A Randomized, Controlled Clinical Study Assessing the Effects of a Marketed Dentifrice Compared to a Regular Fluoride Dentifrice and a Positive Control Dentifrice on Tooth Sensitivity While Undergoing Tooth Bleaching
Phase: PHASE4
Conditions: Dentin Sensitivity
Sponsor: HALEON

Hale o n  
Cli nical Pr ot oc ol  
Pr ot oc ol N u m ber :  3 0 0 1 0 6  
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1  of 5 6  
C LI NI C A L P R O T O C O L  
A R a n d o mi z e d, C o ntr oll e d  Cli ni c al St u d y A s s e s si n g t h e Eff e ct s of a 
M ar k et e d D e ntifri c e C o m p ar e d t o a R e g ul ar Fl u ori d e D e ntifri c e a n d 
a P o siti v e C o ntr ol D e ntifri c e o n T o ot h S e n siti vit y W hil e U n d er g oi n g 
T o ot h Bl e a c hi n g  
Pr ot o c ol N u m b er:  
3 0 0 1 0 6  
C o m p o u n d/ Pr o d u ct N a m e:  
D e ntifri c e c o nt ai ni n g N o v a Mi n ( 5 % w/ w 
C al ci u m S o di u m P h o s p h o sili c at e)  
P h a s e:  
I V 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
T his d oc u me nt c o ntai ns c o nfi de ntialit y state me nts t hat are n ot rele va nt f or t his  
p u blicl y a vaila ble versi o n
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2  of 5 6  
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)  
B uil di n g 5, Fir st Fl o or,  
T h e H ei g ht s,  
W e y bri d g e,  
S urr e y,  
K T 1 3 0 N Y.  
S p o n s or C o nt a ct D et ail s  
H al e o n  
1 8 4 Li b ert y C or n er R o a d, W arr e n, N J, U S A   
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
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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  
 
 
A m e n d m e nt 1  
2. 0  
C h a n g e fr o m a n e x p e ct ati o n t h at 3 0 -5 0 % of 
r a n d o mi z e d s u bj e ct s h a v e cli ni c all y-c o nfir m e d D H t o 
4 0 -5 0 % of t h e r a n d o mi z e d s u bj e ct s h a v e t o h a v e 
cli ni c all y -c o nfir m e d D H.  
M o difi c ati o n of E x c 6 b t o all o w a mi n of 1 1 of t h e 
a nt eri or 1 2 t e et h t o b e all o w a bl e  fr o m r e q uir e m e nt t h at 
all 1 2 b e e v al u a bl e.  
A m e n d m e nt 2  
 
 
 
 
 
Ne w versi o ns i nc or p orat e all re visi o ns t o date pri or t o  s u b missi o n t o i nstit uti o nal re vie w 
b oar ds/et hics c o m mittees ( I R Bs/ E Cs), etc. 
A me n d me nts i nc or p orate all re visi o ns t o d ate, i ncl u di n g a me n d me nts ma de at t he re q u est of 
i nstit uti o nal re vie w b oar ds/et hics c o m mittees (I R Bs/ EC s), etc.   
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
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Pa ge 4  of 5 6  
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 me 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  pri nci ples of  G o o d Cli nical Practice g ui deli nes ( G C P) . 
•  I ac k n o wle d g e t hat I a m res p o nsi ble f or o verall st u d y c o n d uct. I a gree t o pers o nall y c o n d uct 
or s u per vise t he d escri be d st u d y.  
•  I a gree t o e ns ur e 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 me 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 he st u d y. 
•  I a gree t o c o n d u ct t his st u d y i n f ull c o nf or ma n ce wit h t h e la ws a n d re g ulati 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:  
 
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C CI
P P D
P P D
P P D
P P D

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
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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 g e  ........................................................ 4  
Ta ble of C o nte nts  ........................................................................................................ 5  
1  
I N T R O D U C TI O N ...................................................................................................... 8  
1. 1  
Bac k gr o u n d & St u d y Rati o nale  ...................................................................... 8  
2  
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 0  
3  
S T U D Y D E SI G N  ..................................................................................................... 1 1  
4  
S T U D Y P O P U L A TI O N  ........................................................................................... 1 4  
4. 1  
T y pe a n d Pla n ne d N u m b er of S u bjects  ......................................................... 1 4  
4. 2  
I n cl usi o n Criteria........................................................................................... 1 4  
4. 3  
E xcl usi o n Criteria  ......................................................................................... 1 5  
4. 4  
Lifest yle C o nsi derati o ns  ............................................................................... 1 6  
4. 4. 1  
Oral H y gie ne R estricti o ns  ............................................................ 1 6  
4. 4. 2  
Dietar y a n d Al c o h ol, Restricti o ns  ................................................ 1 6  
4. 4. 3  
Use of C os metics  .......................................................................... 1 7  
4. 4. 4  
T o bacc o Pr o d uct Restricti o ns  ....................................................... 1 7  
4. 4. 5  
Me dicati o n a n d Treat me nt Restricti o ns ........................................ 1 7  
5  
S T U D Y P R O C E D U R E S  .......................................................................................... 1 7  
5. 1  
Sc he d ule of A cti vities  ................................................................................... 1 8  
6  
S T U D Y P R O C E D U R E S a n d A S S E S S M E N T S ....................................................... 1 9  
6. 1. 1  
Scree ni n g Pr oce d ures  ................................................................... 1 9  
6. 1. 2  
E nr olle d S u bjects a n d Scree n Fail ures  ......................................... 2 0  
6. 2  
Scree ni n g Asses s me nts ................................................................................. 2 0  
6. 2. 1  
De nti ne H y perse nsiti vit y Assess me nts ......................................... 2 0  
6. 3  
Efficac y Assess me nts  .................................................................................... 2 2  
6. 3. 1  
T o ot h Se nsiti vit y Q uesti o n naire  ................................................... 2 2  
6. 3. 2  
W hite ni n g Hist or y a n d P ost -W hite ni n g Q uesti o n naires  .............. 2 3  
6. 3. 3  
De nti ne H y perse nsiti vit y E x peri e nce Q uesti o n nair e ( D H E Q)  ..... 2 3  
6. 3. 4  
T o ot h S ha de ( C ol or) Ass ess me nt  ................................................. 2 3  
6. 4  
Safet y a n d Ot her Assess me nts  ...................................................................... 2 4  
6. 4. 1  
Oral S oft Tiss ue ( O S T) E xa mi nati o n  ........................................... 2 4  
6. 4. 2  
Oral Har d Tiss ue ( O H T) E xa mi nati o n  ......................................... 2 4  
7  
I N V E S TI G A TI O N A L/ S T U D Y P R O D U C T S .......................................................... 2 4  
7. 1  
I n v esti gati o nal/ St u d y Pr o d uct S u p plies ........................................................ 2 5  
7. 1. 1  
A p plicati o n of t he Per o xi de Bleac hi n g ......................................... 2 6  
7. 2  
Pr o d uct S u p plies Pr o d uct St ora ge, Acc o u nta bilit y, Ret ur ns a n d Destr u cti o n
 ....................................................................................................................... 2 6  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
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Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
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7. 3  
Bli n di n g a n d Ra n d o mizati o n  ........................................................................ 2 7  
7. 4  
Brea ki n g t he Bli n d  ........................................................................................ 2 7  
8  
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  .......................... 2 8  
8. 1  
Sa m ple Size Deter mi nati o n  ........................................................................... 2 8  
8. 2  
P o p ulati o ns f or A nal ysis  ............................................................................... 2 8  
8. 2. 1  
E xcl usi o ns of Data fr o m A nal ysis  ................................................ 2 8  
8. 3  
Statistical A nal yses  ....................................................................................... 2 8  
8. 3. 1  
Pri mar y E n d p oi nt A nal ysis ........................................................... 2 8  
8. 3. 2  
Sec o n dar y E n d p oi nt A nal ys es ...................................................... 2 9  
8. 3. 3  
E x pl orat or y A nal yses  ................................................................... 3 0  
8. 3. 4  
Safet y A nal yses  ............................................................................ 3 0  
8. 3. 5  
De m o gra p hic a n d Baseli ne C haracteristics  .................................. 3 1  
8. 3. 6  
St u d y Pr o d uct C o m plia nce a n d Us e of Ot her T hera pies  .............. 3 1  
8. 3. 7  
Pri or a n d C o nc o mita nt Me d icati o ns ............................................. 3 1  
8. 3. 8  
Ha n dli n g of Dr o p o uts a n d Missi n g Data  ...................................... 3 1  
8. 3. 9  
I nteri m A nal ysis ........................................................................... 3 1  
9  
A P P E N DI C E S  .......................................................................................................... 3 1  
9. 1  
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 1  
9. 1. 1  
Defi niti o n of a n A d verse E ve nt ( A E)  ........................................... 3 2  
9. 1. 2  
Def i niti o n of a Seri o us A d verse E ve nt ( S A E) .............................. 3 2  
9. 1. 3  
Ti me Peri o d a n d Fre q ue n c y f or C ollecti n g A E a n d S A E 
I nf or mati o n ................................................................................... 3 3  
9. 1. 4  
Re p orti n g Pr oce d ures  ................................................................... 3 4  
9. 1. 5  
E val uati n g A d verse E ve nts ........................................................... 3 6  
9. 1. 6  
F oll o w -u p of A Es a n d S A Es  ........................................................ 3 7  
9. 1. 7  
Wit h dra wal D u e t o a n A d verse E ve nt  .......................................... 3 7  
9. 1. 8  
Re g ulat or y Re p orti n g Re q uire me nts f or S A Es  ............................ 3 7  
9. 1. 9  
Pre g na nc y  ..................................................................................... 3 8  
9. 1. 1 0  
Me dical De vic e I n ci de nts  ............................................................. 3 8  
9. 1. 1 1  
Re p orti n g of I nci de nts a n d Malf u ncti o ns  ..................................... 3 9  
9. 1. 1 2  
F oll o w -u p of Me di cal De vice I nci de nts  ....................................... 4 0  
9. 1. 1 3  
Re g ulat or y Re p orti n g Re q uire me nts f or Me dical De vice I n ci de nts
 ...................................................................................................... 4 0  
9. 2  
DI S C O N TI N U A TI O N O F S T U D Y P R O D U C T A N D S U BJ E C T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ..................................................... 4 0  
9. 2. 1  
Disc o nti n uati o n of St u d y Pr o d uct  ................................................ 4 0  
9. 2. 2  
S u bject Disc o nti n uati o n/ Wit h dra wal ............................................ 4 1  
9. 2. 3  
L ost t o F oll o w u p .......................................................................... 4 1  
9. 3  
Data Ma na g e me nt  ......................................................................................... 4 1  
9. 3. 1  
Case Re p ort F or m  ......................................................................... 4 2  
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Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
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9. 3. 2  
Data Ha n dli n g  ............................................................................... 4 2  
9. 3. 3  
Data Q ueries  ................................................................................. 4 2  
9. 4  
Pr ocessi n g Patie nt Re p orte d O utc o mes  ........................................................ 4 2  
9. 5  
Re g ulat or y a n d Et hical C o nsi derati o ns  ......................................................... 4 2  
9. 5. 1  
I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee ............................ 4 2  
9. 5. 2  
Et hical C o n d uct of t he St u d y  ........................................................ 4 3  
9. 5. 3  
S u bject I nf or mati o n  ...................................................................... 4 3  
9. 6  
Rec or ds Rete nti o n  ......................................................................................... 4 3  
9. 7  
Discl os ure a n d P u blicati o n P olic y  ................................................................ 4 3  
9. 8  
A b bre viati o ns  ................................................................................................ 4 4  
9. 9  
St u d y Pr o d uct Usa ge I nstr ucti o ns S heet  ....................................................... 4 4  
9. 1 0  
T o ot h Se nsiti vit y Q uesti o n naire ( E X A M P L E)  ............................................. 4 6  
9. 1 1  
W hite ni n g Hist or y Q uesti o n naire.  ................................................................ 4 8  
9. 1 2  
De nti ne H y perse nsiti vit y E x perie nce Q uesti o n nair e ( E xa m ple)  .................. 4 9  
9. 1 3  
P o st-W hite ni n g Q uesti o n naire.  ..................................................................... 5 3  
9. 1 4  
Refere n ces  ..................................................................................................... 5 4  
 
Li st of i n t e xt t a bl e s 
Ta ble 2 -1  
St u d y O bjecti ves a n d E n d p oi nts  ................................................................. 1 0  
Ta ble 5 -1  
Sc he d ule of A cti vities  ................................................................................. 1 8  
Ta ble 7 -1  
I n v esti gati o nal/ St u d y Pr o d uct S u p plies ...................................................... 2 5  
Ta ble 7 -2  
S u n dr y Ite ms  ............................................................................................... 2 5  
Ta ble 9 -1  
A b bre viati o ns  .............................................................................................. 4 4  
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
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Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
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1  
I N T R O D U C TI O N 
T o ot h bleac hi n g is a wi del y perf or me d pr oce d ure  t hat ai ms t o i m pr o ve t he c ol or (i n crease 
w hite ness) of teet h t o pr o vi de a c os metic be n efit.  T he m ost c o m m o nl y use d bleac hi n g 
i n gre die nt is h y dr o ge n per o xi de ( or h y dr o ge n per o xi de-releasi n g i n gre die nts s uc h as car ba mi de 
per o xi de), w hi c h f u ncti o ns b y diff usi n g t hr o u g h t he t o ot h e na mel a n d o xi dizi n g c hr o m o p h ores 
wit hi n t he p or o us matri x of e na mel a n d t he u n derl yi n g de nti ne.  T his has t he effect of re d u ci n g 
t he c ol or wit hi n teet h a n d ma ki n g t he m a p pear w hiter.   
T o ot h se nsiti vit y ma na ge me nt w or ks o n t he pri n ci ple of eit her e m pl o yi n g p otassi u m -base d 
a ge nts ai mi n g t o sta bilize p ul pal n er ve de p olari zati o n, or d e nti nal t u b ule occl usi o n a ge nts 
ai mi n g t o occl u de pate nt de nti nal t u b ules (P ollar d et al. , 2 0 2 3).  H o we v er, ma n y de ntifric es  
a d vise d b y de ntal pr ofessi o nals t o re d uce t o ot h se nsiti vit y w hilst patie nts are u n der g oi n g  t o ot h 
bleac hi n g c o ntai n p otassi u m i o ns, rat her t ha n occl u di n g a ge nts, li kel y beca use t he n u m ber of 
p u blis he d st u dies i n s u p p ort of occl u di n g a ge nts are fe w (Ale x a n dri n o et al., 2 0 1 7 , Mali k et  al., 
2 0 1 6 , S hi va prasa d et al., 2 0 1 4 ).  T heref ore, c o n cl usi o ns fr o m t hese p u blis he d st u dies are 
diffic ult t o i nter pret wit h a n y certai nt y a n d f urt her st u dies are nee d e d t o de m o nstrate efficac y 
of de ntifrice s f or t o ot h se nsiti vit y re d ucti o n w hilst patie nts are u n der g oi n g  t o oth bleac hi n g a n d 
i nf or m o n p ote ntial treat me nt strate gies rel e va nt t o de ntal pr ofessi o nals. 
N o va Mi n ( Calci u m S o di u m P h os p h osilicate) is a n occl u di n g a ge nt e m pl o ye d i n de ntifrices 
i n dicate d f or t o ot h se nsiti vit y relief t hat is cli nicall y pr o ve n t o pr o vi de relief (Ge n drea u et al., 
2 0 1 1 ) b y f or mi n g a calci u m ric h la yer i n a n d o ver t he s urface of e x p ose d d e nti ne f oll o wi n g 5 
da ys of t wice dail y use (J o nes et al., 2 0 1 5).  T he efficac y of N o va Mi n has bee n s h o w n i n a 
n u m ber of cli nical trials  w here p atie nts u n der g oi n g t o ot h w hite ni n g treat me nt were e xcl u de d  
(Lit k o ws ki a n d Gree ns pa n, 2 0 1 0 , Nar o n g dej et al ., 2 0 1 0, de Freitas et al., 2 0 2 1 ). Gi ve n t hat it 
is n o w c o m m o n practice f or ma n y patie nts t o u n der g o t o ot h bleac hi n g t o ac hie ve w hiter teet h , 
it is of i nterest t o u n dersta n d if patie nts ca n be n efit fr o m u si n g N o va Mi n t o pr o vi de t o ot h 
se nsiti vit y relief w hilst u n der g oi n g t o ot h bleac hi n g. 
T he ai m of t his  e x pl or at or y  st u d y is t o i n vesti gate t he efficac y of a m ar kete d d e ntifrice 
c o ntai ni n g 5 % N o va M i n t o re d uce t o ot h se nsiti vit y d uri n g a n d p ost t o ot h bleac hi n g c o m pare d 
t o a mar ket e d de ntifri ce c o ntai ni n g 5 % p otassi u m nitrate ( K N O3) a n d a mar kete d re g ular 
fl u ori de-c o ntai ni n g de ntifrice.  
1. 1  
B a c k gr o u n d & St u d y R ati o n al e  
T his is a n e x pl orat or y, pr o of -of -pri nci ple st u d y .  T he st u d y will be a ra n d o mize d, e xa mi ner -
bli n d, si n gle -ce nter, c o ntr olle d, t hree ar m, p arallel gr o u p pr o of -of -pri nci pal e x pl orat or y st u d y 
t o e val uate t o ot h se nsiti vit y d uri n g a n d f oll o wi n g at-h o me t o ot h bleac hi n g .  T his st u d y will 
c o m pare t h e efficac y of a de ntifric e c o nt ai ni n g N o va Mi n, a de nti ne t u b ule occl u di n g a g e nt t o 
a p ositi ve c o ntr ol (c o nt ai ni n g 5 % K N O 3) a n d a sta n d ar d fl u ori de-c o ntai ni n g refere n ce 
de ntifrice.  
T he t o ot h se nsiti vit y be n efit ass ociat e d wit h t he use of N o va Mi n c o ntai ni n g de ntifrices (t he 
Test pr o d uct i n t his st u d y) is e xte nsi ve (Ge n drea u et al., 2 0 1 1 , Ara ntes et al., 2 0 1 9 , Rajes h et 
al., 2 0 1 2, N e u ha us et al., 2 0 1 3 ).  N o va Mi n is re p orte d t o f u ncti o n b y a d heri n g t o e x p ose d de nti n 
s urfaces, reacti n g wit h it t o f or m a mi neralize d la yer t hat is resista nt t o aci d c halle n ges a n d is 
mec ha nic all y str o n g (B ur well et al., 2 0 1 0 ).  T his la yer t h us occl u des p ate nt de nti ne t u b ules 
wit h a h y dr o x ya patite -li ke la yer (Earl et al., 2 0 1 1 ) a n d there b y re d u ci n g p ul pal ner ve e xcitati o n 
b y pre ve nti n g t he fl o w of de nti nal fl ui d i nitiate d b y t her mal/ os m otic/tactile sti m uli (A d d y, 
2 0 0 2 ).  H o we ver, t he a bilit y of N o va Mi n t o re d uce t o ot h s e nsiti vit y w hilst patie nts are 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 9  of 5 6  
u n der g oi n g  t o ot h bleac hi n g is less e xte nsi vel y re p orte d i n t he literat ure.  I n o ne st u d y o n t he 
effect of a d e ntifrice c o nt ai ni n g a bi oa cti ve glass si milar t o N o va Mi n, a statisticall y  si g nifica nt 
re d ucti o n i n t o ot h se nsiti vit y (e val uate d b y a V A S) was o bs er ve d c o m pare d t o a pl ace b o 
de ntifrice (Bizre h a n d Mill y, 2 0 2 2 )   
T he a bilit y f or calci u m -c o ntai ni n g bi oacti ve gl asses w he n c o m bi ne d wit h t he per o xi de 
w hite ni n g a ge nt t o re d uce t o ot h se nsit i vit y w hilst patie nts are u n der g oi n g  t o ot h bleac hi n g has 
bee n re vie we d (Fa v oret o et al., 2 0 2 3 ), c o ncl u di n g t hat t here is a s mall b ut p ositi ve i m pact o n 
t hese a g e nts t o re d u ce t o ot h se nsiti vit y w hilst patie nts are u n der g oi n g  t o ot h bleac hi n g.  
H o we ver, t his re vie w s p ecificall y e xcl u de d a n y a nal ysis of st u dies wit h bi o glass -c o ntai ni n g 
de ntifrices.  T he e vi de nce s pecificall y f or N o va Mi n de ntifrices is t heref ore mi ni mal a n d t h us, 
t his st u d y is re q uire d t o i n vesti gate t he p ote ntial f or N o va Mi n t o pr o vi de t o ot h se nsiti vit y relief 
w hilst patie nts are u n der g oi n g  t o ot h bleac hi n g. 
T he t o ot h se nsiti vit y be nefits of K N O 3 co ntai ni n g de ntifrices are well esta blis he d (S har ma et 
al., 2 0 1 2, H u et al., 2 0 1 8 ).  A d diti o nall y , t here is cli nical e vi de nce t o s u p p ort t he r ole of 
p otassi u m i o ns at re d uci n g t o ot h se nsiti vit y w hile patie nts u n der g o i n g t o ot h bleac hi n g.  O ne 
st u d y e val uate d t he t wice-dail y use of a 5 % K N O 3 de ntifrice f or 2 wee ks b ef ore, a n d d uri n g a 
1 4 da y treat me nt wit h a 9. 5 % h y dr o ge n per o xi de gel c o m pare d t o a sta n dar d de ntifrice  
(Ha y w o o d et al., 2 0 0 5 ).  T he st u d y c o ncl u de d t hat use of t he p otassi u m-c o ntai ni n g de ntifrice 
res ulte d i n statisticall y si g nifica ntl y m ore se nsiti ve-free da ys t ha n t he c o ntr ol de ntifrice.  
Si milar fi n di n gs were f o u n d i n a n ot her st u d y (Pier ote et al., 2 0 2 0 ) w here a variet y of de ntifrices 
were use d d uri n g a n d aft er per o xi de bleac hi n g wit h a 2 6 % h y dr o ge n per o xi de gel, c o ncl u di n g 
t hat de ntifrices c o ntai ni n g K N O 3 a n d s o di u m fl u ori de  were a bl e t o re d uce t o ot h se nsiti vit y 
d uri n g per o xi de bleac hi n g.  T he sa me st u d y als o e val uate d t o ot h c ol or fi n di n g t hat all of t he 
teste d de ntifric es (i ncl u di n g c o ntr ols) lea d t o t he sa me t o ot h c ol or at 4 a n d 2 4 wee ks after 
bleac hi n g.  A se parate st u d y b y t he sa me a ut h ors c o ncl u de d t hat a p otassi u m  i o n-c o ntai ni n g 
de ntifrice was effecti ve at hel pi n g t o re d uce t o ot h se nsiti vit y w he n a p plie d via a tra y f or 4 h o urs 
per ni g ht d uri n g t he bleac hi n g peri o d (Pier ote et al., 2 0 1 9 ).  I n a f urt her st u d y (A dil et al., 2 0 2 1 ), 
use of a K N O 3 / s o di u m m o n ofl u o p h os p hate gel p ost bleac hi n g was f o u n d t o be effecti ve at 
re d ucti o n of t o ot h se nsiti vit y w he n a 3 5 % h y dr o ge n per o xi de bleac hi n g treat me nt was use d.  
T o ot h se nsiti vit y relief w hile usi n g a K N O 3 de ntifrice was als o o bser ve d i n a p o p ulati o n wit h 
mil d -t o-m o derate fl u or osis f oll o wi n g 3 5 % h y dr o ge n per o xi de treat me nt (Na nj u n dasett y a n d 
A s hraf ulla, 2 0 1 6).  C o ntrasti n gl y, a p plicati o n of a K N O3 gel i m me diatel y pri or t o bleac hi n g 
wit h h y dr o ge n per o xi de was n ot f o u n d t o re d uce t o ot h se nsiti vit y b ut als o di d n ot a d versel y 
affect t he w hite ni n g effi cac y of t he bleac hi n g tr eat me nt (de Li ma et al., 2 0 2 2 ).  F urt her, a n 
u n p u blis he d st u d y f o u n d t hat use of a 5 % K N O 3 de ntifrice bef ore, d uri n g a n d after a bleac hi n g 
treat me nt lea d t o a n o n-statisticall y si g nifica nt re d ucti o n i n t o ot h se nsiti vit y d uri n g t he 7 da ys 
p ost treat me nt, alt h o u g h statisticall y si g nifica nt fe wer s u bjects re p orte d t o ot h se nsiti vit y 
c o m pare d t o t he c o ntr ol de ntifrice 
  A s yste matic 
re vie w of t o ot h se nsiti vit y ass ociate d wit h t o ot h bleac hi n g, dra wi n g o n 1 3 p u blicati o ns, has 
c o ncl u de d t h at 5 % K N O 3 is effecti ve at re d uci n g t o ot h se nsiti vit y at least u p t o 2 4 h o urs p ost 
c o ncl usi o n of t he bleac hi n g treat me nt (Kris h n a k u mar et al., 2 0 2 2 ). 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 0  of 5 6  
2  
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 2 -1  
St u d y O bj e cti v e s a n d E n d p oi nt s  
O bj e cti v e s  
E n d p oi nt s  
Pri m ar y  
T o c h ar a ct eri z e t h e s u bj e ct -p er c ei v e d s e n siti vit y 
pr ot e cti o n pr ofil e of a 5 % N o v a Mi n -c o nt ai ni n g 
d e ntifri c e, a 5 % K N O 3 -c o nt ai n in g d e ntifri c e a n d 
a r ef er e n c e fl u ori d e d e ntifri c e d uri n g a n d f or 2 
w e e k s p o st t o ot h bl e a c hi n g.  
D ail y r e s p o n s e s fr o m t h e t o ot h s e n sit i vit y 
q u e sti o n n air e t hr o u g h t h e st u d y i n:- 
•  Vi s u al a n al o g u e s c al e  ( V A S) 
•  L a b ell e d M a g nit u d e s c al e s (I nt e n sit y, 
D ur ati o n. T ol er a bilit y, D e s cri pti o n)  - L M S  
•  B ot h er s o m e n e s s s c or e  –  N R S  
•  N u m b er of  s u bj e ct s w h o e x p eri e n c e to ot h 
s e n siti vit y  
•  N u m b er of s u bj e ct s w h o u s e d a n al g e si c s t o 
all e vi at e t o ot h s e n siti vit y  
S e c o n d ar y  
T o i n v e sti g at e t h e a bilit y of a 5 % N o v a Mi n -
c o nt ai ni n g d e ntifri c e t o r e d u c e s elf -p er c ei v e d 
t o ot h s e n siti vit y a s m e a s ur e d b y a s u bj e ct -
c o m pl et e d t o ot h s e n siti vit y q u e sti o n n air e  
c o m p ar e d t o a 5 % K N O 3 -c o nt ai ni n g  d e ntifri c e 
a n d a r ef er e n c e fl u ori d e d e ntifri c e d uri n g t o ot h 
bl e a c hi n g.  
R e s p o n s e s fr o m t h e t o ot h s e n siti vit y 
q u e sti o n n air e c o m pl et e d  d uri n g  t o ot h bl e a c hi n g 
( Vi sit 2-3)  i n:- 
•  M e a n V A S  
•  M e a n L M S  
•  M e a n B ot h er s o m e n e s s  
•  %  t o ot h s e n siti vit y-fr e e d a y s 
•  % d a y s a n al g e si c s u s e d t o all e vi at e t o ot h 
s e n siti vit y  
T o i n v e sti g at e t h e a bilit y of a 5 %  N o v a Mi n -
c o nt ai ni n g d e ntifri c e t o r e d u c e s elf -p er c ei v e d 
t o ot h s e n siti vit y a s m e a s ur e d b y a s u bj e ct -
c o m pl et e d t o ot h s e n siti vit y q u e sti o n n air e 
c o m p ar e d t o a 5 % K N O 3 -c o nt ai ni n g -d e ntifri c e 
a n d a r ef er e n c e fl u ori d e d e ntifri c e f or 2 w e e k s 
fr o m t h e e n d of t o ot h bl e a c hi n g. 
R e s p o n s e s fr o m t h e t o ot h s e n siti vit y 
q u e sti o n n air e c o m pl e t e d d uri n g t h e 2 w e e k s 
p o st c o m pl eti o n of t o ot h bl e a c hi n g ( Vi sit 3-4) i n:- 
•  M e a n V A S  
•  M e a n L M S  
•  M e a n B ot h er s o m e n e s s  
•  % t o ot h s e n siti vit y -fr e e d a y s 
•  % d a y s a n al g e si c s u s e d t o all e vi at e t o ot h 
s e n siti vit y . 
T o c o nfir m t h e t o ot h w hit e ni n g effi c a c y of 
p er o xi d e t o ot h bl e a c hi n g wit h c o n c urr e nt, t wi c e 
d ail y u s e of a 5 % N o v a Mi n -c o nt ai ni n g  d e ntifri c e , 
a 5 % K N O 3 -c o nt ai ni n g d e ntifri c e  a n d a 
r ef er e n c e fl u ori d e d e ntifri c e a s m e a s ur e d b y 
VI T A Bl e a c h e d g ui d e 3 D M a st er.  
C h a n g e i n m e a n VI T A s h a d e s c or e fr o m pr e - t o 
p o st -t o ot h bl e a c hi n g ( Vi sit 2-3)  
E x pl or at or y  
T o e x pl or e s u bj e ct’ s  or al -h e alt h r el at e d q u alit y 
of lif e  d uri n g p er o xi d e t o ot h bl e a c hi n g w h e n 
si m ult a n e o u sl y u si n g  eit h er a 5 % N o v a Mi n -
c o nt ai ni n g d e ntifri c e , a 5 % K N O3 -c o nt ai ni n g 
d e ntifri c e or a r e g ul ar fl u ori d e d e ntifri c e.  
C h a n g e fr o m s cr e e ni n g i n r e s p o n s e s fr o m t h e 
D e nti n e H y p er s e n siti vit y E x p eri e n c e 
Q u e sti o n n air e ( D H E Q ) d uri n g t h e t o ot h 
bl e a c hi n g p eri o d ( Vi sit 2 -3) a n d f or t h e t w o 
w e e k s p o st t o ot h bl e a c hi n g ( Vi sit 3 -4)  
T o i n v e sti g at e t h e a bilit y of a 5 %  N o v a Mi n -
c o nt ai ni n g d e ntifri c e t o r e d u c e s elf -p er c ei v e d 
t o ot h s e n siti vit y a s m e a s ur e d b y a s u bj e ct -
c o m pl et e d t o ot h s e n siti vit y q u e sti o n n air e 
c o m p ar e d t o a  5 %  K N O 3 -c o nt ai ni n g -d e nt ifri c e 
a n d a r ef er e n c e d e ntifri c e f or 2 w e e k s fr o m t h e 
R e s p o n s e s fr o m t h e D H E Q a n d t o ot h s e n siti vit y 
q u e sti o n n air e d uri n g t h e t o ot h bl e a c hi n g p eri o d 
( Vi sit 2-3) a n d s e p ar at el y f or t h e 2 w e e k s p o st 
t o ot h bl e a c hi n g (Vi sit 3 -4 ) i n:- 
•  M e a n V A S  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 1  of 5 6  
e n d of t o ot h bl e a c hi n g s e p ar at el y f or t h o s e 
s u bj e ct s wit h a n d wit h o ut cli ni c all y -c o nfir m e d 
d e nti n e h y p er s e n siti vit y ( D H ). 
•  M e a n L M S  
•  M e a n B ot h er s o m e n e s s  
•  % t o ot h s e n siti vit y -fr e e d a y s 
•  % d a y s a n al g e si c s u s e d t o all e vi at e t o ot h 
s e n siti vit y  
•  C h a n g e fr o m s cr e e ni n g  i n D H E Q  
T o e x pl or e s u bj e ct’ s  e x p eri e n c e  of p er o xi d e 
t o ot h bl e a c hi n g w h e n si m ult a n e o u sl y u si n g  
eit h er a  5 %  N o v a Mi n -c o nt ai ni n g d e ntifri c e , a 5 % 
K N O 3 -c o nt ai ni n g d e ntifri c e or a r e g ul ar fl u ori d e 
d e ntifri c e.  
P o st -w hit e ni n g q u e sti o n n air e  
N o f or mal s uccess criteri o n  has bee n defi ne d f or t his e x pl orat or y st u d y; h o we ver, if t he 
N o va Mi n de ntifric e pr o vi des se nsiti vit y pr otecti o n  d uri n g t o ot h bleac hi n g , it w o ul d be 
e x pecte d t hat s u bject percei ve d t o ot h se nsiti vit y (meas ure d  b y t he s u bject c o m plete d se nsiti vit y 
q uesti o n na ires) f or t he N o va M i n de ntifrice w o ul d be directi o nall y s u peri or t o t he refere nce 
de ntifrice d uri n g t he st u d y peri o d. 
3  
S T U D Y D E SI G N  
T his is a ra n d o mize d, e xa mi ner bli n d, si n gle -ce nter, c o ntr olle d, t hree ar m, parallel gr o u p , 
pr o of -of -pri nci pal st u d y t o e val uate t o ot h se nsiti vit y d uri n g a n d f oll o wi n g a c o urse of t o ot h 
bleac hi n g  i n s u bj ects wit h a n d wit h o ut cli nicall y-c o nfir me d de nti ne h y p erse nsiti vit y .  T he 
st u d y will recr uit ge nerall y healt h y s u bjects w h o wis h t o u n der g o per o xi de t o ot h bleac hi n g.  A 
sc he matic of t he pri nci pal st u d y assess me nts a n d pr oce d ures is pr o vi de d i n Fi g 3 -1.  
S ufficie nt  s u bjects will be scree ne d t o ra n d o mize a p pr o xi matel y 9 0 s u bjects t o st u d y treat me nt 
(a p pr o xi matel y 3 0 per treat me nt gr o u p) . 
S u bjects will atte n d a Scree ni n g visit ( Visit 1) w here, ha vi n g o btai ne d t h eir writte n i nf or me d 
c o nse nt, rele v a nt details of t heir me dical hist or y, de m o gra p h y a n d c urre nt me dicati o ns will be 
rec or de d.  S u bjects will t he n u n der g o oral s oft tiss ue ( O S T) a n d oral har d tiss ue ( O H T) 
e xa mi nati o ns.  T he s ha de (c ol or) of t he facial s urfaces of t he a nteri or 6 ma xillar y a n d 
ma n di b ular teet h (t o ot h n u m bers 6 -1 1 a n d 2 2 -2 7)  will t he n be assesse d cli nicall y usi n g t he 
VI T A Bleac h e d g ui de 3 D -M A S T E R (G ó mez ‐ P ol o et al., 2 0 1 5 ). 
T h ose s u bjects wit h a self -re p orte d hist or y of de nti ne h y perse nsiti vit y ( D H) will be cli nicall y -
e val uate d t o c o nfir m t h eir D H stat us [ Y/ N] (i ncl u di n g Er osi o n/ A brasi o n/ Recessi o n ( E A R) 
assess me nt, gi n gi val assess me nt, t o ot h m o bilit y assess me nt a n d e va p orati ve (air) se nsiti vit y 
assess me nt ( Sc hiff Se nsiti vit y sc ore)).  
S u bjects meeti n g all st u d y criteria will be c o nsi dere d as eli gi ble t o pr ocee d  a n d will c o m plete 
t he t o ot h se nsiti vit y q uesti o n naire a n d t he D H E Q -1 5  after bei n g trai n e d i n t he c orrect usa ge of 
t hese q uesti o n naire s.  Eli gi ble s u bjects will t he n be stratifie d (b ase d u p o n t h eir D H stat us [ Y/ N])  
a n d ra n d o mize d t o treat me nt gr o u p.  S u bjects will t he n be dis pe nse d t heir all ocate d de ntifrice, 
ti mer a n d t oot h br us h  a n d  will u n der g o a s u per vise d br us hi n g wit h t heir all ocate d de ntifrice at 
t he cli nical site a n d sc h e d ule d t o atte n d visit 2 ( 2 wee ks ± 2 da ys aft er Scree ni n g).  S u bjects 
will be i nstr ucte d t o use t heir assi g ne d d e ntifrice t wice dail y ( m or ni n g a n d e ve ni n g) f or  1 ti me d 
mi n ute . 
At Visit 2, s u bjects will u n der g o a re vie w of t heir c urre nt me dicati o ns a n d  c o m plia nce t o 
treat me nt a n d will t he n u n der g o a n O S T e xa mi nati o n.  T he s ha de (c ol or) of t he facial s urfaces 
of t he a nteri or 6 ma xillar y a n d ma n di b ular teet h (t o ot h  n u m bers 6 -1 1 a n d 2 2 -2 7) w ill t he n be 
assesse d i n t he sa me wa y as at Visit 1.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 2  of 5 6  
Fi g ure 3 -1  
Sc he m atic of Fl o w of Ke y St u d y Assess m e nts/ Pr oce d ures  
 
S u bjects will t he n  c o m plete t he w hite ni n g hist or y q uesti o n naire , t he t o ot h se nsiti vit y 
q uesti o n naire  a n d t he DH E Q  aft er bei n g gi v e n i nstr ucti o n i n t he c o m pleti o n of t hese 
q uesti o n naires .  S u bjects will be dis pe nse d t heir at -h o me T o ot h Se nsiti vit y Q uesti o n naires  f or 
c o m pleti o n dail y .  S u bje cts will t he n be dis pe nse d t he t o ot h bleac hi n g kits f or us e at h o m e.  
S u bjects will be i nstr ucte d i n t he c orrect use of t he t o ot h bleac hi n g pr o d uct, t he first a p plicati o n 
of w hic h will be u n dert a ke n at t he st u d y site u n der s u pe r visi o n f oll o we d b y s u per vise d 
t o ot h br us hi n g wit h t heir all ocate d d e ntifrice.  S u bjects will be sc h e d ule d t o ret ur n t o t he st u d y 
site f or Visit 3 ( 7 ± 1 da ys) a n d will c o nti n ue t o use t heir assi g ne d d e ntifri ce t wice dail y a n d 
t heir t o ot h bleac hi n g kit o nce dail y p er i nstr ucti o ns  a n d c o m plete t h eir T o ot h Se nsiti vit y 
Q uesti o n naire at h o me, d ail y i n t he e ve ni n g (i ncl u di n g t he e ve ni n g of Visit 2) .   
At Visit 3, s u bjects will u n der g o a re vie w of t heir c urre nt me dicati o ns , a n d pr o d uct c o m plia nce , 
ret ur n c o m plete d q uesti o n naires a n d will t he n u n der g o a n O S T e xa mi nati o n.  T he s ha de (c ol or) 
of t he faci al s urfaces of t he a nteri or 6 ma xillar y a n d ma n di b ular teet h (t o ot h n u m bers 6-1 1  a n d 
2 2 -2 7 ) will t he n be assesse d i n t he sa me wa y as at Visit 1 .  S u bjects will t he n c o m plete t he p ost 
w hite ni n g q uesti o n naire  a n d t he D E H Q .  S u bjects will be sc he d ule d t o ret ur n t o t he st u d y site 
f or Visit 4 ( 2 w ee ks ± 2 d a ys after t he c o m pleti o n of per o xi de t o ot h bleac hi n g) a n d will c o nti n ue 
t o use t heir assi g ne d de ntifrice t wic e dail y a n d c o m plete t heir T o ot h Se nsiti vit y Q uesti o n naire 
dail y  i n t he e ve ni n g.   
At Visit 4, s u bjects will u n der g o a re vi e w of t heir c urre nt me dicati o ns  a n d pr o d uct c o m plia nce 
a n d ret ur n t h eir c o m plete d T o ot h Se nsiti vit y Q uesti o n naire  a n d st u d y pr o d ucts .  S u bjects will  
t he n u n der g o O S T a n d O H T e x a mi nati o ns  a n d c o m plete t he D E H Q .  S u bjects will t he n e xit 
t he st u d y. 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 3  of 5 6  
Safet y a n d oral t olera bilit y of t he st u d y pr o d u cts will be m o nit ore d b y re vi e w of  re p orte d A Es 
a n d me dical de vic e i nci d e nts c ollecte d at e ver y st u d y visit .  S u bjects of c hil d -beari n g p ot e ntial 
s hall c o nfir m t heir pre g n a nc y stat us at ev er y site visit.  
T he st u d y statisticia n a n d e m pl o yees of t he S p o ns or w h o ma y i nfl ue n ce st u d y o utc o mes are 
bli n de d t o t he pr o d uct all ocati o n of s u bjects. T h e e xa mi ner(s) a n d o utc o me assess or(s) will be 
bli n de d t o t he treat me nt recei ve d.  T o e ns ure t he e xa mi ner(s) a n d o utc o m e assess or(s) re mai n 
bli n de d t hr o u g h o ut t he st u d y, t he y are n ot per mitte d i n t he r o o m w hile pr o d uct is dis pe nse d.  
All st u d y pr o d ucts will be o ver wra p pe d t o c o nceal a n y la belli n g.  T he dis pe nsi n g staff will n ot 
be i n v ol ve d i n a n y cli nical assess me nts or a d mi nistrati o n of st u d y q uesti o n naires  d uri n g t he 
st u d y, alt h o u g h t he y ca n be i n v ol ve d i n t he trai ni n g of s u bjects i n c o m pleti n g t he q uesti o n nair es .   
A par allel gr o u p e x peri m e ntal desi g n was selecte d as s u bjects w o ul d n ot be e x pecte d t o re p eat 
per o xi de t o ot h bleac hi n g  m ore t ha n o nce p er year, precl u di n g t he use of a cr oss -o ver desi g n.  
T his is a si n gle -ce nter st u d y.  T he s a me e x a mi ner(s) will perf or m t he cli n ical assess me nts 
t hr o u g h o ut t he st u d y t o re d uce t he p ossi bilit y of i nter-e x a mi ner varia bilit y.  
T he Sc hiff se nsiti vit y scale, L M S , V A S a n d D H E Q ha ve b ee n pre vi o usl y use d a n d vali dat e d 
f or e val u ati n g de nti ne h y perse nsiti vit y  i n cli nical st u dies e val uati n g t he effecti ve n ess of 
de ntifrices (Mas o n et al., 2 0 1 9 , Heat o n et al., 2 0 1 5 , H olla n d et al., 1 9 9 7 , Gilla m et al., 1 9 9 7 , 
R oc ha et al., 2 0 2 0 , Sc hiff et al., 1 9 9 4 , Ba ker et al., 2 0 1 5 ). 
I n t his st u d y t o ot h se nsiti vit y will be e val uate d d uri n g a n d f or t he 2 wee ks p ost t he c o m pleti o n 
of t o ot h bleac hi n g.  It is e x pecte d t hat t o ot h s e nsiti vit y will i ncrease w hile  t o ot h bleac hi n g is 
u n der wa y a n d f or a peri o d of 1 -1 0 da ys p ost bleac hi n g.  E val uati o n of se nsiti vit y f or 2 wee ks 
is t heref ore c o nsi dere d s ufficie nt ti me p ost bleac hi n g t o e na ble t o ot h se nsiti vit y t o s u bsi de. 
A re g ular fl u ori de de ntifrice has bee n select e d as refere nce d e ntifrice.  F or t he p ur p oses of t his 
e x pl orat or y st u d y, it w as dee me d m or e rele va nt t o c o m pare t he efficac y of t he Test de ntifri ce 
a gai nst a t y pical d ail y -use de ntifric e rat h er t ha n a place b o.  A d diti o nall y, t he refere n ce 
de ntifrice is re prese ntati ve of a sta n dar d fa mil y de ntifrice c o m m o nl y a vail a ble i n t he c o u ntr y 
w here t he st u d y will be p erf or me d ( Ca n a da).   T h e p ositi ve c o ntr ol de ntifri ce c o ntai ns 5 % w/ w 
p otassi u m nitrate  w hic h ha ve bee n pre vi o usl y s h o w n t o re d uce t o ot h se nsiti vit y e x perie nce d 
w hilst pati e nts are u n der g oi n g  t o ot h bleac hi n g (Kris h na k u mar et al., 2 0 2 2 ). 
T he usa ge re gi me n of t wice dail y br us hi n g ( m or ni n g a n d e ve ni n g) will be t he sa me f or all 
s u bjects a n d is base d o n wi del y rec o mme n de d oral h y gie ne practice/t y pical c o ns u mer ha bit. 
St u d y s u bjects will be re q uire d t o br us h f or 1 ti me d mi n ute wit h t heir assi g ne d st u d y de ntifrice 
o n eac h br us hi n g occasi o n.  O n eac h br us hi n g o ccasi o n, t he t o ot h br us h will be d ose d wit h a 
ri b b o n of de ntifrice (c o v eri n g t he e ntire le n gt h of t he t o ot h br us h), i n li ne wit h t he pr o d uct 
la belli n g f or t he st u d y de ntifrices. 
T he test de ntifrice  is i n di cate d f or D H.  H o we ver, it is a ntici pate d t hat it will be p urc hase d b ot h 
b y c o ns u mers wit h D H a n d t h ose w h o d o n ot, b ut w h o are rec o m me n de d ( b y a de ntal healt h 
care pr ofessi o nal) t o use a se nsiti vit y de ntifrice pri or t o, d uri n g a n d p ost per o xi de de nta l 
bleac hi n g  treat me nt.  A mi xe d p o p ulati o n of t h ose  wit h cli nicall y -dia g n ose d D H a n d t h ose wit h 
n o D H s y m pt o ms is t heref ore a p pr o priate.  S u bjects will be str atifie d acc or di n g t o t heir D H 
stat us [ D H p ositi ve or ne gati ve (D H p ositi ve defi n e d as at least 1 t o ot h wit h a Sc hiff s c ore ≥2 )] 
t o e ns ure a b ala nce d p o p ulati o n acr oss treat me nt gr o u ps. 
T he s u bjects i n t his st u d y w h o h a ve s elf -dia g n os e d D H will be cli nicall y e v al uate d t o c o nfir m 
t heir D H stat us.  D H is pre vale nt at 3 0 -5 0 % of t he p o p ulati o n (West, 2 0 2 3 ) a n d t he e nr oll me nt 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 4  of 5 6  
t o t his st u d y is desi g ne d t o mirr or t his wit h a re q uire me nt t hat a p pr o xi matel y 4 5 % [ wit h a 
wi n d o w of 4 0 -5 0 %] of t h e ra n d o mize d s u bj ects t o ha ve cli nicall y c o nfir me d D H . 
De m o gra p h y i nf or mati o n will be rec or de d as part of t his st u d y, i ncl u di n g a ge, race a n d ge n der. 
I n acc or da nce wit h t he U nite d States F o o d a n d Dr u g A d mi nistrati o n ( U S F D A) g ui deli nes 
(F D A, 2 0 0 5 ) t he et h nicit y of s u bjects will als o be ca pt ure d. 
Acc or di n g t o t he I nt er nati o nal C o nfere n ce o n Har m o nisati o n (I C H) g ui deli nes (I C H, N o v 
2 0 1 6 ), f or a st u d y t o be classifie d as tr ul y d o u ble-bli n d, n ot o nl y d oes t he e xa mi ner (a n d a n y 
a p pr o priate me m ber of staff w h o ma y be i n v ol ve d i n t he dis pe nsi n g of pr o d ucts, a nal ysis of 
data etc.) n ee d t o be bli n d t o t h e treat me nt a s u bject recei ves, b ut t he pr o d ucts u n der test m ust 
be i de ntical i n e v er y w a y (c ol or, fla v or, r he ol o g y, a p peara nce, pac ka gi n g).  Gi ve n t he 
e x peri me ntal de ntifrices a n d t he refere nce d e ntifri ce will differ i n a p peara nce a n d fl a v or, t he 
le vel of bli n d ness f or t his st u d y is descri be d as ‘e x a mi ner bli n d’ o nl y.  T he st u d y will be bli n de d 
wit h res pect t o t he d e ntal e xa mi ner(s) a n d ot her o utc o me assess ors t o e ns ure t here is n o bias i n 
t he assess me nts. 
W hilst t he pr o d ucts bei n g teste d i n t his st u d y are  n ot c o ntra -i n dicat e d f or pre g na nc y t he 
preca uti o ns f or t he per o xi de w hite ni n g gel state t hat “ Pre g na nt or n ursi n g w o me n s h o ul d n ot 
use teet h w hite ni n g pr o d ucts”.  Pre g na nt fe males a n d t h ose i nte n di n g t o bec o me pre g na nt are 
t h us e xcl u de d i n t his st u d y.  Pr e g na n c y stat us will be ver ball y c o nfir me d b y s u bjects at eac h 
site visit. 
4  
S T U D Y P O P U L A TI O N  
4. 1  
T y p e a n d Pl a n n e d N u m b er of S u bj e ct s  
Healt h y v ol u nteers of eit her se x a n d a n y ge n der, a ge d 1 8 –  6 5 y ears will be recr uite d w h o wis h 
t o ha ve t heir teet h w hite n e d a n d meet all t he i ncl usi o n/e xcl usi o n criteria.  
S ufficie nt s u bjects will b e scree ne d t o ra n d o mize a p pr o xi matel y  9 0 s u bjects (a p pr o xi matel y 3 0 
per treat me nt gr o u p) t o e ns ure a p pr o xi matel y 8 8  e val ua ble s u bjects c o m plete t he st u d y  
(ass u mi n g a 2 % dr o p o ut rate) .  
T his st u d y ca n f ulfill its o bjecti ves o nl y if a p pr o priate s u bjects are e nr olle d.  T he f oll o wi n g 
eli gi bilit y criteria are d esi g ne d t o select s u bjects f or w h o m p artici pati o n i n t he st u d y i s 
c o nsi dere d a p pr o priate.  All rele va nt me dical a n d n o n -me dical c o n diti o ns s h o ul d be ta ke n i nt o 
c o nsi derati o n w he n d eci di n g w het her a s u bject is s uita ble f or t his pr ot oc ol.   
S u bject eli gi bilit y t o partici pate i n t he cli nical 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 priat e me m ber of t he i n vesti gat or’s st u d y tea m bef ore s u bjects are i ncl u de d i n t he 
st u d y. 
4. 2  
I n cl u si o n Crit eri a 
A n i n di vi d ual m ust meet all t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble t o be i ncl u de d i nt o 
t he st u d y: 
1.  S u bject pr o visi o n of a si g ne d a n d date d i nf or me d c o nse nt d oc u me nt i n dicati n g t hat t he 
s u bject has bee n i nf or me d of all perti ne nt as pects of t he st u d y bef ore a n y assess me nt is 
perf or me d.  
2.  S u bject is of eit her se x a n d a n y ge n der w h o, at t h e ti me of scree ni n g, is bet w ee n t he a g es 
of 1 8 -6 5 years, i ncl usi ve.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 5  of 5 6  
3.  S u bject is willi n g a n d a ble t o c o m pl y wit h sc he d ule d visits, a n d ot her st u d y pr oce d ures 
a n d restricti o ns.  
4.  S u bject i n g o o d ge neral a n d me ntal healt h wit h, i n t he o pi ni o n of t he i n vesti gat or or 
me dicall y q ualifie d desi g nee, n o cli nicall y si g nifica nt or rele va nt a b n or malities i n 
me dical hist or y (f or e xa m ple, a me dical c o n diti o n c o nfir me d t o be ca usi n g xer ost o mia),or 
u p o n oral e xa mi nati o n , t hat w o ul d i m pact t he s u bject’s safet y, well bei n g or t he o utc o mes 
of t he st u d y, if t he y were t o partici pate i n t he st u d y, or affect t he s u bject’s a bilit y t o 
u n dersta n d a n d f oll o w st u d y pr oce d ures a n d re q uire me nts . 
5.  S u bject w h o wis hes a n d is a ble t o u n der g o at -h o m e per o xi de t o ot h bleac hi n g . 
6.  S u bject wit h ge nerall y g o o d oral healt h t hat f ulf il all of t he f oll o wi n g: 
a. Ha vi n g n o lesi o ns of t he teet h or oral ca vit y t hat c o ul d i nterfere wit h t he st u d y 
e val uati o ns.  
b.  At least a t otal of 1 1 of t he f aci al s urfaces of m a xillar y a n d ma n di b ular a nt eri or 6 
teet h (t o ot h n u m bers 6-1 1  a n d 2 2 -2 7 ) s uita ble f or per o xi de w hite ni n g a n d 
gra da ble f or VI T A Bleac he d g ui de e val u ati o n wit h n o si g nifica nt defects, calc ul us , 
rest orati o ns, cr o w ns or v e neers t h at c o ul d i m pact t o ot h bleac hi n g perf or ma nce or 
st u d y e val uati o ns as j u d ge d b y t he cli nical e xa mi ner . 
c. a mi ni m u m of 1 6  n at ural teet h.  
4. 3  
E x cl u si o n Crit eri a  
A n i n di vi d ual w h o me ets a n y of t he f oll o wi n g e xcl usi o n criteria will be  e xcl u de d fr o m t h e 
st u d y: 
1.  S u bject w h o is a n e m pl o yee of t he i n vesti gati o nal site, eit her directl y i n v ol ve d i n t he 
c o n d uct of t he st u d y or a me m ber of t h eir i m me diate fa mil y; or a n e m pl o yee of t he 
i n vesti gati o nal site ot her wise s u per vise d b y t he i n vesti gat or; or, a Hal e o n e m pl o yee 
directl y i n v ol ve d i n t he c o n d uct of t he st u d y or a me m ber of t heir i m me diate fa mil y.  
2.  S u bject w h o has partici p ate d i n ot her st u d ies (i ncl u di n g n o n-me dici nal st u dies) i n v ol vi n g 
i n vesti gati o nal pr o d uct(s) wit hi n 6 0 da ys pri or t o st u d y e ntr y a n d/ or d uri n g st u d y 
partici pati o n.  
3.  S u bject wit h, i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d desi g nee, a n ac ute 
or c hr o nic me di cal or ps y c hiatric c o n diti o n or la b orat or y a b n or m alit y t hat ma y i ncreas e 
t he ris k ass ociate d wit h st u d y partici pati o n or i n vesti gati o nal pr o d uct a d mi nistrati o n or 
ma y i nterfere wit h t he i nter pret ati o n of st u d y res ults a n d, i n t he j u d g me nt of t he 
i n vesti gat or or me dicall y q ualifie d desi g nee, w o ul d ma ke t he s u bject i na p pr o priate f or 
e ntr y i nt o t his st u d y.  
4.  S u bject w h o is pre g na nt or i nte n di n g t o bec o me pre g na nt o ver t he d urati o n of t he st u d y or 
w h o is breastfee di n g.  
5.  S u bject wit h k n o w n or s us pecte d i nt olera n ce or h y perse nsiti vit y t o t he st u d y materials 
[i ncl u di n g t he per o xi de w hite ni n g gel ] ( or cl os el 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.  
6.  S u bject w h o, i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d desi g nee, has a 
c o n diti o n t hat w o ul d i m pact o n t heir safet y or well bei n g or affect t heir a bilit y t o 
u n dersta n d a n d f oll o w st u d y pr oce d ures a n d re q uire me nts or w h o s h o ul d n ot partici pate 
i n t he st u d y f or ot her reas o ns. 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 6  of 5 6  
7.  S u bject u n willi n g or u na ble t o c o m pl y wit h t he Lifest yle C o nsi derati o ns  descri be d i n t his 
pr ot oc ol.  
8.  S u bject wit h a rece nt hist or y ( wit hi n t he last year) of alc o h ol or ot her s u bsta nce a b use.  
9.  S u bject wit h gr oss peri o d o ntal disease  or w h o h as ha d treat me nt f or peri o d o ntal disease 
(i ncl u di n g s ur ger y) wit hi n 1 2 m o nt hs of Scree ni n g or w h o has h a d scali n g or r o ot pla n ni n g 
wit hi n 3 m o nt hs of Scree ni n g.  
1 0.  S u bject w h o has ha d a t o o t h bleac hi n g pr oce d ure (eit her pr ofessi o nall y-dis pe nse d or at -
h o me) wit hi n 1 2  m o nt hs of Scree ni n g.  
1 1.  S u bject wit h a fi xe d or re m o va ble partial pr ost hesis, m ulti ple de ntal i m pla nts or ort h o d o ntic 
braces/ b a n ds or fi xe d ret ai ne r or t o g ue/li p pierci n g w hic h, i n t he o pi ni o n of t he i n vesti gat or, 
co ul d i m pact st u d y o utc o mes.  
1 2.  D uri n g t he peri o d fr o m scree ni n g till 2 wee ks p ost c o m pleti o n of t o ot h bleac hi n g, s u bject 
ta ki n g dail y d oses of me dicati o n/treat me nts w hic h, i n t he o pi ni o n of t he i n vesti gat or or 
me dicall y q ualifie d desi g nee, c o ul d i nterfere wit h t heir perce pti o n of t o ot h  se nsiti vit y 
(e xa m ples of s uc h m e dicati o ns i ncl u de a nal gesi cs, a ntic o n v ulsa nts, a nti hista mi nes t hat 
ca use mar k e d or m o derat e se dati o n, se dati ves, tra n q uilizers, a nti de pressa nts, m o o d -alteri n g 
a n d a nti -i nfla m mat or y dr u gs). 
1 3.  S u bject w h o has pre vi o usl y bee n e n r olle d i n t his st u d y. 
1 4.  S u bject w h o has use d a n oral care pr o d u ct i n dicate d f or t he relief of D H or care of 
se nsiti ve teet h wit hi n 8 wee ks of Scree ni n g (s u bjects will be re q uire d t o ver ball y c o nfir m 
t he na me of t heir c urre nt oral care pr o d u cts t o e na ble site staff t o verif y t h e a bse nce of 
k n o w n se nsiti vit y i n gre die nts).  
1 5.  S u bject w h o is ta ki n g dail y d oses of a me dicati o n w hic h, i n t he o pi ni o n of t he i n vesti gat or 
or me dicall y q ualifie d desi g nee, is ca usi n g xer ost o mia.  
1 6.  S u bject w h o has ha d de nt al pr o p h yla xis wit hi n 4 wee ks of Scree ni n g  or w h o re q uires 
a nti bi otic pr o p h yla xis f or de ntal pr oce d ures.  
4. 4  
Lif e st yl e C o n si d er ati o n s  
4. 4. 1  
Or al H y gie ne Restricti o ns  
F or t he D ur ati o n of t he St u d y  
•  S u bjects s h o ul d n ot use a n y oral care pr o d ucts (f or e xa m ple, t o ot h pastes, t o ot h br us hes, 
or al ri nses, t o n g ue cle a ners, 
w hite ni n g/ bleac hi n g pr o d ucts, i nter de nt al clea ni n g 
pr o d ucts , t o ot h se nsiti vit y pr o d ucts) ot her t ha n t h ose pr o vi de d d uri n g t he st u d y. 
4. 4. 2  
Diet ar y a n d Alc o h ol, Restricti o ns  
Bef ore a Cli nic al Assess me nt Visit s: Visits 2-3  
•  S u bjects will a bstai n fr o m eati n g a n d dri n ki n g ( wit h t he e xce pti o n of s mall a m o u nts 
of water re q uir e d f or ta ki n g me dicati o n) f or at le ast 2 h o urs pri or t o a n d d uri n g t heir 
cli nical assess me nt visits.  
•  S u bjects s h o ul d refrai n fr o m e xcessi ve alc o h ol c o ns u m pti o n f or 2 4 h o urs bef ore a st u d y 
visit.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 7  of 5 6  
4. 4. 3  
U s e of C o s m eti c s  
•  Visits 1, 2  &  3:  S u bjects will refrai n fr o m a p pl yi n g li pstic k or c ol ore d li p c o veri n gs  
pri or t o a n d d uri n g t heir cli nical  t o ot h c ol or assess me nt visits . 
4. 4. 4  
T o b a c c o Pr o d u ct R e stri cti o n s  
•  Visit 1 o n w ar ds:  S u bjects will n ot be per mitte d t o use c he wi n g t o bacc o fr o m 
scree ni n g t o t he e n d of t h e st u d y. 
•  Visits 1 -4:  S u bjects will n ot be per mitte d t o s m o ke, va pe or use t o bacc o pr o d ucts 
d uri n g t heir sc he d ule d visits t o t he st u d y site.  
4. 4. 5  
M e di c ati o n a n d Tr e at m e nt  R e stri cti o n s  
•  Visits 1 -4:  S u bjects will be as ke d t o dela y electi v e de ntal treat me nt (f or e x a m ple, 
de ntal pr o p h yla xis) f or t h e d urati o n of t he st u d y. T he y will be re q uir e d t o i nf or m site 
staff of a n y e mer g e nc y tr eat me nt t he y recei ve d uri n g t he st u d y. 
•  Visits  1 -4:  S u bjects will be as ke d t o i nf or m site st aff of c ha n ges t o t heir 
me dicati o ns/treat me nts f or t he d urati o n of t he st u d y. S h o ul d a s u bject c o m me nce a 
c o urse of me di cati o n w hi c h, i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d 
desi g nee, c o ul d i m pact st u d y o utc o mes, t he s u bject ma y be wit h dra w n.   
•  Visits 1 -4:   S u bjects w h o use a d h oc , te m p orar y me dicati o n t o relie ve t o ot h 
se nsiti vit y s h o ul d n ote t his i n t heir t o ot h se nsiti vit y q uesti o n naire.  
5  
S T U D Y P R O C E D U R E S  
All st u d y pr oce d ures f or eac h visit a n d t he or der i n w hic h t he y s h o ul d be perf or me d ( w here 
practicall y feasi ble) s h o ul d be c o m plete d i n acc or da nce wit h T a bl e  5 -1  
S c h e d ul e  
of 
A cti viti e s . 
A d here n ce t o t h e st u d y d esi g n re q uir e me nts, i ncl u di n g all pr oce d ures are esse ntial a n d re q uire d 
f or st u d y c o n d uct.  All pr oce d ures will be c o n d uct e d b y t he I n v esti gat or  (or s uita bl y q ualifie d 
desi g nee ) a n d all i nf or m ati o n a n d data c ollecte d will be d oc u me nte d i n t he C R F .  Cli nical 
e xa mi ner(s) i n v ol ve d i n t he scree ni n g, safet y a n d efficac y assess me nts will be a p pr o priat el y 
q ualifie d de ntal pr ofessi o nals, re gistere d t o pr actice i n Ca na da.  
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 8  of 5 6  
5. 1  
S c h e d ul e of A cti viti e s  
T a bl e  5 -1  
S c h e d ul e of A cti viti e s  
Pr o c e d ur e/ A s s e s s m e nt  
S cr e e ni n g  
St u d y P eri o d  
Vi sit 1  
( D a y 1) 
 
Vi sit 2  
[ st art of 
t o ot h 
bl e a c hi n g]  
( D a y 15 ) 
 
Vi sit 3  
[ c o m pl eti o n 
of t o ot h 
bl e a c hi n g] 
( D a y 2 2 ) 
 
Vi sit 4  
[2 w e e k s p o st 
c o m pl eti o n of 
t o ot h bl e a c hi n g) 
( D a y 3 6 ) 
I nf or m e d c o n s e nt 
X  
1 4 d a y s  ± 2 d a y s  
 
7  d a y s  ( + 1 d a y) 
 
1 4 d a y s  ± 2 d a y  
 
M e di c al hi st or y  
X  
 
 
 
D e m o gr a p hi c s  
X  
 
 
 
C urr e nt/ pri or/ c o n c o mit a nt 
m e di c ati o n r e vi e w  
X  
X  
X  
X  
R e vi e w of pr o d u ct c o m pli a n c e  
 
X  
X  
X  
R et ur n of c o m pl et e d T o ot h 
S e n siti vit y Q u e sti o n n air e s  
 
 
X  
X  
R et ur n st u d y pr o d u ct s  
 
 
 
X  
O S T E x a mi n ati o n  
X  
X  
X  
X  
O H T E x a mi n ati o n  
X  
 
 
X  
A s s e s s m e nt of t o ot h c ol or 2  
X  
X  
X  
 
D H a s s e s s m e nt s ( E A R, M GI, 
t o ot h m o bilit y a n d e v a p or ati v e 
air s e n siti vit y) 6  
X  
 
 
 
R e vi e w of i n cl u si o n/ e x cl u si o n 
crit eri a  
X  
 
 
 
S u bj e ct eli gi bilit y  
X  
 
 
 
S u bj e ct c o m pl et e d t h e 
W hit e ni n g H i st or y q u e sti o n n air e  
at sit e  
 
X  
 
 
S u bj e ct c o m pl et e s  t o ot h 
s e n siti vit y q u e sti o n n air e at sit e  
X  
X  
 
 
S u bj e ct c o m pl et e s t h e P o st -
W hit e ni n g q u e sti o n n air e  at sit e  
 
 
X  
 
S u bj e ct c o m pl et e s t h e D H E Q  at 
sit e 8  
X  
X  
X  
X  
Str atifi c ati o n a n d 
R a n d o mi z ati o n t o tr e at m e nt s 7  
X  
 
 
 
Di s p e n s e st u d y pr o d u ct s  
X  
 
 
 
S u p er vi s e d t o ot h br u s hi n g  
X  
 
 
 
S u bj e ct di s p e n s e d t o ot h 
s e n siti vit y q u e sti o n n air e f or at 
h o m e c o m pl eti o n 3  
 
X  
 
 
S u bj e ct di s p e n s e d t o ot h 
bl e a c hi n g  kit f or at h o m e u s e 
wit h fir st a p pli c ati o n f oll o w e d b y 
t o ot h br u s hi n g at st u d y sit e 
u n d er s u p er vi si o n 4  
 
X  
 
 
A d v er s e e v e nt s r e vi e w 1  
X  
X  
X  
X  
M e di c al d e vi c e i n ci d e nt s r e vi e w
1  
X  
X  
X  
X  
St u d y c o n cl u si o n  
 
 
 
X  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 1 9  of 5 6  
A b bre viati o ns: O S T: Oral S oft Tiss ue, O H T: Oral Har d Tiss ue , D H: De nti ne H y perse nsiti vt y 
F o ot n otes:  
1.  A d verse E ve nts ( A Es), Seri o us A d verse E ve nts ( S A Es) c ollecte d i m me diatel y after s u bject pr o vi des 
c o nse nt t o partici pate i n t he st u d y b y t he c o m pleti o n of t he I nf or me d C o nse nt F or m (I C F).   Me dical de vice 
i n t his st u d y is t he s u p plie d t o ot h br us h a n d me dical de vice i nci de nts  will be rec or de d fr o m first use of a 
me dical de vice . 
2.  T o ot h c ol or assesse d o n t he facial s urfaces of t he a nteri or 6 ma xillar y  a n d ma n di b ular  teet h (t o ot h n u m bers 
6 -1 1  a n d 2 2 -2 7 ) usi n g t he VI T A Bleac he d g ui de 3 D Master. 
3.  T he  t o ot h se nsiti vit y q uesti o n naire will  e val uate  o verall t o ot h se nsiti vit y wit h L M S a n d V A S assess me nts.   
T he q uesti o n naire will be c o m plete d f or t he d urati o n of t o ot h bleac hi n g treat me nt a n d f or 2 wee ks p ost 
c o m pleti o n of t o ot h bleac hi n g.  
4.  T he s u p plie d t o ot h bleac hi n g kit  will be use d o nce u n der s u per visi o n at t he st u d y site a n d t he n o nce per da y 
at h o me (f o r a t otal of 7  da ys) i n acc or da nce wit h t he ma n ufact urer’s i nstr ucti o ns.  
5.  Fe male s u bjects of c hil d -beari n g p ote ntial o nl y.  
6.  D H assess me nts  t o be a d mi nistere d o nl y t o s u bjects wit h self-dia g n ose d D H.  
7.  Stratificati o n will be base d o n cli nicall y -dia g n ose d D H ( Y/ N) at scree ni n g.  
8.  Secti o ns 1 & 2 t o be c o m plete d at V 2.  Secti o n 1 ( q uesti o ns 7 -9 o nl y) a n d Secti o n 2 t o be c o m plete d at 
V 3 & 4.   D H E Q t o be c o m plete d at t he st u d y site.  
6  
S T U D Y P R O C E D U R E S a n d A S S E S S M E N T S  
E ver y eff ort s h o ul d b e ma de t o e ns ure t h at pr ot oc ol -re q uir e d tests a n d pr oce d ures are 
c o m plete d as descri b e d.  H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y be 
circ u msta nces, o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma y ma ke it u nfeasi ble t o c o m plete 
a n assess me nt.  I n t hese cases , t he i n vesti gat or m ust ta ke all ste ps necessar y t o e ns ure t he safet y 
a n d well -bei n g of t he s u bject.  W he n a pr ot oc ol -re q uire d assess me nt ca n n ot be perf or m e d, t he 
i n vesti gat or ( or desi g nee) will d oc u me nt t h e reas o n f or t h e misse d assess me nt as a pr ot oc ol 
d e viati o n a n d a n y c orrecti ve a n d pre ve ntati ve acti o ns t hat he or s he has ta ke n t o e ns ure t h at 
re q uire d pr ocesses are a d here d t o as s o o n as p ossi ble.  T he S p o ns or m ust b e i nf or me d of a n y 
misse d assess me nts i n a ti mel y ma n ner.  
Oral e xa mi nati o ns t o det er mi ne s u bject eli gi bilit y a n d t o m o nit or t he safet y/ perf or ma nce of 
st u d y pr o d ucts will be perf or me d b y a p pr o priat el y trai ne d cli nical e x a mi ner(s), wit h pri or 
rele va nt cli nical e x perie n ce.  Cli nical e xa mi ner(s) will als o be e x peri e nce d i n use of t he Sc hiff 
Se nsiti vit y scale f or deter mi nati o n of t o ot h se nsiti vit y.  
6. 1. 1  
S cr e e ni n g Pr o c e d ur e s  
6. 1. 1. 1  
I nf or m e d C o n s e nt 
T he i n vesti gat or  (or desi g nee ) m ust o btai n i nf or me d c o nse nt fr o m eac h s u bject partici pati n g i n 
t his st u d y after a de q uat e e x pla nati o n of t he ai ms, met h o ds, o bjecti ves, p ote ntial hazar ds of t he 
st u d y a n d t heir ri g hts t o ref use t o e nter t he st u d y or t o wit h dra w fr o m it at a n y ti me.  
I nf or me d c o nse nt m ust b e o btai ne d b ef ore a n y st u d y -s pecific acti vit y is perf or me d. T w o c o pies 
of t he i nf or me d c o nse nt f or m (I C F) will be si g ne d a n d date d b y t he s u bject, a n d t he s u bject 
will be pr o vi de d wit h  o ne c o p y a n d t he ot h er will be ke pt at site.  
If, d uri n g a s u bj ect’s partici pati o n i n t he st u d y, a n y ne w i nf or mati o n b ec o mes a vaila ble t hat 
ma y affect t he s u bject’s willi n g ness t o partici pate  i n t he st u d y, eac h o n g oi n g s u bject s h o ul d 
recei v e a c o p y of t his ne w i nf or mati o n a n d b e re-c o nse nte d i nt o t he st u d y. Eac h s u bject s h o ul d 
be pr o vi de d wit h a c o p y of t he si g ne d a n d dat e d a me n de d c o nse nt f or m.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 0  of 5 6  
6. 1. 1. 2  
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 mat i o n will be c ollecte d:  year of birt h, se x at birt h, race a n d 
et h nicit y. 
6. 1. 1. 3  
I n cl u si o n/ E x cl u si o n Crit eri a 
I n cl usi o n a n d e xcl usi o n criteria as per Secti o n  4. 2  a n d 4. 3 . 
6. 1. 1. 4  
M e di c al Hi st or y a n d Pri or M e di c ati o n/ Tr e at m e nt  
Rele va nt me dical a n d/ or s ur gical hist or y (i n t he last y ear), i ncl u di n g aller gies or dr u g 
se nsiti vit y a n d pri or me dicati o ns/treat me nts, i ncl u di n g prescri pti o n a n d n o n-prescri pti o n dr u gs, 
dietar y s u p ple me nts a n d her bal re me di es, ta ke n i n t he last 2 8  da ys, t hat be ga n bef ore o btai ni n g 
i nf or me d c o nse nt will be rec or de d as t he M e dical Hist or y/ C urre nt Me dical C o n diti o ns. 
6. 1. 1. 5  
S u bj e ct Eli gi bilit y  
T he i n vesti gat or a n d/ or me dicall y q ualifie d desi g nee will re vie w i ncl usi o n/e xcl usi o n criteri a, 
me dical hist or y  a n d pri or me dicati o ns t o c o nfir m s u bject eli gi bilit y t o part ici pate i n t he st u d y.  
6. 1. 2  
E nr oll e d S u bj e ct s a n d S cr e e n  F ail ur e s  
A n e nr olle d s u bject is o ne w h o has a gree d t o partici pate i n t he cli nical st u d y f oll o wi n g 
c o m pleti o n of t he i nf or me d c o nse nt pr ocess directl y or via t heir le gall y a ut h orize d 
re pres e ntati ve a n d s u ccessf ull y met eli gi bilit y criteria t o pr ocee d be y o n d t he scre e ni n g visit . 
Scree n fail ures are defi n e d as s u bjects w h o c o ns e nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y ra nd o mize d.  
T o e ns ure tra ns pare nt re p orti n g of scree n fail ure s u bjects, a mi ni mal set of scree n fail ure 
i nf or mati o n will i ncl u de de m o gra p h y, scree n fail ure details (e. g. , wit h dra wal of c o nse nt), 
eli gi bilit y criteria, a n y pr ot oc ol de viati o ns a n d a n y a d verse e ve nts or i nci d e nts as a p plica ble.  
I n di vi d uals w h o d o n ot meet t he criteri a f or p arti ci pati o n i n t his st u d y (scree n fail ure) ma y n ot 
be  re-s cree ne d. 
6. 2  
S cr e e ni n g A s s e s s m e nt s  
6. 2. 1  
D e nti n e H y p er s e n siti vit y A s s e s s m e nt s  
At Visit 1, pri or t o ra n d o mizati o n, s u bjects wit h a self -re p orte d hist or y of D H s h o ul d u n der g o 
f urt her cli nical assess me nts.  F or a s u bject t o be cli nicall y -dia g n ose d as ha vi n g D H t he y m ust 
ha ve at le ast o ne of t he teet h t h at will be per o xi de ble ac he d  t o meet all of t he f oll o wi n g 
i ncl usi o n criteria a n d n o n e of t he f oll o wi n g e x cl usi o n criteria: 
I n cl usi o n criteria f or a t o ot h t o be c o nsi dere d t o h a ve D H: 
•  T o ot h wit h e x p ose d de nti ne d ue t o facial/cer vi cal er osi o n, a brasi o n or gi n gi val 
recessi o n ( E A R). 
•  T o ot h wit h a n M GI sc ore = 0 directl y a djace nt t o t h e affecte d de nti ne.  
•  T o ot h wit h a cli nical t o ot h m o bilit y sc ore = 0.  
•  T o ot h de m o nstrati n g a p ositi ve res p o nse t o t he e v a p orati ve (air) se n siti vit y 
assess me nt [ defi n e d as t h ose wit h a Sc hiff se nsiti vit y sc ore ≥2].  
E xcl usi o n criteria f or a t o ot h t o be c o nsi dere d t o h a ve D H:  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 1  of 5 6  
•  T o ot h wit h e vi de nce of c urre nt or rece nt cari es or re p orte d tr eat me nt of d eca y.  
•  T o ot h wit h dee p, defecti ve or facial rest orati o ns, f ull cr o w ns or ve n eers.  
•  T o ot h wit h c o ntri b uti n g aeti ol o gies ot her t ha n er osi o n, a brasi o n or recessi o n t o 
e x p ose d de nti ne.  
6. 2. 1. 1  
Er o si o n, A br a si o n a n d R e c e s si o n ( E A R)  
Teet h t hat will be per o xi de bleac h e d a n d t hat e x hi bit n o ne of t he de ntiti o n e xcl usi o n  criteria 
f or t o ot h D H, will be e xa mi ne d f or si g ns of cer vical E A R (A d d y et al., 2 0 0 0 ).  O nl y t eet h t hat 
de m o nstrate si g ns of E A R will be assesse d f urt her f or D H. 
6. 2. 1. 2  
M o difi e d Gi n gi v al I n d e x ( M GI)  
T he M GI is a n o n -i n vasi ve vis ual assess me nt of gi n gi val healt h (L o b e ne, 1 9 8 6 ). M GI will be 
assesse d f or teet h t hat will be per o xi de bleac he d a n d t hat e x hi bit n o ne of t he de ntiti o n e xcl usi o n 
criteria f or t o ot h D H a n d w hic h s h o w si g ns of E A R.  M GI s h o ul d be s c ore d f or t he faci al 
gi n gi va, directl y a djace nt t o t he area of e x p ose d d e nti ne o nl y, as descri be d b el o w.  
 
Sc ore  
Descri pti o n  
0  
A bse nce of i nfla m mati o n  
1  
Mil d i nfla m mati o n; sli g ht c ha n ge i n c ol or , little c ha n ge i n c ol or; little c ha n ge i n te xt ure 
of a n y p orti o n of t he mar gi nal or pa pillar y gi n gi val u nit.  
2  
Mil d i nfla m mati o n; criteria as a b o ve b ut i n v ol vi n g t he e ntire mar gi nal or pa pillar 
gi n gi val u nit.  
3  
M o derate i nfla m mati o n; glazi n g, re d ness, oe de ma, a n d/ or h y pertr o p h y of t he mar gi nal 
or pa pillar y gi n gi val u nit.  
4  
Se vere i nfla m mati o n; mar ke d re d ness, oe de ma a n d/ or h y pertr o p h y of t he mar gi nal or 
pa pillar y gi n gi val u nit, s p o nta ne o us blee di n g, c o n gesti o n, or ulcerati o n.  
6. 2. 1. 3  
Cli ni c al M o bilit y  
Cli nical t o ot h m o bilit y will be assesse d f or teet h t hat will be per o xi de bleac he d a n d t hat e x hi bit 
n o ne of t he de ntiti o n e x cl usi o n criteria f or t o ot h D H, w hic h s h o w si g ns of E A R a n d w hic h 
ha ve a n M GI = 0 dir ectl y a djace nt t o t he e x p os e d de nti ne o nl y, usi n g a m o dificati o n of t he Miller 
I n d e x (Last er et al., 1 9 7 5 ) as descri be d bel o w.  
 
De gree  Descri pti o n  
0  
N o m o ve me nt or m o bilit y of t he cr o w n of t he t o ot h < 0. 2 m m i n a h oriz o ntal directi o n  
1  
M o bilit y of t he cr o w n of t he t o ot h 0. 2 - 1 m m i n a h oriz o ntal directi o n  
2  
M o bilit y of t he cr o w n of t he t o ot h e xcee di n g 1 m m i n a h oriz o ntal directi o n  
3  
M o bilit y of t he cr o w n of t he t o ot h i n a vertical directi o n as well.  
6. 2. 1. 4  
E v a p or ati v e  ( Air) S e n siti vit y A s s e s s m e nt ( S c hiff s e n siti vit y s c or e) 
T he E va p orati ve (air) Se nsiti vit y Assess me nt will be assesse d f or teet h t hat will be per o xi de 
bleac he d a n d t hat e x hi bit n o ne of t he d e ntiti o n e xcl usi o n criteria f or t o ot h D H, w hic h s h o w 
si g ns of E A R, w hic h ha v e a n M GI = 0 directl y a djace nt t o t he e x p ose d de nti ne a n d w hic h h a ve 
cli nical m o bilit y = 0 o nl y.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 2  of 5 6  
T he e xa mi ner will a p pl y a n e v a p orati ve air sti m ul us b y directi n g a m a xi m u m o ne sec o n d 
a p plicati o n of air fr o m a de ntal air s yri n ge t o t he e x p ose d de nti ne s urface fr o m a dista n ce of 
a p pr o xi matel y 1 c m.  T h e s u bject res p o ns e will be sc ore d usi n g t he Sc hiff Se nsiti vit y scale 
i m me diatel y f oll o wi n g t h e e v a p orati ve air sti m ul us.  T he Sc hiff Se nsiti vit y scale  is a n e xa mi ner 
base d i n de x (Sc hiff et al., 1 9 9 4 ) f oc usi n g o n a c o m bi nati o n of s pecific, o bser va ble, p h ysical, 
be ha vi oral  a n d ver bal res p o nses fr o m t he s u bject as a res ult of t he sti m ulati o n of e x p ose d 
de nti ne, rat h er t ha n s ol el y a n oral re q u est fr o m t h e s u bject t o disc o nti n ue sti m ulati o n a n d ma y 
facilitate discri mi nati o n. T he e xa mi ner will i n dicate t he s u bject’s res p o nse t o t he e va p orati ve 
air sti m ul us, after t h e sti m ulati o n of eac h i n di vi d ual t o ot h, usi n g t he Sc hif f Se nsiti vit y scale as 
bel o w.  
 
S c or e  
S u bj e ct R e s p o n s e  
0  
S u bj e ct d o e s n ot r e s p o n d t o air sti m ul ati o n  
1  
S u bj e ct r e s p o n d s t o air sti m ul u s b ut d o e s n ot r e q u e st di s c o nti n u ati o n of sti m ul u s  
2  
S u bj e ct r e s p o n d s t o air sti m ul u s a n d r e q u e st s di s c o nti n u ati o n or m o v e s fr o m sti m ul u s  
3  
S u bj e ct r e s p o n d s t o sti m ul u s, c o n si d er s sti m ul u s t o b e p ai nf ul, a n d r e q u e st s 
di s c o nti n u ati o n of t h e sti m ul u s  
6. 3  
Effi c a c y A s s e s s m e nt s  
T he f oll o wi n g effic ac y assess me nts will be p erf or me d b y a p pr o pri atel y tr ai ne d staff /cli nical 
e xa mi ners, at t h e ti mes a n d i n t he or der defi ne d i n t he Sc he d ule of E ve nts  secti o n of t his 
pr ot oc ol.  
If i n t he o pi ni o n of t he e xa mi ner a s u bject is bet wee n defi ne d gra des/sc ores, a c o nser vati ve 
a p pr oac h s h o ul d be use d t o pr o vi de t he fi n al sc ore.  T h e sa me a p pr oac h s h o ul d be a p plie d 
t hr o u g h o ut t he st u d y t o e ns ure c o nsiste nc y i n t he gra di n g of t he sc ores at all ti me p oi nts.  
6. 3. 1  
T o ot h S e n siti vit y Q u e sti o n n air e  
T he t o ot h se nsiti vit y q uesti o n naire [i ncl u di n g V A S a n d L M S] will be c o m plete d b y t he s u bject 
at t he scree ni n g visit, at Visit 2 ( pri or t o bleac hi n g) t o descri be t he o verall t o ot h se nsiti vit y 
e x perie n ce d b y t he s u bj ect o n t hat d a y .  T he q uesti o n naire s h o ul d t he n b e dis pe nse d t o t he 
s u bject t o c o m plete at h o me, i n t he e ve ni n g, e ver y da y u ntil  t he y c o m plete t he st u d y.   T h us o n 
t he da y of Visit 2 t he s u bject s h o ul d c o m plete 2 q u esti o n naires, o ne at site a n d o ne i n t he h o me.  
T hereafter t h e s u bject s h o ul d c o m plete 1 q uesti o n naire per da y at h o me.  
S u bjects will i n dicate w het her t he y ha v e felt t o ot h  se nsiti vit y d uri n g t he pre vi o us 2 4 h o urs .  
T h ose w h o i n dicate t he y ha ve n ot felt t o ot h se nsiti vit y will n ot be re q uire d t o c o m plete t he rest 
of t he q u esti o n naire.  S u bjects w h o i n dicate t he y di d feel t o ot h se nsiti vit y will c o m plete t h e 
re mai n der of t he q u esti o n naire c o m prisi n g t he V A S, L M S a n d B ot hers o me ness n u merical 
rati n g scale ( N R S). 
S u bjects will rate t heir o verall t o ot h se nsiti vit y usi n g a 1 0 0 m m V A S wit h e n d a nc h ors of ‘ N o 
Se nsiti vit y’ t o ‘ E xtre me Se nsiti vit y’.   
T he L M S a p pl y ps yc h o p h ysical pr oce d u res ( ma g nit u de esti mati o n a n d cr oss-m o dalit y 
ma g nit u de matc hi n g) t o c o n diti o n s pecific des cri pti ve w or ds rele va nt t o t he s u bject’s res p o ns e 
(Gracel y et al., 1 9 7 8 ).  T he descri pti ve w or ds are t he n ali g ne d al o n g a Vis ual A nal o g ue Scale 
( V A S) at dista nces t hat reflect t he ps y c h ol o gical dista nces bet wee n w or ds. T hese scales ha v e 
bee n pil ote d a n d vali date d i n a pre vi o usl y re p orte d de nti ne h y perse nsiti vit y trials (Heat o n et 
al., 2 0 1 3, Mas o n et al., 2 0 1 9 ). T he L M S will be use d t o rate t he i nte nsit y, d urati o n, t olera bilit y 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 3  of 5 6  
a n d descri pti ve q ualit y of t heir t o ot h se nsiti vit y usi n g t h e f o ur i n di vi d ual 1 0 0 milli metre ( m m) 
L M S.  
T he st u d y staff will meas ure t he li ne se g me nt mar ke d -off i n m m fr o m b ott o m t o t o p  al o n g t he 
li ne (f or L M S) a n d fr o m left t o ri g ht (f or t he V A S) a n d rec or d t his i n t he C R F. 
T he s u bject will als o c o m plete a N R S f or b ot hers o me ness f or w hic h t he s u bject s h o ul d circle 
a n a p pr o pri ate n u m ber o n t he scale.  
All q uesti o n naire data s h all be rec or de d i n t he C R F u p o n ret ur n of c o m plet e d q uesti o n naire.  
All q uesti o n naire data s h all be rec or de d i n t he C R F.  
6. 3. 2  
W hit e ni n g Hi st or y a n d P o st -W hit e ni n g Q u e sti o n n air e s  
S u bjects will be dis pe nse d t he W hite ni n g Hist or y a n d P ost -W hite ni n g Q uesti o n naires  t o 
c o m plete at .  S u bjects s h o ul d c o m plete t hese i n di vi d uall y at t he st u d y site wit h o ut refere nce 
t o ot her s u bjects.  Site staff s h o ul d e ns ure t he q u esti o n naires  are c orrectl y c o m plete d b ef ore 
t he s u bject lea ves t h e site. 
6. 3. 3  
D e nti n e H y p er s e n siti vit y E x p eri e n c e Q u e sti o n n air e  ( D H E Q) 
A ‘s h ort f or m’ D H E Q -1 5  will be c o m plete d b y eac h eli gi ble s u bject at Visits 1, 2 ( pri or t o first 
a p plicati o n of t o ot h bleac hi n g), 3 a n d 4. 
T he D H E Q -1 5  is di vi de d i nt o t w o secti o ns - Secti o n 1 as ks q uesti o ns a b o ut ‘ y o ur se nsiti ve 
teet h a n d t he i m pact it has o n y o ur e ver y da y life’; Secti o n 2 as ks q uesti o ns a b o ut ‘t he wa ys i n 
w hic h t he se ns ati o ns i n y o ur teet h affect y o u i n y o ur dail y life’ gr o u pe d i nt o t he f oll o wi n g 
d o mai ns.  
•  Restricti o ns ( Secti o n 2, Q 1 -3)  
•  A da ptati o n ( Secti o n 2, Q 4 -6)  
•  S ocial I m pa ct ( Se cti o n 2, Q 7-9)  
•  E m oti o nal I m pa ct ( Secti o n 2, Q 1 0 -1 2)  
•  I d e ntit y ( Secti o n 2, Q 1 3-1 5)  
At Visit 1  all q uesti o ns will be a ns were d - Secti o n 1 ( Q 1 -9) a n d Secti o n 2 ( Q 1 -1 5)  
A t Visits 2, 3 a n d 4  Secti o n 1 ( Q 7 -9 o nl y) a n d Secti o n 2 ( Q 1 -1 5) will be a ns were d.  
6. 3. 4  
T o ot h S h a d e  ( C ol or) A s s e s s m e nt  
T o ot h s ha de (c ol or) of t he facial s urfaces of t he facial s urfaces of t he a nt eri or 6  ma xillar y a n d 
ma n di b ular teet h (t o ot h n u m bers 6 -1 1  a n d 2 2 -2 7 ) will be assesse d  b y a si n gle , trai ne d cli nical 
e xa mi ner usi n g t he V I T A Bleac he d g ui de 3 D -M A S T E R .  T he arc h t o ot h p ositi o n will be 
parallel t o t he fl o or.   
Assess me nt c o n diti o ns s h o ul d be sta n dar dize d: c ol or c orrect e d li g hti n g i n t he ra n ge of 
5 0 0 0  Kel vi n ; a gre y  bi b will be place d o v er t h e s u bject’s cl ot hi n g ; su bjects will be  as ke d n ot 
t o wear li pstic k; assess me nts will be perf or me d i n t he sa me r o o m ( necess ar y) at a p pr o xi matel y 
t he sa me ti me of da y (if p ossi ble); o utsi de li g ht will be c o ntr olle d b y c o veri n g t he wi n d o ws or 
usi n g a wi n d o wless r o o m.  C ol or deter mi nati o n s h o ul d be ma de wit hi n 5 -7 sec o n ds of starti n g 
a n assess me nt t o a v oi d e ye fati g ue.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 4  of 5 6  
If re q uir e d, t he e xa mi ner will br us h t he s u bject’s a nteri or teet h wit h a wette d t o ot h br us h a n d/ or 
fl oss t o re m o ve a n y de bris w hic h c o ul d i m pact t he acc urac y of t he c ol or assess me nt.  
T h e V I T A Bleac h e d g ui de 3 D -M A S T E R (Para vi n a, 2 0 0 8 ) uses  a val ue-ra n ke d or dere d scale 
fr o m 1 (t he li g htest) t o 2 9 (t he dar kest).  T he s ha de le vel of eac h t o ot h s urface is sc ore d  vis uall y 
b y t he cli nical e xa mi ner wit h refere nce t o t he Bleac he d g ui de.   
A si n gle V I T A Bleac he d g ui de will be use d f or all assess me nts t hr o u g h o u t t he st u d y w here ver 
p ossi ble . 
6. 4  
S af et y a n d Ot h er A s s e s s m e nt s  
T he f oll o wi n g safet y assess me nts will be perf or me d b y a p pr o priatel y tr ai ne d staff/cli nical 
e xa mi ners, at t he ti mes a n d i n t he or der defi ne d i n t he Sc he d ule of Acti vities  of t his pr ot oc ol.   
6. 4. 1  
Or al S oft Ti s s u e ( O S T) E x a mi n ati o n  
T his pr oce d ure will be c o n d ucte d b y a q ualifie d, e x perie nce d cli nical e x a mi ner.  T he O S T 
e xa mi nati o n will be acc o m plis he d b y direct o bser vati o n a n d pal pati o n wit h retracti o n ai ds, as 
a p pr o priate. T he e xa mi nati o n will c o ve r t he oral la bial m uc osa (i ncl u di n g li ps), b uccal m uc osa, 
m uc o gi n gi val f ol ds, gi n gi val m uc osa, har d palat e, s oft palate, t o nsillar area, p har y n geal area, 
t o n g ue, s u bli n g ual area, s u b ma n di b ular area a n d sali var y gla n ds.  Fi n di n gs fr o m t he 
e xa mi nati o n will b e rec or de d i n t h e C R F as eit her n or mal or a b n or mal, wit h details of a n y 
a b n or malities. T he res ults of t he O S T e xa mi nati o n perf or me d at scree ni n g will be use d t o 
deter mi ne s u bject eli gi bilit y. A n y ne w O S T a b n or malit y or w orse ni n g of a pre -e xisti n g 
c o n diti o n  o bser ve d b y t he cli nical e xa mi ner or re p orte d b y t he s u bject after t h e scree ni n g 
e xa mi nati o n will be rec or de d as a n A E.  
W here p ossi ble, t his pr oce d ure s h o ul d be c o n d ucte d b y a si n gle cli nical e xa mi ner.   
6. 4. 2  
Or al H ar d Ti s s u e ( O H T) E x a mi n ati o n  
T his pr oce d ure s h o ul d be c o n d ucte d b y a q u alifie d, e x perie n ce d cli nical e xa mi ner.  T he O H T 
e xa mi nati o n will be acc o m plis he d b y direct o bser vati o n, usi n g retracti o n ai ds as a p pr o priate 
a n d will i de ntif y a n y gr ossl y cari o us lesi o ns, si g ns of er osi ve wear, e na mel irre g ularit ies, t o ot h 
fract ur e, gr oss ge n eralize d de ntal caries d eca y, decalcifi cati o n a n d fa ult y rest or ati o ns. T he 
prese nce of a n y i m pla nts, fi xe d or re m o va ble de nt ures, fi xe d or re m o va ble ort h o d o ntic 
braces/ b a n ds, fi xe d ort h o d o ntic retai ners, f ull cr o w ns or ve neers  will be rec or de d. O bser vati o ns 
will be liste d as eit her a bse nt or prese nt, a n d c o n diti o ns n ote d as prese nt will be descri be d i n 
t he C R F. A n y c ha n ge o bser ve d b y t he cli nical e x a mi ner or re p orte d b y t he s u bject after t he 
scree ni n g e xa mi nati o n will be rec or de d as a n A E . 
T he res ults of t he O H T e xa mi nati o n perf or me d at Scree ni n g will be us e d t o deter mi ne s u bject 
eli gi bilit y.  
W here p ossi ble, t his pr oce d ure s h o ul d be c o n d ucte d b y a si n gle cli nical e xa mi ner.  
7  
I N V E S TI G A TI O N A L/ S T U D Y P R O D U C T S 
F or t he p ur p oses of t his  st u d y, per I nter n ati o nal C o nfere n ce o n Har m o nizati o n (I C H) g ui deli nes, 
a n d Hale o n  p olic y, st u d y i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), 
mar kete d pr o d uct(s), pla ce b o, or me dical de vice(s) i nte n de d t o be a d mi nistere d t o a st u d y 
parti ci pa nt acc or di n g t o t he st u d y pr ot oc ol.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 5  of 5 6  
T his i ncl u des a pr o d uct wit h a mar keti n g a ut h orizati o n w he n use d or asse m ble d (f or m ulate d or 
pac ka g e d) i n a wa y differe nt fr o m t he a p pr o ve d f or m, or w he n use d f or a n u na p pr o ve d 
i n dicati o n, or w he n use d t o gai n f urt her i nf or m ati o n a b o ut a n a p pr o ve d use.  
7. 1  
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
T he f oll o wi n g st u d y pr o d ucts will be s u p plie d b y t he Cli nical S u p plies De part me nt, Hale o n : 
T a bl e 7 -1  
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
 
Test De ntifri ce  
P ositi ve C o ntr ol  
De ntifrice  
Refere nce 
De ntifrice  
Pr o d uct 
Descri pti o n  
De ntifrice c o ntai ni n g 
5 % w/ w N o va Mi n a n d 
1 0 4 0 p p m fl u ori de as 
s o di u m fl u ori de 
De ntifrice c o ntai ni n g 
5 % w/ w K N O 3 a n d 
1 1 5 0 p p m fl u ori de as 
s o di u m fl u ori de 
De ntifrice c o ntai ni n g 
1 1 0 0 p p m fl u ori de as 
s o di u m fl u ori de 
Pr o d uct N a me  
Se ns o d y ne Re pair a n d 
Pr otect Ori gi nal Mi nt  
Se ns o d y ne Fres h 
Mi nt  
Crest Ca vit y 
Pr otecti o n Re g ular  
Pr o d uct M aster 
F or m ul ati o n 
C o de  
C o m mercial pr o d uct –  
Ca na da mar k et place 
 
C o m mercial pr o d uct 
–  Ca na da 
mar ket place 
 
C o m mercial pr o d uct 
–  Ca na da 
mar ket place  
P ac k Desi g n  
Cart o n of o ver wra p p e d t u bes  
Dis pe nsi n g 
Det ails  
De ntifrice kit dis pe nse d at Scree ni n g Visit  
Ret ur n 
Re q uire me nts  
All use d/ u n use d sa m ples t o be ret ur ne d  
D ose/ A p plic ati o n  
S u bjects will d ose t he t o ot h br us h pr o vi de d wit h a stri p of de ntifrice (a 
f ull br us h hea d) o n eac h br us hi n g occasi o n.  S u bjects will br us h f or 
o ne ti me d mi n ute t wice dail y ( m or ni n g  a n d e ve ni n g); s u bjects will be 
per mitte d t o ri nse wit h water p ost -br us hi n g.  
R o ute of 
A d mi nistr ati o n  
Oral t o pical  
T a bl e 7 -2  
S u n dr y It e m s  
S u n dr y Ite ms t o be s u p plie d:  
It e m 
S u p pli e d 
B y  
P a c k D e si g n  
Di s p e n si n g 
D et ail s  
R et ur n/ Di s p o s al D et ail s  
U s e d S a m pl e s  
U n u s e d 
S a m pl e s  
S e n s o d y n e 
S e n siti v e 
C ar e s oft 
bri stl e 
t o ot h br u s h e s 
[ C a n a d a 
M ar k et pl a c e]  
H al e o n  
T wi n P a c k  
O n e  p a c k at 
S cr e e ni n g ( V i sit 1) 
D e str o y at sit e 
u si n g sit e 
di s p o s al 
pr o c e d ur e s  
R et ur n  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 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 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 6  of 5 6  
C o u nt d o w n 
Ti m er  
H al e o n  
I n di vi d u al 
c o m m er ci al 
p a c k  
At S cr e e ni n g ( V i sit 
1)  
T o b e k e pt b y 
s u bj e ct or 
di s p o s e d of.  
R et ur n  
O p al e s c e n c e 
G o 1 5 %  
P er o xi d e Kit  
[ C a n a d a 
M ar k et pl a c e]  
St u d y Sit e  
C o m m er ci al 
p a c k  
Fir st u s e at sit e, 
di s p e n s e d f or at -
h o m e u s e at Vi sit 2  
D e str o y at sit e 
u si n g sit e 
di s p o s al 
pr o c e d ur e s  
D e str o y at 
sit e u si n g 
sit e di s p o s al 
pr o c e d ur e s  
P etr ol e u m 
J ell y  
H al e o n  
C o m m er ci al 
p a c k  
Fir st u s e at sit e, 
di s p e n s e d f or at -
h o m e u s e at V i sit 2 
D e str o y at sit e 
u si n g sit e 
di s p o s al 
pr o c e d ur e s  
R et ur n  
T he t o ot h br us h is a mar kete d me dical de vice a n d will be use d i n acc or da nce wit h t he la bel 
i nstr ucti o ns. 
7. 1. 1  
A p pli c ati o n of t h e P er o xi d e Bl e a c hi n g  
T he per o xi de bleac hi n g s h o ul d be perf or me d at -h o me (e xce pt f or t he first a p plicati o n w hic h 
will be perf or me d u n der s u per visi o n at t he st u d y site).  S u bjects s h o ul d a p pl y t heir per o xi de -
c o ntai ni n g tra y s t o t heir teet h ( b ot h ma xillar y a n d ma n di b ular) o nce pe r da y f or 1 5 ti me d 
mi n utes  i n acc or da n ce wit h t he ma n ufact ur er’s i nstr ucti o ns.  S u bjects s h o ul d t he n br us h t heir 
teet h i n acc or da n ce wit h t he t o ot h br us hi n g i nstr ucti o ns.  S u bjects s h o ul d atte m pt t o perf or m 
t he t o ot h bleac hi n g at t he sa me ti me of da y w herever p ossi ble.  S u bjects s h o ul d perf or m 
per o xi de 
bleac hi n g f or 
7  c o nsec uti ve 
da ys.  
S h o ul d s u bjects 
e x perie n ce 
g u m 
se nsiti vit y/irritati o n d ue t o t he per o xi de, t he y s h o ul d a p pl y a t hi n la yer of t he s u p plie d 
petr ole u m jell y t o t he affecte d g u m tiss ue pri or t o  a p pl yi n g t he per o xi de, ta ki n g care n ot t o 
c o ntact t he teet h wit h t he petr ole u m jell y.  
7. 2  
Pr o d u ct S u p pli e s P r o d u ct S t or a g e, A c c o u nt a bilit y, R et ur n s a n d  
D e str u cti o n  
All st u d y pr o d ucts s u p plie d are f or use o nl y i n t his cli nical st u d y a n d s h o ul d n ot be us e d f or 
a n y ot her p ur p os e.  
G ui da nce will be pr o vi de d t o t he I n v esti gat or a n d site staff f or t he recei pt, st ora g e a n d 
ma na ge me nt of pr o d ucts f or t he d urati o n of t h e tria l b y Hale o n Cli nical S u p plies d uri n g t he 
Site I nitiati o n Visit a n d wit h f urt her i nstr ucti o ns i ncl u de d wit h t he s hi p pi n g d oc u me ntati o n.  
T he site s h o ul d e ns ure t hat t he r o o m or area set asi de f or st ora ge is a ble t o mai ntai n t he c orrect 
te m perat ur e t o meet t he pr o d uct la bel st ora ge c o n diti o ns, is s ufficie nt t o st ore all pr o d u cts a n d 
is sec ure a n d access c o ntr olle d. 
A n y te m perat ure e x c ursi o ns or discre pa ncies d uri n g tra nsit or w hilst st u d y pr o d ucts are st ore d 
at site re q uire t he affecte d pr o d ucts t o b e q u ara nti ne d a n d t his m ust be c o m m u nicate d 
i m me diatel y t o t he S p o ns or w h o will pr o vi de d oc u me ntati o n t o a p pr o ve f urt her usa ge. 
Use of a n y of t he affecte d pr o d uct(s) pri or t o s p o ns or a p pr o val will be c o nsi dere d a pr ot oc ol 
de viati o n.  
St u d y pr o d ucts are t o b e dis pe nse d o nl y t o s u bjects e nr olle d i n t he st u d y i n acc or da nce wit h 
t he pr ot oc ol, b y a ut h orize d  site staff. S u bjects will be i nf or me d o n pr o d uct usa ge, st ora ge, 
ret ur n a n d w h at t o d o i n t he e v e nt of pr o d uct l oss w he n t he y are first dis pe nse d aft er e nr ol me nt. 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 7  of 5 6  
All s t u d y pr o d ucts will b e acc o u nte d f or usi n g t he i n vesti gati o nal/st u d y pr o d uct acc o u nta bilit y 
f or m/rec or d. T he I n vesti gat or is res p o nsi ble f or st u d y pr o d uct acc o u nta bilit y, rec o nciliati o n, 
a n d rec or d mai nte na n ce.   
Detaile d i nstr ucti o ns f or t he ret ur n of st u d y pr o d uct/st u d y s u p plies will be pr o vi de d b y Hale o n 
d uri n g t he st u d y i n ti me f or st u d y cl ose o ut. I n v esti gati o nal pr o d ucts ca n o nl y be destr o ye d at 
site i n a gree me nt wit h a n d after a p pr o val fr o m t he S p o ns or. 
7. 3  
Bli n di n g a n d R a n d o mi z ati o n  
S u bjects will be ra n d o mize d i nt o t he st u d y pr o vi d e d t he y ha v e satisfie d all s u bject selecti o n 
criteria.  
S u bjects will  be  ra n d o mize d t o o ne of t he st u d y pr o d ucts wit h  a 1: 1: 1 all ocati o n rati o usi n g a n 
I nteracti ve Res p o nse Tec h n ol o g y (I R T). T he ra n d o mizati o n sc he d ule will use a  stratifie d 
ra n d o ml y per m ute d bl oc k desi g n. Stratif icati o n will be base d o n t h e cli nicall y  dia g n os is of D H  
at -Scree ni n g ( Yes/ N o).   A p pr o xi matel y 4 5 % ( 4 0-5 0 %) of ra n d o mize d s u bjects s h o ul d ha ve 
cli nicall y-c o nfir me d D H.  
St u d y pr o d ucts  will be pr o vi de d t o s u bjects i n i n di vi d ual pac ks (cart o ns); eac h cart o n will 
c o ntai n o ver wra p pe d  t u b es of st u d y pr o d uct . T he cart o n a n d t u bes of st u d y pr o d uct will be 
la belle d wit h t he sa me u ni q ue c o ntai ner n u m ber. S u bjects will be assi g ne d t o c o nt ai ner 
n u m bers ass ociate d wit h cart o ns c o ntai ni n g o nl y t heir ra n d o mize d st u d y pr o d uct  usi n g a n 
I nteracti ve Res p o nse Tec h n ol o g y (I R T); pr o d uct c o des will n ot be use d. 
Ret ur ne d st u d y pr o d ucts s h o ul d n ot be re -dis pe nse d t o a n y s u bject.  
T his st u d y is descri be d as e xa mi ner-bli n d (t he cli nical e xa mi ner will be bli n de d t o t he pr o d uct 
recei v e d).  
T o e ns ur e t he e x a mi ner re mai ns bli n de d t hr o u g h o ut t he st u d y, staff i n v ol ve d i n t he pre p arati o n 
a n d dis pe nsi n g of st u d y pr o d ucts will w or k i n a se parate area.  
S u bjects will be i ns tr ucte d n ot t o re m o ve st u d y pr o d ucts fr o m t he o pa q ue ba gs pr o vi de d/cart o ns 
o utsi de of t he dis pe nsi n g r o o m, w hile at t he st u d y site. Dis pe nsi n g staff will n ot be i n v ol ve d i n 
a n y effi cac y/safet y ass ess me nt pr oce d ures d uri n g t he st u d y.   
Site staff, st u d y sta tisticia n(s), data ma na g e me nt staff a n d ot her e m pl o yees of t he s p o ns or a n d 
ve n d ors acti n g o n be h alf of t he s p o ns or, w h o ma y i nfl ue nce st u d y o ut c o mes will be bli n de d t o 
t he pr o d uct all ocati o n. 
7. 4  
Br e a ki n g t h e Bli n d  
At t he i nitiati o n of t he st u d y, t he st u d y sit e will b e i nstr ucte d o n t he met h o d f or brea ki n g t h e 
bli n d.  T he met h o d will be a n ele ctr o nic pr ocess.  
T he ele ctr o nic s yste m will be pr o gra m me d wit h bli n d -brea ki n g i nstr ucti o ns. I n cas e of a n 
e mer ge n c y, t he i n vesti gat or has t h e s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g of a 
s u bject’s pr o d uct assi g n me nt is warra nte d. S u bject safet y m ust al w a ys be t he first c o nsi d erati o n 
i n ma ki n g s uc h a deter mi nati o n. If t he i n vesti gat or deci des t h at u n bli n di n g is warra nte d, t he 
i n vesti gat or s h o ul d ma ke e ver y eff ort to c o ntact t he s p o ns or pri or t o u n bli n di n g a s u bject’s 
pr o d uct assi g n me nt u nless t his c o ul d dela y e mer ge nc y treat me nt of t h e s u bject.  
If a s u bject’s pr o d uct assi g n me nt is u n bli n de d, t he s p o ns or m ust be n otifi e d wit hi n 2 4 h o urs 
after brea ki n g t he bli n d. T he date a n d reas o n t hat t he bli n d was br o ke n m ust be rec or de d i n t he 
s o urce d oc u m e ntati o n a n d case re p ort f or m, as a p plica ble. 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 8  of 5 6  
8  
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  
8. 1  
S a m pl e Si z e D et er mi n ati o n  
N o f or mal sa m ple siz e calc ulati o n was p erf or m e d  f or t his st u d y. T he sa m pl e size re q uir e me nt 
of a p pr o xi matel y 3 0 ra n d o mize d s u bjects per ar m is base d o n feasi bilit y d ue t o t he e x pl orat or y 
( pr o of-of -pri nci pal) nat ure of t he st u d y, w hilst e ns uri n g a n a d e q uate n u m ber of s u bj ects t o 
a d dress t he st u d y o bjecti ves  (Kieser a n d Wass mer, 1 9 9 6 ). 
8. 2  
P o p ul ati o n s  f or A n al y si s 
•  T he Safet y p o p ulati o n will c o m pri se all ra n d o mize d s u bjects w h o recei ve at least o ne 
d ose of t he st u d y pr o d uct. T his p o p ulati o n will be base d o n t he pr o d u ct t he s u bject 
act uall y recei ve d.  
•  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 ra n d o mize d s u bjects 
w h o c o m plete at l east o ne use of st u d y pr o d uct a n d ha ve at least o ne V A S sc ore f or t o ot h 
se nsiti vit y rec or de d d uri n g t he t o ot h-bleac hi n g peri o d . T his p o p ulati o n will be base d o n 
t he st u d y pr o d uct t o w hic h t he s u bject was ra n d o mize d. A n y s u bject w h o recei ves a 
ra n d o mizati o n n u m ber will be c o nsi dere d t o ha ve bee n ra n d o mize d.  
•  T he Per -Pr ot oc ol ( P P) p o p ulati o n will i ncl u de all ra n d o mize d s u bjects w h o d o n ot ha ve 
a n y pr ot oc ol de viati o ns t hat c o ul d c o nf o u n d t he i nter pretati o n of a nal yses c o n d ucte d o n 
t he mI T T. 
8. 2. 1  
E x cl u si o n s of D at a f r o m A n al y si s 
E xcl usi o n of a n y dat a fr o m t he a nal yses will be a gree d d uri n g a Bli n de d Data Re vie w ( B D R) 
Meeti n g pri or t o d ata base l oc k. A n y reas o ns f or e xcl usi o n of a s u bj ect fr o m a n a nal ysis 
p o p ulati o n or data fr o m a n a nal ysis will be liste d, if a p plica ble . 
8. 3  
St ati sti c al A n al y s e s  
T his secti o n descri bes  t he pla n ne d statistical a nal ys es of t he st u d y e n d p oi nts.   A n y a me n d me nts 
or clarificati o ns t o t he details here 
will be d oc u me nte d i n t he bli n de d data re vie w 
d oc u me ntati o n pri or t o d ata base l oc k a n d u n bli n di n g.  
Cate g orical v aria bles will be s u m mariz e d b y t he n u m ber a n d p erce nta ge of s u bjects wit h eac h 
rele va nt c haracteristic i n eac h st u d y pr o d uct  gr o u p. C o nti n u o us varia bles will be s u m marize d 
b y mea n, sta n dar d d e viati o n ( S D), st a n dar d err or ( S E), me dia n, mi ni m u m a n d ma xi m u m val ues 
i n eac h st u d y pr o d uct  gr o u p. T he n u m b er of missi n g a n d n o n -missi n g data will als o b e 
prese nte d.  
8. 3. 1  
Pri m ar y E n d p oi nt A n al y si s  
T he m o difie d I nte nt -t o-Treat ( mI T T) p o p ulati o n will be use d f or t he pri m ar y a nal ys es.  
T he pri mar y e n d p oi nts  are:  
•  Dail y  V A S sc ore s c ollect e d t hr o u g h t he st u d y  
•  Dail y  L M S sc ores c ollect e d t hr o u g h t he st u d y  
•  Dail y B ot hers o me ness sc ores c ollect e d t hr o u g h t he st u d y  
•  Dail y n u m ber a n d % of s u bjects wit h a  t o ot h se nsiti vit y-free da y t hr ou g h t h e st u d y  
•  Dail y n u m ber a n d % of s u bjects wit h a nal gesic us e d t o alle viate t o ot h se nsiti vit y t hr o u g h 
t he st u d y 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 2 9  of 5 6  
Eac h e n d p oi nt will be s u m marize d descri pti vel y  at Scree ni n g  a n d Visit 2 ( pre-bleac hi n g) as 
well as b y eac h rel ati ve d a y  wit hi n t he t o ot h bleac hi n g  a n d p ost -t o ot h bleac hi n g  peri o d .  
D a ys wit hi n t he t o ot h-bleac hi n g peri o d will be relati ve t o t he Visit 2  [at h o me] res ult ( da y 1) 
u p t o a n d i ncl u di n g t he res ult rec or de d o n t he da y pri or t o  Visit 3 . Da ys wit hi n t he p ost -t o ot h 
b leac hi n g peri o d wil l be relati ve t o t he res ult f oll o wi n g Visit 3  (at h o me) ( da y 1) a n d i ncl u de  
a n y res ults u p t o a n d i ncl u di n g t he da y of Visit 4 . T he dail y mea n ( ± S E) pr ofiles  of V A S, L M S 
a n d B ot hers o me ness s c ores  acr oss t he st u d y  (clearl y de n ot i n g eac h peri o d) will be pl otte d b y 
st u d y pr o d uct gr o u p.  
8. 3. 2  
S e c o n d ar y  E n d p oi nt  A n al y s e s  
T he V A S s c ore f or t o ot h se nsiti vit y  f or t he first 7 da y s d uri n g t he t o ot h  bl eac hi n g p eri o d  will 
be a nal yz e d usi n g a Mi xe d M o del wit h Re peate d Meas ures (M M R M ), wit h st u d y pr o d uct, D H 
dia g n osis at scree ni n g ( yes/ n o),  da y s of bleac hi n g a n d st u d y pr o d uct b y da ys of bleac hi n g  
i nteracti o n as fi xe d effects.  T he V A S sc ore at scree ni n g will  als o  be i n cl u de d as a c o variate. 
S u bject will be i ncl u de d as a re peat e d meas ure wit h co m p o u n d sy m metr y c o varia nce str uct ure . 
Ke n war d R o gers de grees of free d o m a p pr oac h will be a p plie d (Ke n war d a n d R o ger, 1 9 9 7 ). 
T he o verall (acr oss all da ys) least s q uare mea ns (wit h S E a n d 9 5 % c o nfi de nce i nter vals [ CI]) 
f or eac h st u d y pr o d uct will be prese nte d  al o n g wit h t he differ e nce ( wit h S E a n d 9 5 % CI ).  
A se parate M M R M  will be a p plie d  t o e val uate t he pair wise differe nces bet wee n pr o d ucts f or 
eac h d a y . T his will be i de ntical t o t he a b o ve M M R M  b ut s u bject will be i ncl u de d as a re peate d 
meas ure wit h u nstr uct ur e d c o varia nce matri x.  I n case of c o n ver ge nce iss ues, t he T oe plitz , 
A ut ore gressi ve ( 1), C o m p o u n d S y m metr y c o varia nce str uct ur es 
will be a p plie d u ntil 
c o n ver ge n ce is attai ne d (all heter o ge ne o us v ersi o ns first a n d t he n t he sa me se q ue nce of 
h o m o ge ne o us versi o ns). T he least s q uare mea ns ( wit h S E a n d 9 5 % CI) f or eac h st u d y pr o d uct 
will be prese nte d al o n g wit h t he pair wise differe nces ( wit h S E a n d 9 5 % CI) bet w ee n pr o d ucts 
f or eac h da y usi n g t he a p pr o priate c o ntr asts fr o m t he M M R M res ults. 
As a f urt her se nsiti vit y a nal ysis, t he mea n V A S sc ore f or t o ot h se nsiti vit y  o ver  t he t o ot h-
bleac hi n g peri o d ( Visit 2 [at h o me] t o Visit 3) f or a s u bject will be a nal yze d usi n g an A nal ysis 
of C o varia nce ( A N C O V A) m o del  will be use d wit h st u d y pr o d uct  a n d D H dia g n osis at 
scree ni n g ( yes/ n o) as fi x ed effects  a n d the V A S sc ore at scree ni n g as a c o variate . T he least 
s q uare mea ns ( wit h S E a n d 9 5 % CI) f or eac h st u d y pr o d uct will be prese nte d al o n g wit h t he 
differe n ce ( wit h S E a n d 9 5 % CI).  
T he  L M S a n d t he B ot here ds o me ness sc ore s d uri n g t he t o ot h -bleac hi n g  peri o d will be a nal yze d 
a n d prese nte d i n i de ntical fas hi o n t o t he V A S sc ores e n d p oi nt usi n g t he sa me M M R M s a n d 
A N C O V A  (re placi n g t he res pecti ve s cree ni n g res ult as a c o vari ate ).  
F or th e %  t o ot h se nsiti vit y-free da ys a n d t h e % da ys a nal gesi cs use d t o alle viate t o ot h 
se nsiti vit y d uri n g t he t o ot h bleac hi n g peri o d, a ne gati ve bi n o mial m o del will be a p plie d t o t he 
n u m ber of d a ys wit h t he e ve nt. St u d y pr o d uct a n d D H dia g n osis at s cree ni n g ( yes/ n o ) will be 
fitte d as fi xe d effects. A n offset varia ble f or t he n u m ber of da ys t he dail y q uesti o n relate d t o 
t o ot h se nsiti vit y ( Yes/ N o) was c o m plete d d uri n g t he t o ot h bleac hi n g peri o d will be i ncl u de d t o 
a dj ust f or missi n g da ys i n esti mati n g t he rates. T he b ac k tra nsf or me d rates f or eac h st u d y 
pr o d uct gr o u p a n d rati os bet wee n rates will be prese nte d al o n g wit h 9 5 % CIs.  
Eac h a n al ysis assessi n g t o ot h se nsiti vit y d uri n g t he t o ot h  bleac hi n g peri o d will als o be a p plie d 
t o t he sa me t o ot h se nsiti vit y e n d p oi nts d uri ng t he p ost -t o ot h bleac hi n g peri o d.  
T he t o ot h se nsiti vit y sc ores at Visit 2 ( pri or t o bleac hi n g) will n ot be i ncl u de d i n t he a nal ys es 
as a c o variate  beca use it is e x pecte d t hat t he ra n d o mize d pr o d uct gr o u p at S cree ni n g will ha ve 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 0  of 5 6  
a ca us al effect o n t his o utc o me. L o w t o ot h se nsiti vit y f oll o wi n g t o ot h bleac hi n g s h o ul d n ot be 
a dj uste d i n t he a nal ysis f or l o w t o ot h se nsiti vit y at Visit 2, as t his c o ul d b e l o wer i n g e neral f or 
s u bjects ra n d o mize d t o test a n d refere n ce de ntifrice gr o u ps at Visit 1.  
A n A N C O V A m o del will be a p plie d t o a nal yze t he cha n g e i n t he m ea n VI T A  S ha d e s c ore 
fr o m pre- t o p ost-t o ot h bleac hi n g ( Visit 2-3)  wit h st u d y pr o d uct as a fi xe d effect a n d t he mea n 
VI T A -S ha d e c ol or  sc ore at scree ni n g fitte d as a c o variate . T h e least s q uare mea ns ( wit h S E 
a nd 9 5 % CI) f or eac h st u d y pr o d uct will be prese nte d al o n g wit h t he differe nce ( wit h S E a n d 
9 5 % CI) . 
T he ass u m pti o n of n or malit y a n d h o m o ge neit y of varia nce i n eac h  para metric test a p plie d  (i.e. 
A N C O V A / M M R M) will be i n vesti gate d. I n case of vi olati o n of t hese ass u m pti o ns, a s uita ble 
n o n -para m etric test will be perf or me d, a n d res ults will be pr o vi de d t o s u p p ort t he para metri c  
res ults. 
8. 3. 3  
E x pl or at or y A n al y s e s  
Res p o nses t o t he P ost  w hite ni n g q uesti o n naire  (se parate q uesti o ns a n d t otal sc ore) will 
anal yze d b et wee n pr o d uct gr o u ps usi n g a n i n de pe n de nt t -test. 
T he c ha n g e fr o m  scree ni n g i n D H E Q t otal a n d d o mai n sc ores at Visit 3  a n d Visit 4  will be 
a nal yze d bet w ee n gr o u ps usi n g se parate A N C O V A m o del s wit h st u d y pr o d uct as a fi x e d effect 
a n d t he res p ecti v e D H E Q t otal or d o mai n sc ore at scree ni n g  as a c o v ariate . T he least s q uare 
mea ns ( wit h S E a n d 9 5 % CI) f or eac h st u d y pr o d uct will be prese nte d al o n g wit h t he differe n ce 
( wit h S E a n d 9 5 % CI).  
All t o ot h -se nsiti vit y e n d p oi nts will be s u m marize d f urt her, s plit b y t he w het her t he s u bject ha d 
c o nfir me d D H at t he scree ni n g assess me nt. A d diti o nal statistical testi n g ma y be perf or me d 
usi n g si milar met h o ds t o t h ose perf or m e d o n t he f ull mI T T datas et.  
8. 3. 4  
S af et y A n al y s e s  
T he Safet y p o p ulati o n will be use d f or safet y a nal yses. Safet y a nal yses will be p rese nte d b y 
st u d y pr o d uct gr o u p (a n d o verall) acc or di n g t o st u d y pr o d uct recei ve d.  
Safet y a nal yses will f oc us o n:  
•  E x p os ure a n d c o m plia nce wit h st u d y pr o d ucts  
•  A d verse E v e nts ( A Es)  
All A Es will be re vie we d b y t he safet y e x a mi ner or PI t o cate g orize t he m as Oral/ N o n-Oral. 
A Es will be re g ar de d as ‘treat me nt’ e mer ge nt if t he y occ ur o n or after t he first use of st u d y 
pr o d uct at t he Scree ni n g  visit.  
T he f oll o wi n g safet y s u m maries ( n u m ber of disti nct A Es a n d fre q ue nc y/ pr o p orti o n of s u bjects 
affecte d will be prese nte d b y st u d y pr o d uct gr o u p a n d o verall:  
•  Treat me nt E mer g e nt A Es  ( T E A Es) 
•  Oral T E A Es  
•  N o n -Oral T E A Es  
•  Treat me nt e mer ge nt treat me nt relate d A Es  
•  Oral Treat me nt e mer ge nt treat me nt relat e d A Es 
•  Oral Treat me nt e mer ge nt bleac hi n g  rel ate d A Es 
•  Seri o us A Es  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 1  of 5 6  
•  Seri o us T E A Es  
•  Treat me nt e mer ge nt treat me nt relate d seri o us A Es  
•  Me dical de vice i nci de nts  
A listi n g of all A Es will be prese nt e d f or all s u bjects i n t he Safet y p o p ulati o n.  
8. 3. 5  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
De m o gra p hic d ata will be s u m marize d d escri pti vel y  b y st u d y pr o d uct gr o u p a n d o verall . 
8. 3. 6  
St u d y Pr o d u ct C o m pli a n c e a n d U s e of Ot h er T h er a pi e s  
8. 3. 6. 1  
St u d y Pr o d u ct C o m pli a n c e  
T he n u m ber a n d perce nta ge of s u bjects w h o are n ot c o m plia nt wit h st u d y pr o d uct  usa ge 
i nstr ucti o ns, as rec or de d at eac h st u d y visit, will b e s u m marize d usi n g des cri pti ve statistics at 
eac h st u d y visit (a n d a n y n o n -c o m plia nce o verall). T he perce nta ge will be base d o n s u bjects 
w h o atte n de d eac h visit.  
8. 3. 6. 2  
Ot h er T h er a p y  
N u m ber of bleac hi n g occ urre n ces, bleac hi n g c o m plia nce ( %), n u m ber of misse d/a d diti o nal 
bleac hi n g oc c urre nces will be s u m marize d usi n g descri pti ve statistics b y c u m ulati ve visit.  
8. 3. 7  
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 will be liste d o nl y.  
8. 3. 8  
H a n dli n g of Dr o p o ut s a n d Mi s si n g D at a  
T he use of 
M M R M a nal yses acc o u nt f or missi n g data ass u mi n g a missi n g at ra n d o m 
ass u m pti o n, i.e., t here is a s yste matic rel ati o ns hi p bet wee n t he pr o pe nsit y of missi n g val ues 
a n d t he o bser ve d data, b ut n ot t he missi n g data.  
It is t heref ore ass u me d t hat a s ubject wit h missi n g data w o ul d ha ve o btai ne d a si milar efficac y 
res ult c o m pare d t o a s u bj ect usi n g t he sa me st u d y pr o d uct wit h si milar n o n-missi n g res ults at 
ot her ti me p oi nts ( scree ni n g a n d p ost -scree ni n g). Se nsiti vit y a nal yses ma y be a d de d t o t he S A P 
pri or  t o u n bli n di n g i n case of hi g h rates of missi n g dail y q uesti o n naire  dat a, dr o p -o ut s a n d/ or 
e xcl usi o n fr o m P P p o p ulati o n.  
8. 3. 9  
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.  
9  
A P P E N DI C E S  
9. 1  
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  
T he i n vesti gat or a n d a n y q ualifie d d esi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
re p orti n g e v e nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble f or f oll o wi n g 
u p A Es t hat are seri o us, c o nsi dere d rel ate d t o t he st u d y pr o d uct  or t he st u d y, or t hat ca use d t he 
s u bject t o disc o nti n ue t he st u d y pr o d uct or st u d y. 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 2  of 5 6  
9. 1. 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 n ce i n a cli nical st u d y s u bject, te m p orall y ass ociate d 
wit h t he use of a st u d y pr o d uct i ncl u di n g a n y w as h o ut or lea d -i n pr o d uct ( or me dical de vice), 
w het her or n ot c o nsi dere d relate d t o t he st u d y pr o d uct, i ncl u di n g a n y was h o ut or lea d -i n 
pr o d uct ( or me dical de vi ce).  
N O T E: A n A E ca n t h eref ore b e a n y u nfa v ora bl e 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 borat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he 
use of a st u d y pr o d uct i n cl u di n g a n y was h o ut or l ea d -i n pr o d u ct ( or me dical de vice). 
E ve nts Meeti n g  t he A E Defi niti o n:   
•  A n y a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or uri nal ysis) 
or ot her safet y assess 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 hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y si g nifica nt i n t he 
me dical a n d scie ntific j u d g me nt of t he i n vesti g at or (i.e., n ot relat e d t o pr o gressi o n of 
u n derl yi n g disease).  
•  E xacer bati o n of a c hr o ni c 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 detect e d or dia g n ose d after st u d y pr o d uct a d mi nistrati o n e ve n t h o u g h 
it ma y ha ve bee n prese nt bef ore t h e start of t he st u d y. 
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.  
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y 
pr o d u ct or a c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p ort e d as a n 
A E/ S A E u nless it is a n i nte nti o nal o ver d ose ta ke n wit h p ossi ble s uici dal/self -har mi n g 
i nte nt. S uc h o ver d oses s h o ul d be re p orte d re gar dless of se q uelae. 
•  " Lac k of effic ac y" or "f ail ure of e x p ecte d p har mac ol o gical acti o n" per se will n ot be 
re p orte d as a n A E. S uc h i nsta nces will be ca pt ure d i n t he efficac y ass ess me nts. 
H o we ver, t he si g ns, s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of 
effic ac y will be re p orte d as A E if t he y f ulfill t he defi niti o n of a n A E.  
E ve nts N O T  meeti n g t he A E defi niti o n:  
•  A n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs (if a p plica ble) or ot her 
a b n or mal safet y assess m e nts w hic h are ass ociat e d wit h t he u n derl yi n g disease, u nless 
j u d ge d b y t he i n vesti gat or t o be m ore se v ere t h a n e x pecte d f or t he s u bject’s 
c o n diti o n.  
•  T he disease/ dis or der bei n g st u die d or e x pect e 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 pect e d f or t h e s u bject’s 
c o n diti o n.  
•  Me di cal or s ur gic al pr oce d ure (e. g. e n d osc o p y, a p pe n dect o m y) is n ot t he 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 n ce di d n ot occ 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-d a y fl uct uati o ns of pre -e xisti n g disease(s) or c o n diti o n(s) prese nt 
or detecte d at t he start of t he st u d y t hat d o n ot w orse n.  
9. 1. 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 v e nt w here t he a d v erse 
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 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 3  of 5 6  
e ve n if s eri o us c o n diti o ns are met (e. g. h os pitalizati o n f or si g ns/s y m pt o ms of t he dise ase 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 war d me dical occ urre nce at a n y d ose t h at:  
•  Res ults i n de at h  
•  Is life- t hre ate ni n g  
▪ T he ter m 'life -t hr eate ni n g' i n t he defi niti o n of 'seri o us' refers t o a n e v e nt i n w hic h 
t he s u bject was at ris k of deat h at t he ti me of t he e ve nt. It d o es n ot refer t o a n 
e ve nt, w hic h h y p ot heticall y mi g ht ha ve ca 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 g e neral, h os pitalizati o n si g nifies t hat t he s u bject has bee n detai n e 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 g e nc y war d f or 
o bser vati o n a n d/ or tr eat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he 
p h ysicia n’s offic e or o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g 
h os pita lizati 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 seri o us. W he n i n d o u bt as t o w het her 
“ h os pitalizati o n” occ urre d, or was necessar y, t he A E s h o ul d be c o nsi dere d 
seri o us. 
▪ H os pitalizati o n f or el ecti ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot 
w orse n fr o m b aseli ne is n ot c o nsi dere d a n A E.  
•  Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y  
▪ T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct 
n or mal li fe 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 n ces of relati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea dac he, n a 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 nterfere wit h or 
pre ve nt e v er y da y life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n  
•  Res ults i n c o n ge nit al a n o m al y/ birt h defect  
•  Ot her sit u ati o ns:  
▪ Me dical or scie ntifi c j u d g me nt s h o ul d be e xercise d i n deci di n g w het her S A E 
re p orti n g is a p pr o priat e i n ot her sit uati o ns s uc h as i m p orta nt me dical e ve nts t hat 
ma y n ot be i m me diatel y life -t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut 
ma y je o par dize t he s u bject or ma y re q uir e me dical or s ur gical i nter ve nti o n t o 
pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve def i niti o n. T hese e v e nts 
s h o ul d us uall y be c o nsi dere d seri o us. 
▪ E xa m ples of s uc h e v e nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve 
treat 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 nc y or dr u g a b use.  
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. 
9. 1. 3  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E I nf or m ati o n  
All A Es, a n d t heref ore all S A Es will be c ollecte d i m me diatel y after a s u bject pr o vi des c o nse nt 
t o partici pate i n t he st u d y b y t he c o m pleti o n (si g nat ure) of t he I C F a n d u ntil 5 da ys f oll o wi n g 
last a d mi nistrati o n of t he st u d y pr o d uct ( or last pr oce d ure).  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 4  of 5 6  
Me dical occ urre nces t hat be ga n bef ore o btai ni n g i nf or me d c o nse nt  will be rec or de d i n t he 
Me dical Hist or y/ C urre nt Me dical C o n diti o ns  secti o n of t he C R F n ot t he A E secti o n. 
Details rec or de d b y t he s u bject o n a diar y or si milar d oc u me nt t h at meet t he defi niti o n of a n 
A E m ust als o be disc usse d wit h t he s u bjects a n d tra nscr i be d i n t he A E s ecti o n of t he C R F.  
All S A Es will be rec or de d a n d re p orte d t o t he s p o ns or or d esi g nee i m me diatel y a n d u n der n o 
circ u msta nce s h o ul d t his e xcee d 2 4 h o urs. T he i n v esti gat or will s u b mit a n y u p date d S A E data 
t o t he s p o ns or wit hi n 2 4 h o urs of it bei n g a vaila bl e . 
I n v esti gat ors are n ot o bli gate d t o acti vel y see k A Es or S A Es after t he c o n cl usi o n of t he st u d y 
partici pati o n . H o we ver, if t he i n vesti gat or lear ns of a n y S A E, i ncl u di n g a deat h, at an y ti me 
after a s u bject h as bee n disc har ge d fr o m t he st u d y , a n d he/s he c o nsi ders t he e v e 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 i n vesti gat or m ust pr o m ptl y 
n otif y t he s p o ns or.  
9. 1. 4  
R e p orti n g Pr o c e d ur e s  
T he i n vesti gat or a n d a n y desi g nees are res p o nsi bl e f or detecti n g, d oc u me nti n g a n d  re p orti n g 
e ve nts t hat meet t he d efi niti o n of a n A E a n d re m ai n res p o nsi ble f or f oll o wi n g u p o n A Es t hat 
are s eri o us, c o nsi dere d relate d t o t he st u d y pr o d uct(s), partici pati o n i n t h e st u d y, or a st u d y 
pr oce d ure, or t hat c a use d t he s u bject t o disc o nti n ue t he  st u d y pr o d uct or st u d y.  
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o 
n o n -lea di n g s uc h as “ H o w d o y o u feel” will be assesse d a n d a n y A E’s rec or de d i n t he C R F a n d 
re p orte d a p pr o priat el y. 
T he i n vesti gat or ( or m e dicall y q ualifie d desi g nee) is t o re p ort all directl y o bser ve d A Es a n d all 
A Es s p o nta ne o usl y re p orte d b y t he st u d y s u bject. I n a d diti o n, eac h st u d y s u bject will be 
q uesti o ne d a b o ut A Es.  
Eac h A E is t o be assess e d t o deter mi ne if it meets t he criteria f or a S A E.  If a n S A E o cc urs, 
e x pe dite d re p orti n g will f oll o w l ocal a n d i nter nati o nal re g ulati o ns, as a p pr o priate.  
W he n a n A E o cc urs, it is t he res p o nsi bilit y of t he i n vesti gat or ( or me dicall y q ualifie d desi g nee) 
t o re vie w all d oc u me ntati o n (e. g. h os pital pr o gress n otes, la b orat or y, a n d dia g n ostics re p orts) 
relate d t o t he e v e nt. 
T he i n vesti gat or or site staff will t he n rec or d all rele va nt i nf or mati o n re gar di n g a n A E i n t he 
C R F a n d all details relati n g t o a n S A E i n t he pa per S A E F or m pr o vi de d.  
It is n ot  acce pta ble f or t he i n vesti gat or ( or me dicall y q ualifie d desi g ne e) t o se n d p h ot oc o pies 
of t he s u bject’s me dical rec or ds t o Hale o n i n lie u of c o m pleti o n of t h e A E C R F pa ge/ S A E f or m. 
T here ma y b e i nsta nces w he n c o pi es of me dical rec or ds f or certai n cases  are re q ueste d b y 
Hale o n .  I n t his i nsta nce, all s u bject i de ntifiers, e x ce pt f or t he s u bject n u m ber, will be re d acte d 
o n t he c o pies of t he me di cal rec or ds pri or t o s u b missi o n t o Hale o n  . 
T he i n vesti gat or ( or me dicall y q ualifie d desi g nee) will atte m pt t o es ta 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 w here k n o w n a n d n ot t he i n di vi d ual si g ns/s y m pt o ms. (e. g. u p per 
res pirat or y tr act i nfecti o n, seas o nal aller g y, etc. i nstea d of r u n n y n ose).  
A Es elicite d b y t he i n vesti gat or ( or me di call y q ualifie d desi g nee) i n a st a n dar d ma n ner at t h e 
st u d y visits s h o ul d als o be rec or de d i n t he A E secti o n of t he C R F a n d/ or usi n g t he S A E f or m 
(s u bject t o t he classificati o n of t he A E). Care will be ta ke n n ot t o i ntr o d uce bias w he n 
q uesti o ni n g a s u bject a b o ut a n y c ha n g es i n t heir healt h. O pe n -e n de d a n d n o n -lea di n g ver bal 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 5  of 5 6  
q uesti o ni n g s h o ul d be use d.   A Es will be cate g orize d as oral or n o n -oral b y t he e xa mi ner pri or 
t o data base l oc k. 
9. 1. 4. 1  
R e p orti n g of a n A d v er s e E v e nt  
All A Es will be re p orte d o n t he A E pa ge of t he C R F b y t he i n vesti gat or or site staff.  It s h o ul d 
be n ote d t hat t he f or m f or c ollecti o n of S A E i nf or m ati o n is n ot t he sa me as t h e A E C R F.  W h ere 
t he sa me data are c ollecte d, t he A E CR F p a ge a n d t he S A E f or m m ust be c o m plete d i n a 
c o nsiste nt ma n ner.  F or e xa m ple, t he sa me A E ter m s h o ul d be use d o n b ot h.  A Es s h o ul d be 
re p orte d usi n g c o ncise me dical ter mi n ol o g y o n t he C R F as well as o n t he f or m f or c ollecti o n 
of S A E i nf or mati o n.  
9. 1. 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 o n t he A E C R F pa ge, a n S A E f or m s h o ul d b e 
c o m plete d, as f ull y as p ossi ble. Har d c o pies of t he ‘ pa per’ S A E f or m will be pr o vi de d i n t he 
i n vesti gat or st u d y master file. Ori gi nal S AE f or ms will be retai ne d i n t he i n vesti gat or st u d y 
master file.  
It is esse ntial t o e nt er t he f oll o wi n g i nf or mati o n:  
•  Pr ot oc ol a n d s u bject i de ntifiers  
•  S u bject de m o gra p h y  
•  Descri pti o n of e v e nts, wit h dia g n osis if a vaila ble  
•  I n v esti gat or o pi ni o n of relati o ns hi p t o st u d y pr o d uct ( or st u d y pr oce d ure, if 
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 a n d Hale o n 
assess me nt of t he S A E re p ort:  
•  Date of o nset of A E  
•  Date A E st o p pe d, if rele v a nt  
•  St u d y pr o d uct start date  
•  St u d y pr o d uct e n d date if rele va nt  
•  Acti o n ta ke n i n relati o n t o t he st u d y pr o d uct  
•  O utc o me if k n o w n  
T he S A E f or m, c o m plet e d as f ull y as p ossi ble, m ust be sca n ne d a n d e -maile d t o t he Case 
Ma na ge me nt Gr o u p  mail b o x 
wit h c o p y t o t he 
a p pr o priate  St u d y Ma na ger , wit h t he st u d y n u m ber a n d s u bject n u m ber i n t he s u bject li ne of 
t he e mail i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 h o urs after st u d y 
site pers o n nel le ar n of t he e ve nt. T he i n v esti gat or will s u b mit a n y u p dat e d S A E data t o t he 
s p o ns or, i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 h o urs of it bei n g 
a vaila ble.  
T he i nitial re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q u este d b y t he  
st u d y ma na ger. 
T he St u d y Ma na g er will be res p o nsi ble f or f or war di n g t he S A E f or m t o ot her Hale o n  pers o n nel 
as a p pr o priat e.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI
P P D

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 6  of 5 6  
9. 1. 5  
E v al u ati n g A d v er s e E v e nt s  
9. 1. 5. 1  
A s s e s s m e nt of I nt e n sit y  
T he i n vesti gat or  or me di call y q ualifie d desi g ne e will ma ke a n assess me nt of i nte nsit y f or eac h 
A E re p orte d d uri n g t he st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories:  
•  Mil d:  A n e ve nt t hat is easil y t olerate d b y t he s u bj ect, 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.  
•  M o derate:  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 pr e ve nts n or mal e ver y da y acti vities.  
N O T E: A n A E t h at is assesse d as se v ere s h o ul d n ot be c o nf u s e 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; a n d b ot h n o n -seri o us A Es a n d S A Es ca n 
be assess e d as s e vere. F or e xa m ple, a h ea d ac he ma y be s e vere (i nterferes si g nifica ntl y wit h t he 
s u bject's us ual f u ncti o n) b ut w o ul d not be classifie d as seri o us u nless it met o ne of t he criteria 
f or S A Es, liste d a b o ve. A n e ve nt is d efi ne d as ‘seri o us’ w he n it meets at least 1 of t h e 
pre defi n e d o utc o mes as descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.  
9. 1. 5. 2  
A s s e s s m e nt of C a u s alit y  
T he ca us alit y assess me nt is o ne of t he criteria use d w he n d eter mi ni n g re g ulat or y re p orti n g 
re q uire me nts.  
F or eac h A E (seri o us a n d n o n -seri o us), t he i n vesti gat or ( or me di call y q ualifie d desi g nee) m ust  
pr o vi de a n assess me nt of ca us alit y o n t he A E C R F pa ge a n d t he S A E f or m (s u bject t o t he 
classificati o n of t he A E). T he i n vesti gat or will als o d oc u me nt i n t he me dical n otes t hat t he y 
ha ve  re vi e we d t he A E a n d assesse d ca usalit y, w here a p plica bl e.  
A “reas o na ble p ossi bilit y” of a rel ati o ns hi p c o n ve ys t hat 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 h er t ha n a relati o ns hi p ca n n ot be r ule d o ut. 
Ge nerall y, t he facts (e vi d e nce) or ar g u me nts t o 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.  
T he i n vesti gat or will use c li nical j u d g me nt t o deter mi ne t he rel ati o ns hi p a n d will als o c o ns ult 
t he Safet y Stat eme nt , i n t he deter mi nati o n of his/ her assess me nt.  Alter n ati ve ca uses, s uc h as 
u n derl yi n g disease(s), c o nc o mita nt t hera p y, ot her 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 uct will be c o nsi dere d a n d i n vesti gate d. 
F or eac h A E/ S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat he/s he h as 
re vie we d t h e A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y. 
T he i n vesti gat or’s assess me nt of ca usalit y m ust be pr o vi de d f or all A Es (seri o us a n d n o n -
seri o us); t he i n vesti gat or m ust rec or d t he ca usal relati o ns hi p i n t he C R F, as a p pr o priat e, a n d 
re p ort s uc h a n assess me nt i n acc or da n ce wit h t he S A E re p orti n g re q uir e me nts if a p plica ble. 
T here ma y be s it uati o ns w he n a n S A E h as occ urre d, a n d t he i n v esti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o Hale o n .  H o we ver, it is ver y i m p ort a nt t h at t he 
i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y f or e ver y e v e nt pri or t o t he i niti al 
tra ns missi o n of t he S A E d at a t o Hale o n . T he i n vesti gat or ma y c ha n ge his/ her 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 he u p date d 
ca usalit y assess me nt.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 7  of 5 6  
9. 1. 6  
F oll o w -u p of A E s a n d S A E s   
After t he i nitial A E/ S A E rep ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll o w u p wit h eac h 
s u bject a n d pr o vi de f urt h er i nf or mati o n o n t he s u bject’s c o n diti o n. 
All 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 s u bject is l ost t o f oll o w-u p.   
T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e v al uati o ns as ma y be i n dicate d or as re q ueste d b y Hale o n 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 he A E. T his ma y i ncl u de a d diti o nal 
la b orat or y tests or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt h care pr ofessi o nals.  
Ne w or u p date d i nf or mati o n will be rec or de d o n t he A E C R F p a ge a n d o n t he S A E f or m 
(s u bject t o t he classificati o n of t he A E). 
T he i n vesti gat or will s u b mit a n y u p date d S A E data t o Hale o n wit hi n 2 4 h o urs of recei pt of t he 
i nf or mati o n. 
I n v esti gat ors are n ot o bli ge d t o acti vel y see k A Es i n f or mer s u bjects.  H o we ver, if t h e 
i n vesti gat or lear ns of a S A E, i ncl u di n g deat h, at a n y ti me after a s u bject has bee n disc har ge d 
fr o m t he st u d y, a n d c o nsi ders t he e ve nt 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 i n vesti gat or will pr o m ptl y n otif y Hale o n b y e ma ili n g t he i nf or mati o n t o t he 
Case Ma na ge me nt Gr o u p  mail b o x at Hale o n 
wit h 
c o p y t o t he a p pr o pri ate St u d y Ma na ger. 
T he i n vesti gat or will s u b mit a n y u p date d S A E data t o Hale o n wit hi n t he desi g nate d re p orti n g 
ti me fra mes. 
9. 1. 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 u e 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 h er ca uses, acc or di n g 
t o t he defi niti o n of a n A E n ote d earlier, a n d rec or de d o n t he a p pr o priate A E C R F  pa ge.  
W he n a s u bject 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. 
9. 1. 8  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s 
Hale o n h as a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t he l o cal re g ulat or y a ut h orit y a n d 
ot her re g ulat or y a ut h oriti es a b o ut t he safet y of a pr o d uct u n der cli nical i n v esti gati o n.  Pr o m pt 
n otificati o n of S A Es b y t he i n vesti gat or t o Hale o n is esse ntial s o t h at le gal o bli gati o ns a n d 
et hical res p o nsi bilities t o war ds t he safet y of s u bjects are met.  
Hale o n will c o m pl y wit h c o u ntr y s p ecific re g ulat or y re q uir e 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, I R B/ E C a n d i n vesti gat ors. 
B ot h t he i n vesti gat or a n d t he s p o ns or will c o m pl y wit h all l ocal me dical de vice re p orti n g 
re q uire me nts  
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x p ecte d seri o us a d verse reacti o ns 
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uir e me nts a n d s p o ns or p olic y a n d for war de d t o 
i n vesti gat ors as necessar y. 
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a S A E or ot her s pecific 
safet y i nf or m ati o n e. g. s u m mar y or listi n g of S A E fr o m t he s p o ns or will re vie w a n d t he n file 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI
P P D

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 8  of 5 6  
it al o n g wit h t he I n vesti g at or’s Br oc h ure i n t he i n vesti gat or st u d y master file, a n d will n otif y 
t he I R B/I E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts. 
9. 1. 9  
Pr e g n a n c y  
9. 1. 9. 1  
Ti m e P eri o d f or C oll e cti n g Pr e g n a n c y I nf or m ati o n  
Pre g na nc y i nf or mati o n will be c ollect e d o n all pre g na ncies re p orte d w hile a fe male s u bject is 
partici pati n g i n t he st u d y fr o m t he si g ni n g of i nf or me d c o nse nt u ntil 5 da ys  after last 
a d mi nistrati o n of st u d y pr o d uct.  
9. 1. 9. 2  
A cti o n t o b e T a k e n if Pr e g n a n c y O c c ur s  
T he i n vesti gat or will r ec or d pre g n a nc y i nf or mati o n o n t he a p pr o priate f or m sca n a n d e-mail it 
t o t he Case Ma na g e me nt Gr o u p mail b o x 
 wit h c o p y 
t o t he a p pr o pri ate St u d y Ma na ger. Ori gi nal pre g n a nc y i nf or m ati o n f or ms will be retai n e d i n 
t he i n vesti gat or st u d y master file.  
T he s u bject will be f oll o we d t o d eter mi ne t he o ut c 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 na nc y) will be  f or war de d b y t he i n vesti gat or t o t he Case Ma na ge me nt 
Gr o u p mail b o x at Hale o n 
wit h c o p y t o t he a p pr o priate   
St u d y Ma na ger. G e 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 f oll o wi n g t he 
esti mate d deli ver y date. A n y t er mi nati o n of t he pre g na nc y will be re p orte d.  
W hile pre g na n c y itself is n ot c o nsi dere d t o be a n A E, a b n or mal pre g n a n c y o utc o mes (e. g. 
s p o nta ne o us a b orti o n, fet al deat h, still birt h, c o n ge nital a n o malies, ect o pic pre g na nc y) are, a n d 
s h o ul d be rec or de d as a n S A E.  
A n y fe male s u bject w h o bec o mes pre g na nt w hile partici pati n g will be wit h dra w n fr o m t he 
st u d y. 
9. 1. 1 0  
M e di c al D e vi c e I n ci d e nt s  
T he defi niti o ns a n d pr oce d ures det aile d are i n acc or da nce wit h I S O 1 4 1 5 5 . 
B ot h t he i n vesti gat or a n d t he s p o ns or will c o m pl y wit h all  l ocal me dical de vice re p orti n g 
re q uire me nts. 
Me dical de vi ces are bei n g pr o vi de d b y Hale o n f or use i n t his st u d y; t he me dical de vice i n t his 
st u d y is t he s u p plie d t o ot h br us h. 
9. 1. 1 0. 1  D efi niti o n of a n I n ci d e nt  
A me dical de vic e i nci de nt is a n y malf u n cti o n or deteri o rati o n i n t he c haracteristics a n d/ or 
perf or ma n ce of a de vic e as well as a n y i na de q uac y i n t he la beli n g or t he i nstr ucti o ns f or use 
w hic h, directl y or i n directl y, mi g ht lea d t o or mi g ht ha ve le d t o t he deat h of a s u bject/ user/ ot her 
pers o n or t o a seri o us de t eri orati o n i n his/ her state of healt h. 
N ot all i nci de nts lea d t o deat h or s eri o us det eri orati o n i n healt h. T he n o n o cc urre n ce of s uc h a 
res ult mi g ht ha ve bee n d ue t o ot her f ort u nate cir c u msta nces or t o t he i nter ve nti o n of healt h care 
pers o n nel.  
It is s ufficie nt t h at: 
A n i nci de nt ass ociate d wit h a de vice h a p pe ne d a n d  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI
P P D
P P D

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 3 9  of 5 6  
•  T he i nci de nt was s uc h t h at, if it occ urre d a gai n, mi g ht lea d t o deat h or a s eri o us 
deteri orati o n i n he alt h.  
•  A seri o us deteri orati o n i n state of healt h ca n i ncl u de a n y of t he f oll o wi n g:  
•  Life -t hreate ni n g ill ness 
•  Per ma ne nt i m pair me nt of b o d y f u ncti o n or per ma n e nt da ma ge t o b o d y str uct ure 
•  C o n diti o n necessitati n g me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he a b o ve  
•  Fetal distress, f etal deat h, or a n y c o n ge nital a b n or malit y or birt h defects  
E x a m ples of i nci de nts:  
•  A s u bject, user, care gi ver, or healt hcare pr ofessi o n a l is i nj ure d as a res ult of a 
me dical de vice fail ure or its mis use.  
•  A s u bject’s st u d y treat me nt is i nterr u pte d or c o m pr o mise d b y a me dical de vi ce 
fail ure. 
•  A mis dia g n osis d ue t o me dical de vice fail ure lea ds t o i na p pr o priate treat me nt.  
•  A s u bject’s healt h det eri orates d ue t o me dical de vice fail ure.  
9. 1. 1 1  
R e p orti n g of I n ci d e nt s a n d M alf u n cti o n s  
All i nci de nts m ust be re p orte d t o  Hale o n  i m me di atel y a n d u n der n o circ u mst a nce s h o ul d 
t his e xcee d 2 4 h o urs of t he i n vesti gat or or desi g n ee bec o mi n g a ware of t h e sit uati o n.  
A n y  me dical de vice i nci de nt occ urri n g d uri n g t h e st u d y will be d oc u me nte d i n t he s u bject's 
me dical rec or ds, if i n acc or da nce wit h t he i n vesti gat or's n or mal cli nical practice, a n d o n t h e 
a p pr o priate I n ci de nt Re p ort F or m.  I n a d diti o n, f or i nci de nts f ulfilli n g t he defi niti o n of a n A E 
(seri o us a n d n o n-seri o us), t he a p pr o priate A E C R F pa ge a n d S A E f or m will be c o m plete d a n d 
re p orte d as per t he A E a n d S A E re p orti n g secti o ns. 
T he I nci de nt Re p ort F or m will be c o m plete d as t h or o u g hl y as p ossi ble a n d si g ne d b y t he 
i n vesti gat or bef ore tra ns mittal t o Hale o n .  It is v er y i m p orta nt t hat t he i n vesti gat or descri b es 
a n y c orrecti ve or re me di al acti o ns ta ke n t o pr e ve nt rec urre nce of t he i nci de nt.  
T he c o m plete d I n ci de nt Re p ort F or m s h o ul d be s ca n ne d a n d e maile d t o  t h e Case Ma na g eme nt 
Gr o u p  mail b o x 
wit h c o p y t o t he a p pr o priate   St u d y 
Ma na ger ,  wit h t he st u d y n u m ber a n d s u bject n u m ber i n t he s u bject li ne of t he e mail 
i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 h o urs after st u d y site 
pers o n nel lear n of t he e ve nt. If t here is a n S A E, t he c o m plete d S A E f or m s h o ul d be se nt 
t o get her wit h t his re p ort f or m.  H o we v er, if a c o p y of t he S A E re p ort is se nt wit h t his f or m, 
t his d oes not re place t he pr oce d ure t o re p ort a n S A E.  T he ori gi nal I nci d e nt Re p ort F or m will 
be retai ne d i n t he i n v esti gat or st u d y master file.  
T he i nitial re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q u este d b y t he   
st u d y ma na ger. 
T he i n v esti gat or will f oll o w t he f oll o wi n g dir ecti o ns re gar di n g t he re p orti n g of a de vice fail ure 
( malf u ncti o n): 
•  N otif y Hale o n i m me diatel y ( b y f oll o wi n g t he pr ocess descri be d a b o ve). 
•  Sc he d ule t he s u bject t o ret ur n t o t he site pr o m ptl y t o ret ur n t he faile d d e vice.  
•  Rec or d a n y i nci d e nts o n t he C R F a n d I n ci de nt Re p ort F or m f oll o wi n g i nstr u cti o ns 
gi ve n i n t he secti o n a b o v e.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI
P P D

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 0  of 5 6  
•  F or a n y i n ci de nt/ malf u ncti o n occ urri n g wit h a me dical de vice (i ncl u di n g t h ose t hat 
are part of c o m bi nati o n pr o d ucts) s u p plie d b y Hal e o n, r et ur n t he faile d de vice t o t he 
s p o ns or as s o o n as p ossi ble, i ncl u di n g d oc u me ntati o n of t he details of t he fail ure  
•  F or a n y i n ci de nt/ malf u ncti o n occ urri n g wit h a me dical de vice (i ncl u di n g t h ose t hat 
are part of c o m bi nati o n pr o d ucts) s u p plie d b y t he I n vesti gat or site, re p ort t h e i nci de nt 
t o t he de vice ma n ufact ur er a n d f oll o w t he m a n ufact urer i nstr ucti o ns f or t h e ret ur n of 
t he faile d de vic e ( w hilst kee pi n g Hale o n i nf or me d). 
9. 1. 1 2  
F oll o w -u p of M e di c al D e vi c e I n ci d e nt s  
Me dical de vi ce i n ci de nts i n v ol vi n g a n A E will be f oll o we d a n d re p orte d i n t he sa m e ma n ner 
as ot her A Es. T his a p plies t o all s u bjects, i ncl u di n g t h ose w h o disc o nti n ue st u d y pr o d uct or are 
wit h dra w n fr o m t he st u d y.  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat f oll o w -u p i ncl u des a n y s u p ple m e nta l 
i n vesti gati o ns as i n dicate d t o el uci date t he nat ur e a n d/ or ca us alit y of t he i nci de nt. 
Ne w or u p dat e d i nf or m ati o n will be rec or de d o n t h e ori gi nall y c o m plete d I n ci de nt Re p ort f or m 
wit h all c ha n ges si g ne d a n d date d b y t he i n vesti gat or.  
9. 1. 1 3  
R e g ul at or y R e p orti n g  R e q uir e m e nt s f or M e di c al D e vi c e I n ci d e nt s 
T o f ulfill re g ulat or y re p orti n g o bli gati o ns w orl d wi de, t he i n vesti gat or is res p o nsi ble f or t he 
detecti o n a n d d oc u me nt ati o n of e ve nts meeti n g t he defi niti o ns of i nci de nt or malf u ncti o n t hat 
occ ur d uri n g all peri o ds  of t he st u d y i n w hic h t he me dical de vice is us e d.  
T he i n vesti gat or will pr o m ptl y re p ort all i nci de nts occ urri n g wit h a n y me dical de vice pr o vi d e d 
f or use i n t he st u d y i n or der f or t h e s p o ns or t o f ulfill t he le gal res p o nsi bilit y t o n otif y 
a p pr o priate re g ul at or y a ut h orities a n d ot her e ntities a b o ut certai n safet y i nf or mati o n relati n g t o 
me dical de vices b ei n g us e d i n cli nical st u dies.  
T he i n vesti gat or, or res p o nsi ble pers o n acc or di n g t o l ocal re q uire m e nts (e. g. t he hea d of t he 
me dical i nstit uti o n), will c o m pl y wit h t he a p plica ble l ocal re g ulat or y re q uir e me nts relati n g t o 
t he re p orti n g of i nci de nts t o t he I R B/I E C. 
9. 2  
DI S C O N TI N U A TI O N O F S T U D Y P R O D U C T  A N D S U B J E C T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  
If a s u bject is disc o nti n ue d earl y fr o m t he st u d y pr o d uct (Secti o n 9. 2. 1 ) or disc o nti n ue d or 
pre mat urel y 
wit h dra ws fr o m t he st u d y (Secti o n 9. 2. 2 ), t he reas o n(s) f or i nter ve nti o n 
disc o nti n uati o n or wit h dra wal a n d t h e ass ociat e d date m ust be d oc u me nt e d i n t he rele va nt 
secti o n(s) of t h e C R F. If a s u bject is disc o nti n ue d earl y fr o m t he st u d y pr o d uct, t he s u bject 
sh o ul d sta y i n t he st u d y a n d c o m plete t he re mai ni n g assess me nts u nless t he y nee d t o be 
wit h dra w n (see Secti o n 9. 2. 2 ). 
9. 2. 1  
Di s c o nti n u ati o n of St u d y Pr o d u c t  
A s u bject ma y be dis c o nti n ue d  fr o m t he st u d y pr o d uct at a n y ti me w hilst still i n t he st u d y at 
t he discreti o n of t he i n vesti gat or relate d t o safet y, s u bject c o nse nt or a p ote ntial w orse ni n g of 
t he ris k / be nefit assess m e nt fr o m t he s u bject of re mai ni n g on t he i nter ve nti o n f or t he f oll o wi n g 
reas o ns: 
•  A d verse E v e nt  
•  Lac k of effic ac y fr o m t he i nter ve nti o n  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 1  of 5 6  
•  S u bject re q uest  
•  S u bject t o be wit h dra w n fr o m t he st u d y (see Secti o n  9. 2. 2 )  
9. 2. 2  
S u bj e ct Di s c o nti n u ati o n/ Wit h dr a w al  
A s u bject ma y wit h dra w fr o m t he st u d y at a n y ti me at his or her o w n re q uest or ma y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or or s p o ns or f or safet y, be h a vi oral 
reas o ns, or t he i na bilit y of t he s u bject t o c o m pl y wit h t he pr ot oc ol-re q uire d sc he d ule of st u d y 
visits or pr oce d ures.   
T he f oll o wi n g circ u msta n ces re q uire disc o nti n uati o n of st u d y pr o d uct a n d/ or pre mat ure s u bj ect 
wit h dra wal:  
•  Pr ot oc ol vi olati o n t hat ma y i m pact t he s u bject’s s afet y  
•  Wit h dra wal of i nf or me d c o nse nt  
•  S u bject l ost t o f oll o w -u p  
•  U n bli n di n g of t he s u bject  
•  Pre g na nc y  
If t he s u bj ect wit h dr a ws fr o m t he st u d y a n d wit h dra ws c o ns e nt f or discl os ure of f ut ure 
i nf or mati o n, n o f urt her e val uati o ns s h o ul d b e p erf or me d, a n d n o a d diti o nal data s h o ul d be 
c ollecte d.  T he s p o ns or ma y retai n a n d c o nti n ue t o use a n y data c oll ecte d bef ore s uc h 
wit h dra wal of c o nse nt.  
9. 2. 3  
L o st t o F oll o w u p  
If a s u bject fails t o ret ur n t o t he site f or a re q uire d st u d y visit, t he i n vesti gat or or desi g nee m ust 
ma ke e v er y eff ort t o re g ai n c o ntact wit h t h e s u bject ( w here p ossi ble, 3 tel e p h o ne calls or e mails 
or l ocal e q ui vale nt met h o ds)  a n d resc h e d ule t he misse d visit as s o o n as p ossi ble a n d c o u nsel 
t he s u bject o n t he i m p orta nce of m ai ntai ni n g t he assi g ne d visit sc he d ule a n d ascert ai n w het her 
t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he st u d y. 
A s u bject will be c o nsi dere d l ost t o f oll o w u p  a n d wit h dra w n fr o m t he st u d y  if he or s he 
re peat e dl y fails t o ret ur n f or sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.  
If c o nta ct is ma de wit h t he s u bject, t he i n vesti gat or s h o ul d i n q uire a b o ut t he reas o n f or 
wit h dra wal, re q uest t hat t he s u bject ret ur n all pr o d ucts t hat t he y ha d bee n dis pe nse d a n d if 
a p pr o priate re q uest t hat t he s u bjec t ret ur n f or a fi nal visit a n d f oll o w-u p wit h t he s u bject 
re gar di n g a n y u nres ol ve d a d verse e ve nts ( A Es). 
9. 3  
D at a M a n a g e m e nt  
As use d i n t his pr ot oc ol, t he ter m C R F is u n d erst o o d t o refer t o eit her a pa per f or m or a n 
electr o nic d ata rec or d or b ot h, de pe n di n g o n  t he data c ollecti o n met h o d.  
T he s o urce d oc u me nts w hic h c o ntai n t he s o urce of data rec or de d i n t he C R F s h o ul d  be 
s pecifie d.  T he C R F ca n be use d as a s o urce d o c u me nt at t he discreti o n of data ma na g e me nt.  
Eac h s u bject will be assi g ne d a n d i de ntifie d b y a u ni q ue Scree ni n g S u bject N u m ber. A n y 
refere nce ma d e t o a n i n di vi d ual s u bject wit hi n t he st u d y m ust be d o ne usi n g t heir u ni q ue 
Scree ni n g S u bject N u m b er.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 2  of 5 6  
9. 3. 1  
C a s e R e p ort F or m  
A C R F is a pri nte d, o ptical, or ele ctr o nic d o c u me nt desi g ne d t o rec or d t h e pr ot oc ol re q u ir e 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 trial s u bject. 
F or eac h s u bject w h o h as gi ve n i nf or me d c o nse nt/asse nt t he C R F m ust be c o m plete d a n d 
si g ne d b y t he Pri nci pal I n vesti gat or ( or a ut h ori ze d desi g nee) t o certif y t hat t he data are 
c o m plete an d c orrect.  T he i n vesti gat or m ust mai ntai n acc urate d o c u me nt ati o n (s o urce data) 
t hat s u p p orts t he i nf or mati o n e ntere d i n t he C R F. 
9. 3. 2  
D at a H a n dli n g  
D oc u me ntati o n of all data ma na ge me nt acti vities s h o ul d all o w ste p -b y -ste p retr os pecti ve 
assess me nt of data q u al it y a n d st u d y perf or m a nce.  
A n y c ha n ges or c orrecti o ns t o data will be trac ke d a n d will i ncl u de t he rati o nale f or t h e c ha n g e .  
A  c o m plete rec or d of t h e c ha n ges a n d c orrecti o ns will be e n d orse d b y t he I n vesti gat or . 
9. 3. 3  
D at a Q u eri e s  
Re p orts a n d listi n gs o n t he C R F data will be r u n  a n d ma n ual q ueries will be raise d as nee de d 
f or site clarifi cati o n or c orrecti o n.  
T he st u d y m o nit or will perf or m o n g oi n g re vie w t he of t he C R Fs i n acc or da nce wit h t he 
m o nit ori n g pla n, t o c o nfir m t hat data e ntere d i nt o t he C R F b y a ut h or ize d site pers o n nel are 
acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; t hat t he safet y a n d ri g hts of 
partici pa nts are b ei n g pr otecte d; a n d t hat t he st u d y is bei n g c o n d ucte d i n acc or da n ce wit h t he 
c urre ntl y a p pr o ve d pr ot o c ol a n d a n y ot her st u d y a gree me nts . F or t his st u d y n ot all ele me nts of 
I C H G C P will be a p plie d.  
9. 4  
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  
Pa per base d p atie nt re p orte d o utc o me ( P R O) data (e g st u d y q uesti o n naires) will  be e ntere d i nt o 
t he C R F  
All P R O s o urce data s h o ul d be re vie we d b y t he st u d y staff a n d t he st u d y mo nit or t o e ns ure 
acc urate tra nscri pti o n of data a n d t hat a n y p ote nti al A Es or c o nc o mita nt m e dicati o ns re p orte d 
o n t hese d o c u me nts are disc usse d wit h t he s u bject a n d tra nscri be d acc uratel y t o t he C R F . P R Os 
t hat are classe d as s o urce data will be retai ne d b y t he i n vesti gat or a n d tr ue/ certifie d c o pi es ma y 
be se nt t o a desi g nate d ve n d or or Hale o n  as re q uire d.  A n y A Es or c o nc o mita nt me dicati o ns 
c ollecte d as P R O  will be re vie we d a n d tra ns cri be d t o t he C R F  b y t he site.  
T o  pr otect t he pri vac y of s u bjects, n o Pers o nal I nf or mati o n ( PI) (i ncl u di n g t he s u bject's na me 
or i nitials or birt h date) is t o be rec or de d o n a n y P R O  Data  t hat will be f or war de d t o Hale o n  or 
T hir d -Part y Ve n d or.  
9. 5  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s  
9. 5. 1  
I n stit uti o n al R e vi e w B o ar d/ Et hi c s C o m mitt e e  
It is t he res p o nsi bilit y of t he i n vesti gat or 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 o c u me nt, i n vesti gat or br oc h ure/safet y state m e nt 
(i ncl u di n g a n y u p dates) a n d ot her rele va nt d oc u me nts, e. g. recr uit me nt a d vertise me nts, if 
a p plica ble, fr o m t he I R B/ E C.  All c orres p o n de nce wit h t he I R B/ E C s h o ul d be retai ne d i n t he 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 3  of 5 6  
i n vesti gat or file.  C o pies of I R B/ E C a p pr o vals s h o ul d be f or war de d t o Hale o n  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 ue nt a me n d me nts t o t he pr ot oc ol are ma de. 
T he o nl y circ u msta nce i n w hic h a n a m e n d me nt ma y be i nitiate d pri or t o I R B/ E C a p pr o val is 
w here t he c ha n g e is necessar y t o eli mi nate a p pare nt i m me diate hazar ds t o t he s u bjects.  I n t hat 
e vent, t he i n vesti gat or m ust n otif y t he I R B/ E C a n d Hale o n  i n writi n g i m me diatel y after t he 
i m ple me ntati o n. 
9. 5. 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 nce 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 well as t he ge neral pri nci ples set f ort h i n t he I nter nati o nal Et hical G ui deli nes 
f or Bi o me dical Researc h I n v ol vi n g H u ma n S u bjects (C o u ncil f or I nt er nati o nal Or g a nizati o ns 
of Me dical Scie nces, 2 0 0 2 ), I nter nati o nal Et hical G ui deli nes f or Healt h-Rela te d Researc h 
I n v ol vi n g H u ma ns), g ui d eli nes f or G C P (C o u ncil f or I nter n ati o nal Or ga nizati o ns of Me dical 
Scie nces, 2 0 1 6 , I C H, 1 9 9 6), 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 ucte 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 I S O 1 4 1 5 5: 2 0 1 1 , a n d a p plica ble l o cal re g ulat or y re q uire m e nts a n d la ws. 
9. 5. 3  
S u bj e ct I nf or m ati o n  
All parties will e ns ure pr otecti o n of s u bject pers o nal data a n d will n ot i ncl u de s u bject na mes 
or ot her i de ntifia ble data i n a n y re p orts, p u blicati o ns, or ot her discl os ures, e xce pt w here 
re q uire d b y la ws.  
W he n st u d y data are c o m pile d f or tra nsfer t o 
Hale o n a n d ot h er a ut h orize d parties, s u bject 
na mes, a d dresses, a n d ot her i de ntifia bl e dat a will be re place d b y n u m erical c o des base d o n a  
n u m beri n g s yste m pr o vi de d b y Hale o n  i n or d er t o de-i de ntif y st u d y s u bjects.   
T he st u d y site will mai ntai n a c o nfi de ntial list of s u bjects w h o partici pate d i n t he st u d y, li n ki n g 
eac h s u bj ect’s n u merical c o de t o his or her act ual i de ntit y.  I n case of dat a  tr a nsfer, Hale o n  will 
mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr otecti o n of s u bjects’ pers o nal data c o nsiste nt 
wit h a p plica ble pri va c y la ws.  
9. 6  
R e c or d s R et e nti o n  
F oll o wi n g cl os ure of t he st u d y, t he i n vesti gat or m ust mai ntai n all site st u d y rec or ds (e x ce pt f or 
t h ose re q uire d b y l oc al re g ulati o ns t o be mai ntai ne d else w here), i n a s afe a n d sec ure l o cati o n.   
W here p er 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 n e d i n a f or mat ot her t ha n h ar d c o p y (e . g., micr ofi c he, sca n ne d, electr o nic); 
h o we ver, ca uti o n nee ds t o be e xercise d bef ore s u c h acti o n is ta ke n.  
T he i n vesti gat or m ust n otif y Hale o n  of a n y c h a n g es i n t he arc hi val arra n g e me nts, i ncl u di n g, 
b ut n ot li mite d t o, arc hi val at a n off -site facilit y or tra nsfer of o w ners hi p of t he rec or ds i n t he 
e ve nt t he i n vesti gat or is n o l o n ger ass ociate d wit h t he site.  
9. 7  
Di s cl o s ur e  a n d P u bli c ati o n P oli c y  
St u d y i nf or mati o n fr o m t his pr ot oc ol ma y be  p oste d o n p u blicl y a vaila ble cli nical trial re gisters 
bef ore e nr oll me nt of s u bj ects be gi ns i n acc or da n ce wit h a p plica ble Hal e o n  p olicies . 
Hale o n  i nte n ds t o ma ke a n o n y mize d s u bject-le vel data fr o m t his st u d y a vaila ble t o e xter nal 
researc hers f or scie ntific a nal yses or t o c o n d uct f urt her researc h t hat ca n h el p a d va nce me dical 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 4  of 5 6  
scie nce. T his hel ps e ns ur e t he data pr o vi de d b y st u d y partici pa nts are us e 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 derst a n di n g. 
T he pr oce d ures a n d ti mi n g f or p u blic discl o s 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 us cri pt f or p u blicati o n will be i n acc or da n ce wit h s p o ns or p olic y  a n d as per t he c o u ntr y 
s pecific re q uire me nts f or discl os ure. 
9. 8  
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 9 -1  
A b br e vi ati o n s  
A b br e vi ati o n  
T er m  
A E  
a d v er s e e v e nt  
A N O V A  
a n al y si s of v ari a n c e  
B D R  
bli n d e d d at a r e vi e w  
CI  
c o nfi d e n c e i nt er v al  
C R F  
c a s e r e p ort f or m  
D H  
D e nti n e H y p er s e n siti vit y  
E A R  
Er o si o n, A br a si o n, R e c e s si o n ( a s s e s s m e nt of)  
e C R F  
El e ctr o ni c C a s e R e p ort F or m  
F D A  
F o o d a n d Dr u g A d mi ni str ati o n ( U nit e d St at e s)  
G C P  
G o o d Cli ni c al Pr a cti c e  
I C H 
I nt er n ati o n al C o nf er e n c e o n H ar m o ni s ati o n 
I R B 
i n stit uti o n al r e vi e w b o ar d 
L M S  
L a b ell e d M a g nit u d e S c al e  
L S L V  
l a st s u bj e ct l a st vi sit  
M e d D R A  
m e di c al Di cti o n ar y f or R e g ul at or y A cti viti e s  
M GI  
M o difi e d Gi n gi v al I n d e x  
M M R M  
Mi x e d m o d el wit h r e p e at e d m e a s ur e s  
N/ A  
n ot a p pli c a bl e  
O S T  
Or al S oft Ti s s u e ( e x a mi n ati o n)  
O H T  
Or al H ar d Ti s s u e ( e x a mi n ati o n)  
PI  
pri n ci p al i n v e sti g at or  
S A E  
S eri o u s A d v er s e E v e nt  
U S A  
U nit e d St at e s  of A m eri c a  
V A S  
Vi s u al A n al o g u e S c al e  
 
9. 9  
St u d y Pr o d u ct U s a g e I n str u cti o n s S h e et  
 
I N S T R U C TI O N S F O R P R O D U C T U S E 
Br us h y o ur teet h t wice a da y ( m or ni n g a n d e v e ni n g). 
Eac h ti me y o u br us h:  
•  Dis pe nse a ri b b o n of t o ot h paste c o veri n g t he le n gt h of t he t o ot h br us h hea d (see bel o w 
pict ure).  O nl y t he s u p plie d t o ot h br us h ma y be use d.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 5  of 5 6  
•  Set y o ur ti mer f or 1  mi n ute s, a n d t he n br us h y o ur t eet h i n y o ur us ual ma n ner f or 1  ti me d 
mi n ute.  
 
 
 
•  Bri n g y o ur t o ot h paste , t o ot h br us h a n d t o ot h bleac hi n g kit t o all st u d y visits. 
Per o xi de ble ac hi n g us a ge  
O n da ys w here t he st u d y staff ha ve i n dicate d y o u s h o ul d use y o ur per o xi de t o ot h  bleac hi n g 
kit:  
•  A p pl y t he per o xi de -c o ntai ni n g de ntal tra y s t o y o ur teet h acc or di n g t o t he i nstr ucti o ns  
pr o vi de d b y t he st u d y site .  Y o u s h o ul d use t he per o xi de o nce-per -da y f or a t otal of 7  
da ys.  If p ossi ble tr y t o p erf or m y o ur t o ot h bleac hi n g at r o u g hl y t he sa me ti me eac h d a y.  
Y o u s h o ul d place t he tra y o n y o ur teet h a n d kee p t he tra y i n place f or 1 5 mi n utes ( please 
use t he s u p plie d ti mer).  After re m o vi n g t he tra ys please br us h y o ur t eet h acc or di n g t o t he 
br us hi n g i nstr ucti o ns a b o ve .  S h o ul d y o u e x perie n ce a n y g u m s ore ness or irritati o n please 
a p pl y a t hi n s mear of t he s u p plie d petr ole u m jell y t o y o ur g u ms pri or t o ne xt weari n g 
y o ur tra y s.  Tr y t o a v oi d getti n g t he petr ole u m jell y i n c o ntact wit h y o ur teet h. 
 
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 6  of 5 6  
 
9. 1 0  
T o ot h Se nsiti vit y Q uesti o n n aire ( E X A M P L E) 
S u bject #  
 
 
 
 
 
Date:  
W he n c o m pleti n g t his f or m ple ase c o nsi der y o ur e x perie nce o v er t he l ast 2 4 h o urs   
 
 
Ha ve y o ur te et h bee n s e nsiti ve ?   Y/ N      If N O  d o n ot c o m plete a n y f urt her q uesti o ns.  
 
Please ma ke a si n gle v ertical mar k at t he p oi nt o n t he li ne w hic h re prese nts t he de gree of 
o verall t o ot h se nsiti vit y (e g t wi n ges, pai n a n d ot her se nsati o ns i n y o ur teet h) t hat y o u ha ve 
e x perie n ce d o ver t he l ast 2 4 h o urs  
 
N o  
 
 
 
 
 
 
 
 
 
E xtre me  
Se nsiti vit y  
 
 
 
 
 
 
 
 
Se nsiti vit y  
 
F or Site use o nl y:                         m m                                                            I niti als  
 
 
 
 
 
 
 
 
I n t he l ast 2 4 h o urs, h a ve y o u use d a n y p ai n killi n g me dic ati o ns t o reli ve t o ot h 
se nsiti vit y/ p ai n ? 
Yes  □ 
N o  □ 
 
 
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 7  of 5 6  
 
T O L E R A BI LI T Y
L a b ell e d M a g nit u d e S c al e s
T O L E R A B L E
U N C O M F O R T A B L E
U N N E R VI N G
U N B E A R A B L E
N O P AI N
I N T E N SI T Y
D U R A TI O N
DI M
D U L L
S H A R P
S T A B BI N G
N O P AI N
T E M P O R A R Y
Q UI C K
LI N G E RI N G
C H R O NI C
N O P AI N
S cr e e ni n g N o. S _ _ _ _ _ _ _ _ _ _ _ _
Pr ot o c ol:  2 0 4 9 3 0 
Vi sit N o: _ _ _ _ D at e : _ _ _ _/ _ _ _ _/ _ _ _ _
S c or e:
S c or er i niti al s ( sit e st aff):
m m
m m
m m
T o ot h N o:
m m
T WI N G E
A C H E
T H R O B BI N G
S H O O TI N G
N O P AI N
D E S C RI P TI O N
Pl e a s e r at e t h e I N T E N SI T Y/ D U R A TI O N/ T O L E R A BI LI T Y/ D E S C RI P TI O N of t hi s f e eli n g or s e n s ati o n.
M ar k t h e s c al e s b el o w wit h a n “ X ” t o i n di c at e t h e b e st d e s cri pti o n of t h at f e eli n g or s e n s ati o n. 
R e m e m b er, y o u c a n m ar k a n y w h er e o n t h e li n e, i n cl u di n g b et w e e n t h e d e s cri pti v e w or d s.
Fi n al v 1. 0 1 6 O ct 1 5
 
N O T T O S C A L E  
 
 
 
O n a scale of 1 t o 1 0 h o w b ot here d  ha ve y o u b ee n b y a n y t o ot h se nsiti vit y (e g 
t wi n ges, pai n, ac he or ot her se nsati o ns i n y o ur teet h) t hat y o u ha ve e x p erie nce d 
o ver t he l ast 2 4 h o urs  ( please cir cle y o ur a ns wer) 
 
N ot at all  
   1        2        3       4       5       6       7        8        9     1 0  
E xtre mel y  
B ot here d  
 
 
 
 
 
 
 
 
B ot here d  
 
 
 
 
 
Please rate t h e I N T E N SI T Y/ D U R A TI O N/ T O L L E R A BI LI T Y/ D E S C RI P TI O N of y o ur 
o verall t o ot h se nsiti vit y (e g t wi n ges, pai n a n d ot her se nsati o ns i n y o ur teet h) e x peri e nce d o v er 
t he p ast 2 4 h o urs .  Mar k t he scales bel o w wit h a n “ x ”  t o i n dicate t he best descri pti o n of y o ur 
se nsiti vit y.  Re me m ber y o u ca n mar k a n y w here o n t he li ne, i ncl u di n g bet wee n t he des cri pti ve 
w or ds.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 8  of 5 6  
9. 1 1  
W hite ni n g Hist or y Q uesti o n n aire . 
 
T o be c o m plete d at Visit 2 pri or t o first t o ot h w hite ni n g a p plic ati o n  
 
 
Ha ve y o u e ver ha d 
y o ur teet h 
pr ofessi o nall y 
w hite ne d?  
Yes  □ 
N o  □ 
If y o u ha ve ha d t o ot h 
w hite ni n g treat me nt  
pre vi o usl y, h o w ma n y 
ti mes? 
 
If y o u pre vi o usl y ha d 
y o ur teet h w hite ne d 
a p pr o xi matel y h o w 
l o n g a g o was y o ur last 
w hite ni n g treat me nt?  
 
 
Please tic k t he b o x t hat best a ns wers t he state me nt:  
 
Str o n gl y 
A gree  
A gree  
A gree 
a Little  
Neit her 
A gree n or 
Disa gree  
Disa gree 
a Little  
Disa gree  
Str o n gl y 
Disa gree  
( 7) 
( 6) 
( 5) 
( 4) 
( 3) 
( 2) 
( 1) 
1) I a m c o n cer ne d 
a b o ut p ossi ble t o ot h 
pai n d uri n g t o ot h 
w hite ni n g . 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
 
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 4 9  of 5 6  
9. 1 2  
De nti ne H y perse nsiti vit y E x perie nce Q uesti o n n aire ( E x a m ple)  
 
S E C TI O N O N E  
 
T he f oll o wi n g q uesti o ns are a b o ut y o ur se nsiti ve teet h, a n d t he i m pact it has o n y o ur e ver y da y life.  
 
Fr o m n o w o n i n t his q uesti o n naire we are g oi n g t o call w hat y o u feel as ‘ se ns ati o ns i n y o ur teet h’ or 
‘se ns ati o ns’. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 5 0  of 5 6  
 
 
 
 
 
 
 
 
 
 
 
 
 
T he f oll o wi n g q uesti o ns are a b o ut y o ur se nsiti ve teet h, a n d t he i m pact it has o n y o ur e ver y da y life. 
 
 
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 5 1  of 5 6  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S E C TI O N T W O  
T he f oll o wi n g q uesti o ns are a b o ut t he w ays i n w hic h a ny se ns ati o ns i n y o ur teet h affect y o u i n y o ur d aily life.  
T hi n ki n g a b o ut y o urself over t he l ast wee k t o w hat e xte nt w o ul d y o u a gree or disa gree wit h t he f oll o wi n g 
state me nts ( Please tic k o nl y o ne res p o nse f or eac h q uesti o n)  
 
Str o n gl y 
a gree  
 
( 7) 
A gree  
 
 
( 6) 
A gree a 
little 
 
( 5) 
Neit her 
a gree n or 
dis a gree  
( 4) 
Dis a gree a 
little 
 
( 3) 
Dis a gree  
 
 
( 2) 
Str o n gl y 
dis a gree  
 
( 1) 
1) Ha vi n g se nsati o ns i n 
m y teet h ta kes a l ot of 
t he pleas ure o ut of 
eati n g a n d dri n ki n g.  
 
 
 
 
 
 
 
2) It ta kes a l o n g ti me t o 
fi nis h s o me f o o ds a n d 
dri n ks beca use of 
se nsati o ns i n m y teet h. 
 
 
 
 
 
 
 
3) T here ha v e bee n 
ti mes w h e n I ha v e ha d 
pr o ble ms eati n g ice 
crea m beca use of t hese 
se nsati o ns. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4) I ha ve t o c ha n ge t he 
wa y I eat or dri n k 
certai n t hi n gs. 
 
 
 
 
 
 
 
5) I ha ve t o be caref ul 
h o w I breat he o n a c ol d 
da y.  
 
 
 
 
 
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 5 2  of 5 6  
6) W he n eati n g s o me 
f o o ds I ha v e ma de s ure 
t he y d o n’t t o uc h certai n 
teet h. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7) Beca use of t he 
se nsati o ns I ta ke l o n ger 
t ha n ot hers t o fi nis h a 
meal.  
 
 
 
 
 
 
 
8) I ha ve t o be caref ul 
w hat I eat w he n I a m 
wit h ot hers beca use of 
t he se nsati o ns i n m y 
teet h. 
 
 
 
 
 
 
 
9) G oi n g t o t he de ntist is 
har d f or me beca use I 
k n o w it is g oi n g t o be 
pai nf ul as a res ult of 
se nsati o ns i n m y teet h. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 0) I’ ve bee n a n xi o us 
t hat s o met hi n g I eat or 
dri n k mi g ht ca use 
se nsati o ns i n m y teet h. 
 
 
 
 
 
 
 
 
1 1) T he se nsati o ns i n 
m y teet h ha ve bee n 
irritati n g. 
 
 
 
 
 
 
 
 
1 2) T he se nsati o ns i n 
m y teet h ha ve bee n 
a n n o yi n g. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 3) Ha vi n g t hese 
se nsati o ns i n m y teet h 
ma k es me feel ol d.  
 
 
 
 
 
 
 
1 4) Ha vi n g t hese 
se nsati o ns i n m y teet h 
ma k es me feel d a ma ge d.  
 
 
 
 
 
 
 
1 5) Ha vi n g t hese 
se nsati o ns i n m y teet h 
ma k es me feels as 
t h o u g h I a m u n healt h y. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 5 3  of 5 6  
9. 1 3  
P ost -W hite ni n g Q uesti o n n aire.  
T o be c o m plete d at Visit 3 after t he c o m pleti o n of t he per o xi de t o ot h w hite ni n g . 
Please tic k t he b o xes t hat best a ns wers t he state me nts:  
 
Str o n gl y 
A gree  
A gree  
A gree 
a Little  
Neit her 
A gree n or 
Disa gree  
Disa gree 
a Little  
Disa gree  
Str o n gl y 
Disa gree  
( 7) 
( 6) 
( 5) 
( 4) 
( 3) 
( 2) 
( 1) 
1) I a m s atisfie d 
wit h t he res ults of 
m y t o ot h w hite ni n g.  
□ 
□ 
□ 
□ 
□ 
□ 
□ 
2) I f o u n d it 
i nc o n ve nie nt t o 
s witc h m y t o ot h paste 
f or t his st u d y. 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
3) I f o u n d m y teet h 
t o be p ai nf ul  d uri n g 
t he t o ot h w hite ni n g 
treat me nt. 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
4) I w o ul d 
rec o m me n d  t o ot h 
w hite ni n g t o a frie n d 
or relati ve.  
□ 
□ 
□ 
□ 
□ 
□ 
□ 
5) I w o ul d c o nsi der 
f urt her t o ot h 
w hite ni n g treat me nts 
i n t he f ut ure. 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
6) I ha d t o c h a n ge 
t he wa y I at e or 
dra n k certai n t hi n gs 
d uri n g t he t o ot h 
w hite ni n g  treat me nt. 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
7) Ha vi n g se nsati o ns 
i n m y teet h d uri n g 
t o ot h w hite ni n g t o o k 
ple as ure o ut of 
e ati n g a n d 
dri n ki n g.  
□ 
□ 
□ 
□ 
□ 
□ 
□ 
8) Ha vi n g se nsati o ns 
i n m y teet h d uri n g 
t o ot h w hite ni n g was 
w orr yi n g  t o me. 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
9) Ha vi n g se nsati o ns 
i n m y teet h d uri n g 
t o ot h w hite ni n g was 
u n ple as a nt  f or me. 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 5 4  of 5 6  
9. 1 4  
R ef er e n c e s  
[ A d d y M ( 2 0 0 2)] De nti n e h y perse nsiti vit y: Ne w pers pecti ves o n a n ol d pr o ble m. I nt. De nt. J.; 
5 2( S 5 P 2): 3 6 7 -7 5.  
[ A d d y M, E m ber y G, E d gar W, et al. ( 2 0 0 0)] De nti ne h y perse nsiti vit y: defi niti o n, pre vale nce, 
distri b uti o n a n d aeti ol o g y. I n T o ot h Wear a n d Se nsiti vit y. L o n d o n: Mart n D u n itz. 
[ A dil H M, J o u har R, A h me d M A, et al. ( 2 0 2 1)] C o m paris o n of Casei n P h os p h o pe pti de wit h 
P otassi u m Nitrate a n d S o di u m M o n ofl u or o p h os p hate Des e nsitizi n g Efficac y after I n -Office 
Vital Bleac hi n g — A Ra n d o mize d Trial. A p plie d S cie nces; 1 1( 1 9): 9 2 9 1.  
[ Ale xa n dri n o L D, Ale n car C d M, SI L V EI R A A D S d, et al. ( 2 0 1 7)] Ra n d o mi ze d cli nical trial of 
t he effect of N o va Mi n a n d C P P-A C P F i n c o m bi nati o n wit h de ntal bleac hi n g. J o ur nal of 
A p plie d Oral Scie nce; 2 5: 3 3 5 -4 0.  
[ Ara ntes D C, Li meira FI R, Ya ma uti M, et al. ( 2 0 1 9)] C o m paris o n of cli nical effi cac y of pr o-
ar gi n a n d N o va Mi n t o ot h pastes i n relie vi n g de nti n h y perse nsiti vit y: A s yste matic re vie w a n d 
meta -a nal ysis. Oral Healt h Pre v De nt; 1 7( 5): 4 0 3 -1 2.  
[ Ba ker S R, Gi bs o n BJ, S ufi F, et al. ( 2 0 1 5)] T he de nti ne h y perse nsiti vit y e x perie nce 
q uesti o n naire ( D H E Q): A l o n git u di nal vali dati o n st u d y. I n De nti ne H y perse nsiti vit y. Else vier.  
[ Bizre h Y, Mill y H ( 2 0 2 2)] Effect of bi oacti ve glass paste o n efficac y a n d p ost-o perati v e 
se nsiti vit y ass ociate d wit h at-h o me bleac hi n g usi n g 2 0 % car ba mi de  per o xi de: a ra n d o mize d 
c o ntr olle d cli nical trial. E ur o pea n J o ur nal of Me di cal Researc h; 2 7( 1): 1 -7.  
[ B ur well A, J e n ni n gs D, Gree ns p a n D C ( 2 0 1 0)] N o va Mi n a n d de nti n h y p erse nsiti vit y--i n vitr o 
e vi de nce of efficac y. J. Cli n. De nt.; 2 1( 3): 6 6 -7 1.  
[ C o u ncil f or I nter nati o n al Or ga nizati o ns of Me dical Scie nces ( 2 0 0 2)] I nter nati o nal et hical 
g ui deli nes f or bi o me dical researc h i n v ol vi n g h u ma n s u bjects. B ulleti n of me dical et hics; ( 1 8 2): 
1 7 -2 3.  
[ C o u ncil f or I nter nati o n al Or ga nizati o ns of Me dical Scie nces ( 2 0 1 6)] I nternati 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 ma ns. 
[ de Freitas S A A, de Oli veira N M A, de Ge us J L, et al. ( 2 0 2 1)] Bi oacti ve t o ot h pastes i n de nti n 
h y perse nsiti vit y treat me nt: A s yste matic re vie w. T he Sa u di De ntal J o ur nal; 3 3( 7): 3 9 5 -4 0 3 . 
[ de Li ma T M, Fra nca F M G, A maral F L B d, et al. ( 2 0 2 2)] T he use of dese nsitizi n g a ge nts d uri n g 
i n-office bleac hi n g mi g ht n ot decrease t o ot h bleac hi n g se nsiti vit y: a ra n d o mize d cli nical trial. 
I nter nati o nal J o ur n al of Est hetic De ntistr y; 1 7( 1). 
[ Earl J, Leary R, M uller K, et al. ( 2 0 1 1)] P h ysical a n d c he mical c haracterizati o n of de nti n 
s urface f oll o wi n g treat m e nt wit h N o va Mi n tec h n ol o g y. J. Cli n. De nt.; 2 2( 3): 6 2 -7.  
[ Fa v oret o M W, d e S o uza Car neir o T, F or ville H, et al. ( 2 0 2 3)] Use of calci u m-c o ntai ni n g 
bi oacti ve dese nsitizers i n de ntal bleac hi n g: A s yste matic re vie w a n d meta -a n al ysis. J. A m. De nt. 
Ass oc.  
[ F D A ( 2 0 0 5)] G ui d a nce f or I n d ustr y Gi n gi vitis: De vel o p me nt a n d E val uati o n of Dr u gs f or 
Treat me nt or Pre ve nti o n.  
[ Ge n drea u L, Barl o w A, Mas o n S C ( 2 0 1 1)] O ver view of t he cli nical e vi d e nce f or t he use of 
N o va Mi n i n pr o vi di n g relief fr o m t he p ai n of de nti n h y perse nsiti vit y. J. Cli n. De nt.; 2 2( 3): 9 0 -
5.  
[ Gilla m D, B ul ma n J, Ne w ma n H ( 1 9 9 7)] A pil ot assess me nt of alter nati ve met h o ds of 
q ua ntif yi n g de ntal pai n wit h par tic ular refere n ce t o de nti ne h y perse nsiti vit y. C o m m u nit y de ntal 
healt h; 1 4( 2): 9 2 -6.  
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
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Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 5 5  of 5 6  
[ Gó mez ‐ P ol o C, G ó mez ‐ P ol o M, Mart í nez Vaz q uez De Par ga J A, et al. ( 2 0 1 5)] 3 D Master 
T o ot h g ui de acc or di n g t o L *, C *, a n d h * c o or di nates . C ol or Researc h & A p plicati o n; 4 0( 5): 
5 1 8 -2 4.  
[ Gracel y R H, Mc Grat h P, D u b ner R ( 1 9 7 8)] Rati o scales of s e ns or y a n d affecti ve ver bal pai n 
descri pt ors. Pai n; 5( 1): 5 -1 8.  
[ Hatc her R A, Nels o n A L 2 0 0 7] C o ntrace pti ve T ec h n ol o g y. Ne w Y or k, Ar de nt Me dia.  
[ Ha y w o o d V B, C or der o R, Wri g ht K, et al. ( 2 0 0 5)] Br us hi n g wit h a p otassi u m nitrate d e ntifrice 
t o re d uce ble ac hi n g se nsiti vit y. J. Cli n. De nt.; 1 6( 1): 1 7 -2 2.  
[ Heat o n LJ, Barl o w A P, C ol d well S E ( 2 0 1 3)] De vel o p me nt of la bele d m a g nit u de scales f or 
t he assess me nt of pai n of de nti n h y perse nsiti vit y. J. Or ofacial Pai n; 2 7( 1): 7 2. 
[ Heat o n LJ, Barl o w A P, C ol d well SE ( 2 0 1 5)] De vel o p me nt of c o n diti o n -s pecific scales f or 
re p orti n g t he pai n of d e nti ne h y perse nsiti vit y. I n De nti ne H y perse nsiti vit y. Else vier. 
[ H olla n d G, Nar hi M, A d d y M, et al. ( 1 9 9 7)] G ui d eli nes f or t he desi g n a n d c o n d uct of cli nical 
trials o n de nti ne h yperse nsiti vit y. J. Cli n. Peri o d o nt ol.; 2 4( 1 1): 8 0 8 -1 3.  
[ H u M-L, Z h e n g G, Z ha n g Y -D, et al. ( 2 0 1 8)] Effect of dese nsitizi n g t o ot h pastes o n de nti ne 
h y perse nsiti vit y: A s yste matic re vie w a n d meta -a nal ysis. J o ur nal of de ntistr y; 7 5: 1 2 -2 1.  
[I C H ( 1 9 9 6)] G E N E R A L C O N SI D E R A TI O N S F O R C LI NI C A L T RI A L S E 8.  
[I C H ( N o v 2 0 1 6)] T o pic E 6 ( R 2) G ui deli ne f or G o o d Cli nical Practice. 
[J o nes S B, Par ki ns o n C R, Jeffer y P, et al. ( 2 0 1 5)] A ra n d o mise d cli nical trial i n vesti gati n g 
calci u m s o di u m p h os p h osilicate as a de nti ne mi n eralisi n g a ge nt i n t he oral e n vir o n me nt. 
J o ur nal of De ntistr y; 4 3( 6): 7 5 7-6 4.  
[ Ke n w ar d M G, R o ger J H ( 1 9 9 7)] S mall sa m ple i nfere nce f or fi xe d effects fr o m restricte d 
ma xi m u m li keli h o o d. Bi o metrics: 9 8 3 -9 7.  
[ Kieser M, Wass mer G ( 1 9 9 6)] O n t he use of t he u p per c o nfi de n ce li mit f or t he varia n ce fr o m 
a pil ot sa m ple f or sa m ple size deter mi nati o n. Bi o metrical j o ur nal; 3 8( 8): 9 4 1 -9.  
[ Kris h na k u mar K, T a n dale A, Me hta V, et al. ( 2 0 2 2)] P ost-O perati ve Se nsiti vit y a n d C ol or 
C ha n ge D ue t o I n -Office Bleac hi n g Wit h t he Pr i or Use of Differe nt Dese nsitizi n g A ge nts: A 
S yste matic Re vie w. C ure us; 1 4( 4).  
[ Laster L, L a u de n bac h K W, St oller N H ( 1 9 7 5)] A n e val uati o n of cli nical t o ot h m o bilit y 
meas ure me nts. J o ur n al of peri o d o nt ol o g y; 4 6( 1 0): 6 0 3 -7.  
[ Lit k o ws ki L, Gree ns pa n D C ( 2 0 1 0)] A cli nical st u d y of t he effect of calci u m s o di u m 
p h os p h osilicate o n de nti n h y perse nsiti vit y — pr o of of pri nci ple. J o ur nal of Cli nical De ntistr y; 
2 1( 3): 7 7.  
[ L o be ne R ( 1 9 8 6)] A m o difie d gi n gi val i n de x f or use i n cli nical trials. Cli n. pre ve nt. De nt.; 8: 
3 -6.  
[ Mali k A, Ka ul V, Ka ul R, et al. ( 2 0 1 6)] C o m parati ve cli nical efficac y of f o ur differe nt 
dese nsitisi n g a ge nts i n relie vi n g p ost -bleac hi n g se nsiti vit y. A n nals of Pr ost h o d o ntics & 
Rest orati ve De ntistr y; 2( 4): 1 2 0 -5.  
[ Mas o n S, B ur nett G R, P atel N, et al. ( 2 0 19)] I m p act of t o ot h paste o n oral healt h -relate d q ualit y 
of life i n pe o ple wit h de nti ne h y perse nsiti vit y. B M C Oral Healt h; 1 9( 1): 1 -1 1.  
[ Na nj u n dasett y J K, As hraf ulla M ( 2 0 1 6)] Efficac y of d ese nsitizi n g a g e nts o n p ost o perati ve 
se nsiti vit y f oll o wi n g a n i n-off ice vital t o ot h bleac hi n g: A ra n d o mize d c o ntr olle d cli nical trial. 
J o ur nal of c o nser vati ve d e ntistr y: J C D; 1 9( 3): 2 0 7. 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
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C CI

Hale o n  
 
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber :  3 0 0 1 0 6   
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 A b bre viate d Cli nical Pr ot oc ol Te m plate v 1 . 0 
Pa ge 5 6  of 5 6  
[ Nar o n g dej T, Sa k o ol na mar ka R, B o o nr o u n g T ( 2 0 1 0)] T he effecti ve n ess of a calci u m s o di u m 
p h os p h osilicate dese nsitizer i n re d u ci n g cer vica l d e nti n h y perse nsiti vit y. J. A m. De nt. Ass o c.; 
1 4 1( 8): 9 9 5 -9.  
[ Ne u ha us K W, Mille ma n J L, Mille ma n K R, et al. ( 2 0 1 3)] Effecti ve ness of a calci u m s o di u m 
p h os p h osilicate c o ntai ni n g pr o p h yla xis paste i n re d uci n g de nt i ne h y p erse nsiti vit y i m me diatel y 
a n d 4 wee ks  after a si n gle a p plicati o n: a d o u ble ‐ bli n d ra n d o mize d c o ntr olle d trial. J. Cli n. 
Peri o d o nt ol.; 4 0( 4): 3 4 9 -5 7.  
[ Para vi na R D ( 2 0 0 8)] Ne w s ha de g ui de f or t o ot h w hite ni n g m o nit ori n g: vis ual assess me nt. J. 
Pr ost het. De nt.; 9 9( 3): 1 7 8 -8 4.  
[ Pier ote JJ A, B ar b osa I F, Priet o L T, et al. ( 2 0 1 9)] Effects of des e nsitizi n g de ntifrices o n t h e 
re d ucti o n of pai n s e nsiti vit y ca use d b y i n-office de ntal w hite ni n g: a d o u ble -bli n d c o ntr olle d 
cli nical st u d y. Cli nical, C os metic a n d I n vesti gati o nal De ntistr y: 2 1 9 -2 6.  
[ Pier ote JJ A, Priet o L T, Dias C T d S, et al. ( 2 0 2 0)] Effects of des e nsitizi n g pr o d ucts o n t he 
re d ucti o n of pai n se nsiti vit y ca use d b y i n-office t o ot h bleac hi n g: a 2 4 -wee k f oll o w -u p. J o ur nal 
of A p plie d Oral Scie n ce; 2 8.  
[ P ollar d AJ, K ha n I, D a vies M, et al. ( 2 0 2 3)] C o m parati ve effi cac y of self-a d mi nistere d 
de ntifrices f or t he ma n a g e me nt of de nti ne h y p erse nsiti vit y – A s yste matic re vie w a n d net w or k 
meta -a nal ysis. J o ur nal of De ntistr y; 1 3 0: 1 0 4 4 3 3.  
[ Rajes h K, H e d ge S, K u mar M A, et al. ( 2 0 1 2)] E val uati o n of t he efficac y of a 5 % calci u m 
s o di u m p h os p h osilicate ( N o va mi n ®) c o ntai ni n g de ntifrice f or t he relief of de nti nal 
h y perse nsiti vit y: a cli nical st u d y. I n dia n J o ur nal of De ntal Researc h; 2 3( 3): 3 6 3.  
[ R oc ha M O C, Cr uz A A C F, Sa nt os D O, et al. ( 2 0 2 0)] Se nsiti vit y a n d s pecificit y of assess me nt 
scales of de nti n h y perse nsiti vit y– a n acc urac y st u d y. Brazilia n oral r esearc h; 3 4: e 0 4 3.  
[ Sc hiff T, D ots o n M, C o he n S, et al. ( 1 9 9 4)] Efficac y of a d e ntifrice c o ntai ni n g p otassi u m 
nitrate, s ol u ble p yr o p h os p hate, P V M/ M A c o p ol y mer, a n d s o di u m fl u ori d e o n de nti nal 
h y perse nsiti vit y: a t wel ve -wee k cli nical st u d y. J. Cli n. De nt.; 5: 8 7 -9 2.  
[ S har ma S, S hett y NJ, U p p o or A ( 2 0 1 2)] E val u ati o n of t he cli nical efficac y of p otassi u m nitrat e 
dese nsitizi n g m o ut h was h a n d a t o ot h paste i n t he treat me nt of de nti nal h y perse nsiti vit y. J o ur nal 
of cli nical a n d e x p eri me ntal de ntistr y; 4( 1): e 2 8.  
[ S hi va prasa d B, Pa d ma vati P, Sa n g ha ni N N ( 2 0 1 4)] C hair si de a p plicati o n of N o va Mi n f or t he 
treat me nt of de nti nal h y perse nsiti vit y-A n o vel tec h ni q ue. J o ur nal of Cli nical a n d Dia g n ost ic 
Researc h: J C D R; 8( 1 0): Z C 0 5.  
[ West N X ( 2 0 2 3)] Se ve n C o u ntr y E ur o pea n Pre vale nce Data o n T o ot h wear a n d De nti ne 
H y perse nsiti vit y. J De nt Res; 1 0 2( S pec Iss B): 0 7 1 1 -4.  
[ W orl d 
Me dic al Ass oci ati o n ( 2 0 1 3)] Declarati o n of Helsi n ki, 6 4t h Ge neral Asse m bl y, 
F orta le za. 
 
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Si g nat ure Pa ge f or  3 0 0 1 0 6 T M F- 2 4 8 2 3 0 v 2. 0
Si g nat ure Pa ge f or T M F- 2 4 8 2 3 0 v 2. 0
Reas o n f or si g ni n g: A p pr o ve d
Na me:
R ole: A p pr o ver
Date of si g nat ure: 
3 0 0 1 0 6 Pr ot oc ol 3 0 0 1 0 6 Pr ot oc ol 2 7 Se p 2 0 2 4 | T M F- 2 4 8 2 3 0 | 2. 0
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P P D
P P D