p pr o val/fa v ora ble o pi ni o n of the st u d y , t he i n vesti gat or 
s h o ul d pr o m ptl y n otif y t he s p o ns or a n d pr o vi de t he s p o ns or wit h a detaile d writte n e x pla nati o n 
f or t he ter mi nati o n or s us pe nsi o n. 
U p o n c o m pleti o n or pre mat ure disc o nti n uati o n of t he st u d y, t he s p o ns or’s m o nit or will c o n d uct 
site cl os ure acti vities wit h t he i n vesti gat or a n d site staff, as a p pr o priat e, i n acc or da nce wit h 
a p plica ble re g ulati o ns , i ncl u di n g G C P a n d s p o ns or Sta n dar d O perati n g Pr oce d ures.  
1 4  
R E F E R E N C E S  
[A bsi  E G, A d d y M, A d a ms D ( 1 9 8 7)] De nti ne h y perse nsiti vit y: A st u d y of t he p ate nc y of 
de nti nal t u b ules i n se nsiti ve a n d n o n -se nsiti ve cer vical de nti ne. J Cli n Peri o d o nt ol 1 9 8 7; 1 4( 5): 
2 8 0 -2 8 4.  
[A d d y  M, M ostafa P, A bsi E , et al., e dit ors ( 1 9 8 5)] Cer vical de nti n h y perse nsiti vit y: Eti ol o g y 
a n d ma na g e me nt wit h partic ular refere n ce t o de ntifrices. Pr ocee di n gs of S y m p osi u m o n 
H y perse nsiti ve De nti n: Ori gi n a n d Ma na ge m e nt 1 9 8 5: U ni versit y of Mic hi ga n.  
[A d d y  M, M ostafa  P, Ne wc o m be  R G ( 1 9 8 7)] De nti ne h y perse nsiti vit y: t he distri b uti o n of 
recessi o n, se nsiti vit y a n d pla q ue. J De nt 1 9 8 7; 1 5( 6): 2 4 2 -2 4 8.  
[A d d y  M. ( 2 0 0 0)] 
D e nti ne h y perse nsiti vit y: defi niti o n, pre v ale nce, distri b uti o n a n d 
aeti ol o g y.  T o ot h wear a n d se nsiti vit y: Cli nical a d va nces i n rest orati ve de ntistr y.  L o n d o n: 
Marti n D u nitz  2 0 0 0: 2 3 9 -2 4 8.  
[A d d y , M ( 2 0 0 2)] De nti ne h y perse nsiti vit y: Ne w pers pecti ves o n a n ol d pr o ble m. I nt De nt J 
2 0 0 2; 5 2: 3 6 7 -3 7 5.  
[A g h az a de h  Z, Be hr o ozia n A, N ajafi H , et al. ( 2 0 1 9)] C o m paris o n of gi n gi val a n d de ntal 
i n dices i n lactati n g an d n o n -lactati n g m ot hers d uri n g first 6 m o nt h after deli ver y. Pes q ui Bras 
O d o nt o pe diatria Clí n I nt e gr 2 0 1 9; 1 9:  e 4 5 8 6. 
[A mi ni  P, Kl u k o ws ka M, E use bi o R, et al. ( 2 0 1 9)] A nti-Se nsiti vit y Efficac y of Bi oa vaila bl e 
Sta n n o us Fl u ori de De ntifrice vs. Ne g ati ve C o nt r ol ( A bstract # 2 3 2 2). I A D R. Va nc o u v er, 
Ca na da.  
[As h bec k  E L, Bell M L. ( 2 0 1 6)] Si n gle ti me p oi nt c o m paris o ns i n l o n git u di nal ra n d o mize d 
c o ntr olle d trials: p o wer a n d bias i n t he prese nce of missi n g data. B M C Me d Res Met h o d ol 2 0 1 6; 
1 6: 4 3.  
[B a d a d he  S, Ga n gar de G, et al. ( 2 0 2 3)] I m pact of a nti-se nsiti vit y t o ot h paste o n oral healt h. 
W orl d J P har m Res 2 0 2 3; 1 2( 7): 1 0 4 3 -1 0 6 0.   
[B ae  J H, Ki m Y K, M y u n g S K ( 2 0 1 5)] Dese nsitizi n g t o ot h paste vers us place b o f or d e nti n 
h y perse nsiti vit y: A s yste matic re vie w a n d m et a-a nal ysis. J Cli n Peri o d o nt ol 2 0 1 5; 4 2( 2): 1 3 1 -
1 4 1.  
[B a ker  S R, Gi bs o n BJ, S ufi F, et al. ( 2 0 1 4)] T he de nti n h y perse nsiti vit y e x perie nce 
q uesti o n naire ( D H E Q): A l o n git u di nal vali dati o n st u d y. J Cli n Peri o d o nt ol 2 0 1 4; 4 1: 5 2-5 9. 
d oi: 1 0. 1 0 1 6/ B 9 7 8 0 -1 2 -8 0 1 6 3 1 -2. 0 0 0 0 9 -9.  
[B ar o n  G, Ra va u d P, Sa ms o n A, et al. ( 20 0 8)] Missi n g data i n ra n d o mize d c o ntr olle d trials of 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 3  of 1 1 3  
r he u mat oi d art hritis wit h ra di o gra p hic o utc o m es: A si m ulati o n st u d y. Art hritis R he u m-Art hritis 
Care Res 2 0 0 8; 5 9: 2 5 -3 1.  
[B art ol d  P M. ( 2 0 0 6)] De nti n al h y perse nsiti vit y: a re vie w. A ust D e nt J 2 0 0 6; 5 1( 3): 2 1 2 -2 1 8.  
[B aş ar a n  S, Celi k C. ( 2 0 1 8)] T ur kis h a d a ptati o n of de nti n h y p erse nsiti vit y e x perie nce 
q uesti o n naire ( D H E Q). C o m m u nit y De nt Healt h 2 0 1 8; 3 5( 1): 4 7 -5 1.  
[B oi k o  O V, Ba ker S R, Gi bs o n BJ, et al. ( 20 1 0)]  C o nstr ucti o n a n d vali dati o n of t he q ualit y of 
life meas ure f or de nti n h y perse nsiti vit y ( D H E Q). J o ur nal of cli nical peri o d o nt ol o g y. 2 0 1 0; 
3 7( 1 1): 9 7 3 -9 8 0.  
[Br ä n nstr ö m  M ( 1 9 6 3)] A h y dr o d y na mic mec ha nis m i n t he tra ns m issi o n of pai n pr o d uci n g 
sti m uli t hr o u g h t he de nti n. I n: A n ders o n DJ: Se ns or y mec ha nis m i n d e nti n. O xf or d, Per ga m m o n 
Press, 1 9 6 3; 7 3 -7 9.  
[B ur nett  G R, Wills o n RJ, L ucas R A . ( 2 0 1 3)] I n vitr o st u dies i n vesti gati n g t he de nti n t u b ule 
occl usi o n pr o perties of a n e x peri me ntal a n h y dr o us sta n n o us fl u ori de de ntifrice. A m  J De nt; 2 6 
( S pIss A): 1 0 A-1 4 A.  
[C a n a di a n A d vis or y B o ar d o n De nti n H y perse nsiti vit y  ( 2 0 0 3)] Ca na di a n A d vis or y B oar d 
o n 
De nti n 
H y perse nsiti vit y, 
C o nse ns us -base d rec o m me n dati o ns f or t he dia g n osis a n d 
ma n a ge me nt of d e nti n h y perse nsiti vit y. J Ca n De nt Ass oc 2 0 0 3; 6 9: 2 2 1 -2 2 6.  
[C h a k nis  P, Pa na ga k os F S, De Vizi o W, et al. ( 2 0 1 1)] Assess me nt of h y perse nsiti vit y re d ucti o n 
of a de ntifric e c o ntai ni n g 0. 3 % tricl osa n, 2. 0 % P V M/ M A c o p ol y mer, 0. 2 4 3 % Na F a n d 
s peciall y-desi g ne d silica as c o m pare d t o a de ntifrice c o ntai ni n g 0. 4 5 4 % sta n n o us fl u ori d e, 
s o di u m he xa meta p h os p hate a n d zi nc lact ate a n d t o a de ntifrice c o ntai ni n g 0. 2 4 3 % Na F o n 
de nti n h y perse nsiti vit y re d ucti o n: A n 8 -wee k st u d y. A m J De nt; 2 4( A): 1 4 -2 0.  
[C o x  C F, 
W hite K C, Ra m us D L, et al. ( 1 9 9 2)] Re parati ve de nti n: fact ors affecti n g its 
de p ositi o n. Q ui ntesse nce I nt 1 9 9 2; 2 3: 2 5 7 -2 7 0.  
[Creet h  J, Gall o b J, S ufi F, et al. ( 2 0 1 9[a])] Ra n d o mise d cli nical st u dies i n vesti gati n g 
i m me diate a n d s h ort-ter m efficac y of a n occl u di n g t o ot h paste i n pr o vi di n g de nti ne 
h y perse nsiti vit y relief. B M C Oral Healt h  2 0 1 9; 1 9: 9 8.  
[Creet h  J, 
M acl ur e R, Se o n g J, et al. ( 2 0 1 9[b ])] T hree ra n d o mize d st u dies of de nti ne 
h y perse nsiti vit y re d ucti o n after s h ort‐ter m S n F 2 t o ot h paste use J Cli n Peri o d o nt ol 2 0 1 9; 4 6: 
1 1 0 5 -1 1 1 5.  
[Creet h  J E, B ur nett 
G R. ( 2 0 2 1)] Effi cac y of a n E x peri me ntal 
Occl usi o n Tec h n ol o g y 
T o ot h paste i n t he Relief of De nti nal H y perse nsiti vit y: A n 8 -wee k Ra n d o mise d C o ntr olle d Trial. 
Oral Healt h & Pre ve nti ve De ntistr y 2 0 2 1; 1 9( 1 ): 1 9 5-2 0 2.  
[C u n h a -Cr uz  J, Wata ha J C, Heat o n LJ, et al. ( 2 0 1 3)] T he pre v ale nce of de nti n h y perse nsiti vit y 
i n ge neral de ntal practices i n t he n ort h west U nite d States. J A m De nt Ass oc 2 0 1 3; 1 4 4( 3): 2 8 8-
2 9 6.  
[D a b a b ne h  R H, K h o uri A T, A d d y M . ( 1 9 9 9)] De nti ne h y perse nsiti vit y - a n e ni g ma? A re vie w 
of ter mi n ol o g y, mec ha nis ms, aeti ol o g y a n d ma na ge me nt. Br De nt J 1 9 9 9;  1 8 7( 1 1):  6 0 6 -1 1 . 
D isc ussi o n 6 0 3. D OI:  1 0. 1 0 3 8/sj. b dj. 4 8 0 0 3 4 5. P MI D: 1 6 1 6 3 2 8 1.   
[D a y  T, Ei n wa g J, Her ma n n J, et al. ( 2 0 1 0)] A cli nical assess me nt of t he efficac y of a sta n n o us 
c o ntai ni n g s o di u m fl u ori de de ntifrice o n de nti nal h y perse nsiti vit y. J C o nte m p De nt Pract 2 0 1 0; 
1 1( 1): E 0 0 1 -E 8.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 4  of 1 1 3  
[De m pse y  P J, T o w nse n d GC. ( 2 0 0 1)]  Ge netic a n d e n vir o n me ntal c o ntri b uti o ns t o variati o n i n 
h u ma n t o ot h size. Here dit y 2 0 0 1;  8 6( 6):  6 8 5.  
[D oci m o  R, M o ntesa ni L, Mat ur o P, et al. ( 2 0 0 9)] C o m pari n g t he Efficac y i n Re d uci n g De nti n 
H y perse nsiti vit y of a N e w T o ot h paste C o ntai ni n g 8. 0 % Ar gi ni ne, Calci u m Car b o nate, a n d 1 4 5 0 
p p m Fl u ori de t o a C o m mercial Se nsiti ve T o ot h pas te C o ntai ni n g 2 % P otassi u m I o n: A n Ei g ht-
Wee k Cli nical St u d y i n R o me, Ital y . J Cli n De nt 2 0 0 9; 2 0( 1) ( S pec Iss): 1 7-2 2.  
[D o u gl as -de -Oli veir a  D W , Vit or 
G P , Sil veira J O,  et al. ( 2 0 1 8)] 
Effect of de nti n 
h y perse nsiti vit y treat me nt o n oral h ealt h relate d q u alit y of life –  A s yste matic re vi e w a n d meta -
a nal ysis. J De nt 2 0 1 8; 7 1: 1-8.  
[D’ S o uz a  R N, Bac h ma n T, Ba u m gar d ner K R, et al.  (1 9 9 5) ] C haracterizati o n of cell ular 
res p o nses i n v ol ved i n re p arati ve de nti n o ge n esis i n rat m olars. J De nt Res 1 9 9 5; 7 4: 7 0 2-7 0 9.  
[D u  M, Jia n g H, Tai B, et al. ( 2 0 1 1)] De-se nsitizi n g effect of a sta n n o us c o ntai ni n g s o di u m 
fl u ori de n o vel de ntifri ce ( A bstract # 2 8 2 6). I A D R 2 0 1 1 , Sa n Die g o, Calif or nia.  
[E arl  J S, La n gf or d R M ( 2 0 1 3)] P h ysical a n d c he mical c haracterizati o n of t he s urface la yers 
f or me d o n d e nti n f oll o wi n g treat me nt wit h a n e x peri me ntal a n h y dr o us sta n n o us fl u ori d e 
de ntifrice. A m J D e nt 2 0 1 3; 2 6 ( S pIss A): 1 9 A -2 4 A.  
[Elli n gse n  J E, R olla G. ( 1 9 8 7)] Treat ment of de nti n wit h sta n n o us fl u ori de – S E M a n d electr o n 
micr o pr o be st u d y. E ur o p ea n J Oral Sci 1 9 8 7; 9 5( 4): 2 8 1 -2 8 6.  
[E xter k ate  R A M. ( 2 0 2 2)] W hat is t he f u ncti o ni n g of ti n i n sta n n o us fl u ori de? Ne d erla n ds 
tij dsc hrift v o or ta n d heel k u n de 2 0 2 2; 1 2 9( 5): 2 1 9-2 2 2.  
[Fisc her  C, Fisc her R G, We n n ber g A. ( 1 9 9 2)]  Pre vale nce a n d distri b uti o n of cer vical de nti ne 
h y perse nsiti vit y i n a p o p ulati o n i n Ri o de Ja neir o, Brazil J De nt 1 9 9 2 ; 2 0 : 2 7 2 -2 7 6.  
[Fl y n n  J, Gall o wa y R, Orc har ds o n R. ( 1 9 8 5)] T he i nci de nce of “ h y p erse nsiti ve” teet h i n t he 
West of Sc otla n d. J De nt 1 9 8 5; 1 3 : 2 3 0 -2 3 6.  
[G a gliese  L, Weiz blit N, Ellis W, et al. ( 20 0 5)]  T he meas ure me nt of p ost o perati ve pai n: a 
c o m paris o n of i nte nsit y scales i n y o u n ger a n d ol der s ur gical patie nts. Pai n 2 0 0 5; 1 1 7( 3): 4 1 2 -
4 2 0.  
[G all o b  J, S ufi F, A mi ni P, et al. ( 2 0 1 7)] A ra n d o mise d e x pl orat or y cli nical e v al uati o n of 
de ntifrices us e d as c o ntr ols i n de nti nal h y perse nsiti vit y st u dies. J o ur nal of d e ntistr y; 6 4: 8 0 -8 7.  
[Gerl ac h  R W, Sa g el P ( 2 0 1 7)] C o nc urre nt  Se nsiti vit y a n d Gi n gi vitis Effects of S n F 2/ H2O 2 
H y gie ne: I ncl usi ve Met a -A nal ysis ( A bstract # 3 0 4 2). I A D R 2 0 1 7 Sa n Fra n cisc o, Calif or nia.  
[Gi bs o n  BJ, B oi k o O V, Ba ker S R, et al. ( 2 0 1 5)] T he e v er y da y i m pact of de nti n  se nsiti vit y: 
Pers o nal a n d f u n cti o nal as pects.  De nti n  H y perse nsiti vit y: Else vier; 2 0 1 5. p. 8 9 -1 0 7.  
[Gill a m  D G, Aris A, B ul ma n J S, et al. (2 0 0 2 )] De nti ne h y perse nsiti vit y i n s u bjects recr uite d 
f or cli nical trials: cli nical e val uati o n, pre val e nce a n d i ntra-oral distri b uti o n . J Oral Re ha b 2 0 0 2 ; 
2 9 : 2 2 6 -2 3 1 . 
[G ysi  A  ( 1 9 0 0)] A n atte m pt t o e x plai n t he se nsiti ve ness of de nti ne. Br De nt J  1 9 0 0;  4 3:  8 6 5 -
8 6 8 .  
[H all  C, 
Mas o n S, C o o ke J. ( 2 0 1 7)] E x pl orat or y ra n d o mise d c o ntr olle d cli nical st u d y t o 
e val uate t he c o m parati v e effic ac y of t w o occl u di n g t o ot h pastes  –  a 5 % calci u m s o di u m 
p h os p h osilicate t o ot h paste a n d a n 8 % ar gi ni ne/cal ci u m car b o nat e t o ot h paste  –  f or t he l o n ger-
ter m relief of de nti ne h y p erse nsiti vit y. J De nt 2 0 1 7; 6 0 : 3 6 -4 2.  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 5  of 1 1 3  
[H aze n  S, V ol pe A, Ki n g W ( 1 9 6 8)] C o m parati ve dese nsitizi n g effect of d e ntifrices c o nt ai ni n g 
s o di u m m o n ofl u or o p h os p hate, sta n n o us fl u ori de, a n d f or mali n. Peri o d o ntics  1 9 6 8 ; 6( 5): 2 3 0- 
2 3 2.   
[He  T, Bar ker M L, Bies br oc k A, et al. ( 2 0 1 4 [a])] A ra n d o mize d c o ntr olle d cli nical trial t o assess 
t he dese nsitizi n g effect of a sta n n o us fl u ori de d e ntifrice. A m J D e nt; 2 7( 2): 1 0 6 -1 1 0.  
[He  T, Bar ker M L, Bies br oc k A R, et al. ( 2 0 1 4[ b])] A Cli nical St u d y t o Assess t he Effect of a 
Sta bilize d Sta n n o us Fl u ori de De ntifrice o n H y perse nsiti vit y Relati ve t o a Mar kete d S o di u m 
Fl u ori de/ Tricl osa n C o ntr ol. J Cli n De nt 2 0 1 4; 2 5( 2): 1 3 -1 8.   
[He  S, Wa n g J.  ( 2 0 1 5[a])] De v el o p me nt of t he c hi nese versi o n of t he d e nti n  h y perse nsiti vit y 
e x perie n ce q uesti o n nair e.  De nti n  H y perse nsiti vit y ; Else vier 2 0 1 5 : 1 6 5 -1 7 5.  
[He  Sl, Wa n g J H . ( 2 0 1 5[ b])] Relia bilit y a n d vali dit y of t he c hi nese versi o n of t he s h ort f or m of 
t he de nti n h y perse nsiti vit y e x perie nce q uesti o n n aire (D H E Q -1 5). Q ualit y of Life Researc h 
2 0 1 5a;  2 4( 6):  1 4 6 5 -1 4 6 9.  
[He  T, Peters J, G o yal C R, et al. ( 2 0 1 9)] Cli ni cal Dese nsitizi n g Effect of Bi oa vaila ble S n F 2 
De ntifrice ( A bstract # 2 2 1 0). I A D R 2 0 1 9 Va n c o u ver, Ca na d a.  
[He at o n  LJ, Barl o w A P, C ol d well S E. ( 2 0 1 3)] De vel o p me nt of la bel e d ma g nit u de scales f or 
t he assess me nt of pai n of de nti n h y perse nsiti vit y. J Or ofac Pai n 2 0 1 3; 2 7( 1): 7 2-8 1.  
[Hi nes  D, X u S, Stra nic k M, et al. ( 2 0 1 9)] Effect of a sta n n o us fl u ori de t o ot h paste o n de nti nal 
h y perse nsiti vit y: I n vitr o a n d cli nical e val u ati o n. J A m De nt Ass oc 2 0 1 9; 1 5 0( 4): S 4 7 -S 5 9.  
[H oll a n d  G R, Nar hi M N, A d d y M, et al. ( 1 9 9 7)] G ui deli nes f or t he d esi g n a n d c o n d u ct of 
cli nical trials o n de nti ne h y perse nsiti vit y. J Cli n Peri o d o nt ol 1 9 9 7;  2 4( 1 1):  8 0 8 -1 3.  
[K a n o uté  A, N da me Die n g S, Di o p M, et al. ( 2 0 2 2)] C he mical vs. nat ural t o ot h paste: w hic h 
f or m ulas f or w hic h pr o perties? A sc o pi n g re vi e w . JP HI A 2 0 2 2 ; 1 3 (3 ): 1 -1 3 . htt ps:// d oi. or 
g/ 1 0. 4 0 8 1/j p hia. 2 0 2 2. 1 9 4 5.  
[Ke n w ar d  M G, R o ger J H . ( 1 9 9 7)] S mall sa m ple i nfere n ce f or fi xe d effects fr o m restricte d 
ma xi m u m li keli h o o d. Bi o metrics 1 9 9 7 ; 5 3( 3): 9 8 3 -9 9 7.   
[Ki m  J Y, et al. (2 0 2 1 )] Cli nical a n d In -Vitr o St u dies of O ur Ne w S n F 2 T o ot h paste. 2 0 2 1 
I A D R/ A A D R/ C A D R Ge neral Sessi o n.  
[K o nr a dss o n K, Li n gstr ö m P, E mils o n C G, et al. ( 2 0 2 0)] Sta bilize d sta n n o us fl u ori d e 
de ntifrice i n relati o n t o de ntal caries, de ntal er osi o n a n d de nti n h y perse nsiti vit y: A s yste matic 
re vie w. A m J D e nt 2 0 2 0; 3 3( 2): 9 5-1 0 5.  
[L aster  L, La u de n bac h K W, St oller N H. ( 1 9 7 5)] A n e val uati o n of cli nical t o ot h m o bilit y 
meas ure me nts. J. Peri o d o nt ol 1 9 7 5; 4 6 : 6 0 3 -6 0 7.   
[Lei g ht  R, S ufi F, Gr oss R, et al. ( 2 0 0 8 )] De nti nal h y perse nsiti vit y: A 1 2 -wee k st u d y of a n o vel 
de ntifrice deli ver y s yste m c o m pari n g differe nt br us hi n g ti mes a n d assessi n g t he efficac y f or 
har d -t o-reac h m olar teet h. J C li n D e nt 2 0 0 8;  1 9( 4):  1 4 7 -5 3.  
[Li n de  A, G ol d ber g M. ( 1 9 9 3)] De nti n o ge n esis. Cri t Re v Oral Bi ol Me d 1 9 9 3; 4( 5): 6 7 9-7 2 8.  
[L o be ne  R R, Weat herf or d T, R oss N M, et al. ( 1 9 8 6)] A m o difie d gi n gi val i n de x f or use i n 
cli nical trials. Cli n Pre v De nt 1 9 8 6; 8 : 3 -6.   
[M ac h uc a  C, Ba ker S, S ufi F, et al. ( 2 0 1 4)] Deri vati o n of a s h ort f or m of t he de nti ne 
h y perse nsiti vit y e x perie n ce q uesti o n nair e. J Cli n Peri o d o nt ol 2 0 1 4;  4 1:  4 6 -5 1.   
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
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Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 6  of 1 1 3  
[M a gl oire  H, B o u vier M, J offre A. ( 1 9 9 2)] O d o nt o blast res p o nse u n der cari o us lesi o ns. Pr oc 
Fi n n De nt S oc 1 9 9 2; 8 8( S u p pl 1): 2 5 7 -2 7 4.  
[M a ki n  S A. ( 2 0 1 3)] Sta n n o us fl u ori de de ntifrices. A m J De nt 2 0 1 3 ; 2 6 S pec N o  A:  3 A –  9 A.   
[M arti ns  C C, Fir mi n o R T, Ri va JJ, et al. ( 2 0 2 0)] Dese nsitizi n g T o ot h pastes f or De nti n 
H y perse nsiti vit y: A Net w or k Meta -a nal ysis. J De nt Res 2 0 2 0; 9 9: 5 1 4-2 2.  
[M arti ns  C C, Ri va J J, Fir mi n o R T, et al. ( 2 0 2 2)] F or m ulati o ns of dese nsitizi n g t o ot h pastes f or 
de nti n h y perse nsiti vit y: a sc o pi n g re vie w. J 
A p pl 
Oral Sci 2 0 2 2; 3 0: e 2 0 2 1 0 4 1 0. 
htt ps:// d oi. or g/ 1 0. 1 5 9 0/ 1 6 7 8 -7 7 5 7 -2 0 2 1 -0 4 1 0.  
[M art o  C, Ba ptista P A, N u nes T, et al. ( 2 0 2 0)] E val u atio n of t h e efficac y of de nti n 
h y perse nsiti vit y treat me nts - A s yste matic re vie w a n d f oll o w -u p a nal ysis. J Oral Re ha b 2 0 2 0; 
4 6: 9 5 2 -9 0.  
[M as o n  S, Ki n gst o n R, S h ne yer L, et al. ( 2 0 1 7)]. Cli nical st u d y t o 
m o nit or de nti nal 
h y perse nsiti vit y wit h e pis o dic use of  a d ese nsitisi n g de ntifrice.  B DJ  o pe n  2 0 1 7;  3( 1) : 1 -6.   
[M as o n  S, B ur nett G R, Patel N, et al. ( 2 0 1 9)] I m pact of t o ot h paste o n oral healt h -relate d q ualit y 
of life i n pe o ple wit h de nti ne h y perse nsiti vit y. B M C Oral Healt h 2 0 1 9; 1 9: 1 -1 1.  
[Miller  S, Tr u o n g T, He u R, et al. ( 1 9 9 4)] Rece nt a d va nces i n sta n n o us fl u ori de tec h n ol o g y: 
a nti bacterial efficac y a n d mec ha nis m of acti o n t o war ds h y p erse nsiti vit y. I nt  D e nt J 1 9 9 4; 4 4  
( S u p pl. 1): 8 3-9 8.   
[Mj ör  I A. ( 2 0 0 2)] Cli nical 
Ma n a ge me nt a n d Tiss ue C ha n ges Ass ociat e d wit h 
Wear a n d 
Tra u ma, i n P ul p -De nti n Bi ol o g y i n Rest orati ve De ntis tr y 2 0 0 2: 8 0-8 3. I S B N: 0 -8 6 7 1 5 -4 1 2 -8.  
[Ni  L X, He T, C ha n g A, et al. ( 2 0 1 0)] T he dese nsitizi n g efficac y of a n o vel sta n n o us-c o ntai ni n g 
s o di u m fl u ori de de ntifri ce: A n 8-wee k ra n d o mi ze d a n d c o ntr olle d cli ni cal trial. A m J De nt 
2 0 1 0; 2 3( S pIss B): 1 7 B -2 1 B.  
[Ni  L , He T, C ha n g J, et al. ( 2 0 1 1)] De-se nsitizi n g effect of a sta n n o us c o ntai ni n g s o di u m 
fl u ori de t o ot h paste ( A bstract # 2 8 2 5). I A D R 2 0 1 1 Sa n Die g o, Calif or nia. 
[P ar ki ns o n  C R , Wills o n  RJ ( 2 0 1 1)]  A c o m parati ve i n vitr o st u d y i n vesti gati n g t he occl usi o n 
a n d mi ne ralizati o n pr o perties of c o m merci al de ntifrices i n a f o ur-d a y de nti ne disc m o del. J. 
Cli n. De nt 2 0 1 1; 2 2( 3): 7 4 -8 1.  
[P ar ki ns o n  C, H u g hes N, Jeffer y P, et al. ( 2 0 1 3)] T he efficac y of a n e x p eri me ntal de ntifrice 
c o ntai ni n g 0. 4 5 4 % w/ w sta n n o us fl u ori de i n pr o vi di n g relief fr o m t he pai n of de nti n 
h y perse nsiti vit y: a n 8 -wee k cli nical st u d y. A m J D e nt 2 0 1 3; 2 6( S pIss A): 2 5 A -3 1 A.  
[P ar ki ns o n  C R, Jeff er y P, Mille ma n J L, et al. ( 2 0 1 5[a])] C o nfir mati o n of efficac y i n pr o vi di n g 
relief fr o m t he pai n of d e nti n h y perse nsiti vit y of a n a n h y dr o us de ntifrice c o ntai ni n g 0. 4 5 4 % 
wit h or wit h o ut sta n n o us fl u ori de i n a n 8 -wee k ra n d o mize d cli nical trial. A m J De nt; 2 8 ( 4): 
1 9 0 -1 9 6.  
[P ar ki ns o n  et al ( 2 0 1 5 [ b])] R C Ts of Sta n n o us Fl u ori de T o ot h paste A nti micr o bial Acti vit y; 
E val uati o n of t he Pla q ue Gl yc ol ysis a n d Re gr o wt h M o del. J De nt Res 2 0 1 5; 9 4 B: A bstract # 
3 4. B S O D R Car diff, U K.  
[P as hle y  D H  (1 9 9 4 )] De nti ne per mea bilit y  a n d its r ole i n t he pat h o bi ol o g y of de nti ne 
se nsiti vit y. Arc h O ral B i ol 1 9 9 4; 3 9:  S 7 3 -8 0.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
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Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 7  of 1 1 3  
[Pereir a  J C, de Car val h o Sales-Peres S H, Fra n cis c o ni -d os -Ri os L F, et al. ( 2 0 1 5)] C urre nt a n d 
n o vel cli nical a p pr oac hes f or t he treat me nt of de nti n h y perse nsiti vit y. De nti ne H y perse nsiti vit y: 
A d va nces i n Di a g n osis, Ma na ge me nt, a n d Treat me nt 2 0 1 5:  1 0 1 -3 2.  
[P oll ar d  AJ , K ha n I, D a vies M, et al. ( 2 0 2 3)] C o m parati ve efficac y of self -a d mi nistere d 
de ntifrices f or t he ma n a g e me nt of de nti ne h y p erse nsiti vit y - A s yste matic re vie w a n d n et w or k 
meta -a nal ysis . J D e nt 2 0 2 3;  1 3 0: 1 0 4 4 3 3 . 
[P ols o n  A M, Cat o n J G, Yea ple R N, et al. ( 1 9 8 0) ] Hist ol o gical deter mi nati o n of pr o be ti p 
pe netrati o n i nt o gi n gi val s ulc us of h u ma ns usi n g a n electr o nic press ure -s e nsiti ve pr o be. J Cli n 
Peri o d o nt ol  1 9 8 0 ; 7( 6): 4 7 9-8 8 . 
[P orritt  J M, S ufi F, Ba ker S R. ( 2 0 1 6)] Utilisi n g dail y diaries t o e xa mi ne oral healt h e x peri e nces 
ass ociate d wit h de nti n  h y perse nsiti vit y. B M C Oral H ealt h 2 0 1 6;  1 6:  1 -1 1.  
[Rees  J S. ( 2 0 0 0)] T he pre vale nce of de nti ne h y p erse n siti vit y i n ge neral de ntal practice i n t he 
U K. J Cli n Peri o d o nt ol 2 0 0 0; 2 7 : 8 6 0 – 8 6 5.  
[R o bi ns o n  P G.  ( 2 0 1 4)] De nti n  h y perse nsiti vit y: De vel o pi n g a pers o n -ce ntre d a p pr oac h t o oral 
healt h . Aca d e mic Press; 2 0 1 4.  
[S a m a nt  A, Mali k C, C ha bra S, et al. ( 1 9 7 6)] Gi n gi vitis a n d peri o d o ntal disease i n pre g n a nc y. 
J Peri o d o nt ol 1 9 7 6; 4 7( 7): 4 1 5-8.  
[Sc hiff  T, D ots o n M, C o he n S , et al. (1 9 9 4 )] Efficac y of a de ntifrice c o ntai ni n g p otassi u m 
nitrate, s ol u ble p yr o p h os p hate, P V M/ M A c o p ol y mer, a n d s o di u m fl u ori de o n de nti nal 
h y perse nsiti vit y: a t wel ve-wee k cli nical st u d y. J Cli n De nt 1 9 9 4; 5: 8 7-9 2. P MI D: 8 5 3 4 3 8 0.  
[Sc hiff  T, Saletta L, Ba ker R, et al. ( 2 0 0 5)] Dese nsitizi n g effect of a sta bilize d sta n n o us 
fl u ori de/s o di u m he xa meta p h os p hate de ntifrice. C o m pe n d C o nt E d De nt; 2 6( 9 S u p pl. 1): 3 5 -4 0.  
[Sc hiff  T, H e T, Sa gel L, et al. ( 20 0 6)]  Efficac y a n d safet y of a n o vel sta bilize d sta n n o us 
fl u ori de a n d s o di u m he xa meta p h os p hate de ntifrice f or de nti nal h y perse nsiti vit y. J C o nte m p 
De nt Pract 2 0 0 6 ; 7 : 1 -8.  
[Seltzer  S, Be n der I.  ( 1 9 7 5)] T he De ntal P ul p: Bi ol o gic C o nsi derati o ns i n De ntal Pr oce d ure s, 
2 n d E diti o n, P hila del p hia, P A:  JB  Li p pi nc ott  C o  1 9 7 5 . 
[S h ar m a  N, R o y S, Ka kar A, et al. ( 2 0 1 0)] A cli nical st u d y c o m pari n g oral f or m ulati o ns 
c o ntai ni n g 7. 5 % calci u m s o di u m p h os p h osilicate ( N o va Mi n), 5 % p otassi u m nitrate, a n d 0. 4 % 
sta n n o us fl u ori de f or the ma na ge me nt of d e nti n h y perse nsiti vit y. J Cli n De nt; 2 1( 3): 8 8 -9 2.  
[S hi  Y, C he n H, S u n L. ( 2 0 1 2)] De nti n T u b ule Occl usi o n wit h a N o vel S n Cl 2/ Na F/ Silica 
De ntifrice ( A bstract # 1 3 5 4). A A D R A n n ual Me eti n g 2 0 1 2 Ta m pa, Fl ori da.  
[S pliet h  C H, Tac h o u A. ( 2 0 1 3)] E pi de mi ol o g y of de nti n h y perse nsiti vit y. Cli n Oral I n v est 
2 0 1 3; 1 7: 3 -8.  
[v a n Berc kel  M M, B os ma N H, Ha ge ma n 
M G, et al. 
( 20 1 7)]  T he c orrelati o n bet wee n a 
n u merical rati n g scale of patie nt satisfacti o n wit h c urre nt ma na g e me nt of a n u p per e xtre mit y  
dis or der a n d a ge neral meas ure of satisfacti o n wit h t he me dical visit. Ha n d 2 0 1 7;  1 2( 2):  2 0 2 -
2 0 6.  
[Vi n a y a  K R, S h u b has hi ni N, Ses ha n H, et al. ( 2 0 1 0)] A cli nical tri al c o m pari n g a sta n n o us 
fl u ori de base d de ntifric e a n d a str o nti u m c hl ori de base d de ntifrice i n alle viati n g de nti nal 
h y perse nsiti vit y. J I nt Oral Healt h; 2( 1): 3 7 -5 0.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
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Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 8  of 1 1 3  
[West  N, A d d y M, Jac ks o n R, et al. ( 1 9 9 7 )] De nti ne h y perse nsiti vit y a n d t h e place b o res p o nse: 
A c o m paris o n of t he effect of str o nti u m acetate, p otassi u m nitrate a n d fl u ori de t o ot h pastes. J  
C li n P eri o d o nt ol  1 9 9 7;  2 4( 4):  2 0 9 -1 5.  
[West  N X . ( 2 0 0 8)] De nti ne h y perse nsiti vit y: pre ve nti ve a n d t h era p e utic a p pr oac hes t o 
treat me nt. Peri o d o nt ol 2 0 0 0; 4 8( 1) : 3 1 -4 1.  
[West  N X, Sa n z M, L ussi A, et al. (2 0 1 3) ] Pre v ale nce of de nti ne h y p erse nsiti vit y a n d st u d y of 
ass ociate d fact ors: a E ur o pea n p o p ulati o n -base d cr oss -secti o nal st u d y. J D e nt 2 0 1 3;  4 1( 1 0) : 
8 4 1 -8 5 1.  
[West  N, Se o n g J, Da vies M . ( 2 0 1 4)] De nti ne h y perse nsiti vit y. M o n o gr Oral Sci 2 0 1 4 ; 2 5: 1 0 8-
1 2 2.  
[West  N X, Se o n g J, Da vies M . ( 2 0 1 5)] Ma n a ge me nt of de nti ne h y perse nsiti vit y: efficac y of 
pr ofessi o nall y a n d self‐a d mi nistere d a ge nts. J Cli n Peri o d o nt ol 2 0 1 5;  4 2:  S 2 5 6 -S 3 0 2.  
[West  N, Da vies M, He T, et al. ( 2 0 1 9)] Effects of bi oa vaila ble S n F 2 de ntifrice o n er osi o n a n d 
se nsiti vit y: meta-a nal ysis ( A bstract # 2 3 2 3). I A D R 2 0 1 9 Va nc o u ver, Ca na d a. 
[West  N X, He T, Z o u Y, et al. ( 2 0 2 1)] Bi oa vaila ble gl uc o nate c helate d sta n n o us fl u ori de 
t o oth paste meta -a nal yses: Effects o n de nti ne h y perse nsiti vit y a n d e na mel er osi o n. J De nt 2 0 2 1; 
1 0 5: 1 0 3 5 6 6.  
[West  N X  ( 2 0 2 2)] P ositi o n pa per b y Pr ofess or Nic ola West o n de nti ne h y perse nsiti vit y i n 
c hil dre n. A vaila ble o n re q uest . 
[W hite  DJ, La wless M, Fata d e A, et al. ( 2 0 0 7)] Sta n n o us fl u ori de/s o di u m he xa meta p h os p hat e 
de ntifrice i ncreases de nti n resista nce t o t u b ule e x p os ure i n vitr o. J Cli n De nt  2 0 0 7 ; 1 8( 2): 5 5-
5 9.  
[Y a n g  S, Yi n g K, Wa n g F, et al. ( 2 0 1 6)] Dese nsitizi n g effect of sta n n o us fl u ori de -c o ntai ni n g 
t o ot h paste f or patie nts wit h de nti ne h y perse nsiti vit y: a m eta-a nal ysis. West C hi na J  St o mat ol; 
3 4( 2): 1 5 0 -1 5 5.  
[Zsis k a  M. 
( 2 0 1 2)] De nti nal t u b ule occl usi o n wit h sta n n o us fl u ori de a n d K N O 3/ Ga ntrez 
de ntifrices. J D e nt Res; 9 1: 7 4 4.  
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 8 9  of 1 1 3  
1 5  
A P P E N DI CI E S  
1 5. 1  
A b br e vi ati o n s  
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y b e use d i n t he pr ot oc ol.  
T a bl e 1 5 -1  
A b br e vi ati o n s  
A b br e vi ati o n  
T er m  
A E  
A d v er s e E v e nt  
B D R  
Bli n d e d D at a R e vi e w  
CI  
C o nfi d e n c e I nt er v al  
C R F  
C a s e R e p ort F or m  
C R S  
Cli ni c al R e s e ar c h S ci e nti st  
C S M  
Cli ni c al St u d y M a n a g er  
C S R  
Cli ni c al St u d y R e p ort  
D H  
D e nti n H y p er s e n siti vit y  
D H E Q  
D e nti n H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e  
E A R  
Er o si o n/ A br a si o n/ Attriti o n  
e C R F  
El e ctr o ni c C a s e R e p ort F or m  
E D C  
El e ctr o ni c D at a C a pt ur e  
E u dr a C T  
E ur o p e a n Cli ni c al Tri al s D at a b a s e  
F D A  
F o o d a n d Dr u g A d mi ni str ati o n (U nit e d St at e s ) 
g  
Gr a m  
G C P  
G o o d Cli ni c al Pr a cti c e  
G D S  
Gl o b al D at a S h e et  
G R A S E  
G e n er all y R e c o g ni z e d a s S af e a n d Eff e cti v e  
G S K C H  
Gl a x o S mit h Kli n e C o n s u m er H e alt h c ar e  
I B 
I n v e sti g at or’ s Br o c h ur e 
I C F 
I nf or m e d C o n s e nt F or m 
I C H 
I nt er n ati o n al C o nf er e n c e o n H ar m o ni s ati o n  
I N D 
I n v e sti g ati o n al N e w Dr u g  
I R B 
I n stit uti o n al R e vi e w B o ar d 
I R T 
I nt er a cti v e R e s p o n s e T e c h n ol o g y 
L M S  
L a b ell e d M a g nit u d e S c al e  
L S L V  
L a st S u bj e ct L a st Vi sit  
M e d D R A  
M e di c al Di cti o n ar y for R e g ul at or y A cti viti e s  
M GI  
M o difi e d Gi n gi v al I n d e x  
mI T T  
M o difi e d I nt e nti o n -t o-Tr e at  
ml  
Millilit er  
m m  
Milli m et er  
M M R M  
Mi x e d M o d el wit h R e p e at e d M e a s ur e s  
M o A  
M o d e of A cti o n  
N/ A  
N ot A p pli c a bl e  
N R S  
N u m eri c R ati n g S c al e  
O Hr Q o L  
Or al H e alt h -R el at e d Q u alit y of Lif e  
O H T  
Or al H ar d Ti s s u e  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 0  of 1 1 3  
A b br e vi ati o n  
T er m  
O S T  
Or al S oft Ti s s u e  
O T C  
O v er -t h e-C o u nt er  
PI  
P er s o n al  I nf or m ati o n 
P P  
P er Pr ot o c ol  
p p m  
P art s p er Milli o n  
P R O  
P ati e nt -R e p ort e d O ut c o m e  
P T  
Pr ef err e d T er m  
Q  
Q u e sti o n  
Q C  
Q u alit y C o ntr ol  
S A E  
S eri o u s A d v er s e E v e nt  
S A P  
St ati sti c al A n al y si s Pl a n  
S D  
St a n d ar d D e vi ati o n  
S E  
St a n d ar d Err or  
S n F 2  
St a n n o u s Fl u ori d e  
S O C  
S y st e m Or g a n Cl a s s  
S O P  
St a n d ar d O p er ati n g Pr o c e d ur e  
T E A E  
Tr e at m e nt E m er g e nt A d v er s e E v e nt  
U S  
U nit e d St at e s  
V A S  
Vi s u al A n al o g u e S c al e  
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 1  of 1 1 3  
1 5. 2  
D e nti n e  H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e (E x a m pl e 
D H E Q -4 8)  
 
S E C TI O N O N E  
 
T he f oll o wi n g q uesti o ns are a b o ut y o ur se nsiti ve teet h, a n d t he i m pact it has o n y o ur e ver y da y life.   
 
 
Fr o m n o w o n i n t his q uesti o n naire we are g oi n g t o call w hat y o u feel as ‘se ns ati o ns i n y o ur teet h’ or 
‘se ns ati o ns’. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 2  of 1 1 3  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 3  of 1 1 3  
T he f oll o wi n g q uesti o ns are a b o ut y o ur se nsiti ve teet h, a n d t he i m pact it has o n y o ur  e ver y da y life. 
 
 
 
 
 
 
 
 
 
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 4  of 1 1 3  
S E C TI O N T W O  
T he  f oll o wi n g q uesti o ns are a b o ut t he w a ys i n w hic h a n y se ns ati o ns i n y o ur teet h affect y o u 
i n y o ur d ail y life. T hi n ki n g a b o ut y o urself over t h e l ast m o nt h  t o w hat e xte nt w o ul d y o u a gree 
or disa gree wit h t he f oll o wi n g state me nts ( Please tic k o nl y o ne res p o nse f or eac h q u esti o n).    
  
Str o n gl y 
a gr e e  
( 7)  
A gr e e  
  
( 6)  
A gr e e a 
littl e  
( 5)  
N eit h er 
a gr e e 
n or  
di s a gr e e  
( 4)  
Di s a gr e e 
a littl e  
( 3)  
Di s a gr e e  
 
( 2)  
Str o n gl y 
di s a gr e e  
( 1)  
1) H a vi n g s e n s ati o n s i n m y t e et h 
t a k e s a l ot of t h e pl e a s ur e o ut of 
e ati n g a n d dri n ki n g.  
  
  
  
  
  
  
  
2) T h er e h a v e b e e n ti m e s w h e n I 
c a n’t fi ni s h m y m e al b e c a u s e of 
t h e s e n s ati o n s.  
  
  
  
  
  
  
  
3) It t a k e s a l o n g ti m e t o fi ni s h 
s o m e f o o d s a n d dri n k s b e c a u s e of 
s e n s ati o n s i n m y t e et h.  
  
  
  
  
  
  
  
4) T h er e h a v e b e e n ti m e s w h e n I 
h a v e h a d pr o bl e m s e ati n g i c e 
cr e a m b e c a u s e of t h e s e 
s e n s ati o n s.  
  
  
  
  
  
  
  
 
T he  f oll o wi n g q uesti o ns are a b o ut t he w a ys i n w hic h t he se ns ati o ns i n y o ur teet h h a ve 
f orce d y o u t o c h a n ge t hi n gs i n y o ur d ail y life. T hi n ki n g a b o ut y o urself over t he l ast m o nt h  
t o w hat e xte nt w o ul d y o u a gree or disa gree wit h t he f oll o wi n g state me nts ( Please tic k o nl y o ne 
res p o nse f or eac h q uesti o n).   
  
Str o n gl y 
a gr e e  
( 7)  
A gr e e  
 
( 6)  
A gr e e a 
littl e  
( 5)  
N eit h er 
a gr e e n or  
di s a gr e e  
( 4)  
Di s a gr e e  
a littl e  
(3)  
Di s a gr e e  
 
( 2)  
Str o n gl y 
di s a gr e e  
( 1)  
5) I h a v e t o c h a n g e t h e w a y I e at 
or dri n k c ert ai n t hi n g s.  
  
  
  
  
  
  
  
6) I h a v e t o b e c ar ef ul h o w I 
br e at h e o n a c ol d d a y.  
  
  
  
  
  
  
  
7) I h a v e t o l e a v e s o m e c ol d 
f o o d s or dri n k s t o w ar m u p 
b ef or e I c a n h a v e t h e m.  
  
  
  
  
  
  
  
8) I h a v e t o c o ol s o m e f o o d s or 
dri n k s d o w n b ef or e I c a n h a v e 
t h e m.  
  
  
  
  
  
  
  
9) I h a v e t o c ut u p s o m e fr uit s 
b ef or e b ei n g a bl e t o e at t h e m.  
  
  
  
  
  
  
  
1 0) I h a v e t o w e ar a s c arf o v er 
m y m o ut h o n c ol d d a y s.  
  
  
  
  
  
  
  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 5  of 1 1 3  
T he  f oll o wi n g q uesti o ns are a b o ut t he t hi n gs y o u d o i n y o ur d ail y life t o a v oi d  e x perie nci n g 
t he se ns ati o ns i n y o ur teet h. T hi n ki n g a b o ut y o urself over t he l ast m o nt h  t o w hat e xte nt 
w o ul d y o u a gree or disa gree wit h t he f oll o wi n g state me nts ( Please tic k o nl y o ne res p o nse f or  
eac h q u esti o n).    
  
Str o n gl y 
a gr e e  
( 7)  
A gr e e  
  
( 6)  
A gr e e a 
littl e  
( 5)  
N eit h er 
a gr e e n or  
di s a gr e e  
( 4)  
Di s a gr e e  
a littl e  
( 3)  
Di s a gr e e  
 
( 2)  
Str o n gl y 
di s a gr e e  
( 1)  
1 1) I h a v e a v oi d e d v er y c ol d 
dri n k s or f o o d s.  
  
  
  
  
  
  
  
1 2) I h a v e a v oi d e d v er y h ot 
dri n k s or f o o d s.  
  
  
  
  
  
  
  
1 3) W h e n e ati n g s o m e f o o d s I 
h a v e m a d e s ur e t h e y d o n’t 
t o u c h c ert ai n t e et h.  
  
  
  
  
  
  
  
1 4) I h a v e c h a n g e d t h e w a y I 
br u s h m y t e et h.  
  
  
  
  
  
  
  
1 5) W h e n e ati n g s o m e f o o d s I 
h a v e m a d e s ur e I bit e i n s m all 
pi e c e s.  
  
  
  
  
  
  
  
1 6) T h er e ar e ot h er f o o d s I 
h a v e a v oi d e d.  
  
  
  
  
  
  
  
  
T he  f oll o wi n g q uesti o ns are a b o ut t he w a y t he se ns ati o ns affect y o u w he n y o u are wit h ot her 
pe o ple or i n cert ai n sit u ati o ns . T hi n ki n g a b o ut y o urself over t he l ast m o nt h  t o w hat e xte nt 
w o ul d y o u a gree or disa gree wit h t he f oll o wi n g state me nts ( Please tic k o nl y o ne res p o nse f or 
eac h q u esti o n).    
  
Str o n gl y 
a gr e e  
( 7)  
A gr e e  
 
( 6)  
A gr e e a 
littl e  
( 5)  
N eit h er 
a gr e e n or  
di s a gr e e  
( 4)  
Di s a gr e e  
a littl e  
( 3)  
Di s a gr e e  
  
( 2)  
Str o n gl y 
di s a gr e e  
( 1)  
1 7) B e c a u s e of t h e s e n s ati o n s I 
t a k e l o n g er t h a n ot h er s t o fi ni s h 
a m e al.  
  
  
  
  
  
  
  
1 8) I h a v e t o b e c ar ef ul w h at I 
e at w h e n I a m wit h ot h er s 
b e c a u s e of t h e s e n s ati o n s i n 
m y t e et h.  
  
  
  
  
  
  
  
1 9) I hi d e t h e w a y I a m e ati n g 
w h e n I a m wit h ot h er s b e c a u s e 
of t h e s e n s ati o n s i n m y t e et h.  
  
  
  
  
  
  
  
2 0) I a m u n a bl e t o f ull y t a k e 
p art i n c o n v er s ati o n s b e c a u s e 
of t h e s e n s ati o n s i n m y t e et h.  
  
  
  
  
  
  
  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 6  of 1 1 3  
2 1) G oi n g t o t h e d e nti st i s h ar d 
f or m e b e c a u s e I k n o w it i s 
g oi n g t o b e p ai nf ul a s a r e s ult 
of s e n s ati o n s i n m y t e et h.  
  
  
  
  
  
  
  
 
T he f oll o wi n g q uesti o ns are a b o ut t he w a y t he se ns ati o ns i n y o ur teet h m a ke y o u feel. 
T hi n ki n g a b o ut y o urself over t he l ast m o nt h  t o w hat e xte nt w o ul d y o u a gree or disa gree wit h 
t he f oll o wi n g state me nts ( Please tic k o nl y o ne res p o nse f or eac h q u esti o n).   
  
Str o n gl y 
a gr e e  
( 7) 
A gr e e  
 
( 6) 
A gr e e a 
littl e 
( 5) 
N eit h er 
a gr e e 
n or  
di s a gr e e  
( 4) 
Di s a gr e e 
a littl e  
( 3) 
Di s a gr e e  
 
( 2) 
Str o n gl y 
di s a gr e e  
( 1) 
2 2) I’ v e b e e n fr u str at e d b e c a u s e I 
c a n’t fi n d a n yt hi n g t h at d e al s wit h 
t h e s e n s ati o n s I h a v e i n m y t e et h.  
  
  
  
  
  
  
  
2 3) I’ v e b e e n a n xi o u s t h at 
s o m et hi n g I e at or dri n k mi g ht 
c a u s e s e n s ati o n s i n m y t e et h.  
  
  
  
  
  
  
  
2 4) T h e s e n s ati o n s i n m y t e et h 
h a v e b e e n irrit ati n g.  
  
  
  
  
  
  
  
2 5) I h a v e b e e n a n n o y e d wit h 
m y s elf b e c a u s e I di d s o m et hi n g 
t h at I k n e w c a u s e d t h e s e 
s e n s ati o n s.  
  
  
  
  
  
  
  
2 6) I f elt g uilt y b e c a u s e I mi g ht 
h a v e c o ntri b ut e d t o t h e s e n s ati o n s 
I a m h a vi n g wit h m y t e et h.  
  
  
  
  
  
  
  
2 7) T h e s e n s ati o n s i n m y t e et h 
h a v e b e e n a n n o yi n g.  
  
  
  
  
  
  
  
2 8) T h e s e n s ati o n s i n m y t e et h 
h a v e b e e n e m b arr a s si n g.  
  
  
  
  
  
  
  
2 9) I h a v e b e e n a n xi o u s b e c a u s e 
of t h e s e n s ati o n s i n m y t e et h.  
  
  
  
  
  
  
  
 
T he f oll o wi n g q uesti o ns are a b o ut w h at t he se ns ati o ns i n y o ur teet h me a n f or y o u.  T hi n ki n g 
a b o ut y o urself over t he l ast m o nt h  t o w hat e xte nt w o ul d y o u a gree or disa gree wit h t he 
f oll o wi n g state me nts ( ple ase tic k o nl y o ne res p o nse f or eac h q u esti o n). 
  
Str o n gl y 
a gr e e  
( 7)  
A gr e e  
 
( 6)  
A gr e e a 
littl e  
( 5)  
N eit h er 
a gr e e n or  
di s a gr e e  
( 4)  
Di s a gr e e  
a littl e  
( 3)  
Di s a gr e e  
 
( 2)  
Str o n gl y 
di s a gr e e  
( 1)  
3 0) I fi n d it diffi c ult t o a c c e pt 
t h at I a m a p er s o n w h o h a s 
t h e s e s e n s ati o n s i n m y t e et h.  
  
  
  
  
  
  
  
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 7  of 1 1 3  
3 1) H a vi n g t h e s e s e n s ati o n s i n 
m y t e et h 
m a k e s 
m e f e el 
diff er e nt fr o m ot h er s.  
  
  
  
  
  
  
  
3 2) H a vi n g t h e s e s e n s ati o n s i n 
m y t e et h m a k e s m e f e el ol d.  
  
  
  
  
  
  
  
3 3) H a vi n g t h e s e s e n s ati o n s i n 
m y t e et h 
m a k e s 
m e f e el 
d a m a g e d.  
  
  
  
  
  
  
  
3 4) H a vi n g t h e s e s e n s ati o n s i n 
m y t e et h m a k e s m e f e el s a s 
t h o u g h I a m u n h e alt h y.  
  
  
  
  
  
  
  
 
 
T he last fi ve q uesti o ns as k a b o ut h o w m uc h t he se ns ati o ns i n y o ur teet h affect  y o ur life 
o ver all .  
  
E x c ell e nt  
( 1)  
V er y  
g o o d  
( 2)  
G o o d   
 ( 3)  
F air  
( 4)  
P o or  
( 5)  
V er y p o or  
( 6)  
3 5) O v er all h o w w o ul d y o u r at e t h e 
h e alt h of y o ur m o ut h, t e et h a n d g u m s ?   
  
  
  
  
  
  
 
 
  
V er y M u c h  
( 4) 
Q uit e a bit  
( 3) 
S o m e w h at  
( 2) 
A littl e  
( 1) 
 
N ot at all  
( 0) 
 
3 6) O v er all h o w m u c h d o t h e s e n s ati o n s i n 
y o ur t e et h b ot h er y o u ?  
  
  
  
  
  
3 7) O v er all, h o w m u c h d o t h e t hi n g s y o u 
d o t o m a n a g e t h e s e n s ati o n s b ot h er y o u ?  
  
  
  
  
  
3 8) O v er all, h o w m u c h d o t h e s e n s ati o n s 
i n y o ur t e et h aff e ct y o ur q u alit y of lif e ?  
  
  
  
  
  
3 9) O v er all, h o w m u c h d o t h e t hi n g s y o u 
d o t o m a n a g e t h e s e n s ati o n s i n y o ur t e et h 
aff e ct y o ur q u alit y of lif e ?   
  
  
  
  
  
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 8  of 1 1 3  
1 5. 3  
L a b ell e d M a g nit u d e S c al e s : I nt e n sit y, D ur ati o n, T ol er a bilit y & 
D e s cri pti o n  ( E x a m pl e L M S s) 
 
N O T T O S C A L E  
 
 
 
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 9 9  of 1 1 3  
 
N O T T O S C A L E  
 
 
 
 
 
 
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 0  of 1 1 3  
1 5. 4  
L M S Tr ai ni n g E x er ci s e ( E x a m pl e) 
 
S T U D Y S T A F F I N S T R U C TI O N S  
S u bjects will be gi ve n a har d c o p y of t h e i nstr ucti o ns f or c o m pleti n g  t he L M Ss; the i n vesti gat or  
(or desi g ne e ) s h o ul d rea d t he ‘ S u bject Instr u cti o ns ’ al o u d w hile t he s u bject rea ds al o n g. 
S u bjects s h o ul d be e nc o ura ge d  t o as k q u esti o ns if t he y are u ns ure a b out a n yt hi n g t he y rea d.   
T he s u bject will t he n c o m plete t he L M S tr ai ni n g e xercise, a n d the i n vesti gat or  (or desi g ne e ) 
will deter mi ne w het her t he s u bject u n dersta n ds h o w t o use t he L M S base d o n t he ir trai ni n g 
e xercis e res p o nses a n d t h e g ui da nce  b el o w.  
 
I nter pret ati o n of t he Li ne Sc ale Tr ai ni n g E xercise  
T he o bjecti ve of t h e trai ni n g  e xercise is N O T t o deter mi ne w het her  t he s u bject ca n pr o vi de 
s pecific ‘c orrect’ a ns wers b ut t o deter mi ne if t he y u n dersta n d t he c o nce pt of L M S c o m pleti o n . 
T he f oll o wi n g ge ner al assess me nt criteria are s u g geste d .  
•  Is t he s u bject placi n g t h eir mar ks o nl y o n t he ver bal descri pt ors? If s o, re mi n d t he m t he y 
s h o ul d use  t he e ntire scale, i ncl u di n g areas of t he li ne bet wee n d escri pt ors.  
•  Is t he s u bject placi n g t heir mar ks i n t he sa me place o n all f o ur L M Ss. If s o, e x plai n 
a gai n t hat eac h L M S  me as ure s a differe nt as p ect of t heir res p o nse  (i nte nsit y, d urati o n, 
t heir a bilit y t o t olerate  it, a n d h o w t he y w o ul d descri be it ) a n d t his li kel y pr o d uce mar ks 
i n differe nt places o n eac h scal e.  
•  T he s u bject s h o ul d i n dicate t heir res p o ns e b y mar ki n g a n ‘X ’ o n t he L M S . If t he y are 
circli n g descri pt ors  or  m a ki n g u nclear mar ks, re mi nd  t he m of t he c orrect w a y t o rec or d 
t heir res p o nse.  
If t he s u bject a p pears u na ble t o c o m plete t he L M S s (i nte nsit y, d urati o n, t olera bilit y a n d 
descri pti o n) wit h a p pr o priate res p o nses, t he i n vesti gat or  ( or d esi g nee ) s h o ul d tal k t hr o u g h t heir 
gra di n g of t he first t w o sce nari os. If t he mar ks are ge nerall y c orrectl y or dere d b ut far fr o m t heir 
li kel y tr ue p ositio ns, as k t he s u bject t o ver balize w h y t he y place d t he mar ks w here  t he y di d. 
H o we ver, t he i n vesti gat or/ desi g nee s h o ul d be caref ul n ot t o press ure t he s u bject t o c ha n ge t h eir 
res p o nses. S tart wit h a n ite m t he s u bject rate d ‘well ’, as k a b o ut t hat, t he n c o ntin ue b y as ki n g 
a b o ut a n ite m w here t he y di d less well.  
If t he i n vesti gat or ( or desi g nee) dee ms a s u bject u n a ble t o pr o vi de a p pr o pri ate  res p o nses t o t he 
L M S trai ni n g q uesti o ns, it is u nli kel y t he y will pr o vi de relia ble L M S res p o nses f oll o wi n g 
a p plicati o n of  t he e v a p orati ve (air) sti m ul us. T he s u bject s h o ul d be wit h dra w n.   
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 1  of 1 1 3  
S U B J E C T I N S T R U C TI O N S  
T he p ur p ose of t his tr ai ni n g e xercise is t o i ntr o d uce y o u t o f o ur differe nt li ne scal es y o u will b e 
as ke d t o us e d uri n g t he st u d y . E ac h o ne h a s differe nt w or ds p ositi o ne d al o n g t he li ne t h at ca n 
be use d t o rate t h e feeli n gs or se nsati o ns pe o ple ca n e x peri e nce  i n t heir m o ut hs.  
T here are n o ri g ht or w r o n g a ns wers.  
R ea d t he descri pti o n of eac h e x a m ple se nsati o n or feeli n g caref ull y , the n tr y t o re me m ber or 
ima gi ne w hat eac h o ne  feels li ke. If y o u ha v e n’t e x perie n ced e x actl y w hat is  descri be d, tr y t o 
t hi n k of s o met hi n g si milar. As y o u t hi n k a b o ut t he e xa m ple, t hi n k a b o ut t he w or d o n t he li ne 
t hat best descri bes w h at t hat se nsati o n feels li ke. Y o u ca n  ‘fi ne t u ne’ y o ur rati n g t o best reflect 
t hat e x peri e nce b y mar ki n g t he li ne b et wee n t hat w or d a n d t he w or d s ne xt t o it, u p or d o w n t he 
scale.  
I N DI C A T E H O W Y O U W O U L D R A T E T H E F E E LI N G D E S C RI B E D B Y P L A CI N G A N 
‘X ’ O N T H E LI N E.  
Y O U C A N  P L A C E Y O U R M A R K A N Y W H E R E  A L O N G T H E LI N E , E X A C T L Y O N A 
D E S C RI P TI V E W O R D O R B E T W E E N W O R D S.  
Ple ase t ur n t o t he ne xt p a ge f or t he fi rst e x a m ple i n t his e xercise.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 2  of 1 1 3  
 
Let ’s start wit h t his e xa m ple.  
T he t o uc h of a pill o n y o ur t o n g ue.  
Ha ve y o u e v er e x perie n ce d t his feeli n g or se nsati o n bef ore?  Yes / N o  ( Ple as e circle o ne) 
First please rate t he I N T E N SI T Y of t his feeli n g or se nsati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o in dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 3  of 1 1 3  
 
Still t hi n ki n g a b o ut t he t o uc h of a pill o n y o ur t o n g ue, please rate t he D U R A TI O N  of t his 
feeli n g or se ns ati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
  
 
N O T T O  S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 4  of 1 1 3  
 
Still t hi n ki n g a b o ut t he t o uc h of a pill o n y o ur t o n g ue, please rat e h o w m uc h y o u are a ble t o 
T O L E R A T E  wit h t his feeli n g or se nsati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 5  of 1 1 3  
 
Fi nall y, still t hi n ki n g a b o ut t he t o uc h of a pill o n y o ur t o n g ue , please gi ve a rati n g t hat 
D E S C RI B E S  t he ki n d of feeli n g or s e nsati o n t his is.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet we e n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 6  of 1 1 3  
 
Let’s tr y t his e xa m ple.  
T he p ai n fr o m biti n g y o ur t o n g ue.  
Ha ve y o u e v er e x perie n ce d t his feeli n g or se nsati o n bef ore? Yes / N o  ( Ple as e circle o ne) 
First please rate t he I N T E N SI T Y of t his feeli n g or se nsati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber , y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 7  of 1 1 3  
 
Still t hi n ki n g a b o ut t he p ai n fr o m biti n g y o ur t o n g ue, please rate t he D U R A TI O N  of t his 
feeli n g or se ns ati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
  
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt  p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 8  of 1 1 3  
 
Still t hi n ki n g a b o ut t he p ai n fr o m biti n g y o ur t o n g ue, please rate h o w m uc h y o u are a ble t o 
T O L E R A T E  wit h t his feeli n g or se nsati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u c a n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
  
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 0 9  of 1 1 3  
 
Fi nall y, still t hi n ki n g a b o ut t he p ai n fr o m biti n g y o ur t o n g ue, please gi ve a rati n g t hat 
D E S C RI B E S  t he ki n d of feeli n g or s e nsati o n t his is.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 1 0  of 1 1 3  
 
Let’s tr y o ne last e x a m ple.  
T he p ai n of a persiste nt t o ot h ac he.  
Ha ve y o u e v er e x perie n ce d t his feeli n g or se nsati o n bef ore? Yes / N o  ( Ple as e circle o ne) 
First please rate t he I N T E N SI T Y of t his feeli n g or se nsati o n.  
Mar k  t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 1 1  of 1 1 3  
 
Still t hi n ki n g a b o ut t he p ai n of a persiste nt t o ot h ac he, pleas e rate t h e D U R A TI O N  of t his 
feeli n g or se ns ati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u  ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 1 2  of 1 1 3  
Still t hi n ki n g a b o ut t he p ai n of a persiste nt t o ot h ac he, pleas e rate h o w m uc h y o u are a ble t o 
T O L E R A T E  wit h t his feeli n g or se nsati o n.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
Ple ase t ur n t o t he ne xt p a ge.  
 
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 1 0 4   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0 . 0 
Pa ge 1 1 3  of 1 1 3  
 
Fi nall y, still t hi n ki n g a b o ut t he p ai n of a persiste nt t o ot h ac he, pleas e gi ve a rati n g t h at 
D E S C RI B E S  t he ki n d of feeli n g or s e nsati o n t his is.  
Mar k t he scale b el o w wit h a n ‘X ’ t o i n dicate t he best descri pti o n of t hat feeli n g or se nsati o n. 
Re me m ber, y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve w or ds.  
 
 
N O T T O S C A L E  
 
 
Y o u h a ve fi nis he d t he tr ai ni n g e xercise a n d are n o w re a d y t o t a ke p art i n t he m ai n p art 
of t he st u d y.  
If y o u h a ve a n y q uesti o ns a b o ut t his tr ai ni n g, ple ase as k t he me m ber of st aff tr ai ni n g y o u.  
If y o u feel t h at y o u u n derst a n d h o w t o use t hese sc ales, ple ase tell t he me m ber of st aff t o o .  
 
T h a n k y o u f or y o ur ti me!  
 
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
C CI


Si g nat ure Pa ge f or  3 0 0 1 0 4 T M F- 2 5 2 7 7 5 v 2. 0
Si g nat ure Pa ge f or T M F- 2 5 2 7 7 5 v 2. 0
Reas o n f or si g ni n g: A p pr o ve d
Na me:
R ole: A p pr o ver
Date of si g nat ure:
G M T + 0 0 0 0
Reas o n f or si g ni n g: A p pr o ve d
Na me:
R ole: A p pr o ver
Date of si g nat ure: 
G M T + 0 0 0 0
Reas o n f or si g ni n g: A p pr o ve d
Na me:
R ole: A p pr o ver
Date of si g nat ure:
G M T + 0 0 0 0
3 0 0 1 0 4 Pr ot oc ol  0 7 Fe b 2 0 2 4 | T M F- 2 5 2 7 7 5 | 2. 0
P P D
P P D
P P D
P P D
P P D
P P D

SAP_001.pdf: 
0. 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
3 0 0 1 0 4  
Pr o p ert y of H al e o n  
C o nfi d e nti al  
M a y n ot b e u s e d, di v ul g e d, p u bli s h e d , or ot h er wi s e di s cl o s e d  
wit h o ut t h e c o n s e nt of H al e o n  
 St ati sti c al A n al y si s P l a n T e m pl at e v 6. 0  
P a g e 1  of 4 8  
S T A TI S TI C A L  A N A L Y SI S P L A N 
A N 8 -W E E K, R A N D O MI Z E D, C O N T R O L L E D, E X A MI N E R -B LI N D, 
C LI NI C A L S T U D Y T O E V A L U A T E T H E E F FI C A C Y O F A S T A N N O U S 
F L U O RI D E T O O T H P A S T E F O R T H E R E LI E F O F D E N TI N 
H Y P E R S E N SI TI VI T Y I N A P O P U L A TI O N O F D E N TI N 
H Y P E R S E N SI TI VI T Y S U F F E R E R S  
Pr ot o c ol N u m b er:  3 0 0 1 0 4  
P h a s e:  
N/ A  
T hi s d o c u m e nt c o nt ai n s c o nfi d e nti alit y st at e m e nt s t h at ar e n ot r el e v a nt f or t hi s 
p u bli cl y a v ail a bl e v er si o n
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D o c u m e nt Hi st or y  
 
D oc u m e nt  
Versi o n D ate  
S u m m ar y of C h a n ges ( Ne w a n al ysis or 
C h a n ge i n pl a n ne d a n al ysis)  
Ori gi nal A nal ysis Pla n  
0 2 -Ma y -2 0 2 4  
N ot a p plica ble ( N/ A)  
 
 
 
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T a bl e of c o nt e nt s  
D oc u me nt Hist or y  ............................................................................................................... 2  
Ta ble of c o nt e nts  ................................................................................................................. 3  
List of Ta bles  ....................................................................................................................... 4  
List of Fi g ures  ...................................................................................................................... 4  
A b bre viati o ns .............................................................................................................................. 5  
1  
S u m mar y of Ke y Pr ot oc ol I nf or mati o n  ............................................................................... 6  
1. 1  
St u d y Desi g n  ............................................................................................................ 7  
1. 2  
St u d y O bjecti ves  .................................................................................................... 1 1  
1. 3  
St u d y Pr o d ucts  ....................................................................................................... 1 2  
1. 4  
Sa m ple Size Calc ulati o n  ........................................................................................ 1 3  
2  
Pla n ne d A nal yses  ............................................................................................................... 1 4  
2. 1  
I nteri m A nal ysis ..................................................................................................... 1 4  
2. 2  
Fi nal A nal yses  ....................................................................................................... 1 4  
3  
C o nsi derati o ns f or Data A nal yses a n d Data Ha n dli n g C o n ve nti o ns  ................................. 1 4  
3. 1  
Baseli ne Defi niti o n  ................................................................................................ 1 4  
3. 2  
S u b gr o u ps/ Stratificati o ns  ....................................................................................... 1 5  
3. 3  
Ce nters  P o ols  ......................................................................................................... 1 5  
3. 4  
Ti me p oi nts a n d Visit Wi n d o ws  ............................................................................. 1 5  
4  
Data A nal ysis  ..................................................................................................................... 1 5  
4. 1  
P o p ulati o ns f or A nal ysis  ........................................................................................ 1 5  
4. 1. 1  
S u bject Dis p ositi o n  ............................................................................... 1 5  
4. 1. 2  
Pr ot oc ol De viati o ns  ............................................................................... 1 6  
4. 1. 3  
A nal ysis P o p ulati o ns  ............................................................................. 1 7  
4. 2  
S u bject De m o gra p hics a n d Ot her Baseli ne C haracteristics  ................................... 1 8  
4. 2. 1  
De m o gra p hic a n d Baseli ne C haracteristics  ........................................... 1 8  
4. 2. 2  
Ge neral Me dical Hist or y  ....................................................................... 1 8  
4. 3  
Treat me nts ( St u d y Pr o d uct, Resc ue Me dicati o n, ot her C o nc o mita nt 
T hera pies, C o m plia nce)  ......................................................................................... 1 8  
4. 3. 1  
St u d y Pr o d uct C o m plia nce a n d E x p os ure  ............................................. 1 8  
4. 3. 2  
Pri or a n d C o nc o mita nt Me dicati o n  ....................................................... 1 9  
4. 4  
A nal ysis of Effic ac y  .............................................................................................. 1 9  
4. 4. 1  
Pri mar y Efficac y E n d p oi nt  .................................................................... 2 0  
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4. 4. 2  
Sec o n dar y Efficac y E n d p oi nts  .............................................................. 2 1  
4. 4. 3  
E x pl orat or y Effi cac y Varia bles  ............................................................. 2 6  
4. 4. 4  
Ha n dli n g of Missi n g Val ues/ Ce ns ori n g/ Disc o nti n uati o ns  .................... 2 9  
4. 5  
A nal ysis of Safet y  .................................................................................................. 2 9  
4. 5. 1  
A d verse E v e nts a n d Seri o us A d verse E v e nts  ........................................ 2 9  
4. 5. 2  
Ot her Safet y V aria bles  .......................................................................... 3 0  
4. 6  
A nal ysis of Ot her V aria bles  ................................................................................... 3 1  
4. 6. 1  
D H E Q -4 8 a n d L M Ss Relati o ns hi p ........................................................ 3 1  
4. 6. 2  
Sc hiff Se nsiti vit y Sc ore a n d L M Ss Relati o ns hi p  .................................. 3 1  
5  
C ha n ges t o t he Pr ot oc ol Defi ne d Statistical A nal ysis Pla n  ............................................... 3 2  
A p pe n di x 1: List of Data Dis pla ys  .................................................................................... 3 3  
 
Li st of T a bl e s  
Ta ble 1 -1  
Sc he d ule of Acti vities  ............................................................................. 8  
Ta ble 1 -2  
St u d y O bjecti ves a n d E n d p oi nts  ........................................................... 1 1  
Ta ble 1 -3  
Accli matizati o n/I n vesti g ati o nal T o ot h pastes  ........................................ 1 3  
 
Li st of F i g ur e s 
Fi g ure 4 -1  
N u merical Rati n g Scale ( 0 t o 1 0)  .......................................................... 2 8  
 
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A b br e vi ati o n s  
 
A b br e vi ati o n  
T er m  
A E  
A d v er s e E v e nt s  
B D R M  
Bli n d e d D at a R e vi e w M e eti n g  
CI s  
C o nfi d e n c e I nt er v al s  
C R F  
C a s e R e p ort F or m  
D H  
D e nti n H y p er s e n siti vit y  
D H E Q  
D e nti n H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e  
E A R  
Er o si o n/ A br a si o n/ R e c e s si o n  
e C R F  
El e ctr o ni c C a s e R e p ort F or m  
I C F 
I nf or m e d C o n s e nt F or m 
L S M  
L a b ell e d M a g nit u d e S c al e  
M e d D R A  
M e di c al Di cti o n ar y f or R e g ul at or y A cti viti e s  
mI T T  
M o difi e d I nt e nt -T o -Tr e at  
M M R M  
Mi x e d M o d el wit h R e p e at e d M e a s ur e s  
N/ A  
N ot A p pli c a bl e  
N R S  
N u m eri c R ati n g S c al e  
O H R Q o L  
Or al h e alt h -r el at e d q u alit y of lif e  
O H T  
Or al H ar d Ti s s u e  
O S T  
Or al S oft Ti s s u e  
P P  
P er -Pr ot o c ol  
P T  
Pr ef err e d T er m  
S A E  
S eri o u s A d v er s e E v e nt s  
S A P  
St ati sti c al A n al y si s Pl a n  
S D  
St a n d ar d D e vi ati o n  
S E  
St a n d ar d Err or  
S n F 2  
St a n n o u s Fl u ori d e  
S O C  
S y st e m Or g a n Cl a s s  
T E A E s  
Tr e at m e nt E m er g e nt A d v er s e E v e nt s  
W H O D D  
W orl d H e alt h Or g a ni z ati o n Dr u g Di cti o n ar y  
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T he p ur p ose of t his Statistical A nal ysis Pla n  ( S A P) is t o descri be t he pla n ne d a nal yses a n d 
o ut p ut s t o be i ncl u de d i n t he Cli nical St u d y Re p ort f or Pr ot oc ol 3 0 0 1 0 4  (versi o n 2 .0 , date d 
0 7 -Fe b -2 0 2 4 ). 
1  
S u m m ar y of K e y Pr ot o c ol I nf or m ati o n  
T he p ur p ose of t his trial is t o e val uate t he a nti -se nsiti vit y efficac y of a sta n n o us fl u ori de 
t o ot h paste i n a p o p ulati o n of D e nti n H y perse nsiti vit y ( D H) s ufferers. T he cli nical efficac y of 
t he 0. 4 5 4 % Sta n n o us Fl u ori de ( S n F 2) t o ot h paste will be c o m pare d wit h t hat of a re g ular fl u ori de 
t o ot h paste wit h n o k n o w n a nti-se nsiti vit y efficac y ( ne gati ve c o ntr ol). T he st u d y will f oll o w a 
si n gle ce nter, 8-wee k, ra n d o mize d, c o ntr olle d, e xa mi ner -bli n d, 2 -treat me nt ar m, parallel 
desi g n, stratifie d ( b y ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore of t he t w o selecte d ‘ Test 
Teet h’) cli nical st u d y t o e val uate t he a nti -se nsiti vit y efficac y of a 0. 4 54 % S n F 2 t o ot h paste i n a 
D H p o p ulati o n. T he cli nical efficac y of t he 0. 4 5 4 % S n F 2 t o ot h paste ( Test T o ot hpaste) will be 
c o m pare d wit h t hat of a Refere nce T o ot h paste, a c o m merciall y a vaila ble, re g ular fl u ori d e 
t o ot h paste wit h n o k n o w n a nti-se nsiti vit y pr o perties ( ne gati ve c o ntr ol).  
At Scree ni n g ( Visit 1), f oll o wi n g pr o visi o n of writte n Inf or me d C o nse nt  F or m (I C F) , s uita bilit y 
t o partici pate will be re vie we d a g ai nst t he pr ot oc ol i ncl usi o n/e xcl usi o n criteria. Eli gi ble 
s u bjects will e nter a n accli matizati o n peri o d ( 1 4-2 8 da ys) pri or t o Baseli ne assess me nts d uri n g 
w hic h t he y will br us h t wice dail y ( m or ni n g a n d e ve ni n g ) wit h t he accli matizati o n t o ot h paste (a 
differe nt c o m merciall y a vaila ble, re g ular fl u ori de t o ot h paste fr o m t he Refere nce T o ot h paste). 
At Baseli ne ( Visit 2), eli gi bilit y t o c o nti n ue will be assesse d. S u bjects w h o de m o nstrate t h e 
re q uire d q ualif yi n g le vels of D H at Scree ni n g ( Visit 1) a n d Baseli ne ( Visit 2) will b e 
ra n d o mize d t o st u d y treat me nt a n d i nstr ucte d t o br us h wit h t heir assi g ne d i n vesti gati o nal 
t o ot h paste t wice dail y (m or ni n g a n d e ve ni n g) f or t he d urati o n of t he 8 -wee k treat me nt peri o d.  
D H will be assesse d at Scree ni n g ( Visit 1) a n d Baseli ne ( Visit 2), a n d after 2 8 - a n d 5 6-da ys 
treat me nt ( Visits 3 a n d 4, res pecti vel y) usi n g t w o i n de pe n de nt cli nical meas ures: (i) tactile 
t hres h ol d ( g) f oll o wi n g a tactile sti m ul us a n d (ii) Sc hiff s e nsiti vity sc ore f oll o wi n g a n 
e va p orati ve (air) sti m ul us.  
Oral h ealt h -rel ate d q u alit y of life ( O H R Q o L) will be m o nit ore d o v er t h e treat me nt peri o d usi n g 
t he De nti n H y p erse nsiti vit y E x perie nce Q uesti o n naire ( D H E Q-4 8), c o m plete d b y st u d y 
s u bjects at Baseli ne ( Visit 2), a n d after 2 8- a n d 5 6 -da ys treat me nt ( Visits 3 a n d 4, res pecti vel y). 
S u bject -percei ve d D H will als o be i n v esti gate d acr oss t he 8 -wee k treat me nt peri o d usi n g f o ur 
La belle d 
Ma g nit u de Scales ( L M Ss) t o ca pt ure t he I nte nsit y, D urati o n, T olera bilit y a n d 
Descri pti o n of t h eir res p o nse t o t he e v a p orati ve (air) sti m ul us. At t he fi nal visit ( Da y 5 6), 
s u bjects will rate t heir le vel of satisfacti o n wit h t heir assi g ne d i n vesti gati o nal t o ot h paste f or t he 
o verall ma na g e me nt of t heir D H, usi n g a N u meri c Rati n g Scale ( N R S).  
Safet y a n d oral t olera bilit y of t he i n vesti gati o nal t o ot h pastes will be m o nit or e d o ver t he 8 -wee k 
usa ge peri o d b y re vie w of treat me nt e mer ge nt a d verse e v e nts ( T E A Es).  
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1. 1  
St u d y D e si g n  
T his will be a si n gle ce nt er, 8 -wee k, ra n d o mize d, c o ntr olle d, e x a mi ner-bli n d, 2 -treat me nt ar m, 
parallel gr o u p, stratifie d st u d y i n healt h y s u bjects wit h D H. S u bjects w h o meet t he re q uire d 
st u d y criteria at Scree ni n g a n d Baseli ne will be ra n d o mize d t o o ne of t w o st u d y treat me nts: 
0. 4 5 4 % S n F 2 t o ot h paste ( Test T o ot h paste) or a re g ular fl u ori de t o ot h paste ( Refere n ce 
T o ot h paste)  
T w o i n de pe n d e nt sti m ul us -base d cli nical meas ures will be e m pl o ye d t o assess t he efficac y of 
t he i n vesti gati o nal t o ot h pastes.  
•  A tactile sti m ul us will be a d mi nistere d usi n g a c o nsta nt press ure pr o be - Yea ple Pr o be 
( P ols o n, 1 9 8 0); s u bject res p o nse t o t he sti m ul us deter mi nes t he tactile t hres h ol d i n gra ms 
( g).  
•  A n e va p orati ve (air) sti m ul us (i.e., a t her mal sti m ul us) will be a d mi nistere d usi n g a de ntal 
air s yri n ge; s u bject r es p o nse t o t he sti m ul us will be e xa mi ner -e v al uate d usi n g t he Sc hiff 
se nsiti vit y scale ( Sc hiff, 1 9 9 4). 
D H will be assesse d at S cree ni n g, Da y 0 ( Bas eli ne), Da y 2 8 ( Wee k 4) a n d Da y 5 6 ( Wee k 8). 
O n c o m pleti o n of t he Baseli ne assess me nts, t he cli nical e xa mi ner will select t w o ‘ Test T eet h’ 
f or assess me nt of tactile a n d e va p orati ve (air) s e nsiti vit y at all s u bse que nt visits. T o q ualif y f or 
selecti o n as a ‘ Test T o ot h’, t he t o ot h m ust meet t he pr ot oc ol-s pecific i ncl usi o n/e xcl usi o n 
criteria ( Secti o n 5. 2 I n cl usi o n Criteria 6 & 7; Secti o n 5. 3 E xcl usi o n Criteri o n 2 6  of pr ot oc ol ), 
s pecificall y ta ctile t hres h ol d ≤ 2 0 g a n d Sc hiff s e nsiti vit y sc ore ≥ 2 at b ot h Scree ni n g a n d 
Baseli ne visits. I n a d diti o n, t he n u m ber of ‘ Se nsiti ve Teet h’ will be d eter mi ne d at eac h st u d y 
visit ( Sc hiff se nsiti vit y sc ore ≥ 2) as des cri be d i n Secti o ns 8. 1. 5, 8. 2. 1. 5, 8. 2. 2. 5 a n d 8. 2. 3. 5  of 
t he pr ot oc ol.  
A p pr o xi matel y 1 1 0 q ualif yi n g s u bjects will be stratifie d acc or di n g t o t he ma xi m u m Baseli ne 
Sc hiff se nsiti vit y sc ore of t heir t w o ‘ Test Teet h’ a n d ra n d o mize d t o tr eat me nt (a p pr o xi matel y 
5 5 s u bjects per treat me nt gr o u p). Ra n d o mize d s u bjects will be i nstr ucte d t o br us h t wice dail y 
( m or ni n g a n d e ve ni n g) wit h t heir assi g ne d i n vesti gati o nal t o ot h paste f or t he ne xt 5 6 da ys ( 8 
wee ks) a n d rec or d eac h br us hi n g i n t he diar y pr o vi de d. First use will be perf or me d u n der 
s u per visi o n at t he i n vesti gat or site; t o facilitate c o m plia nce a n a d diti o nal s u per vise d o n -site 
br us hi n g will be c o m plete d at t he e n d of Visit 3.  
C ha n ges i n O H R Q o L will be m o nit ore d o ver t he treat me nt peri o d usi n g t he vali date d D H E Q -
4 8. T he D H E Q -4 8 will be c o m plete d b y st u d y s u bjects at Baseli ne, a n d after 2 8 - a n d 5 6-d a ys 
treat me nt. S u bject-percei ve d D H will als o be i n v esti gate d f or t he t w o s electe d  ‘ Test Teet h’ 
usi n g L M Ss. S u bjects will c o m plete f o ur L M Ss t o ca pt ur e t he I nte nsit y, D urati o n, T olera bilit y 
a n d Descri pti o n of t heir res p o nse t o t he e va p orati ve (air) sti m ul us a d mi nistere d at Bas eli ne, 
Da y 2 8 a n d D a y 5 6. At t he fi nal visit ( Da y 5 6), after all cli nical pr oce d ures h a ve b ee n 
c o m plete d, s u bjects will rate t heir le vel of s atisfacti o n wit h t heir assi g ne d i n vesti gati o nal 
t o ot h paste f or t he o verall ma na ge me nt of D H usi n g a n N R S.  
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T o sta n dar dize oral h y gi e ne practice i n t he st u d y p o p ulati o n pri or t o treat me nt a n d t o hel p 
mi ni mize t he p ote ntial i m pact of ‘ place b o’/‘ n o treat me nt’ effects, eli gi ble s u bjects will 
c o m plete a n accli matizati o n peri o d ( 1 4 -2 8 da ys d urati o n) bet wee n t he Scree ni n g a n d Baseli n e 
visits d uri n g w hic h t he y will br us h t wice dail y ( m or ni n g a n d e ve ni n g) wit h a re g ular fl u ori de 
t o ot h paste (a differe nt c o m merciall y a vaila ble pr o d uct fr o m t he Refere nce T o ot h paste). First 
use of accli matizati o n t o ot h paste will be perf or me d  u n der s u per visi o n at t he i n vesti gat or site.  
Safet y a n d oral t olera bilit y of t he i n vesti gati o nal t o ot h pastes will be m o nit ore d o ver t he 
treat me nt peri o d b y r e vie w of T E A Es. 
Ta ble 1 -1  prese nts t he sc he d ule of acti vities.  
T a bl e 1 -1  
S c h e d ul e of A cti viti e s  
 
Pr o c e d ur e/ A s s e s s m e nt  
St u d y Vi sit s  
Vi sit 1  
S cr e e ni n g  
 
Vi sit 2  
D a y 0  
B a s eli n e  
Vi sit 3  
D a y 2 8  
( ± 2 
d a y s)  
Vi sit 4  
D a y 
5 6  ( ± 
3 
d a y s)  
I nf or m e d c o n s e nt 
x  
A c cli m ati z ati o n P eri o d ( 1 4 -2 8 d a y s)  
 
 
 
D e m o gr a p hi c s  
x  
 
 
 
R e vi e w S u bj e ct’ s Or al C ar e Pr o d u ct s  
x  
 
 
 
R e vi e w M e di c al Hi st or y & C urr e nt/ Pri or 
C o n c o mit a nt M e di c ati o n/ Tr e at m e nt 1  
x  
 
 
 
R e vi e w C h a n g e s i n H e alt h & 
M e di c ati o n s/ Tr e at m e nt s
1  
 
x  
x  
x  
R et ur n A c cli m ati z ati o n T o ot h p a st e, T o ot h br u s h & 
Di ar y 2  
 
x  
 
 
R et ur n I n v e sti g ati o n al T o ot h p a st e, T o ot h br u s h & 
Di ar y 2  
 
 
 
x  
C o m pli a n c e C h e c k s 2  
 
x  
x  
x  
S u bj e ct -C o m pl et e d D H E Q 3  
 
x  
x  
x  
S u bj e ct -C o m pl et e d L M S Tr ai ni n g E x er ci s e  
x  
 
 
 
Or al S oft Ti s s u e ( O S T) E x a mi n ati o n  
x  
x  
x  
x  
Or al H ar d Ti s s u e ( O H T) E x a mi n ati o n  
x  
 
 
x  
Eli gi bl e T e et h A s s e s s m e nt s ( D e ntiti o n 
E x cl u si o n s, Er o si o n/ A br a si o n/ R e c e s si o n [ E A R], 
M o difi e d Gi n gi v al I n d e x [ M GI], T o ot h M o bilit y)  
x  
 
 
 
Q u alif yi n g Cli ni c al A s s e s s m e nt of T a ctil e 
S e n siti vit y 4  
x  
x  
 
 
Q u alif yi n g Cli ni c al A s s e s s m e nt of E v a p or ati v e 
( Air) S e n siti vit y ( S c hiff s e n siti vit y s c or e)5  
x  
x  
 
 
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Pr o c e d ur e/ A s s e s s m e nt  
St u d y Vi sit s  
Vi sit 1  
S cr e e ni n g  
 
Vi sit 2  
D a y 0  
B a s eli n e  
Vi sit 3  
D a y 2 8  
( ± 2 
d a y s)  
Vi sit 4  
D a y 
5 6  ( ± 
3 
d a y s)  
S u bj e ct -P er c ei v e d E v a p or ati v e ( Air) S e n siti vit y 
( L M S s)6  
 
x  
 
 
Cli ni c al A s s e s s m e nt of E v a p or ati v e ( Air) 
S e n siti vit y of t h e R e m ai ni n g ‘ Eli gi bl e T e et h’ 
I d e ntifi e d at S cr e e ni n g5  
 
x  
 
 
Cli ni c al E x a mi n er S el e ct s T w o ‘ T e st T e et h’ 
( Q u alif yi n g S u bj e ct s O nl y)7  
 
x  
 
 
R e vi e w I n cl u si o n/ E x cl u si o n Crit eri a  
x  
x  
 
 
C o nfir m S u bj e ct Eli gi bilit y/ Q u alifi c ati o n  
x  
x  
 
 
Di s p e n s e A c cli m ati z ati o n T o ot h p a st e, 
T o ot h br u s h, Ti m er, Ri n si n g C u p s & Di ar y  
x  
 
 
 
S u p er vi s e d Br u s hi n g wit h A c cli m ati z ati o n 
T o ot h p a st e  
x  
 
 
 
Str atifi c ati o n/ R a n d o mi z ati o n  
 
x  
 
 
Di s p e n s e I n v e sti g ati o n al T o ot h p a st e, 
T o ot h br u s h, Ri n si n g C u p s & Di ar y  
 
x  
x 8  
 
S u p er vi s e d Br u s hi n g wit h I n v e sti g ati o n al 
T o ot h p a st e  
 
x  
 
 
Cli ni c al A s s e s s m e nt of T a ctil e S e n siti vit y: T w o 
‘ T e st T e et h’ o nl y4  
 
 
x  
x  
Cli ni c al A s s e s s m e nt of E v a p or ati v e ( Air) 
S e n siti vit y ( S c hiff s e n siti vit y s c or e) :  
A s s e s s t h e T w o ‘ T e st T e et h’ Fir st, t h e n t h e 
R e m ai ni n g ‘ Eli gi bl e T e et h’ I d e ntifi e d at 
S cr e e ni n g 5  
 
 
x  
x  
S u bj e ct -P er c ei v e d E v a p or ati v e ( Air) S e n siti vit y 
( L M S s): T w o ‘ T e st T e et h’ O nl y6  
 
 
x  
x  
S u p er vi s e d Br u s hi n g wit h I n v e sti g ati o n al 
T o ot h p a st e  
 
 
x  
 
S ati sf a cti o n wit h Tr e at m e nt: S u bj e ct -C o m pl et e d 
N R S  
 
 
 
x  
St u d y C o n cl u si o n  
 
 
 
x  
M o nit or A d v er s e E v e nt s ( A E s) a n d M e di c al 
D e vi c e I n ci d e nt s 9  
x  
x  
x  
x  
A E: A d v er s e E v e nt; D H E Q: D e nti n H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e ; E A R: Er o si o n/ A br a si o n/ 
R e c e s si o n ; L M S: L a b ell e d M a g nit u d e S c al e s ; MGI: M o difi e d Gi n gi v al I n d e x ; O H T: Or al H ar d Ti s s u e ; 
O S T: Or al S oft Ti s s u e . 
F o ot n ot e s:  
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1. F e m al e s u bj e ct s of c hil d -b e ari n g  p ot e nti al s h o ul d b e a s k e d t o c o nfir m pr e g n a n c y st at u s at e a c h   
    vi sit . 
 
2.  S u bj e ct s will b e r e q uir e d t o bri n g t h eir st u d y s u p pli e s ( mi n u s ti m er & ri n si n g c u p s) t o e v er y vi sit.  
    P erf or m vi s u al c h e c k of r et ur n e d st u d y s u p pli e s, r e vi e w di ar y & e v al u at e c o m pli a n c e.  
    Vi sit 2 : C h e c k c o m pli a n c e wit h u s e of a c cli m ati z ati o n t o ot h p a st e.  
    Vi sit 3 & Vi sit  4 : C h e c k c o m pli a n c e wit h u s e of i n v e sti g ati o n al t o ot h p a st e.  
    Vi sit s 2 -4 : C h e c k c o m pli a n c e wit h Lif e st yl e G ui d eli n e s/ M e di c ati o n r e q uir e m e nt s.  
3. D H E Q -4 8  m u st b e c o m pl et e d pri or t o t h e O S T e x a mi n ati o n a n d cli ni c al a s s e s s m e nt s.  
    Vi sit 2 : C o m pl et e all q u e sti o n s.  
    Vi sit s 3 & 4 : C o m pl et e S e cti o n 1, Q u e sti o n s 7 -9 & S e cti o n 2, all q u e sti o n s.  
4. T a ctil e T hr e s h ol d A s s e s s m e nt s: Vi sit s 1 -2:  M a xi m u m f or c e 2 0 g ( S cr e e ni n g a n d B a s eli n e);  
    Vi sit s 3 -7:  M a xi m u m f or c e 8 0 g.  
5. E v a p or ati v e ( air) s e n siti vit y ( S c hiff s e n siti vit y s c or e) s h o ul d b e a s s e s s e d aft er t a ctil e s e n siti vit y,    
    e n s ur e mi ni m u m 5 -mi n ut e d el a y aft er t h e l a st t a ctil e a s s e s s m e nt b ef or e t h e fir st e v a p or ati v e ( air)    
    a s s e s s m e nt f or t o ot h r e c o v er y.  
    Vi sit 1 ( S cr e e ni n g): A s s e s s e v a p or ati v e ( air) s e n siti vit y f or all t e et h wit h a S cr e e ni n g t a ctil e    
    t hr e s h ol d ≤ 2 0 g.  
    Vi sit 2  ( B a s eli n e): Fir st a s s e s s e v a p or ati v e ( air) s e n siti vit y f or all ‘ Eli gi bl e T e et h’ i d e ntifi e d at    
    S cr e e ni n g wit h a B a s eli n e t a ctil e t hr e s h ol d of ≤ 2 0 g, t h e n a s s e s s t h e r e m ai ni n g ‘ Eli gi bl e T e et h’ (i. e.,    
    t h e r e m ai ni n g t e et h fr o m t h e p o ol of ‘ Eli gi bl e T e et h’ i d e ntifi e d at S cr e e ni n g, wit h a B a s eli n e t a ctil e   
    t hr e s h ol d > 2 0 g).  
    Vi sit 3  ( D a y 2 8) & Vi sit 4  ( D a y 5 6): Fir st a s s e s s e v a p or ati v e ( air) s e n siti vit y f or t h e t w o ‘ T e st T e et h’    
    fir st, t h e n a s s e s s t h e r e m ai ni n g ‘ Eli gi bl e T e et h’ i d e ntifi e d at S cr e e ni n g ( e x cl u di n g t h e t w o ‘ T e st    
    T e et h’). ‘ Eli gi bl e T e et h’ = T e et h wit h n o d e ntiti o n e x cl u si o n s w hi c h m et E A R, M GI & m o bilit y crit eri a,    
    wit h S cr e e ni n g t a ctil e t hr e s h ol d ≤ 2 0 g & S cr e e ni n g S c hiff s e n siti vit y s c or e ≥ 2.  
6. Vi sit 2  ( B a s eli n e): C o m pl et e 4 L M S s (I nt e n sit y, D ur ati o n, T ol er a bilit y & D e s cri pti o n) f or e a c h t o ot h   
   wit h a B a s eli n e S c hiff s e n siti vit y s c or e ≥ 2 o nl y, i m m e di at el y aft er t h e B a s eli n e S c hiff s e n siti vit y   
   s c or e h a s b e e n r e c or d e d f or t h at t o ot h.  
   Vi sit 3  ( D a y 2 8) & Vi sit 4  ( D a y 5 6): C o m pl et e 4 L M S s  f or e a c h ‘ T e st T o ot h’, i m m e di at el y aft er it s    
   S c hiff s e n siti vit y s c or e h a s b e e n r e c or d e d.  
7. S el e ct e d ‘ T e st T e et h’ s h o ul d b e i n diff er e nt q u a dr a nt s, wit h t h e r e q ui sit e q u alif yi n g l e v el s of D H at     
    b ot h S cr e e ni n g ( Vi sit 1) a n d B a s eli n e ( Vi sit 2),  i. e., t a ctil e t hr e s h ol d ≤ 2 0 g a n d S c hiff s e n siti vit y    
    s c or e ≥ 2.  
8. Vi sit 3 : S u p pl y n e w di ar y o nl y.  
9. A E s, a n d t h er ef or e all s eri o u s a d v er s e e v e nt s ( S A E s) will b e r e c or d e d fr o m i m m e di at el y aft er  I C F    
   u ntil 5 d a y s aft er t h e l a st u s e of i n v e sti g ati o n al t o ot h p a st e. I n ci d e nt s will b e r e c or d e d fr o m fir st t o l a st    
   u s e of t h e m e di c al d e vi c e (t h e m a n u al t o ot h br u s h u s e d t o a p pl y t h e a c cli m ati z ati o n a n d    
    i n v e sti g ati o n al t o ot h p a st e s). 
 
 
 
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1. 2  
St u d y O bj e cti v e s  
St u d y o bjecti ves a n d e n d p oi nts are defi ne d i n  T a ble 1 -2 : 
T a bl e 1 -2  
St u d y O bj e cti v e s a n d E n d p oi nt s  
O bj e cti v e s  
E n d p oi nt s  
Effi c a c y  
Pri m ar y  
T o d e m o n str at e t h e cli ni c al effi c a c y of a 
0. 4 5 4 % w/ w S n F 2  t o ot h p a st e i n r e d u ci n g D H 
t o a n e v a p or ati v e ( air) sti m ul u s ( a s m e a s ur e d 
b y S c hiff s e n siti vit y s c or e), c o m p ar e d t o a 
n e g ati v e c o ntr ol t o ot h p a st e, aft er 8 w e e k s 
t wi c e d ail y u s e. 
C h a n g e fr o m B a s eli n e i n S c hiff s e n siti vit y s c or e 
at D a y 5 6 ( W e e k 8).  
S e c o n d ar y  
T o d e m o n str at e t h e cli ni c al effi c a c y of a 
0. 4 5 4 % w/ w S n F 2  t o ot h p a st e i n r e d u ci n g D H 
t o a t a ctil e sti m ul u s ( a s m e a s ur e d b y t a ctil e 
t hr e s h ol d i n gr a m s [ g]), c o m p ar e d t o a 
n e g ati v e c o ntr ol t o ot h p a st e, aft er 8 w e e k s 
t wi c e d ail y u s e.  
C h a n g e fr o m B a s eli n e i n t a ctil e t hr e s h ol d ( g) at 
D a y 5 6 ( W e e k 8).  
T o d e m o n str at e t h e cli ni c al effi c a c y of a 
0. 4 5 4 % w/ w S n F 2  t o ot h p a st e i n r e d u ci n g D H 
t o e v a p or ati v e ( air) a n d t a ctil e sti m uli ( a s 
m e a s ur e d b y S c hiff s e n siti vit y s c or e a n d 
t a ctil e t hr e s h ol d ( g), r e s p e cti v el y), c o m p ar e d 
t o a n e g ati v e c o ntr ol t o ot h p a st e, aft er 4 
w e e k s t wi c e d ail y u s e.  
C h a n g e fr o m B a s eli n e i n S c hiff s e n siti vit y s c or e 
at D a y 2 8 ( W e e k 4).  
 
C h a n g e fr o m B a s eli n e i n t a ctil e t hr e s h ol d ( g) at 
D a y 2 8 ( W e e k 4).  
T o d e s cri b e s u bj e ct -p er c ei v e d c h a n g e s i n 
or al h e alt h -r el at e d q u alit y of lif e ( O Hr Q o L), 
a s m e a s ur e d b y t h e D e nti n H y p er s e n siti vit y 
E x p eri e n c e Q u e sti o n n air e ( D H E Q -4 8), aft er 
4 - a n d 8 -w e e k s t wi c e d ail y u s e of t h eir 
a s si g n e d i n v e sti g ati o n al t o ot h p a st e . 
At D a y 2 8 ( W e e k 4) & D a y 5 6 ( W e e k 8):  
C h a n g e fr o m B a s eli n e i n D H E Q -4 8 e n d p oi nt s.  
S e cti o n 1  
•  
I m p a ct o n E v er y d a y Lif e ( Q 7-9)  
S e cti o n 2  
•  
T ot al S c or e ( Q 1 -3 4)  
•  
I n di vi d u al D o m ai n S c or e s 
 
o  
R e stri cti o n s ( Q 1 -4)  
o  
A d a pt ati o n ( Q 5 -1 6)  
o  
S o ci al I m p a ct ( Q 1 7 -2 1)  
o  
E m oti o n al I m p a ct ( Q 2 2 -2 9)  
o  
I d e ntit y ( Q 3 0-3 4)  
•  
Gl o b al Or al H e alt h S c or e ( Q 3 5)  
•  
Eff e ct o n Lif e O v er all S c or e ( Q 3 6 -3 9)  
E x pl or at or y  
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O bj e cti v e s  
E n d p oi nt s  
Effi c a c y  
T o d et er mi n e t h e n u m b er of ‘ S e n siti v e T e et h’ 
( e v a p or ati v e ( air) s e n siti vit y o nl y) i n t h e p o ol 
of ‘ Eli gi bl e T e et h’ i d e ntifi e d at S cr e e ni n g, 
B a s eli n e, a n d aft er 4 a n d 8 w e e k s t wi c e d ail y 
u s e of a s si g n e d i n v e sti g ati o n al t o ot h p a st e.  
At S cr e e ni n g, B a s eli n e, D a y 2 8 ( W e e k 4) & D a y 
5 6 ( W e e k 8):  
N u m b er of ‘ S e n siti v e T e et h’  
D efi n e d a s t h e n u m b er of ‘ Eli gi bl e T e et h’ (i d e ntifi e d at 
S cr e e ni n g) wit h a S c hiff S e n siti vit y S c or e ≥ 2.  
T o i n v e sti g at e s u bj e ct -p er c ei v e d c h a n g e s i n 
D H t o a n e v a p or ati v e ( air) sti m ul u s, a s 
m e a s ur e d b y L a b ell e d M a g nit u d e S c al e s 
( L M S s), aft er 4 a n d 8 w e e k s t wi c e d ail y u s e 
of t h eir a s si g n e d i n v e sti g ati o n al t o ot h p a st e.  
At D a y 2 8 ( W e e k 4) & D a y 5 6 ( W e e k 8):  
C h a n g e fr o m B a s eli n e i n L M S e n d p oi nt s.  
•  
I nt e n sit y  
•  
D ur ati o n  
•  
T ol er a bilit y  
•  
D e s cri pti o n  
T o i n v e sti g at e t h e r el ati o n s hi p b et w e e n 
s u bj e ct r e s p o n s e s t o t h e D H E Q -4 8 a n d t h e 
L M S s at B a s eli n e, a n d aft er 4 a n d 8 w e e k s 
t wi c e d ail y u s e of a s si g n e d i n v e sti g ati o n al 
t o ot h p a st e.  
At B a s eli n e, D a y 2 8 ( W e e k 4) & D a y 5 6 ( W e e k 
8):  
D H E Q -4 8 e n d p oi nt s, a s li st e d a b o v e.  
L M S e n d p oi nt s, a s li st e d a b o v e.  
T o i n v e sti g at e t h e r el ati o n s hi p b et w e e n t h e 
S c hiff s e n siti vit y s c al e a n d t h e L M S s at 
B a s eli n e, a n d aft er 4 a n d 8 w e e k s t wi c e d ail y 
u s e of a s si g n e d i n v e sti g ati o n al t o ot h p a st e.  
At B a s eli n e, D a y 2 8 ( W e e k 4) & D a y 5 6 ( W e e k 
8):  
M e a n S c hiff s e n siti vit y s c or e of t h e t w o ‘ T e st 
T e et h’.  
L M S e n d p oi nt s, a s li st e d a b o v e.  
T o i n v e sti g at e s u bj e ct s ati sf a cti o n wit h t h eir 
a s si g n e d i n v e sti g ati o n al t o ot h p a st e f or t h e 
o v er all m a n a g e m e nt of D H, a s m e a s ur e d b y 
a N u m eri c R ati n g S c al e ( N R S), aft er 8 w e e k s 
tr e at m e nt.  
At D a y 5 6 ( W e e k 8):  
S ati sf a cti o n N R S s c or e  
S af et y  
T o m o nit or t h e s af et y a n d or al t ol er a bilit y of 
t h e i n v e sti g ati o n al t o ot h p a st e s o v er 8 w e e k s 
t wi c e d ail y u s e.  
Tr e at m e nt e m er g e nt a d v er s e e v e nt s ( T E A E s).  
T his st u d y will be c o nsi dere d s uccessf ul if t he 0. 4 5 4 % S n F 2 t o ot h paste de m o nstrates 
statisticall y si g nifica nt, s u peri or a nti-h y perse nsiti vit y efficac y, c o m pare d t o t he ne gati ve c o ntr ol 
t o ot h paste, as meas ur e d b y Sc hiff se nsiti vit y sc ore at Da y 5 6 ( Wee k 8).  
1. 3  
St u d y Pr o d u ct s  
Ta ble 1 -3  pr e s e nt s t h e st u d y pr o d u ct s . 
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T a bl e 1 -3  
A c cli m ati z ati o n/I n v e sti g ati o n al T o ot h p a st e s  
D e s cri pti o n  
A c cli m ati z ati o n 
T o ot h p a st e  
T e st T o ot h p a st e  
R ef er e n c e 
T o ot h p a st e ( N e g ati v e 
C o ntr ol)  
Pr o d u ct N a m e  
R e g ul ar fl u ori d e 
t o ot h p a st e 
( C ol g at e C a vit y 
Pr ot e cti o n 1 ) 
0. 4 5 4 % w/ w S n F 2 
t o ot h paste 
R e g ul ar fl u ori d e 
t o ot h p a st e 
( Cr e st C a vit y 
Pr ot e cti o n 1 ) 
Fl u ori d e L e v el  
1 0 0 0 p p m fl u ori d e 2  
1 1 0 0  p p m fl u ori d e 3  
1 1 0 0 p p m fl u ori d e 4  
M a st er F or m ul ati o n 
C o d e ( M F C)  
N/ A  
 
N/ A  
Di s p e n si n g D et ail s  
O n e c art o n c o nt ai ni n g 
2 t u b e s of t o ot h p a st e 
at S cr e e ni n g ( Vi sit 1)  
O n e c art o n c o nt ai ni n g 4 o v er -wr a p p e d t u b e s of 
t o ot h p a st e at B a s eli n e ( Vi sit 2) 
R o ut e of 
A d mi ni str ati o n  
T o pi c al Or al U s e  
T o ot h p a st e  
U s a g e  
I n str u cti o n s 
D o s e t h e t o ot h br u s h wit h a ri b b o n of t o ot h p a st e, a cr o s s t h e f ull br u s h 
h e a d.  
St art t h e ti m er ( pr e -s et f or 1 -mi n ut e).  
Br u s h t h e e ntir e  
d e ntiti o n t h or o u g hl y 
f or at l e a st 1 -ti m e d 
mi n ut e,  t wi c e d ail y 
( m or ni n g & e v e ni n g).  
Br u s h t h e e ntir e 
d e ntiti o n  t h or o u g hl y f or 
at l e a st 1 -ti m e d mi n ut e, 
t wi c e d ail y ( m or ni n g & 
e v e ni n g),  m a ki n g s ur e 
t o br u s h t h e s e n siti v e 
ar e a s of t h e t w o  ' T e st 
t e et h' c ar ef ull y fir st. 
Br u s h t h e e ntir e  
d e ntiti o n t h or o u g hl y  
f or at l e a st 1-ti m e d 
mi n ut e, t wi c e d ail y  
( m or ni n g & e v e ni n g). 
S u bj e ct s w h o wi s h t o ri n s e aft er br u s hi n g will b e i n str u ct e d t o ri n s e wit h 1 0 
ml  w at er u si n g gr a d u at e d ri n si n g c u p pr o vi d e d.  
D ur ati o n of 
Tr e at m e nt  
A p pr o xi m at el y 8 w e e k s ( 5 6 ± 3 d a y s)  
R et ur n R e q uir e m e nt s  
All u s e d/ u n u s e d t u b e s t o b e r et ur n e d t o t h e s p o n s or.  
N/ A: N ot A p pli c a bl e  
1.  C o m m er ci all y a v ail a bl e d ail y u s e, r e g ul ar fl u ori d e t o ot h p a st e, U S  m ar k et.  
2.  A s s o di u m m o n ofl u or o p h o s p h at e  
3.  A s S n F 2  
4.  A s N a F  
1. 4  
S a m pl e Si z e C al c ul ati o n  
S ufficie nt s u bjects will b e scree ne d a n d e nt ere d i nt o t he accli matizati o n peri o d t o ra n d o mize 
a p pr o xi matel y 1 1 0 s u bjects t o i n vesti gati o nal pr o d uct (a p pr o xi matel y 5 5 s u bjects per treat me nt 
gr o u p) t o e ns ur e a p pr o xi matel y 1 0 0 c o m plete t he st u d y (a p pr o xi matel y 5 0 s u bjects per 
treat me nt gr o u p), all o wi n g f or a p pr o xi matel y 1 0 % dr o p o uts.  
C CI
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T he st u d y will be s ufficie ntl y p o were d t o de m o nstrate statistical s u peri orit y of t he Test 
T o ot h paste c o m pare d t o t he Refere nce T o ot h paste ( ne gati ve c o ntr ol) f or t he c ha n ge fr o m 
Baseli ne i n t he Sc hiff se nsiti vit y sc ore ( pri mar y o bjecti ve) a n d tactile t hres h ol d ( ke y s ec o n dar y 
o bjecti ve) after 5 6 d a ys ( 8 w ee ks) treat me nt. A sa m ple siz e of 5 0 e val ua ble s u bjects per 
treat me nt gr o u p will pr o vi de at least 9 0 % p o wer t o detect a mea n differe n ce of 0. 4 u nits ( S D = 
0. 6) i n c ha n g e fr o m Bas eli ne i n Sc hiff se nsiti vit y sc ore after 5 6 da ys tr eat m e nt, usi n g a 2 -taile d 
2 -sa m ple t-test wit h a 5 % si g nifica nce le vel. T he sa m ple size calc ulati o n was perf or me d usi n g 
P A S S s oft ware versi o n 2 3. 0. 1.  
T he dr o p o ut rate a n d S D esti mates are b ase d o n t he res ults of D H efficac y st u dies of si milar 
desi g n a n d d urati o n e val uati n g 0. 4 5 4 % S n F 2 t o ot h pastes ( Cli nical St u dies 2 0 5 7 9 4, 2 0 8 1 5 3 a n d 
2 1 6 9 5 4: s p o ns or data hel d o n file, a vaila ble o n re q uest) . 
2  
Pl a n n e d A n al y s e s  
2. 1  
I nt eri m A n al y si s 
N o i nteri m a nal ysis is pla n ne d.  
2. 2  
Fi n al A n al y s e s  
T he fi nal pla n n e d pri mar y a nal yses will be perf or me d aft er t he c o m pleti o n of t he f oll o wi n g 
se q ue ntial ste ps: 
•  All s u bjects ha ve c o m plete d t he st u d y as defi ne d i n t he pr ot oc ol . 
•  All re q uire d data b ase cl ea ni n g acti vities i ncl u di n g a n y e xter nal d ata rec o nciliati o n 
ha ve bee n c o m plete d a n d data base h as bee n l o c ke d.  
•  All criteria f or u n bli n di n g t he ra n d o mizati o n c o des ha v e bee n 
met a n d t he 
ra n d o mizati o n c o des h a v e bee n distri b ute d.  
3  
C o n si d er ati o n s f or D at a A n al y s e s a n d D at a  H a n dli n g 
C o n v e nti o n s  
3. 1  
B a s eli n e D efi niti o n  
F or all e n d p oi nts,  t he bas eli ne val ue will be t he Da y 0 ( Visit 2)  pre -treat m e nt assess me nt wit h 
a n o n-missi n g val ue.  
U nless ot her wise state d, if baseli ne data is missi n g n o deri vati o n will be perf or me d a n d t he 
baseli ne val ue will be s et t o missi n g.  
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3. 2  
S u b gr o u p s/ Str atifi c ati o n s  
S u bjects will be ra n d o mize d i nt o t he st u d y pr o vi de d t he y ha ve satisfie d all s u bject selecti o n 
criteria. E ac h eli gi ble s u bject will be stratifie d b y t he ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore 
of t heir t w o select e d ‘Test Teet h’ . T he str atificati o n fact or will gi ve rise t o t w o strata. 
•  Str at u m 1: Ma xi m u m Sc hiff se nsiti vit y sc ore = 2.  
•  Str at u m 2: Ma xi m u m Sc hiff se nsiti vit y sc ore = 3.  
I n t he e v e nt of mis-stratificati o n, t he c orrect strat a acc or di n g t o C R F i nf or mati o n will be use d 
i n t he a nal ysis i.e. deri ve d stratificati o n varia ble fr o m A D S L will be use d f or a nal ysis . 
3. 3  
C e nt er s  P o ol s  
Si nce t his is si n gle ce nter  st u d y, p o oli n g of ce ntres is n ot a p plica ble. 
3. 4  
Ti m e p oi nt s a n d Vi sit Wi n d o w s  
T he ti me p oi nts a n d visits f or t his st u d y are defi ne d i n  t he Ta ble 1 -1  “ Sc h e d ule of Acti vities”. 
A n y de viati o n fr o m t he st u d y sc he d ule ma y be re vie we d o n case -b y -case basis at t he Bli n de d 
Data Re vie w Meeti n g ( B D R M) t o deter mi ne w het her t he data s h o ul d be e xcl u de d fr o m t he Per -
Pr ot oc ol ( P P) a nal yses . 
4  
D at a A n al y si s  
Data a nal ysis will be perf or me d b y 
wit h o versi g ht fr o m Hale o n . T he statistical 
a nal ysis s oft ware use d will be S A S versi o n 9. 4  or hi g her.   
Pri or t o data base cl os ur e a B D R M will be c o n d ucte d i n w hic h vari o us as pects of t he trial will 
be disc usse d a n d a gree d.  
E xce pt as des cri be d b el o w, all listi n gs will be pr o d uce d f or all ra n d o mize d s u bjects.  
4. 1  
P o p ul ati o n s f or A n al y si s  
4. 1. 1  S u bj e ct D i s p o siti o n 
Scree n fail ures are defi n e d as s u bjects w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y ra n d o mize d. A n e nr olle d s u bject is a s u bject w h o has si g ne d i nf or me d c o nse nt 
a n d is eli gi ble t o pr ocee d be y o n d t he scree ni n g visit.  
T he n u m ber of s u bjects scree ne d, e nr olle d, a n d ra n d o mize d s u bjects will be prese nte d i n 
Ta ble  1 4. 1. 1 . 
T he n u m ber a n d perce nt a ge of scree n fail ure s u bjects (s u bjects n ot ra n d o mize d) wit h reas o ns 
w h y s u bjects are n ot ra n d o mize d will be dis pla ye d. Perce nta ges f or scree n fail ure s u bjects will 
be base d o n t he t otal n u m ber of s u bjects scree n e d.  
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T he n u m ber a n d perce nt a ge of ra n d o mize d s u bjects w h o c o m plete a n d disc o nti n ue t he st u d y, 
br o ke n d o w n b y reas o n f or disc o nti n uati o n, b y st u d y pr o d uct a n d o verall will als o be dis pla ye d. 
T he perce nta g es will be base d o n t he n u m ber of s u bjects ra n d o mize d.  
Ta ble 1 4. 1. 1  will als o prese nt t he n u m ber a n d perce nta ge of s u bjects i n eac h of t he d efi ne d 
a nal ysis p o p ulati o ns (as d efi ne d i n Secti o n 4. 1. 3 ) b y st u d y pr o d uct a n d o v erall. Perce nta ges will 
be base d o n t he n u m ber of s u bjects ra n d o mize d.  
S u bject dis p ositi o n i ncl u di n g de m o gra p hic data (a ge, se x , race, a n d et h nicit y ), scree ni n g date, 
st u d y pr o d uct  start date a n d ti me, s u bject stat us (c o m pleter, Yes/ N o), st u d y c o m pleti o n 
/ wit h dra wal date, d urati o n (i n da ys) i n t he st u d y ( defi ne d as [( date of c o m pl eti o n or wit h dra wal 
–  start dat e of st u d y pr o d uct ) + 1], a n d t h e pri mar y reas o n f or wit h dra wal will be liste d (Listi n g 
1 6. 2. 1. 1 ) b y st u d y pr o d uct. 
S u bject dis p ositi o n i nf or mati o n will be liste d f or n o n -ra n d o mize d s u bjects (Listi n g 1 6. 2. 1. 2 ), 
dis pla yi n g s u bject n u m ber, de m o gr a p hic i nf or mati o n (a ge, se x , race a n d et h nicit y ), scree ni n g 
date, reas o n f or scree n fail ure a n d a n y f urt her details of reas o n f or s cree n. 
4. 1. 2  Pr ot o c ol D e vi ati o n s  
Pr ot oc ol de viati o ns will be trac k e d b y t he st u d y tea m t hr o u g h o ut t he c o n d uct of t he st u d y. Dat a 
will be re vie we d pri or t o u n bli n di n g a n d cl os ure of t he data base t o e ns ure all i m p orta nt 
de viati o ns are ca pt ure d a n d cate g orise d. S u bjects wit h i m p orta nt pr ot oc ol de viati o ns lia ble t o 
i nfl ue nce t he effi cac y o ut c o mes will ha ve affecte d data e xcl u d e d  fr o m t he P P a nal ys es. S u bjects 
ma y als o be i de ntifie d as ha vi n g i m p orta nt pr ot oc ol de viati o ns n ot lea di n g t o e xcl usi o n of dat a  
fr o m t he P P a nal yses . 
I m p ort a nt de viati o ns of t he pr ot oc ol pr oce d ures m a y i ncl u de, b ut will n ot n ecessaril y be  li mite d 
t o t he f oll o wi n g: 
•  C o nse nt pr oce d ures  
•  I n cl usi o n/ E xcl usi o n criteria 
•  C o nc o mita nt me dicati o n/t hera p y  
•  St u d y pr oce d ures  
•  Ra n d o mizati o n pr oce d ures  
•  St u d y dr u g d osi n g/st u d y pr o d uct a d mi nistrati o n/st u d y pr o d uct c o m plia nce  V isit 
sc he d ule/i nter val 
•  Ot her  
T he s pecific d etails of t he i m p orta nt pr ot oc ol de viati o ns will be liste d i n Pr ot oc ol De viati o n 
Ma na ge me nt Pla n a n d assess me nt pr ocess will be s pecifie d i n t he Bli n d Data Re vie w Pla n a n d 
s u bjects wit h i m p orta nt pr ot oc ol de viati o ns will be i de ntifie d at t he B D R M. 
T he n u m ber a n d perce nta ge of s u bjects wit h at least o ne i m p orta nt pr ot oc ol de viati o n, s u bjects 
wit h i m p orta nt pr ot oc ol de viati o ns n ot lea di n g t o e xcl usi o n fr o m P P p o p ulati o n wit h reas o ns 
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f or de viati o ns a n d s u bjects wit h i m p orta nt pr ot oc ol de viati o ns lea di n g t o e xcl usi o n fr o m t he P P 
p o p ulati o n wit h reas o ns f or de viati o ns will be prese nte d b y  st u d y pr o d uct  a n d o verall, f or all 
ra n d o mize d s u bjects (Ta ble 1 4. 1. 2 ) a n d liste d i n Listi n g 1 6. 2. 2. 1 . 
All pr ot oc ol de viati o ns c ollecte d o n t he pr ot oc ol de viati o n case re p ort f or m pa ge will be liste d 
i n Listi n g 1 6. 2. 2. 2 . T he listi n g will prese nt date of de viati o n, t y pe of d e viati o n, a n d de viati o n 
descri pti o n.  
4. 1. 3  A n al y si s P o p ul ati o n s  
T hree  a nal ysis p o p ulati o ns are defi ne d.  
P o p ul ati o n  
D efi niti o n / Crit eri a  
A n al y s e s E v al u at e d  
S af et y  
C o m pri s e of all r a n d o mi z e d s u bj e ct s w h o r e c ei v e s 
at l e a st o n e d o s e  of st u d y pr o d u ct . A n y s u bj e ct 
w h o r e c ei v e s a r a n d o mi z ati o n n u m b er will b e 
c o n si d er e d t o h a v e b e e n r a n d o mi z e d.  
T hi s p o p ul ati o n will b e b a s e d o n t h e tr e at m e nt t h e 
s u bj e ct a ct u all y r e c ei v e d.  
•  Safet y  
M o difi e d I nt e nt-
T o -Tr e at ( mI T T ) 
C o m pri s e all r a n d o mi z e d s u bj e ct s w h o c o m pl et e 
at l e a st o n e d o s e  of st u d y pr o d u ct  a n d c o m pl et e  
at l e a st o n e p o st -b a s eli n e  D H effi c a c y 
a s s e s s m e nt.  
A n y s u bj e ct w h o r e c ei v e s a r a n d o mi z ati o n 
n u m b er will b e c o n si d er e d t o h a v e b e e n 
r a n d o mi z e d. 
T hi s p o p ul ati o n will b e b a s e d o n t h e st u d y  pr o d u ct 
t o w hi c h t h e s u bj e ct w a s r a n d o mi z e d. 
•  De m o gra p hic  
•  Baseli ne 
C haracteristics  
•  Efficac y A nal ysis  
 
P er -Pr ot o c ol  
C o m pri s e all s u bj e ct s i n t h e mI T T p o p ul ati o n w h o 
h a v e at l e a st o n e D H effi c a c y a s s e s s m e nt 
c o n si d er e d t o b e u n aff e ct e d b y pr ot o c ol 
d e vi ati o n s . 
Pr ot o c ol d e vi ati o n s t h at w o ul d e x cl u d e s u bj e ct s 
fr o m t h e P P p o p ul ati o n ar e d efi n e d i n S e cti o n 
4. 1. 2  ( Pr ot o c ol D e vi ati o n s). 
T hi s p o p ul ati o n will b e b a s e d o n t h e st u d y pr o d u ct 
t o w hi c h t h e s u bj e ct w a s r a n d o mi z e d. 
•  Efficac y A nal ysis  
N O T E S :  
Pl e a s e r ef er t o A p p e n di x 1 : Li st of D at a Di s pl a y s w hi c h d et ail s t h e p o p ul ati o n t o b e u s e d f or e a c h 
di s pl a y s b ei n g g e n er at e d.  
T he n u m bers of s u bjects i ncl u de d i n eac h of t he a n al ysis p o p ulati o ns will be s u m marize d ( T a ble 
1 4. 1. 1 ). S u bjects e xcl u de d fr o m a n y of t he a nal ysis p o p ulati o ns will be liste d i n Listi n g 1 6. 2. 3. 1 , 
wit h t he reas o n f or e xcl usi o n . 
T he pri mar y p o p ulati o n f or assess me nt of efficac y will be t he m I T T P o p ulati o n. A P P  a nal ysis 
will be perf or me d o n t h e D H  e n d p oi nts  if at least  1 0 %  of t he m I T T s u bjects are e x cl u de d fr o m 
t he P P P o p ulati o n. Efficac y data deter mi ne d t o ha ve bee n p ote ntiall y i m pacte d b y a pr ot oc ol 
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de viati o n will be e xcl u d e d fr o m t he P P a nal ysis. A  decisi o n o n w het her a pr ot oc ol de viati o n 
i m pacts efficac y data a n d w het her t o perf or m a P P a nal ysis will be ma de pri or t o st u d y 
u n bli n di n g (release of t he ra n d o mizati o n c o d es). 
4. 2  
S u bj e ct  D e m o gr a p hi c s  a n d O t h er B a s eli n e C h ar a ct eri sti c s  
4. 2. 1  D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
Descri pti ve statistics ( n u m ber of s u bjects [ n], 
mea n, sta n d ar d de vi ati o n [ S D], 
me dia n, 
mi ni m u m,  a n d ma xi m u m f or c o nti n u o us varia bles a n d fre q ue n c y c o u nt [ n] a n d perce nt a ge [ %] 
of s u bjects f or cate g orical varia bles) will be prese nte d f or de m o gr a p hic c haracteristics b y st ud y 
pr o d uct  a n d o verall . T hese varia bles i ncl u de a ge, se x, race, et h nicit y, a n d stratificati o n gr o u p  
a n d will be prese nte d f or t he Safet y p o p ulati o n (Ta ble 1 4. 1. 3. 1 ) a n d t he mI T T p o p ulati o n ( Ta ble 
1 4. 1. 3. 2 ). 
De m o gra p hic i nf or mati o n will be liste d (Listi n g 1 6. 2. 4. 1 ) f or all ra n d o mize d s u bjects. 
4. 2. 2  G e n er al M e di c al H i st or y 
M e dical a n d s ur gical hist or y (i n t he last y ear) i n cl u di n g aller gies or dr u g se nsiti vit y will be 
liste d i n Listi n g 1 6. 2. 4. 2 , wit h start date a n d e n d d ate or o n g oi n g at t he start of st u d y pr o d uct . 
4. 3  
Tr e at m e nt s ( S t u d y Pr o d u ct , R e s c u e M e di c ati o n, ot h er C o n c o mit a nt 
T h er a pi e s, C o m pli a n c e)  
Ra n d o mizati o n details will be liste d, i ncl u di n g t he ra n d o mizati o n n u m ber, stratificati o n gr o u p, 
t he pla n ne d st u d y pr o d uct , t he act ual st u d y pr o d uct  t he s u bject was ra n d o mize d t o a n d t he 
ra n d o mizati o n date (Listi n g 1 6. 1. 7. 1 ) f or all ra n d o mize d s u bjects. 
T he st u d y pr o d uct kit all ocati o ns will be liste d ( Listi n g 1 6. 1. 7. 2), i ncl u di n g kit n u m ber a n d 
st u d y pr o d uct i nf or mati o n. 
4. 3. 1  St u d y Pr o d u ct  C o m pli a n c e  a n d E x p o s ur e  
C o m plia nce data will be s u m marize d f or t he m I T T p o p ulati o n a n d will be assesse d b y n u m ber 
of br us hi n gs .  
N u m ber of act ual br us hi n gs, br us hi n g c o m plia nce ( %), n u m ber of misse d br us hi n gs, n u m ber of 
a d diti o nal br us hi n gs will be s u m marize d usi n g descri pti ve statistics b y c u m ulati ve visit a n d b y 
st u d y pr o d uct ( Ta ble 1 4. 2. 1).  
N u m ber of act u al br us hi n gs is defi ne d as: [( date of Visit x –  date of Visit 2) m ulti plie d b y 2 –  
n u m ber of missi n g br us hi n gs + n u m ber of a d diti o nal br us hi n gs] , w here x = 3 a n d 4 , 
res pecti vel y. 
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Br us hi n g c o m plia nce ( %) is defi ne d as: [ 1 0 0 ×  ( N u m ber of act ual br us hi n gs / E x pecte d n u m b er 
of br us hi n gs)], w here e x pecte d n u m ber of br us hi n gs is defi ne d as: [( date of Visit x  –  date of 
Visit 2) m ulti plie d b y 2].  
St u d y pr o d uct c o m plia nce ( n u m ber of act u al br us hi n gs / br us hi n g c o m plia nce [ %] / n u m ber of 
misse d br us hi n gs / n u m bers of a d diti o nal br us hi n gs) will be liste d i n Listi n g  1 6. 2. 5. 1 f or all 
ra n d o mize d s u bjects b y st u d y pr o d uct. 
S u per vise d st u d y pr o d uct a p plicati o n (s u bject n u m ber, c o m pleti o n stat us, d ate of visit a n d ti me 
of t he s u per vise d pr oce d ure) will be liste d ( Listi n g  1 6. 2. 5. 2 ) f or all s u bjects i n safet y p o p ulati o n. 
4. 3. 2  Pri or a n d C o n c o mit a nt M e di c ati o n  
Pri or 
me dicati o ns/treat me nts, i ncl u di n g prescri pti o n a n d n o n -prescri pti o n dr u gs, dietar y 
s u p ple me nts a n d her bal re me dies, ta ke n i n t he l ast 3 0 da ys a n d pri or t o si g ni n g t he i nf or me d 
c o nse nt f or m, will be d oc u me nte d i n t he C R F . T he pri or a n d c o nc o mita nt me dicati o ns will be 
c o de d usi n g a  vali date d me dicati o n dicti o nar y, W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y 
(W H O D D ). 
Pri or me dicati o ns a n d pri or n o n -dr u g treat me nts will be liste d b y s u bject, wit h dr u g na me, 
W H O D D Dr u g S y n o n y m , reas o n f or me dicati o n, r o ute, d ose, fre q ue n c y, start date, start d a y 
relati ve t o t he st u d y pr o d uct start date, e n d date a n d e n d da y relati ve t o t h e st u d y pr o d uct start 
date ( Listi n g 1 6. 2. 4. 3 ) f or all safet y s u bjects. Pri or me dicati o ns are defi ne d as t h ose w hic h 
st o p pe d bef ore t he first use of t he st u d y pr o d uct . 
C o nc o mita nt me dicati o ns a n d si g nifica nt n o n -dr u g t hera pies ta ke n d uri n g treat me nt  will be 
liste d si milarl y ( Listi n g 1 6. 2. 4.4 ) f or all safet y s u bjects wit h eit her o n g oi n g or e n d date 
dis pla ye d. C o nc o mita nt me dicati o ns are defi ne d as me dicati o ns t hat starte d or st o p pe d o n or 
after t he first use of t he st u d y pr o d uct or  are o n g oi n g.  
U n k n o w n dates will n ot be i m p ute d . H o we v er , if t he start or st o p date is u n k n o w n, t he n it will 
be ass u me d t o be c o n c o mita nt me dicati o n u nless t he p artial start date or st o p date i n dicates 
differe ntl y.  
4. 4  
A n al y si s of E ffi c a c y 
T he pri mar y p o p ulati o n f or assess me nt of efficac y will be t he mI T T P o p ulati o n . 
All p -val ues prese nt e d will be t w o -si de d a n d assess e d at t h e 5 % si g nifica nce le vel. A s e q ue ntial 
testi n g strate g y will be use d t o a dj ust f or t he c o m paris o ns bet wee n t he Test a n d Refere nce 
T o ot h pastes i n c ha n g e fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore a n d tactile t hres h ol d ( g) at eac h 
assess me nt ti me p oi nt.  
At eac h ti me p oi nt, c ha n ge fr o m Baseli ne i n tactile t hres h ol d ( g) will o nl y be assesse d f or 
c o nfir mat or y e vi de nce if t he c ha n g e fr o m Baseli ne i n Sc hiff s e nsiti vit y sc ore ac hie ves a 
statisticall y si g nifica nt greater re d u cti o n f or t he Test T o ot h paste c o m pare d t o t he Refere n ce 
T o ot h paste ( ne gati ve c o ntr ol). T his strate g y will be gi n at Da y 5 6, t he n m o ve t o Da y 2 8, o nl y 
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m o vi n g t o t he earlier ti me p oi nt f or c o nfir mat or y e vi de nce if t he Da y 5 6 ti me p oi nt ac hie ves 
statisticall y si g nifica nt greater re d ucti o ns f or t he Test T o ot h paste c o m pare d t o t he Refere nce 
T o ot h paste ( ne gati ve c o ntr ol) f or b ot h Sc hiff se nsiti vit y sc ore a n d tactile t hres h ol d ( g). T here 
will be n o f urt her a dj ust me nts f or m ulti plicit y f or t he ot her sec o n d ar y e n d p oi nts ( D H E Q -4 8).  
T he res ults fr o m eac h Mi xe d M o del wit h Re p eate d Meas ures ( M M R M) will be ta b ulate d, 
prese nti n g t he f oll o wi n g i nf or mati o n, i n a d diti o n t o t he res ults s pecifie d f or t he pri mar y a n d 
sec o n dar y a nal yses b el o w: least s q uare mea n c h a n ge fr o m Bas eli ne f or eac h i n ve sti gati o nal 
pr o d uct at Da ys 2 8 a n d 5 6 ( base d o n t he o bser ve d stratificati o n mar gi ns f or t h ose M M R M wit h 
a ter m f or ra n d o mize d str ata) a n d use d t o test f or a n y c ha n ge fr o m Baseli ne, wit h t w o -si de d p-
val ues a n d 9 5 % CIs . 
4. 4. 1  Pri m ar y E ffi c a c y E n d p oi nt  
4. 4. 1. 1  
C h a n g e fr o m B a s eli n e i n S c hiff S e n siti vit y S c or e at D a y 5 6  
T he pri mar y efficac y varia ble is t he c ha n g e fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore at Da y 5 6 . 
Sc hiff se nsiti vit y sc ore will be deri ve d as t he mea n sc ore f or t he t w o ‘ Test Teet h’ (select e d at 
Baseli ne). C ha n ge fr o m Baseli ne will be deri v e d f or eac h i n di vi d ual t o ot h first bef ore 
calc ulati n g mea n c ha n g e f or t he t w o ‘ Test Teet h’ w here c h a n ge fr o m Baseli ne i n Sc hiff 
se nsiti vit y sc ore at Da y x is defi ne d as [( Sc hiff se nsiti vit y sc ore at Da y x) mi n us ( Baseli ne Sc hiff 
se nsiti vit y sc ore)]. 
Descri pti ve statistics ( n, mea n, S D, sta n dar d err or [ S E], me dia n, mi ni m u m, a n d ma xi m u m) will 
be prese nte d f or Sc hiff s e nsiti vit y sc ore calc ulate d as t he a vera ge sc ore of t he t w o test teet h at 
eac h assess me nt ti me p oi nt i n Ta ble 1 4. 2. 2. 1. 1 f or all s u bjects i n mI T T p o p ulati o n b y st u d y 
pr o d uct. Ra w mea ns ( ± S E) of t he Sc hiff se nsiti vit y sc ore at eac h ti me p oi nt will be pl otte d b y 
st u d y pr o d uct i n Fi g ure 1 4. 2. 2. 1. 1 f or all s u bjects i n mI T T p o p ulati o n.  
I n di vi d ual Sc hiff s e nsiti vit y sc ore data will be liste d f or eac h s u bject b y visit a n d st u d y pr o d uct 
gr o u p i n Listi n g 1 6. 2. 6. 1  a n d Listi n g 1 6. 2. 6. 2 , f or Scree ni n g a n d Baseli ne,  a n d se paratel y f or 
t w o test teet h res pecti vel y, f or all ra n d o mize d s u bjects.  
4. 4. 1. 2  
St ati sti c al H y p ot h e si s, M o d el, a n d M et h o d of A n al y si s  
T he  f oll o wi n g n ull a n d al ter nati ve h y p ot hes es will be e val uat e d : 
•  H 0: T here is n o differe n ce i n c ha n g e fr o m b aseli ne i n S c hiff se nsiti vit y sc ore i n t he Test 
T o ot h paste  c o m pare d t o Refere n ce T o ot h p aste   
•  H 1: T here is a differe n ce i n c ha n ge fr o m bas eli ne i n S c hiff se nsiti vit y sc ore i n t he Test 
T o ot h paste  c o m pare d t o Refere n ce T o ot h p aste   
C ha n ge fr o m Baseli ne i n Sc hiff se nsiti vit y sc ore at Da y 5 6 will be a nal ys e d usi n g a M M R M 
wit h st u d y pr o d uct, visit a n d [st u d y pr o d uct x visit] i nteracti o n as fi xe d effects, a n d Baseli ne 
Sc hiff se nsiti vit y sc ore as a c o variate.  N ote t hat si nce t he Baseli ne Sc hiff s e nsiti vit y sc ore will 
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be i ncl u de d as a c o vari ate, t he B aseli ne Sc hiff str atificati o n val ue will n ot be i ncl u d e d i n t h e 
m o del.  S u bject will be i ncl u de d as a re peate d meas ure wit h u nstr uct ure d c o varia n ce matri x. 
Ke n war d -R o ger’s de grees of free d o m a p pr oac h will be a p plie d ( Ke n war d, 1 9 9 7). T h e 
differe n ce bet w ee n t he least s q uare mea n c ha n ges fr o m Baseli ne f or t he Test T o ot h paste 
c o mpare d t o R efere nce T o ot h paste ( ne g ati ve c o ntr ol) at Da y 5 6 fr o m t he M M R M will be 
prese nte d, al o n g wit h t he t w o -si de d p-val ue a n d 9 5 % CIs.  I n t he e v e nt t hat t he m o del d oes n ot 
c o n ver ge o n t h e u nstr uct ure d c o varia nce matri x, a n a p pr o priate alter nati ve will be c o nsi dere d . 
Usi n g t he a b o ve m o d el, t he a dj uste d mea n c ha n ge fr o m baseli ne i n t he Sc hiff se nsiti vit y sc ore 
will be re p orte d b y st u d y pr o d uct al o n g wit h 9 5 % c o nfi d e nce i nter vals ( CIs)  a n d p -val ues  
testi n g f or a n o n-zer o c h a n ge fr o m bas eli ne a n d will be pr o vi de d i n Ta ble 1 4. 2. 2. 2. 1 . Als o, 
mea n  differe nces bet w ee n Test T o ot h paste c o m pare d t o t he Refere nce T o ot h paste i n t he c ha n ge 
fr o m baseli ne i n Sc hiff se nsiti vit y sc ore at Da y 5 6 will be pres e nte d al o n g wit h 9 5 % CIs a n d p -
val ues i n t he sa me Ta bl e 1 4. 2. 2. 2. 1 . 
T he ass u m pti o ns of n or malit y a n d h o m o ge neit y of varia nce i n t he M M R M will be i n vesti gate d. 
I n case of vi olati o n of t hese ass u m pti o ns, a s uita ble n o n-para metric test ( Va n Eltere n T est, 
a dj uste d f or t he ra n d o mi zati o n stratificati o n, Ma xi m u m Baseli ne Sc hiff Se nsiti vit y Sc ore) will 
be perf or me d t o assess t he c ha n g e fr o m Baseli ne c o m paris o n ( Test T o ot h paste vs. Refere nce 
T o ot h paste at Da y 5 6); t h e res ults will be pr o vi de d t o s u p p ort t he M M R M  res ults. 
4. 4. 1. 3  
S u p p orti v e A n al y s e s  
If t here is at least  1 0 % differe n ce i n t he o v erall n u m ber of s u bjects b et wee n P P a n d mI T T 
P o p ulati o ns, a s u m mar y a n d statistical a nal ysis of t he Sc hiff se nsiti vit y sc ore will be prese nte d 
f or t he P P P o p ulati o n i n Ta ble 1 4. 2. 2. 1. 2 a n d Ta ble 1 4. 2. 2. 2 . 2, res pecti vel y. I n a d diti o n, Sc hiff 
se nsiti vit y sc ore ( Fi g ur e 1 4. 2. 2. 1. 2) at eac h ti me p oi nt will be pl otte d b y st u d y pr o d uct i n f or 
all s u bjects i n P P P o p ulati o n.  
A decisi o n o n w het her a P P a nal ysis will be perf or me d will be ma de pri or t o st u d y u n bli n di n g 
(rele ase of t he ra n d o mizati o n c o des). 
4. 4. 2  S e c o n d ar y E ffi c a c y E n d p oi nt s  
4. 4. 2. 1  
C h a n g e fr o m B a s eli n e i n T a ctil e T hr e s h ol d ( g)  at D a y 5 6  
T he ke y sec o n dar y varia ble is t he c ha n ge fr o m Baseli ne i n tactile t hres h ol d ( g) at Da y 5 6. 
Tactile t hres h ol d ( g) will be deri ve d as t he mea n val ue f or t h e t w o ‘ Test Teet h’ (selecte d at 
Baseli ne). C ha n ge fr o m Baseli ne will be deri v e d f or eac h i n di vi d ual t o ot h first bef ore 
calc ulati n g mea n c ha n g e f or t he t w o ‘ Test Teet h’ w here c h a n ge fr o m Baseli ne i n tactile 
t hres h ol d ( g) at Da y x is defi ne d as [(tactile t hres h ol d at Da y x) mi n us ( Baseli ne tactil e 
t hres h ol d)]. 
Descri pti ve statistics ( n, mea n, S D, S E, me dia n, mi ni m u m, a n d ma xi m u m) will be prese nt e d 
f or Tactile t hres h ol d ( g) calc ulate d as t he a v era g e sc ore of t he t w o test teet h at eac h ass ess me nt 
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ti me p oi nt i n Ta ble 1 4. 2. 3 . 1. 1 f or all s u bjects i n mI T T p o p ul ati o n b y st u d y pr o d uct. Ra w mea ns 
( ± S E) of t he Tactile t hres h ol d ( g)  of t he t w o test teet h at eac h ti me p oi nt will be pl otte d b y 
st u d y pr o d uct i n Fi g ure 1 4. 2. 2.2 . 1 f or all s u bjects i n mI T T p o p ulati o n. 
I n di vi d ual T actile t hres h ol d ( g) data will be liste d f or eac h s u bject b y visit a n d st u d y pr o d uct 
gr o u p  i n Listi n g 1 6. 2. 6.3 a n d Listi n g 1 6. 2. 6. 4 , f or Scree ni n g a n d Baseli ne, a n d se paratel y f or 
t w o test teet h res pecti vel y, f or all ra n d o mize d s u bjects. 
4. 4. 2. 1. 1  St ati sti c al H y p ot h e si s, M o d el a n d M et h o d of A n al y si s  
T he f oll o wi n g n ull a n d alter nati ve h y p ot heses will be e val uat e d:  
•  H 0: T here is n o differe nce i n c ha n ge fr o m bas eli ne i n tactile t hres h ol d ( g) i n t he Test 
T o ot h paste  c o m pare d t o Refere n ce T o ot h p aste   
•  H 1: T here is a differe nce i n c ha n ge fr o m baseli ne i n tactile t hres h ol d ( g) i n t he Test 
T o ot h paste  c o m pare d t o Refere n ce T o ot h p aste   
Ke y sec o n dar y e n d p oi nt, c ha n ge fr o m Bas eli ne i n tactile t hres h ol d ( g) at Da y 5 6, will be 
a nal yse d usi n g t he sa me M M R M met h o d detaile d i n  Secti o n 4. 4. 1. 2  b ut wit h Baseli ne tactile 
t hres h ol d ( g) as a c o variate (rat her t ha n Baseli n e Sc hiff s e nsiti vit y sc ore). I n a d diti o n, t he 
ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore of t he t w o ‘ Test Teet h’ ( 2 or 3) will be fitte d as a 
fi xe d effect. T h e res ults will be prese nte d i n Ta bl e 1 4. 2. 3 . 2. 1. 
4. 4. 2. 1. 2  S u p p orti v e A n al y s e s  
A P P a nal ysis will be perf or me d o n t he c ha n ge fr o m baseli ne i n t actile t hr es h ol d ( g) as det aile d 
i n Secti o n 4. 4. 1. 3  a n d t he sa me M M R M m o del will be use d as detaile d i n Secti o n 4. 4. 2. 1. 1 . 
T he res ults will be prese nte d i n Ta ble 1 4. 2. 3 .1 .2  a n d Ta ble 1 4. 2. 3 . 2.2  res p ecti vel y f or s u m mar y 
ta ble a n d a nal ysis ta ble. Als o, Fi g ur e 1 4. 2. 2. 2 . 2 will be ge n erate d f or all s u bjects i n P P 
p o p ulati o n.  
4. 4. 2. 2  
C h a n g e fr o m B a s eli n e i n S c hiff S e n siti vit y S c or e at D a y 2 8  
T he ot her s ec o n d ar y e ffi cac y en d p oi nt will be t he C ha n ge fr o m Baseli ne i n Sc hiff Se nsiti vit y 
Sc ore at Da y 2 8 . 
T he s u m mar y res ults f or t his e n d p oi nt will be o btai ne d as detaile d i n Secti o n 4. 4. 1. 1 . T he res ults 
will be prese nte d i n Ta bl e 1 4. 2. 2. 1. 1.  
4. 4. 2. 2. 1  St ati sti c al H y p ot h e si s, M o d el a n d M et h o d of A n al y si s  
T h e a nal ysis is sa me as pri mar y e n d p oi nt a n d t he details will be  o btai ne d fr o m  Secti o n 4. 4. 1. 2 . 
Als o, the res ults will be prese nte d i n Ta bl e 1 4. 2. 2. 2. 1  a n d Fi g ur e 1 4. 2. 2. 1. 1 . 
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4. 4. 2. 2. 2  S u p p orti v e A n al y s e s  
A P P a nal ysis will be p erf or me d o n t he c ha n ge fr o m baseli ne i n Sc hiff se nsiti vit y sc ore as 
detaile d i n Secti o n 4. 4. 1. 3  a n d t he sa me M M R M m o del will be use d as detaile d i n Secti o n 
4. 4. 1. 2 . T he res ults will be prese nte d i n Ta ble 1 4. 2. 2. 1. 2 a n d Ta ble 1 4. 2. 2. 2. 2 res pecti vel y f or 
s u m mar y ta ble a n d a nal ysis ta ble. Als o, Fi g ure 1 4. 2. 2. 1. 2 will be ge nerate d f or all s u bjects i n 
P P p o p ulati o n.  
4. 4. 2. 3  
C h a n g e fr o m B a s eli n e i n T a ctil e T hr e s h ol d ( g)  at D a y 2 8  
T he ot her sec o n d ar y efficac y e n d p oi nt will be t he C ha n ge fr o m Baseli ne i n tactile thres h ol d ( g) 
at Da y 2 8. 
T he s u m mar y res ults f or t his e n d p oi nt will be o btai ne d as detaile d i n Secti o n 4. 4. 2. 1 . T he res ults 
will be prese nte d i n Ta bl e 1 4. 2. 3 . 1. 1 a n d Fi g ure 1 4. 2. 2. 2. 1 . 
4. 4. 2. 3. 1  St ati sti c al H y p ot h e si s, M o d el a n d M et h o d of A n al y si s  
T he a nal ysis is sa me as t he ke y sec o n dar y e n d p oi nt a n d t he details  will be o btai ne d fr o m t he 
M M R M detaile d i n  Secti o n 4. 4. 2. 1. 1 . Als o, the res ults will be prese nte d i n Ta ble 1 4. 2. 3 . 2. 1. 
4. 4. 2. 3. 2  S u p p orti v e A n al y s e s  
A P P a nal ysis will be perf or me d o n t he c ha n ge fr o m baseli ne i n tactile thres h ol d ( g) as det aile d 
i n Secti o n 4. 4. 2. 1. 2 . T he res ults will be prese nt e d i n Ta ble 1 4. 2. 3 . 1. 2 a n d Ta ble 1 4. 2. 3 . 2.2  
res pecti vel y f or s u m mar y ta ble a n d a nal ysis ta ble. Als o, Fi g ure 1 4. 2. 2.2 . 2 will be ge nerate d f or 
all s u bjects i n P P p o p ulati o n . 
4. 4. 2. 4  
C h a n g e fr o m B a s eli n e i n D H E Q -4 8 e n d p oi nt s  at D a y 5 6 a n d D a y 2 8  
D H E Q -4 8:  
T he D H E Q -4 8 is a c o n diti o n -s pecific meas ure of O Hr Q o L i n relati o n t o D H ( B oi k o, 2 0 1 0) t hat 
has bee n pre vi o usl y vali date d i n l o n git u di nal st u dies a n d s h o w n t o be res p o nsi ve t o treat me nt 
( Ba ker, 2 0 1 4). T he D H E Q t otal sc ore ca n be br o ke n d o w n i nt o 5 se parate ‘ d o mai n’ sc ores t o 
pr o vi de a m ore gra n ular u n dersta n di n g of t he s pecific areas of i m pr o ve me nt s u bjects e x perie n ce 
i n t heir O Hr Q O L. 
•  Restricti o ns: Deri ve d fr o m partici pa nt res p o nses t o Secti o n 2, Q 1 -4 ( ‘t he wa ys i n w hic h 
a n y se nsati o ns i n y o ur te et h affect y o u i n y o ur dail y life’).  
•  A d a pt ati o n: Deri ve d fr o m partici pa nt res p o nses t o Secti o n 2, Q 5 -1 6 (‘t he wa ys i n w hic h 
t he se nsati o ns i n y o ur teet h ha ve f orce d y o u t o c ha n ge t hi n gs i n y o ur dail y life’; ‘t hi n gs 
y o u d o i n y o ur dail y life t o a v oi d e x perie n ci n g t he se nsati o ns i n y o ur teet h’ ). 
•  S oci al I m p act: Deri v e d fr o m partici pa nt res p o nses t o Secti o n 2, Q 1 7 -2 1 (‘t he wa y t he 
se nsati o ns affect y o u w h e n y o u are wit h ot her pe o ple or i n cert ai n sit uati o ns’).  
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•  E m oti o n al I m p act: Deri ve d fr o m partici p a nt res p o nses t o Secti o n 2, Q 2 2 -2 9 (‘t he wa y 
t he se nsati o ns i n y o ur teet h ma ke y o u feel’). 
•  I de ntit y: Deri ve d fr o m p artici pa nt res p o ns es t o Secti o n 2, Q 3 0 -3 4 (‘w hat t h e se nsati o ns i n 
y o ur teet h mea n f or y o u’).  
T he D H E Q als o pr o vi des s pecific i nf or mati o n o n h o w m uc h t he se ns ati o ns i n t he p artici pa nt ’s 
teet h affect t heir life o v erall: 
•  Gl o b al Or al He alt h: Deri ve d fr o m partici pa nt res p o nse t o Secti o n 2, Q 3 5 (‘rate t he 
healt h of y o ur m o ut h, teet h a n d g u ms’).  
•  Effect o n Life O ve r all: Deri ve d fr o m partici pa nt res p o nses t o Secti o n 2, Q 3 6 -3 9 (i m pact 
of D H o n o verall q ualit y of life).  
T he  ot her  sec o n dar y efficac y en d p oi nt s will be t h e c ha n ge fr o m b aseli ne i n D H E Q -4 8 e n d p oi nts 
(as descri be d bel o w) at r es pecti ve visits f or eac h st u d y pr o d uct. 
C ha n ge fr o m Baseli ne will be calc ulate d at Da y 2 8 a n d Da y 5 6 f or all D H E Q e n d p oi nts.  
Secti o n 1  
1.  I m pa ct o n E ver y da y Life: Q7 , Q8  & Q 9  (se parate sc ores) 
Secti o n 2  
1.  D H E Q T otal Sc ore (s u m of Q 1 -3 4)  
2.  D H E Q Restricti o ns D o m ai n sc ore (s u m of Q 1 -4)  
3.  D H E Q A da pt ati o n D o mai n sc ore (s u m of Q 5 -1 6)  
4.  D H E Q S ocial I m pa ct D o mai n sc ore (s u m of Q 1 7 -2 1)  
5.  D H E Q E m oti o nal I m pact D o mai n sc ore (s u m of Q 2 2 -2 9)  
6.  D H E Q I de ntit y D o mai n sc ore (s u m of Q 3 0 -3 4)  
7.  D H E Q Gl o bal Oral Healt h sc ore ( Q 3 5) 
8.  D H E Q Effect o n Life O v erall sc ore (s u m of Q 3 6-Q 3 9)  
C ha n ge fr o m Baseli ne will be calc ulate d at t he s u bject -le vel first t he n mea n c ha n ge fr o m 
Baseli ne will be calc ulat e d f or eac h D H E Q e n d p oi nt (me nti o ne d a b o ve ) acr oss all s u bjects.  
Descri pti ve statistics ( n, mea n, S D, S E, me dia n, mi ni m u m, a n d ma xi m u m) will be prese nt e d 
f or eac h D H E Q -4 8 e n d p oi nt ( me nti o ne d a b o ve)  at eac h ass ess me nt ti me p oi nt i n 
Ta ble  1 4. 2. 4 . 1. 1 a n d 1 4. 2. 5. 1 -8. 1. 1, f or Secti o n 1  a n d Secti o n 2 res pecti vel y a n d f or all s u bjects 
i n mI T T p o p ulati o n b y st u d y pr o d uct. Ra w mea ns ( ± S E) f or eac h D H E Q e n d p oi nt, a n d t he 
i n di vi d ual 
D H E Q q uesti o ns, at eac h assess m e nt will be pl otte d b y st u d y pr o d uct i n 
Fi g ure  1 4. 2. 2. 1 1 .1 a n d Fi g ure 1 4. 2. 2. 3 -1 0 . 1, f or Secti o n 1 a n d Secti o n 2 res pecti vel y a n d f or 
all s u bjects i n mI T T p o p ulati o n.  
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I n di vi d ual D H E Q e n d p oi nt  data f or eac h e n d p oi nt ( me nti o ne d a b o ve) will be liste d f or eac h 
s u bject b y visit a n d st u d y pr o d uct gr o u p i n Listi n g 1 6. 2. 6. 5 , 1 6. 2. 6. 6. 1 -7 , f or Secti o n 1 a n d 
Secti o n 2 res pecti vel y, f or all ra n d o mize d s u bjects. 
4. 4. 2. 4. 1  St ati sti c al H y p ot h e si s, M o d el a n d M et h o d of A n al y si s  
T he  f oll o wi n g n ull a n d alter nati ve h y p ot hes es will be e val uat e d : 
•  H 0: T here is n o differe n ce bet wee n b aseli ne a n d p ost -baseli ne ( Da y 2 8, Da y 5 6)  D H E Q 
sc ores i n t he test t o ot h paste c o m pare d t o t he refere nce t o ot h paste  
•  H 1: T here is a differe nce bet wee n baseli ne a n d p ost -baseli ne ( Da y 2 8, Da y 5 6)  D H E Q 
sc ores i n t he test t o ot h paste c o m pare d t o t he refere nce t o ot h paste  
C ha n ge fr o m Baseli ne f or eac h D H E Q e n d p oi nt liste d a b o ve will be a nal yze d usi n g a M M R M 
wit h visit a n d stratificati o n [ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore of t he t w o ‘Test Teet h’ 
( 2 or 3)] as fi xe d effects, a n d t he res pecti ve Baseli ne D H E Q sc ore as a c o v ariate. S u bject will 
be i ncl u de d as a re p eat e d meas ure wit h u nstr uct ure d c o varia n ce matri x. Ke n war d -R o ger’s 
de grees of free d o m will be a p plie d. T he esti mates of t he a dj uste d mea n ( S E) c h a n ge  fr o m 
Baseli ne will be pres e nte d al o n g wit h 9 5 % C Is f or eac h treat me nt gr o u p.  I n t he e v e nt t hat t he 
m o del d oes n ot c o n ver ge o n t he u nstr uct ure d c o varia nce matri x, t he n a n a p pr o priate alter nati ve 
will be c o nsi dere d.  
Usi n g t he a b o v e m o del, t he a dj uste d m ea n c ha n g e fr o m baseli ne i n eac h D H E Q e n d p oi nt liste d 
a b o ve will be re p orte d b y st u d y pr o d uct gr o u p al o n g wit h 9 5 % CIs  a n d p -val ues  testi n g f or a 
n o n -zer o c ha n g e fr o m b aseli ne will be pr o vi de d i n Ta ble 1 4. 2. 4 . 2. 1 a n d 1 4. 2. 5. 1 -8. 2. 1 , f or 
Secti o n 1 a n d Secti o n 2 res pecti vel y . 
T he ass u m pti o ns of n or malit y a n d h o m o ge neit y of varia nce i n t he M M R M will be i n vesti gate d. 
I n case of vi olati o n of t hese ass u m pti o ns, a s uita ble n o n-para m etric test ( Wilc o x o n Si g ne d Ra n k 
Test) will be p erf or m e d t o assess t he c ha n g e fr o m Baseli ne c o m paris o n ( P ost -Baseli ne  vs. 
Baseli ne ); t he res ults will be pr o vi de d t o s u p p ort t he M M R M res ults. 
4. 4. 2. 4. 2  S u p p orti v e A n al y s e s  
If t here is at least  1 0 % differe n ce i n t he o v erall n u m ber of s u bjects b et wee n P P a n d mI T T 
P o p ulati o n s, a s u m mar y a n d statistical a nal ysis of eac h of t he D H E Q -4 8  Sc ore e n d p oi nt will be 
prese nte d f or t he P P P o p ulati o n  i n (Ta ble 1 4. 2. 4 . 1. 2 a n d 1 4. 2. 5. 1 -8 . 1. 2 f or Secti o n 1 a n d Secti o n 
2 res pecti vel y) a n d (T a ble 1 4. 2. 4. 2 . 2 a n d 1 4. 2. 5. 1 -8 .2 . 2 f or Secti o n 1 a n d Secti o n 2 
res pecti vel y), res p ecti vel y f or s u m mar y ta ble a n d a nal ysis ta ble. I n a d diti o n, D H E Q -4 8  sc ore 
(Fi g ure  1 4. 2 . 2.1 1 .2 a n d Fi g ure  1 4. 2. 2. 3 -1 0 . 2 f or S ecti o n 1 a n d Secti o n 2 res pecti vel y) f or eac h 
me nti o ne d e n d p oi nt at eac h ti me p oi nt will be pl otte d b y st u d y pr o d uct i n f or all s u bjects i n P P 
P o p ulati o n . 
A decisi o n o n w het her a P P a nal ysis will be perf or me d will be ma de pri or t o st u d y u n bli n di n g 
(rele ase of t he ra n d o mizati o n c o des). 
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4. 4. 3  E x pl or at or y Effi c a c y V ari a bl e s  
4. 4. 3. 1  
N u m b er of S e n siti v e T e et h  
T he n u m ber of teet h se nsiti ve t o a n e va p orati ve (air) sti m ul us i n t he p o ol of ‘ Eli gi ble Teet h’ 
i de ntifie d at Scree ni n g will be m o nit ore d acr oss t he st u d y peri o d. F or t his p ur p ose, a ‘ Se nsiti ve 
T o ot h’ will be defi ne d as ha vi n g a Sc hiff se nsiti vit y sc ore ≥ 2 .  
‘ Eli gi ble Teet h’ = Teet h wit h n o de ntiti o n e xcl usi o ns w hic h meet E A R, M GI a n d m o bilit y 
i ncl usi o n criteria, a n d h a v e a Scree ni n g tactile t hr es h ol d ≤ 2 0 g a n d a Scree ni n g Sc hiff se nsiti vit y 
sc ore ≥ 2.  
T he n u m ber of ‘ Se nsiti ve Teet h’ (i.e., t he n u m ber of ‘ Eli gi ble Teet h’ wit h Sc hiff se nsiti vit y 
sc ore ≥ 2) will be calc ulate d at Scree ni n g, Bas eli ne, Da y 2 8 a n d Da y 5 6.  
•  At Scree ni n g, t he n u m ber of ‘ Se nsiti ve Teet h’ will be e q ual t o t he n u m ber of ‘ Eli gi ble 
Teet h’. Eli gi ble Teet h’ = Teet h wit h Scree ni n g tactile t hres h ol d ≤ 2 0 g a n d Scree ni n g 
Sc hiff se nsiti vit y sc ore ≥2.  
•  At Baseli ne, Da y 2 8 a n d Da y 5 6, all ‘ Eli gi ble Teet h’ will be teste d f or e va p orati ve (air) 
se nsiti vit y. T he n u m ber of ‘ Se nsiti ve Teet h’ will b e t he n u m ber of ‘ Eli gi ble Teet h’ wit h a 
Sc hiff se nsiti vit y sc ore ≥ 2 at t hat visit.  
Descri pti ve statistics ( n, mea n, S D, S E, me dia n, mi ni m u m, a n d ma xi m u m) will be prese nt e d 
f or N u m ber of Se nsiti ve Teet h at eac h assess me nt ti me p oi nt i n Ta ble 1 4. 2. 5. 9. 1 f or all s u bjects 
i n mI T T p o p ulati o n b y st u d y pr o d uct. Ra w mea ns ( ± S E) of N u m ber of Se nsiti ve Teet h at eac h 
ti me p oi nt will be pl otte d b y st u d y pr o d uct i n Fi g ure 1 4. 2. 4. 1 f or all s u bjects i n mI T T 
p o p ulati o n.  
I n di vi d ual Sc hiff s e nsiti vit y Sc ore ( of eac h eli gi ble t o ot h) data will be liste d f or eac h s u bject b y 
visit a n d st u d y pr o d uct gr o u p i n Listi n g 1 6. 2. 6. 7 , f or all ra n d o mize d s u bjects. 
N o f or mal statistical a nal ysis is pla n ne d . 
4. 4. 3. 2  
L a b ell e d M a g nit u d e S c al e ( L M S s)  
S u bjects will rate I nte nsit y, D urati o n , T olera bilit y of t heir res p o nse t o t h e e va p orati ve (air) 
sti m ul us a n d D escri b e t h eir res p o nse, usi n g f o ur 1 0 0 -milli metre ( m m) L M Ss, at Baseli ne, Da y 
2 8 a n d Da y 5 6.  
L M Ss s h o ul d be c o m plete d i m me diatel y after t he cli nical e xa mi ner has rec or de d t he Sc hiff 
se nsiti vit y sc ore f or a gi ve n t o ot h. T o a v oi d bias, t he s u bject s h o ul d be u na ware of t he 
e xa mi ner’s sc ore a n d t h e cli nical e xa mi ner s h o ul d n ot ha ve visi bilit y of t he s u bject’s L M S 
res p o nses.  
Baseli ne: C o m plete f o ur L M Ss f or eac h t o ot h wit h a Baseli ne tactile t hres h ol d of ≤ 2 0 g a n d a 
Baseli ne Sc hiff se nsiti vit y sc ore ≥ 2.  
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Da ys 2 8 & 5 6: C o m plete f o ur L M Ss f or eac h ‘ Test T o ot h’ (i.e., t he t w o teet h selecte d b y t he 
cli nical e xa mi ner at Baseli ne).  
St u d y staff will meas ure t he dista nce t o t he s u bj ect’s mar k (‘ X’) fr o m left t o ri g ht al o n g t he 1 0 0 
m m li ne a n d rec or d t his val ue (i n m m) i n t he e C R F f or eac h L M S c o m plet e d.  
4. 4. 3. 2. 1  C h a n g e fr o m B a s eli n e i n L M S e n d p oi nt s at D a y 2 8 a n d D a y 5 6  
T he ke y e x pl orat or y vari a ble is t he c ha n ge fr o m Baseli ne i n L M Ss at Da y 2 8 a n d Da y 5 6 f or 
eac h of t h e bel o w L M S e n d p oi nts:  
•  I nte nsit y  
•  D urati o n  
•  T olera bilit y  
•  Descri pti o n  
L M S data will be a nal yse d  f or t he t w o ‘ Test Teet h’ o nl y. C ha n ge fr o m Baseli ne will be deri ve d 
f or eac h ‘ Test T o ot h’ first bef ore calc ul ati n g mea n c ha n g e f or t he t w o ‘ Test Teet h’ f or eac h 
s u bject. 
Descri pti ve statistics ( n, mea n, S D, S E, me dia n, mi ni m u m, a n d ma xi m u m) will be prese nt e d 
f or eac h of L M S e n d p oi nts calc ulate d i n di vi d uall y (i n m m) as t he a vera ge s c ore of t he t w o test 
teet h at eac h assess me nt ti me p oi nt i n Ta ble 1 4. 2. 5. 1 0. 1 -4. 1 f or all s u bjects i n mI T T p o p ulati o n 
b y st u d y pr o d uct. Ra w mea ns ( ± S E) f or eac h of L M S e n d p oi nts at eac h ti me p oi nt will be 
pl otte d b y st u d y pr o d uct i n Fi g ure 1 4. 2. 5. 1 -4 f or all s u bjects i n mI T T p o p ul ati o n. 
I n di vi d ual L M S e n d p oi nts data will be liste d f or eac h s u bject b y visit a n d st u d y pr o d uct gr o u p 
i n Listi n g 1 6. 2. 6. 8  f or eac h visit, a n d se paratel y f or t w o test teet h res pecti vel y, f or all 
ra n d o mize d s u bjects. 
4. 4. 3. 2. 2  St ati sti c al H y p ot h e si s, M o d el a n d M et h o d of A n al y si s  
T he  f oll o wi n g n ull a n d alter nati ve h y p ot hes es will be e val uat e d : 
•  H 0: T here is n o differe nce bet w ee n b aseli ne a n d p ost -baseli ne ( Da y 2 8, Da y 5 6)  L M S 
sc ores i n t he test t o ot h paste c o m pare d t o t he refere nce t o ot h paste  
•  H 1: T here is a differe nce bet wee n baseli ne a n d p ost -baseli ne ( Da y 2 8, Da y 5 6)  L M S 
sc ores i n t he test t o ot h paste c o m pare d t o t he refere nce t o ot h paste  
C ha n ge fr o m Baseli ne f or eac h L M S e n d p oi nt liste d a b o ve will be a nal yze d usi n g a M M R M 
wit h visit a n d stratificati o n [ ma xi m u m Baseli ne Sc hiff se nsiti vit y sc ore of t he t w o ‘ Test T eet h’ 
( 2 or 3)] as fi xe d effects, a n d t he res pecti ve Baseli ne L M S sc ore as a c ovari ate. S u bject will be 
i ncl u de d as a re p eate d me as ure wit h u nstr uct ure d c o varia nce matri x. Ke n war d-R o ger’s d e grees 
of free d o m will be a p plie d. T he esti mates of t he a dj uste d mea n ( S E) c ha n ge fr o m Baseli ne will 
be pres e nte d al o n g wit h 9 5 % CIs f or eac h trea t me nt gr o u p. I n t he e ve nt t hat t he m o del d oes n ot 
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c o n ver ge o n t he u nstr uct ure d c o v aria n ce matri x, t he n a n a p pr o priate alter nati ve will be 
c o nsi dere d.  
Usi n g t he a b o ve m o del, t he a dj uste d mea n c ha n ge fr o m baseli ne i n eac h L M S e n d p oi nt liste d 
a b o ve will be re p orte d b y st u d y pr o d uct gr o u p al o n g wit h 9 5 % c o nfi de nce i nter vals ( CIs) a n d 
p -val ues testi n g f or a n o n -zer o c ha n g e fr o m b aseli ne will be pr o vi de d i n T a ble 1 4. 2. 5. 1 0. 1 -4. 2 . 
T he ass u m pti o ns of n or malit y a n d h o m o ge neit y of varia nce i n t he M M R M will be i n vesti gate d. 
I n case of vi olati o n of t hese ass u m pti o ns, a s uita ble n o n-para m etric test ( Wilc o x o n Si g ne d Ra n k 
Test) will be p erf or m e d t o assess t he c ha n g e fr o m Baseli ne c o m paris o n ( P ost -Baseli ne vs. 
Baseli ne); t he res ults will be pr o vi de d t o s u p p ort t he M M R M res ults.  
4. 4. 3. 3  
S ati sf a cti o n wit h Tr e at m e nt  u si n g  N R S  
At t he e n d of t he st u d y ( Visit 4 ), s u bjects will be as ke d t o rate t heir le vel of satisfacti o n wit h 
t heir all ocate d st u d y pr o d uct usi n g N R S. T he N R S is a n 1 1 -p oi nt or di nal scale use d t o assess 
t he s u bject’s satisfacti o n wit h t he pr o d uct’s o verall ma na ge me nt of t heir D H. T he scale ra n g es 
fr o m 0 (c o m pletel y dissatisfie d) t o 1 0 (c o m pletel y satisfie d), wit h hi g her sc ores i n dicati ve of 
g reater satisfacti o n ( va n Berc kel, 2 0 1 7): 
see e xa m ple bel o w. S u bjects will be as ke d t o rec or d t he n u meric val ue o n t he se g me nte d scale 
t hat best descri bes t heir le vel of satisfacti o n after 8 wee ks t wice dail y use a n d i n dicate w h y t he y 
selecte d a partic ular s c ore i n a ns w er t o t h e q uesti o n ‘ Please g i v e m ore det ails o n w h y y o u are 
satisfie d or dissatisfie d wit h t he pr o d uct’ (free te xt res p o nse).  
Fi g ur e 4 -1  
N u m eri c al R ati n g S c al e ( 0 t o 1 0)  
 
4. 4. 3. 3. 1  S ati sf a cti o n N R S S c or e  
Descri pti ve statistics ( n, mea n, S D, S E, me dia n, mi ni m u m, a n d ma xi m u m) will be prese nt e d 
f or N R S Sc ore at D a y 5 6 i n Ta ble 1 4. 2. 5. 1 2. 2  f or all s u bjects i n mI T T p o p ulati o n b y st u d y 
pr o d uct.  
Als o, s u m mar y of t he n u m ber of s u bjects ( %) re p orti n g at eac h le vel of t he N R S a n d t he 
c u m ulati ve n u m ber of s u bjects ( %) re p orti n g at eac h le vel or hi g her at Da y 5 6 will be prese nte d 
i n Ta ble 1 4. 2. 5. 1 2. 1  b y st u d y pr o d uct. 
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I n di vi d ual N R S Sc ore  data will be liste d f or eac h s u bject f or Da y 5 6 b y  st u d y pr o d uct gr o u p i n 
Listi n g  1 6. 2. 6. 9 , f or all ra n d o mize d s u bjects. 
4. 4. 3. 3. 2  St ati sti c al H y p ot h e si s, M o d el a n d M et h o d of A n al y si s  
N o f or mal statistical a nal ysis is pla n ne d f or assess me nt of N R S  e n d p oi nt.  
4. 4. 4  
H a n dli n g of M i s si n g V al u e s/ C e n s ori n g/ D i s c o nti n u ati o n s 
Missi n g data will n ot be re place d or i m p ute d. S u bjects w h o wit h dra w fr o m t he st u d y 
pre mat urel y will be i ncl u de d i n t he statistical a nal yses u p t o t he p oi nt of disc o nti n uati o n.  
T he use of 
M M R M a nal yses acc o u nt f or missi n g data ass u mi n g a missi n g at ra n d o m 
ass u m pti o n,  i.e., t here is a s yste matic relati o ns hi p bet wee n t he pr o pe nsit y of missi n g val ues a n d 
t he o bser ve d d ata, b ut n ot t he missi n g data.  
It is t heref ore ass u me d t hat a s u bject wit h missi n g data at o n e p ost-Bas eli ne ass ess me nt visit 
w o ul d ha ve o btai ne d a si milar efficac y res ult at t hat visit c o m pare d t o a s u bject usi n g t he sa me 
st u d y pr o d uct wit h si milar n o n-missi n g res ults at ot her ti me p oi nts ( Ba seli ne a n d t he ot her p ost-
Baseli ne assess me nt visits).  Se nsiti vit y a nal yses  ma y be a d d e d t o t he S A P pri or t o u n bli n di n g 
i n case of hi g h dr o p-o ut r ates a n d/ or e x cl usi o n  fr o m P P a nal yses. 
4. 5  
A n al y si s of S af et y  
T he safet y pr ofile of t h e st u d y pr o d ucts  will be assesse d wit h res pect t o A Es or i nci de nts a n d 
O S T/ O H T a b n or malities i n oral healt h st u d y.  
4. 5. 1  
A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s  
All A Es will be re vie we d b y t he Cli nical Researc h Scie ntist or Desi g nee pri or t o data base l oc k 
a n d will be c o de d t o a s yste m or ga n class ( S O C) a n d preferre d ter m ( P T) usi n g t he Me dical 
Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A ). 
A Es will be classifie d as oral a n d n o n -oral o n t he A E pa ge of e C R F.  
Treat me nt e mer ge nt a d v erse e ve nts ( T E A Es) are d efi ne d as n e w A Es t hat o cc ur o n or after t he 
first st u d y pr o d uct use  (if t his date is missi n g a s uita ble alter nati ve will be use d e. g., date of 
ra n d o mizati o n). A Es  wit h a n o nset date/ti me pri or t o t he first st u d y pr o d uct use  will be 
c o nsi dere d as n o n -treat me nt e mer ge nt. 
T he f oll o wi n g s u m mar y ta bles a n d listi n gs will be prese nte d b y st u d y pr o d uct o n Safet y 
p o p ulati o n . 
•  Ta ble of T E A Es b y S O C a n d P T ( Ta ble 1 4. 3. 1. 1 ). 
•  Ta ble of T E A Es b y Oral/ N o n -Oral a n d P T ( Ta ble 1 4. 3. 1. 2 ) 
•  Ta ble of treat me nt relat e d T E A Es b y S O C a n d P T ( Ta ble 1 4. 3. 1. 3 ) 
•  Ta ble of treat me nt relat e d T E A Es b y Oral/ N o n -Oral  a n d P T ( Ta bl e 1 4. 3. 1. 4 ) 
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•  Ta ble of n o n -s eri o us T E A Es b y S O C a n d P T ( Ta ble 1 4. 3. 1.5 ) [ o nl y pr o d u ce d if t here are 
m ore t ha n 5 S A Es]  
•  T a ble of seri o us T E A Es b y S O C a n d P T ( Ta ble 1 4. 3. 1. 6 ) [ o nl y pr o d uce d if t here are m or e 
t ha n 5 S A Es ] 
•  Listi n g of all A Es ( Listi n g 1 6. 2. 7. 1)  
•  Listi n g of deat hs ( Listi n g 1 4. 3. 2. 1 ) 
•  Listi n g of n o n -fatal S A Es ( Listi n g 1 4. 3. 2.2 ) 
•  Listi n g of T E A Es lea di n g t o st u d y or pr o d uct  disc o nti n uati o n  ( Listi n g 1 4. 3. 2.3 ) 
•  Listi n g of T E A Es classifie d as O ral ( Listi n g 1 4. 3. 2.4 ) 
I n t he e ve nt t hat t here is n ot hi n g t o re p ort, a n ull ta ble or listi n g will be pr o d uce d.  
All inci de nts will be liste d i n Listi n g 1 6. 2. 7. 2  f or all ra n d o mize d p o p ulati o n. I n t he e ve nt t hat 
t here is n ot hi n g t o re p ort, a n ull listi n g will be pr o d uce d. 
4. 5. 2  
Ot h er S af et y V ari a bl e s  
Ot her safet y varia bl es are liste d bel o w:  
•  O S T e xa mi nati o n  
•  O H T e xa mi nati o n  
4. 5. 2. 1  
O S T E x a mi n ati o n  
T his pr oce d ure will be c o n d ucte d b y a q ualifie d, e x perie n ce d cli nical e xa mi ner. T he O S T 
e xa mi nati o n will be acc o m plis he d b y direct vis ual o bser vati o n a n d pal pati o n, usi n g retracti o n 
ai ds as a p pr o pri ate, a n d will i ncl u de e xa mi nati o n of t he la bial m uc osa (i n cl u di n g li ps), b uccal 
m uc osa, 
m uc o gi n gi val f ol ds, gi n gi val 
m uc osa, har d palate, 
s oft palate, t o nsillar area, 
p har y n geal area, t o n g ue, s u bli n g ual area, s u b ma n di b ular area a n d s ali var y gla n ds. T he res ults 
of t he e xa mi nati o n will be rec or de d i n t he e C R F as ei t her ‘n or mal ’ or ‘a b n or mal ’; d etails of a n y 
a b n or malities will be d oc u me nte d i n t he e C R F.  
A n y o bser vati o n t hat c ha n ges fr o m ‘n or mal ’ t o ‘a b n or m al ’, or w ors e ns, fr o m t he O S T 
e xa mi nati o n c o m plete d at Scree ni n g will be rec or de d as a n A E. 
O S T will be s u m marize d ( n u m ber a n d p erce nta ges of s u bjects wit h a b n or malities, wit h o ut 
a b n or malities , or O S T n ot e xa mi ne d) b y visit a n d st u d y pr o d uct i n Ta ble 1 4. 3. 4. 1 f or all s u bjects 
i n Safet y P o p ulati o n. O S T e xa mi nati o n will be liste d ( Listi n g 1 6. 2. 8. 1) f or Safet y P o p ulati o n . 
4. 5. 2. 2  
O H T E x a mi n ati o n  
T his pr oce d ure s h o ul d b e c o n d uct e d b y a q ualifi e d, e x perie nce d cli nical e xa mi ner. T h e O H T 
e xa mi nati o n will be acc o m plis he d b y dir ect vis ual o bser vati o n, usi n g retr acti o n ai ds as 
a p pr o priate, a n d will i de ntif y e na mel irre g ularities, t o ot h fract ur es, gr ossl y cari o us lesi o ns/ gr oss 
deca y, d efecti ve/fa ult y rest orati o ns ( b ot h direct a n d i n dir ect rest orati o ns, i ncl u di n g fi xe d/ 
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Pa ge 3 1  of 4 8  
re m o va ble pr ost h eses), n o n-cari o us t o ot h s urface l oss (a brasi o n, attriti o n, a bfracti o n a n d 
er osi o n), a n y ot her h ar d tiss ue irre g ularities (e. g., h y p o - a n d h y per mi neralizati o n, 
decalcifi cati o n) a n d si g nifica nt t o ot h stai ni n g. O bser vati o ns will b e liste d as ‘abse nt ’ or 
‘prese nt’; c o n diti o ns n ote d as ‘pres e nt ’ will be des cri be d i n t he e C R F.  
A n y o bser vati o n t hat c ha n ges fr o m ‘a bse nt’ t o ‘ prese nt’ or w ors e ns fr o m t he O H T e xa mi nati o n 
c o m plete d at Scree ni n g will be rec or de d as a n A E. T he pres e nce of a n y i m pla nts, fi xe d or 
re m o va ble de nt ur es, fi xe d or re m o va ble ort h o d o ntic braces/ ba n ds, fi xe d ort h o d o ntic retai ners, 
f ull cr o w ns or ve neers will be rec or de d, al o n g wit h e vi de nce of gr oss i ntra -oral ne glect or t he 
nee d f or e xte nsi ve de nt al t hera p y.  
O H T e xa mi nati o n will be liste d ( Listi n g 1 6. 2. 8. 2) f or safet y p o p ulati o n. 
4. 6  
A n al y si s of O t h er V ari a bl e s  
4. 6. 1  
D H E Q -4 8 a n d L M S s R el ati o n s hi p  
T he rel ati o ns hi p bet wee n s u bject res p o ns es t o t he D H E Q -4 8 a n d t h e f o ur L M Ss will be 
i n vesti gate d. F or eac h D H E Q d o mai n ( Restricti o ns, A da ptati o n, S ocial I m pact, E m oti o nal 
I m pa ct, I de ntit y), eac h L M S e n d p oi nt (I nte nsit y, D urati o n, T olera bilit y, Descri pti o n) will be 
pl otte d a gai nst d o mai n sc ore at eac h ass ess me nt ti me p oi nt ( Baseli ne, 2 8 a n d 5 6 da ys). A matri x 
of c orrelati o n pl ots will be prese nt e d f or eac h d o m ai n  i n Fi g ure 1 4. 2. 6. 1. S p ear ma n’s c orrelati o n 
c oeffi cie nt will be calc ul ate d al o n g wit h t he ass ociat e d p-val ue a n d prese nt e d wit h its res pecti ve 
c orrel ati o n pl ot  ( Fi g ure 1 4. 2. 6. 1) f or 
mI T T p o p ulati o n. Als o, f or eac h D H E Q d o mai n 
( Restricti o ns, A da ptati o n, S ocial I m pact, E m oti o nal I m p act, I d e ntit y) a n d eac h L M S e n d p oi nt 
(I nte nsit y, D urati o n, T olera bilit y, Descri pti o n), S pear ma n’s c orrel ati o n c oeffi cie nt will be 
calc ulate d al o n g wit h t he ass ociate d p -val u e a n d prese nte d at eac h assess me nt ti me p oi nt 
( Baseli ne, 2 8 a n d 5 6 da ys) i n Ta ble 1 4. 2. 5. 1 1. 1 f or all s u bjects i n t he mI T T P o p ulati o n. 
4. 6. 2  
S c hiff S e n siti vit y S c or e a n d L M S s R el ati o n s hi p  
T he rel ati o ns hi p bet wee n Sc hiff se nsiti vit y sc ore a n d t he f o ur L M Ss will be i n vesti gate d. Sc hiff 
se nsiti vit y sc ore ( mea n s c ore of t he t w o ‘ Test Teet h’) a n d t he f o ur L M S e n d p oi nts (I nt e nsit y, 
D urati o n, T olera bilit y, Descri pti o n) will be pl otte d at eac h asse ss me nt ti me p oi nt ( Baseli ne, 2 8 
a n d 5 6 da ys) i n a matri x of c orrelati o n pl ots  ( Fi g ure 1 4. 2. 6. 2) f or mI T T p o p ulati o n. S pear ma n’s 
c orrel ati o n c oefficie nt will be calc ulate d al o n g wit h t he ass ociate d p -val ue a n d prese nte d wit h 
its res pecti ve c orrelati o n pl ot (Fi g ure 1 4. 2. 6. 2). Als o, f or Sc hiff s e nsiti vit y sc ore a n d eac h L M S 
e n d p oi nt (I nte nsit y, D urati o n, T olera bilit y, Descri pti o n), S pear ma n’s c orrelati o n c oeffi cie nt 
will be calc ulate d al o n g wit h t he ass ociate d p -v al ue a n d pres e nte d at eac h assess me nt ti me p oi nt 
( Baseli ne, 2 8 a n d 5 6 da ys) i n Ta ble 1 4. 2. 5. 1 1. 2 f or all s u bjects i n t he mI T T P o p ulati o n. 
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5  
C h a n g e s t o t h e Pr ot o c ol D efi n e d St ati sti c al A n al y si s Pl a n  
T here were n o  c ha n ges t o t he ori gi nall y pla n ne d statistical a nal ysis s pecifie d fr o m t he pr ot oc ol 
versi o n 2 . 0 ( Dat e d: 0 7 -Fe b -2 0 2 4 ). 
 
 
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Pa ge 3 3  of 4 8  
A p p e n di x 1 : Li st of D at a Di s pl a y s 
 
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
1 4. 1 D e m o gr a p hi c D at a S u m m ar y T a bl e s a n d Fi g ur e s  
  
T a bl e  
1 4. 1. 1  
S u bj e ct Di s p o siti o n  
All S cr e e n e d 
S u bj e ct s  
1 4. 1. 1  
Y e s  
 
T a bl e  
1 4. 1. 2  
I n ci d e n c e of I m p ort a nt Pr ot o c ol D e vi ati o n s 
All R a n d o mi z e d 
S u bj e ct s  
1 4. 1. 2  
 
 
T a bl e  
1 4. 1. 3. 1  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
S af et y  P o p ul ati o n  
1 4. 1. 3. 1  
 
 
T a bl e  
1 4. 1. 3. 2  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
mI T T P o p ul ati o n  
1 4. 1. 3. 1  
Y e s  
1 4. 2 Effi c a c y D at a S u m m ar y T a bl e s a n d Fi g ur e s  
  
T a bl e  
1 4. 2. 1  
S u m m ar y of Br u s hi n g C o m pli a n c e  
mI T T P o p ul ati o n  
1 4. 2. 1  
  
 
T a bl e  
1 4. 2. 2. 1. 1  
S u m m ar y of S c hiff S e n siti vit y S c or e  of t h e  T w o T e st 
T e et h  
mI T T P o p ul ati o n  
1 4. 2. 2. 1. 1  
Y e s  
 
T a bl e  
1 4. 2. 2. 1. 2  
S u m m ar y of S c hiff S e n siti vit y S c or e  of t h e  T w o T e st 
T e et h  
P P P o p ul ati o n  
1 4. 2. 2. 1. 1  
 
 
T a bl e  
1 4. 2. 2. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n S c hiff 
S e n siti vit y S c or e of t h e  T w o T e st T e et h  O v er Ti m e  
mI T T P o p ul ati o n  
1 4. 2. 2. 2. 1  
Y e s  
 
T a bl e  
1 4. 2. 2. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n S c hiff 
S e n siti vit y S c or e of t h e  T w o T e st T e et h  O v er Ti m e  
P P P o p ul ati o n  
1 4. 2. 2. 2. 1  
 
 
T a bl e  
1 4. 2. 3. 1. 1  
S u m m ar y of T a ctil e T hr e s h ol d ( g)  of t h e  T w o T e st T e et h  
mI T T P o p ul ati o n  
1 4. 2. 3. 1. 1  
Y e s  
 
T a bl e  
1 4. 2. 3. 1. 2  
S u m m ar y of T a ctil e T hr e s h ol d ( g)  of t h e T w o T e st T e et h  
P P P o p ul ati o n  
1 4. 2. 3. 1. 1  
 
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Pa ge 3 4  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
T a bl e  
1 4. 2. 3. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n T a ctil e 
T hr e s h ol d ( g) of t h e T w o T e st T e et h O v er Ti m e  
mI T T P o p ul ati o n  
1 4. 2. 3. 2. 1  
Y e s  
 
T a bl e  
1 4. 2. 3. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n T a ctil e 
T hr e s h ol d ( g) of t h e T w o T e st T e et h O v er Ti m e  
P P P o p ul ati o n  
1 4. 2. 3. 2. 1  
 
 
T a bl e  
1 4. 2. 4. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 1 I m p a ct of E v er y d a y Lif e, 
Q 7 t o Q 9)  
mI T T P o p ul ati o n  
1 4. 2. 4. 1. 1  
 
 
T a bl e  
1 4. 2. 4. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 1 I m p a ct of E v er y d a y Lif e, 
Q 7 t o Q 9)  
P P P o p ul ati o n  
1 4. 2. 4. 1. 1  
 
 
T a bl e  
1 4. 2. 4. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 1 I m p a ct of E v er y d a y Lif e, Q 7 t o Q 9) 
mI T T P o p ul ati o n  
1 4. 2. 4. 2. 1  
 
 
T a bl e  
1 4. 2. 4. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 1 I m p a ct of E v er y d a y Lif e, Q 7 t o Q 9) 
P P P o p ul ati o n  
1 4. 2. 4. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 1. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 1. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 1. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e  
P P P o p ul ati o n  
1 4. 2. 5. 1. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 1. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e O v er Ti m e 
mI T T  P o p ul ati o n  
1 4. 2. 5. 1. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 1. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e O v er Ti m e 
P P P o p ul ati o n  
1 4. 2. 5. 1. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 2. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n 
D o m ai n T ot al S c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 2. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 2. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n 
D o m ai n T ot al S c or e  
P P P o p ul ati o n  
1 4. 2. 5. 2. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 2. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n D o m ai n T ot al S c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 2. 2. 1  
 
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C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
T a bl e  
1 4. 2. 5. 2. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n D o m ai n T ot al S c or e 
P P P o p ul ati o n  
1 4. 2. 5. 2. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 3. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n 
D o m ai n T ot al S c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 3. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 3. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n 
D o m ai n T ot al S c or e  
P P P o p ul ati o n  
1 4. 2. 5. 3. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 3. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n D o m ai n T ot al S c or e 
mI T T P o p ul ati o n  
1 4. 2. 5. 3. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 3. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n D o m ai n T ot al S c or e 
P P P o p ul ati o n  
1 4. 2. 5. 3. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 4. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al 
I m p a ct D o m ai n T ot al S c or e 
mI T T P o p ul ati o n  
1 4. 2. 5. 4. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 4. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al 
I m p a ct D o m ai n T ot al S c or e 
P P P o p ul ati o n  
1 4. 2. 5. 4. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 4. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al I m p a ct D o m ai n T ot al 
S c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 4. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 4. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al I m p a ct D o m ai n T ot al 
S c or e  
P P P o p ul ati o n  
1 4. 2. 5. 4. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 5. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al 
I m p a ct D o m ai n T ot al S c or e 
mI T T P o p ul ati o n  
1 4. 2. 5. 5. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 5. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al 
I m p a ct D o m ai n T ot al S c or e 
P P P o p ul ati o n  
1 4. 2. 5. 5. 1. 1  
 
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C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
T a bl e  
1 4. 2. 5. 5. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al I m p a ct D o m ai n T ot al 
S c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 5. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 5. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al I m p a ct D o m ai n T ot al 
S c or e  
P P P o p ul ati o n  
1 4. 2. 5. 5. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 6. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y 
D o m ai n T ot al S c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 6. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 6. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y 
D o m ai n T ot al S c or e  
P P P o p ul ati o n  
1 4. 2. 5. 6. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 6. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y D o m ai n T ot al S c or e 
mI T T P o p ul ati o n  
1 4. 2. 5. 6. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 6. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y D o m ai n T ot al S c or e 
P P P o p ul ati o n  
1 4. 2. 5. 6. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 7. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2 Gl o b al Or al H e alt h S c or e, 
Q 3 5)  
mI T T P o p ul ati o n  
1 4. 2. 5. 7. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 7. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2 Gl o b al Or al H e alt h S c or e, 
Q 3 5)  
P P P o p ul ati o n  
1 4. 2. 5. 7. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 7. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2 Gl o b al Or al H e alt h S c or e, Q 3 5) 
mI T T P o p ul ati o n  
1 4. 2. 5. 7. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 7. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2 Gl o b al Or al H e alt h S c or e, Q 3 5) 
P P P o p ul ati o n  
1 4. 2. 5. 7. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 8. 1. 1  
S u m m ar y of D H E Q ( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n 
Lif e O v er all s c or e  
mI T T P o p ul ati o n  
1 4. 2. 5. 8. 1. 1  
 
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
3 0 0 1 0 4  
 
 
 
 
Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 3 7  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
T a bl e  
1 4. 2. 5. 8. 1. 2  
S u m m ar y of D H E Q ( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n 
Lif e O v er all s c or e  
P P P o p ul ati o n  
1 4. 2. 5. 8. 1. 1  
 
 
T a bl e  
1 4. 2. 5. 8. 2. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n Lif e O v er all s c or e 
mI T T P o p ul ati o n  
1 4. 2. 5. 8. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 8. 2. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n Lif e O v er all s c or e 
P P P o p ul ati o n  
1 4. 2. 5. 8. 2. 1  
 
 
T a bl e  
1 4. 2. 5. 9. 1  
S u m m ar y of N u m b er of S e n siti v e T e et h  
mI T T P o p ul ati o n  
1 4. 2. 5. 9. 1  
 
 
T a bl e  
1 4. 2. 5. 1 0. 1. 1  S u m m ar y of L a b ell e d M a g nit u d e S c al e –  I nt e n sit y (i n 
m m)  
mI T T P o p ul ati o n  
1 4. 2. 5. 1 0. 1. 1   
 
T a bl e  
1 4. 2. 5. 1 0. 1. 2  St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e –  I nt e n sit y (i n m m) 
mI T T P o p ul ati o n  
1 4. 2. 5. 1 0. 1. 2   
 
T a bl e  
1 4. 2. 5. 1 0. 2. 1  S u m m ar y of L a b ell e d M a g nit u d e S c al e - D ur ati o n  (i n 
m m)  
mI T T P o p ul ati o n  
1 4. 2. 5. 1 0. 1. 1   
 
T a bl e  
1 4. 2. 5. 1 0. 2. 2  St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e - D ur ati o n  (i n m m) 
mI T T P o p ul ati o n  
1 4. 2. 5. 1 0. 2. 2   
 
T a bl e  
1 4. 2. 5. 1 0. 3. 1  S u m m ar y of L a b ell e d M a g nit u d e S c al e - T ol er a bilit y  (i n 
m m)  
mI T T P o p ul ati o n  
1 4. 2. 5. 1 0. 1. 1   
 
T a bl e  
1 4. 2. 5. 1 0. 3. 2  St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e - T ol er a bilit y  (i n m m) 
mI T T P o p ul ati o n  
1 4. 2. 5. 1 0. 3. 2   
 
T a bl e  
1 4. 2. 5. 1 0. 4. 1  S u m m ar y of L a b ell e d M a g nit u d e S c al e - D e s cri pti o n  (i n 
m m)  
mI T T P o p ul ati o n  
1 4. 2. 5. 1 0. 1. 1   
 
T a bl e  
1 4. 2. 5. 1 0. 4. 2  St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e - D e s cri pti o n  (i n m m) 
mI T T  P o p ul ati o n  
1 4. 2. 5. 1 0. 4. 2   
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 3 8  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
T a bl e  
1 4. 2. 5. 1 1. 1  
S p e ar m a n' s C orr el ati o n b et w e e n D H E Q -4 8 D o m ai n s 
a n d L M S E n d p oi nt s  
mI T T P o p ul ati o n  
1 4. 2. 5. 1 1. 1  
 
 
T a bl e  
1 4. 2. 5. 1 1. 2  
S p e ar m a n' s C orr el ati o n b et w e e n S c hiff S e n siti vit y S c or e 
a n d L M S E n d p oi nt s  
mI T T  P o p ul ati o n  
1 4. 2. 5. 1 1. 2  
 
 
T a bl e  
1 4. 2. 5. 1 2. 1  
S u m m ar y of S ati sf a cti o n ( %) wit h Tr e at m e nt N u m eri c al 
R ati n g S c or e ( N R S)  
mI T T P o p ul ati o n  
1 4. 2. 5. 1 2. 1  
 
 
T a bl e  
1 4. 2. 5. 1 2. 2  
S u m m ar y of S ati sf a cti o n wit h Tr e at m e nt N u m eri c al 
R ati n g S c or e ( N R S)  
mI T T  P o p ul ati o n  
1 4. 2. 5. 1 2. 2  
 
 
Fi g ur e  
1 4. 2. 2. 1. 1  
M e a n ( ± S E) S c hiff S e n siti vit y S c or e of t h e T w o T e st 
T e et h O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 1. 1  
 
 
Fi g ur e  
1 4. 2. 2. 1. 2  
M e a n ( ± S E) S c hiff S e n siti vit y S c or e of t h e T w o T e st 
T e et h O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 1. 1  
 
 
Fi g ur e  
1 4. 2. 2. 2. 1  
M e a n ( ± S E) T a ctil e T hr e s h ol d ( g) of t h e T w o T e st T e et h 
O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 2. 1  
 
 
Fi g ur e  
1 4. 2. 2. 2. 2  
M e a n ( ± S E) T a ctil e T hr e s h ol d ( g) of t h e T w o T e st T e et h 
O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 2. 1  
 
 
Fi g ur e  
1 4. 2. 2. 3. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e 
O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 3. 1  
 
 
Fi g ur e  
1 4. 2. 2. 3. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e 
O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 3. 1  
 
 
Fi g ur e  
1 4. 2. 2. 4. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n 
D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 4. 1  
 
 
Fi g ur e  
1 4. 2. 2. 4. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n 
D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 4. 1  
 
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 3 9  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
Fi g ur e  
1 4. 2. 2. 5. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n 
D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 5. 1  
 
 
Fi g ur e  
1 4. 2. 2. 5. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n 
D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 5. 1  
 
 
Fi g ur e  
1 4. 2. 2. 6. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al 
I m p a ct D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 6. 1  
 
 
Fi g ur e  
1 4. 2. 2. 6. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al 
I m p a ct D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 6. 1  
 
 
Fi g ur e  
1 4. 2. 2. 7. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al 
I m p a ct D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 7. 1  
 
 
Fi g ur e  
1 4. 2. 2. 7. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al 
I m p a ct D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 7. 1  
 
 
Fi g ur e  
1 4. 2. 2. 8. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y 
D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 8. 1  
 
 
Fi g ur e  
1 4. 2. 2. 8. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y 
D o m ai n T ot al S c or e O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 8. 1  
 
 
Fi g ur e  
1 4. 2. 2. 9. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2 Gl o b al Or al H e alt h S c or e, 
Q 3 5) O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 9. 1  
 
 
Fi g ur e  
1 4. 2. 2. 9. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2 Gl o b al Or al H e alt h S c or e, 
Q 3 5) O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 9. 1  
 
 
Fi g ur e  
1 4. 2. 2. 1 0. 1  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n 
Lif e O v er all s c or e O v er Ti m e b y  St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 1 0. 1  
 
 
Fi g ur e  
1 4. 2. 2. 1 0. 2  
M e a n ( ± S E) D H E Q ( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n 
Lif e O v er all s c or e O v er Ti m e b y  St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2. 1 0. 1  
 
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 0  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
Fi g ur e  
1 4. 2 . 2.1 1 . 1 
M e a n ( ± S E) D H E Q ( S e cti o n 1, Q 7 t o Q 9) s c or e O v er 
Ti m e b y Q u e sti o n, St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 2. 1 1 . 1 
 
 
Fi g ur e  
1 4. 2. 2. 1 1 . 2 
M e a n ( ± S E) D H E Q ( S e cti o n 1, Q 7 t o Q 9) s c or e O v er 
Ti m e b y  Q u e sti o n, St u d y Pr o d u ct  
P P P o p ul ati o n  
1 4. 2. 2 . 11. 1  
 
 
Fi g ur e  
1 4. 2. 4. 1  
M e a n ( ± S E) N u m b er of S e n siti v e T e et h O v er Ti m e b y 
St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 4. 1  
 
 
Fi g ur e  
1 4. 2. 5. 1  
M e a n ( ± S E) L a b ell e d M a g nit u d e S c al e - I nt e n sit y (i n 
m m)  O v er Ti m e b y St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 5. 1  
 
 
Fi g ur e  
1 4. 2. 5. 2  
M e a n ( ± S E) L a b ell e d M a g nit u d e S c al e - D ur ati o n  (i n 
m m)  O v er Ti m e b y St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 5. 1  
 
 
Fi g ur e  
1 4. 2. 5. 3  
M e a n ( ± S E) L a b ell e d M a g nit u d e S c al e - T ol er a bilit y  (i n 
m m)  O v er Ti m e b y St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 5. 1  
 
 
Fi g ur e  
1 4. 2. 5. 4  
M e a n ( ± S E) L a b ell e d M a g nit u d e S c al e - D e s cri pti o n  (i n 
m m)  O v er Ti m e b y St u d y Pr o d u ct  
mI T T P o p ul ati o n  
1 4. 2. 5. 1  
 
 
Fi g ur e  
1 4. 2. 6. 1  
C orr el ati o n Pl ot for D H E Q -4 8 D o m ai n s a n d L M S 
E n d p oi nt s  
mI T T P o p ul ati o n  
1 4. 2. 6. 1  
 
 
Fi g ur e  
1 4. 2. 6. 2  
C orr el ati o n Pl ot f or S c hiff S e n siti vit y S c or e a n d L M S 
E n d p oi nt s  
mI T T P o p ul ati o n  
1 4. 2. 6. 2  
 
1 4. 3 S af et y D at a S u m m ar y T a bl e s a n d Fi g ur e s  
1 4. 3. 1 Di s pl a y s of A d v er s e E v e nt s  
  
 T a bl e  
1 4. 3. 1. 1  
Tr e at m e nt E m er g e nt A d v er s e E v e nt s b y S y st e m Or g a n 
Cl a s s a n d Pr ef err e d T er m  
S af et y P o p ul ati o n  
 1 4. 3. 1. 1  
Y e s  
 
T a bl e  
1 4. 3. 1. 2  
Tr e at m e nt E m er g e nt A d v er s e E v e nt s b y Or al/ N o n -Or al 
a n d Pr ef err e d T er m  
S af et y P o p ul ati o n  
1 4. 3. 1. 2  
 
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 1  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
T a bl e  
1 4. 3. 1. 3  
Tr e at m e nt R el at e d Tr e at m e nt E m er g e nt A d v er s e E v e nt s 
b y S y st e m Or g a n Cl a s s a n d Pr ef err e d T er m  
S af et y P o p ul ati o n  
1 4. 3. 1. 1  
 
 
T a bl e  
1 4. 3. 1. 4  
Tr e at m e nt R el at e d Tr e at m e nt E m er g e nt A d v er s e E v e nt s 
b y Or al/ N o n -Or al a n d Pr ef err e d T er m  
S af et y P o p ul ati o n  
1 4. 3. 1. 2  
 
 
T a bl e  
1 4. 3. 1. 5  
N o n -S eri o u s Tr e at m e nt E m er g e nt A d v er s e E v e nt s b y 
S y st e m Or g a n Cl a s s a n d Pr ef err e d T er m  
S af et y P o p ul ati o n  
1 4. 3. 1. 1  
 
 
T a bl e  
1 4. 3. 1. 6  
S eri o u s Tr e at m e nt E m er g e nt A d v er s e E v e nt s b y S y st e m 
Or g a n Cl a s s a n d Pr ef err e d T er m  
S af et y P o p ul ati o n  
1 4. 3. 1. 1  
 
1 4. 3. 2 Li sti n g s of D e at h s, Ot h er S eri o u s a n d Si g nifi c a nt A d v er s e E v e nt s  
  
Li sti n g  
1 4. 3. 2. 1  
D e at h  
S af et y P o p ul ati o n  
1 6. 2. 7. 1  
 
 
Li sti n g  
1 4. 3. 2. 2  
N o n -f at al S eri o u s A d v er s e E v e nt s  
S af et y P o p ul ati o n  
1 6. 2. 7. 1  
 
 
Li sti n g  
1 4. 3. 2. 3  
Tr e at m e nt E m er g e nt A d v er s e E v e nt s l e a di n g t o St u d y or 
Pr o d u ct Di s c o nti n u ati o n  
S af et y P o p ul ati o n  
1 6. 2. 7. 1  
 
 
Li sti n g  
1 4. 3. 2. 4  
Tr e at m e nt E m er g e nt A d v er s e E v e nt s Cl a s sifi e d a s Or al  
S af et y P o p ul ati o n  
1 6. 2. 7. 1  
 
1 4. 3. 3 N arr ati v e s of D e at h s, Ot h er S eri o u s a n d C ert ai n Ot h er Si g nifi c a nt A d v er s e E v e nt s  
1 4. 3. 4 Ot h er O b s er v ati o n s R el at e d t o S af et y a n d A b n or m al L a b or at or y V al u e s  
  
T a bl e  
1 4. 3. 4. 1  
S u m m ar y of O r al S oft Ti s s u e E x a mi n ati o n  
S af et y P o p ul ati o n  
1 4. 3. 4. 1  
 
A P P E N DI X  
1 6. 1. 6 Li sti n g of S u bj e ct s R e c ei vi n g T e st Dr u g( s)/I n v e sti g ati o n al Pr o d u ct( s) fr o m S p e cifi c B at c h e s, w h er e m or e t h a n o n e b at c h w a s u s e d  
  
N A  
  
  
  
  
  
1 6. 1. 7 R a n d o mi z ati o n S c h e m e a n d C o d e s ( S u bj e ct i d e ntifi c ati o n a n d tr e at m e nt a s si g n e d)  
  
Li sti n g  
1 6. 1. 7. 1  
R a n d o mi z ati o n I nf or m ati o n  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 1. 7. 1  
  
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 2  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
Li sti n g  
1 6. 1. 7. 2  
Kit Li st All o c ati o n  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 1. 7. 2  
 
1 6. 1. 9 D o c u m e nt ati o n of St ati sti c al M et h o d s  
  
R a w O ut p ut  1 6. 1. 9. 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n S c hiff 
S e n siti vit y S c or e  of t h e T w o T e st T e et h  O v er Ti m e 
( R ef er e n c e T a bl e 1 4. 2. 2. 2. 1) 
mI T T P o p ul ati o n  
N A  
Y e s  
 
R a w O ut p ut  1 6. 1. 9. 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n S c hiff 
S e n siti vit y S c or e of t h e T w o T e st T e et h  O v er Ti m e 
( R ef er e n c e T a bl e 1 4. 2. 2. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 3  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n T a ctil e 
T hr e s h ol d ( g) of t h e T w o T e st T e et h  O v er Ti m e 
( R ef er e n c e T a bl e 1 4. 2. 3. 2. 1) 
mI T T P o p ul ati o n  
N A  
Y e s  
 
R a w O ut p ut  1 6. 1. 9. 4  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n T a ctil e 
T hr e s h ol d ( g) of t h e T w o T e st T e et h  O v er Ti m e 
( R ef er e n c e T a bl e 1 4. 2. 3. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 5  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 1 I m p a ct of E v er y d a y Lif e, Q 7 t o Q 9) 
( R ef er e n c e T a bl e 1 4. 2. 4. 2. 1) 
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 6  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 1 I m p a ct of E v er y d a y Lif e, Q 7 t o Q 9) 
( R ef er e n c e T a bl e 1 4. 2. 4. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 7  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e O v er Ti m e 
( R ef er e n c e T a bl e 1 4. 2. 5. 1. 2. 1) 
mI T T P o p ul ati o n  
N A  
 
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Pa ge 4 3  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
R a w O ut p ut  1 6. 1. 9. 8  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 3 4) T ot al S c or e O v er Ti m e 
( R ef er e n c e T a bl e 1 4. 2. 5. 1. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 9  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n D o m ai n T ot al S c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 2. 2. 1) 
mI T T  P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 0  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 t o Q 4) R e stri cti o n D o m ai n T ot al S c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 2. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n D o m ai n T ot al S c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 3. 2. 1) 
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 5 t o Q 1 6) A d a pt ati o n D o m ai n T ot al S c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 3. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 3  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al I m p a ct D o m ai n T ot al 
S c or e ( R ef er e n c e T a bl e 1 4. 2. 5. 4. 2. 1)  
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 4  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 1 7 t o Q 2 1) S o ci al I m p a ct D o m ai n T ot al 
S c or e ( R ef er e n c e T a bl e 1 4. 2. 5. 4. 2. 2)  
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 5  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al I m p a ct D o m ai n T ot al 
S c or e ( R ef er e n c e T a bl e 1 4. 2. 5. 5. 2. 1)  
mI T T P o p ul ati o n  
N A  
 
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 4  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
R a w O ut p ut  1 6. 1. 9. 1 6  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 2 2 t o Q 2 9) E m oti o n al I m p a ct D o m ai n T ot al 
S c or e ( R ef er e n c e T a bl e 1 4. 2. 5. 5. 2. 2)  
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 7  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y D o m ai n T ot al S c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 6. 2. 1) 
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 8  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 0 t o Q 3 4) I d e ntit y D o m ai n T ot al S c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 6. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 1 9  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2 Gl o b al Or al H e alt h S c or e, Q 3 5) ( R ef er e n c e 
T a bl e 1 4. 2. 5. 7. 2. 1)  
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 2 0  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2 Gl o b al Or al H e alt h S c or e, Q 3 5) ( R ef er e n c e 
T a bl e 1 4. 2. 5. 7. 2. 2)  
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 2 1  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n Lif e O v er all s c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 8. 2. 1) 
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 2 2  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n D H E Q 
( S e cti o n 2, Q 3 6 t o Q 3 9) Eff e ct o n Lif e O v er all s c or e 
( R ef er e n c e T a bl e 1 4. 2. 5. 8. 2. 2) 
P P P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 2 3  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e - I nt e n sit y ( R ef er e n c e T a bl e 
1 4. 2. 5. 1 0. 1. 2)  
mI T T  P o p ul ati o n  
N A  
 
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 5  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
R a w O ut p ut  1 6. 1. 9. 2 4  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e - D ur ati o n ( R ef er e n c e T a bl e 
1 4. 2. 5. 1 0. 2. 2)  
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 2 5  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e - T ol er a bilit y ( R ef er e n c e T a bl e 
1 4. 2. 5. 1 0. 3. 2)  
mI T T P o p ul ati o n  
N A  
 
 
R a w O ut p ut  1 6. 1. 9. 2 6  
St ati sti c al A n al y si s of C h a n g e fr o m B a s eli n e i n L a b ell e d 
M a g nit u d e S c al e - D e s cri pti o n ( R ef er e n c e T a bl e 
1 4. 2. 5. 1 0. 4. 2)  
mI T T P o p ul ati o n  
N A  
 
1 6. 2 S u bj e ct D at a Li sti n g s  
1 6. 2. 1 Di s c o nti n u e d S u bj e ct s  
  
Li sti n g  
1 6. 2. 1. 1  
S u bj e ct Di s p o siti o n  
All r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 1. 1  
 
 
Li sti n g  
1 6. 2. 1. 2  
S u bj e ct Di s p o siti o n  
N o n -r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 1. 2  
 
1 6. 2. 2 Pr ot o c ol D e vi ati o n s  
  
Li sti n g  
1 6. 2. 2. 1  
I m p ort a nt Pr ot o c ol D e vi ati o n s 
All r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 2. 1  
 
 
Li sti n g  
1 6. 2. 2. 2  
All Pr ot o c ol D e vi ati o n s  
All r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 2. 2  
 
1 6. 2. 3 P ati e nt s E x cl u d e d fr o m t h e Effi c a c y A n al y si s  
  
Li sti n g  
1 6. 2. 3. 1  
E x cl u si o n s fr o m A n al y si s P o p ul ati o n s  
All r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 3. 1  
 
1 6. 2. 4 D e m o gr a p hi c D at a  
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 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 6  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
  
Li sti n g  
1 6. 2. 4. 1  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
All r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 4. 1  
 
 
Li sti n g  
1 6. 2. 4. 2  
M e di c al Hi st or y a n d C urr e nt M e di c al C o n diti o n s  
All r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 4. 2  
 
 
Li sti n g  
1 6. 2. 4. 3  
Pri or m e di c ati o n s  
S af et y P o p ul ati o n  
1 6. 2. 4. 3  
 
 
Li sti n g  
1 6. 2. 4. 4  
C o n c o mit a nt m e di c ati o n s a n d si g nifi c a nt n o n -dr u g 
t h er a pi e s 
S af et y P o p ul ati o n  
1 6. 2. 4. 4  
 
1 6. 2. 5 C o m pli a n c e a n d/ or Dr u g C o n c e ntr ati o n D at a (if a v ail a bl e)  
  
Li sti n g  
1 6. 2. 5. 1  
Br u s hi n g C o m pli a n c e  
All r a n d o mi z e d 
s u bj e ct s  
1 6. 2. 5. 1  
 
 
Li sti n g  
1 6. 2. 5. 2  
S u p er vi s e d Br u s hi n g  
S af et y P o p ul ati o n  
1 6. 2. 5. 2  
 
1 6. 2. 6 I n di vi d u al Effi c a c y R e s p o n s e D at a  
  
Li sti n g  
1 6. 2. 6. 1  
I n di vi d u al Effi c a c y D at a f or S c hiff S e n siti vit y S c or e 
( S cr e e ni n g a n d B a s eli n e) 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 1  
 
 
Li sti n g  
1 6. 2. 6. 2  
I n di vi d u al Effi c a c y D at a f or S c hiff S e n siti vit y S c or e of t h e 
T w o T e st T e et h  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 2  
 
 
Li sti n g  
1 6. 2. 6. 3  
I n di vi d u al Effi c a c y D at a f or T a ctil e T hr e s h ol d ( g) at 
S cr e e ni n g a n d B a s eli n e  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 3  
 
 
Li sti n g  
1 6. 2. 6. 4  
I n di vi d u al Effi c a c y D at a f or T a ctil e T hr e s h ol d ( g) of t h e 
T w o T e st T e et h  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 4  
 
 
Li sti n g  
1 6. 2. 6. 5  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 1 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 5  
 
 
Li sti n g  
1 6. 2. 6. 6. 1  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 2 
( R e stri cti o n s D o m ai n) 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 6. 1  
 
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Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 7  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
Li sti n g  
1 6. 2. 6. 6. 2  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 2 
( A d a pt ati o n s D o m ai n) 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 6. 2  
 
 
Li sti n g  
1 6. 2. 6. 6. 3  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 2 ( S o ci al 
I m p a ct D o m ai n) 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 6. 3  
 
 
Li sti n g  
1 6. 2. 6. 6. 4  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 2 ( E m oti o n al 
I m p a ct D o m ai n) 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 6. 4  
 
 
Li sti n g  
1 6. 2. 6. 6. 5  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 2 (I d e ntit y 
D o m ai n)  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 6. 5  
 
 
Li sti n g  
1 6. 2. 6. 6. 6  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 2 ( T ot al 
S c or e, Q 1 t o Q 3 4)  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 6. 6  
 
 
Li sti n g  
1 6. 2. 6. 6. 7  
I n di vi d u al Effi c a c y D at a f or D H E Q S e cti o n 2 ( Q 3 5 t o 
Q 3 9)  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 6. 7  
 
 
Li sti n g  
1 6. 2. 6. 7  
I n di vi d u al Effi c a c y D at a f or N u m b er of S e n siti v e T e et h 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 7  
 
 
Li sti n g  
1 6. 2. 6. 8  
I n di vi d u al Effi c a c y D at a f or L a b ell e d M a g nit u d e S c al e of 
t h e t w o t e st t e et h (i n m m) 
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 8  
 
 
Li sti n g  
1 6. 2. 6. 9  
I n di vi d u al Effi c a c y D at a f or N u m eri c al R ati n g S c al e at 
D a y 5 6  
All R a n d o mi z e d 
S u bj e ct s  
1 6. 2. 6. 9  
 
1 6. 2. 7 A d v er s e E v e nt Li sti n g s  
  
Li sti n g  
1 6. 2. 7. 1  
All A d v er s e E v e nt s  
S af et y P o p ul ati o n  
1 6. 2. 7. 1  
Y e s  
 
Li sti n g  
1 6. 2. 7. 2  
I n ci d e nt s 
S af et y P o p ul ati o n  
1 6. 2. 7. 2  
 
1 6. 2. 8 Ot h er Li sti n g s a n d Li sti n g of L a b or at or y M e a s ur e m e nt s, w h e n r e q uir e d b y r e g ul at or y a ut h oriti e s (if a p pli c a bl e)  
  
Li sti n g  
1 6. 2. 8. 1  
Or al S oft Ti s s u e e x a mi n ati o n  
S af et y P o p ul ati o n  
1 6. 2. 8. 1  
 
C CI


0 . 4 5 4 perce nt w ei g ht/ wei g ht S ta n n o us F l u ori de T o ot h paste  
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Hale o n  C o nfi de ntial  
 Statistical A nal ysis Pla n  T e m plate v 6. 0  
Pa ge 4 8  of 4 8  
C S R S e cti o n  T L F  
N u m b er  
Titl e  
P o p ul ati o n  
T e m pl at e  
T o pli n e  
 
Li sti n g  
1 6. 2. 8. 2  
Or al H ar d Ti s s u e e x a mi n ati o n  
S af et y P o p ul ati o n  
1 6. 2. 8. 2  
 
1 6. 4 I n di vi d u al S u bj e ct D at a Li sti n g s  
  
N A  
  
  
  
  
  
 
C CI