An 8-Week, Randomized, Controlled, Examiner-Blind, Clinical Study to Evaluate the Efficacy of a Stannous Fluoride Toothpaste for the Relief of Dentin Hypersensitivity in a Population of Dentin Hypersensitivity Sufferers
Phase: NA
Conditions: Dentin Sensitivity
Sponsor: HALEON

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  of 1 1 3  
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: 
N/ A  
Ot h er R e g ul at or y A g e n c y 
N u m b er:  
N/ A  
P h a s e:  
N/ A  
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
T his d oc u me nt c o ntai ns c o nfi de ntialit y state me nts t hat are n ot rele va nt  f or t his 
p u blicl y a vaila ble versi o n
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  of 1 1 3  
 
S p o n s or I nf or m ati o n  
 
S p o n s or N a m e & L e g al 
R e gi st er e d A d dr e s s  
 
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,  
S urr e y,  
K T 1 3 0 D E,  
U K  
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  of 1 1 3  
D o c u m e nt Hi st or y  
 
D o c u m e nt  
V er si o n  S u m m ar y of C h a n g e s  
Ori gi n al P r ot o c ol 
1. 0  
N/ A  
Pr ot o c ol  
2. 0  
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.   
 
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  of 1 1 3  
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  
 
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
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 5  of 1 1 3  
T a bl e of C o nt e nt s  
S p o ns or I nf or mati o n  ............................................................................................................ 2  
D oc u me nt Hist or y  ............................................................................................................... 3  
I n v esti gat or Pr ot oc ol A gree me nt Pa ge ................................................................................ 4  
Ta ble of C o nte nts  ................................................................................................................ 5  
1  
P R O T O C O L S U M M A R Y  ................................................................................................ 1 0  
1. 1  
S y n o psis  ................................................................................................................. 1 0  
1. 2  
Sc he d ule of A cti vities  ............................................................................................ 1 4  
2  
I N T R O D U C TI O N ............................................................................................................. 1 8  
2. 1  
Bac k gr o u n d a n d Rati o nal e f or St u d y  ..................................................................... 1 9  
2. 2  
Be nefit/ Ris k Assess me nt  ....................................................................................... 1 9  
2. 3  
Mec ha nis m of Acti o n/I n dicati o n  ........................................................................... 2 0  
3  
S T U D Y O BJ E C TI V E S A N D E N D P OI N T S  .................................................................... 2 1  
4  
S T U D Y D E SI G N  .............................................................................................................. 2 3  
4. 1  
O verall Desi g n  ....................................................................................................... 2 3  
4. 2  
Scie ntific Rati o nale f or St u d y Desi g n  ................................................................... 2 4  
4. 3  
J ustificati o n f or D ose ............................................................................................. 2 8  
4. 4  
E n d of St u d y Defi niti o n  ......................................................................................... 2 9  
5  
S T U D Y P O P U L A TI O N  .................................................................................................... 2 9  
5. 1  
T y pe a n d Pla n ne d N u m b er of S u bjects  ................................................................. 2 9  
5. 2  
I n cl usi o n Criteria ................................................................................................... 2 9  
5. 3  
E xcl usi o n Criteria  .................................................................................................. 3 0  
5. 4  
Ra n d o mizati o n Criteria  .......................................................................................... 3 2  
5. 5  
Lifest yle C o nsi derati o ns  ........................................................................................ 3 2  
5. 5. 1  
Oral H y gie ne R estricti o ns  ..................................................................... 3 3  
5. 5. 2  
Dietar y a n d Al c o h ol Restr icti o ns .......................................................... 3 3  
5. 5. 3  
C o ntrace pti o n  ........................................................................................ 3 3  
5. 6  
Scree n Fail ures ....................................................................................................... 3 3  
5. 7  
S p o ns or’s Q ualifie d Me dical Pers o n nel  ................................................................ 3 3  
5. 8  
Rater/ Cli nical Assess or Q ualificati o ns  .................................................................. 3 4  
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................................................................... 3 4  
6. 1  
St u d y Pr o d u ct S u p plies .......................................................................................... 3 4  
6. 1. 1  
Me dical De vices  .................................................................................... 3 6  
6. 1. 2  
D osa ge F or m a n d Pac k a gi n g  ................................................................. 3 6  
6. 1. 3  
Pr o d uct Dis pe nsi n g  ............................................................................... 3 6  
6. 2  
A d mi nistrati o n  ....................................................................................................... 3 7  
6. 2. 1  
Me dicati o n/ D osi n g Err ors  ..................................................................... 3 7  
6. 2. 2  
O ver d ose  ............................................................................................... 3 8  
6. 3  
St u d y Pr o d uct St ora ge  ........................................................................................... 3 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 6  of 1 1 3  
6. 4  
St u d y Pr o d uct Acc o u nta bilit y  ................................................................................ 3 8  
6. 4. 1  
Destr ucti o n of St u d y Pr o d uct S u p plies  ................................................. 3 9  
6. 5  
Bli n di n g a n d All ocati o n/ Ra n d o mizati o n  ............................................................... 3 9  
6. 6  
Brea ki n g t he Bli n d  ................................................................................................. 4 0  
6. 7  
C o m plia nce  ............................................................................................................ 4 1  
6. 8  
C o nc o mita nt Me dicati o n/ Treat me nt  ...................................................................... 4 1  
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 BJ E C T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ......................................................................... 4 2  
7. 1  
S u bject Disc o nti n uati o n/ Wit h dra wal  ..................................................................... 4 2  
7. 2  
L ost t o F oll o w U p  .................................................................................................. 4 3  
8  
S T U D Y P R O C E D U R E S  ................................................................................................... 4 3  
8. 1  
Visit 1 / Scree ni n g  ................................................................................................. 4 3  
8. 1. 2  
De m o gra p hics  ....................................................................................... 4 4  
8. 1. 3  
Re vie w of Oral Care Pr o d ucts ............................................................... 4 4  
8. 1. 4  
Me dical Hist or y a n d Pri or Me dicati o ns/ Treat me nts  ............................. 4 4  
8. 1. 5  
Cli nical E xa mi nati o ns a n d Assess me nts  ............................................... 4 4  
8. 1. 6  
I n cl usi o n/ E xcl usi o n Criteria ................................................................. 4 5  
8. 1. 7  
S u bject Eli gi bilit y  ................................................................................. 4 5  
8. 2  
St u d y Peri o d  .......................................................................................................... 4 6  
8. 2. 1  
Visit 2 / Baseli ne ( Da y 0)  ...................................................................... 4 6  
8. 2. 2  
Visit 3 / Da y 2 8 ( ± 2 da ys)  .................................................................... 4 9  
8. 2. 3  
Visit 4 / Da y 5 6 ( ± 3 da ys)  .................................................................... 5 1  
8. 3  
St u d y C o ncl usi o n  ................................................................................................... 5 2  
8. 4  
F oll o w -U p C o ntact  ................................................................................................ 5 2  
9  
S T U D Y A S S E S S M E N T S  ................................................................................................. 5 3  
9. 1  
Scree ni n g E xa mi nati o ns/ D H Assess me nts  ............................................................ 5 3  
9. 1. 1  
Er osi o n , A brasi o n a n d R ecessi o n ( E A R) .............................................. 5 3  
9. 1. 2  
M o difie d Gi n gi val I n d e x ( M GI)  ........................................................... 5 3  
9. 1. 3  
Cli nical M o bilit y  ................................................................................... 5 4  
9. 1. 4  
Scree ni n g Tactile Se nsiti vit y Assess me nt  ............................................. 5 4  
9. 1. 5  
Scree ni n g E va p orati ve ( Air) Se nsiti vit y Asses s me nt ........................... 5 6  
9. 2  
D H Efficac y Ass ess me nts ...................................................................................... 5 6  
9. 2. 1  
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  
9. 2. 2  
Tactile Se nsiti vit y Assess me nts  ............................................................ 5 7  
9. 2. 3  
E va p orati ve ( Air) Se nsiti vit y Assess me nts  ........................................... 5 8  
9. 2. 4  
La belle d Ma g nit u de Scales ( L M Ss)  ...................................................... 5 8  
9. 3  
Safet y Assess me nts  ................................................................................................ 5 9  
9. 3. 1  
Oral S oft Tiss ue ( O S T) E xa mi nati o n  .................................................... 5 9  
9. 3. 2  
Oral Har d Tiss ue ( O H T) E xa mi nati o n  .................................................. 5 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 7  of 1 1 3  
9. 3. 3  
Pre g na nc y  .............................................................................................. 5 9  
9. 3. 4  
Satisfacti o n wit h Treat m e nt  .................................................................. 6 0  
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  ......................................... 6 0  
1 0. 1  
Defi niti o n of a n A d verse E ve nt ( A E)  .................................................................... 6 0  
1 0. 2  
Defi niti o n of a Seri o us A d verse E ve nt ( S A E)  ....................................................... 6 2  
1 0. 3  
Ti me Peri o d a n d Fre q ue n c y f or C ollecti n g A E a n d S A E I nf or mati o n  .................. 6 3  
1 0. 4  
Re p orti n g Pr oce d ures ............................................................................................. 6 3  
1 0. 4. 1  
Re p orti n g a n A E  .................................................................................... 6 4  
1 0. 4. 2  
Re p orti n g a n S A E  ................................................................................. 6 4  
1 0. 5  
E val uati n g A Es  ...................................................................................................... 6 5  
1 0. 5. 1  
Assess me nt of I nte nsit y  ........................................................................ 6 5  
1 0. 5. 2  
Assess me nt of Ca usalit y  ....................................................................... 6 5  
1 0. 6  
F oll o w -u p of A Es a n d S A Es .................................................................................. 6 6  
1 0. 7  
Wit h dra wal D u e t o a n A d verse E ve nt  ................................................................... 6 6  
1 0. 8  
Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...................................................... 6 6  
1 0. 9  
Pre g na nc y  .............................................................................................................. 6 7  
1 0. 9. 1  
Ti me Peri o d f or C ollecti n g Pre g na nc y I nf or mati o n .............................. 6 7  
1 0. 9. 2  
Acti o n t o be Ta ke n if Pre g na nc y Occ urs  .............................................. 6 7  
1 0. 1 0  Me dical De vic e I n ci de nts  ...................................................................................... 6 7  
1 0. 1 0. 1  
Defi niti o n of a n I nci d e nt  ....................................................................... 6 7  
1 0. 1 0. 2  
Re p orti n g of I nci de nts a n d Malf u ncti o ns  .............................................. 6 8  
1 0. 1 0. 3  
F oll o w -u p of Me di cal De vice I nci de nts ................................................ 6 9  
1 0. 1 0. 4  
Re g ulat or y Re p orti n g Re q uire me nts f or Me dical De vice I n ci de nts  ..... 6 9  
1 1  D A T A M A N A G E M E N T  .................................................................................................. 6 9  
1 1. 1  
Case Re p ort F or m  .................................................................................................. 7 0  
1 1. 2  
Data Ha n dli n g  ........................................................................................................ 7 0  
1 1. 2. 1  
Data Q ueries  .......................................................................................... 7 0  
1 1. 3  
Pr ocessi n g S u bject R e p orte d O utc o mes  ................................................................ 7 1  
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  .................................. 7 1  
1 2. 1  
Sa m ple Size Deter mi nati o n  ................................................................................... 7 1  
1 2. 2  
P o p ulati o ns f or A nal ysis  ........................................................................................ 7 1  
1 2. 2. 1  
Defi niti o ns of A nal ysis P o p ulati o ns  ..................................................... 7 1  
1 2. 2. 2  
E xcl usi o ns of Data fr o m A nal ysis ......................................................... 7 2  
1 2. 3  
Statistical A nal yses  ................................................................................................ 7 2  
1 2. 3. 1  
Pri mar y E n d p oi nt A nal ysis  ................................................................... 7 3  
1 2. 3. 2  
Sec o n dar y E n d p oi nt A nal yses ............................................................... 7 3  
1 2. 3. 3  
E x pl orat or y A nal yses  ............................................................................ 7 5  
1 2. 3. 4  
Safet y A nal yses  ..................................................................................... 7 6  
1 2. 3. 5  
De m o gra p hic a n d Baseli ne C haract eristics  ........................................... 7 7  
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  of 1 1 3  
1 2. 3. 6  
St u d y Pr o d uct C o m plia nce a n d Us e of Ot her T hera pies  ...................... 7 7  
1 2. 3. 7  
Ha n dli n g of Dr o p o uts a n d Missi n g Data  .............................................. 7 7  
1 2. 3. 8  
I nteri m A nal ysis .................................................................................... 7 8  
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 .............................................................. 7 8  
1 3. 1  
Q ualit y C o ntr ol  ...................................................................................................... 7 8  
1 3. 2  
Q ualit y Ass ura nce  .................................................................................................. 7 8  
1 3. 3  
Re g ulat or y a n d Et hical C o nsi derati o ns  ................................................................. 7 9  
1 3. 3. 1  
I nstit uti o nal Re vie w B oar d (I R B) ......................................................... 7 9  
1 3. 3. 2  
Et hical C o n d uct of t he St u d y  ................................................................ 7 9  
1 3. 3. 3  
S u bject I nf or mati o n a n d C o nse nt  .......................................................... 7 9  
1 3. 3. 4  
S u bject Recr uit me nt  .............................................................................. 8 0  
1 3. 3. 5  
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 
I C H G C P ............................................................................................... 8 0  
1 3. 4  
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  
1 3. 5  
Pr o visi o n of St u d y Res ults t o I n vesti gat ors  ........................................................... 8 0  
1 3. 6  
Rec or ds Rete nti o n  .................................................................................................. 8 1  
1 3. 7  
C o n diti o ns f or Ter mi nati n g t he St u d y  ................................................................... 8 1  
1 4  R E F E R E N C E S  .................................................................................................................. 8 2  
1 5  A P P E N DI CI E S .................................................................................................................. 8 9  
1 5. 1  
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
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 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
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 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
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 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