A Real-World Evidence Study Evaluating Oral Health Related Quality Of Life With Use Of A Stannous Fluoride Anti-Sensitivity Toothpaste For Dentin Hypersensitivity Management
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 0 5 8  
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
C LI NI C A L P R O T O C O L  
A R E A L -W O R L D E VI D E N C E S T U D Y E V A L U A TI N G O R A L H E A L T H 
R E L A T E D Q U A LI T Y O F LI F E WI T H  U S E O F A S T A N N O U S 
F L U O RI D E A N TI -S E N SI TI VI T Y  T O O T H P A S T E  F O R D E N TI N  
H Y P E R S E N SI TI VI T Y M A N A G E M E N T  
Pr ot o c ol N u m b er:  
3 0 0 0 5 8  
C o m p o u n d/ Pr o d u ct N a m e:  
0. 4 5 4 % St a n n o u s  Fl u ori d e  ( S n F2 ) 
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 I d e ntifi e d 
N u m b er:  
N/ A  
P h a s e:  
N/ A 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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)  
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 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  ( U S) 
1 8 4 Li b ert y C or n er R d,  
W arr e n, N e w J er s e y ( N J) 0 7 0 5 9,  
U nit e d St at e s ( U S)  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 pr ot o c ol  
1. 0  
N ot a p pli c a bl e ( N/ A)  
N e w V er si o n  
2. 0  
•  R e m o v al of o bj e cti v e s , e n d p oi nt s a n d st ati sti c al 
a n al y s e s r el ati n g t o p o p ul ati o n s u b -gr o u p s . 
•  R e -str u ct uri n g of o bj e cti v e s , e n d p oi nt s  a n d 
st ati sti c al a n al y s e s.  
A m e n d m e nt 1  
3. 0  
•  Cl arifi e d p arti ci p a nt s’ c o m pli a n c e i n s e cti o n 6. 7   
•  Cl arifi e d t h e q ue sti o n of t h e pr o d u ct n a m e i n O H Q 
s e cti o n 1 5. 3  
A me n d me nts i nc or p orate all re visi o ns t o dat e, i ncl u di n g a me n d m e nts ma de at t he re q u est of 
c o u ntr y h ealt h a ut h orities, i nstit uti o nal re vie w b oar ds/et hics c o m mittees (I R Bs/ E Cs), etc.   
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
Pri n ci p al 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.  
•  I ac k n o wle d ge t hat I a m res p o nsi ble f or o verall st u d y c o n d u ct. I a gree t o pers 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 es all a p pr o priate i nf or mati o n t hr o u g h o ut t h e 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 esti gat or Na me: 
 
I n v esti gat or Q ualificati o ns: 
 
I n v esti gat or Si g nat ure: 
Date of Si g nat ure/ A gree me nt:  
 
D D -M m m -Y Y Y Y  
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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  
Pri nci pal 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 2  
2  
I N T R O D U C TI O N ............................................................................................................. 1 4  
2. 1  
St u d y R ati o nale  ...................................................................................................... 1 4  
2. 2  
Bac k gr o u n d  ............................................................................................................ 1 4  
2. 3  
Be nefit/ Ris k Assess me nt  ....................................................................................... 1 6  
2. 4  
Mec ha nis m of Acti o n/I n dicati o n  ........................................................................... 1 6  
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  .................................................................... 1 6  
4  
S T U D Y D E SI G N  .............................................................................................................. 1 7  
4. 1  
O verall Desi g n  ....................................................................................................... 1 7  
4. 2  
Scie ntific Rati o nale f or St u d y Desi g n  ................................................................... 1 8  
4. 3  
J ustificati o n f or D ose ............................................................................................. 1 9  
4. 4  
E n d of St u d y Defi niti o n  ......................................................................................... 1 9  
5  
S T U D Y P O P U L A TI O N  .................................................................................................... 2 0  
5. 1  
T y pe a n d Pla n ne d N u m b er of Partici pa nts  ............................................................ 2 0  
5. 2  
I n cl usi o n Criteria ................................................................................................... 2 0  
5. 3  
E x cl usi o n Criteria  .................................................................................................. 2 0  
5. 4  
Ra n d o mizati o n Criteria  .......................................................................................... 2 1  
5. 5  
Lif est yle C o nsi derati o ns  ........................................................................................ 2 1  
5. 6  
Scree n Fail ures ....................................................................................................... 2 1  
5. 7  
S p o ns or’s Q ualifie d Me dical Pers o n nel  ................................................................ 2 1  
5. 8  
Rater/ Cli nical Assess or Q ualificati o ns  .................................................................. 2 1  
6  
S T U D Y P R O D U C T  .......................................................................................................... 2 1  
6. 1  
St u d y Pr o d uct S u p pl y  ............................................................................................ 2 1  
6. 1. 1  
D osa ge F or m a n d Pac k a gi n g  ................................................................. 2 2  
6. 1. 2  
Pre parati o n a n d Dis patc h  ...................................................................... 2 2  
6. 2  
A d mi nistrati o n  ....................................................................................................... 2 3  
6. 2. 1  
Me dicati o n/ D osi n g Err ors  ..................................................................... 2 3  
6. 2. 2  
O ver d ose  ............................................................................................... 2 3  
6. 3  
St u d y Pr o d uct St ora ge  ........................................................................................... 2 3  
6. 4  
St u d y Pr o d uct Acc o u nta bilit y  ................................................................................ 2 4  
6. 4. 1  
Destr ucti o n of St u d y Pr o d uct S u p plies  ................................................. 2 4  
6. 5  
Bli n di n g a n d All ocati o n/ Ra n d o mizati o n  ............................................................... 2 4  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
6. 6  
Brea ki n g t he Bli n d  ................................................................................................. 2 4  
6. 7  
C o m plia nce  ............................................................................................................ 2 4  
6. 8  
C o nc o mita nt Me dicati o ns/ Treat me nts  ................................................................... 2 4  
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 P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ......................................................................... 2 5  
7. 1  
Partici pa nt Disc o nti n uati o n/ Wit h dra wal  ............................................................... 2 5  
7. 2  
L ost t o F oll o w -U p  ................................................................................................. 2 5  
8  
S T U D Y P R O C E D U R E S  ................................................................................................... 2 5  
8. 1  
Scree ni n g  ............................................................................................................... 2 5  
8. 1. 1  
I nf or me d C o nse nt .................................................................................. 2 5  
8. 1. 2  
Scree ni n g Q u esti o n naire  ....................................................................... 2 6  
8. 1. 3  
De m o gra p hics  ....................................................................................... 2 6  
8. 1. 4  
Me dical Hist or y a n d Pri or Me dicati o ns/ Treat me nts  ............................. 2 6  
8. 1. 5  
I n cl usi o n/ E x cl usi o n Criteria ................................................................. 2 7  
8. 2  
St u d y Peri o d  .......................................................................................................... 2 7  
8. 2. 1  
Wee k 0 ( Baseli ne)  ................................................................................. 2 7  
8. 2. 2  
Wee ks 1 a n d 2  ....................................................................................... 2 7  
8. 2. 3  
Wee ks 4, 8, 1 2, 1 6 a n d 2 0  ..................................................................... 2 7  
8. 2. 4  
Wee k 2 4  ................................................................................................ 2 7  
8. 3  
St u d y C o n cl usi o n  ................................................................................................... 2 8  
8. 4  
S A E F oll o w -u p  ...................................................................................................... 2 8  
9  
S T U D Y A S S E S S M E N T S  ................................................................................................. 2 8  
9. 1  
Scree ni n g Assess me nts  .......................................................................................... 2 8  
9. 2  
Q ualit y of Lif e ( Q o L) Assess me nt  ........................................................................ 2 8  
9. 2. 1  
De nti n H y p erse nsiti vit y E x perie nce Q uesti o n nair e ( D H E Q -4 8)  .......... 2 8  
9. 3  
Safet y a n d Ot her Assess me nts  ............................................................................... 2 9  
9. 3. 1  
D H Pai n Assess me nt  ............................................................................. 2 9  
9. 3. 2  
Partici pa nt Satisfacti o n wit h Treat me nt  ................................................ 2 9  
9. 3. 3  
Ot her  ...................................................................................................... 3 0  
1 0  A D V E R S E E V E N T A N D S E RI O U S A D V E R S E E V E N T S  ........................................... 3 0  
1 0. 1  
Defi niti o n of a n A d verse E ve nt ( A E)  .................................................................... 3 0  
1 0. 2  
Defi niti o n of a Seri o us A d verse E ve nt ( S A E)  ....................................................... 3 1  
1 0. 3  
Ti me Per i o d a n d Fre q ue n c y f or C ollecti n g A E & S A E I nf or mati o n .................... 3 2  
1 0. 4  
Re p orti n g Pr oce d ures ............................................................................................. 3 3  
1 0. 4. 1  
Re p orti n g of a n A d verse E ve nt  ............................................................. 3 3  
1 0. 4. 2  
Re p orti n g of a Seri o us A d verse E ve nt  .................................................. 3 3  
1 0. 5  
E val uati n g A d v erse E ve nts  .................................................................................... 3 4  
1 0. 5. 1  
Assess me nt of I nte nsit y  ........................................................................ 3 4  
1 0. 5. 2  
Assess me nt of Ca usalit y  ....................................................................... 3 5  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 0. 6  
F oll o w -u p of A Es a n d S A Es .................................................................................. 3 5  
1 0. 7  
Wit h dra wal D ue t o a n A d verse E ve nt  ................................................................... 3 6  
1 0. 8  
Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...................................................... 3 6  
1 0. 9  
Pre g n a nc y  .............................................................................................................. 3 6  
1 0. 9. 1  
Acti o n t o be Ta ke n if Pre g na n c y Occ urs  .............................................. 3 6  
1 1  D A T A M A N A G E M E N T  .................................................................................................. 3 7  
1 1. 1  
Case Re p ort F or m  .................................................................................................. 3 7  
1 1. 2  
Data Ha n dli n g  ........................................................................................................ 3 7  
1 1. 2. 1  
Data Q ueries  .......................................................................................... 3 8  
1 1. 3  
Pr ocessi n g  Patie nt Re p orte d O utc o mes  ................................................................. 3 8  
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  .................................. 3 8  
1 2. 1  
Sa m ple Siz e Deter mi nati o n  ................................................................................... 3 8  
1 2. 2  
P o p ulati o ns f or A nal ysis  ........................................................................................ 3 8  
1 2. 2. 1  
A nal ysis P o p ulati o ns  ............................................................................. 3 8  
1 2. 2. 2  
E x cl usi o n of Data fr o m A nal ys es  ......................................................... 3 9  
1 2. 3  
Statistical A nal yses  ................................................................................................ 3 9  
1 2. 3. 1  
Pri mar y A n al yses  .................................................................................. 3 9  
1 2. 3. 2  
Sec o n dar y A nal ys es  .............................................................................. 4 0  
1 2. 3. 3  
Safet y A nal yses  ..................................................................................... 4 0  
1 2. 3. 4  
De m o gra p hic a n d Baseli ne C haracteristics  ........................................... 4 1  
1 2. 3. 5  
St u d y Pr o d uct C o m plia nce a n d Us e of Ot her T hera pies  ...................... 4 1  
1 2. 3. 6  
Ha n dli n g of Dr o p o uts a n d Missi n g Data  .............................................. 4 1  
1 2. 3. 7  
I nteri m A nal ysis .................................................................................... 4 1  
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 .............................................................. 4 1  
1 3. 1  
Q ualit y C o ntr ol  ...................................................................................................... 4 1  
1 3. 2  
Q ualit y Ass ura nce  .................................................................................................. 4 2  
1 3. 3  
Re g ulat or y a n d Et hical C o nsi derati o ns  ................................................................. 4 2  
1 3. 3. 1  
I nstit uti o nal Re vie w B oar d (I R B) ......................................................... 4 2  
1 3. 3. 2  
Et hical C o n d uct of t he St u d y  ................................................................ 4 3  
1 3. 3. 3  
Partici pa nt I nf or mati o n a n d C o nse nt  .................................................... 4 3  
1 3. 3. 4  
Partici pa nt Recr uit me nt  ......................................................................... 4 3  
1 3. 3. 5  
Re p orti n g of Saf et 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 ............................................................................................... 4 3  
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  ................. 4 4  
1 3. 5  
Pr o visi o n of St u d y Res ults t o t he I n vesti gat or  ...................................................... 4 4  
1 3. 6  
Rec or ds Rete nti o n  .................................................................................................. 4 4  
1 3. 7  
C o n diti o ns f or Ter mi nati n g t he St u d y  ................................................................... 4 5  
1 4  R E F E R E N C E S  .................................................................................................................. 4 6  
1 5  A P P E N DI CI E S .................................................................................................................. 5 1  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 5. 1  
A b bre viati o ns  ......................................................................................................... 5 1  
1 5. 2  
Scree ni n g  Q u esti o n naire  ........................................................................................ 5 3  
1 5. 3  
Oral  H y gie ne Q uesti o n naire ( O H Q)  ...................................................................... 5 6  
1 5. 4  
De nti n H y p erse nsiti vit y E x perie nce Q uesti o n nair e ( D H E Q -4 8)  .......................... 5 8  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
Li st of In T e xt T a bl e s  
Ta ble 1 -1  
Sc he d ule of Acti vities  ........................................................................... 1 3  
Ta ble 3 -1  
St u d y O bjecti ves a n d E n d p oi nts  ........................................................... 1 6  
Ta ble 6 -1  
St u d y Pr o d uct S u p pl y  ............................................................................ 2 1  
Ta ble 1 5 -1  
A b bre viati o ns  ........................................................................................ 5 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 h ort Titl e:   
A real -w orl d e vi de n ce st u d y e val uati n g oral healt h relate d q ualit y of life wit h  use of a sta n n o us 
fl u ori de a nti-se nsiti vit y t o ot h paste f or de nti n  h y perse nsiti vit y m a na ge m e nt  
B a c k gr o u n d a n d R ati o n al e : 
T his st u d y will e val uat e t he i m pa ct of l o n g-ter m use of a dese nsitizi n g t o ot h paste c o ntai ni n g 
0. 4 5 4 % sta n n o us fl u ori de ( S n F2) o n oral healt h relate d q ualit y of life  ( O HrQ o L)  i n a p o p ulati o n 
of self-re p orte d de nti n h y p erse nsiti vit y ( D H) s ufferers . Data ge nerate d will pr o vi de real w orl d 
i nf or mati o n o n t he D H e x perie nce a n d D H ma na ge me nt wit h a d ail y use a nti -se nsiti vit y 
treat me nt. 
O bj e cti v e s a n d E n d p oi nt s :  
O bjecti ves  
E n d p oi nts  
Pri m ar y  
T o descri be c h a n ges i n O Hr Q o L o ver 2 4 
wee ks  use of a n a nti-se nsiti vit y t o ot h paste 
c o ntai ni n g 0. 4 5 4 %  S n F 2, 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 naire ( D H E Q -4 8 : T otal Sc ore a n d 
D o mai n Sc ores ), i n a D H p o p ulati o n . 
C ha n ge fr o m Bas eli ne i n D H E Q e n d p oi nts  at 
W ee ks 4, 8, 1 2, 1 6, 2 0 &  2 4.   
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)   
Sec o n d ar y  
T o descri be c h a n ges i n O Hr Q o L o ver 2 4 
wee ks use of a n a nti -se nsiti vit y t o ot h paste 
c o ntai ni n g 0. 4 5 4 % S n F 2, as meas ure d b y 
t he D H E Q -4 8  ( ot her e n d p oi nts), i n a D H 
p o p ulati o n . 
C ha n ge fr o m Bas eli ne i n D H E Q e n d p oi nts  at 
W ee ks 4, 8, 1 2, 1 6, 2 0 &  2 4.   
Secti o n 1  
•  I m pact o n E ver y d a y L ife ( Q 1-3)  
Secti o n 2  
•  Gl o bal Oral H ealt h Sc ore ( Q 3 5)  
•  Effect o n Lif e O verall Sc ore ( Q 3 6-3 9)  
T o 
s u m marize t he i n di vi d ual D H E Q 
d o mai n ite ms 
of c o ncer n  i n a 
D H 
p o p ulati o n bef ore a n d aft er  2 4 wee ks use  of 
a n a nti -se nsiti vit y t o ot h paste c o ntai ni n g 
0. 4 5 4 %  S n F 2. 
B aseli ne a n d Week 2 4 : 
•  Perce nta ge ( %) of p artici pa nts w h o ‘a gree ' 
(sc ore 5-7) wit h eac h ite m (state me nt) i n 
t he 5 D H E Q d o mai n s ( D H E Q Secti o n 2, 
Q 1 -3 4) .   
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
St u d y D e si g n : 
T his will be a dece ntrali ze d , pr os pecti ve, 2 4 -wee k, m o na dic desi g n, o pe n la bel  st u d y i n a  D H 
p o p ulati o n . T h e st u d y will e val uate c ha n ges i n O Hr Q o L i n partici pa nts  wit h self -re p orte d D H 
s y m pt o ms o ver  2 4 wee ks of use of a D H treat me nt (a nti-se nsiti vit y t o ot h paste). O Hr Q o L will 
be 
meas ure d usi n g a vali date d q uesti o n naire , 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 p artici pa nts at B aseli ne, a n d W ee ks 4, 8, 1 2, 
1 6, 2 0 a n d 2 4 . 
Partici pa nts  will be recr uite d t hr o u g h s ocial me dia a n d ot her di gital platf or ms. I n di vi d uals w h o 
are i ntereste d i n t he st u d y will be se nt t o a la n di n g pa ge after clic ki n g o n a n a d vertise me nt  or 
st u d y li n k w here t he y will c o m plete  a n i nitial pre -scree ni n g q u esti o n naire. If eli gi ble  t o 
partici pate , t he y will be s e nt a n e m ail  i n vitati o n t o d o w nl oa d t he 
 a p plicati o n (a p p). 
After d o w nl o a di n g a n d l o g gi n g i nt o t he 
 a p p, t h e y will be a ble t o re vie w t h e 
electr o nic I nf or m e d C o nse nt (eI C) , as k q uesti o ns a b o ut t he st u d y, a n d c o m m u nicate wit h t he 
virt ual site tea m via t he a p p c hat, p h o ne ( usi n g t he st u d y n u m b er liste d i n t he eI C) 
or e mail.  I n di vi d uals w h o deci de t o p artici pate  ma y t h e n c h o ose t o si g n t he  eI C  (electro ni c 
si g nat ur e). N o st u d y-s pecific data will be c ollecte d  pri or t o si g ni n g t he eI C. I n di vi d uals w h o d o 
n ot acti vel y access t he st u d y -s pecific a p p a n d pr o vi de c o nse nt will n ot be per mitte d t o 
partici pate i n t he st u d y .  
O nce t he partici p a nt ha s si g ne d t he eI C, t he y will c o m plete a detaile d scree ni n g q uesti o n nair e 
t o i de ntif y a n d e x cl u de i n di vi d uals w h ose t o ot h se nsiti vit y c o ul d b e ca use d b y ot her 
fact ors/cli nical p at h ol o g y f or w hic h de ntal h ealt hcare pr ofessi o nal a d vice s h o ul d be s o u g ht. I n 
a d diti o n t o t he scree ni n g q uesti o n naire, p artici pa nts will be re q uir e d t o pr o vi de de m o gra p hi c 
i nf or mati o n a n d c o m plet e Me dical Hist or y a n d C o nc o mita nt Me dicati o ns for m s. Partici pa nts 
w h o q ualif y , b ase d o n t heir res p o nses t o t he scree ni n g q uesti o n nair e a n d t he pr ot oc ol 
i ncl usi o n/e x cl usi o n criteria, will be e nr olle d a n d se nt s ufficie nt st u d y tr eat me nt (dese nsitizi n g 
t o ot h paste c o ntai ni n g 0. 4 5 4 % S n F 2) t o c o m plete t he st u d y. Partici pa nts will c o nfir m recei pt of 
st u d y t o ot h paste i n t he 
 a p p ( date of c o nfir mati o n of recei pt = Da y 0 ) a n d will be 
i nstr ucte d t o start usi n g  it o n t he sa me da y . T he y will use t he st u d y t o ot h paste f or 2 4 wee ks 
acc or di n g t o t he i nstr ucti o ns o n t he c o m mercial p ac k  a n d t heir n or mal oral healt hcare ha bits .  
Partici pa nts will c o m plete a D H E Q -4 8  at Bas eli ne ( bef ore  first treat me nt use) a n d at 4 -wee k  
i nter vals t hr o u g h o ut t he treat me nt peri o d  (Wee ks 4, 8, 1 2, 1 6, 2 0 a n d 2 4). I n a d diti o n t o t he 
T o descri be  c ha n ges i n t h e i nte nsit y of s elf-
re p orte d D H pai n  o v er  2 4 wee ks us e  of a n 
a nti-se nsiti vit y  
t o ot h paste  
c o ntai ni n g 
0. 4 5 4 %  S n F 2, as meas ur e d b y a N u meric 
Pai n 
Rati n g Scale ( N P R S) , i n a D H 
p o p ulati o n .  
C ha n ge fr o m Bas eli ne i n N P R S sc ore  at 
W ee ks 1, 2, 4, 8, 1 2, 1 6, 2 0 &  2 4.   
T o descri be  partici pa nt satisfacti o n wit h t he 
D H treat me nt (a nti-se nsiti vit y t o ot h paste 
c o ntai ni n g 0. 4 5 4 % S n F 2), as meas ure d b y a 
Satisfacti o n N u meric R ati n g S cale ( N R S) .    
Week 2 4 : 
Satisfacti o n N R S sc ore   
T o descri be t he oral h y gi e ne ha bits of a D H 
p o p ulati o n 
usi n g 
a n  
oral 
h y gie ne 
q uesti o n naire ( O H Q) . 
B aseli ne : 
O H Q res p o ns es 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
D H E Q -4 8 , t he y will rate t heir D H-relate d pai n usi n g a N u meric Pai n Rati n g Scal e  (N P R S ) at 
Baseli ne, a n d aft er 1, 2 , 4, 8, 1 2, 1 6, 2 0 a n d 2 4 wee ks of treat me nt.  
Partici pa nts will descri be t heir oral h y gie ne ha bits at Baseli ne  b y c o m pleti o n of a n Oral H y gie ne 
Q uesti o n naire ( O H Q) . O n c o m pleti o n of t he 2 4 -wee k st u d y , t he y will rate t heir satisfacti o n wit h 
t he D H treat me nt usi n g a N u meric Rati n g Scale ( N R S ). 
Self -re p ort e d a d verse e v e nts ( A Es) will be c ollecte d re m otel y vi a t he 
 a p p.  
St u d y Pr o d u ct : 
P r o d uct Descri pti o n  
A nti -se nsiti vit y t o ot h paste c o ntai ni n g 0. 4 5 4 % S n F 2 
P r o d uct N a me  
Se ns o d y ne R e pair a n d P r otect ( U S mar ket)  
M aster F or m ul ati o n C o de  
 
Fl u ori de C o nte nt  
1 1 0 0 parts per milli o n ( p p m) fl u ori de as S n F 2 
T y p e a n d Pl a n n e d N u m b er of P arti ci p a nt s : 
S ufficie nt n u m ber s will be scree ne d ( esti mate d  u p t o 5 0 % scree n fail ure rate) t o e nr oll 
a p pr o xi matel y 5 0 0 p artici pa nts t o e ns ure a p pr o xi matel y 4 0 0 e val ua bl e p artici pa nts c o m plet e 
t he e ntire st u d y (esti mate d  u p t o 2 0 % dr o p o ut  rate).  
St ati sti c al A n al y si s S u m m ar y:  
D H E Q  data will be a nal yze d usi n g a m o difie d I nte nt -T o -Treat ( mI T T) p o p ulati o n . 
C ha n ge fr o m Bas eli ne i n D H E Q T otal Sc ore a n d eac h i n di vi d ual D o mai n  acr oss all p ost -
baseli ne ti me p oi nts will be a nal yz e d usi n g a M M R M wit h ti me p oi nt fitte d as a fi x e d effect, 
B aseli ne D H E Q sc ore as a c o variate a n d partici pa nt fitte d as a re peate d meas ure wit h 
u nstr uct ure d c o varia nce matri 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 of t he a dj uste d mea n ( S E) ch a n ge fr o m Baseli ne at eac h ti me p oi nt  will be prese nte d 
f or eac h D H E Q e n d p oi nt al o n g wit h 9 5 % CIs.   
1. 2  
S c h e d ul e of A cti viti e s  
T he S c he d ule of A cti vities (Ta ble 1 -1 ) pr o vi des a n o ver vie w of t he st u d y pr oce d ures. 
 virt ual st u d y t ea m  ma y sc he d ul e ot her (u n pla n ne d)  i nteracti o ns, a d diti o n al t o 
t h ose liste d in t he sc he d ule of acti vities, t o ma ke assess me nts re q uire d t o pr otect t he well -bei n g 
of st u d y partici pa nts. 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T a bl e 1 -1  
S c h e d ul e of A cti viti e s  
F o ot n otes:    
1.  B aseli ne acti vities m ust be c o m plete d b y partici pa nt wit hi n 1 4 da ys of e nr oll me nt .    
2.  St u d y t o ot h paste will  be dis patc he d t o q ualif yi n g partici pa nts  o nl y  after all ‘B aseli ne’ acti vities  ha ve bee n c o m plete d .  
3.  Partici pa nt will  c o nfir m recei pt of st u d y t o ot h paste i n t he 
 a p p ( date of c o nfir mati o n of recei pt = Da y 0) a n d will be i nstr ucte d t o start usi n g it o n t he sa me da y.  
4.  Self -re p orte d cha n ges i n healt h a n d me dical occ urre nces fr o m i m me diatel y after partici pa nt  pr o vi des e-c o nse nt si g nat ure u ntil t he last use  of st u d y t o ot h paste will be rec or de d as A Es ; t h us, seri o us A Es ( S A Es) will 
als o be c ollecte d fr o m i m me diatel y after partici pa nt  pr o vi des e-c o nse nt si g nat ure u ntil last use  of st u d y t o ot h paste.  
Pr o ce d ure  
Pre -
Scree ni n g  
B aseli ne  
A cti vities 1 
D a y 0 3 
Wee k 1  
Da y 7  
( ± 1 da ys) 
Wee k 2  
Da y 1 4  
( ± 2 da ys 
Wee k 4  
Da y 2 8  
( ± 7 da ys) 
Wee k 8  
Da y 5 6  
( ±7  da ys)  
Wee k 1 2  
Da y 8 4  
( ±7  da ys)  
Wee k 1 6  
Da y 1 1 2  
( ±7  da ys)  
Wee k 2 0  
Da y 1 4 0  
( ±7  da ys)  
Wee k 2 4  
Da y 1 6 8  
( ±7  da ys)  
Pre -Scree ni n g Q uesti o n naire  
X  
 
 
 
 
 
 
 
 
 
 
C o nfir m I nitial  Eli gi bilit y  
X  
 
 
 
 
 
 
 
 
 
 
e Mail i n vitati o n t o d o w nl oa d 
 a p p 
wit h U ni q ue P artici pa nt I D  
X  
 
 
 
 
 
 
 
 
 
 
e-I nf or me d C o nse nt (eI C)  
 
X  
 
 
 
 
 
 
 
 
 
Scree ni n g Q uesti o n naire  
 
X  
 
 
 
 
 
 
 
 
 
De m o gra p hics  
 
X  
 
 
 
 
 
 
 
 
 
Me dical Hist or y  
 
X  
 
 
 
 
 
 
 
 
 
C o nc o mita nt Me dicati o ns  
 
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
C hec k I ncl usi o n/ E xcl usi o n Criteria 
 
X  
 
 
 
 
 
 
 
 
 
C o nfir m P artici pa nt  Eli gi bilit y 1   
 
X  
 
 
 
 
 
 
 
 
 
D H E Q -4 8 C o m pleti o n    
 
X  
 
 
 
X  
X  
X  
X  
X  
X  
N P R S C o m pleti o n    
 
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
O H Q C o m pleti o n  
 
X  
 
 
 
 
 
 
 
 
 
St u d y T o ot h paste  Dis patc he d 2 
 
X  
 
 
 
 
 
 
 
 
 
P artici pa nt C o nfir ms Recei pt of S t u d y T o ot h paste  
i n 
 A p p 
 
 
X  
 
 
 
 
 
 
 
 
S u bj ect Instr uct e d  t o S tart U sin g  St u d y T o ot h paste  
 
 
X  
 
 
 
 
 
 
 
 
D H Treat me nt Satisfacti o n N R S C o m pleti o n  
 
 
 
 
 
 
 
 
 
 
X  
C o m plete E n d of St u d y ( E O S) / O pe n E n de d 
S ur ve y Q uesti o ns  
 
 
 
 
 
 
 
 
 
 
X  
Self -re p orte d A Es4  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
St u d y C o ncl usi o n  
 
 
 
 
 
 
 
 
 
 
X  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
2  
I N T R O D U C TI O N 
2. 1  
St u d y R ati o n al e  
Cli nical data  s u p p orti n g t he effic ac y of a nti-se nsiti vit y to ot h pastes are  t y picall y ge nerate d i n  
ra n d o mize d c o ntr olle d trials ( R C Ts), c o n d ucte d i n well -defi ne d p o p ulati o n s (self-re p orte d a n d 
cli nicall y c o nfir me d D H) , wit h t he i n vesti gati o nal pr o d ucts use d a n d e v al u ate d acc or di n g t o  a 
strict set of st u d y pr oce d ures. S uc h st u dies d o n ot necessaril y f ull y refl ect t he ge n eral D H 
p o p ulati o n be ha vi or. Real -w orl d e vi de nce ( R W E) st u dies offer a n o p p ort u nit y t o gat h er 
i nf or mati o n o n  mar k ete d pr o d uct s fr o m real-w orl d heter o ge ne o us p o p ulati o ns t hat ca n 
c o m ple me nt cli nical e vi de nce, c o ns u mer i nsi g ht data , a n d p ost -mar keti n g s ur veilla nce. Real 
w orl d data ( R W D) ca n be ge nerat e d  i n a n u m b er of differe nt  st u d y desi g ns ra n gi n g fr o m 
o bser vati o nal ( pr os p ecti ve/retr os pecti ve) t o i nter ve nti o nal st u dies, 
wit h 
or 
wit h o ut 
ra n d o mizati o n, a n d hel p t o a d dress t he acce pte d li mitati o ns of ra n d o mize d  c o ntr olle d st u dies 
w hic h ca n ma ke it diffic ult t o ge neralize fi n di n gs t o lar ger, m ore i ncl usi ve 
p o p ulati o n s 
(S her ma n et al, 2 0 1 6).  
Fe w  p u blis he d R W E st u dies f oc us o n D H a n d m os t f or me d p art of lar ge r, o bser vati o nal d e ntal 
practice -base d st u dies i n vesti gati n g t he ra n ge of met h o ds use d f or dia g n osi n g a n d tr eati n g D H 
(C u n ha -Cr uz et al , 2 0 1 0; Heft et al, 2 0 1 8; K o p yc k a Ke dziera ws ki et al, 2 0 1 7a; K o p yc k a -
Ke dziera ws ki et al , 2 0 1 7 b; Lita ker et al, 2 0 1 9). T he effecti ve n ess of a v ariet y of tr eat me nts 
use d t o ma na ge D H i n cli nical pract ice has bee n i n vesti gate d i n a ‘real-w orl d’ setti n g (Heft et 
al , 2 0 1 8). Patie nts self-assesse d t he effecti ve ness  of t heir de ntist -select e d met h o d  f or D H 
ma na ge me nt (e. g., de ntal treat me nt, a nti -se nsiti vit y pr o d uct use , oral h y gi e ne  a d vice, dietar y 
a d vice) usi n g Vis ual A n al o g u e  Scal es ( V A S ), La belle d Ma g nit u de S cales ( L M S), a n d  patie nt 
satisfacti o n q uesti o n naire . Patie nts w h o e x perie nce d a re d ucti o n i n D H pai n  als o re p orte d a  
p ositi ve satisfacti o n rati n g f or t heir tr eat me nt strat e g y. T he R W D  ge nerate d i n s uc h st u dies ca n 
be use d t o i m pr o ve cli nical practice f or t he ma na ge me nt of D H (Heft et al, 2 0 1 8). T he s p o ns or  
of t his st u d y  rece ntl y c o m plete d a R W E st u d y e val u at i n g t he i m pact of a c o m merciall y a v aila ble 
a nti-se nsiti vit y t o ot h paste c o ntai ni n g 5 % p otassi u m nitrate ( K N O3) o n O Hr Q o L i n a self-
re p orte d D H p o p ulati o n  (Hale o n cli nical st u d y 2 1 6 9 5 3 ). R W D s u p p orte d t he effecti ve n ess of a 
5 % K N O 3  t o ot h paste i n i m pr o vi n g O Hr Q o L i n t his p o p ulati o n.   
T he ai m of t his st u d y is t o e val uate t he i m pact of a c o m merciall y a vaila ble dese nsitizi n g 
t o ot h paste c o ntai ni n g 0. 4 5 4 % S n F 2 o n O Hr Q o L  i n a D H p o p ulati o n i n a real-w orl d setti n g.  
Sta n n o us fl u ori de 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 he treat me nt 
of D H si nce t he 1 9 9 0s (S c hiff, 2 0 0 6 ), wit h l o n git u di nal data ge n erate d i n R C Ts s u p p ort i n g its 
cli nical efficac y (Ni, 2 0 1 0 ; Par ki ns o n, 2 0 1 1 ; Ma ki n, 2 0 1 3 ; Par ki ns o n et al, 2 0 1 3; Par ki ns o n et 
al , 2 0 1 5. It is t heref ore rele va nt t o e x pl ore its effecti ve ness i n a real -w orl d setti n g a n d  o btai n 
data reflecti ve of D H s ufferers i n t heir o w n e n vir o n me nt.    
2. 2  
B a c k gr o u n d  
De nti n h y pers e nsiti vit y ( D H) h as bee n defi ne d as ‘ pai n deri ve d f r o m e x p ose d de nti n  i n res p o ns e 
t o c he mical, t her m al, tactile, or os m otic sti m uli w hic h ca n’t b e e x plai ne d as arisi n g fr o m a n y 
ot her de ntal defect or disease’ ( A d d y et al, 1 9 8 5; Ca na dia n A d vis or y B oar d o n De nti n 
H y p erse nsiti vit y, 2 0 0 3 ).  T he h y dr o d y na mic t he or y of D H h y p ot hesizes t hat a sti m ul us e xter nal 
t o t he t o ot h (f or e x a m ple, a te m perat ur e/ os m otic differe ntial, press ur e) ca uses m o ve me nt of t he 
fl ui d resi de nt wit hi n e x p ose d de nti nal t ub ules ( Brä n nstr ö m, 1 9 6 3 ). T his m o ve me nt ma y 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
sti m ulate ner ve pr ocesses i n t he de ntal p ul p (A d d y, 2 0 0 2 ; Hall et al, 2 0 0 0), res ulti n g i n t he 
c haracteristic s h ort, s har p pai n of D H.   
C urre ntl y t h ere are t w o a p pr oac hes f or t he ma na ge me nt of D H: n er ve d ese nsitizati o n a n d t he 
occl usi o n of e x p ose d de nti n t u b ules. T he de nti n  occl usi o n a p pr oac h uses t u b ule occl u di n g 
a ge nts w hic h p h ysicall y bl oc k t he e x p ose d e n d of t he de n ti nal t u b ules, t h us re d uci n g de nti nal 
fl ui d m o ve me nt a n d p ul pal irritati o n. De nti n t u b ule occl u di n g a ge nts, s uc h as str o nti u m salts, 
sta n n o us salts, bi o glass es, ar gi ni ne/cal ci u m car b o nate c o m ple x , or silicas ser ve t o p h ysicall y 
bl oc k or narr o w t he e x p ose d e n ds of de nti n t u b ules, re d uci n g d e nti nal fl ui d m o ve me nt, t here b y 
decreasi n g t he effect of e xter nal sti m uli. N u mer o us cli nical st u dies d e m o nstrate t he D H efficac y 
of S n F 2-c o ntai ni n g f or m ulati o ns [ e. g., s h ort ter m (t y picall y 1-1 4 da ys treat me nt): ( He et al., 
2 0 1 4a , He et al ., 2 0 1 1 a, He et al., 2 0 1 1 b, He et al., 2 0 1 1c, He et al., 2 0 1 1 d, Ce pe da -Bra v o et 
al ., 2 0 1 4, Creet h et al., 2 0 1 7a, Creet h et al., 2 0 1 7 b, G o yal et al ., 2 0 1 7, Par ki ns o n et al., 2 0 1 6 , 
Se o n g et al., 2 0 1 7, S har ma et al., 2 0 1 1, Creet h et al., 2 0 2 1); l o n ger ter m (t y picall y 4 -1 2 wee ks 
treat me nt): (C ha k nis et al., 2 0 1 1, Da y et al., 2 0 1 0, D u et al ., 2 0 1 1, Gall o b et al., 2 0 1 7, Haze n 
et al., 1 9 6 8, He et al., 2 0 1 4 b , Ni et al., 2 0 1 1, Ni et al., 2 0 1 0, Par ki ns o n et al., 2 0 1 3, Par ki ns o n 
et al., 2 0 1 5a, Sc hif f et al., 2 0 0 6, Sc hiff et al., 2 0 0 5, S har ma et al., 2 0 1 0, Vi na ya et al., 2 0 1 0, 
Hi nes et al., 2 0 1 9, A mi ni et al., 2 0 1 9, He et al., 2 0 1 9, Mas o n et al., 2 0 1 9, Hal e o n Cli nical St u d y 
2 0 9 7 2 3, 2 0 2 0 , Creet h a n d B ur nett, 2 0 2 1 , Ki m et al., 2 0 2 1). 
Rece ntl y, greater c o nsi derati o n has bee n gi ve n t o t he ps yc h os o cial i m pacts of D H o n e ver y d a y 
life (Gi bs o n et al , 2 0 1 5). O ne q ualitati ve st u d y s h o we d t hat D H ca n be tri g gere d b y se veral 
sti m uli a n d prese nt m ulti ple res p o nses, n ot al wa ys des cri be d as pai n, affecti n g e v er y d a y 
acti vities s uc h as eati n g, dri n ki n g, t o ot h br us hi n g, tal ki n g , a n d s oci al i nteracti o ns ( Gi bs o n et al, 
2 0 1 5).   
Oral healt h -relate d q ualit y of life ( O Hr Q o L) q uesti o n naires are i ncreasi n gl y use d i n de ntistr y 
t o ca pt ure t he i m pact of cli nical i nter ve nti o ns o n O Hr Q o L; t he y t y pi call y c o ver a n u m ber of 
oral healt h c o n diti o ns a n d s o ma y n ot detect t he n ua nces of a s p ecific c o n diti o n ( Be kes et al, 
2 0 0 9).  T he D e nti n  H y perse nsiti vit y E x perie n ce Q uesti o n naire ( D H E Q) is a vali date d, c o n diti o n 
s pecific meas ure of O Hr Q o L i n rel ati o n t o D H (Ba ker et al , 2 0 1 4, B oi k o et al, 2 0 1 0). It was 
de vel o pe d b y t he s p o ns or i n c olla b orati o n wit h S heffiel d U ni versit y t hr o u g h a r o b ust t he oretical 
fra me w or k, s pecifi c t o D H ( B oi k o et al , 2 0 1 0), 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 n eral p o p ul ati o n ( P orritt et al, 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 et al, 2 0 1 5). 
T he c o n ce pti o n, de v el o p me nt, vali dati o n , a n d i nitial usa ge of t he D H E Q has bee n p u blis he d 
(R o bi ns o n, 2 0 1 4 ). T he meas ure has b ee n v ali date d as b ot h l o n g - (D H E Q -4 8 ) a n d s h ort - 
( D H E Q-1 5) f or m v ersi o ns, c o m prisi n g 4 8 (Ba k er et al, 2 0 1 4; B oi k o et al, 2 0 1 0 ) a n d 1 5 
(Mac h uca et al , 2 0 1 4) q uesti o ns res pecti vel y, a n d has bee n tra nslat e d i nt o m ulti ple la n g ua ges 
(e. g., C hi nese, T ur kis h, P ort u g ues e) c o nfir mi n g its gl o bal rele va nce (Başara n a n d Celi k, 2 0 1 8 , 
D o u glas -De -Oli veira et al, 2 0 1 8, He a n d Wa n g, 2 0 1 5a , He a n d Wa n g, 2 0 1 5 b ). 
Data ge nerate d i n cli nical efficac y st u dies pr o vi d e  r o b ust a n d p ositi ve s u p p ort f or t he use  of t he 
s p o ns or’s dese nsitizi n g t o ot h pastes f or t he relief a n d ma na ge me nt of D H, as meas ure d b y 
cli nical i n dices  a n d t he D H E Q . H o we v er, t hes e res ults were ge nerate d u n der t he hi g hl y 
c o ntr olle d c o n diti o ns of a R C T i n res p o nse t o c o ntr olle d b ut c o ntri ve d D H sti m uli. T hese 
st u dies ma y n ot necessaril y f ull y reflect t he e x perie nce of t he ge neral D H p o p ulati o n w he n 
c halle n ge d wit h r eal w orl d sti m uli  f or D H.   
Base d o n t hes e ass u m pti o ns, t his R W E st u d y will i ncl u de p artici p a nts fr o m t he ge n eral 
p o p ulati o n w h o s uffer wit h D H  (s elf-re p orte d s y m pt o ms) a n d will e v al uate t he i m pact of dail y 
use of an a nti -se nsiti vit y t o ot h paste c o ntai ni n g 0. 4 5 4 %  S n F 2  o n D H -rel ate d O Hr Q o L. Dat a 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
ge n erat e d will pr o vi de real w orl d i nf or m ati o n o n t he i m pact of dail y us e of a d ese nsitizi n g  
treat me nt f or D H ma na ge me nt.  
2. 3  
B e n efit/ Ri s k A s s e s s m e nt  
T he st u d y pr o d uct is a c o m merciall y a vaila ble a nti-se nsiti vit y t o ot h paste c o ntai ni n g 0. 4 5 4 %  
S n F 2, mar kete d i n t he U nite d States ( U S ), a n d will be s u p plie d t o st u d y partici p a nts i n its  
c o m mercial pac k. S afet y i nf or mati o n is pri nte d o n  t he c o m mercial p ac k . 
2. 4  
M e c h a ni s m of A cti o n/I n di c ati o n  
S ta n n o us fl u ori de is a n o ccl usi o n a ge nt t hat reacts i n t he oral e n vir o n me nt t o f or m d e p osits o n 
t he s urface of e x p ose d  de nti n a n d wit h i n e x p ose d de nti n t u b ules ( Miller, 1 9 9 4 ). T hese d e p osits  
act as a barrier t o e xter nal sti m uli b y p h ysi call y bl oc ki n g or narr o wi n g t he o pe ni n gs of t h e 
e x p ose d t u b ules, t here b y re d uci n g de nti nal 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 i ntra-de ntal ner ves a n d e v o ke a pai n res p o ns e ( Miller, 1 9 9 4 , A d d y, 2 0 0 2 ; 
Par ki ns o n a n d Wills o n, 2 0 1 1 , B ur nett et al 2 0 1 3 ). 
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  
T a bl e 3 -1  
St u d y O bj e cti v e s a n d E n d p oi nt s  
 
 
O bjecti ves  
E n d p oi nts  
Pri m ar y  
T o descri be c h a n ges i n O Hr Q o L o ver 2 4 
wee ks  use  of a n a nti -se nsiti vit y t o ot h paste 
c o ntai ni n g 0. 4 5 4 %  S n F 2, 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 naire ( D H E Q -4 8 : T otal Sc ore a n d 
D o mai n Sc ores ), i n a D H p o p ulati o n . 
C ha n ge fr o m Bas eli ne i n D H E Q e n d p oi nts  at 
W ee ks 4, 8, 1 2, 1 6, 2 0 &  2 4.   
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)   
Sec o n d ar y  
T o descri be c h a n ges i n O Hr Q o L o ver 2 4 
wee ks use of a n a nti -se nsiti vit y t o ot h paste 
c o ntai ni n g 0. 4 5 4 % S n F 2, as meas ure d b y 
t he D H E Q -4 8  ( ot her e n d p oi nts), i n a D H 
p o p ulati o n . 
C ha n ge fr o m Bas eli ne i n D H E Q e n d p oi nts  at 
W ee ks 4, 8, 1 2, 1 6, 2 0 &  2 4.   
Secti o n 1  
•  I m pact o n E ver y d a y L ife ( Q 1-3)  
Secti o n 2  
•  Gl o bal Oral H ealt h Sc ore ( Q 3 5)  
•  Effect o n Lif e O verall Sc ore ( Q 3 6 -3 9)  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T his st u d y will be c o nsi dere d s uccessf ul if a tre n d of i m pr o ve me nt i n O Hr Q o L is o bser ve d o ver 
t he 2 4-wee k treat me nt peri o d ; h o we ver, it is e x pecte d t hat statisticall y si g nifi ca nt i m pr o ve me nts 
fr o m Bas eli ne will be o bser ve d i n D H E Q e n d p oi nts, partic ularl y D H E Q  T otal Sc ore.  
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 dece ntralize d , pr os pecti ve, 2 4-wee k, m o na dic desi g n, o pe n la bel , st u d y i n a D H 
p o p ulati o n.  T he st u d y will e val uate c ha n ges i n O Hr Q o L i n partici pa nts wit h self -re p orte d D H 
s y m pt o ms o ver  2 4 wee ks of use of a D H treat me nt (a nti -se nsiti vit y t o ot h paste). O Hr Q o L will 
be 
meas ure d usi n g a vali date d q uesti o n naire, 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 p artici pa nts at Baseli ne, a n d Wee ks 4, 8, 1 2, 
1 6, 2 0.  
Partici pa nts will be recr uite d t hr o u g h s ocial me dia a n d ot her di gital platf or ms. I n di vi d uals w h o 
are i ntereste d i n t he st u d y will be se nt t o a la n di n g pa ge after clic ki n g o n a n a d vertise me nt  or 
st u d y li n k w here t he y will c o m plete a n i nitial pre-scree ni n g q u esti o n naire. If eli gi ble t o 
partici pate, t he y will be se nt a n e mail c o ntai ni n g t heir u ni q ue partici pa nt I D a n d a n i n vitati o n 
t o d o w nl oa d t he 
 a p p. After d o w nl o a di n g a n d l o g gi n g i nt o t he 
 a p p, 
t he y will be a ble t o re vie w t he electr o nic I nf or me d C o nse nt (eI C), as k q uesti o ns a b o ut t he st u d y, 
a n d c o m m u nicate wit h t he 
 virt ual site tea m via t h e a p p c hat, p h o ne ( usi n g t he 
st u d y n u m ber liste d i n t he eI C), or e mail.  I n di vi d uals w h o deci de t o partici pate ma y t h e n c h o ose 
t o si g n t he eI C (el ectr o ni c si g n at ure). N o st u d y-s p ecific d ata will be c ollect e d pri or t o si g ni n g 
t he eI C. I n di vi d uals w h o d o n ot acti vel y access t he st u d y-s pecific a p p a n d pr o vi de c o nse nt will 
n ot be per mitte d t o partici pate i n t h e st u d y.  
O nce t he partici p a nt has si g ne d t he eI C, t he y will c o m plete a detaile d scree ni n g q uesti o n nair e 
t o i de ntif y a n d e x cl u de i n di vi d uals w h ose t o ot h se nsiti vit y c o ul d b e ca use d b y ot her 
T o 
s u m marize t he i n di vi d ual D H E Q 
d o mai n ite ms 
of c o ncer n  i n a 
D H 
p o p ulati o n bef ore a n d aft er  2 4 wee ks use  of 
a n a nti -se nsiti vit y t o ot h paste c o ntai ni n g 
0. 4 5 4 %  S n F 2. 
B aseli ne a n d Week 2 4 : 
•  Perce nta ge ( %) of p artici pa nts w h o ‘a gree ' 
(sc ore 5-7) wit h eac h ite m (state me nt)  i n 
t he 5 D H E Q d o mai n s ( D H E Q Secti o n 2, 
Q 1 -3 4).   
T o descri be  c ha n ges i n t h e i nte nsit y of s elf-
re p orte d D H pai n  o v er  2 4 wee ks us e  of a n 
a nti-se nsiti vit y  
t o ot h paste  
c o ntaini n g 
0. 4 5 4 %  S n F 2, as meas ur e d b y a N u meric 
Pai n 
Rati n g Scale ( N P R S) , i n a D H 
p o p ulati o n .  
C ha n ge fr o m Bas eli ne i n N P R S sc ore  at 
W ee ks 1, 2, 4, 8, 1 2, 1 6, 2 0 &  2 4.   
T o descri be  partici pa nt satisfacti o n wit h t he 
D H treat me nt (a nti-se nsiti vit y t o ot h paste 
c o ntai ni n g 0. 4 5 4 % S n F 2), as meas ure d b y a 
Satisfacti o n N u meric R ati n g S cale ( N R S) .    
Week 2 4 : 
Satisfacti o n N R S sc ore   
T o descri be t he oral h y gi e ne ha bits of a D H 
p o p ulati o n 
usi n g 
a n  
oral 
h y gie ne 
q uesti o n naire ( O H Q) . 
B aseli ne : 
O H Q res p o ns es 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
fact ors/cli nical p at hol o g y f or w hic h de ntal h ealt hcare pr ofessi o nal a d vice s h o ul d be s o u g ht. I n 
a d diti o n t o t he scree ni n g q uesti o n naire, p artici pa nts will be re q uir e d t o pr o vi de de m o gra p hi c 
i nf or mati o n (year of birt h, a ge, ge n der, g e o gra p hic area , et h nicit y a n d race) a n d c o m plete 
Me dical Hist or y a n d C o n c o mita nt Me dicati o ns f or ms. Partici pa nts w h o q u alif y, b ase d o n t heir 
res p o nses t o t he scree ni n g q uesti o n nair e a n d t he pr ot oc ol i ncl usi o n/e x cl usi o n criteria, will be 
e nr olle d a n d se nt s ufficie nt st u d y treat me nt ( des e nsitizi n g t o ot h paste c o ntai ni n g 0. 4 5 4 % S n F 2) 
t o c o m plete t he st u d y. Partici pa nts will c o nfir m recei pt of st u d y t o ot h paste i n t he 
 
a p p ( date of c o nfir mati o n of recei pt = Da y 0 ) a n d will be i nstr ucte d t o start usi n g it o n t he sa m e 
da y . T he y will use t he st u d y t o ot h paste  f or 2 4 wee ks acc or di n g t o t he i nstr ucti o ns o n t he 
c o m mercial pac k a n d t heir n or mal oral healt hcare ha bits.   
Partici pa nts will c o m plet e a D H E Q -4 8  at Baseli ne ( pri or t o first tr eat me nt use) a n d at 4 -wee k  
i nter vals t hr o u g h o ut t he treat me nt peri o d (Wee ks 4, 8, 1 2, 1 6, 2 0 a n d 2 4 ). I n a d diti o n t o t he 
D H E Q -4 8 , t he y will rate t heir D H-relate d pai n usi n g a N u meric Pai n Rati n g Scal e (N P R S ) at 
Baseli ne, a n d aft er 1, 2, 4, 8, 1 2, 1 6, 2 0 a n d 2 4 wee ks of treat me nt.   
Partici pa nts will descri be t heir oral h y gie ne ha bits at Baseli ne b y c o m pleti o n of a n Oral H y gie ne 
Q uesti o n naire ( O H Q). O n c o m pleti o n of t he 2 4 -wee k st u d y, t he y will rate t heir satisfacti o n wit h 
t he D H treat me nt usi n g a N u meric Rati n g Scal e (N R S ) a n d c o m plete  a n u m ber of E n d of St u d y 
( E O S)/ o pe n e n d e d 's ur ve y' q uesti o ns. 
Self -re p ort e d a d verse e v e nts ( A Es) will be c ollecte d re m otel y vi a t he 
 a p p.  
4. 2  
S ci e ntifi c R ati o n al e f or St u d y D e si g n  
N u mer o us cli nical st u dies de m o nstrate t he D H efficac y of S n F 2-c o ntai ni n g f or m ulati o ns (e. g., 
sh ort ter m st u dies (t y pic all y 1-1 4 d a ys tr eat me nt): He et al., 2 0 1 4 a, He et al ., 2 0 1 1a, He et al., 
2 0 1 1 b , He et al., 2 0 1 1c, He et al., 2 0 1 1 d, Ce pe da -Bra v o et al., 2 0 1 4, Creet h et al., 2 0 1 7a, Creet h 
et al., 2 0 1 7 b, G o yal et al., 2 0 1 7, Par ki ns o n et al., 2 0 1 6, Se o n g et al., 2 0 1 7, S har ma et al., 2 0 1 1, 
Creet h et al., 2 0 2 1; lo n ger ter m st u dies (t y picall y 4-1 2 wee ks treat me nt): C ha k nis et al., 2 0 1 1, 
Da y et al., 2 0 1 0, D u et al ., 2 0 1 1, Gall o b et al., 2 0 1 7, Haze n et al., 1 9 6 8, He et al., 2 0 1 4 b, Ni et 
al ., 2 0 1 1, Ni et al ., 2 0 1 0, Par ki ns o n et al., 2 0 1 3, Par ki ns o n et al., 2 0 1 5a, Sc hiff et al., 2 0 0 6, 
Sc hiff et al., 2 0 0 5, S har ma et al., 2 0 1 0, Vi na ya et al., 2 0 1 0, Hi nes et al., 2 0 1 9, A mi ni et al., 
2 0 1 9,  He  et al., 2 0 1 9, M as o n et al., 2 0 1 9, G S K C H Cli nical St u d y 2 0 9 7 2 3, 2 0 2 0 , Creet h a n d 
B ur nett, 2 0 2 1 , Ki m et al., 2 0 2 1). S u c h R C T s i ncl u de a well-defi ne d D H p o p ulati o n a n d  f oll o w 
defi ne d st u d y pr oce d ures a n d ma y n ot, t heref ore, f ull y refl ect t he e x perie nce a n d be ha vi ors  of 
t he ge neral D H  p o p ulati o n.  R W E st u dies ma y  m or e acc urat el y re prese nt p o p ulati o n res p o nses 
t o a n i nter ve nti on w he n t he pr o d uct is use d as part of e v er y da y life , t h ere b y ma ki n g t he res ults 
m ore easil y ge neralize d . T he y offer o p p ort u nities t o gat her i nf or mati o n o n mar kete d pr o d ucts 
t o b olster e xisti n g cli nical e vi de nce a n d gai n a d diti o nal i nsi g hts i n t he tar get p o p ulati o n.   
T he fe w D H -relat e d R W E st u dies p u blis he d t o date were c o n d u cte d as part of lar ger, 
o bser vati o nal de ntal practice -base d st u dies i n vesti gati n g met h o ds a vaila ble  f or dia g n osi n g a n d 
treati n g D H (C u n ha -Cr uz et al, 2 0 1 0; Heft et al, 2 0 1 8; K o p yc ka Ke dziera ws ki et al, 2 0 1 7a; 
K o p yc ka -Ke dziera ws ki et al, 2 0 1 7 b; Lita ker et al, 2 0 1 9). T h e s p o ns or has c o m plete d a R W E 
st u d y e val uati n g t he i m pact of a nti-se nsiti vit y t o ot h paste o n O Hr Q o L i n a D H p o p ulati o n 
(Hale o n cli nical st u d y 2 1 6 9 5 3 ). R W D  ge nerate d i n t his st u d y  s u p p orts t h e effecti ve ness of a 
mar kete d 5 % K N O 3  t o ot h paste i n i m pr o vi n g O Hr Q o L  i n a D H p o p ulati o n .   
A m o na dic desi g n h as b ee n sele cte d f or t his c urre nt st u d y. Acce pti n g t he li mitati o ns of t his 
desi g n, t he rati o nale f or its selecti o n is d escri b e d i n t he p u blicati o n f or a si milar e xte n de d us e 
cli nical st u d y w hic h als o e val uated  partici pa nt re p orte d O Hr Q o L o utc o m es i n a D H p o p ulati o n 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
(Mas o n et al, 2 0 1 9 ): a n e gati ve-c o ntr olle d st u d y w o ul d re q uir e D H s ufferers t o use a re g ular 
fl u ori de t o ot h paste wit h n o dese nsitizi n g pr o perties f or nearl y 6 m o nt hs, with ass ociate d et hical 
i m plicati o ns; a d diti o nall y, a p ositi ve c o ntr ol st u d y d esi g n w o ul d re q uire far hi g her partici pa nt 
n u m bers t o ac hie v e its scie ntific o bjecti ves (e. g., e q ui vale nce/ n o n -i nf eri orit y). 
A c o m merciall y a vaila bl e t o ot h paste will be use d i n t his  o pe n la bel st u d y; partici pa nts  will use 
t he pr o d uct acc or di n g t o t he la bel i nstr ucti o ns o n  c o m mercial  p ac k , as fits t he nat ure of t he 
R W E st u d y.  
T y pic all y, t o partici p ate i n a  cli nical efficac y st u d y , partici pa nts are re q uir e d t o ha ve cli nicall y 
c o nfir me d D H  ( deter mi n e d b y cli nical e x a mi nati o n) , wit h eac h q ualif yi n g t est t o ot h i de ntifie d 
a gai nst pr ot oc ol -defi ne d  i ncl usi o n/e xcl usi o n criteria. I n t his R W E st u d y, p artici pa nts will be 
i de ntifie d as D H s ufferers fr o m t he ge n eral p o p ul ati o n usi n g a s cree ni n g q uesti o n naire (P orritt 
et al, 2 0 1 6) t o i de ntif y a n d e x cl u de i n di vi d uals w h ose se nsiti vit y c o ul d be ca use d b y ot h er 
fact ors/cli nical p at h ol o g y.  
T he a ge ra n ge o v er  w hi c h a n i n di vi d ual ca n e x perie nce D H is wi d e (earl y t ee ns t o 7 0s) (Fisc her 
et al, 1 9 9 2) , wit h pea k i nci de nce k n o w n t o occ ur bet wee n t he a ges of 2 0-4 0 years (Fl y n n et al, 
1 9 8 5) . T h e 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 ne a n d p ul p of t he t o ot h w hic h act t o re d u ce b ot h de nti ne 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 a n d Be n der, 1 9 7 5 ; Da ba b n e h et al , 1 9 9 9; West, 
2 0 0 6 ; Pas hle y, 2 0 0 8) . T h e de ntal p ai n e x perie nce d b y m u c h 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 ge of 1 8 -6 5  years has bee n 
selecte d f or t his st u d y t o tar get i n di vi d uals wit h t o ot h se nsiti vit y d ue t o D H. 
Eli gi ble partici pa nts will c o m plet e t he De nti n  H y p erse nsiti vit y E x perie nce Q uesti o n nair e 
( D H E Q) - a v ali date d, c o n diti o n -s pecific m eas ure of i m pacts o n t he e v er y da y life f or D H 
s ufferers (Ba k er et al, 2 0 1 4) (B oi k o et al, 2 0 1 0) - at B as eli ne a n d at 4 -wee kl y i nter vals o v er 2 4 -
wee k peri o d. T he c h oic e of t he ti me p oi nts ( Baseli ne, Wee ks 4, 8, 1 2, 1 6, 2 0 a n d 2 4) reflects 
t he desi g ns of a p u blis he d s p o ns or st u d y (Mas o n et al, 2 0 1 9) a n d a rece ntl y c o m plete d R W E 
st u d y (Hale o n cli nical st u d y 2 1 6 9 5 3 ). Mas o n et al re p orte d statisticall y si g nifica nt, o n g oi n g 
i m pr o ve me nts i n O Hr Q o L (c o m p are d t o Bas eli ne): D H E Q T otal Sc ore was statisticall y 
si g nifica nt fr o m Wee k 8; d o mai ns sc ores a n d Effect o n Life O verall f oll o we d a si milar patter n . 
T he y  c o ncl u d e d t hat l o n g -ter m use of a n a nti-s e nsiti vit y t o ot h paste h a d a be neficial  i m pact o n 
t he O Hr Q o L  of D H s ufferers  (M as o n et al, 2 0 1 9).  
I n a d diti o n, partici pa nts wi ll be as ke d t o self-re p ort t he i nte nsit y of t heir D H pai n at Bas eli ne, 
a n d Wee ks 1, 2,  4, 8, 1 2, 1 6, 2 0 & 2 4 usi n g a N u m eric P ai n R ati n g Scale ( N P R S ).T he pr o p orti o n 
of partici p a nt s w h o e x perie nce > 3 0 % re d ucti o n i n N P R S  sc ore i n t his st u d y will be deter mi ne d ; 
a re d ucti o n of > 3 0 % has bee n descri be d as cli nicall y i m p orta nt i n pai n -relat e d cli nical efficac y 
st u dies (Ha w ker et al, 2 0 1 1). At t he e n d of t he st u d y  ( Wee k 2 4), partici pa nts will be as ke d t o 
rate t heir satisf acti o n wit h t he D H  treat me nt (Heft  et al, 2 0 1 8; va n Berc kel et al, 2 0 1 7). 
4. 3  
J u stifi c ati o n f or D o s e  
Directi o ns f or us e of t he st u d y t o ot h paste will be as state d o n its’ c o m merci al t u be.  
4. 4  
E n d of St u d y D efi niti o n  
T he e n d of t h e st u d y is defi ne d f or eac h partici pa nt as 1 6 8 da ys (±  7 d a ys ) fr o m t he dat e of 
c o nfir mati o n of recei pt of st u d y t o ot h paste  ( Da y 0), partici pa nt  deat h, earl y wit h dra wal fr o m 
t he st u d y, partici pa nt l ost t o f oll o w-u p , or o verall st u d y ter mi nati o n.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 P arti ci p a nt s  
S ufficie nt n u m bers  will be scree ne d ( esti mate d  u p t o 5 0 % scree n fail ure rate) t o e nr oll 
a p pr o xi matel y 5 0 0 p artici pa nts t o e ns ure 4 0 0 e v al ua ble p artici pa nts c o m plete t he e ntire st u d y 
(esti mate d u p t o 2 0 % dr o p o ut  rate).  
A n e nr olle d partici pa nt is o ne w h o has a gree d t o partici pate i n t he R W E  st u d y f oll o wi n g 
c o m pleti o n of t he eI C pr ocess a n d has s uccessf ull y met t he eli gi bilit y criteria t o pr ocee d be y o n d 
t he scree ni n g pr oce d ures,  as a p plica ble f or t he pr ot oc ol desi g n .  
T his st u d y ca n f ulfill its o bjecti ves o nl y if a p pr o priate partici pa nts are e nr olle d.  T he f oll o wi n g 
eli gi bilit y criteria are desi g ne d t o select i n di vi d uals 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. R ele 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 d eci di n g w het h er a p ote n tial p artici pa nt is s uita ble.   
E li gi bilit y t o partici pate i n t his R W E st u d y s h o ul d be re vie we d a n d d oc u me nte d b y a n 
a p pr o priate me m ber of t he 
 st u d y tea m bef ore a partici pa nt 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 
A n i n di vi d ual m ust me et t he f oll o wi n g i n cl usi o n criteria t o b e eli gi ble f or e nr oll me nt i nt o t he 
st u d y:  
1.  Partici pa nt w h o has pr o vi de d  c o nse nt i n dicati n g t he y ha v e bee n i nf or m e d of all perti ne nt 
as pects of t he st u d y.  
2.  All ge n d ers w h o, at t he ti me of scree ni n g , are a ge d bet wee n  1 8 a n d 6 5 years (i ncl usi ve). 
3.  Partici pa nt w h o is willi n g t o c o m plete all acti vities as descri be d  i n t he Sc h e d ule of Acti vities  
(Ta ble 1 -1 ).  
4.  Partici pa nt w h o is a ble t o i n de pe n de ntl y c o m plet e all acti vities o n t heir s mart de vices as 
descri be d  i n t he Sc h e d ule of Acti vities  (Ta bl e 1 -1 ). 
5.  Partici pa nt w h o has t o ot h se nsiti vit y (self -re p orte d s y m pt o ms). 
5. 3  
E x cl u si o n Cri t eri a 
A n i n di vi d ual w h o meets a n y of t he f oll o wi n g e x cl usi o n criteria will n ot be eli gi ble f or 
e nr oll me nt i nt o t he st u d y:  
1.  Partici pa nt w h ose se nsiti vit y c o ul d be ca use d b y ot her fact ors or cli nical pat h ol o g y  t ha n 
D H , as self-re p ort e d o n t he scree ni n g q uesti o n nair e, w hic h i ncl u de:    
•  Partici pa nt w h o has bee n/is o n m ulti ple prescri pti o n  me dicati o ns t o treat se vere aci d 
refl u x o n a re g ular b asis or has ha d  s ur ger y f or aci d refl u x.  
•  Partici pa nt wit h f ull or  partial de nt ure (s).  
•  Partici pa nt w h o has u n der g o ne tr eat me nt f or p eri o d o ntal or g u m dise ase wit hi n 6 
m o nt hs of scree ni n g or is c urre ntl y u n d er g oi n g  tr eat me nt f or p eri o d o ntal or g u m disease.  
•  Partici pa nt w h o has  bee n i nf or me d b y a De ntal Healt h Care Pr ofes si o nal ( D H C P) t hat 
t he y h a ve acti ve peri o d o ntitis .  
•  Partici pa nt w h o has  bee n i nf or me d b y a D H C P  t h at t he y h a ve acti ve caries .  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
•  Partici pa nt wit h a n y c hr o nic a n d/ or se v ere p ai nf ul healt h c o n diti o n (s) w hic h lea d t o 
re g ular use of pai n relief me dicati o ns ( m ore  t ha n 3 da ys a wee k).  
2.  Partici pa nt wit h k n o w n or s us pecte d i nt olera nce or h y p erse nsiti vit y t o t he st u d y materi als 
( or cl osel y relate d c o m p o u n ds) or a n y of t heir state d i n gre die nts. 
5. 4  
R a n d o mi z ati o n Crit eri a  
T here will be n o ra n d o mizati o n i n t his st u d y.  
5. 5  
Lif e st yl e C o n si d er ati o n s  
T his R W E st u d y will n ot i ncl u de a n y lifest yle c o nsi derati o ns or restricti o ns . 
5. 6  
S cr e e n F ail ur e s  
Scree n fail ures are defi n e d as p artici pa nts w h o c o nse nt t o partici pat e i n t he cli nical st u d y b ut 
are n ot s u bs e q ue ntl y e nr olle d i n t he st u d y (i.e., d o n ot meet  t he pr ot oc ol i ncl usi o n/e xcl usi o n 
criteria). T o e ns ure tr a ns pare nt re p orti n g of s cree n fail ure s, a mi ni mu m  set of scree n fail ure 
i nf or mati o n will be c ollecte d i ncl u di n g d e m o gra p h y, reas o n f or scree n fail ure (e. g., wit h dra wal 
of c o nse nt), eli gi bilit y criteria, pr ot oc ol de vi ati o ns , a n d A Es , as a p pr o priate.  
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) or ca n n ot 
c o m plete S cree ni n g/ Baseli ne acti vities  d ue t o a tec h nical iss u e wit h t he 
 a p p will 
n ot  be re -scree 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 pri atel y q ualifie d m e dical/ de nt al pers o n nel f or t he 
st u d y will be  d oc u me nte d i n t he St u d y C o ntact List hel d b y 
.  
T he c o ntact n u m ber s h o ul d o nl y b e use d b y 
 staff see ki n g a d vi ce 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 est a blis he d c o m m u nicati o n pat h wa ys are n ot 
a vaila ble. T he c o ntact n u m ber is n ot i nte n de d f or direct use b y st u d y par tici pa nts.  
T o facilitate access t o a p pr o priatel y q ualifie d me dical/ de ntal pers o n nel o n st u d y -relat e d 
me dical/ de ntal q uesti o ns or pr o ble ms, partici pa nts will be pr o vi de d wit h c o ntact i nf or mati o n i n 
t he 
 a p p or will be a ble t o use t he c h at f u nctio n i n t he 
 a p p. 
5. 8  
R at er/ Cli ni c al A s s e s s or Q u alifi c ati o n s  
N/ A  
6  
S T U D Y P R O D U C T  
6. 1  
St u d y Pr o d u ct S u p pl y  
T he f oll o wi n g st u d y pr o d uct will be s u p plie d b y t h e s p o ns or’s Cli nical S u p plies De part me nt . 
T a bl e 6 -1  
St u d y Pr o d u ct S u p pl y  
Pr o d uct Descri pti o n  
A nti -se nsiti vit y t o ot h past e c o ntai ni n g 0. 4 5 4 % S n F 2 
Pr o d uct N a me  
Se ns o d y ne Re p air a n d Pr otect ( U S mar ket)  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
Fl u ori de C o nte nt  
1 1 0 0 p p m fl u ori de as S n F 2 
P ac k D esi g n  
Cart o n c o ntai ni n g 1 2 t u b es of t o ot h paste  
Dis pe nsi n g Det ails  
O ne cart o n dis patc h e d  t o partici pa nt (o n c o m pleti o n of 
all ‘B as eli ne’ acti vities)  
M aster F o r m ul ati o n C o de  
 
R o ute of A d mi nistr ati o n  
T o pical Oral Us e  
D ose/ A p plic ati o n  
As per directi o ns pri nte d  o n c o m mercial pac k  
Us a ge I nstr ucti o ns  
As per directi o ns pri nte d  o n c o m mercial pac k   
Ret ur n Re q uire me nts  
Partici pa nts ma y  kee p t heir use d  a n d u n use d pr o d uct at 
t he e n d of t he st u d y or  dis p ose of it, after first defaci n g or 
re m o vi n g t he st u d y la bel.  
Partici pa nts will re p ort h o w ma n y u n use d t u bes of st u d y 
pr o d uct re mai n at t he e n d of t he 2 4 -wee k treat me nt 
peri o d , a n d c o nfir m t he a b o ve i nstr ucti o ns f or dis p osal 
ha ve bee n f oll o we d , i n t h e 
 a p p.  
T hese q ue sti o ns will be i ncl u de d i n t he E O S q uesti o ns. 
6. 1. 1  
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 uct  will be s u p plie d b y t he s p o ns or i n its c o m mercial pac k t o 
 
preferre d v e n d or .  
St u d y la b els will be a p plie d t o t he t o ot h paste t u bes a n d t o t he o uter cart o n. T he c o nte nt of t he 
la bels will be i n acc or da nce wit h all a p plica bl e 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 Gl o bal Cli nical S u p plies gr o u p. Eac h st u d y la bel will c o ntai n, 
b ut n ot be li mite d t o, t he pr ot oc ol n u m ber  a n d  directi o ns f or us e  (i. e., t o f oll o w usa ge  
i nstr ucti o ns o n t he c o m mercial pac k) . I n a d diti o n, t he o uter cart o n la bel will c o ntai n pr o d uct 
st ora ge re q uire m e nts. St u d y  la b els s h o ul d n ot o bsc ure t h e usa ge i nstr ucti o ns a n d s afet y 
i nf or mati o n o n t he c o m mercial  pac k.  
It is i m p orta nt t hat pr o d uct  la bels re mai n i ntact a n d le gi ble f or t he d urati o n of t he st u d y. 
Partici pa nts will  be i nstr ucte d t o n ot re m o ve or deface a n y p art of t he st u d y l a bel  u ntil  t he e n d 
of t he st u d y . 
St u d y p r o d uct is s u p plie d f or use i n t his 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  
or b y a n y o ne ot her t ha n e nr olle d partici pa nt .  
6. 1. 2  
Pr e p ar ati o n a n d Di s p at c h   
T he st u d y pr o d uct will be pac k a ge d  a n d dis patc he d t o st u d y p artici pa nts b y 
 
preferre d ve n d or acc or di n g t o 
 i nstr ucti o ns a n d t he  ve n d or’s  sta n dar d pr oce d ures . 
Pr o d uct s hi p me nt will be trac ke d . 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
O nl y e nr olle d partici pa nts w h o ha ve c o m plete d all Baseli ne acti vities will recei ve st u d y 
pr o d uct.  Eac h eli gi ble partici pa nt will recei ve 1 2 t u bes of st u d y pr o d uct, s ufficie nt t o c o ver 
usa ge f or t he d urati o n of t he st u d y. Partici pa nts will c o nfir m recei pt of st u d y t o ot h paste i n t he 
 a p p ( date of c o nfir mati o n of recei pt = Da y 0) a n d will be i nstr ucte d t o start usi n g 
it o n t he sa me da y. 
6. 2  
A d mi ni str ati o n  
T he a p p will  a d vise partici pa nts t o f oll o w t he i nstr ucti o ns o n t he c o m merci al pac k . Partici pa nts 
will be as ke d t o c o nfir m t he ir first use of t he pr o d uct t hr o u g h t he 
 a p p. 
6. 2. 1  
M e di c ati o n/ D o si n g Err or s  
N/ A  
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 pr o d uct at a n a m o u nt hi g her t ha n 
s pecifie d o n t he c o m mercial pac k of t he st u d y pr o d uct.  O ver d ose is n ot li kel y t o occ ur i n t his 
st u d y. 
6. 3  
St u d y Pr o d u ct St or a g e   
, or t heir preferre d ve n d or , m ust c o nfir m a p pr o priate te m perat ure 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 uct  recei ve d. An y discre pa ncies s h o ul d be 
re p orte d t o t he s p o ns or a n d res ol ve d bef 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 . 
 or t heir preferre d ve n d or, will e ns ure t hat all st u d y pr o d uct is st ore d i n a sec ure d 
area, wit h c o ntr olle d access , u n der t he st ora ge c o n diti o ns s pecifie d o n t he c o m mercial pac k, 
a n d i n acc or da nce wit h a p plica ble re g ulat or y re q uire me nts.   
Ve n d or  s yste ms m ust be ca pa ble of meas uri n g a n d d oc u me nti n g (e. g., via a l o g), at a mi ni m u m, 
t he dail y mi ni m u m  a n d ma xi m u m te m perat ures f or all ve n d or site st ora ge l ocati o ns. T his s h o ul d 
be ca pt ure d t hr o u g h o ut t he st u d y  fr o m t h e ti me of first pr o d uct recei pt. E ve n 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 dail y e val u ati o n f or e x c ursi o ns 
s h o ul d be a vaila ble. T he t e m perat ur e-m o nit ori n g s yste m s h o ul d be i ns p ecte d re g ularl y t o e ns ure 
it is o perati n g as e x pecte d a n d mai ntai ne d i n g o o d w or ki n g or der.  
T he ve n d or will re p ort a n y e x c ursi o ns fr o m t he p er mitte d  st ora ge c o n diti o ns t o 
 
u p o n disc o ver y f or c o m m u nicat i o n t o s p o ns or as s o o n as p ossi ble. T he ve n d 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 pr o d uct t o t he re q uire d st ora ge c o n diti o ns as s o o n as 
p ossi ble.  E x c ursi o ns fr o m t he st ora ge re q uire m e nts, i ncl u di n g a n y acti o ns ta ke n, m ust b e 
d oc u me nte d as a pr ot oc ol de viati o n , a n d re p ort e 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 pr o d uct s h o ul d 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 d es writte n  per missi o n t o use. Use of a n y of t he affect e d pr o d uct 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.   
T he s p o ns or’s Cli nical S u p plies De part me nt will pr o vi de 
 wit h writte n g ui da nce 
f or st u d y pr o d uct st ora ge a n d acti o ns t o be t a ke n i n case of e x c ursi o n pri or t o s hi p pi n g t h e 
pr o d uct t o 
 preferre d ve n d or. 
 
will rec or d pr o d uct  st ora ge 
pr oce d ures i n t he ele ctr o nic Trial Master File ( e T M F). 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
6. 4  
St u d y Pr o d u ct A c c o u nt a bilit y  
P r o d uct is s u p plie d f or use i n t his 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.  
 preferre d ve n d or m ust mai ntai n a de q uate rec or ds d o c u me nti n g t he recei pt, 
s hi p me nt, l oss, or ot her dis p ositi o n of all pr o d uct s u p plies. T he preferre d ve n d or  is res p o nsi ble 
f or 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 f or all st u d y pr o d uct st or e d at 
t he ve n d or site.  
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 he st u d y, a n a p pr o priate d esi g n ee of  
 preferre d v e n d or  (wit h 
g ui da n ce fr o m t he s p o ns or’s Cli nical S u p plies S pecialist ) will i n ve nt or y all u n use d  st u d y 
pr o d uct  re mai ni n g at t he ve n d or site  a n d c o m plete  t he re q uire d pr o d uct acc o u nta bilit y 
d oc u me ntati o n . N o n -dis patc he d /u n use d st u d y pr o d uct retai ne d at t he ve n d or site  will be 
ret ur ne d t o t he s p o ns or’s Cli nical S u p plies De p art me nt , or desi g n ate d v e n d or , f or destr u cti o n 
usi n g t he ret ur n i nstr ucti o ns pr o vi de d. T h e s p o ns or will pr o vi de 
 wit h detaile d 
i nstr ucti o ns f or t he ret ur n of st u d y pr o d uct, acc o u nta bilit y c h ec ks a n d s u bse q ue nt destr u cti o n , 
as a p plica ble,  pri or t o  st u d y cl ose o ut. 
O n c o m pleti o n of t he s t u d y, p artici pa nts ma y  k ee p a n y use d/ u n us e d st u d y pr o d uct , or m a y 
c h o ose t o dis p ose st u d y pr o d uct after defaci n g or re m o vi n g t he st u d y la bel.  
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  
T his is a n  o pe n la bel, m o na dic st u d y; bli n di n g a n d ra n d o mizati o n are n ot re q uire d.  
6. 6  
Br e a ki n g t h e Bli n d  
N/ A  
6. 7  
C o m pli a n c e  
Partici pa nts will be as k e d t o f oll o w t he c o m m ercial p ac k usa ge i nstr ucti o ns. T o facilitate 
c o m plia nce, t he 
 a p p will se n d st u d y partici pa nts wee kl y n otificati o ns/re mi n ders 
relate d t o pr o d uct usa ge (e. g., use  t he t o ot h paste e v er y d a y, f oll o w t he usa ge i nstr ucti o ns o n t he 
c o m mercial p ac k ), a n d partici pa nts will c o m plete a q uesti o n naire i n t he a p p t o ca pt ure t heir 
pr o d uct usa ge  i nf or mati o n. 
 virt ual st u d y tea m m a y als o ma ke a d diti o nal c o ntact 
wit h  s pecific partici p a nts if l o w c o m plia nce or ris k of dr o p o ut is detecte d .  
Partici pa nts will be as ke d t o c o nfir m t he d ate of last use of t he st u d y pr o d uct  a n d h o w m a n y 
u n use d t u bes of st u d y pr o d uct re main  at t he e n d of t he st u d y usi n g t he 
 a p p i n t h e 
E O S/ o pe n e n de d 's ur v e y' q uesti o ns .  
6. 8  
C o n c o mit a n t M e di c ati o ns / Tr e at m e nt s 
Partici pa nts will be as ke d t o self -re p ort c ha n ges t o t heir e xisti n g me dicati o ns/treat me nts a n d 
a n y n e w me dicati o ns/treat me nts fr o m ti me of e-c o nse nt  t o last use of st u d y pr o d uct t hr o u g h t h e 
 a p p. R eas o n f or use, u nit d ose, dail y d ose, start a n d st o p dates will be rec or de d, 
as a p pr o priat e.   
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 
P A R TI CI P A N T  DI S C O N TI N U A TI O N/ WI T H D R A W A L  
7. 1  
P arti ci p a nt  Di s c o nti n u ati o n/ Wit h dr a w al  
Partici pa nts ma y wit h dr a w fr o m t he st u d y at a n y ti me at t heir o w n re q uest. T h eir ri g ht t o 
wit h dra w a n d i nf or mati o n a b o ut h o w t o wit h dr a w will be i ncl u de d i n t he  eI C . S h o ul d a  
partici pa nt wit h dra w or be disc o nti n ue d fr o m t he st u d y, all f urt her sc h e d ule d c o m m u nicati o n 
wit h t hat partici pa nt will be disc o nti n ue d (e -mail s, te xt messa ges, a n d/ or n otificati o ns). T he 
reas o n(s) f or wit h dra wal or disc o nti n uati o n will be rec or de d i n t he 
 p ortal.  
If t he partici pa nt wit h dr a ws fr o m t he st u d y a n d wit h dra ws c o nse nt f or discl os ure of f ut ure 
i nf or mati o n, n o a d diti o nal data will  be c ollecte d. T he s p o ns or  ma y retai n a n d c o nti n ue t o use 
data c ollecte d b ef ore t he wit h dra wal of c o nse nt.  
7. 2  
L o st t o F oll o w -U p  
A partici pa nt will be c o nsi dere d l ost t o f oll o w -u p if 
 is re peate dl y u na ble t o c o ntact 
t he m after c o nti n ue d n o n -res p o nse t o re p eate d re mi n ders t o l o gi n a n d c o m plete st u d y acti vities 
(ge nerate d b y  t he 
 a p p) u p t o 2 4 wee ks (+ 7 da ys)  fr o m t he d at e of c o nfir mati o n of 
recei pt of st u d y t o ot h past e ( Da y 0).   
Bef ore a partici pa nt is dee me d l ost t o f oll o w-u p, 
 will ma ke e ver y eff ort t o re gai n 
c o ntact (3 c o m m u nicati o n atte m pts ). C o ntact atte m pts ma de o utsi de of t he 
 a p p 
will be d oc u me nte d.  
S h o ul d a partici pa nt c o nti n ue t o be u nreac ha 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.  
8  
S T U D Y P R O C E D U R E S  
T hi s secti o n descri bes  t he pr oce d ures t o b e c o m plet e d at eac h pl a n ne d st u d y ti me p oi nt; the or der  
i n w hic h pr oce d ure s s h o ul d be c o m plete d is liste d i n t he Sc he d ule of Acti vities  ( Ta ble 1-1 ). 
‘ Start’ a n d ‘e x pirati o n’ wi n d o w s will be set f or eac h st u d y -re q uir e d acti vit y, per  ti mi n g 
t olera nces s pecifie d i n t he Sc he d ule of Acti vities  (Ta ble 1 -1 ). Access t o t h e 
 a p p 
will n ot be i nterr u pte d b ut o utsi de of t h ese t olera nces t he partici pa nt will n ot be a ble t o start 
e nteri n g res p o nses  or s u b mit late res p o nses f or a  misse d ‘ visit’. Partici pa nts a re re q uir e d t o 
c o m plete at least o n e p ost -Baseli ne D H E Q t o be i ncl u de d i n t he m o difie d I nte nt -T o -Treat 
( mI T T) p o p ulati o n. 
 will pr o vi de t he  a p p use d t o c o n d uct all st u d y acti vities, t o pr o vi de partici pa nts 
wit h i nf or mati o n a n d trai ni n g , a n d t o c ollect st u d y data . Self -re p orte d a d verse e ve nts ( A Es) will 
be c ollecte d via t h e 
 a p p.  
8. 1  
S cr e e ni n g  
8. 1. 1  
I nf or m e d C o n s e nt 
Partici pa nts will be recr uite d t hr o u g h s ocial me dia a n d ot her di gital platf or ms. I n di vi d uals w h o 
are i ntereste d i n t he st u d y will be se nt t o a la n di n g pa ge after clic ki n g o n a n a d vertise me nt  or 
st u d y li n k w here t he y will c o m plete a n i nitial pre-scree ni n g q u esti o n naire. If eli gi ble t o 
partici pate, t he y will be se nt a n e mail c o ntai ni n g t heir u ni q ue partici pa nt I D a n d a n i n vitati o n 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
t o do w nl oa d t he 
 a p p. After d o w nl o a di n g a n d l o g gi n g i nt o t he 
 a p p, 
t he y will be a ble t o re vie w t he electr o nic I nf or me d C o nse nt (eI C), as k q uesti o ns a b o ut t he st u d y, 
a n d c o m m u nicate wit h t he 
 site tea m, i ncl u di n g t he i n vesti gat or,  via t he a p p 
c hat, p h o ne ( usi n g t he st u d y n u m ber liste d i n t he eI C) , or e mail.  I n di vi d u als w h o deci de t o 
partici pate ma y t h e n c h o ose t o si g n t he eI C (electr o nic si g nat ur e). N o st u d y -s p ecific data will 
be c ollecte d pri or t o si g ni n g t he eI C. I n di vi d uals w h o d o n ot acti vel y access t he st u d y -s p ecific 
a p p a n d pr o vi de c o nse nt will n ot be per mitte d t o partici pate i n t he st u d y.  
T he eI C will  be I R B -a p pr o ve d  pri or t o first use ; a n y a me n d me nt s t o t he a p pr o ve d eI C will  be 
re-a p pr o ve d b y t he I R B  pri or t o distri b uti o n or use.  Bef ore a n y st u d y-s pecifi c data are c ollecte d, 
eac h p artici pa nt m ust :  
•  Be i nf or m e d of all as p ects of t he st u d y (ris ks a n d be nefits) .  
•  Be gi ve n ti me t o as k q uesti o ns  a b o ut t he st u d y a n d c o nsi der t he ir decisi o n t o partici pate .  
•  V ol u ntaril y a gree t o parti ci pate i n t he st u d y .   
•  Electr o nicall y s i g n a n d d ate t he I R B-a p pr o ve d eI C .  
Eac h  i n di vi dual ’s d ecisi o n t o partici pate i n t he st u d y is e ntirel y v ol u ntar y. It will be clearl y 
state d in t he eI C t hat t heir c o nse nt t o partici pat e ca n be wit h dra w n at a n y ti me.     
T he partici pa nt will be a ble t o sa ve a si g ne d c o p y of t heir eI C . A li mite d n u m ber of virt ual st u d y 
tea m me m bers will ha ve access t o t he o nli ne p ortal w here t he si g ne d eI Cs are st ore d t o e na ble 
t he m t o perf or m t heir assi g ne d st u d y-relate d tas ks (e. g., c h ec ks t h at c o ns e nt si g n at ures h a ve 
bee n pr o perl y c o m plete d b y eac h e nr olle d partici pa nt ).  
If, d uri n g partici pati o n i n t he st u d y, ne w i nf or mati o n bec o mes a vaila ble t hat c o ul d affect  
partici pa nt  willi n g n ess t o c o nti n ue, eac h c o nti n ui n g partici pa nt  will  recei ve t he ne w i nf or mati o n 
a n d be re -c o nse nt e d i nt o t he st u d y.  
8. 1. 2  
S cr e e ni n g Q u e sti o n n air e  
O nce  t he partici p a nt  has  si g ne d t he eI C , t he y will c o m plete a detaile d scree ni n g q uesti o n nair e 
i n t he 
 a p p t o i de ntif y a n d e x cl u de i n di vi d uals w h ose t o ot h s e nsiti vit y c o ul d be 
ca use d b y ot her fact ors/cli nical pat h ol o g y f or w hi c h D H C P  a d vice s h o ul d be s o u g ht.  
8. 1. 3  
D e m o gr a p hi c s  
T he f oll o wi n g de m o gra p hic i nf or mati o n will be rec or de d i n t he 
 a p p: year of birt h, 
a ge, ge n d er, U S state of resi de nc y , et h nicit y a n d race. 
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  
Partici pa nts will self -re p ort d etails of rele va nt m e dical a n d s ur gi cal hist or y, i ncl u di n g aller gies 
a n d dr u g se nsiti vit ies, b y c o m pleti o n  of a Me dical Hist or y f or m i n t he 
 a p p.  
Partici pa nts will list a n y c urre nt me dicati o ns/treat me nts usi n g t he C o nc o mita nt Me dicati o ns 
f or m i n t he 
 a p p. Reas o n f or us e, u nit d ose, dail y d os e, start a n d st o p dates will be 
rec or de d ( w h ere k n o w n a n d as a p pr o pri ate ).  
N ote:  O nce t h e partici pa nt has c o m pleted  t he Me dical Hist or y a n d C o nc o mita nt Me dicati o n 
f or ms, t he ‘ C ha n ge i n H ealt h’ a n d ‘ C ha n ge i n M e dicati o n’ f or ms will be c o me a vaila ble.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
8. 1. 5  
I n cl u si o n/ E x cl u si o n Crit eri a 
Inf or mati o n relati n g t o st u d y i ncl usi o n a n d e x cl usi o n criteria will be d oc u me nte d i n t he 
 a p p. I n di vi d uals w h o  meet  t he st u d y criteria will be eli gi ble t o partici pate a n d 
e nr olle d i nt o t he st u d y.  
8. 2  
St u d y P eri o d  
8. 2. 1  
W e e k 0 ( B a s eli n e) 
P artici pa nts m ust c o m plete t he f oll o wi n g Bas eli ne acti vities wit hi n 1 4 da ys of e nr oll me nt  t o be 
a ble t o c o nti n ue i n t he st u d y.  
•  C o m plete D H E Q -4 8   
•  C o m plete N P R S   
•  C o m plete O H Q    
•  Rec or d a n y c ha n ges i n t heir healt h/ me dical occ urre nces ; rec or d a n y c h a n ges t o t heir 
e xisti n g me dicati o ns/treat me nts a n d a n y ne w me di cati o ns/  treat me nts (i ncl u di n g reas o n 
f or use, u nit d ose, dail y d ose, start a n d st o p dates, w here k n o w n a n d as a p pr o priate ). 
St u d y t o ot h paste will o nl y b e s hi p pe d t o t h ose partici pa nts w h o c o m plete all ‘Baseli ne ’ 
acti vities. Partici pa nts will c o nfir m recei pt of t heir st u d y t o ot h paste i n t he 
 a p p 
( date of c o nfir mati o n of recei pt = Da y 0) a n d will be i nstructe d  t o start usi n g it o n t he sa me da y .  
8. 2. 2  
W e e k s  1  a n d 2  
•  C o m plete N P R S   
•  Rec or d a n y c ha n ges i n healt h/ me dical occ urre n ces; rec or d a n y c ha n ges t o e xisti n g 
me dicati o ns/treat me nts a n d a n y ne w me dicati o ns/ treat me nts (i ncl u di n g reas o n f or use, 
u nit d ose, dail y d ose, start a n d st o p dates, w here k n o w n a n d as a p pr o priate).  
8. 2. 3  
W e e k s  4, 8, 1 2, 1 6 a n d 2 0  
•  C o m plete D H E Q -4 8   
•  C o m plete N P R S   
•  Rec or d a n y c ha n ges i n healt h/ me dical occ urre n c es; rec or d a n y c ha n ges t o e xisti n g 
me dicati o ns/treat me nts a n d a n y ne w me dicati o ns/ treat me nts (i ncl u di n g reas o n f or use, 
u nit d ose, dail y d ose, start a n d st o p dates, w here k n o w n a n d as a p pr o priate).  
8. 2. 4  
W e e k 2 4  
•  C o m plete D H E Q -4 8   
•  C o m plete N P R S  
•  C o m plete Treat me nt Satisfacti o n N R S   
•  Rec or d a n y c ha n ges i n healt h/ me dical occ urre n ces; rec or d a n y c ha n ges t o e xisti n g 
me dicati o ns/treat me nts a n d a n y ne w me dicati o ns/ treat me nts (i ncl u di n g reas o n f or use, 
u nit d ose, dail y d ose, start a n d st o p dates, w here k n o w n a n d as a p pr o priate).  
•  C o m plete E O S a n d ‘o pe n -e n de d s ur ve y’ q uesti o n s.   
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
8. 3  
St u d y C o n cl u si o n  
T he St u d y C o n cl usi o n secti o n of t he 
 a p p will be c o m plete d f or all partici pa nt s b y 
 virt ual site tea m. If a partici pa nt  is disc o nti n ue d earl y, at a n y p oi nt d uri n g t h e 
st u d y, t he pri mar y reas o n f or wit h dra wal (if k n o w n) 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.  
A Es  o n g oi n g at t h e e n d of t he st u d y will be mar ke d ‘u nres ol ve d ’. 
 me di call y 
q ualifie d pers o n  (i n vesti gat or or desi g nee)  will as k t he partici pa nt t o see k a p pr o priate m e dical  
a d vice a n d/ or care, as nee de d . T he s p o ns or will b e n otifie d of  an y  o n g oi n g  A E s at t he e n d of 
t he st u d y. 
8. 4  
S A E F oll o w -u p  
 will f oll o w-u p S A E s u ntil res ol uti o n. F oll o w -u p of o n g oi n g S A Es will c o nti n ue 
p ost -st u d y c o m pleti o n a n d/ or after wit h dra wal or disc o nti n uati o n.
 will atte m pt t o 
c o ntact partici pa nts wit h a n o n g oi n g S A E at least t hree ti mes ; s h o ul d t he p artici pa nt c o nti n ue 
t o be u nreac ha ble t he S A E will be mar ke d as ' u nres ol ve d'.  
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 be ma de t o e ns ure t hat pr ot oc ol -re q uire d pr oce d ures are c o m plete d as 
descri be d  i n t he pr ot o c ol.  
9. 1  
S cr e e ni n g A s s e s s m e nt s  
E li gi bilit y will be deter mi ne d a gai nst t he pr ot oc ol i ncl usi o n/e xcl usi o n criteria, base d o n 
partici pa nt  res p o ns es t o t he i nitial a n d mai n scree ni n g q uesti o n nair e an d p artici pa nt -re p orte d  
healt h a n d me dicati o n/treat me nt i nf ormati o n . 
9. 2  
Q u alit y of L if e ( Q o L) A s s e s s m e nt  
9. 2. 1  
D e nti n  H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e ( D H E Q -4 8 ) 
T he D H E Q -4 8  is a c o n diti o n-s pecific meas ure of O Hr Q o L i n relati o n t o D H (B oi k o et al, 2 0 1 0) 
t hat has bee n pre vi o usl y v ali 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 et al, 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 parat e 
‘d o mai n ’ sc ores t o pr o vi de  a m ore gra n ular u n dersta n di n g of t he s pecific areas of i m pr o ve me nt 
t he partici pa nt s 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 l ife’).  
•  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 : D eri 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’).  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
•  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 Lif e 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). 
9. 3  
S af et y a n d Ot h er A s s e s s m e nt s  
C ha n ges i n h ealt h a n d me dical occ urre n ces self -re p orte d fr o m i m me diatel y after t he partici pa nt  
pr o vi des e-c o nse nt si g n at ure u ntil t he last use  of t he st u d y t o ot h paste will be rec or de d as A Es; 
t h us, S A Es will als o be c ollecte d fr o m i m me diatel y aft er t he partici pa nt  pr o vi des e-c o nse nt 
si g nat ur e u ntil last use  of t he st u d y t o ot h paste.  
9. 3. 1  
D H P ai n A s s e s s m e nt  
Partici pa nts will be as ke d t o self -re p ort t he i nte nsit y of t heir D H pai n at Bas eli ne , 1,  2,  4, 8, 1 2, 
1 6, 2 0 & 2 4 wee ks  usi n g a N u meri c Pai n Rati n g Scale ( N P R S).  T he 1 1 -ite m N P R S is a 
se g me nt e d n u meric versi o n of a V is ual A nal o g ue  S cale ( V A S) fr o m w hic h t he res p o n de nt 
selects t he sc ore ( 0– 1 0) t hat best reflects t he i nte nsit y of t heir pai n ( Ha w ker  et al, 2 0 1 1 ; R oc ha  
et al, 2 0 2 0 ). Si milar t o a V A S, t he N P R S is a nc h ore d b y ter ms des cri bi n g pai n s e verit y 
e xtre mes. It ra n ges fr om ' 0' re prese nti n g o ne p ai n e xtre me (e. g. , ‘n o pai n ’) t o ' 1 0' re prese nti n g 
t he ot her pai n e xtre me (e. g., ‘w orst p ossi ble pai n ’). Hi g her sc ores are i n dicative of  greater pai n 
i nte nsit y. 
 
At eac h assess me nt ti me p oi nt, partici pa nt s will be as ke d t o rec or d t he n u meric val ue o n t h e 
se g me nt e d scal e t hat best descri bes t heir pai n i nte nsit y i n t he l ast 2 4 h o urs.  
9. 3. 2  
P arti ci p a nt  S ati sf a cti o n wit h T r e at m e nt 
P artici pa nts will be as k e d t o rate t h eir satisfacti o n wit h t he D H treat me nt usi n g a N u meri c 
Rati n g Scale ( N R S).  T he N R S  is a n 1 1-p oi nt or di nal scale us e d t o assess s atisfacti o n wit h t he 
o verall ma na ge m e nt of t he c o n diti o n f or w hic h t he i n di vi d ual s o u g ht hel p fr o m treat me nt. It 
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 ve of greater satisfacti o n (va n Berc k el et al, 2 0 1 7). 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
 
P artici pa nts will be as ke d t o rec or d  t he n u meric val ue o n t he se g m e nte d scale t hat best des cri bes 
t heir satisfacti o n wit h t he D H treat me nt after 2 4 wee ks of us e a n d i n dicate w h y t h e y selecte d a 
partic ular s c ore  (e. g., ‘Please gi v e m ore details o n w h y y o u are satisfie d or dissatisfie d wit h t h e 
pr o d uct ’). 
9. 3. 3  
Ot h er  
O n c o m pleti o n of t he st u d y ( Wee k 2 4), partici p a nts will be as k e d t o c o m plete  a n u m ber of  
E O S /‘ o pe n-e n d e d s ur ve y’ q uesti o ns .  
1 0  
A D V E R S E E V E N T A N D S E RI O U S A D V E R S E E V E N T S  
 is 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 eve nts t hat meet t he 
defi niti o n of a n A E or S A E , a n d f or f oll o wi n g u p A Es t hat are seri o us  ( S A Es), c o nsi dere d 
relate d t o eit her t he st u d y pr o d uct or st u d y partici pati o n , or t hat ca use d t he partici pa nt  t o 
disc o nti n ue use of t he st u d y pr o d u ct or st u d y parti ci 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 st u d y p artici pa nt , te m p orall y ass ociat e d wit h 
t he use of a st u d y pr o d u ct, w het her or n ot c o nsi dere d rel ate d t o t he st u d y pr o d uct. 
N ote : A n A E ca n t h eref ore 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 x acer 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.  
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 ass ess me nts (e. g. , E C G, ra di ol o gical sca ns, vital si g n meas ure me nts), 
i ncl u di n g t h ose t h at w orse n fr o m baseli ne, c o nsi dere d cli nicall y si g nifi ca nt i n t he 
me dical a n d scie ntifi c j u d g me nt of  t he i n vesti gat or/
 m e dicall y q ualifie d 
pers o n  (i.e., n ot r elate d t o pr o gressi o n of u n derl yi n g diseas e). 
•  E x acer 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 after st u d y pr o d uct usa ge  e ve n t h o u g h it ma y 
ha ve bee n pres e nt bef ore t he 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.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
•  Si g ns, s y m pt o ms, or t he cli ni cal se q uelae of a s us pecte d o ver 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 o rte d re gar dless of s e q uelae. 
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 diseas e, u nless j u d ge d b y  
t he i n vesti gat or/
 me dicall y q u alifie d pers o n  t o be m or e se vere t ha n 
e x pecte d f or t he p artici pa nt’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 bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he partici pa nt ’s 
c o n diti o n.  
•  Me dical or s ur gic al pr oce d ure (e. g. , e n d os c o p y, a p pe n d ect o m y) is n ot t h e 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 o n 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 ors e n.  
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 a d verse e ve nt ( S A E) is a partic ular cat e g or y of a n a d v erse e ve nt w here t he a d verse 
o utc o me is seri o us. If a n e ve 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 s eri o us c o n diti o ns are m et ( e. g., h os pitalizati o n f or si g ns/s y m pt o ms of t he diseas e u n der 
st u d y, deat h d ue t o pr o gressi o n of disease). 
A seri o us a d verse e v e nt is a n y u nt o w ar d me dical occ urre nce at a n y d ose t h at:  
•  Res ults i n de at h  
•  Is lif e-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 's eri o us' refers t o a n e ve nt i n w hic h 
t he partici pa nt  was at ris k of d eat 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 heti call y mi g ht ha ve ca use 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 ge n eral, h os pitaliz ati o n si g nifies t he partici pa nt  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 pitaliz ati 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 pitaliz ati 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 baseli 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  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
- 
T he ter m disa bilit y me a ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit 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 n ce 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 hic h ma y i nt erfere 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 b sta 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 x ercise 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 b e i m me di atel y life-t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut 
ma y j e o par dize t he p arti ci pa nt  or ma y re q uir e m e 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 d ere d seri o us. 
- 
E x a 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 ulsi 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 o r 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. 
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  & S A E I nf or m ati o n  
A d verse E ve nts ( A Es) a n d t heref ore all Seri o u s A d verse E ve nts ( S A Es) will be c ollecte d fr o m 
ti me of e-c o nse nt si g nat ure u ntil t he last use  of t he st u d y t o ot h paste.  
Me dical occ urre nces t hat be ga n bef ore e-c o nse nt will be partici pa nt -rec or de d o n t he Me dical 
Hist or y f or m i n t he 
 a p p a n d c o nsi d ere d  as M e dical Hist or y ; once t he M e dical 
Hist or y f or m is c o m plete d, t he ‘ C ha n ge i n Healt h’ f or m will bec o me a v aila ble  
I nf or mati o n rec or de d b y t he partici pa nt o n t he 
 a p p t hat p ote ntiall y meet s t he 
defi niti o n of a n A E will  be disc usse d  wit h t he parti ci pa nt  b y 
 me dicall y q u alifie d 
pers o n ( i n vesti gat or or desi g nee)  t o facilitate e v al uati o n a n d e na ble c orrect classificati o n . 
S A Es will be rec or de d b y t he i n vesti gat or or desi g nee  a n d re p orte d t o t he s p o ns or (or desi g n ee ) 
i m me diatel y, a n d u n der n o circ u msta nce s s h o ul d t his e x cee d 2 4 h o urs. T he i n vesti gat or  or 
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 it bei n g a v aila ble . 
 is n ot o bli gat e 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 
partici pati o n. H o we v er, s h o ul d 
 lear n of a n S A E (i ncl u di n g a deat h), at a n y ti me 
after a p artici pa nt  h as bee n disc har ge d fr o m t he st u d y, a n d c o nsi d ers t he e ve nt t o be reas o na bl y 
relate d t o t he st u d y pr o d uct or st u d y partici pati o n, t he y m us t pr o m ptl y n otif y t h e s p o ns or b y 
e maili n g 
t he 
i nf or m ati o n 
t o 
t he 
s p o ns or’s 
Safet y 
Re p orti n g 
e mail 
b o x 
. 
 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 t he desi g nate d re p orti n g ti me fra mes.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 0. 4  
R e p orti n g Pr o c e d ur e s  
Partici pa nts  will self -re p ort c ha n ges i n t heir healt h a n d me dical occ urre nces usi n g t he ‘ C ha n ge 
i n Healt h F or m’ or ‘ C ha n ge i n Me dicati o n F or m’ a vaila ble wit hi n t he 
 a p p.  
 is res po 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 
defi niti o n of a n A E  a n d re mai ns res p o nsi ble f or f oll o w u p of A Es c o nsi d ere d relate d t o t he 
st u d y pr o d uct, partici pati o n i n t he st u d y, or a st u d y pr oce d ure, or t hat ca us e d t he partici pa n t t o 
disc o nti n ue t he st u d y pr o d uct or st u d y , a n d S A Es .  
S h o ul d a partici pa nt  re p ort a c ha n ge i n healt h stat us t hr o u g h t he 
 a p p or b y 
e mail/p h o ne c o m m u nic ati o n, 
 m e dical l y q ualifie d p ers o n (i n vesti gat or or 
desi g nee)  will re vie w t h e i nf or mati o n a n d ass ess if it meets t he defi niti o n of a n A E/ S A E. If 
classifie d as a n S A E, t he i n vesti gat or or desi g n ee  will e nter a vaila ble i nf or mati o n i nt o t he S A E 
f or m a n d f or war d t he c o m plete d S A E f or m t o t he s p o ns or’s Case Ma na ge me nt Gr o u p ( C M G), 
Gl o bal  Safet y ( H ale o n  C M G ) wit hi n 2 4 h o urs of t he partici pa nt re p orti n g t he e ve nt.  
If a d diti o nal details are re q uire d t o deter mi ne if t he A E meets S A E criteria, t he virt ual site tea m 
will c o ntact t he p artici pa nt  t o as k f or m ore  i nf or mati o n. If it is n ot p ossi ble t o re-c o ntact t h e 
partici pa nt  wit hi n 2 4 h o urs, t he i n vesti gat or or desi g nee will c o m plete t he S A E f or m wit h t he 
a vaila ble i nf or mati o n a n d se n d t o Hale o n  C M G wit hi n t he 2 4 -h o ur ti me fra me. T he virt ual site 
tea m will ma ke e ver y eff ort  t o c o ntact t he partici pa nt  (at least 3 c o m m u nicati o n atte m pt s) t o 
c ollect f urt her details a n d will s hare a d diti o nal i nf or mati o n wit h Hale o n  C M G  as a vaila ble . 
W he n a n A E occ urs, it is t he res p o nsi bilit y of 
 me dicall y q ualifie d pers o n  (t h e 
i n vesti gat or or d esi g nee)  t o re vie w all d oc u me nt ati 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 o e ns ure all rele va nt i nf or m ati o n re gar di n g a n A E 
is rec or de d i n t h e 
 a p p, a n d all det ails relati n g t o a n S A E o n  t he pa p er S A E for m 
pr o vi de d.  
It is n ot  acce pt a ble f or 
 t o se n d c o pies of t he partici pa nt ’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 re q uire d A E/ S A E d oc u me ntati o n . T here ma y be i nsta nces 
w h e n c o pi es of me dical rec or ds f or certai n cases are re q ueste d b y t he s p o ns or.  I n t his i nsta nce, 
all partici pa nt  i de ntifiers, e x ce pt f or t he partici pa nt  n u m ber, will be re dact e d pri or t o s u b missi o n 
t o t he s p o ns or. 
 me di call y q ualifie d  p ers o n  (in vesti gat or  or desi g nee) will atte m pt t o esta blis h a 
dia g n osis of t he e ve nt 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. T he 
dia g n osis will be t he d oc u me nte d as t he A E/ S A E  were  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, seas o nal aller g y, et c. , n ot  r u n n y n os e). 
1 0. 4. 1  
R e p orti n g of a n A d v er s e E v e nt  
A Es will be re p orte d usi n g t he 
 platf or m ; S A Es will  be re p ort e d usi n g a pa per  S A E 
for m . W here t h e sa me data are c ollecte d, t he A E re p ort a n d 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 he sa me A E ter m s h o ul d be use d). C o ncise me dical ter mi n ol o g y 
s h o ul d be use d f or b ot h A E a n d S A E re p orti n g. 
1 0. 4. 2  
R e p orti n g of a S eri o u s A d v er s e E v e nt  
I n a d diti o n t o rec or di n g t he details of eac h A E in t he 
 platf or m , 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 wit h t he i nf or mati o n a vaila ble . T he s p o ns or will 
pr o vi de 
 wit h a n ele ctr o nic c o p y of t h e S A E f or m f or t he e T M F pri or t o st u d y st art . 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
S h o ul d a n S A E occ ur, t his f or m will be c o m plete d electr o nicall y (or  pri nte d o ut  a n d c o m plete d 
as a har d c o p y, if ne e de d ).  
It is esse ntial t o e nt er t he f oll o wi n g i nf or mati o n o n t he S A E f or m :  
•  Pr ot oc ol a n d partici pa nt  i de ntifiers 
•  Partici pa nt  de m o gra p h y  
•  Descri pti o n of e v e nts wit h dia g n osis , if a v aila ble 
•  I n v esti gat or (or  me dicall y q ualifie d desi g nee ) 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, as a p pr o priate)  
•  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 ular rele va nce f or i n vesti gat or  (or m e dicall y 
q ualifie d desi g nee ) a n d s p o ns or assess me nt of t he S A E re p ort:  
•  Date of o nset  
•  Date st o p pe d, if rele va nt  
•  St u d y pr o d uct start dat e  
•  St u d y pr o d uct e n d d ate , if rele va nt 
•  Acti o n ta ke n i n relati o n t o t he st u d y pr o d u ct  
•  O utc o me , if k n o w n 
T he S A E f or m, c o m p lete d as f ull y as p ossi ble, will be  e maile d to t he s p o ns or’s C M G mail b o x 
, wit h c o p y t o t he a p pr o priate 
s p o ns or Cli nical St u d y 
Ma na ger  ( C S M) i m me di atel y after  t he i n v esti gat or or desi g nee  lear n of t he e v e nt, u n der n o 
circ u mst a nces s h o ul d t his e xcee d 2 4 h o urs. Har d c o p y S A E f or ms ( or p orti o ns of t he S A E 
f or m t hat ca n n ot be c o m plete d electr o ni call y) s h o ul d be sca n ne d a n d e-m aile d . 
T he i nitial S A E 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 C S M. 
 will s u b mit a n y u p d ate 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 vaila ble; 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 of 
it bei n g a v ail a ble. St u d y n u m ber a n d pa rtici pa nt n u m ber m ust be i ncl u de d i n t he title of all 
S A E -relate d e mails. 
Ori gi nal, c o m plete d S A E f or ms will be retai ne d b y 
 
T he s p o ns or’s C S M 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 h er s p o ns or pers o n nel 
as a p pr o priat e.  
1 0. 5  
E v al u ati n g  A d v er s e E v e nt s  
1 0. 5. 1  
A s s e s s m e nt of I nt e n sit y  
 m e dicall y q ualifie d pers o n (i n vesti gat or or d esi g n ee ) 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 partici pa nt , ca usi n g mi ni mal disc o mf ort 
a n d n ot i nterferi n g wit h e ver y da y acti vities.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
P P D
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
•  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 O T E:  A n A E t hat is assesse d as s e 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; b ot h n o n -seri o us A Es a n d S A Es ca n be 
assesse d as s e vere. F o r e x a m ple, a hea dac he ma y be se vere (i nterferes si g nifica ntl y wit h t he 
partici pa nt '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 h e 
criteria f or S A Es, liste d a b o ve. A n e ve nt is defi ne d as ‘seri o us’ w he n it meets at least 1 of t he 
pre -defi ne d o utc o mes as descri be d i n t he d efi niti o n of a n S A E, 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  
T he ca us alit y ass ess me nt is o ne of t he criteria use d w he n d eter mi ni n g re g ul at or y re p orti n g 
re q uire me nts.  
 m e di call y q ualifie d p ers o n  (i n v esti gat or or d e si g nee) m ust  assi g n  ca usalit y t o 
eac h A E (s eri o us a n d n o n -seri o us) i n t he A E re p ort a n d o n  t he S A E f or m (partici pa nt  t o t he 
classificati o n of t he A E).  Assi g n me nt of ‘reas o na ble p ossi bilit y’ i n dicates 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 relati 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. T he facts (e vi de nce) a n d/or ar g u me nts t hat s u g gest a ca us al rel ati o ns hi p s h o ul d be 
pr o vi de d.  
 me dicall y q u alifie d pers o n (i n vesti gat or o r desi g nee) will use t heir cli nical 
j u d g me nt t o assi g n  t he relati o ns hi p, ha vi n g als o c o ns ult e d t he Pr o d uct I nf or mati o n . Alter nati v e 
ca uses, s uc h as u n derl yi n g diseas e(s), c o n c o mita nt t hera p y, ot her ris k fact ors, a n d t he te m p oral 
relati o ns hi p of t he e ve nt t o t he st u d y pr o d u ct will be c o nsi dere d a n d i n vesti gat e d, as nee de d. 
T here ma y be sit uati o ns w he n  
 me dicall y q u alifie d pers o n (i n vesti gat or or 
desi g nee)  h as 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 w e ver, it is ver y 
i m p ort ant i ncl u de a n assess me nt of c a us alit y i n t he i niti al S A E f or m tr a ns mitte d t o t he 
s p o ns or. 
 me dicall y q ualifi e d pers o n ma y c h a n ge t heir o pi ni o n of ca usalit 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 t h e u p date d ca u salit y 
assess me nt .  
1 0. 6  
F oll o w -u p of A E s a n d S A E s   
 is re q uir e d t o pr oacti vel y f oll o w u p eac h A E/ S A E a n d pr o vi de f urt her i nf or mati o n 
o n t he p artici pa nt ’s c o n diti o n, as a p pr o priate. W hile t he st u d y is i n fiel d, a ll A Es (seri o us a n d 
n o n -seri o us) will 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 partici pa nt  is l ost t o f oll o w-u p. 
 me dicall y 
q ualifie d pers o n ( i n vesti gat or or desi g nee)  will s u b mit a n y u p dat e d A E/ 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.  
A Es  o n g oi n g at t he e n d of a partici pa nt ’s p artici pati o n i n t he st u d y will be m ar ke d ‘u nres ol ve d ’; 
n o f urt her f oll o w -u p is re q uire d . 
 me dicall y q u alifie d pers o n (i n vesti gat or or 
desi g nee)  will  as k t he partici pa nt  t o see k a p pr o priate me dical  a d vice a n d/ or care, as nee de d . 
T he s p o ns or will be n otifie d of  o n g oi n g  A E s at t he e n d of t he st u d y.   
P ost -st u d y c o m pleti o n, 
wit h dra wal, or disc o nti n uati o n, 
 
will c o ntact a n y 
partici pa nt  wit h a n o n g oi n g S A E t o f oll o w u p t h at S A E t o res ol uti o n. 
 m ust ma ke 
e ver y eff ort t o c o ntact t he partici pa nt  ( 3 c o m m u nicati o n atte m pts). S h o ul d t he partici p a nt  
c o nti n ue t o be u nreac ha ble, t he S A E will als o be mar ke d ‘ u nres ol ve d’.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
 is o bli gate d t o perf or m or arra n ge f or t he c o n d u ct of s u p ple m e ntal meas ure me nts 
a n d/ or e val uati o ns as ma y be i n dicate d or as re q u este 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 us alit y of t h e A E. T his ma y i ncl u d e a d diti o nal la b o rat or y tests or 
i n vesti gati o ns, hist o pat h ol o gical e x a mi nati o ns, or c o ns ultati o n 
wit h ot her healt h care 
pr ofessi o nals.  
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 n ote d earlier ( Secti o n 1 0. 1) a n d rec or de d i n t h e 
 a p p. 
W he n a partici pa nt  wit h dra ws beca use of a n S A E, t he S A E m ust be re p orte d i n acc or da n ce wit h 
t he re p orti n g re q uire me nts defi ne d i n Secti o n 1 0.4. 2 . 
1 0. 8  
R e g ul at or y R e p orti n g R e q ui r 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 safet y of a pr o d uct u n der i n vesti gati o n.   
A Es/ S A Es will be re p orte d t o l ocal a n d re gi o nal healt h a ut h orities b y t he s p o ns or, w he n 
a p pr o priate, i n acc or da n ce wit h a p plica ble l ocal a n d re gi o n al re g ulati o ns. T he s p o ns or  will 
c o m pl y wit h c o u ntr y s pecific re g ul at or y re q uire me 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 (l ocal, re gi o nal or n ati o nal) a n d t he I R B. Pr o m pt n otificati o n of S A Es b y 
 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 f or 
partici pa nt  safet y ca n b e met.  Safet y re p orts m ust be pre pare d f or s us pect e d u ne x pecte 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 .  
1 0. 9  
Pr e g n a n c y  
Pre g n a nc y i nf or mati o n will be c ollect e d o n pre g n a ncies self-re p orte d w hile a fe male p artici pa nt  
is partici pati n g i n t he st u d y (self-re p ort e d fr o m ti me of e-c o nse nt si g nat ur e u ntil last use of st u d y 
t o ot h paste). 
1 0. 9. 1  
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 s p o ns or will pr o vi de 
 wit h a n electr o nic c o p y of t he p re g n a nc y re p orti n g for m 
f or t he e T M F pri or t o st u d y start. S h o ul d pre g na nc y b e self -re p orte d b y a fe male p artici pa nt  
d uri n g t he st u d y , t he f or m will be c o m plete d electr o nicall y ( or pri nte d o ut a n d c o m plete d as 
har d c o p y, if n ee de d).  
T he c o m plete d pre g n a nc y re p orti n g f or m will b e e-m ail e d t o t he s p o ns or’s C M G  mail b o x 
, wit h c o p y t o t he s p o ns or’s C S M. Har d c o p y pre g n a nc y 
re p orti n g f or ms ( or p orti o ns of t he pre g na nc y re p orti n g f or m t hat ca n n ot be c o m plete d 
electr o nicall y) s h o ul d b e sca n ne d a n d e -maile d.  
Ori gi nal, c o m plete d pre g na nc y re p orti n g f or ms will be retai ne d b y 
 
T he partici pa nt will be f oll o we d t o deter mi ne t he o utc o me of t he pre g na n c y. I nf or mati o n o n t he 
stat us of t he m ot her a n d i nfa 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 t he pre g n a nc y) will be f or war de d b y 
 t o t he s p o ns or’s C M G mail b o x 
, wit h c o p y t o t he  s p o ns or’s C S M. Ge nerall y, f oll o w-u p will 
be n o l o n ger t ha n 6 t o 8 wee ks after  t he esti mate d deli ver y dat e. T er mi nati o n of t he pre g n a nc y 
will be re p orte d.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 m es (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. 
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 cas e re p ort f or m ( C R F ) is u n d erst o o d t o refer t o a n electr o ni c 
data rec or d. F or t his st u d y, t his is t he 
 a p p ( p ortal), a vali date d s yste m. Partici pa nt  
data will be pri maril y e ntere d i nt o t h e 
 ap p /p ortal  (a d diti o nal d ata relati n g t o S A Es  
a n d pre g na n c y will  be  rec or de d o utsi de of t he a p p  a n d platf or m ). 
 is res p o nsi ble 
f or verif yi n g t hat d ata e ntries are acc urat e, c orrect, a n d a p pr o ve d electr o nicall y. 
Eac h partici pa nt  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 Partici pa nt  N u m ber ; an y 
refere nce ma de t o a n i n di vi d ual partici pa nt  wit hi n t he st u d y m ust be d o ne usi n g t h is nu m ber.  
1 1. 1  
C a s e R e p ort F or m  
A C R F is a pri nte d, o ptical, or electr o ni c d oc u me nt desi g ne d t o rec or d t he 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 partici p a nt . 
F or eac h partici pa nt w h o has gi ve n e -c o nse nt i n t he 
 a p p, t he e C R F m ust b e 
c o m pleted a n d re vie we d f or c o m pleti o n a n d acc urac y. 
 m ust mai ntai n acc urate 
d oc u me ntati o n (s o urce d ata)  as a p pr o pri ate  t o s u p p ort t he i nf or mati o n e ntere d i n t he e C R F. 
St u d y data will be c ollect e d i n t he 
 a p p a n d 
 Electr o nic Data Ca pt ure 
( E D C) Platf or m. 
Ma na ge me nt of 
st u d y d ata will be perf or m e d i n acc or da nce wit h 
 a p plica ble 
sta n dar ds a n d pr o ce d ures wit h s p o ns or o versi g ht t o e ns ure t he i nte grit y of t he data.  
T o pr otect t he pri vac y of partici pa nts, n o pers o nal i nf or mati o n (i ncl u di n g t he na me(s) or 
i nitial(s) or f ull date of birt h ) is t o be rec or de d i n t he e C R F or as p art of t he q uer y t e xt. 
I d e ntifia ble dat a are is olate d t o a s pecial tea m at 
 a n d t hes e data will n ot b e 
tra nsferre d/a v aila ble t o t he S p o ns or. 
All re q uire d eC R F scree ns i n 
 a p p (p ortal)  s h o ul d be c o m plete d at t he a p pr o priate 
ti me p oi nt w he n t he eC R F has b ee n desi g n ate d as t he s o urce. Data s o urce d else w here s h o ul d 
be e ntere d i nt o t he eC R F wit h i n t he ti mefra me a gree d bet w ee n 
 a n d t he sp o ns or.   
T he s p o ns or will o btai n a n d retai n all ass o ciate d st u d y d ata , 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 ge 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 p erf or m a nce .  
A n y c h a n ges or 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 a n d  will i ncl u de t he rati o nale f or c ha n ges. T he E D C s yste m has a n a u dit trail w hic h will 
pr o vi de a c o m plete rec or d of t he c ha n ges a n d c orrect i o ns e n d orse d t he I n vesti gat or. 
A Es will be c o de d usi n g t he 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 ns ter ms usi n g a n i nter nal v ali date d me dicati o n dicti o nar y.   
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 1. 2. 1  
D at a Q u eri e s  
T he 
 data ma na ge me nt tea m will perf or m pr o gra m me d l o gical c hec ks t o e ns ure 
c o nsiste nt a n d c o m plete data e ntr y. T h e 
 dat a ma na ge me nt tea m will perf or m 
l o gical ma n ual c h ec ks, a n d q ueries will be e ntere d o n a Data Iss ues L o g f or dece ntr alize d site 
staff to a d dress. T he Cli nical Dicti o nar y De v el o p me nt a n d M a na ge me nt Gr o u p will rais e 
q ueries o n t he s afet y d ata ( A Es, c o nc o mita nt me dicati o ns), as n ee de d , t o c o de t he ter ms 
a p pr o priatel y.  
1 1. 3  
Pr o c e s si n g  P ati e nt R e p ort e d O ut c o m e s   
Electr o nic Patie nt Re p orte d O utc o me (e P R O) data will be c ollecte d usi n g electr o nic de vices 
a n d a vaila ble electr o ni call y t o t he s p o ns or or 
.  
T o pr otect t he pri vac y of partici pa nts, n o pers o nal i nf or mati o n (i ncl u di n g t he na me(s) or 
i nitial(s) or f ull date of birt h ) is t o be rec or ded i n t he e C R F or as p art of t he q uer y t e xt. 
I d e ntifia ble dat a are is olate d t o a s pecial tea m at 
 a n d t hes e data will n ot b e 
tra nsferre d/a v aila ble t o t he S p o ns 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 p artici pa nts  will be scree ne d ( t o all o w f or u p t o 5 0% scree n fail ure rate) t o e ns ure 
a p pr o xi matel y 5 0 0 p artici pa nts  are e nr olle d a n d a p pr o xi matel y 4 0 0 c o m pl ete ( t o all o w f or u p 
t o 2 0 % dr o p -o ut rate).  
A sa m ple siz e of 4 0 0 partici pa nts w o ul d e ns ure at least 9 0 % p o wer t o ac hie ve a statisticall y 
si g nifica nt (t w o-si de d 5 % si g nifi ca nce le vel) re d ucti o n i n B aseli ne i n D H E Q T otal Sc ore w he n 
usi n g a o ne -sa m ple t-test, ass u mi n g a tr u e p o p ulati o n effect siz e ( mea n re d ucti o n/sta n dar d 
de viati o n [ S D ]) of 0.2 . T he pla n ne d pri mar y a nal ys es ( defi ne d i n Secti o n 1 2. 3. 2) i n t his st u d y 
will use a Mi x e d M o del wit h Re peate d Meas ures ( M M R M) wit h ti me p oi nt as a fi x e d effect, 
B aseli ne D H E Q sc ore as a c o vari ate a n d p artici pa nt as a re p eate d meas ure.   
As well as pr o vi di n g a de q uate p o w er t o de m o nstrate statisticall y si g nifica nt re d ucti o ns fr o m 
B aseli ne at e ac h ti me p oi nt  ( 4, 8, 1 2, 1 6, 2 0 & 2 4 wee ks), 4 0 0 partici pa nts will e ns ure a de q uate 
precisi o n of t he c orres p o n di n g 9 5 % c o nfi de nce i nter vals ( CI s) f or t he m ea n re d u cti o n, a n d 
r o b ust R W E relati n g t o t he ma g nit u de of be nefit fr o m pr o d uct use, at eac h ti me p oi nt. I n a 
pre vi o us st u d y ( Hale o n st u d y 2 1 6 9 5 3 ) assessi n g t he sa me D H E Q -4 8  e n d p oi nts o ver 2 4 wee ks 
i n a R W E setti n g f or a n a nti-se nsiti vit y t o ot h paste c o ntai ni n g 5 % K N O3, t he S D of t he c ha n ge 
fr o m Baseli ne i n D H E Q T otal Sc ore was s h o w n t o i ncrease fr o m ar o u n d 3 0 u nits at Wee k 4 t o 
5 0 u nits at Wee k 2 4.  A n S D of 3 0 u nits a n d 5 0 u nits acr oss 4 0 0 partici pa nts w o ul d e q uate t o 
precisi o n of t he 9 5 % CIs f or t he mea n re d ucti o n wit hi n +/- 3 a n d 5 u nits , res pecti vel y. 
1 2. 2  
P o p ul ati o n s  for A n al y si s  
1 2. 2. 1  
A n al y si s P o p ul ati o n s  
T he Scree ne d p o p ulati o n will i ncl u de partici pa nts  w h o electr o nicall y si g n t he eI C a n d e nt er t he 
scree ni n g pr ocess f or ass ess me nt of i nc l usi o n a n d e x cl usi o n criteria.  
T he E nr olle d p o p ulati o n will i ncl u de all p artici pa nts  w h o meet t he i n cl usi o n/e xcl usi o n criteria 
as i de ntifie d b y t heir res p o nses t o t he scree ni n g q u esti o n naire. 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T he Safet y p o p ulati o n  will i ncl u de all partici pa nts  w h o c o m plete at least o ne use of st u d y 
pr o d uct. Safet y p o p ulati o n will be use d f or t he a n al ysis of A Es . 
T he  m o difie d I nte nt-T o -Treat ( m I T T) p o p ulati o n will i ncl u de all partici pa nts  i n t he Safet y 
p o p ulati o n  w h o ha ve at least o ne p ost -b aseli ne d eri ve d D H E Q T otal Sc ore . Efficac y dat a will 
be a nal yz e d usi n g t h e m I T T p o p ulati o n o nl y. 
1 2. 2. 2  
E x cl u si o n of D at a fr o m A n al y s e s  
E x cl usi o n of a n y data fr o m t he a nal ys es will be deter mi ne d d uri n g a  data re vie w meeti n g  pri or 
t o data base l oc k a n d pr e-defi n e d i n t he S A P . A n y reas o ns f or e x cl usi o n fr o m a n a n al ysis 
p o p ulati o n will be liste d, if a p plica ble . 
1 2. 3  
St ati sti c al  A n al y s e s  
A d diti o nal details of t he pr o p ose d statistical a nal ysis will be d o c 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 n alizati o n of t he pr ot oc ol a n d pri or t o st u d y 
a nal ysi s. T his secti o n is a s u m mar y of t he pla n ne d statistical a nal yses, i ncl u di n g t he pri mar y 
a n d sec o n dar y e n d p oi nt s. A d diti o nal details f or t he sec o n dar y e n d p oi nts will be pr o vi de d i n t he 
S A P.  
De scri pti ve s u m maries of c o nti n u o us e n d p oi nts will i ncl u de c o u nts ( missi n g a n d n o n -missi n g), 
mea n, S D, sta n dar d err or ( S E), me dia n, mi ni m u m,  a n d ma xi m u m. Descri pti ve s u m maries of 
cate g orical e n d p oi nts will i ncl u de c o u nts ( missi n g a n d n o n -missi n g) a n d perce nt a ge ( %) o ut of 
t he partici pa nts  wit h n o n -missi n g data.  
Resi d ual a nal ys es will be c o n d ucte d f or eac h 
M M R M a p plie d. I f t here are a n y o b vi o us 
de part ures fr o m n or malit y a n d/ or i n de pe n d e nce ass u m pti o ns , t hese will be re p orte d; alter nati ve 
a nal ys es will be descri be d i n t he S A P .  
1 2. 3. 1  
Pri m ar y A n al y s e s  
C ha n ge fr o m B aseli ne will be calc ulate d at eac h p ost -B aseli ne ti me p oi nt  ( 4, 8, 1 2, 1 6, 2 0 & 
2 4 wee ks)  f or t he pri mar y  D H E Q e n d p oi nts:  
•  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 p act 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),  
C ha n ge fr o m B aseli ne i n eac h D H E Q  e n d p oi nt  liste d a b o ve will  be a nal yz e d usi n g a M M R M 
wit h ti me p oi nt fitte d as a fi x e d effect , t he res p ecti ve B aseli ne D H E Q sc ore as a c o vari ate  a n d 
partici pa nt fitte d as a re p eate d meas ure wit h u nstr uct ure d c o varia nce matri x. Ke n war d -R o gers 
de grees of free d o m will be a p plie d. T he e sti mates of t he a dj uste d mea n ( sta n dar d err or [S E ]) 
cha n ge fr o m Baseli ne will be prese nte d al o n g wit h 9 5 % CIs.  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 2. 3. 2  
S e c o n d ar y  A n al y s e s  
D H E Q , Sec o n d ar y  E n d p oi nts  
C ha n ge fr o m B aseli ne will be calc ulate d at eac h p ost -B aseli ne ti me p oi nt  ( 4, 8, 1 2, 1 6, 2 0 & 2 4 
wee ks)  f or t he sec o n dar y D H E Q e n d p oi nts:  
•  Secti o n  1  
- 
C ha n ge fr o m Bas eli ne i n I m pact o n E ver y da y L if e: Q 1, Q 2 &  Q 3 (se parate sc ores)  
•  Secti o n 2  
- 
C ha n ge fr o m Baseli ne i n D H E Q Gl o bal O ral H ealt h ( Q 3 5)  
- 
C ha n ge fr o m Baseli ne i n D H E Q  Effect o n  L if e O v erall (s u m of Q 3 6 -Q 3 9)  
Eac h  D H E Q  e n d p oi nt liste d a b o ve will be a nal yz e d usi n g a M M R M wit h ti me p oi nt fitte d as a 
fi x e d effect, t he res pecti ve B as eli ne sc ore as a c o variate  a n d partici pa nt fitte d as a re peat e 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 d e grees of free d o m will be 
a p plie d. T he esti mates of t he a dj uste d mea n ( S E) cha n ge fr o m Baseli ne at eac h p ost -B as eli ne 
ti me p oi nt will be prese nte d al o n g wit h 9 5 % CIs.   
F or eac h  D H E Q e n d p oi nt  liste d a b o ve (Secti o ns 1 2. 3. 1 a n d 1 2. 3. 2) , a n d eac h i n di vi d ual D H EQ 
q uesti o n, t he sc ore at eac h ti me p oi nt (i ncl u di n g Baseli ne) a n d t he c orres p o n di n g c ha n ge fr o m 
Baseli ne (at eac h p ost -Baseli ne ti me p oi nt) will b e s u m marize d des cri pti vel y. P l ots of mea n 
sc ore ( S E) f or eac h D H E Q e n d p oi nt liste d a b o ve (Secti o ns 1 2. 3. 1 a n d 1 2 . 3. 2), a n d t h e 
i n di vi d ual D H E Q q uesti o ns, o ver ti me will als o be pr o vi de d. T hese will als o be prese nte d b y 
a ge a n d ge n der s u b -gr o u ps  wit h f urt her details t o be pr o vi de d i n S A P.  
T he n u m ber a n d  p erce nta ge ( %) of partici pa nts  w h o ‘a gree ’ (sc ore 5-7) wit h t he 3 4 ite ms 
(state me nts) i n 5 d o mai ns  of t he D H E Q (Secti o n 2, Q 1 -Q 3 4 ) will be s u m marize d at Baseli ne 
a n d Wee k 2 4.  T h e perce nta ge f or eac h ite m will be s u m marize d a n d pres e nte d i n desce n di n g 
or der.  
N u meric P ai n R ati n g Sc ale ( N P R S ) 
C ha n ge fr o m B as eli ne will be calc ulate d at eac h p ost -B aseli ne ti me p oi nt  (1, 2, 4, 8, 1 2, 1 6, 2 0 
& 2 4 w ee ks)  f or t h e N P R S sc ore. C ha n ge i n  N P R S sc ore will be a n al yz e d  usi n g i de ntical 
met h o ds t o eac h of t he D H E Q e n d p oi nts detaile d a b o ve. M ea n pr ofil e pl ots, descri pti ve 
s u m maries (i ncl u di n g c h a n ge fr o m B as eli ne) a n d M M R Ms  will be prese nte d .  
A n a d diti o nal s u m mar y of t he n u m ber of partici p a nts  w h o ac hie ve a re d u cti o n fr o m B aseli ne 
i n N P R S of > 3 0 % will be prese nte d at eac h p ost-B as eli ne ti me p oi nt  (1, 2, 4, 8, 1 2, 1 6, 2 0 & 
2 4 wee ks) . 
S atisf acti o n N u meric R ati n g Sc ale ( N R S ) 
Cr oss -ta b ulati o ns of t he n u m ber of partici pa nts  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 partici pa nts  re p orti n g at eac h le vel or hi g h er at 
Wee k 2 4 will be 
prese nte d.  T h e N R S sc ore at W ee k 2 4 will be s u m marize d descri pti vel y.  
1 2. 3. 3  
S af et y A n al y s e s  
A Es will be c o de d usi n g Me d D R A  a n d cate g orize d as eit her oral or  n o n -oral b y 
 
pri or t o dat a base l oc k. T h e n u m ber of A Es / S A Es a n d the n u m ber of partici p a nts  wit h A Es / S A Es 
will be liste d a n d ta b ulate d  o verall a n d b y S yst e m Or ga n Class ( S O C) a n d Preferre d Ter m ( P T). 
T his will be re peate d i n cl u di n g o nl y Oral A Es/ S A Es.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 2. 3. 4  
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  
D e m o gra p hics, Baseli ne c haracteristics (i ncl u di n g D H d ia g n osis (self-di a g n ose d  or dia g n os e d 
b y de ntist ); use of a nti-se nsiti vit y t o ot h paste (c urre nt user, i nter mitte nt  user or  n o n -user ); a n d 
fre que n c y  of D H s y m pt o ms  (c o m pile d fr o m  res p o nses fr o m t he S cree ni n g Q uesti o n naire  a n d 
t he O H Q), a n d oral h y gi e ne ha bits (c o m pile d fr o m res p o nses t o t he O H Q ) will be s u m marize d 
usi n g descri pti ve statistics f or t he m I T T p o p ulati o n. 
1 2. 3. 5  
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. 5. 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 s t u d y pr o d uct usa ge a n d wit h t he st u d y sc h e d ule will be ta b ulate d a n d 
s u m marize d f or t he S afet y p o p ulati o n.  S u m maries will i ncl u de a si m ple yes/ n o fre q ue n c y (a n d 
perce nt) c o u nt at eac h ti me p oi nt:  
•  S u m mar y o f c o m pleti o n t o st u d y sc he d ule a n d ass ess me nts ( yes/ n o) 
•  S u m mar y of pr o d uct usa ge acc or di n g t o pr o d uct i nstr ucti o ns ( yes/ n o)  
•  S u m mar y of n u m ber of t o ot h paste t u bes re mai ni n g at t he e n d of t he st u d y (e. g., ‘2 or 
less t u bes’, ‘3 t o 6 t u bes ’ a n d ‘m ore t ha n 6 t u b es’) 
1 2. 3. 5. 2  Pri or a n d C o n c o mit a nt M e di c ati o n s  
Pri or a n d c o nc o mita nt me dicati o ns ta ke n d uri n g t he st u d y will be liste d f or t he S afet y 
p o p ulati o n.  
1 2. 3. 6  
H a n dli n g of Dr o p o ut s a n d Mi s si n g D at a  
Missi n g data d ue t o dr o p o ut s/ wit h dra wals will be assesse d o n a n o n g oi n g b asis d uri n g t h e st u d y. 
A n y f urt her s e nsiti vit y a n al yses n ee d e d d ue t o missi n g data will be re vie we d at t he ti me of data 
re vie w.  
F or t he D H E Q data, f or a n y ti me p oi nt if res p o nse is missi n g , it will be e x cl u de d fr o m t he 
pri mar y a n al ysis ; t h e dat a a v aila ble f or eac h parti ci pa nt  (e v e n t h o u g h s o m e ti me p oi nts ma y b e 
missi n g) will still be i ncl u de d i n t he a nal ysis.  
T he M M R M a p pr oac h will i ncl u de all partici pa nts  i n t he m I T T p o p ulati o n i n t he a nal ysis. A n y 
missi n g data fr o m s uc h partici pa nts  will be treate d as ‘missi n g at ra n d o m ’, i.e., t heir missi n g 
data at a partic ular ti me p oi nt will be ass u me d t o be ha ve i n si milar fas hi o n t o a partici pa nt  wit h 
n o n -missi n g data at t hat ti me p oi nt  w h o has  si milar dat a at ot her ti me p oi nts . T his a p pr oac h 
e ns ures a n u n biase d a p pr oac h t o ha n dli n g missi n g data u n der t he ‘missi n g at ra n d o m ’ 
ass u m pti o n.  
1 2. 3. 7  
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 ul ati o ns i ncl u di n g G C P a n d s p o ns or pr oce d ures, pri or t o t he 
start of t he st u d y, t he 
 virt ual site tea m will be trai ne d o n t he pr ot oc ol, st u d y 
re q uire me nts, a n d t heir 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 me nts. 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 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 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
W he n re vie wi n g data c ollecti o n pr oce d ure s, 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 e C R F will ser ve as t h e s o urce 
d oc u me nt.   
D uri n g t h e st u d y, t he d at a will be m o nit ore d t o verif y t h at:  
•  Data are a ut he ntic, acc urate, a n d c o m plete.  
•  Safet y a n d ri g hts of partici pa nt s are b ei n g pr otect e d. 
•  St u d y is c o n d ucte d i n acc or da nce 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, 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 nt a n d nat ure of m o nit ori n g will be descri be d i n t he Data Ma n a ge me nt Pla n.  
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 ur a nce assess me nt a n d/ or a u dit of 
 st u d y-relate d rec or ds, 
a n d re g ulat or y a ge ncie s 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 after 
c o m pleti o n of t he st u d y.  
I n t he e ve nt of a n assess me nt, a u dit or i ns pe cti o n, 
 m ust a gree t o gra nt t he 
a d vis or(s), a u dit or(s) a n d i ns pect or(s) direct access t o all rele va nt d oc u me nts a n d t o all ocate 
t heir ti me a n d t he 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 m e 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. 
 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 p ecti o n 
n otificati o n i n relati o n t o t he st u d y. F urt her m ore, 
 will c o o perate wit h t he s p o ns or 
or its a ge nts t o pre pare t h e st u d y 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 n ts, 
w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n. 
 will pr o m ptl y pr o vi de  
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 s. 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, 
 will pr o vi de t he s p o ns or or it s a ge nts wit h a n o p p ort u nit y t o 
re vie w a n d c o m me nt o n r es p o nses t o a n y s uc h fi n di n gs.  
T he s p o ns or will be a vail a ble t o hel p 
 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 al 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 o ha ve pr os pecti ve a p pr o val of t he st u d y pr ot oc ol, 
pr ot oc ol a me n d me nts, i nf or me d c o nse nt d oc u me nts , t he safet y state me nt (i ncl u di n g a n y 
u p dates) a n d ot her rele v a nt d oc u me nts (e. g., recr uit me nt a d vertise me nts), if a pplica ble, fr o m 
t he I R B.  All c orres p o n de nce wit h t he I R B s h o ul d be retai ne d i n 
 master st u d y 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 als o w he n s u bse q u e nt a me n d me nts t o t he pr ot o c ol are ma de.  
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 b e i nitiate d pri or t o I R B a p pr o val is w here 
t he c ha n ge is necessar y t o eli mi nate a p pare nt i m me diate hazar ds t o t he p artici pa nt s.  I n t hat 
e ve 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 t he 
i m ple me ntati o n. 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 ucte d i n acc or da n ce wit h t he pr ot oc ol a n d le gal a n d re g ulat or y 
re q uire me nts, as w ell as t he ge n eral pri nci ples set f ort h i n t he I nter n ati o nal Et hical G ui deli nes 
f or Bi o me di cal Researc h I n v ol vi n g H u m a n S u bjects (C o u ncil f or I nt er nati o nal Or ga nizati o ns 
of 
Me dical Scie n ces 2 0 0 2 ), I nter nati o nal Et hical G ui deli nes f or Healt h-Relate d Researc h 
I n v ol vi n g H u m a ns (C o u ncil f or I nter nati o nal Or ga nizati o ns of 
Me dical Scie nces, 2 0 1 6 ), 
g ui deli nes f or G C P ( I C H 1 9 9 6 a n d re visi o n 2), a n d t he Declarati o n of Helsi n ki (W orl d Me dical 
Ass ociati o n 2 0 1 3 ).  
I n a d diti o n, t he st u d y will be c o n d u cte d i n acc or da nce wit h t he pr ot oc ol, t he I C H g ui deli ne o n 
G C P, 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.  
1 3. 3. 3  
P arti ci p a nt  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 partici pa nt  pers o nal data a n d will n ot i ncl u de partici pa nt  
na mes or ot h er i de ntifi a ble data i n a n y re p orts, p u blicati o ns, or ot her discl os ures, e x ce pt w h ere 
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, 
partici pa nt  na mes, a d dresses, a n d ot her i de ntifia ble data will be re place d b y n u merical c o des 
base 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 t o de-i de ntif y st u d y partici pa nts  ( N ote: 
t he use of i nitials s h o ul d be a v oi de d). 
 will mai ntai n a c o nfi de ntial list of partici pa nts  w h o p artici pate d i n t he st u d y, 
li n ki n g eac h p artici pa nt’s  n u merical c o de t o t heir act ual i de ntit y.  I n case of da ta tra nsfer, t h e 
s p o ns or will mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr ot ecti o n of partici pa nts ’ pers o nal 
data c o nsiste nt wit h a p plica ble pri vac y la ws.  
T he i nf or m e d c o ns e nt d oc u me nts m ust be i n c o m plia nce wit h I C H G C P, l ocal re g ulat or y 
re q uire me nts, a n d l e gal r e q uire me nts, i ncl u di n g a p plica ble pri vac y l a ws. 
T he i nf or me d c o nse nt d oc u me 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 h e I R B bef ore use, a n d a v aila ble f or i ns pecti o n.  
 m us t e ns ure t hat eac h st u d y p artici pa nt  is f ull y i nf or me d a b o ut t he nat ur e a n d 
o bjecti ves of t he st u d y a n d p ossi ble ris ks ass ociate d wit h partici pati o n.  
1 3. 3. 4  
P arti ci p a nt  R e cr uit m e nt  
A d vertise me nts a p pr o ve d b y t he I R B m a y be us e d as part of t he recr uit me nt pr oce dures.   Use 
of a n I R B-a p pr o ve d, ge n eric, prescree ni n g q uesti o n naire t o ass ess basic partici pa nt 
c haracteristics t o deter mi ne ge neral eli gi bilit y f or t his st u d y is all o we d.     
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 nte nt of a n y st u d y 
recr uit me nt materials directe d t o p ote ntial st u d y p artici pa nts  bef ore s uc h m aterials are use d.  
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 partici pa nt or t he relia bilit y a n d r o b ust ness of t he data ge n erate d i n 
Hale o n -s p o ns or e 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  
 is a ware of a n y ne w i nf or mati o n 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 st u d y pr o d uct, t he s p o nsor 
s h o ul d be i nf or me d i m me diatel y.  
I n a d diti o n, 
 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 m eas ures 
ta ke n b y 
 t o pr otect t he st u d y p artici pa nts  a gai nst a n y i m me diate hazar d, a n d of 
a n y s eri o us breac h es of t his pr ot oc ol  or of I C H G C P t hat 
 bec o mes 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 v aila ble cli nical trial re gisters 
bef ore e nr oll me nt of partici pa nt s be gi ns i n acc or da nce wit h a p plica ble s p o ns or pr ocess es.  
T he s p o ns or i nte n ds t o ma ke a n o n y mize d partici pa nt -le vel data fr o m t his st u d y a vaila ble t o 
e xter nal researc h ers f or scie ntific a nal yses or t o c o n d uct f urt her res earc h t hat c o ul d hel p 
a d va nce me dical scie n ce or i m pr o ve p atie nt care. T his hel ps e ns ure t he dat a 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 ge a n d u n dersta n di n g  
1 3. 5  
Pr o vi si o n of St u d y R e s ult s t o t h e I n v e sti g at or 
W here re q uire d b y a p plica ble re g ulat or y re q uir e m e nts, a n i n vesti gat or si g nat or y will be 
i de ntifie d f or t h e a p pr o val of t he Cli nical St u d y Re p ort  ( C S R).  
 will be pr o vi de d 
reas o na bl e 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 
 wit h t he f ull s u m mar y of t he st u d y res ults.  
 is e nc o ura ge d t o s hare t h e s u m mar y res ults wit h t he st u d y p artici pa nts , as 
a p pr o priate.  
T he 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 de vel o p me nt of 
a ma n uscri pt f or p u blicati o n will be i n acc or da n ce wit h s p o ns or polic y.  
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. 
1 3. 6  
R e c or d s R et e nti o n  
F oll o wi n g cl os ur e of t he st u d y, 
 m ust ass ure t hat t he partici pa nt ’s a n o n y mit y will 
be mai ntai ne d. e C R Fs or ot her d o c u me nts s u b mitte d t o t he s p o ns or s h o ul d n ot i de ntify 
partici pa nts b y t heir n a m es or i nitials b ut b y a n i d e ntificati o n c o de. 
 s h o ul d kee p a 
se parat e l o g of partici p a nt  c o des, n a 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 s h o ul d be mai ntai ne d b y 
 i n strict c o nfi de nce. 
 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 ocal re g ulati o ns 
t o be mai ntai ne d else w h ere) i n a safe a n d sec ure l o cati o n.  
 st u d y rec or ds (e T M F) m ust be mai ntai ne d t o all o w eas y a n d ti mel y retri e val, w he n 
nee de d (e. g. , f or a 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 v aila ble f or re vi e 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 yst e ms, a n d rel e va nt st u d y 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 hese 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 nee ds t o be e x ercise d bef ore s u c h acti o n is ta ke n.  
 m ust e ns ur e t hat all re pr o d ucti o ns are le gi ble , are a tr ue a n d acc urate c o p y of t he 
ori gi nal , a n d me et accessi bilit y a n d retrie val sta n d ar ds, i ncl u di n g re -ge n erati n g a har d c o p y, if 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
re q uire d.  F urt h er m ore, 
 m ust e ns ure t here is a n acce pta ble bac k -u p of t hese 
re pr o d ucti o ns a n d t hat a n acce pta ble q ualit y c o ntr ol pr ocess e xists f or 
ma ki n g t hes e 
re pr o d ucti o ns. 
Rec or ds a n d d oc u m e nts, i ncl u di n g si g n e d e I C, pertai ni n g t o t he c o n d uct of t his st u d y m ust be 
retai ne d b y 
 as per t he si g ne d c o ntr act ual a gree me nt, fr o m t h e 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 ul ati o ns or i nstit uti o nal p olicies 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 
site f or t he 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 
. 
 m ust n otif y t h e s p o ns or of a n y  c h a n ges i n t he arc hi val 
arra n ge 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 
 is n o l o n ger ass ociate d wit h t he 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 t er mi nati o n of t his st u d y ma y occ ur b eca use of a re g ulat or y a ut h orit y decisi o n, a 
c ha n ge i n o pi ni o n of t he I R B, a st u d y pr o d uct safet y pr o ble m, or at t he discreti o n of t he s p o ns or.   
If a st u d y is pre mat urel y ter mi nate d, t he s p o ns or will  pr o m ptl y n otif y 
.  After 
n otificati o n, 
 m ust pr o m ptl y c o ntact all partici pati n g partici pa nt s a n d s h o ul d e ns ure  
a p pr o priate t hera p y/f oll o w -u p f or t he partici pa nt s.  As dir ecte d b y t he s p o ns or, all st u d y 
materials m ust be c ollect e d a n d all eC R F’s  c o m pleted t o t he greatest e xte nt p ossi ble. W here 
re q uire d b y t he a p plica bl e re g ul at 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 ulat or y 
a ut h orit y(i es) a n d 
 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 de t he I R B wit h  a 
detaile d writte n e x pla nati o n of t he reas o n(s) f or ter 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 t he st u d y, 
 
s h o ul d pr o m ptl y n otif y t h e s p o ns or a n d pr o vi d e a d etaile d writte n e x pla nati o n of 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 (s) will 
c o n d uct st u d y cl os ur e acti vities wit h 
, as a p pr o pri ate, i n acc or da n ce wit h 
a p plica ble re g ulati o ns i ncl u di n g G C P, a n d t he s p o ns or’s Sta n dar d O p erati n g Pr oce d ures.  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 4  
R E F E R E N C E S  
A d d y M, M ostafa P, A bsi E, et al., e dit ors. Cer vical de nti n h y p erse nsiti vit y: Eti ol o g y a n d 
ma na ge me nt wit h partic ular refere nce t o d e ntifrices. Pr ocee di n gs of S y m p osi u m o n 
H y p erse nsiti ve De nti n: Ori gi n a n d M a na ge m e nt; 1 9 8 5: U ni versit y of  Mic hi ga n.  
A d d y M. D e nti n  h y p erse nsiti vit y: Ne w pers pecti ves o n a n ol d pr o ble m. I nt er nati o nal De nt al 
J o ur nal. 2 0 0 2; 5 2( 5 ( S u p ple me nt 1)): 3 6 7-7 5.  
A d d y M, S mit h S. De nti n h y perse nsiti vit y: A n o v er vie w o n w hi c h t o base t u b ule occl usi o n as 
a ma na ge m e nt c o nce p t. T he J o ur nal of cli nical de ntistr y. 2 0 1 0; 2 1( 2): 2 5.  
A mi ni P, Kl u k o ws ka M, E use bi o R, et al. A nti -Se nsiti vit y Efficac y of Bi oa vaila ble Sta n n o us 
Fl u ori de D e ntifrice vs. N e gati ve C o ntr ol ( A bstract # 2 3 2 2). 2 0 1 9; I A D R. Va nc o u ver, 
Ca na da.  
Ba ker S R, Gi bs o n BJ , S ufi F, et al. T h e de nti n  h y p erse nsiti vit y e x perie n ce q uesti o n naire 
( d he 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 2-9. 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.  
Başara n S, Celi k C. T ur kis h a da ptati o n of de nti n  h y p erse nsiti vit y e x perie n ce q uesti o n naire 
( d he q). C o m m u nit y De nt Healt h. 2 0 1 8; 3 5( 1): 4 7 -5 1.  
Be kes K, J o h n M T, Sc haller H G, et al. Oral healt h ‐ relate d q ualit y of life i n patie nts see ki n g 
care f or de nti n h y perse nsiti vit y. J o ur nal of oral r e ha bilitati o n. 2 0 0 9; 3 6( 1): 4 5 -5 1.  
B oi k o O V, Ba ker S R, Gi bs o n BJ, et al. 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 he 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 -8 0.  
Brä n nstr ö m M. A h y dr o d y n a mic m ec ha nis m i n t he tra n s missi o n of pai n-pr o d uci n g sti m uli 
t hr o u g h t he d e nti n . I n: A n ders o n DJ, e dit or. Se ns or y mec ha nis ms i n de nti n ; R o yal 
S ociet y of M e dici ne, L o n d o n: O xf or d: Per ga m o n Press; 1 9 6 3. p. 7 3 -9.  
Ca na dia n A d vis or y B oar d o n De nti n H y p erse 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 m a na ge me nt of de nti n h y perse nsiti vit y. J o ur nal ( Ca na dia n De ntal 
Ass ociati o n). 2 0 0 3; 6 9( 4): 2 2 1 -6.  
Ce pe da -Bra v o J A, A ya d F, Mate o L R, et al. I nsta nt De nti n H y p erse nsiti vit y Re d ucti o n 
Efficac y of C o m merci all y A v aila ble De ntifrices ( A bstract # 1 5 5 4). 2 0 1 4; I A D R C harl otte, 
N ort h Car oli na.  
C ha k nis P, Pa na ga k os F S, De Vizi o W, et al. Assess me nt of h y p erse nsiti vit y re d ucti o n of a 
de ntifrice c o ntai ni n g  0. 3 % tricl osa n, 2. 0 % P V M/ M A c o p ol y m er, 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 ntifri ce c o ntai ni n g 0. 4 5 4 % sta n n o us 
fl u ori de, s o di u m he x a 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 p erse nsiti vit y  re d ucti o n: A n 8-wee k st u d y. A m eri ca n j o ur nal of 
de ntistr y. 2 0 1 1; 2 4( A): 1 4 -2 0.  
Creet h J E, B ur nett G R Efficac y of a n E x peri me nt al 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 p erse nsiti vit y: A n 8 -wee k R a n d o mise d C o ntr olle d Trial. Oral healt h 
& pre v e nti ve de ntistr y. 2 0 2 1; 1 9( 1): 1 9 5 -2 0 2  
Creet h J, Gall o b J, Qa qis h J, et al. S h ort -ter m efficac y st u dies of a n occl u di n g de ntifri ce o n 
de nti nal h y p erse nsiti vit y (J De nt Res 9 6 A: A bstract # 1 5 4 3). 2 0 1 7a; I A D R  Sa n Fra n cisc o, 
Calif or nia.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
Creet h J, G o y al R C, Qa qis h J, et al. S h ort -ter m efficac y of a n occl u di n g de ntifrice o n de nti nal 
h y perse nsiti vit y ( A bstr act # P 1 2 2). 2 0 1 7 b; F DI.  Ma dri d   
C u n ha -Cr uz J, Wata ha J C, Z h o u L, et al. Treati n g de nti n h y perse nsiti vit y: T hera p e utic 
c h oices ma de b y d e ntists of t he n ort h west pr ece d e nt net w or k. T he J o ur nal of t he 
A merica n D e ntal Ass oci ati o n. 2 0 1 0; 1 4 1( 9): 1 0 9 7 -1 0 5.  
G o yal R C, S ufi F, Q a qis h J, et al. T w o -wee k efficac y of a n o ccl u di n g de ntifric e o n d e nti nal 
h y perse nsiti vit y (J De nt Res 9 6 A: A bstract # 1 5 4 4). 2 0 1 7; I A D R. Sa n Fra n cisc o, 
Calif or nia.  
G S K C H Cli nical St u d y 2 0 9 7 2 3 Ra n d o mize d c o ntr olle d e x a mi ner -bli n d p hase II e x pl orat or y 
cli nical st u d y t o c h aracterise t he efficac y pr ofile of a n e x peri me ntal d ual acti ve 
c o m bi nati o n de ntifrice f or t he relief of de nti n h y perse nsiti vit y, i n s u bjects wit h cli nicall y 
dia g n ose d de nti n h y p erse nsiti vit y. ( G S K C H d ata o n file), 2 0 2 0  
Da ba b ne h R, K h o uri A, A d d y M. D e nti n  h y p erse nsiti vit y - a n e ni g ma? A re vie w of 
ter mi n ol o g y, mec h a nis ms, aeti ol o g y a n d m a na ge me nt. Britis h de ntal j o ur nal. 
1 9 9 9; 1 8 7: 6 0 6 -1 1. D o u gl as -De -Oli veira D W, La ges F S, Pai va S M, et al. Cr oss -c ult ural 
a da ptati o n of t he brazilia n versi o n of t he de nti n  h y p erse nsiti vit y e x perie n ce q uesti o n naire 
( d he q-1 5). Brazilia n oral researc h. 2 0 1 8; 3 2.  
Da y T, Ei n wa g J, Her ma n n J, et al. A cli nical assess me nt of t he efficac y of a 
sta n n o usc o ntai ni n g s o di u m fl u ori de de ntifrice o n de nti nal h y p erse 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.  
D u M, Jia n g H, Tai  B, et al. 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 ntifrice ( A bstract # 2 8 2 6). 2 0 1 1; I A D R. Sa n Die g o, C alif or nia.  
Gall o b J, S ufi F, A mi ni P, et al. A ra n d o mise d e x pl orat or y cli nical e val uati o n of de ntifrices 
use d as c o ntr ols i n de nti n al h y p erse nsiti vit y st u dies. J o ur nal of de ntistr y. 2 0 1 7; 6 4(-): 8 0-
7.  
Gi bs o n BJ, B oi k o O V, Ba ker S R, et al. T he e ver y da y i m pact of de nti n  se nsiti vit y: Pers o nal 
a n d f u ncti o nal as p ects.  De nti n  h y p erse nsiti vit y: Else vier; 2 0 1 5. p. 8 9 -1 0 7.  
Hall R C, E m ber y G, S hellis R P, e dit ors. Bi ol o gical a n d str uct ural f eat ures of e na mel a n d 
de nti n : C urre nt c o nce pts rele va nt t o er osi o n a n d d e nti n  h y perse nsiti vit y. T o ot h Wear a n d 
Se nsiti vit y; 2 0 0 0: Marti n D u nitz.  
Ha w ker G A, Mia n S, Ke n dzers ka T, et al. Meas ures of a d ult pai n: Vis ual a nal o g scale f or 
pai n ( vas pai n), n u meric rati n g s cale f or pai n ( nrs pai n), mc gill pai n q uesti o n naire ( m p q), 
s h ortf or m mc gill pai n q uesti o n naire (sf‐ m p q), c hr o nic pai n gra d e scal e (c p gs), s h ort 
f or m‐ 3 6 b o dil y pai n sc ale (sf ‐ 3 6 b ps), a n d meas ure of i nter mitte nt a n d c o nsta nt 
oste oart hritis pai n (ic oa p). Art hritis care & researc h. 2 0 1 1; 6 3( S 1 1): S 2 4 0 -S 5 2.  
Haze n S, V ol pe A, Ki n g W C o m parati ve dese nsitizi n g effect of de ntifrices c o ntai 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 m ali n. Peri o d o ntics. 1 9 6 8; 6( 5): 2 3 0 -2.  
He S -l, W a n g J-h. Relia bilit y a n d vali dit y of t h e 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 naire ( d he q -1 5). Q u alit y of Lif e Researc h. 
2 0 1 5a; 2 4( 6): 1 4 6 5 -9.  
He S, Wa n g J. De ve l o p m e nt of t he c hi nes e versi o n of t he de nti n  h y p erse nsiti vit y e x perie nce 
q uesti o n naire.  De nti n  h y perse nsiti vit y: Else vier; 2 0 1 5 b. p. 1 6 5 -7 5.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
He T, Bar ker M, Bi es br o c k A R, et al. 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 ntifri ce o n h y perse nsiti vit y rel ati ve t o a mar ket e d s o di u m 
fl u ori de/tricl osa n c o ntr ol. T he J o ur nal of cli nical d e ntistr y. 2 0 1 4a; 2 5( 2): 1 3-8.  
He T, Bar ker M, Qa qis h J, et al. Fast o nset se nsiti vit y relief of a 0. 4 5 4 % sta n n o us fl u ori de 
de ntifrice. T h e J o ur na l of cli nical de ntistr y. 2 0 1 1 a; 2 2( 2): 4 6-5 0.  
He T, Bar ker M L, Bies br oc k A, et al. 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 de ntifrice. A merica n j o ur nal of d e ntistr y. 
2 0 1 4 b; 2 7( 2): 1 0 6 -1 0.  
He T, C ha n g A, C he n g R, et al. I nsta nt a n d ra pi d se nsiti vit y relief of a sta n n o us fl u ori de 
de ntifrice ( A bstract # 1 4 7 7). 2 0 1 1 b; I A D R. Sa n Di e g o, Calif or nia.  
He T, C ha n g J, C he n g R, et al. Cli nical e val uati o n of t he fast o nset a n d s ust ai ne d se nsiti vit y 
relief of a 0. 4 5 4 % sta n n o us fl u ori de de ntifrice c o m pare d t o a n 8. 0 % ar gi ni necalci u m 
car b o nat e-s o di u m m o n ofl u or o p h os p hate de ntifrice. A merica n j o ur nal of d e ntistr y. 2 0 1 1c; 
2 4( 6): 3 3 6 -4 0.  
He T, C he n g R, Bies br oc k A R, et al. Ra pi d dese nsitizi n g efficac y of a sta n n o usc o nt ai ni n g 
s o di u m fl u ori de de ntifric e. J o ur nal of Cli nical De ntistr y. 2 0 1 1 d; 2 2( 2): 4 0 -5.  
He T, Peters J, G o yal C R, et al. Cli nical Dese nsitizi n g Effect of Bi o a vaila ble S n F 2 De ntifrice 
( A bstract # 2 2 1 0). I A D R. 2 0 1 9, Va nc o u ver, Ca na d a.  
Hi nes D, X u S, Stra nic k  M, et al. 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. T he J o ur nal of t he A merica n De ntal 
Ass ociati o n. 2 0 1 9; 1 5 0( 4): S 4 7 -S 5 9.  
Heft M W, Lita ker M S, K o p yc k a -K e dziera ws ki D T, et al. Patie nt -ce ntered de nti nal 
h y perse nsiti vit y treat me nt o utc o mes: Res ults fr o m t he nati o nal de ntal p br n. J D R Cli nical 
& Tra nslati o nal Researc h. 2 0 1 8; 3: 7 6 -8 2.  
I C H T o pi c E 6 ( R 2) G ui d eli ne f or G o o d Cli nical Practice, N o v 2 0 1 6. 
Ki m, J Y et al., Cli nical a n d i n -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 n eral Sessi o n  
K o p yc ka -Ke dziera ws ki D T, Me yer o witz C, Lita k er M S, et al. Ma na ge me nt of de nti n 
h y perse nsiti vit y b y nati o nal de ntal practice -b ase d researc h net w or k practiti o ners: Res ults 
fr o m a q uesti o n nair e a dmi nistere d pri or t o i nitiati o n of a cli nical st u d y o n t his t o pic. 
B M C oral he alt h. 2 0 1 7a; 1 7( 1): 4 1.  
K o p yc ka -Ke dziera ws ki D T, Me yer o witz C, Lita k er M S, et al. Ma na ge me nt of de nti n 
h y perse nsiti vit y b y practiti o ners i n t he nati o nal de ntal practice -base d resea rc h net w or k. 
T he J o ur nal of t he A meri ca n De nt al Ass ociati o n. 2 0 1 7 b; 1 4 8( 1 0): 7 2 8 -3 6.  
Lita ker M S, K o p yc ka -Ke dziera ws ki D T, Ri n dal D B, et al. C o nc or d a nce bet wee n practiti o ner 
q uesti o n naire res p o ns es a n d o bser ve d cli nical treat me nt rec o m me n dati o ns f or treat me n t 
of de nti n h y p erse nsiti vit y: Fi n di n gs fr o m t he nati o nal de ntal practice bas e d researc h 
net w or k. B M C Oral Healt h. 2 0 1 9; 1 9: 1 1 2.  
Mac h uca C, Ba k er S, S ufi F, et al. Deri vati o n of a 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 nair e. J Cli n Per i o d o nt ol 2 0 1 4; 4 1: 4 6– 5 1.  
Mas o n S, B ur nett G R, Patel N, et al. I m pact of t o ot h paste o n oral healt h -rel ate d q ualit y of life 
i n pe o ple wit h de nti n  h y p erse nsiti vit y. B M C Oral Healt h. 2 0 1 9; 1 9: 1 -1 1.  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
Ni L, H e T, C ha n g J, et al. 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). 2 0 1 1; I A D R. Sa n Di e g o, Calif or nia.  
Ni L X, He T, C ha n g A, et al. 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 ntifric e: A n 8-wee k ra n d o mize d a n d c o ntr olle d cli nical tr ial. A merica n 
j o ur nal of de ntistr y. 2 0 1 0; 2 3( S pIss B): 1 7 B-2 1 B.  
Par ki ns o n C, H u g hes N, J effer y P, et al. T he efficac y of a n e x peri me ntal d e 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 -w ee k cli nical st u d y. A merica n j o ur nal of de ntistr y. 2 0 1 3; 
2 6( S pIss A): 2 5 A -3 1 A.  
Par ki ns o n C R, J effer y P, Mille ma n J L, et al. C o nfir mati o n of effi cac y i n pr o vi di n g relief fr o m 
t he pai n of de nti n h y pers e nsiti vit y of a n a n h y dr o us de ntifrice c o nt ai 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 merica n j o ur nal of 
de ntistr y. 2 0 1 5a; 2 8( 4): 1 9 0 -6.   
Par ki ns o n C R, H u g hes N, Hall C, et al. T hree ra n d o mize d cli nical trials t o assess t he s h ort -
ter m efficac y of a n h y dr o us 0. 4 5 4 % w/ w sta n n o us fl u ori de de ntifrices f or t h e relief of 
de nti n h y perse nsiti vit y. A merica n j o ur n al of de ntistr y. 2 0 1 6; 2 9( 1): 2 5 -3 2.  
P orritt J M, S ufi F, Ba ker S R. Utilisi n g dail y di aries t o e x a mi ne oral healt h e x perie nces 
ass ociate d wit h de nti n  h y perse nsiti vit y. B M C Oral healt h. 2 0 1 6; 1 6: 1 -1 1. d oi: 
1 0. 1 1 8 6/s 1 2 9 0 3 0 1 6 -0 2 8 6 -9.  
R o bi ns o n P G. De nti n  h y perse nsiti vit y: De v el o pi n g a p ers o n -ce ntre d a p pr oac h t o oral healt h: 
Aca de mic Press; 2 0 1 4.  
R oc ha  M O C, Cr uz  A A C F, Sa nt os  D O, et al. Se nsiti vit y a n d s p ecificit y of assess me nt scales 
of de nti n h y p erse nsiti vit y – a n acc urac y st u d y. Brazilia n Oral Researc h. 2 0 2 0; 3 4. S her ma n 
R E, Ste ve n A. A n ders o n, Pa n  GJ D, et al. Real -w orl d e vi de nce —  w hat is it a n d w hat ca n 
it tell us? n e n gl j me d 2 0 1 6; 3 7 5: 2 2 9 3-7.  
Sc hiff T, He T, Sa gel L, et al. Efficac y a n d s afet 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 x a meta p h os p hate de ntifrice f or d e nti nal h y perse nsiti vit y. J C o nte m p De nt 
Pract. 2 0 0 6; 7( 2): 1 -1 0.  
Sc hiff T, Saletta L, Ba ker R, et al. 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 x a meta p h os p hate de ntifri ce. C o m pe n di u m of c o nti n ui n g e d u cati o n i n 
de ntistr y. 2 0 0 5; 2 6( 9 S u p pl. 1): 3 5 -4 0.  
Se o n g J, Creet h J, S ufi F, et al. S h ort -ter m efficac y of a n occl u di n g de ntifrice o n de nti nal 
h y perse nsiti vit y ( A bstr act # 0 2 1 5). 2 0 1 7; I A D R. Sa n Fra n cisc o, Calif or nia.  
S har ma N, R o y S, K a kar A, et al. 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 t he ma na ge me nt of d e nti n h y perse nsiti vit y. T he J o ur nal of cli nical 
de ntistr y. 2 0 1 0; 2 1( 3): 8 8 -9 2.  
S har ma N, Qa qis h J, Bar ker M L, et al. I nsta nt Se nsiti vit y Relief of a Sta n n o us - 
C o ntai ni n g S o di u m Fl u ori de De ntifrice ( A bstract # 1 4 7 6). 2 0 1 1; I A D R/ A A D R/ C A D R Ge ner al 
Sessi o n Sa n Die g o, C alif or nia.  
va n Berc k el M M, B os ma N H, Ha ge m a n M G, et al . T he c orrelati o n bet wee n a n u merical 
rati n g s cale of p atie nt satisfacti o n wit h c urre nt ma na ge me nt of a n u p p er e xtre mit y 
dis or der a n d a ge neral m eas ure of satisfacti o n wit h t he me dical visit. Ha n d. 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
2 0 1 7; 1 2( 2): 2 0 2 -6.  
Vi na ya K R, S h u b has hi ni N, Ses ha n H, et al. A cli nical trial c o m pari n g a st a n n o us fl u ori de 
base d de nti fric 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 o ur nal of I nter nati o nal Oral H ealt h. 2 0 1 0; 2( 1): 3 7 -5 0.  
West N. De nti n  h y perse nsiti vit y. I n: L ussi A, e dit or. De ntal er osi o n. M o n o gr oral sci. 2 0. 
Basel: K a ger; 2 0 0 6 . p. 1 7 3-8 9.  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
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 bre vi ati o n  
Ter m  
A E  
A d verse E v e nt  
a p p 
A p plicati o n  
CI  
C o nfi de nce I nter val  
C M G  
Case Ma na ge m e nt Gr o u p  
C R F  
Case Re p ort F or m  
C S M  
Cli nical St u d y Ma n a ger  
C S R  
Cli nical St u d y Re p ort  
D H  
De nti n H y p erse nsiti vit y  
D H C P   
De ntal Healt h Care Pr ofessi o nal  
D H E Q  
De nti n H y p erse nsiti vit y E x perie nce Q uesti o n nair e  
E C  
Et hics C o m mittee  
E C G  
Ec h ocar di o gra m  
e C R F  
Electr o nic Case Re p ort F or m  
E D C  
Electr o nic Data Ca pt ure  
eI C  
Electr o nic I nf or me d C o nse nt  
E O S  
E n d of St u d y  
e P R O  
Electr o nic Patie nt Re p ort e d O utc o me  
e T M F  
Electr o nic Trial M aster File  
G C P  
G o o d Cli nical Practice  
I C H  
I nter nati o nal C o nfere nce o n Har m o nizati o n  
I R B  
Instit uti o nal Re vie w B oar d  
K N O 3  
P otassi u m Nitrate  
Me d D R A  
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
mI T T  
m o difie d I nt e nt-T o -Treat  
M M R M  
Mi x e d M o del wit h Re peate d Meas ures  
N/ A  
N ot A p plica ble  
N P R S  
N u meric Pai n Rati n g Scale  
N R S  
N u meric Rati n g Scale  
O Hr Q o L  
Oral Healt h Relate d Q ualit y of Life  
O H Q  
Oral H y gie ne Q uesti o n naire  
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
PII  
Pers o nal I de ntifia ble I nf or mati o n  
P P M  
Parts Per milli o n  
Q  
Q uesti o n  
Q O L  
Q ualit y of Lif e  
R C T  
Ra n d o mize d C o ntr olle d Trial  
R W D  
Real W orl d Data  
R W E  
Real W orl d E vi de nce  
S A E  
Seri o us A d verse E v e nt  
S A P  
Statistical A nal ysis Pla n  
S D  
Sta n dar d De viati o n  
S E  
S ta n dar d E rr or 
S n F 2 
Sta n n o us Fl u ori de  
S U S A R  
S us pecte d U ne x pecte d S eri o us A d verse E ve nt  
U S  
U nite d States  
V A S  
Vis ual A nal o g ue Scale  
Vs . 
Vers us  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 5. 2  
S cr e e ni n g  Q u e sti o n n air e  
 
We are g oi n g t o c all w h at y o u feel i n y o ur teet h ‘se ns ati o ns’.  
 
1.  W hic h of t he f oll o wi n g b est descri be a n y se nsati o ns y o u ma y h a ve felt i n y o ur teet h?  
(Tick  all t h at a p ply )   
Itc h y  
Ac hi n g  
S h o oti n g   
Pierci n g  
Ti n gli n g   
S har p   
D ull  
Flas hi n g  
S hi ver y   
Li n geri n g  
T wi n gi n g  
Flic keri n g  
Sta b bi n g   
S hatteri n g  
Freezi n g   
Fleeti n g  
Q ui veri n g  
Pric ki n g   
Pai n  
Disc o mf ort  
T wi n ges   
Se nsiti vit y   
N o ne of t he A b o ve  
  
If a ns w er is ‘ n o ne of t he a b o ve’, partici pa nt s h o ul d n ot pr ocee d f urt her  
  
2.  H o w l o n g h a ve y o u bee n e x perie nci n g t h ese se ns ati o ns or se nsiti vit y i n y o ur  teet h?  
(Tick  o nly o ne res p o ns e )  
 
Less t ha n si x m o nt hs  
Pr ocee d  
M ore t ha n si x m o nt hs b ut less t ha n a year  
Pr ocee d  
M ore t ha n a year b ut less t ha n fi ve years   
Pr ocee d  
M ore t ha n fi ve years b ut less t ha n 2 0 years  
Pr ocee d  
M ore t ha n 2 0 years  
Pr ocee d  
N o ne of  t he a b o ve  
E x cl u de  
 
3.  W hic h  teet h ha ve bee n / are affecte d? ( T ic k all t hat a p pl y)  
 
T o p fr o nt teet h 
Pr ocee d  
T o p bac k teet h 
Pr ocee d  
B ott o m fr o nt teet h 
Pr ocee d  
B ott o m bac k teet h 
Pr ocee d  
N o ne of t he a b o ve  
E x cl u de  
  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
4.  W hic h  of t he f oll o wi n g ca use y o u t o ha v e t hese se nsati o ns or se nsiti vit y i n y o ur teet h? 
(T ick all t h at a p ply)  
  
C ol d fl ui ds  
Aci d y fr uits (e. g. , ora n ges)  
Ha vi n g t eet h clea ne d at t he de ntist  
H ot f o o ds   
S weet t hi n gs   
T o ot h w hite ni n g p r o d ucts   
Har d f o o ds   
Stic k y f o o ds   
Metals t o uc hi n g m y teet h   
C ol d air   
Ice c rea m   
F l ossi n g certai n teet h  
Salt y f o o ds   
C ol d f o o ds   
T o ot h br us hi n g  
H ot fl ui ds  
 N o ne   
 
If a ns w er is ‘ n o ne’, parti ci pa nt s h o ul d n ot pr ocee d f urt her  
5.  H o w ofte n d o y o u e x peri e nce t hes e se nsati o ns or se nsiti vit y i n y o ur t eet h?   
(Tick o nly o ne res p o ns e ) 
  
Se veral ti mes a da y  
Pr ocee d  
O nce a d a y  
Pr ocee d  
Se veral ti mes a w ee k  
Pr ocee d  
O nce a wee k  
Pr ocee d  
Se veral ti mes a m o nt h  
Pr ocee d  
O nce a m o nt h  
Pr ocee d  
Less t ha n o nce a m o nt h  
Pr ocee d  
Ne ver  
E x cl u de  
 
6.  If y o u h a ve a n y of t hese  se nsati o ns or s e nsiti vit y i n y o ur teet h , o n a v era ge h o w l o n g d o 
t he y last?  
(T ick o nly o ne res p o ns e)  
 
A fe w sec o n ds   
Pr ocee d  
A b o ut a mi n ute   
Pr ocee d  
Se veral mi n utes  
Pr ocee d  
A b o ut half a n h o ur  
Pr ocee d  
L o n ger t ha n half a n h o ur ( Please s pecif y)  Pr ocee d   
D o n’t ha ve t he m  
E x cl u de  
 
7.  D o y o u h a ve se v ere aci d refl u x?  
(S ever e is defi ne d as t aki n g m ore t h a n o ne me dic ati o n d aily t o tre at y o ur refl ux or 
c o nsi deri n g s ur gery t o c orrect)   
  
Y es  
E x cl u de   
N o  
P r ocee d  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
8.  Ca n y o u tell me if y o u h a ve:   
(Tick all t h at a p ply ) 
All y o ur o w n t eet h  
Pr ocee d  
Mai nl y nat ur al teet h a n d a fe w cr o w ns / bri d ges / i m pla nts  
Pr ocee d  
Fi x e d or re m o va ble ort h o d o ntic braces/ b a n ds or a fi x e d ort h o d o ntic retai ner  
Pr ocee d  
Partial de nt ures  
E x cl u de  
F ull de nt ures  
E x cl u de  
Rece nt treat me nt f or peri o d o ntal disease or g u m disease (i ncl u di n g s ur ger y) 
wit hi n 6 m o nt hs  
E x cl u de  
A cti ve t o ot h deca y   
E x cl u de  
L o ose t eet h as a res ult of se vere g u m disease (acti ve peri o d o ntitis)  
E x cl u de  
A n y c hr o nic a n d/ or se vere pai nf ul healt h c o n diti o ns w hic h lea d t o re g ul ar 
use pai n me dicati o ns ( m ore t ha n 3 da ys a wee k)  
E x cl u de  
 
 
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 5. 3  
Or al  H y gi e n e Q u e sti o n n air e  ( O H Q) 
 
1.  H o w fre q u e ntl y d o y o u n or mall y br us h y o ur teet h ?  
3 or m ore ti mes a da y, t wice a da y, o n ce a da y, less ofte n  
  
2.  Ha ve y o u ha d a pr ofessi o nal or self -a p plie d t o ot h w hite ni n g tr eat me nt i n t h e last 2 wee ks?   
Y or N o  
If a self-a p plie d w hite ni n g  treat me nt was use d, pl ease s pecif y (free te xt)  
  
3.  Ha ve y o u ha d a pr ofessi o nal t o ot h clea ni n g i n t he last 2 wee ks?   
Y  or N o  
  
4.  Ha ve y o u e v er bee n dia g n ose d wit h se nsiti ve teet h b y a d e ntist?   
Y  or N o  
  
5.  W he n was t he last ti me y o u visite d a de ntist/ h y gi e nist?  
Wit hi n t he last 6 m o nt hs  
W it hi n t he last year  
W it hi n 2 years  
B et wee n 2 -3 years a g o  
M ore t ha n 3 years  a g o  
  
6.  D o y o u us e a t o ot h paste desi g ne d s p ecificall y f or se nsiti ve teet h?   
Yes (c urre nt users)   
N o ( n o n-users)   
S o meti mes (i nter mitte nt users)   
U n k n o w n   
 
7.  W hat b ra n d of t o ot h paste d o y o u m ost fre q ue ntl y use? ( Select fr o m dr o p d o w n list)   
If ot her, s pecif y (free te xt)   
 
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
8.  W hat is t he pr o d uct na me  of t he bra n d selecte d i n t he pre vi o us q uesti o n t hat y o u m ost 
fre q ue ntl y use? ( Select fr o m dr o p d o w n list)   
If ot her pr o d u ct na me/ varia nt, s pecif y  (free te xt)  
  
9.  W h ic h t o ot h paste are y o u us i n g ri g ht n o w? If y o u c urre ntl y use m or e  t ha n o ne t o ot h paste, 
please list t he m all ( bra n d a n d pr o d uct na me).  H o w l o n g ha v e y o u bee n usi n g it /t he m f or? 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ (free te xt)  
 
 
1 0.  W h at t y p e of  t o ot h br us h d o y o u use ? ( Select fr o m dr o p d o w n list)   
 
1 1.  Ca n y o u tell me if y o u h a ve a n y of t he f oll o wi n g :  
(T ick all t h at a p ply )  
Crac ke d t o ot h or teet h  
C hi p pe d t o o t h or teet h  
C ol d s ores  
Gri n di n g te et h  
G u m s welli n g or i nfla m mati o n  
Rece di n g g u ms    
Pai nf ul/te n der g u ms w he n br us hi n g  
Ulcers i n t he m o ut h  
Stai ne d/ yell o w teet h   
Seei n g bl o o d w h e n y o u s pit w he n y o u br us h y o ur teet h  
Ba d breat h  
N o ne of t hese  
 
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
1 5. 4  
D e nti n  H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e  ( D H E Q-4 8)  
 
S E C TI O N O N E  
T h e f oll o wi n g q u e sti o n s ar e a b o ut y o ur s e n siti v e t e et h, a n d t h e i m p a ct it  h a s o n y o ur 
e v er y d a y lif e.  
  
 
 
 
 
 
 
 
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
S E C TI O N T W O  
T h e  f oll o wi n g q u e sti o n s ar e a b o ut t h e w a y s i n w hi c h a n y s e n s ati o n s i n y o ur t e et h 
aff e ct y o u i n y o ur d ail y lif e.  T hi n ki n g a b o ut y o ur s elf o v er t h e l a st m o nt h  t o w h at 
e xt e nt w o ul d y o u a gr e e or di s a gr e e wit h t h e f oll o wi n g st at e m e nt s ( Pl e a s e ti c k o nl y 
o n e r e s p o n s e f or e a c h q u e sti 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.  
  
  
  
  
  
  
  
  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T h e  f oll o wi n g q u e sti o n s ar e a b o ut t h e w a y s i n w hi c h t h e s e n s ati o n s i n y o ur t e et h 
h a v e f or c e d y o u t o c h a n g e t hi n g s i n y o ur d ail y lif e . T hi n ki n g a b o ut y o ur s elf o v er 
t h e l a st m o nt h t o w h at e xt e nt w o ul d y o u a gr e e or di s a gr e e wit h t h e f oll o wi n g 
st at e m e nt s ( Pl e a s e ti c k o nl y o n e r e s p o n s e f or e a c h q u e sti 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 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T h e  f oll o wi n g q u e sti o n s ar e a b o ut t h e t hi n g s y o u d o i n y o ur d ail y lif e t o a v oi d  
e x p eri e n ci n g t h e s e n s ati o n s i n y o ur t e et h . T hi n ki n g a b o ut y o ur s elf o v er t h e l a st 
m o nt h  t o w h at e xt e nt w o ul d y o u a gr e e or di s a gr e e wit h t h e f oll o wi n g st at e m e nt s 
( Pl e a s e ti c k o nl y o n e r e s p o n s e f or e a c h q u e sti 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.  
  
  
  
  
  
  
  
  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T h e  f oll o wi n g q u e sti o n s ar e a b o ut t h e w a y t h e s e n s ati o n s aff e ct y o u w h e n y o u 
ar e wit h ot h er p e o pl e or i n c ert ai n sit u ati o n s . T hi n ki n g a b o ut y o ur s elf o v er t h e 
l a st m o nt h t o w h at e xt e nt w o ul d y o u a gr e e or di s a gr e e wit h t h e f oll o wi n g st at e m e nt s 
( Pl e a s e ti c k o nl y o n e r e s p o n s e f or e a c h q u e sti 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.  
  
  
  
  
  
  
  
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.  
  
  
  
  
  
  
  
  
  
  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T h e f oll o wi n g q u e sti o n s ar e a b o ut t h e w a y t h e s e n s ati o n s i n y o ur t e et h m a k e y o u 
f e el. T hi n ki n g a b o ut y o ur s elf o v er t h e l a st m o nt h  t o w h at e xt e nt w o ul d y o u a gr e e or 
di s a gr e e wit h t h e f oll o wi n g st at e m e nt s ( Pl e a s e ti c k o nl y o n e r e s p o n s e f or e a c h 
q u e sti 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.  
  
  
  
  
  
  
  
  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T h e f oll o wi n g q u e sti o n s ar e a b o ut w h at t h e s e n s ati o n s i n y o ur t e et h m e a n f or 
y o u.  T hi n ki n g a b o ut y o ur s elf o v er t h e l a st m o nt h  t o w h at e xt e nt w o ul d y o u a gr e e or 
di s a gr e e wit h t h e f oll o wi n g st at e m e nt s ( pl e a s e ti c k o nl y o n e r e s p o n s e f or e a c h 
q u e sti 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 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.  
  
  
  
  
  
  
  
  
  
 
 
3 0 0 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 3 0 0 0 5 8   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot b e 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 6 5  
T h e l a st fi v e q u e sti o n s a s k a b o ut h o w m u c h 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 lif e o v er 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 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
C CI

Si g nat ure Pa ge f or  3 0 0 0 5 8 T M F- 2 4 5 7 1 0 v 3. 0
Si g nat ure Pa ge f or T M F- 2 4 5 7 1 0 v 3. 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 0 5 8 Pr ot oc ol  1 0 A u g 2 0 2 3 | T M F- 2 4 5 7 1 0 | 3. 0
P P D
P P D