A Prospective Real-World Evidence Study Evaluating the Effects of Voltaren Use on Mobility and Quality of Life in Participants With Knee Osteoarthritis (OA) Pain
Phase: PHASE4
Conditions: Pain
Sponsor: HALEON

Hale o n  
Cli nical Pr ot oc ol  
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1  of 7 0  
C LI NI C A L P R O T O C O L  
Pr ot o c ol N u m b er  
3 0 0 1 2 8  
St u d y titl e  
A Pr os pecti ve Real -W orl d E vi de nce St u d y e val uati n g 
t he effects of V oltare n us e o n M o bilit y a n d Q ualit y of 
Life i n s u bjects wit h k nee oste oart hritis ( O A) pai n.  
I n di c ati o n st u di e d 
K nee Oste o art hritis ( Pai n) 
D e v el o p m e nt p h a s e of st u d y  
I V 
C o m p o u n d / pr o d u ct n a m e  
V oltare n Gel 1 % ( Dicl ofe nac s o di u m 1 %)  
V oltare n Gel 1. 1 6 % ( Dicl ofe nac diet h yla m m o ni u m 
1. 1 6 %)  
V oltare n Gel 2. 3 2 % ( Dicl ofe nac diet h yla m m o ni u m 
2. 3 2 %)  
U nit e d St at e s ( U S) 
I n v e sti g ati o n al N e w Dr u g 
(I N D) N u m b er: 
N ot A p plica ble 
Cli ni c al Tri al I nf or m ati o n 
S y st e m ( C TI S) N u m b er:  
2 0 2 4 -5 1 0 8 3 9 -2 2 -0 0  
Ot h er R e g ul at or y A g e n c y 
I d e ntifi e d N u m b er: 
N ot A p plica ble  
D e s cri pti o n 
. 
T his pr os pecti ve real -w orl d e vi de nce st u d y, 
c o n d ucte d i n a h y bri d f or mat, f oc uses o n ass essi n g 
t he i m pact of V oltare n Gel o n f u ncti o nal m o bilit y 
a n d q ualit y of life ( Q o L) i n i n di vi d uals wit h 
mil d/ n o n -seri o us oste oart hritis ( O A) of t he k nee. T he 
st u d y s pa ns m ulti ple c o u ntries, i ncl u di n g t he U nite d 
States a n d t he E ur o pea n U ni 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  
. 
Hale o n ( C H S A R L) 
R o ute de l’ Etraz 2  
Case P ostale 1 2 7 9  
1 2 6 0 N y o n 1  
S witzerla n d
N a m e of c o m p a n y/ s p o n s or 
si g n at or y  
S p o n s or C o nt a ct D et ail s  
Hale o n ( U K)  
St. Ge or ge’s A v e n ue  
We y bri d ge  
K T 1 3 0 D E  
U nite d Ki n g d o m ( U K)  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 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
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P P D

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2  of 7 0  
C R O N a m e  
 
C R O C o nt a ct D et ail s  
 
 
 
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
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C CI
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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 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3  of 7 0  
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)  
A m e n d m e nt 1  
2. 0  
•  
S c h e d ul e of a cti viti e s u p d at e d t o i n cl u d e Uri n e Pr e g n a n c y T e st  
•  
E x cl u si o n crit eri a 1 3 u p d at e d t o ali g n wit h S e cti o n  1 1. 7. 1  
•  
S e cti o n 1 1. 7. 1 u p d at e d t o i n cl u d e w or di n g s fr o m C T F G 
2 1/ 0 9/ 2 0 2 0 V 1. 1  
•  
S e cti o n 1 4. 6 u p d at e d t o i n cl u d e w or di n g s urr o u n di n g art. 5 8 
R e g u l ati o n 5 3 6/ 2 0 1 4 - ar c hi v e t h e c o nt e nt of t h e cli ni c al tri al 
m a st er fil e  
•  
S e cti o n 1 4. 5 u p d at e d t o i n cl u d e p u bli c ati o n p oli c y of t h e tri al 
d at a b ei n g u pl o a d e d t o t h e C TI S d at a b a s e wit hi n o n e y e ar aft er 
e n d of tri al i n a c c or d a n c e wit h C T R A n n e x I V.  
•  
S e cti o n 1 4. 3. 2 u p d at e d t o i n cl u d e s st at e m e nt t h at t h e cli ni c al 
tri al will b e c o n d u ct e d i n c o m pli a n c e wit h R e g ul ati o n [ E U] N o 
5 3 6/ 2 0 1 4.  
•  
S e cti o n 5. 3 u p d at e d t o i n cl u d e cl e ar d efi niti o n of t h e e n d of t h e 
tri al. 
•  
N e w s e cti o n 1 1. 8 R e p orti n g S eri o u s A d v er s e E v e nt s a n d Ot h er  
S af et y I s s u e s t o R e g ul at or y A ut h oriti e s/ Et hi c s C o m mitt e e s 
a d d e d  
•  
N e w s e cti o n 1 1. 9 Ri s k s a n d b e n efit s r el at e d t o t h e p arti ci p ati o n 
i n t h e cli ni c al tri al i n cl u di n g a ri s k s/ b e n efit s e v al u ati o n. 
 
A m e n d m e nt 2  
3. 0  
•  
S e c o n d ar y E n d p oi nt : D ail y A v er a g e n u m b er of st air s 
cli m b e d/ d e s c e n d e d e n d p oi nt r e m o v e d a s t h e y c a n n ot b e 
m e a s ur e d b y A cti gr a p h i n a cli ni c all y v ali d at e d m a n n er . 
•  
S e m a nti c cl arifi c ati o n s o n s e c o n d ar y e n d p oi nt s .  
•  
S c h e d ul e of a cti viti e s  ( T a bl e 1-1)  u p d at e d  t o pr o vi d e cl arit y o n 
d i s p e n si n g of A cti gr a p h d e vi c e a n d u s a g e of Q o L 
q u e sti o n n air e s .  
•  
I n cl u si o n crit eri a 6 f urt h er cl arifi e d t o i n cl u d e e vi d e n c e w hi c h 
c a n b e a c c e pt e d t o c o nfir m O A.  
•  
E x cl u si o n crit eri a 1 0 f urt h er cl arifi e d t o pr o vi d e cl e ar d efi niti o n of 
e x cl u si o n of p ati e nt s.  
•  
S e cti o n 7 . 8 u p d at e d t o ali g n wit h i n cl u si o n/ e x cl u si o n crit eri a a n d 
t o a v oi d c o nf u si o n wit hi n t e xt.  
•  
S e cti o n 1 1 . 3. 2 u p d at e d t o i n cl u d e T a bl e 1 1-1 wit h u p d at e d 
Si n gl e C a s e Pr o c e s si n g  Gr o u p m ail b o x . 
•  
S e m a nti c u p d at e i n S e cti o n 1 3 . 2 t o pr o vi d e m or e cl arit y o n 
p o p ul ati o n a n al y si s .  
•  
S e m a nti c u p d at e i n S e cti o n 1 3 . 3. 2 t o pr o vi d e m or e cl arit y f or 
s e c o n d ar y a n al y si s . 
•  
S e cti o n 1 6 . 3. 1 ( E n d of St u d y q u e sti o n s) u p d at e d t o i n cl u d e 
r e dr aft e d st air s a s c e n di n g/ d e s c e n di n g q u e sti o n a s e n d of st u d y 
q u e sti o n.  
 
A m e n d m e nt 3  
4. 0  
•  
S e cti o n 5. 3 u p d at e d t o i n cl u d e cl e ar d efi niti o n of t h e e n d of t h e 
st u d y.  
Ne w v ersi o ns i nc or p orat e all re visi o ns t o dat e pri or t o s u b missi o n t o c o u ntr y healt h a ut h orities, 
i nstit uti o nal re vie w b oar ds/et hics c o m mittees (I R Bs/ E Cs), etc. 
A me n d me nts i nc or p orate all re visi o ns t o dat e, i ncl u di n g a me n d me nts ma de at t he re q u est of 
c o u ntr y healt h a ut h orities, i nstit uti o nal re vie w b oar ds/et hics c o m mittees (I R Bs/ E Cs), etc.   
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4  of 7 0  
Pri n ci p al I n v e sti g at or Pr ot o c ol A gr e e m e nt P a g e  
•  I c o nfir m a gree m e nt t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol a n d a n y 
a me n d me nts acc or di n g t o t he c urre nt I nter n ati o nal C o nfere nce o n Har m o nisati o n G o o d 
Cli nical Practice (I C H G C P) g ui deli nes.  
•  I ac k n o wle d g e t hat I a m res p o nsi ble f or o verall st ud y c o n d uct. I a gree t o p ers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.  
•  I a gree t o e ns ure t hat all ass ociates, c ollea g ues a n d e m pl o yees assisti n g i n t he c o n d uct of 
t he st u d y are i nf or m e d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n place t o e ns ure site staff 
recei v 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 uct t his st u d y i n f ull c o nf or ma nce wit h t he la ws a n d re g ul ati o ns of t he 
c o u ntr y i n w hic h t he researc h is c o n d u cte d a n d t he Declarati o n of Helsi n ki.  
 
I n v esti gat or Na me: 
I n v estigat or Q ualificati o ns:  
I n v esti gat or Si g nat ure: 
Date of Si g nat ure/ A gree me nt:  
d d -m m m -y y y y  
 
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
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P P D
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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 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5  of 7 0  
T a bl e of C o nt e nt s  
1  
P R O T O C O L S U M M A R Y  ................................................................................................ 1 0  
1. 1  
Sc he d ule of A cti vities  ............................................................................................ 1 7  
2  
I N T R O D U C TI O N ............................................................................................................. 2 0  
2. 1  
St u d y Rati o nale  ...................................................................................................... 2 0  
2. 2  
Bac k gr o u n d  ............................................................................................................ 2 0  
2. 3  
Mec ha nis m of Acti o n/I n dicati o n  ........................................................................... 2 1  
3  
S T U D Y O BJ E C TI V E S A N D E N D P OI N T S  .................................................................... 2 1  
4  
E S TI M A N D S  .................................................................................................................... 2 2  
5  
S T U D Y D E SI G N  .............................................................................................................. 2 3  
5. 1. 1  
Li mitati o ns of t he st u d y  ........................................................................ 2 4  
5. 2  
J ustificati o n f or D ose ............................................................................................. 2 4  
5. 3  
E n d of St u d y a n d Cli nical Trial Defi niti o n ............................................................ 2 4  
6  
S T U D Y P O P U L A TI O N  .................................................................................................... 2 5  
6. 1  
T y pe a n d Pla n ne d N u m b er of S u bjects  ................................................................. 2 5  
6. 2  
I n cl usi o n Criteria ................................................................................................... 2 5  
6. 3  
E xcl usi o n Criteria  .................................................................................................. 2 6  
6. 4  
Ra n d o misati o n Criteria  .......................................................................................... 2 7  
6. 5  
Lifest yle C o nsi derati o ns  ........................................................................................ 2 7  
6. 6  
Scree n Fail ures ....................................................................................................... 2 8  
6. 7  
S p o ns or’s Q ualifie d Me dical Pers o n nel  ................................................................ 2 8  
6. 8  
Rater/ Cli nical Assess or Q ualificati o ns  .................................................................. 2 8  
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 8  
7. 1  
I n v esti gati o nal/ St u d y Pr o d uct(s) S u p plies ............................................................. 2 9  
7. 2  
A d mi nistrati o n  ....................................................................................................... 2 9  
7. 2. 1  
Me dicati o n/ D osi n g Err ors  ..................................................................... 3 0  
7. 2. 2  
O ver d ose  ............................................................................................... 3 0  
7. 3  
I n v esti gati o nal/ St u d y Pr o d uct(s) St ora ge a n d I nstr ucti o ns .................................... 3 1  
7. 4  
I n v esti gati o nal/ St u d y Pr o d uct Acc o u nta bilit y ....................................................... 3 1  
7. 5  
Bli n di n g a n d All ocati o n/ Ra n d o misati o n  ............................................................... 3 2  
7. 6  
Brea ki n g t he Bli n d  ................................................................................................. 3 2  
7. 7  
C o m plia nce  ............................................................................................................ 3 2  
7. 8  
C o nc o mita nt Me dicati o n/ Treat me nt(s)  .................................................................. 3 2  
8  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D S U BJ E C T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ......................................................................... 3 4  
8. 1  
Disc o nti n uati o n of St u d y I nter ve nti o n  .................................................................. 3 4  
8. 2  
S u bject Disc o nti n uati o n/ Wit h dra wal  ..................................................................... 3 4  
8. 3  
L ost t o F oll o w u p  ................................................................................................... 3 4  
9  
S T U D Y P R O C E D U R E S  ................................................................................................... 3 5  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 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 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 6  of 7 0  
9. 1  
Vis it 1/ ( Pre) Scree ni n g ......................................................................................... 3 5  
9. 1. 1  
I nf or me d C o nse nt .................................................................................. 3 6  
9. 1. 2  
De m o gra p hics  ....................................................................................... 3 6  
9. 1. 3  
Me dical Hist or y a n d Pri or Me dicati o n/ Treat me nt  ................................ 3 7  
9. 1. 4  
S u bject Eli gi bilit y  ................................................................................. 3 7  
9. 2  
St u d y Peri o d  .......................................................................................................... 3 7  
9. 2. 1  
Baseli ne Peri o d ...................................................................................... 3 7  
9. 2. 2  
Da ys 1 -2 1  .............................................................................................. 3 7  
9. 2. 3  
E n d of Treat me nt Peri o d/ E n d Of St u d y  ................................................ 3 8  
9. 3  
Diar y Re vie w  ......................................................................................................... 3 9  
9. 4  
St u d y C o ncl usi o n  ................................................................................................... 3 9  
9. 5  
F oll o w -u p Visit/ P h o ne Call  ................................................................................... 3 9  
1 0  S T U D Y A S S E S S M E N T S  ................................................................................................. 3 9  
1 0. 1  
Scree ni n g Assess me nts  .......................................................................................... 4 0  
1 0. 2  
Q ualit y of Life Assess me nts  .................................................................................. 4 0  
1 0. 3  
Weara ble Assess m e nts ........................................................................................... 4 0  
1 0. 4  
Safet y a n d Ot her Assess me nts  ............................................................................... 4 0  
1 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  ........................................... 4 0  
1 1. 1  
Defi niti o n of a n A d verse E ve nt ( A E)  .................................................................... 4 0  
1 1. 2  
Defi niti o n of a Seri o us A d verse E ve nt ( S A E)  ....................................................... 4 2  
1 1. 3  
Re p orti n g Pr oce d ures ............................................................................................. 4 3  
1 1. 3. 1  
Re p orti n g of a n A d verse E ve nt  ............................................................. 4 3  
1 1. 3. 2  
Re p orti n g of a Seri o us A d verse E ve nt  .................................................. 4 4  
1 1. 4  
E val uati n g A d verse E ve nts  .................................................................................... 4 5  
1 1. 4. 1  
Assess me nt of I nte nsit y  ........................................................................ 4 5  
1 1. 4. 2  
Assess me nt of Ca usalit y  ....................................................................... 4 5  
1 1. 5  
F oll o w -u p of A Es a n d S A Es .................................................................................. 4 6  
1 1. 6  
Wit h dra wal D u e t o a n A d verse E ve nt  ................................................................... 4 6  
1 1. 7  
Pre g na nc y  .............................................................................................................. 4 7  
1 1. 7. 1  
Ti me Peri o d f or C ollecti n g Pre g na nc y I nf or mati o n .............................. 4 7  
1 1. 7. 2  
Acti o n t o be Ta ke n if Pre g na nc y Occ urs  .............................................. 4 7  
1 1. 8  
Re p orti n g Seri o us A d verse E ve nts a n d Ot her Safet y Iss ues t o Re g ulat or y 
A ut h orities/ Et hics C o m mittees  ............................................................................. 4 8  
1 1. 9  
Ris ks a n d be nefits relate d t o t he partici pati o n i n t he cli nical trial  ......................... 4 9  
1 1. 9. 1  
Ris ks relate d t o V oltare n gel  ................................................................. 4 9  
1 1. 9. 2  
Be nefits  ................................................................................................. 5 1  
1 1. 9. 3  
Ris ks/ Be nefits E val uati o n  ..................................................................... 5 2  
1 2  D A T A M A N A G E M E N T  .................................................................................................. 5 3  
1 2. 1  
Case Re p ort F or m  .................................................................................................. 5 3  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
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1 2. 2  
Data Ha n dli n g  ........................................................................................................ 5 4  
1 2. 2. 1  
Data Q ueries  .......................................................................................... 5 4  
1 2. 3  
Pr ocessi n g Patie nt/ S u bject Re p orte d O utc o mes a n d Data C ollecti o n fr o m 
I nter net of M e dical T hi n gs .................................................................................... 5 4  
1 3  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  .................................. 5 5  
1 3. 1  
Sa m ple Size Deter mi nati o n  ................................................................................... 5 5  
1 3. 2  
P o p ulati o ns f or A nal ysis  ........................................................................................ 5 5  
1 3. 3  
Statistical A nal yses  ................................................................................................ 5 5  
1 3. 3. 1  
Pri mar y A nal ysis  ................................................................................... 5 6  
1 3. 3. 2  
Sec o n dar y A n al ysis  ............................................................................... 5 6  
1 3. 3. 3  
Safet y A nal ysis(es) ................................................................................ 5 7  
1 3. 3. 4  
E x pl orat or y A nal ysis(es)  ....................................................................... 5 7  
1 3. 3. 5  
E xcl usi o n of Data fr o m A nal ysis  .......................................................... 5 7  
1 3. 3. 6  
De m o gra p hic a n d Baseli ne C haracteristics  ........................................... 5 7  
1 2. 3. 6  
St u d y Dr u g/ Pr o d uct C o m plia nce a n d Us e of Ot her T hera pies  ............. 5 7  
1 3. 3. 7  
Ha n dli n g of Dr o p o uts a n d Missi n g Data  .............................................. 5 8  
1 3. 3. 8  
I nteri m A nal ysis .................................................................................... 5 8  
1 4  S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S .............................................................. 5 8  
1 4. 1  
Q ualit y C o ntr ol  ...................................................................................................... 5 8  
1 4. 2  
Q ualit y Ass ura nce  .................................................................................................. 5 8  
1 4. 3  
Re g ulat or y a n d Et hical C o nsi derati o ns  ................................................................. 5 9  
1 4. 3. 1  
I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee..................................... 5 9  
1 4. 3. 2  
Et hical C o n d uct of t he St u d y  ................................................................ 5 9  
1 4. 3. 3  
S u bject I nf or mati o n  ............................................................................... 5 9  
1 4. 3. 4  
S u bject Recr uit me nt  .............................................................................. 6 0  
1 4. 3. 5  
Re p orti n g of Safet y Iss ues a n d Seri o us Breac hes of t he Pr ot oc ol or 
I C H G C P ............................................................................................... 6 0  
1 4. 4  
P osti n g of I nf or m ati o n o n P u blicl y A vaila ble Cli nical Trial Re gisters  ................. 6 0  
1 4. 5  
Pr o visi o n of St u d y Res ults t o I n vesti gat ors  ........................................................... 6 1  
1 4. 6  
Rec or ds Rete nti o n  .................................................................................................. 6 1  
1 4. 7  
C o n diti o ns f or Ter mi nati n g t he St u d y  ................................................................... 6 2  
1 5  R E F E R E N C E S  .................................................................................................................. 6 3  
1 6  A P P E N DI CI E S .................................................................................................................. 6 4  
1 6. 1  
A B B R E VI A TI O N S  ............................................................................................... 6 4  
1 6. 2  
S T U D Y Q U E S TI O N N AI R E S  .............................................................................. 6 5  
1 6. 2. 1  
Wester n O nt ari o a n d Mc Master U ni versities Art hritis I n de x 
( W O M A C) 5-p oi nt Li kert scale e xa m ple  ............................................. 6 5  
1 6. 2. 2  
Kar o li ns ka Slee pi ness Scale E xa m ple .................................................. 6 6  
1 6. 2. 3  
Self -Re p orte d Pai n N u m erical Rati n g Scale a n d Vis ual A nal o g ue 
Scale E xa m ples  ..................................................................................... 6 7  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 8  of 7 0  
1 6. 2. 4  
E Q -5 D -5 L Q u alit y of Life Q uesti o n naire e xa m ple  .............................. 6 8  
1 6. 3. 1  
E n d of t he st u d y q uesti o ns  .................................................................... 6 9  
1 6. 4  
A C TI G R A P H I N F O R M A TI O N  ........................................................................... 7 0  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 9  of 7 0  
Li st of i n t e xt t a bl e s  
Ta ble 1 -1  
Sc he d ule of Acti vities  ........................................................................... 1 8  
Ta ble 3 -1  
St u d y O bjecti ves a n d E n d p oi nts  ........................................................... 2 1  
Ta ble 7 -1  
I n v esti gati o nal/ St u d y Pr o d uct(s) a n d De vice ........................................ 2 9  
Ta ble 1 1 -1  
Si n gle Case Pr ocessi n g mail b o x  ........................................................... 4 5  
Ta ble 1 6. 1  
A b bre viati o ns  ........................................................................................ 6 4  
 
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 0  of 7 0  
1  
P R O T O C O L S U M M A R Y  
   
Title of St u d y  
A Pr os pecti ve Real -W orl d E vi de nce St u d y e val u ati n g t he 
effects of V oltare n use o n M o bilit y a n d Q o L of s u bjects 
wit h k nee oste oart hritis ( O A) pai n.  
Pr ot oc ol N u m ber  
3 0 0 1 2 8  
I n vesti g at ors/ St u d y Sites 
St u d y Si des: 8  
C o u ntries: U nite d States a n d E ur o pea n U ni o n ( P ola n d)  
P h ase of De vel o p me nt  
P hase I V ( Real W orl d E vi de nce St u d y)  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 1  of 7 0  
O bjecti ves  
T he p ur p os e of t he st u d y is t o i n vesti gate h o w t o pical 
dicl ofe nac use ca n i m pr o ve f u ncti o nal 
m o bilit y a n d 
p h ysical acti vit y pri maril y, as well as ot her q ualit y -of -life 
para me ters s uc h as slee p, m o o d, a n d e n ga g e me nt i n dail y 
acti vities.  
Pri mar y O bjecti ve:  
•  T o e val uate t he effects of V oltare n Gel o n p h ysi cal 
acti vit y, 
meas ure d t hr o u g h c o n nect e d acti vit y 
trac ker. 
 
Sec o n dar y O bj ecti ves:  
•  T o e val uate t he effects of 
V oltare n 
Gel o n 
f u ncti o nal m o bilit y, meas ure d t hr o u g h c o n nect e d 
acti vit y trac ker.  
•  T o assess t he f u ncti o nal m o bilit y, meas ure d t hr o u g h 
c o n necte d acti vit y trac k er.  
•  T o e val uate t he effects of 
V oltare n 
Gel o n 
f u ncti o nal 
m o bilit y, 
meas ure d t hr o u g h S u bject 
relate d o utc o mes. 
•  T o e val uat e t he effects of V oltare n Gel o n pai n 
i nte nsit y. 
•  T o e val uate t he effects of V oltare n Gel o n acti vit y -
relate d pai n a n d stiff ness. 
•  T o e val uat e t he effects of V oltare n Gel o n c orrelates 
of q ualit y of life.  
 
E x pl orat or y:  
•  T o e x pl ore t he li n k bet wee n V oltare n usa g e, le vel 
of pai n relief a n d f u n cti o nal m o bilit y/ q ualit y of life  
•  T o e val uate ti me -t o m ea ni n gf ul pai n relief aft er 
V oltare n Gel us e.  
 
Safet y:  
•  T o 
m o nit or a d verse e v e nts ( A Es) d uri n g st u d y 
peri o d.  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 2  of 7 0  
St u d y E n d p oi nts  
Pri m ar y e n d p oi nt:  
C ha n ge fr o m bas eli ne i n t he a vera ge mi n utes of M o derate 
a n d Vi g or o us P h ysical Acti vit y ( M V P A), at Wee k 1 ( da ys 
1 -7), Wee k 2 ( da ys 8 -1 4), a n d Wee k 3 ( da ys 1 5 -2 1).  
Sec o n d ar y e n d p oi nts:  
C ha n ge fr o m bas eli ne o n Da ys 7, 1 4, a n d 2 1 i n: 
•  Dail y A vera g e n u m ber of ste ps ta ke n  
•  Rati o of se de ntar y/ n o n -s e de ntar y ti me  
•  Gait, assesse d t hr o u g h s pee d a n d ste p irre g ularit y  
( meas ure d vi a ca d e nce a n d gait s pee d) 
•  I n dices of 
m or ni n g stiff ness (ass esse d t hr o u g h 
le vels of acti vit y  3 0 - a n d 6 0-mi ns  p ost -wa ke)  
I n dices of le vel of stiff n ess t hr o u g h o ut t he da y as assesse d 
via t he W O M A C stiff ness s u bscale C ha n ge fr o m baseli ne 
i n: 
•  W O M A C P h ysical F u n cti o n s u bscale o n Da ys 7, 
1 4, a n d 2 1  
•  St u d y s u bjects’ percei ve d a bilit y t o e xercise m or e 
re g ularl y. Ass esse d usi n g t he 
W O M A C P h ysical 
F u ncti o n s u bscale o n Da ys 7, 1 4, a n d 2 1  
•  C ha n ge fr o m 
baseli ne i n self -re p orte d 
pai n 
i nte nsit y, assesse d t hr o u g h N u meric Rati n g Scale 
( N R S) ( dail y assess me nt) 
C ha n ge fr o m baseli ne i n t he 
W O M A C t otal sc ore a n d 
s u bscales o n Da ys 7, 1 4, a n d 2 1:  
•  Pai n (c o m p osite)  
•  Stiff ness (c o m p osite)  
C ha n ge fr o m bas eli ne i n o n Da ys 7, 1 4, a n d 2 1  
•  Slee p/alert ness: Kar oli ns ka Slee pi ness Scale 
assesse d 1 x/ da y.  
•  Healt h -relate d q ualit y of life: E Q-5 D -5 L  
E x pl or at or y e n d p oi nts:  
•  C orrelati o ns b et wee n V oltare n usa ge, pai n reli ef 
a n d m o bilit y a n d q ualit y of life i n dices t hr o u g h o ut 
t he trial. 
•  Ela pse d ti me fr o m V oltare n Gel use t o ac hie vi n g 
ti me t o mea ni n gf ul pai n relief t o e n d of st u d y. 
Esti m a n ds  
N/ A  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 3  of 7 0  
St u d y Desi g n  
T his is a pr os pecti ve, o pe n -la bel, si n gle-ar m, m ulti -c o u ntr y 
( U S a n d E U ( P ola n d)) real-w orl d e vi d e nce st u d y assessi n g 
t he effects of V oltare n Gel use o n f u ncti o nal m o bilit y a n d 
Q o L i n s u bjects wit h mil d/ n o n -seri o us oste oart hritis ( O A) 
of t he k nee.  
T his st u d y will utilise a researc h -gra de vali date d weara ble 
de vice: 
Acti gra p h, t o o bjecti vel y 
meas ure c h a n ges i n 
f u ncti o nal m o bilit y, t o get her wit h t he use of s u bjecti ve 
assess me nts, t o pr o vi de first -e ver s u bject -ce ntric data o n 
t he real-w orl d be n efits of usi n g V oltare n Gel, be y o n d pai n 
relief. 
T he tar g et p o p ulati o n c o m prises male a n d fe m ale a d ults 
a ge d bet w ee n 4 0 a n d 8 5 years, di a g n ose d wit h mil d/ n o n -
seri o us oste oart hritis of t he k nee a n d self-re p orte d pai n at 
t he ti me of recr uit me nt. A p pr o xi matel y 1 9 5 s u bjects are 
e x pecte d t o be e nr olle d i n t he st u d y, wit h a n a ntici pati o n 
t hat a p pr o xi matel y 1 4 7 of t hese s u bjects will s uccessf ull y 
c o m plete t he e ntire st u d y.  
T his st u d y a d o pts a h y bri d a p pr oac h, w herei n partici pa nts 
are o nl y o bli gate d t o be p h ysicall y prese nt f or o n -site 
scree ni n g ( Da y -7), e n d of baseli ne ( Da y 0), a n d e n d -of -
st u d y visits ( Da y 2 1). T h e re mai ni n g tr eat me nt p h ase ( Da y 
1 -2 1) will be c o n d ucte d i n a re m ote ma n ner (e. g. at h o me)  
t o o bser ve t he real-w orl d usa ge of t he pr o d uct. St u d y peri o d 
f or eac h s u bject will last a ma xi m u m of 2 8 da ys. 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 4  of 7 0  
Selecti o n of S u bjects  
Mai n I n cl usi o n Criteria:  
•  A S u bject bet wee n t h e a g e of 4 0 a n d 8 5 y ears.  
•  A s u bject wit h dia g n ose d k nee mil d/ n o n -seri o us 
oste oart hritis, pr o ve n via ra di ol o gical e vi de n ce 
c ollecte d wit hi n t he last 3 year s. 
•  A s u bject wit h self -re p orte d k nee pai n, wit h a 
sc ore of ≥ 4 0 m m ≤ 7 0 m m o n t he pai n i nte nsit y 
vis ual a nal o g ue scale at t he Scree ni n g Visit.  
•  A s u bject willi n g t o use V oltare n Gel f or u p t o 3 
wee ks.  
Mai n E xcl usi o n Criteria:  
•  A s u bject wit h c o nfir me d r he u mat ol o gic disease.  
•  A s u bject w h o has e x p eri e nce d tr a u ma t o t he k nee 
wit hi n t he last 2 m o nt hs t hat res ulte d i n pai n a n d/ or 
s welli n g. 
•  A s u bject t hat has bee n a d mi nistere d l ocal ster oi ds 
or ot her N S AI Ds i njecti o ns t o t he k nee wit hi n t he 
last 6  m o nt hs.  
•  A s u bject wit h rece nt hist or y of maj or k nee i nj ur y 
or s ur ger y.  
•  A s u bject wit h k nee s ki n area p at h ol o gical 
c o n diti o n w hic h pre ve nts a p plicati o n of pr o d uct t o 
t he s ki ns. C o n diti o ns s uc h as: o pe n s ki n w o u n ds, 
i nfecti o ns, i nfla m mati o ns, or e xf oliati ve der matitis 
c o n diti o ns.  
•  A s u bject w h o is pre g n a nt, lactati n g or pla n t o be 
pre g na nt or lactati n g d uri n g t he st u d y.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 5  of 7 0  
Pl a n ne d S a m ple Size  
S ufficie nt i n di vi d uals 
will 
be 
scree ne d t o 
e nr ol 
a p pr o xi matel y 1 9 5 s u bjects ass u mi n g a n esti m ate d 2 5 % 
dr o p o ut rate. It is belie ve d t hat f or t his st u d y 1 4 7 c o m plete d 
s u bjects are dee me d s ufficie nt t o o bser ve a n i m pr o ve me nt 
i n Q o L. 
T here were n o pre vi o us si milar st u dies meas uri n g M V P A 
c o u ple d wit h dail y use of a dicl ofe nac g el. T h us, t he effect 
size was c h ose n bas e d o n literat ure re vie w t o det ect e ve n 
mil d i m pr o ve me nt i n Q o L fact ors: “ A n effect ma g nit u de 
bet wee n 0. 2 a n d 0. 5 i n di cates mil d i m pr o ve me nt, bet wee n 
0. 5 a n d 0. 8 i n dicates m o derate i m pr o ve me nt, a n d greater 
t ha n 0. 8 i n dicates c o nsi dera ble i m pr o ve me nt i n s y m pt oms 
a n d Q o L.” T he s a m ple size was bas e d o n a si g nifica nce 
le vel ( α) = 0. 0 5, P o wer ( 1-β) = 8 0 %, a n d a sta n dar dize d 
effect size of 0. 2 5  
Literat ure re vie w als o i n dicate d t hat Q o L sc ores are n ot 
n or mall y 
distri b ute d. 
S u bjects 
wit h 
w orse 
baseli ne 
s y m pt o ms s h o wed lar ger i m pr o ve me nt i n Q o L sc ores. 
T heref ore, a t w o -si de d n o n-para m etric 
Wilc o x o n Si g ne d 
Ra n k test calc ulati o n was perf or me d.  
Usi n g t he a b o ve para meters, we o btai n a sa m ple size N 
= 1 9 5 t o retai n t he re q uire d 1 4 7 c o m plete d s u bjects. 
T heref ore, it has b ee n d eter mi ne d t hat 1 9 5 eli gi ble s u bjects 
will be recr uite d f or t h e trial, wit h a n a ntici pate d 1 4 7 st u d y 
s u bjects e x pect e d t o s uccessf ull y c o m plete t he st u d y. 
 
I n vesti g ati o n al T her a p y 
V oltare n Gel 1 % ( dicl of e nac s o di u m) ( U S O nl y)  
V oltare n Gel 1. 1 6 % ( di cl ofe na c diet h yla m m o ni u m) ( E U 
O nl y)  
V oltare n Gel 2. 3 2 % ( di cl ofe nac diet h yla m m o ni u m) ( E U 
O nl y)  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 6  of 7 0  
Tre at me nt 
D ur ati o n/I nter ve nti o n  
Acti gra p h de vice will be pr o vi de d p ost patie nt c o nse nt at 
Da y -7 t o c ollect b aseli ne i nf or mati o n.  
T he baseli ne peri o d will last bet wee n  3 ( mi ni m u m) a n d 7 
da ys ( ma xi m u m), t o c ollect e n o u g h i nf or mati o n o n b ot h 
s u bjecti ve a n d o bjecti v e as pects of m o bilit y a n d slee p 
q ualit y.  
E n d of baseli ne peri o d will be c o nsi dere d da y 0.  
P ost baseli ne peri o d, (at Da y 7 of t he st u d y) s u bjects will 
be pr o vi de d wit h t he pr o d uct ( V oltare n) a n d Acti gra p h 
de vice w here t here will be a t otal of 2 1 da ys of pr o d uct 
usa ge a n d assess me nt of para meters as hi g hli g hte d i n t he 
o bjecti ves.  
Eac h s u bject will be i n t h e st u d y f or 2 8 da ys ma xi m u m.  
S afet y  
N u m ber a n d perce nt of st u d y s u bjects re p orti n g A Es or 
seri o us A Es ( S A Es) w hil e o n treat me nt. 
•  Treat me nt Relate d.  
•  N o n -Treat me nt Relate d.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 7  of 7 0  
St atistic al Met h o ds a n d 
Pl a n ne d A n al yses  
F or t h e pri mar y o bjecti ve, a Mi xe d M o d el wit h Re peate d 
Meas ures ( M M R M) will be use d t o a n al yse t h e c ha n g e 
fr o m baseli ne i n M V P A a vera ge mi n utes as t he res p o nse 
varia ble. S u bject will be i ncl u de d as a ra n d o m effect.  
A vera g e mi n utes of M V P A o ver Wee k 1 will be calc ulate d 
o ver all n o n -missi n g da ys bet wee n st u d y da y 1 ( pr o d uct 
usa ge) t hr o u g h 7, i ncl usi ve. A vera g e mi n utes of M V P A 
o ver Wee k 2 will be calc ulate d o ver all n o n -missi n g da ys 
bet wee n st u d y d a y 8 t hr o u g h 1 4, i ncl usi ve. 
A vera g e 
mi n utes of M V P A o ver Wee k 3 will be cal c ulate d o ver all 
n o n -missi n g da ys bet wee n st u d y da y 1 5 t hr o u g h 2 1, 
i ncl usi ve. A n y da ys be y o n d da y 2 3 will be e xcl u de d fr o m 
all s u m maries a n d a nal ys es a n d will o nl y be prese nt i n liste d 
data.  
F or t he sec o n d ar y o bjecti ve, f u ncti o nal 
m o bilit y as 
meas ure d t hr o u g h 
weara bles a n d P R O, pai n i nte nsit y 
assesse d t hr o u g h N R S  ( dail y assess me nt), acti vit y -relate d 
pai n a n d stiff ness as 
meas ure d i n t he ( Li kert Scale) 
W O M A C s u bscales f or c o m p osite pai n a n d c o m p osite 
stiff ness will be a nal yse d i n t he sa me ma n ner as t he pri mar y 
o bjecti ve.  
F or t he e x pl or at or y e n d p oi nts, c orrelati o ns b et w ee n p ai n 
relief, m o bilit y, a n d q ualit y of life i n dices will be meas ure d 
t hr o u g h o ut t he trial. A d diti o nall y, t he use of c o nc o mita nt 
me dicati o ns a n d a n y c ha n ges i n use of pai n relief 
me dicati o ns will be rec or de d t hr o u g h o ut t he trial.  
Ti me t o pai n relief will be e val uate d usi n g Ka pl a n -Meier 
c ur ves of Q o L fact ors. T he me dia n ti me t o res ol uti o n of 
s y m pt o ms base d o n t he 
Ka pla n-M eier c ur ve 
will be 
prese nte d as well.  
   
 
 
1. 1  
S c h e d ul e of A cti viti e s  
T he sc he d ule of acti vities ta ble pr o vi des a n o ver vie w of t he s u bject visits a n d st u d y pr oce d ures.   
T he i n vesti gat or ma y sc he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d o n t he 
sc he d ule of acti vities, t o c o n d uct e val uati o ns or assess me nts re quire d t o pr otect t he well -bei n g.  
T his st u d y a d o pts a h y bri d a p pr oac h, w herei n partici pa nts are o nl y o bli gate d t o be p h ysicall y 
prese nt f or o n -site scree ni n g ( Da y -7  –  Visit 1 ), e n d of baseli ne ( Da y 0–  Visit 2 ), a n d e n d-of -
st u d y visits ( Da y 2 1–  Visit 3 ). The re mai ni n g treat me nt p hase ( Da y 1 -2 1) will be c o n d ucte d at 
h o me or i n areas of i nterest t o o bser ve t he real -w orl d e vi de nce ( R W E) us a ge of t he pr o d uct. 
St u d y peri o d will last a ma xi m u m of 2 8 da ys.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 8  of 7 0  
T a bl e 1 -1  
S c h e d ul e of A cti viti e s  
 
Pr o c e d ur e/ A s s e s s m e nt  
S cr e e ni n g 
a n d 
E nr ol m e nt  
B a s eli n e *  
St u d y Tr e at m e nt P h a s e **  
D a y -7  
( Vi sit 1) 
D -7 t o D 0  
( Vi sit 2) 
D 1  
D 1 t o 
D 6  
D 7  
D 8 t o 
D 1 3  
D 1 4  
D 1 5 
t o 
D 2 0  
D 2 1  
( Vi sit 3) 
I nf or m e d C o n s e nt 
X  
 
 
 
 
 
 
 
 
I n cl u si o n/ E x cl u si o n Crit eri a 
X  
 
 
 
 
 
 
 
 
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  
X  
X  
X  
X  
X  
S u bj e ct Eli gi bilit y  
X  
 
 
 
 
 
 
 
 
St u d y Pr o d u ct u s e  
 
 
X  
X  
X  
X  
X  
X  
X  
Uri n e Pr e g n a n c y T e st***  
X  
 
 
 
 
 
 
 
X  
Di s p e n si n g of ( A cti gr a p h)  a  
X  
 
 
 
 
 
 
 
 
Di s p e n si n g of Pr o d u ct 
( V olt ar e n) a  
 
X  
 
 
 
 
 
 
 
P ai n  
N u m eri c R ati n g S c al e b  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Vi s u al A n al o g u e S c al e b  
X  
X  
 
 
 
 
 
 
 
W e st er n O nt ari o a n d 
M c M a st er U ni v er sit y 
O st e o art hriti s i n d e x 
( W O M A C) P ai n S u b s c al e b  
 
X  
X  
 
X  
 
X  
 
X  
M o bilit y  
Tr a c k er -d eri v e d m o bilit y 
a s s e s s m e nt  c 
 
X  
X  
X  
X  
X  
X  
X  
X  
W e st er n O nt ari o a n d 
M c M a st er U ni v er sit y 
O st e o art hriti s i n d e x 
( W O M A C) Stiff n e s s 
S u b s c al e b  
 
X  
X  
 
X  
 
X  
 
X  
W e st er n O nt ari o a n d 
M c M a st er U ni v er sit y 
O st e o art hriti s i n d e x 
( W O M A C) F u n cti o n 
S u b s c al e b  
 
 
 
 
 
 
X  
X  
 
X  
 
X  
 
X  
Sl e e p  
Tr a c k er -d eri v e d sl e e p 
a s s e s s m e nt  
 
X  
X  
X  
X  
X  
X  
X  
X  
K ar oli n s k a Sl e e pi n e s s 
S c al e  b  
 
X  
X  
X  
X  
X  
X  
X  
X  
Q u alit y of Lif e  
E Q -5 D -5 L Q u alit y of Lif e 
Q u e sti o n n air e  
 
X  
X  
 
X  
 
X  
 
X  
S af et y  
A d v er s e E v e nt s ( A E s) 
R e vi e w c 
X  
X  
X  
X  
X  
X  
X  
X  
X  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 1 9  of 7 0  
Pr o c e d ur e/ A s s e s s m e nt  
S cr e e ni n g 
a n d 
E nr ol m e nt  
B a s eli n e *  
St u d y Tr e at m e nt P h a s e **  
D a y -7  
( Vi sit 1) 
D -7 t o D 0  
( Vi sit 2) 
D 1  
D 1 t o 
D 6  
D 7  
D 8 t o 
D 1 3  
D 1 4  
D 1 5 
t o 
D 2 0  
D 2 1  
( Vi sit 3) 
St u d y C o n cl u si o n  
R et ur ni n g A cti gr a p h d e vi c e 
a n d t h e all o c at e d pr o d u ct  
 
 
 
 
 
 
 
 
X  
E n d of St u d y 
Q u e sti o n n air e s  
 
 
 
 
 
 
 
 
X  
 
F o ot n otes:  
a Acti gra p h trac ker is dis pe nse d at scree ni n g visit  p ost c o nse nt of patie nt d uri n g e nr ol me nt f or t he st u d y  ( D -7  –  Visit 1 ). a n d 
V oltare n is dis pe nse d i m me diatel y p ost eli gi bilit y of t he s u bject at t h e e n d of Baseli ne peri o d ( Da y 0 –  Visit 2).  
b T h e q uesti o n naires s uc h as: Pai n Vis ual A nal o g ue Scale ( V A S) / N u meric Rati n g Scale  ( N R S), will i nitiall y be perf or me d o n 
site d uri n g e nr ol me nt peri o d ( Visit 1) a n d pri or t o dis pe nsi n g of V oltare n ( Visit 2), t o c o m plete t he baseli ne assess me nt. S u bjects 
are t h e n re q u ire d t o perf or m t he assess m e nt of N R S, Wester n O ntari o a n d 
Mc Master U ni versit y Oste oart hritis i n de x 
( W O M A C), Kar oli ns ka Slee pi ness Scale  a n d t he E Q -5 D -5 L Healt h q uesti o n naire  at site pri or t o dis pe nsi n g of V oltare n ( Da y 
0 –  Visit 2) a n d t h e n at h o me d uri n g t he st u d y peri o d a n d re p ort t he sc ore wit hi n t h e e Diar y.  
c A d verse E v e nts ( A Es) a n d t h eref ore all Seri o us A d verse E v e nts ( S A Es) will be c ollecte d i m me diatel y after a s u bject  pr o vi d es 
c o nse nt t o partici p ate i n t h e st u d y b y t h e c o m pleti o n of t h e I nf or me d C o nse nt F or m (I C F).  
* Baseli ne peri o d will be fle xi ble a n d last a mi ni m u m of 3 da ys a n d ma xi m u m 7 da ys t o c ollect s ufficie nt baseli ne i nf or mati o n  
fr o m st u d y s u bjects. W he n pai n le vels reac h ≥4 0 m m ≤ 7 0 m m i n t h e V A S/ N R S scale, t h e da y bef ore starti n g t h e use of V oltare n, 
st u d y s u bjects will be pr o m pte d t o a ns wer rele va nt q uesti o n naires t o assess bas eli ne le vels. Site staff t o m o nit or s u bjects e Diar y 
a n d dis pe nse V oltare n w he n pat ie nts h a ve e n de d baseli ne peri o d. S u bjects ca n als o n otif y site staff w he n t heir baseli ne peri o d 
has e n de d t o c o m me nce t h e st u d y.   
* * St u d y peri o d will last a ma xi m u m of 2 8 da ys. St u d y s u bjects are all o we d t o st o p usi n g V oltare n if t he y feel t h at t heir pa i n 
has s uccessf ull y res ol ve d a n d d o n ot nee d t o use t he pr o d uct a n y m ore.  
* * * Uri ne test o nl y nee de d f or w o me n of c hil d beari n g p ote ntial a n d p ost me n o pa usal w o me n w h o are n ot s ur gicall y sterile. 
U ri n e sa m ples are c ollecte d t o detect t h e prese nce of h u ma n c h ori o nic g o na d otr o pi n ( h C G), a h or m o ne pr o d uce d d uri n g 
pre g na nc y.  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 0  of 7 0  
2  
I N T R O D U C TI O N 
Real w orl d e vi de nce ( R W E) st u dies pr o vi de a n o p p ort u nit y t o gat her i nf or mati o n o n t he real -
life effecti ve n ess of a pr o d uct i n a p o p ulati o n t hat is refl ecti ve of t he c o ns u m er b ase. T h e prese nt 
st u d y ai ms t o use a pr os pecti ve R W E desi g n t o ass ess t he real-life i m pact of usi n g V oltare n Gel 
( dicl ofe nac) o n f u ncti o nal m o bilit y a n d q ualit y of life. T his is t he first Hale o n st u d y t hat will 
g o be y o n d s u bjecti ve assess me nt of t hes e b e nefits , usi n g researc h-gra d e weara ble de vices 
( Acti gra p h) t o acc uratel y meas ure c ha n ges i n f u ncti o nal m o bilit y a n d as pects of q ualit y of life 
(O’ Brie n et al. 2 0 2 0 ). T o get her wit h o bjecti ve a n d s u bjecti ve assess me nts of t hese be nefits, t his 
st u d y will pr o vi de us wit h first-e ver s u bject -ce ntric data o n t he real -w orl d be nefits of usi n g 
V oltare n, be y o n d p ai n relief.  
2. 1  
St u d y R ati o n al e  
T his st u d y is desi g ne d t o assess t he real -life i m pact of usi n g V oltare n Gel ( dicl ofe n ac) o n 
f u ncti o nal m o bilit y a n d q ualit y of life. T his st u d y will utilise a researc h-gra de vali date d 
weara ble de vic e: Acti gra p h, t o acc uratel y meas ure o bjecti ve c ha n g es i n f u n cti o nal m o bilit y.  
2. 2  
B a c k gr o u n d  
T o pical dicl ofe nac pr o d ucts are well -esta blis he d gl o ball y f or t he treat me nt  of pai n a n d 
i nfla m mati o n d ue t o ac ute tra u ma (s prai ns, strai ns, m uscle ac hes, s p orts i nj uries) as w ell as f or 
t he relief of mil d/ n o n-seri o us oste oart hritis pai n. T o pical N o n-ster oi dal a nti-i nfla m mat or y 
dr u gs ( N S AI Ds) w hic h are a p plie d l ocall y t o t he site of s y m pt o ms pe netrate t he s ki n a n d 
per meate t o dee p er tiss u es t o e xert a t h era p e utic effect ( Ha ge n a n d Ba k er, 2 0 1 7 ). Cli nical 
st u dies of t o pical N S AI D S i n O A of t he h a n d a n d k nee ha ve de m o nstrate d statisticall y 
si g nifica nt a nd cli nicall y mea ni n gf ul pai n relief ( B art hel et al 2 0 0 9 , Alt ma n et al 2 0 1 1). 
Wit h re gar ds t o oste oart hritis, t he pri mar y g oal of disease ma na ge m e nt is t o c o ntr ol s y m pt o ms, 
s uc h as pai n a n d i m pair e d f u ncti o n (J or da n et al 2 0 0 3, Kl o p pe n b ur g et al 2 0 1 9). A net w or k 
meta -a nal ysis f o u n d t hat N S AI Ds are t he m ost effecti ve i n di vi d ual treat me nt t o i m pr o ve pai n 
a n d f u ncti o n i n oste oart hritis ( Je vse var et al 2 0 1 8). T he a ut h ors  c o n cl u de t hat t o pical dicl ofe nac, 
re gar dl ess of d ose, ha d t he lar gest effect o n pai n a n d p h ysical f u ncti o n c o m pare d t o ot her t o pical 
treat me nts i ncl u di n g N S AI Ds. I n a rece nt met a-a nal ysis of 1 9 2 cli nical trials, t he a ut h ors 
assesse d t he effecti ve n ess a n d safet y of differe nt pre parati o ns a n d d oses of N S AI Ds, o pi oi ds, 
a n d paracet a m ol t o hel p healt h care pr o vi d ers m a na ge k n ee a n d hi p O A pai n a n d p h ysical 
f u ncti o n (Da C osta et al. 2 0 2 1 ).  
T he use of t o pical N S AI Ds is rec o m me n de d i n e vi de nce-b ase d tr eat me nt g ui deli nes f oc use d o n 
t he ma na ge m e nt of O A.  T o pical N S AI Ds are rec o m me n de d b y t he A merica n C olle ge of 
R he u mat ol o g y ( A C R) a n d t he Oste oart hritis Researc h S ociet y I nt er nati o nal ( O A R SI) f or t h e 
s y m pt o matic treat me nt of O A of t h e knee. A d diti o nall y, t he A C R als o str o n gl y rec o m me n ds 
t o pical N S AI Ds f or patie nts/s u bjects wit h k nee O A, a n d n otes t hat t o pical N S AI Ds s h o ul d be 
c o nsi dere d pri or t o t he use of oral N S AI Ds, t o mi ni mize s yste mic e x p os ure ( K olasi n s ki et al 
2 0 1 9 ).  T he 
O A R SI g ui deli nes str o n gl y rec o m me n d t o pical 
N S AI Ds f or k nee 
O A 
patie nts/s u bjects wit h a n d wit h o ut gastr oi ntesti nal or car di o vas c ular c o m or bi dities a n d f or 
patie nts/s u bjects wit h frailt y ( Ba n n ur u et al 2 0 1 9 ). 
Des pite t hese well -esta blis he d be nefici al effects of dicl ofe n ac f or t he treat me nt of pai n a n d 
i nfla m mati o n i n O A, t he real-life m o bilit y a n d q ualit y of life be nefits of usi n g dicl ofe nac f or 
pai n relief ha ve n ot bee n e xa mi ne d. C o nsi deri n g t he lar ge i m p act t hat k n ee O A pai n c o ul d h a ve 
o n s u bjects a bilit y t o m o ve, e x ercise, a n d perf or m dail y acti vities, it is hi g hl y li kel y t hat 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 1  of 7 0  
dicl ofe nac rel ate d pai n relief ca n lea d t o s u bsta ntial i m pr o ve me nt i n pe o ple’s q ualit y of life 
(Va n Walse m et al 2 0 1 5).  Acc or di n g t o t he A C R, e xercis e is c o nsi dere d a hi g hl y effecti ve a n d 
rec o m me n de d i nter ve nti o n i n k nee O A, t here b y c o nce pt ualizi n g m o bilit y n ot o nl y as a n 
o utc o me t hat is affecte d b y k nee O A b ut als o as a n e na bler of i m pr o ve d disease o u tc o mes i n 
O A ( K olasi ns ki et al 2 0 1 9 ). T he p ur p ose of t he st u d y is t o i n vesti gate h o w t o pical dicl ofe nac 
use ca n i m pr o ve f u ncti o nal m o bilit y a n d p h ysical acti vit y pri maril y, as well as ot her q u alit y -of -
life para m eters s uc h as slee p, m o o d, a n d e n g a ge m e nt i n dail y acti vities. 
2. 3  
M e c h a ni s m of A cti o n/I n di c ati o n  
V oltare n Gel c o ntai ns dicl ofe nac as a n acti ve i n gr e die nt. It is a n o nster oi dal a nti -i nfla m mat or y 
dr u g ( N S AI D) t h at is use d f or t he treat me nt of i nfl a m mati o n a n d pai n. T he pri ma r y mec h a nis m 
res p o nsi ble f or t hese effects is t h o u g ht t o be t he i n hi biti o n of pr osta gla n di n s y nt hesis via 
i n hi biti o n of C ycl o o x y ge nase 1 ( C O X-1) a n d C O X -2.  
3  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S  
T a bl e 3 -1  
St u d y O bj e cti v e s a n d E n d p oi nt s  
O bjecti ve(s)  
E n d p oi nt(s)  
Pri m ar y  
T o e v al uate t he effects of V oltare n Gel o n p h ysical 
acti vit y, meas ure d t hr o u g h c o n necte d acti vit y trac ker.  
C ha n ge fr o m baseli ne i n t he a vera ge 
mi n utes of 
M o derate a n d Vi g or o us P h ysical Acti vit y ( M V P A), at 
Wee k 1 ( da ys 1 -7), Wee k 2 ( da ys 8 -1 4), a n d Wee k 3 
( da ys 1 5-2 1).  
Sec o n d ar y  
T o e v al uate t he effects of V oltare n Gel o n f u ncti o nal 
m o bilit y, meas ure d t hr o u g h c o n necte d acti vit y trac ker  
C ha n ge fr o m baseli ne o n Da ys 7, 1 4, a n d 2 1 i n:  
• Dail y A vera ge n u m ber of ste ps ta ke n   
• Rati o of se de ntar y/ n o n -se de ntar y ti me  
• Gait, assesse d t h r o u g h s pee d a n d ste p irre g ularit y 
( meas ure d via ca de nce a n d gait s pee d) 
• I n dices of m or ni n g stiff ness (assesse d t hr o u g h 
le vels of acti vit y  3 0 - a n d 6 0-mi ns p ost -wa k e)  
 
I n dices of le vel of stiff ness t hr o u g h o ut t he da y as 
assesse d via t he W O M A C stiff ness s u bscale C ha n ge 
fr o m baseli ne i n: 
• W O M A C P h ysical F u ncti o n s u bscale o n Da ys 7, 
1 4, a n d 2 1  
T o assess t he f u ncti o nal m o bilit y, meas ure d t hr o u g h 
c o n necte d acti vit y trac ker.  
M o derate a n d Vi g or o us P h ysical Acti vit y ( M V P A) 
o n eac h da y of t he st u d y ( Baseli ne t o fi nal treat me nt 
da y 2 1).  
T o e v al uate t he effects of V oltare n Gel o n f u ncti o nal 
m o bilit y, meas ure d t hr o u g h s u bject relate d o utc o mes  
St u d y s u bjects’ percei ve d a bilit y t o e xercise m ore 
re g ularl y. Assesse d usi n g t he W O M A C P h ysical 
F u ncti o n s u bscale o n Da ys 7, 1 4, a n d 2 1 
T o e v al uate t he effects of V oltare n Gel o n pai n 
i nte nsit y 
C ha n ge fr o m baseli ne i n self -re p orte d pai n i nte nsit y, 
assesse d t hr o u g h N u meric Rati n g Scale ( N R S) ( dail y 
assess me nt).  
T o e v al uate t he effects of V oltare n Gel o n acti vit y -
relate d pai n a n d stiff ness 
C ha n ge fr o m baseli ne i n t he W O M A C t otal sc ore a n d 
s u bscales o n Da ys 7, 1 4, a n d 2 1: 
•  
Pai n (c o m p osite)  
•  
Stiff ness (c o m p osite)  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Hale o n  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 2  of 7 0  
 
T o e v al uate t he effects of V oltare n Gel o n c orrelates 
of q ualit y of life  
C ha n ge fr o m baseli ne i n o n Da ys 7, 1 4, a n d 2 1  
•  
Slee p/alert ness: Kar oli ns ka Sl ee pi ness Scale 
assesse d 1 x/ da y.  
•  
Healt h -relate d q ualit y of life: E Q-5 D -5 L  
 
S afet y  
T o m o nit or a n y rec or d a d verse e v e nts ( A Es) d uri n g 
st u d y peri o d. 
N u m ber a n d perce nt of st u d y s u bjects re p orti n g A Es 
or seri o us A Es ( S A Es) w hile o n treat me nt.  
•  
Treat me nt Relate d.  
•  
N o n -Treat me nt Relate d.  
E x pl or at or y  
 
T o e x pl ore t he li n k bet wee n V oltare n usa ge, le vel of 
pai n relief a n d f u ncti o nal m o bilit y/ q ualit y of life  
C orrelati o ns bet wee n V oltare n usa ge, pai n relief a n d 
m o bilit y a n d q ualit y of life i n dices t hr o u g h o ut t he 
trial. 
T o e v al uate ti me -t o mea ni n gf ul p ai n relief after 
V oltare n Gel use  
Ela pse d ti me fr o m V oltare n Gel use t o ac hie vi n g ti me 
t o mea ni n gf ul pai n relief t o e n d of st u d y. 
 
4  
E S TI M A N D S  
N ot A p plica ble.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
 
Pr ot oc ol N u m ber: 3 0 0 1 2 8  
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 3  of 7 0  
 
5  
S T U D Y D E SI G N  
T his pr os pecti ve o pe n -la bel, si n gle-ar m, m ulti -c o u ntr y ( U S a n d E U) real -w orl d e vi de nce 
st u d y ( R W E) st u d y, c o n d ucte d i n a h y bri d f or m at f oc usi n g o n ass essi n g t he i m pact of 
V oltare n Gel o n f u ncti o nal m o bilit y a n d q ualit y of life ( Q o L) i n i n di vi d uals wit h mil d/ n o n -
seri o us oste oart hritis ( O A) of t he k nee.  
T he tar get p o p ulati o n c o m prises a d ults a ge d bet w ee n 4 0 a n d 8 5 years, dia g n ose d wit h k nee 
mil d/ n o n -seri o us oste oart hritis a n d self-re p orti n g pai n at t he ti me of recr uit me nt. 
A p pr o xi matel y 1 9 5 s u bjects are e x p e cte d t o be e nr olle d i n t he st u d y, wit h a n a ntici pati o n 
t hat ar o u n d 1 4 7 of t hese s u bjects will s uccessf ull y c o m plete t he e ntire st u d y. 
I n t his h y bri d st u d y d esi g n, partici pa nts will be re q uire d t o p h ysicall y atte n d o n-site visits 
f or scree ni n g, b aseli ne assess me nts, a n d e n d -of -st u d y e val uati o ns. H o we ver, f or t h e 
re mai n der of t h e st u d y peri o d, data c ollecti o n will be e xec ute d re m otel y f oll o wi n g t he 
g ui deli nes pr o vi de d b y
 utilisi n g a n (electr o nic) e Diar y s yste m. 
I n t he E U, t w o varia nts of V oltare n Gel are a vail a ble, na mel y 1. 1 6 % a n d 2. 3 2 % D D E A. 
D uri n g t he scree ni n g a n d e nr ol me nt pr ocess, t he i n vesti gat or will assess t he s u bjects' 
pr o d uct prefere n ce as well as t he nee d a n d t he se v erit y of oste oart hritis ( O A) t o deter mi ne 
a n d dis pe nse t he a p pr o priate perce nta ge of g el. T he ai m is t o i ncl u de a mi ni m u m of 2 5 
patie nts utilisi n g t he 1. 1 6 % V oltare n Gel t o e n a bl e u n dersta n di n g of real -w orl d usa ge f or 
t he 1. 1 6 % V oltare n v aria nt. 
A d vertise me nts a p pr o ve d b y (I n vesti gati o n Re vie w B oar d) I R Bs/ Et hics C o m mittee ( E Cs) 
a n d i n vesti gat or data bas es ma y be use d as recr uit me nt pr oce d ures.  Use of E C a p pr o ve d 
ge neric, pre -scree ni n g q uesti o n naire t o ass ess basic s u bject c h aracteristics t o deter mi ne 
ge neral eli gi bilit y f or t his st u d y is all o we d.   
Hale o n will re vie w a n d a p pr o ve t he c o nte nt of a n y st u d y recr uit me nt materials direct e d t o 
p ote ntial st u d y s u bjects bef ore s u c h materi als are use d.  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 4  of 7 0  
 
5. 1. 1  
Li mit ati o n s of t h e st u d y  
Gi ve n t he nat ural c o urse of O A a n d pai n, dat a c ollecte d d uri n g t his st u d y ma y be 
c o nf o u n de d b y t he nat ur al c o urse of t he disease. Wit hi n 2 4 h o urs of p ai n o nset, s u bjects 
ge nerall y re p ort a n i ncrease i n t he se verit y a n d n u m ber of s y m pt o ms t he y e x perie nce.  
Gi ve n t he n at ural c o urse of t he dise ase, e ns uri n g s u bjects ha ve access t o tr eat me nt w he n 
O A s y m pt o ms are pres e nt will all o w f or s u bse q ue nt q ualit y of life ( Q o L) data t o be 
ca pt ure d, re d uci n g t he i nfl ue nce of c o nf o u n di n g v aria bles.  
S u bjects ma y li kel y be usi n g ot her o ver -t he-c o u nter a nti p yretics/a n al gesics f or se vere p ai n, 
w hic h ma y i nfl ue nce t h eir o verall Acti gr a p h a n d Q o L data a n d c o nf o u n d t he effect of 
V oltare n. D uri n g t his st u d y, s u bjects will be pr o m pte d t o re p ort me dicati o ns t he y ta ke f or 
s y m pt o m relief, al o n g wit h a n y c ha n g es i n me dicati o n o ver t he c o urse of t heir st u d y 
partici pati o n, t o better u n dersta n d t he res ults.  
Acti gra p h  is as a cli nic all y a p pr o ve d, res earc h-gra de, a n d v ali date d de vice. It b oasts 
c o m me n da ble acc urac y a n d a p plica bilit y i n its de vice a n d al g orit h m, e ns uri n g relia ble data 
q ualit y. W hile s o me li mitati o ns of its usa ge i n a real -w orl d e n vir o n me nt ma y e xist, t he 
de vice's r o b ust d esi g n mi ni mises t he li keli h o o d of fals e data, affir mi n g its o verall 
de pe n da bilit y. H o we v er, s u bjects ma y n ot be c o mf orta ble weari n g a weara bl e de vice 
c o nti n u o usl y as well as s u bject n o n -wear c o m plia nce a n d user relate d err ors ma y ha ve a n 
i m pact o n t he data c ollecte d.  
At t he start of t he st u d y, site staff will be gi ve n tr ai ni n g b y Acti gra p h or rele va nt trai ne d 
pers o n nel or t hr o u g h o nli ne vi de os o n h o w t o us e t he de vice (see t ut orial li n k i n a p pe n di x), 
wit h trai ni n g o n h o w t o use a n d wear t h e de vice a p pr o priatel y. After recei vi n g trai ni n g, 
site staff ca n t h e n a p pr o priatel y trai n s u bjects, p artic ularl y d uri n g t he dis pe nsi n g of t he 
pr o d uct.  
5. 2  
J u stifi c ati o n f or D o s e  
T he st u d y pla ns t o c ollect a n d e val u ate data fr o m all V olta re n t o pical mar kete d d oses. 
D osi n g i nstr ucti o ns will be f oll o we d as liste d o n t he st u d y pr o d uct c o m mercial la bel.  
5. 3  
E n d of St u d y a n d Cli ni c al Tri al D efi niti o n  
A s u bject is c o nsi dere d t o ha ve c o m plete d t he st u d y if t he y ha ve c o m plete d all pr oce d ures 
a n d assess me nts of t he st u d y i ncl u di n g t he last sc he d ule d pr oce d ure s h o w n i n t he Sc he d ule 
of Acti vities .  
S u bjects will ha ve t he o pti o n t o disc o nti n ue treat m e nt at t heir discreti o n, if t he y deter mi ne 
t he y n o l o n ger wa nt treat me nt. T he reas o ns f or disc o nti n ui n g treat me nt will be ca pt ur e d 
w he ne ver p ossi ble. T he e n d of t his st u d y  is defi n e d as last visit of t he last s u bject. At t he 
e n d of t he st u d y eac h st u d y s u bject s hall c o m plete a n e xit s ur ve y as d etaile d i n t he 
a p pe n di x .  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 5  of 7 0  
 
6  
S T U D Y P O P U L A TI O N  
6. 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  
A d ults bet wee n 4 0 -8 5 y ears of a g e wit h a dia g n osis of k nee oste o art hritis a n d self -re p orte d 
pai n at recr uit me nt will u n der g o scree ni n g f or i ncl usi o n i n t he st u d y. A ntici pa ti n g a 
dr o p o ut rate of a p pr o xi m atel y 2 5 %, t he trial ai ms t o e nr ol a t otal of 1 9 5 eli gi ble s u bjects, 
wit h a n e x pect e d c o m pleti o n rate of a p pr o xi mat el y 1 4 7 st u d y partici pa nts.  
Eli gi bilit y criteria f or partici pati o n i n t he st u d y i ncl u de a d ult s u bjects dia g n os e d wit h k nee 
oste oart hritis, s u p p orte d b y ra di ol o gical e vi de nce o btai ne d wit hi n t he last t hree years. 
A d diti o nall y, partici pa nts m ust self -re p ort k nee p ai n, re gisteri n g a sc ore of ≥ 4 0 m m a n d 
≤ 7 0 m m o n t he pai n i nte nsit y vis ual a nal o g ue scale ( V A S). Pr os p ecti ve partici pa nts m ust 
e x press willi n g ness a n d a bilit y t o a d here t o sc he d ule d visits, f oll o w a n o n -la bel V oltare n 
gel use, c o m pl y wit h ot her st u d y pr oce d ures, a n d c o m mit t o usi n g V oltare n gel f or u p t o 
t hree w ee ks. F or c o m pr e he nsi ve det ails, refer t o t he i ncl usi o n a n d e xcl usi o n criteria 
pr o vi de d bel o w.  
A Scree ne 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 orise d 
re pres e ntati ve. 
A n e nr olle d s u bje ct 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 orise d 
re pres e ntati ve a n d s uccessf ull y met eli gi bilit y criteria t o pr ocee d b e y o n d t he scree ni n g visit 
as a pplica ble f or t he pr ot oc ol desi g n.   
T his st u d y ca n f ulfil its o bjecti ves o nl y if a p pr o pri ate 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 partici pati o n i n t he st u d y is 
c o nsi dere d a p pr o priate.  All rele v a nt me dical a n d n o n -me dical c o n diti o ns s h o ul d be ta ke n 
i nt o c o nsi derati o n w he n deci di n g w het 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 priate 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. 
6. 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 p ects of t he st u d y bef ore a n y 
assess me nt is perf or m e d.  
2.  S u bject is male or fe male w h o, at t he ti me of scree ni n g, is bet wee n t he a g es of 4 0 a n d 
8 5 yea rs, i ncl usi ve. 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 6  of 7 0  
 
3.  A s u bject w h o is willi n g a n d a ble t o c o m pl y wit h sc he d ule d visits, o n -la bel V oltare n 
Gel use pla n, a n d ot her st u d y pr oce d ures.  
4.  A s u bject willi n g t o wear Acti gra p h c o nti n u o usl y 2 4/ 7 f or t he st u d y peri o d.  
5.  A s u bject  i n g o o d ge neral a n d me ntal healt h.  
6.  A s u bject wit h dia g n ose d k nee mil d/ n o n -seri o us oste oart hritis, pr o ve n via 
ra di ol o gical e vi de n ce c ollecte d wit hi n t he last 3 years (A n y d oc u me ntati o n t hat 
i n dicates mil d/ m o derate O A is acce pta ble –  s uc h as Kell gre n/ La wre n ce ( K/ L) met h o d 
of assess me n t). 
7.  A s u bject wit h self -re p orte d k nee pai n, wit h a s c ore of ≥ 4 0 m m ≤ 7 0 m m o n t he pai n 
i nte nsit y vis ual a nal o g ue scale at t he ti me of I nf or me d C o nse nt F or m (I C F) si g nat ure.  
8.  A s u bject willi n g t o use V oltare n Gel f or u p t o 3 wee ks . 
9.  A s u bject of p ote ntial c h il d beari n g willi n g t o f oll o w a n effecti ve m et h o d of 
c o ntrace pti o n (as liste d b el o w i n secti o n 1 1. 7) fr o m t he ti me of scree ni n g  ( p ost 
c o nse nt pri or t o t he use of pr o d uct)  a n d u p t o e n d of st u d y visit.  
 
6. 3  
E x cl u si o n Crit eri a  
A n i n di vi d ual w h o meets a n y of t he f oll o wi n g e xcl usi o n criteria will be e xcl u de d fr o m t he 
st u d y: 
1.  A s u bject w h o is a n e m pl o yee of t he i n vesti gati o n al 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 heir 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 other wise s u per vise d b y t h e i n vesti gat or; or a Hale 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 h eir 
i m me diate fa mil y. 
2.  A s u bject w h o has partici pate d i n ot her st u dies (i n cl 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 pro d uct(s) wit hi n 1 m o nt h 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.  A 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 dical or ps yc hiatric c o n diti o n or la b orat or y a b n or malit y t hat ma y 
i ncreas e t he ris k ass oci ate 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 pretati 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 h e s u bject 
i na p pr o priate f or e ntr y i nt o t his st u d y. 
4.  A s u bject wit h c o nfir me d r he u mat ol o gic disease  
5.  A s u bject w h o has e x p eri e nce d tr a u ma t o t he k nee wit hi n t he last 2 m o nt hs t hat 
res ulte d i n pai n a n d/ or s welli n g. 
6.  A s u bject t hat has bee n a d mi nistere d l ocal ster oi ds or ot her N S A I Ds i njecti o ns t o t he 
k nee wit hi n t he last 6  m o nt hs.  
7.  A s u bject wit h rece nt hist or y of maj or k nee i nj ur y or s ur ger y.  
8.  A s u bject wit h k nee s ki n area p at h ol o gical c o n diti o n w hic h pre v e nts a p plicati o n of 
pr o d uct t o t he s ki ns. C o n diti o ns s uc h as: o pe n s ki n w o u n ds, i nfecti o ns, 
i nfla m mati o ns, or e xf oliati ve der matitis c o n diti o ns.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 7  of 7 0  
 
9.  A s u bject wit h c o n diti o ns n ot li mite d t o t he f o ll o wi n g:  Gastr oi ntesti nal diseases, 
ast h ma, h y perte nsi o n, m y ocar dial i nfarcti o n, t hr o m b otic e ve nts, str o ke, c o n gesti ve 
heart fail ure, i m paire d re nal f u ncti o n, or li ver disease as j u d ge d b y i n vesti g at or or 
Site Staff.  
1 0.  A s u bject dia g n ose d wit h ot her rele va n t me dical c o n diti o ns (e. g., ps yc hiatric, 
ne ur ol o gical  - T his e x cl u des s u bjects wit h well -c o ntr olle d de pressi o n, a n xi et y or 
mi grai nes w h o are o n a sta ble d ose of me dicati o n w hic h ma y be all o we d –  t his is u p 
t o t he discreti o n of site staff a n d i n v esti gat ors). 
1 1.  A s u bject w h o ta kes me dicati o n relati n g t o a b o ve c o n diti o ns, s uc h as tric yclic 
a nti de pressa nts or a ntic o n v ulsa nts  
1 2.  A s u bject wit h a n acti ve i nfecti o n.  
1 3.  A Fe male s u bject w h o is pre g na nt at Scree ni n g as e vi de nce d b y a p ositi ve U P T , or 
i nte n di n g t o bec o me pre g na nt (see secti o n 1 1. 7 Pre g na nc y).  
1 4.  A s u bject wit h use of as piri n, Oral N o nster oi dal A nti -i nfla m mat or y Dr u gs, t o pical 
treat me nt wit h a n y N S AI Ds, warfari n, A C E i n hi bit ors, c ycl os p ori ne, di ureti cs, 
lit hi u m or met h otre xate, c ortic oster oi ds, or ot her a ntic oa g ula nt t hera p y wit hi n 3 0 
da ys of st u d y.  
1 5.  A s u bject wit h k n o w n or s us pecte d i nt olera nce or h y perse nsiti vit y t o t he st u d y 
materials ( or cl osel y relate d c o m p o u n ds) or a n y of t heir state d i n gre die nts, i ncl u di n g 
h y perse nsiti vit y t o N S AI Ds a n d as piri n tri a d.  
1 6.  A s u bject wit h a n y ot her ac ute or c hr o nic ill ness t hat c o ul d c o m pr o mise t h e i nte grit y 
of st u d y data or place t he s u bject at ris k b y partici pati n g i n t he st u d y.  
1 7.  A 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, 
s h o ul d n ot partici pate i n t he st u d y. 
 
6. 4  
R a n d o mi s ati o n Crit eri a  
T here will be n o ra n d o misati o n of t he pr o d uct as t he ai m is t o o btai n real w orl d usa ge of 
V oltare n.  
6. 5  
Lif e st yl e C o n si d er ati o n s  
St u d y s u bjects are e x pecte d t o c o nti n ue dail y lifest yle acti vities w hilst weari n g Acti gra p h.  
St u d y s u bjects s h o ul d wear t he Acti gra p h o n t he n o n -d o mi na nt wrist t o a v oi d disc o mf ort.  
Acti gra p h is w ater resist a nt a n d ca n b e w or n i n t he s h o wer, bat h, or s wi m mi n g p o ol. T he 
o nl y restricti o n is t hat it ca n n ot be w or n w he n i n salt water (i. e., t he ocea n). T heref ore, 
w here p ossi ble st u d y s u bjects s h o ul d wear Acti gra p h c o nti n u o usl y 2 4/ 7 t hr o u g h o ut t he 
da y.  
Acti gra p h will b e pr o vi de d f ull y c h ar ge d d uri n g scree ni n g a n d li kel y will n ot nee d t o 
c har ge d uri n g f ull d urati o n of t he st u d y. Ne v ert h ele ss, if t here are a n y iss ues wit h t he 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 8  of 7 0  
 
de vice, t he site staff are t o be n otifie d i m me diatel y, a n d t he de vice s h o ul d be re place d t o 
e ns ure c o nti n uati o n of d ata c ollecti o n f or t hat s u bj ect f or t he re mai n der of t he st u d y.  
D uri n g t he st u d y, s u bject will be as ke d t o press a n e ve nt b utt o n o n t he Acti gra p h w he n 
t he y get i nt o b e d a n d w h e n t he y g et u p. T his will assist i n a nal ysi n g t he data a n d i de ntif yi n g 
t he a m o u nt of ti me s pe nt i n be d/a wa ke etc. 
S u bjects s h o ul d mi ni mise or a v oi d Acti gra p h e x p os ure t o nat ur al o r artificial s u nli g ht (e. g., 
s u n be ds) w he n e ver p ossi ble. A d diti o nall y, t he y s h o ul d refrai n fr o m da ma gi n g t he pr o d uct 
i n a n y wa y t hat c o m pr o mises its i nte grit y, as t his is esse ntial f or t he c o nti n u o us m o nit ori n g 
of t he de vice t hr o u g h o ut t he st u d y.  
6. 6  
S cr e e n F a il ur e s 
Scree n fail ures are defi n e d as s u bjects w h o c o nse nt t o partici pate i n t he st u d y b ut are n ot 
s u bse q ue ntl y e nr olle d i n t he st u d y i.e., d o n ot f ulfil all t he eli gi bilit y criteria.  
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 s et of scree n fail ure 
i nf or mati o n will i ncl u de de m o gra p h y ( year of birt h, ge n der, race), s cree n fail ure d etails 
(e. g., wit h dra w al of c o ns e nt), a n d eli gi bilit y criteria.  
Pr os pecti ve s u bjects w h o d o n ot meet t he criteria f or e nr ol me nt i n t his st u d y (scree n 
fail ure) ma y n ot be re -s cree n e d u nless d ue t o tec h nical iss ues wit hi n t he st u d y or t he 
weara ble de vic e. If re -scree ni n g is a p plica ble, i n di vi d uals will be re-i n vite d wit h a ne w 
scree ni n g n u m ber a n d rec o nse nte d o nt o t he st u d y wit h ne w c o nse nt f or m a n d ne w s u bject 
n u m ber.   
6. 7  
S p o n s or’ s Q u alifi e d M e di c al P er s o n n el  
C o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y q ualifie d me dical pers o n nel f or t he 
st u d y is d oc u me nte d i n t he St u d y C o ntact List ( T M F -1 8 7 8 7 0) l o cate d i n t he i n vesti gat or 
st u d y master file hel d at t he st u d y site.  
T he c o ntact n u m ber is o nl y t o be use d b y i n vesti gati o nal staff see ki n g a d vi ce o n me dical/ 
de ntal q uesti o ns or pr o ble ms if t he esta blis he d c o m m u nicati o n pat h wa ys bet wee n t he 
i n vesti gati o nal site a n d t he st u d y tea m are n ot a vaila ble.   
6. 8  
R at er/ Cl i ni c al A s s e s s or Q u alifi c ati o n s  
N o rater/ cli nical assess or q ualificati o ns are re q uir e d f or t his st u d y.  
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 nt er nati 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 Hal e 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 k ete d pr o d uct(s), place 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 partici pa nt acc or di n g t o t he st u d y pr ot oc ol.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 2 9  of 7 0  
 
T his i ncl u des a pr o d uct wit h a 
mar keti n g a ut h orisati 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 h er i nf or mati 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) S u p pli e s 
T he f oll o wi n g st u d y pr o d ucts will be us e d a n d will be s u p plie d t o t he site b y t he Cli nical 
S u p plies De part me nt, Hale o n. T he site staff will s u p pl y o ne of t he pr o d ucts t o t he st u d y 
s u bjects. 
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) a n d D e vi c e  
 
 
Test Pr o d uct ( U S o nl y)  
Test Pr o d uct ( E U o nl y)  
Test Pr o d uct ( E U o nl y)  
Acti gra p h De vice  
Pr o d u ct N a m e  
V oltare n Gel 1 % 
( dicl ofe nac s o di u m) 
V oltare n Gel 1. 1 6 % 
( dicl ofe nac 
diet h yla m m o ni u m)  
V oltare n Gel 2. 3 2 % 
( dicl ofe nac 
diet h yla m m o ni u m)  
Acti gra p h w G T 3 X -B T or 
si milar de vice pr o vi de d b y 
Acti gra p h  
P a c k D e si g n  
La belle d c o m mercial pac k  
La belle d c o m mercial pac k  
La belle d c o m mercial pac k  
La belle d c o m mercial pac k  
Di s p e n si n g D et ail s  
As per site discreti o n  
As per site discreti o n  
 As per site discreti o n  
 O ne per s u bject  
Pr o d u ct M a st er 
F or m ul ati o n C o d e 
( M F C) 
U S C o m mercial Pr o d uct  
E U C o m mercial Pr o d uct  
E U C o m mercial Pr o d uct  
N/ A  
D o s e/ A p pli c ati o n  
As per la bel a n d leaflet 
i nstr ucti o ns 
As per la bel a n d leaflet 
i nstr ucti o ns 
As per la bel a n d leaflet 
i nstr ucti o ns 
As per la bel, leaflet or site -
s pecific i nstr ucti o ns p ost 
trai ni n g 
R o ut e of 
A d mi ni str ati o n  
T o pical  
T o pical  
T o pical  
N/ A ( De vice w or n o n 
wrist)  
 
7. 2  
A d mi ni str ati o n  
O nl y s u bjects e nr olle d i n t he st u d y ma y recei ve st u d y pr o d ucts a n d o nl y a ut h orise d site 
staff ma y s u p pl y or a d mi nister st u d y pr o d ucts. All st u d y i nter ve nti o ns m ust be st ore d i n a 
sec ure, e n vir o n m e ntall y c o ntr olle d, a n d 
m o nit ore d ( m a n ual or a ut o mate d) area i n 
acc or da nce wit h t h e la belle d st ora ge c o n diti o ns wit h access li mite d t o t he a ut h orize d site 
staff o nl y. 
S u bjects will be pr o vi de d pr o d uct fr o m st u d y t ea ms l ocate d i n E U ( P ola n d) a n d U S 
f oll o wi n g scree ni n g a n d baseli ne assess me nts. S u bjects will be as ke d t o f oll o w t he 
mar kete d pr o d uct o n -la b el i nstr ucti o ns f or V oltare n wit h o ut f urt her i nstr ucti o n fr o m t he 
s p o ns or or i n vesti gat or.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 0  of 7 0  
 
F or Acti gra p h, b ot h site staff a n d s u bjects will be gi ve n trai ni n g b y Acti gra p h or rele va nt 
trai ne d pers o n nel or o nli ne vi de os o n h o w t o use t he de vice ca n als o be f oll o we d ( see 
t ut orial li n k i n a p pe n di x). 
7. 2. 1  
M e di c ati o n/ D o si n g Err or s  
Me dicati o n/ d osi n g err ors ma y res ult, i n t his st u d y, fr o m t he a d mi nistrati o n or c o ns u m pti o n 
of:  
•  t he wr o n g pr o d uct, 
•  b y t he wr o n g s u bject,  
•  at t he wr o n g ti me,  
S uc h me dicati o n/ d osi n g err ors o cc urri n g t o a st u d y s u bject are t o b e ca pt ure d i n t he 
electr o nic cas e re p ort f or m (e C R F).  I n t he e ve nt of me dicati o n/ d osi n g err or, t he s p o ns or 
s h o ul d be n otifie d 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.  
Me dicati o n/ d osi n g err ors are re p orta ble irres pecti ve of t he prese nce of a n ass ociate d 
(A d vers e E ve nt) A E, i n cl u di n g:  
•  Me dicati o n/ d osi n g err ors i n v ol vi n g s u bject e x p os ure t o a n y of t he st u d y 
pr o d ucts;  
•  P ote ntial me dicati o n/ d osi n g err ors or uses o utsi d e of w hat is f ores ee n i n t he 
pr ot oc ol t hat d o or d o n ot i n v ol ve t he partici pati n g s u bject.  
If a me dicati o n/ d osi n g err or is acc o m pa nie d b y a n A E, as deter mi ne d b y t he i n vesti gat or, 
t he me dicati o n/ d osi n g err or a n d, a n y ass ociat e d a d verse e ve nt(s) are t o be ca pt ure d i n t h e 
e C R F A E f or m.  
7. 2. 2  
O v er d o s e  
A n o ver d ose is a deli berate or i na d verte nt a d mi nistrati o n of a  pr o d uct at a n a m o u nt hi g her 
t ha n s pecifie d i n t he pr ot oc ol. 
O ver d ose is n ot li kel y t o occ ur i n t his st u d y.  
Li mite d q ua ntities of t he st u d y pr o d uct(s) will be s u p plie d, a n d cl osel y m o nit ore d b y t he 
site f or eac h s u bject. 
O ver d ose per se is n ot a n A E. H o we v er, a n y cli nical se q uelae of a n o ver d ose s h o ul d be 
re p orte d as a n A E (a n d s eri o us a d verse e ve nt ( S A E), if a p pr o priate). F or re p orti n g, f oll o w 
t he A E a n d S A E re p orti n g i nstr ucti o ns. 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 1  of 7 0  
 
7. 3  
I n v e sti g ati o n al/ St u d y Pr o d u ct( s) St or a g e a n d I n str u cti o n s  
T he i n vesti gat or m ust c o nfir m a p pr o priat e te m perat ure c o n diti o ns ha ve b ee n mai ntai ne d 
d uri n g tra nsit f or all st u d y pr o d ucts recei ve d a n d a n y discre pa ncies are re p orte d a n d 
res ol ve d bef ore us e acc or di n g t o t he s u p plie d s hi p pi n g d oc u me ntati o n. 
T he i n vesti gat or will e ns ure t h at all st u d y pr o d ucts are st ore d i n a sec ure d area wit h 
c o ntr olle d access u n der re q uire d st or a ge c o n diti o ns a n d i n acc or da n ce wit h a p plica ble 
re g ulat or y re q uire me nts a n d t he pr o d uct la b el.   
Site s yste ms m ust be ca pa ble of meas uri n g a n d d o c u me nti n g (f or e x a m ple, via a l o g), at a 
mi ni m u m, dail y mi ni m u m, a n d ma xi m u m te m perat ures f or all site st ora g e l ocati o ns (as 
a p plica ble, i ncl u di n g fr oze n, refri gerat e d, a n d/ or r o o m -te m perat ur e pr o d ucts).  T his s h o ul d 
be ca pt ure d fr o m t he ti me of first pr o d uct recei pt t hr o u g h o ut t he st u d y.  E ve n f or 
c o nti n u o us m o nit ori n g s yste ms, a l o g or site pr oce d ure t hat e ns ures acti ve d ail y e val uati o n 
f or e x c ursi o ns s h o ul d be a vaila ble.  T h e o perati o n of t he te m perat ur e-m o nit ori n g de vice 
a n d st ora ge u nit (f or e x a m ple, refri gerat or), as a p plica ble, s h o ul d be re g ul arl y i ns pecte d t o 
e ns ure it is mai ntai ne d i n w or ki n g or der.  
A n y e xc ursi o ns fr o m t he pr o d uct -la bel st ora g e c o n diti o ns s h o ul d be re p orte d t o a p pr o priate 
site staff u p o n disc o v er y a n d c o m m u nicat e d t o s p o ns or as s o o n as p ossi ble.  T he site s h o ul d 
acti vel y p urs ue o pti o ns f or ret ur ni n g t he pr o d uct t o t he st ora ge c o n diti o ns as descri be d i n 
t he la belli n g, as s o o n as p ossi ble.  E xc ursi o ns fr o m t he st ora ge re q uire me nts, i ncl u di n g 
a n y acti o ns ta ke n, m ust be d oc u me nte d as a pr ot oc ol de viati o n, a n d re p orte d t o t he 
S p o ns or.   
O nce a n e x c ursi o n is i de ntifie d, t he affecte d pr o d uct ( or pr o d ucts) m ust be q uara nti ne d a n d 
n ot use d u ntil t he s p o ns or pr o vi des d oc u me nt ati o n of per missi o n t o use. Us e of a n y of t he 
affecte d pr o d u ct(s) pri or t o s p o ns or a p p r o val will be c o nsi dere d a pr ot oc ol de viati o n.   
Site staff will i nstr uct s u bjects o n t he pr o per st ora ge re q uir e me nts f or all ta ke -h o me 
pr o d ucts. S u bjects will be i nstr ucte d t o f oll o w t he a p pr o ve d o n -la bel i nstr ucti o ns o n h o w 
t o st ore t he pr o d uct a n d Acti gra p h d e vice. F or f urt her i nstr ucti o ns, s u bj ects ca n directl y 
f oll o w t he details pr o vi de d d uri n g st u d y i nitiati o n.  
7. 4  
I n v e sti g ati o n al/ St u d y Pr o d u ct A c c o u nt a bilit y 
All 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 use d f or a n y 
ot h er p ur p ose.  
All st u d y pr o d ucts m ust be recei ve d b y a d esi g nate d pers o n at t he st u d y sites, ha n dle d a n d 
st ore d safel y a n d pr o perl y, a n d ke pt i n a s ec ure d l ocati o n t o w hic h o nl y t he staff h a ve 
access. U p o n recei pt, all st u d y pr o d ucts s h o ul d be st ore d acc or di n g t o t he i nstr ucti o ns 
s pecifie d o n t he pr o d uct l a bels. St u d y pr o d ucts are t o be 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 n ce wit h t he pr ot oc ol, b y a ut h orize d site staff. 
T he i n vesti gati ve site m ust mai ntai n a de q uate rec or ds d oc u me nti n g t he recei pt, use, l oss, 
or ot her dis p ositi o n of all t he pr o d uct s u p plies. All st u d y pr o d ucts will be acc o u nte d f or 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 2  of 7 0  
 
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 nt a bilit y, rec o nciliati o n, a n d rec or d mai nte na nce.  
T he acc o u nta bilit y rec or ds m ust be a vaila ble f or i ns pecti o n b y t he st u d y m o nit or d uri n g 
t he st u d y. M o nit ori n g of pr o d uct acc o u nta bilit y will be perf or me d b y t he m o nit or d uri n g 
site visits a n d at t he c o m pleti o n of t he st u d y.  
At t he e n d of t he st u d y ( Da y 2 8 ), Acti gra p h d e vice a n d t he all ocate d pr o d uct ( use d a n d 
u n use d) f or t his cli nical st u d y, s h o ul d be ret ur ne d t o t he Hale o n Cli nical S u p plies 
De part me nt or
usi n g t he ret ur n i nstr ucti o ns pr o vi de d.  
Detaile d i nstr ucti o ns f or t he ret ur n of st u d y pr o d uct f or t he acc o u nta bilit y c hec ks a n d 
s u bse q ue nt destr ucti o n will be pr o vi de d b y Hale o n or 
 d uri n g t he st u d y i n ti me 
f or st u d y cl ose o ut visit. 
7. 5  
Bli n di n g a n d All o c ati o n/ R a n d o mi s ati o n  
N ot A p plica ble.  
7. 6  
Br e a ki n g t h e Bli n d  
N ot A p plica ble.  
7. 7  
C o m pli a n c e  
St u d y s u bjects will be t ol d t o use t he pr o d ucts as per la bel i nstr ucti o ns. C o m plia nce a n d 
pr o d uct use will be m o nit ore d t hr o u g h o ut t he st u d y. Acti gra p h will c ollect m o bilit y a n d 
slee p-rel ate d i nf or mati o n c o nti n u o usl y ( 2 4/ 7) t hr o u g h o ut t he st u d y. 
S u bjecti ve 
q uesti o n naires a n d ite ms will be a d mi nistere d at pre -s pecifi e d ti me-p oi nts d uri n g t he st u d y. 
Safet y, a d vers e e ve nts, a n d use of c o nc o mita nt me dicati o ns will be m o nit ore d t hr o u g h o ut 
t he st u d y. If a s u bject st o p usi n g t he pr o d uct bef ore Da y 2 8, t he y will be pr o m pte d t o 
c o m plete all rele v a nt q uesti o n naires a n d ite ms bef ore c o ncl u di n g t he st u d y.  
Misse d assess me nts will be rec or de d as s uc h. E xce pti o ns will be ma de f or s u bjects w h o 
re p ort ha vi n g e x perie nce d tec h nical or c o n n ecti vit y iss ues t hat pre ve nte d t he m fr om usi n g 
Acti gra p h. If a s u bject has faile d/f or g ot t o press t he e ve nt b utt o n, t he y s h o ul d ma ke a n ot e 
i n t he e Diar y of a p pr o xi mate date/ti me of misse d e ve nt.   
C o m plia nce will be cal c ulate d as a n o n g oi n g meas ure t hr o u g h o ut t he treat me nt. F or 
s u bjects w h o are wit h dra w n or wit h dra w pri or t o t he e n d of t he treat me nt peri o d, perce nt 
a d here n ce will be b ase d o n t he n u m ber of da ys acti ve i n t he st u d y i nter ve nti o n pri or t o 
wit h dra wal.  
7. 8  
C o n c o mit a nt M e di c ati o n/ Tr e at m e nt( s)  
As t his is R W E st u d y, c o nc o mita nt treat me nts a re all o we d d uri n g t he e ntire peri o d of t he 
st u d y at t he discreti o n of t he i n vesti gat or.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
C CI
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 3  of 7 0  
 
At scree ni n g, s u bjects will c o nfir m t heir me dical hist or y a n d c o nc o mita nts me dicati o n use 
t o t he i n vesti gat or, a n d s u bjects o n e xcl usi o nar y me dicati o ns will n ot m o v e for war d base d 
o n t heir res p o nses ( see e xcl usi o n criteri a). T h ereafter, if a n y c h a n ge i n c o nc o mita nt 
me dicati o n is re p ort e d w hile t he s u bject is still e nr olle d i n t he st u d y, t he i n vesti gat or will 
be alerte d t o fill o ut t he c o nc o mita nt me dicati o ns f or m. 
If t he c o nc o mita nt me dicati o n nee ds t o be n ote d, t his f or m will be a vaila ble f or i n vesti gat or 
t o fill-o ut. If t he s u bject re p orts t o t he i n vesti g at or i nci de nces of b ei n g a d mi nistere d 
me dicati o n, s u p ple me nts, or vacci nes d u e t o a h ealt h reas o n after si g ni n g c o nse nt, t he 
i n vesti gat or will n ote t his i n c o nc o mita nt me dicati o n f or m wit h its i n dicati o n, u nit d ose, 
dail y d ose, a n d start a n d st o p dates of a d mi nistrati o n i n t he st u d y p ortal. Please see secti o n 
8. 1. 4 f or details o n n oti n g me dical hist or y a n d secti o n 1 2 f or A E/ S A E m o nit ori n g.  
T he f oll o wi n g pr o hi biti o ns or restricti o ns f or c o nc o mita nt t hera pies are i n effect d uri n g  
t he st u d y:  
•  Oral, i ntra m usc ular, s oft tiss ues i njecti o ns of c ortic oster oi ds or i ntra -artic ular 
pr oce d ure o r p eriartic ul ar i njecti o ns i n t he tar get j oi nt wit hi n 6 m o nt hs pri or t o 
e nr ol me nt pri or t o e nr ol me nt.  
•  A s u bject w h o ta k es me dicati o n relati n g t o c o n diti o ns o utli ne d i n t he e x cl usi o n 
criteria . 
•  S u bjects are str o n gl y a d vise d n ot t o ta ke a n y disall o we d me dic ati o n; h o we ver, 
s u bjects were n ot t o be disc o nti n ue d f or i nta ke of disall o we d treat me nt u nless t here 
was a safet y iss ue. T his is t o be j u d ge d b y t he i n vesti gat or a n d t he site staff. T he 
s u bjects d uri n g t he st u d y are per mitte d t o use:  
•  Nasal s pra ys wit h l oc al m o de of acti o n, e ye dr o ps, a n d a nal oi nt me nts are 
per mitte d.  
•  O piates, N S AI Ds or a n y ot her a nal gesi cs.  
•  D oses of o n e or t w o 5 0 0 -m g paraceta m ol/aceta mi n o p he n ta blets were p er mitte d u p 
t o a ma xi m u m of 8 ta blets ( 4 g) per d a y. A mi ni m u m of 4 h o urs bet wee n d oses are 
a d vise d a n d per mitte d d uri n g t he st u d y.  
T he a b o v e me dicati o n usa ge will be rec or de d b y i n vesti gat or at scree ni n g a n d b y s u bjects 
i n e Diar y d uri n g t he st u d y peri o d a n d m ust be clearl y o utli ne d d uri n g t he st u d y peri o d 
w here p ossi ble.  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 4  of 7 0  
 
8  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
S U B J E C T DI S C O N TI N U A TI O N/ WI T H D R A W A L  
8. 1  
Di s c o nti n u ati o n of St u d y I nt er v e nti o n  
A s u bject ma y c h o ose t o disc o nti n ue or ma y be disc o nti n ue d fr o m t he st u d y i nter ve nti o n 
earl y at a n y ti me w hilst still i n t he st u d y at t h e dis creti o n of t he i n v esti gat or f or t he 
f oll o wi n g reas o ns relate d t o safet y, s u bject c o ns e nt or a p ote ntial w orse ni n g of t he ris k / 
be nefit assess me nt fr o m t he s u bject of re mai ni n g o n t he i nter ve nti o n:  
•  A d verse E v e nt  
•  Lac k of effic ac y fr o m t he i nter ve nti o n  
•  S u bje ct t o be wit h dra w n fr o m t he st u d y (see b el o w - secti o n 8. 2)  
If a s u bject is disc o nti n ue d earl y fr o m t he i nter ve nti o n, t he reas o n(s) f or disc o nti n uati o n 
a n d t he ass o ciate d d ate m ust be d oc u me nte d i n t he rele va nt secti o n(s) of t he e C R F. T h e 
s u bject s h 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 (s ee secti o n 8. 2). 
8. 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 b e 
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 ha vi o ural 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 nces re q uir e disc o nti n uati o n of st u d y pr o d uc t a n d/ or pre mat ure 
s u bject 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 a s u bject is disc o nti n ue d or pre mat urel y wit h dra ws fr o m t he st u d y, t he reas o n(s) f or 
disc o nti n uati o n or wit h dra wal a n d t he ass ociate d date m ust be d oc u me nte d i n t he rele va nt 
secti o n(s) of t he e C R F.  
8. 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 site m ust atte m pt t o 
c o ntact t he s u bject a n d resc he d ule t he misse d visit as s o o n as p ossi ble a n d c o u nsel t h e 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 5  of 7 0  
 
s u bject o n t he i m p orta nce of mai ntai ni n g t he assi g ne d visit sc he d ule a n d ascertai 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 ns i dere d l ost t o f oll o w u p if he or s he re peate 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 h e st u d y site. Bef ore a s u bject is dee me d 
l ost t o f oll o w u p, t he i n vesti gat or m ust ma ke e ver y eff ort t o re gai n c o nt act wit h t he s u bject 
( w here p ossi ble, 3 tele p h o ne calls a n d, if necessar y, a certifie d letter t o t he s u bject’s last 
k n o w n maili n g a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be 
d oc u me nte d. 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 h e 
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 bj ect 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 Es.  
Fi nal safet y a ssess me nts ma y be carrie d o ut w he n t he s u bject ret ur ns t o t he st u d y site, at 
t he i n vesti gat or’s discreti o n, w hic h c o ul d i ncl u de t he f oll o wi n g: 
S h o ul d t he s u bject c o nti n ue t o be u nreac h a ble, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y a n d l os t t o f oll o w u p.  
Lac k of c o m pleti o n of all or a n y of t he earl y ter mi nati o n pr oce d ures will n ot be vie we d as 
pr ot oc ol de viati o ns s o l o n g as t he s u bject’s safet y was pres er ve d.  
If t he s u bject wit h dra ws fr o m t he st u d y a n d wit h dra ws c o ns e nt f or discl os ure of fut ure 
i nf or mati o n, n o f urt her e val uati o ns s h o ul d be perf 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 ollecte d bef ore s uc h 
wit h dra wal of c o nse nt.  
9  
S T U D Y P R O C E D U R E S  
T his secti o n lists t he pr oce d ures t o be c o m plete d at eac h pla n ne d st u d y visit.  T he ti mi n g 
of eac h pr oce d ure is liste d i n t he Sc he d ule of Acti vities  secti o n. 
A d here n ce t o t he st u d y desi g n re q uire me nts, i ncl u di n g all pr oce d ures are esse ntial a n d 
re q uire d f or st u d y c o n d u ct. 
T his secti o n lists t he pr oce d ures t o be c o m plet e d f or eac h pla n ne d st u d y ti me p oi nt.  
H o we ver, as per nat ure of R W E st u dies, if a s u bject fails t o c o m plete t heir dail y 
q uesti o n naires at a n y ti me p oi nt p ost -baseli ne, s u bjects will be per mitte d t o c o nti n ue i n  t he 
st u d y wit h misse d dates rec or de d i n t he e-d air y.  
9. 1  
Vi sit 1/ ( Pr e) S cr e e ni n g  
S u bjects willi n g a n d a bl e t o c o m pl y wit h s c he d ule d visits, a n d use V oltare n Gel as per 
la bel, a n d ot her st u d y pr oce d ures, a n d are willi n g t o use V oltare n Gel f or u p t o 3 wee ks 
are eli gi ble t o ta ke p art i n t he st u d y (f or f ull details see i ncl usi o n a n d e xcl usi o n criteria).  
Scree ni n g pr oce d ures will be c o n d ucte d b y t he i n vesti gat or, or s uita bl y q ualifie d desi g nee.  
T he f oll o wi n g data will b e c ollecte d f or scree ni n g:  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 6  of 7 0  
 
•  I nf or me d C o nse nt. 
•  Uri ne Pre g na n c y Test.  
•  De m o gra p hics & S hi p pi n g i nf or mati o n.  
•  Scree ni n g Q u esti o n naire.  
•  Me dical Hist or y/ C o nc o mita nt me dicati o n c hec klist.  
•  Pai n Vis ual A nal o g ue Scale t o c o nfir m O A l e vels.  
•  N u meric Rati n g Scale f or re p orti n g.  
S u bjects t hat pr o vi de c o nse nt wi ll be pr o m pte d t o c o nti n ue. i n vesti gat ors will w or k wit h 
s u bjects a n d c o m plete t he scree ni n g q uesti o n naire, c o nfir m t heir me dical hist or y a n d 
c o nc o mita nt me dicati o n, a n d c o m plete t heir  de m o gra p hics f or ms. 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 b y t he i n vesti gat or, or s uita bl y 
q ualifie d desi g nee w he n deci di n g w het her a partic ular s u bject is s uita ble.  
9. 1. 1  
I nf or m e d C o n s e nt 
T he i n vesti gat or m ust o btai n i nf or me d c o nse nt fr o m eac h s u bject p artici pati n g i n t his st u d y 
after ade q u ate e x pla nati o n of t he ai ms, met h o ds, o bjecti ves, a n d p ote ntial hazar ds of t he 
st u d y a n d bef ore a n y st u d y-s pecific acti vit y is p erf 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 dat e d b y t he s u bject, t he s u bject will retai n o ne  c o p y 
a n d t he ot her will be ke pt at site.  
T he i n vesti gat or m ust als o e x plai n t o t he s u bjects t hat t he y are c o m pletel y free t o ref use t o 
e nter t he st u d y or t o wit h dra w fr o m it at a n y ti me.  A p pr o priate f or ms f or d oc u me nti n g a 
si g ne d a n d date d c o ns e nt will be pr o vi de d b y eit her t he i n vesti gat or or b y Hale o n.  
T he i n vesti gat or s h o ul d si g n a n d date eac h c o p y of t he I C F t o c o nfir m t hat t he c o nse nt 
pr ocess w as c o m plete d c orrectl y after t he s u bject has si g ne d.   
T he date a n d ti me t he s u bject si g ne d t he i nf or me d c o n se nt f or m will be ca pt ure d i n t h e 
e C R F. 
If, d uri n g a s u bject’s partici pati o n i n t he st u d y, a n y ne w i nf or mati o n bec o mes a vaila ble 
t hat ma y affect t he s u bject’s willi n g ness t o p artici pate i n t h e st u d y, eac h o n g oi n g s u bject 
s h o ul d recei ve a c o p y of t his ne w inf or mati o n a n d be re -c o ns e 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 date d a me n de d c o nse nt f or m. 
T he date of re -c o nse nt will be rec or de d o n t he e C R F.  
9. 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 mati o n will b e rec or de d i n t he e C R F: year of birt h, 
bi ol o gical se x at birt h a n d race.  
I n cl usi o n a n d e xcl usi o n criteria i nf or mati o n will be d oc u me nte d i n t he e C R F. 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 7  of 7 0  
 
9. 1. 3  
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  
Details of rel e va nt me dical a n d s ur gical hist or y (i n t he last 1 year), i ncl u di n g aller gies or 
dr u g se nsiti vit y, will be d oc u me nte d i n t he e C R F.  
Pri or me dicati o ns/treat me nts, i ncl u di n g prescri pti o n a n d n o n -prescri pti o n dr u gs, dietar y 
s u p ple me nts, a n d her bal re me dies, ta ke n i n t he last 6 0 da ys a n d pri or t o si g ni n g t he 
i nf or me d c o nse nt f or m, will be d oc u me nte d i n t he e C R F. 
9. 1. 4  
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 n cl usi o n/e xcl usi o n 
criteria, me dical hist or y, pri or me dicati o ns t o c o nfir m s u bject eli gi bilit y t o partici pate i n 
t he cli nical st u d y. T his will be d oc u me nte d i n t he e C R F.  
9. 2  
St u d y P eri o d  
9. 2. 1  
B a s eli n e P eri o d  
T he n u m ber of da ys eac h s u bject will acti vel y e n ga ge wit h t he st u d y will be u p t o 2 8 d a ys 
i ncl u di n g baseli ne (See A p pe n di x ).  
St u d y s u bje cts w h o f ulfil criteria a n d dee me d s uita ble b y t he i n vesti gat or f or partici pati o n 
will be pr o vi de d wit h t he Acti gra p h weara ble de vice w hic h will meas ure as p ects of 
f u ncti o nal m o bilit y d uri n g t he bas eli ne peri o d. T he bas eli ne peri o d will last bet wee n 3 
( mi ni m u m) a n d 7 da ys ( ma xi m u m), t o c ollect e n o u g h i nf or mati o n o n b ot h s u bjecti ve a n d 
o bjecti ve as pects of m o bilit y a n d slee p q ualit y. E n d of baseli ne peri o d will be c o nsi dere d 
da y 0.  
T he bas eli ne peri o d will be vari a ble a n d will de p e n d o n st u d y s u bjects reac h i n g ≥ 4 0 m m 
≤7 0 m m of self -re p orte d pai n o n t he pai n i nte nsit y vis ual a nal o g ue scale ( V A S). O nce t he 
s u bject reac hes a n y val ue at t his le vel o n t he V A S scale, e v e n f or a si n gle o bser vati o n, t he 
baseli ne peri o d will be ter mi nate d, a n d st u d y p has e ca n c o m me n ce.  
At t he e n d of t h e baseli ne peri o d, t he site staff will dis pe nse t he st u d y pr o d uct t o t he s u bject 
t o ta ke h o me a n d use t hr o u g h o ut t he st u d y peri o d as per la bel i nstr ucti o ns. Bef ore t he y 
start usi n g t he pr o d uct, st u d y s u bjects will c o m plete t he q uesti o n nair es t o c ollect 
i nf or mati o n o n t heir bas eli ne le vels of q u alit y of life a n d s u bjecti ve perce pti o ns of m o bilit y 
a n d e xercise ca pacit y.  
 
All me dicati o ns ta ke n d uri n g t he 6 0 d a ys pri or t o t he scree ni n g visit a n d t hr o u g h o ut t he 
trial ( ot her t ha n st u d y me dicati o n) will be rec or de d o n t he e C R F.  
9. 2. 2  
D a y s 1 -2 1    
T he n u m ber of da ys eac h s u bject will acti vel y e n ga ge wit h t he st u d y will var y acc or di n g 
t o t he baseli ne meas ur e me nts. V oltare n Gel use will be li mite d t o 2 1 da ys, b ut st u d y 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 8  of 7 0  
 
s u bjects are all o we d t o st o p usi n g t he pr o d uct if t h e y d o n ot feel t he nee d t o c o nti n ue usi n g 
it (e. g., if t he p ai n s u bsi des). St u d y s u bjects will be t ol d t o us e t he pr o d ucts as p er la bel 
i nstr ucti o ns. Acti gra p h will c ollect m o bilit y a n d slee p-relate d i nf or mati o n c o nti n u o usl y 
( 2 4/ 7) t hr o u gh o ut t he st u d y.  
All q uesti o n naires will b e pr o vi de d at pre -s p ecifi e d ti me-p oi nts d uri n g t h e st u d y ( please 
see sc he d ul e of acti vities ta ble). Safet y, a d verse e ve nts, a n d us e of c o nc o mita nt 
me dicati o ns will  be m o nit ore d t hr o u g h o ut t he st u d y. If a s u bject st o ps usi n g t he pr o d uct 
bef ore 
Da y 2 1 ( p ost baseli ne), t h e y 
will be pr o m pte d t o c o m plet e all rele va nt 
q uesti o n naires bef ore c o ncl u di n g t he st u d y.  
T he f oll o wi n g assess me nts will be c o m plete d b y s u bjects d uri n g t he st u d y peri o d:  
•  S u bjects will re p ort a n y c ha n ges i n healt h, c o nc o mita nt me dicati o ns, or n o n -dr u g 
treat me nts/ pr oce d ures.  
•  S u bjects will use Acti gra p h a n d c o m plete a d diti o n al Q o L q uesti o ns eac h d a y.  
•  S u bjects will c o m plete a n e Diar y t o rec or d pr o d uct use  eac h da y.  
•  S u bjects will re p ort a n y a d verse e v e nts.  
•  S u bjects will re p ort t he e n d of pr o d uct us e a n d a ns wer e n d of t he st u d y q u esti o ns 
pri or t o e xiti n g t he st u d y.  
S u bjects w h o d o n ot us e t he pr o d uct at all t hr o u g h o ut t he st u d y will be c o nsi dere d as 
dr o p o ut s. Partial usa ge of t he pr o d uct acr oss t he treat me nt peri o d ( Da y 7 t o Da y 2 1) is 
all o we d t o ca pt ur e R W E usa ge of t he pr o d uct.  
9. 2. 3  
E n d of Tr e at m e nt P eri o d/ E n d Of St u d y  
S u bjects will ha ve t he o pti o n t o disc o nti n ue treat me nt at t heir discreti o n. T he reas o ns f or 
disc o nti n ui n g treat me nt will be ca pt ure d w he ne v er p ossi ble.  
S u bjects ma y c h o ose t o disc o nti n ue treat me nt if t he y feel t hat t heir s y m pt o ms d o n ot 
warra nt f urt her us e of t he st u d y pr o d uct.  
S u bjects w h o wis h t o c o nti n ue t o use t he st u d y pr o d uct w ill be pr o m pte d t o disc o nti n ue 
treat me nt after t he e n d of t he st u d y ( 2 8 da ys) a n d see k a d vice fr o m t heir g e neral 
practiti o ner f or f urt her assess me nt a n d treat me nt o n t heir c o n diti o n if nee de d.  
S u bjects  will als o be i nf or me d t hat t he st u d y will e n d o n Da y 2 1 ( or t he da y after t he last 
treat me nt, if earlier t ha n 2 1 da ys), a n d will be as k e d t o fill i n a n e xit s ur ve y a n d p erf or m 
fi nal uri ne pre g n a nc y test . 
At t he e n d of t he st u d y ( Da y 2 8), Acti gra p h d e vice a n d t he all ocate d pr o d uct ( use d a n d 
u n use d) f or t his cli nical st u d y, s h o ul d be ret ur ne d t o t he Hale o n Cli nical S u p plies 
De part me nt or 
 usi n g t he ret ur n i nstr ucti o ns pr o vi de d.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 3 9  of 7 0  
 
9. 3  
Di ar y R e vi e w  
T he e Diar y s h o ul d be re vie we d at t he e n d of St u d y, d uri n g Da y 7, 1 4 a n d 2 1 b y t he 
i n vesti gat or, a n d peri o di call y u p t o t he discreti o n of i n vesti gat or (re m otel y via tele p h o ne 
call or via e mail c o m m u nicati o ns –  t his is u p t o t he discreti o n of t he site staff a n d t he 
s u bject). A n y s u bject c o m me nt ca pt ure d i n t he e Diar y w hic h is c o nsi dere d a n a d verse 
e ve nt will be assess e d a n d re p orte d as per t he defi ne d pr oce d ure i n t his pr ot oc ol. A d verse 
e ve nt re p orti n g pr oce d ures are s u m marise d i n A d verse E v e nt a n d Seri o us A d verse E v e nts .  
A n y a d diti o nal c o m me nts relati n g t o me dicati o ns/treat me nts pr o vi de d i n t he e Diar y will 
be re vie we d b y t he i n vesti gat or or me dicall y q ualifie d desi g nee wit h t he s u bject a n d 
i n vesti gat or e ntere d t h e e C R F as a p pr o pri ate.  
9. 4  
St u d y C o n cl u si o n  
T he St u d y C o ncl usi o n pa ge of t he e C R F will be c o m plete d f or all s u bjects w het her t he y 
c o m plete d all st u d y pr oce d ures or if t he y were disc o nti n ue d fr o m t he st u d y earl y.  If t he 
s u bject disc o nti n ue d earl y, at a n y p oi nt d uri n g t he st u d y, t he pri mar y reas o n f or wit h dra wal 
s h o ul d be rec or de d o n t h e St u d y C o ncl usi o n pa ge. 
If a s u bject has a n y cli nicall y si g nifica nt, st u d y-rel ate d a b n or malities or A Es at t he e n d of 
t he st u d y, t he Hale o n me dical m o nit or ( or desi g nate d re prese ntati ve) s h o ul d be n otifie d 
a n d, t he s u bject ma y b e as ke d t o re mai n at t he cli nical site or be as k e d t o ret ur n f or a 
f oll o w-u p visit t o e ns ure a n y iss ue is res ol ve d or d ee me d n ot cli nicall y si g nifica nt.  
9. 5  
F oll o w -u p Vi sit/ P h o n e C all  
T he st u d y site ma y c o nta ct a s u bject t o f oll o w u p a n A E p ost -st u d y 
c o m pleti o n/ wit h dra wal a n d, i n s o me circ u msta nces, re q uest t he y ret ur n t o t he site  f or 
a d diti o nal f oll o w -u p visits (fi nal safet y assess me nts). If nee de d, a d diti o nal e xa mi nati o ns 
ma y be carrie d o ut at s uc h visits.  
1 0  
S T U D Y A S S E S S M E N T S  
E ver y eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol -re q uire d t ests a n d pr oce d ures are 
c o m plete d as d escri b e d.  H o we v er, it is a ntici p ate d t hat fr o m ti me t o ti me t here ma y b e 
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 hes e cases, t he i n vesti gat or m ust ta ke all ste ps necessar y t o 
e ns ure t he s afet y a n d w ell -bei n g of t he s u bject.  W he n a pr ot oc ol -re q uir e d assess me nt 
ca n n ot be perf or me d, t he i n vesti gat or will d oc u me nt t he reas o n f or t he misse d assess me nt 
as a pr ot oc ol de viati o n a n d a n y c orrecti ve a n d pre v e ntati ve acti o ns t hat he or s he has ta ke n 
t o e ns ure t hat 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 be 
i nf or me d of a n y misse d assess me nts i n a ti mel y ma n ner. 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 0  of 7 0  
 
1 0. 1  
S cr e e ni n g A s s e s s m e nt s  
S u bject e nr ol me nt will be deter mi ne d base d o n t he i ncl usi o n/e xcl usi o n criteria d uri n g 
scree ni n g.  
1 0. 2  
Q u alit y of Lif e A s s e s s m e nt s  
T he f oll o wi n g q ualit y of life t o ols will be c o m plete d b y s u bjects dail y i n t he s u bject e Diar y 
fr o m recei pt of pr o d uct t o st u d y c o ncl usi o n. 
•  W O M A C, N R S a n d E Q -5 D -5 L Q uesti o n nair e.  
•  Q o L a n d Slee p/alert ness Q uesti o n naires.  
1 0. 3  
W e ar a bl e A s s e s s m e nt s  
T he f oll o wi n g weara bl e assess me nts will be perf or me d b y Acti gra p h dail y a n d will be 
c orrel ate d wit h Q o L assess me nts fr o m recei pt of pr o d uct t o st u d y c o ncl usi o n.  
•  M o derate a n d Vi g or o us P h ysical Acti vit y.  
•  P h ysical a n d slee p base d acti vities.  
1 0. 4  
S af et y a n d Ot h er A s s e s s m e nt s  
S u bject s will re p ort a n y a d verse e v e nts t hr o u g h o ut t he st u d y fr o m c o nse nt t o st u d y 
c o ncl usi o n.  
S u bject s will c o m plete a n e Diar y t o rec or d pr o d uct use eac h da y.  
S u bject s will c o m plete e n d o f t he st u d y q uesti o ns as o utli ne d t o t he m d uri n g c o nse nt.  
T he l ocal i n vesti gat or will rec or d a n y rele va nt me dical a n d s ur gical hist or y, i ncl u di n g 
aller gies or dr u g s e nsiti vit y, a n d a d v erse e ve nts. T he l ocal i n v esti gat or will als o rec or d use 
of a n y c urre nt  m e 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 r e me dies.  
1 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 desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, 
a n d re p o rti 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 relate 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. 
1 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 nce i n a cli nical st u d y s u bject, te m p orall y 
ass ociate d wit h t he use of a st u d y pr o d uct i ncl u di n g a n y was h o ut or lea d -i n pr o d uct ( or 
me dical de vic e), w h et her or n ot c o nsi dere d relat e 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 u ct ( or me dical de vice). 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 1  of 7 0  
 
N O T E: A n A E ca n t heref ore be a n y u nfa v o ura ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bat e 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 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 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 ( hae 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 n cl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli ni call y 
si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or (i.e., n ot 
relate d t o pr o gressi o n of u n derl yi n g disease). 
•  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 ncrease i n fre q ue n c 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 i nf or m e d c o nse nt si g ni n g ( pri or t o 
st u d y pr o d uct a d mi nistrati o n) e ve n t h o u g h it ma y ha ve bee n pres e nt bef ore t he 
start of t he st u d y. 
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.  
•  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 uct or a c o nc o mita nt me dicati o n. O ver d ose pe r 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 dl ess of se q uel ae.  
•  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 eff icac 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. Als o, "lac k of 
effic ac y" or "f ail ure of e x pecte d p har mac ol o gical acti o n" c o nstit utes 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 ociate 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 s e vere t ha 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 pecte d pr o gressi o n, si g ns, or s y m pt o ms of 
t he disease/ dis or der b ei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he 
s u bject’s c o n diti o n.  
•  Me dical or s ur gical pr oce d ure (e. g. e n d osc o p y, a p pe n dect o m y) is n ot 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-da 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 det ecte d at t he start of t he st u d y t hat d o n ot w orse n.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 2  of 7 0  
 
1 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 cate g or y of a n a d verse e v e nt w here t he 
a d verse o utc o me is s eri o us. If a n e ve nt is n ot a n A E per d efi niti o n a b o ve, t h e n it ca n n ot b e 
a n S A E e v e n if seri o us c o n diti o ns are met (e. g. h os pitalisati o n f or si g ns/s y m pt o ms of t he 
disease u n der st u d y, d eat h d ue t o pr o gressi o n of 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 v e nt, w hic h h y p ot heticall y mi g ht ha ve ca use d deat h, if it were 
m ore se vere;  
•  Re q uires i n p atie nt h os pit alis ati o n or pr ol o n g ati o n of e xisti n g h os pit alis ati o n   
▪ I n g e neral, h os pitalisati 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 ge n c y 
war d f or o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o pri ate 
i n t he p h ysicia n’s office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur 
d uri n g h os pitalisati o n are A Es. If a c o m plicati o n pr ol o n gs h os pitalisati o n or 
f ulfils a n y other seri o us criteria, t he e v e nt is seri o us. W he n i n d o u bt as t o 
w het her “ h os pitalisati 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 pitalisati o n f or electi ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot 
w orse n fr o m b aseli ne is n ot c o nsi dere d a n A E. 
•  Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y  
▪ T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o 
c o n d uct n or mal life f u ncti o ns.  
▪ T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie n ces of relati v el y mi n or 
me dical si g nifica nce s uc h as u nc o m plicate d hea d ac he, n a usea, v o miti n g, 
diarr h oea, i nfl ue nza, a n d acci de nt al tra u ma (e. g., s prai ne d a n kle) w hic h ma y 
i nterfere wit h or pre v e nt e ver 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 
•  R es 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 ng or res ult i n deat h or 
h os pitalisati o n b ut ma y je o par dize t he s u bject or ma y re q uire m e 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 
defi niti o n. T hese e ve nts s h o ul d us uall y be c o nsi dere d seri o us.  
▪ E xa m ples of s uc h e 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 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 3  of 7 0  
 
d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalisati o n, or de vel o p me nt 
of dr u g de pe n d e nc y or dr u g a b use.  
N ote:  Class ificati 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 det er mi ni n g re p orti n g re q uire me nts. 
1 1. 3  
R e p orti n g Pr o c e d ur e s  
T he i n vesti gat or is res p o nsi ble f or detecti n g, d oc u me nti n g, a n d re p orti n g e ve nts t hat meet 
t he defi niti o n of a n A E a n d re mai n res p o nsi ble f or f oll o wi n g u p o n A Es t hat are seri o us, 
c o nsi dere d relate d t o t he st u d y pr o d uct(s), p artici p ati o n i n t he st u d y, or a  st u d y pr oce d ure, 
or t hat ca use d t h e 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.  
Eac h A E is t o be assesse d t o deter mi ne if it meets t he criteria f or a S A E.  If a n S A E occ urs, 
e x pe dite d re p orti n g will f oll o w l ocal a n d i nter nati o nal re g ulati o ns, as a p pr o priate.  
W he n a n A E occ 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) relat e d t o t he e ve nt.  
T he i n vesti gat or or site st aff will t he n rec or d all rele va nt i nf or m ati o n re gar di n g a n A E i n 
t he e C R F a n d all det ails 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 nee) t o se n d 
p h ot oc o pies of t h e 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 he A E 
e C R F pa ge/ S A E f or m.  
T he i n vesti gat or ( or me dicall y q ualifie d desi g nee) will atte m pt t o esta blis h a dia g n osis of 
t he e ve nt b ase 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 pir at or y tr act i nfecti o n, seas o nal all er 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 dicall y q ualifie d desi g nee) i n a sta n dar d ma n ner at 
t he 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 e 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 ges 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 q uesti o ni n g s h o ul d be use d.  
1 1. 3. 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 e 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 mati o n is n ot t he sa me as t he A E 
e C R F.  W h ere t h e sa me data are c ollecte d, t he A E e C R F pa g e a n d t h e 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 x a 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 e 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. 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 4  of 7 0  
 
1 1. 3. 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 e C R F pa ge, a n S A E f or m s h o ul d 
be c o m plete d, as f ull y as p ossi ble. Har d c o pi es 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 A E 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 nt s, 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 d esira ble a n d are of p artic 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 va nt  
•  St u d y pr o d uct start date  
•  St u d y pr o d uct e n d date if rele va nt  
•  Acti o n ta ke n i n relati o n t o 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 plete d as f ull y as p ossi ble, m ust be sca n ne d a n d e -mail e d t o t he Si n gle 
Case Pr ocessi n g  mail b o x (T a ble 1 1 -1 ), , wit h a c o p y t o t he a p pr o priate Hale o n or 
St u d y Ma na g er, wit h t h e st u d y n u m ber a n d s u bject n u m b er 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 h e i n vesti gat or will s u b mit a n y u p d ate d S A E dat a 
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 niti al re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rel e va nt, or as re q u este d 
b y t he st u d y ma na ger.  
T he Hale o n St u d y Ma na ger will be res p o nsi ble f or f or war di n g t he S A E f or m t o ot her 
Hale o n pers o n n el as a p pr o priate.  
T he i n vesti gat or (s) will be res p o nsi ble f or n otif yi n g t he I R B/I E C of S A Es t hat occ ur 
d uri n g t he st u d y.  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 5  of 7 0  
 
T a bl e 1 1 -1  
Si n gl e C a s e Pr o c e s si n g  m ail b o x  
U nite d States  
A mericas ( N o n -U S): 
 Ca na da/ Me xic o/ S o ut h 
& Lati n A merica  
 
E M E A: E ur o pe, Mi d dle East, C o m m o n wealt h 
of I n de pe n d e nt State ( CI S), Africa  
T ur ke y  
A P A C c o u ntries (e xcl u di n g Ja pa n)  
 
Ja pa n 
 
1 1. 4  
E v al u ati n g A d v er s e E v e nt s  
1 1. 4. 1  
A s s e s s m e nt of I nt e n sit y  
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E re p ort e d d uri n g t he 
st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories: 
•  Mil d:  A n e ve nt t hat is easil y t olerate d b y t he s u bject, ca usi n g mi ni mal disc o mf ort 
a n d n ot i nterferi n g wit h e ver y da y acti vities.  
•  M o derate:  A n e v e nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfe re 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 hat is ass esse d as se vere s h o ul d n ot be c o nf use d wit h a n S A E. Se vere is a 
cate g or y utilize d f or rati n g t he i nte nsit y of a n e ve nt; a n d b ot h n o n -serio us A Es a n d S A Es 
ca n be assesse d as se v ere. F or e xa m ple, a hea dac h e ma y be se 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 n ot b e classifi e 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 defi ne d as ‘seri o us’ w he n it meets at 
least 1 of t he pre defi ne d s eri o us ness criteria as d es cri be d i n t he d efi niti o n of a n S A E, N O T 
w he n it is rate d as se v ere.  
1 1. 4. 2  
A s s e s s m e nt of C a u s alit y  
T he ca usalit y assess me nt is o ne of t he criteria use d w he n deter 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 dicall y q ualifie d desi g nee) 
m ust  pr o vi de a n assess me nt of ca usalit y o n t h e A E e C R F p a 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 he/s he has re vi e we d t he A E a n d ass esse d ca usalit y, w here a p plica ble.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
P P D
P P D
P P D
P P D
P P D
P P D

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 6  of 7 0  
 
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 he r 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 de nce) or ar g u m e nts t o s u g gest a ca usal relati o ns hi p s h o ul d be 
pr o vi de d.  
T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p a n d will als o 
c o ns ult t he I n vesti gat or Br oc h ure (I B), Safet y State me nt a n d/ or Pr o d uct I nf or mati o n, f or 
mar kete d pr o d ucts, i n t he deter mi nati o n of his/ her assess me nt.  Alter nati 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 eve 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 has 
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 (s eri 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 us al relati o ns hi p i n t he e C R F, as a p pr o priate, 
a n d re p ort s uc h a n assess me nt i n acc or da nce wit h t he S A E re p orti n g re q uire me nts if 
a p plica ble.  
T here ma y b e sit uati o ns  w he n a n S A E has occ urre d, a n d t he i n vesti 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 v er, 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 v er y e ve nt pri or t o t he 
i niti al tr a ns missi on 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 us alit y assess me nt.  
1 1. 5  
F oll o w -u p of A E s a n d S A E s  
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 u este d b y Hale o n t o 
el uci date as f ull y as p ossi ble t he nat ur e a n d/ or ca usalit y of t he S A E or 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 d ate d i nf or mati o n will be rec or de d o n t he A E 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 ga t 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.  
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.  
1 1. 6  
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 her ca us es, 
acc or di n g t o t he defi niti o n of a n A E n ote d earli er, a n d rec or de d o n t he a p pr o priate A E 
e C R F pa ge.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 7  of 7 0  
 
W he n a s u bject wit h dr a 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 uir e me nts defi ne d.  
1 1. 7  
Pr e g n a n c y  
1 1. 7. 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  
Alt h o u g h st u d y pr o d uct use is n ot rec o m me n de d d uri n g pre g na nc y, a n d t his is a n e xcl usi o n 
criteri o n f or partici pati n g i n t he st u d y, pre g na nc y test will be perf or me d at Scree ni n g (site 
V isit 1) a n d E n d of St u d y ( V isit 3) ( See Sc h e d ule of Acti vities) a n d pre g na n c y i nf or mati o n 
will be c ollecte d o n all pre g na nci es re p orte d w hil e 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 1 da y after last a d mi nistrati o n of s t u d y 
pr o d uct.  
W o me n of c hil d beari n g p ote ntial i ncl u de d i n t he st u d y are a d vise d t o us e a n effecti ve 
met h o d of c o ntrace pti o n fr o m t he ti me of scree ni n g a n d u ntil 1 da y after last a d mi nistrati o n 
of st u d y pr o d uct.  
A n effecti ve m et h o d of c o ntrace pti o n ca n ac h ie ve a fail ure rat e less t ha n 1 % per y ear w he n 
use d c o nsiste ntl y a n d c orrectl y. As per rec o m me n dati o ns relat e d t o c o ntrace pti o n a n d 
pre g na nc y testi n g i n cli nical trials ( Cli nical Trials Facilitati o n a n d C o or di nati o n Gr o u p 
C T F G 2 1/ 0 9/ 2 0 2 0 Versi o n 1. 1), s uc h  met h o ds i ncl u de:  
 
• c o m bi ne d ( oestr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n ( oral, i ntra va gi n al or tra ns der mal)  
• pr o gest o ge n-o nl y h or m o nal c o ntrace pti o n ass oci ate d wit h i n hi biti o n of o v ulati o n ( oral , 
i njecta ble, i m pla nta ble, i ntra uteri ne de vice (I U D)  
• i ntra uteri ne h or m o ne-releasi n g s yste m (I U S)  
 
• s ur gical sterilisati o n (e. g., bilateral t u bal occl usi o n) 
 
• vasect o mise d part n er 
 
• se x ual a bsti ne nce 
 
1 1. 7. 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 rec or d pre g na 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 Si n gle Case Pr ocessi n g  mail b o x (T a ble 1 1 -1 ),  wit h c o p y t o t he a p pr o priate 
St u d y Ma na ger. Ori gi nal pre g na nc y i nf or mati o n f or ms will be retai ne d i n t h e i n vesti gat or 
st u d y master file.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 8  of 7 0  
 
T he s u bject will be f oll o we d t o deter mi ne t he o ut c o me of t he pre g na nc y. I nf or mati o n o n 
t he stat us of t he m ot her a n d infa nt / ne o n ate (i n cl 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 Si n gle Case 
Pr ocessi n g  mail b o x at Hale o n (T a ble 1 1 -1 ), wit h c o p y t o t he a p pr o priat e   St u d y Ma na ger. 
Ge nerall y, f oll o w -u p will be n o l o n ger t ha n 6 t o 8 wee ks f oll o wi n g t he esti mate d deli ver y 
date. A n y ter mi nati o n of t he pre g na n c y will be re p orte d.  
W hile pre g na nc y itself is n ot c o nsi dere d t o be a n A E, a b n or mal pre g na n c y o utc o mes (e. g. 
s po nta ne o us a b orti o n, f oetal 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.  
T he i n vesti gat or will c ollect pre g na n c y i nf or mati o n o n a n y s u bject w h o bec o mes pre g na nt 
w hile partici pati n g i n t he st u d y after a d m i nistrati o n of t he i n vesti gati o nal pr o d uct. T he 
i n vesti gat or will rec or d pre g na nc y i nf or mati o n o n t he a p pr o priate f or m a n d s u b mit it t o 
 wit hi n 2 4 h o urs of lear ni n g of t h e s u bj ect bec o mi n g pre g na nt. T he s u bject will 
be f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y. I nf or m ati o n o n t he stat us of t he 
m ot her a n d i nfa nt/ ne o nat e (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 t o 
Ge nerall y, f oll o w -u p will be n o l o n ger 
t ha n 6 t o 8 wee ks f oll owi n g t he esti mate d deli ver y date. A n y ter mi nati o n of t he pre g na n c y 
will be re p orte d.  
will sca n a n d e mail t he pre g na nc y f or m t o t he Si n gle Case Pr ocessi n g  mail b o x 
at Hale o n (T a ble 1 1 -1 ) wit h c o p y t o t he a p pr o p riate St u d y Ma na ger. Ori gi nal pre g na nc y 
i nf or mati o n f or ms will be retai ne d i n t he i n v esti gat or st u d y master file.  
1 1. 8  
R e p orti n g S eri o u s A d v er s e E v e nt s a n d Ot h er S af et y I s s u e s 
t o R e g ul at or y A ut h oriti e s/ Et hi c s C o m mitt e e s 
 
All S us pecte d U ne x pecte d Seri o us A d ver se Reacti o n (S U S A Rs ) t hat occ ur wit h t he I M Ps 
wit hi n or o utsi de t he c o ncer ne d cli nical trial, if re q uire d, will be re p orte d b y Hale o n t o 
E u dra vi gila nce ( E V C T M) i n c o m plia nce wit h t he ti meli nes a n d sta n dar ds f or re p orti n g 
S U S A Rs set o ut i n t he E U Cli nical T rial Re g ulati o n 5 3 6/ 2 0 1 4. I n vesti gat ors will be 
i nf or me d a b o ut a n y safet y pr ofile c ha n g es a n d will  recei ve S U S A Rs via C o u ncil f or 
I nter nati o nal Or ga ni zati o ns of Me dical Scie nces ( CI O M S) f or m or b y peri o dic li ne-listi n gs 
pr o d uce d b y H ale o n.  
Re gar di n g  re g ulati o ns i n f orce f or p h ar mac o vi gila nce, i n vesti gat ors m ust f ulfil t heir 
o bli gati o ns acc or di n g t o t he la w i n f orce i n t heir c o u ntr y, i ncl u di n g re p orti n g of ( Seri o us) 
A d verse E v e nts or a n y ot her i nf or mati o n/listi n g as per t heir E Cs/I R B re q uir e me nt.  
I n a d diti on t o S U S A Rs, all u ne x pecte d e ve nts t hat mi g ht materiall y i nfl ue nce t h e 
be nefit -ris k assess me nt of t he me dici nal pr o d uct will be perf or me d a n d Et hics C o m mittee  
will be n otifie d as set o ut i n E U Cli nical Trial Re g ulati o n 5 3 6/ 2 0 1 4.  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
C CI
C CI
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 4 9  of 7 0  
 
1 1. 9  
Ri s k s a n d b e n efit s r el at e d  t o t h e p arti ci p ati o n i n t h e cli ni c al 
tri al 
 
1 1. 9. 1  
Ri s k s r el at e d t o V olt ar e n g el  
 
T he I n v esti gati o nal Me di ci nal Pr o d uct (I M P), V oltare n g el, is re gistere d a n d mar kete d i n 
c o u ntries c o ncer ne d b y t he st u d y. T he I M P will be use d i n acc or da n ce wit h t he i n dicati o ns, 
p os ol o g y a n d safet y pr o d uct i nf or mati o n a p pr o ve d.  
 
V oltare n gel is c o ntr ai n dicate d i n t he f oll o wi n g cir c u msta nces:  
 
•  I n patie nts wit h a k n o w n h y perse nsiti vit y t o dicl ofe nac or t o a n y of t he pr o d uct 
e xci pie nts.  
•  I n p atie nts i n w h o m ast h ma, a n gi oe de ma, urticari a, or ac ute r hi nitis are preci pitate d 
b y acet ylsalic ylic aci d or ot her n o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds).  
•  D uri n g t he last tri mester of pre g na n c y a n d d uri n g lactati o n/ breastf ee di n g.  
 
S pecial War n i n gs & Preca uti o ns f or Use:  
 
T he p ossi bilit y of e x perie nci n g s yste mic a d verse e ve nts (t h ose ass ociat e d wit h t he use of 
s yste mic f or ms of dicl ofe nac) s h o ul d be c o nsi dere d if V oltare n gel is us e d at a hi g her 
d osa ge or f or a l o n ger peri o d of ti me t ha n rec o m m e n de d.  
 
V oltare n gel s h o ul d be a p plie d o nl y t o i ntact, n o n -disease d s ki n, a n d n ot t o s ki n w o u n ds 
or o pe n i nj uries. It s h o ul d n ot be all o we d t o c o me i nt o c o ntact wit h t he e yes or m uc o us 
me m bra nes a n d s h o ul d n ot be i n geste d. V oltare n E m u gel ca n be use d wit h n o n -occl usi ve 
ba n da ges b ut s h o ul d n ot be use d wit h a n airti g ht o ccl usi ve dressi n g.  
 
I nteracti o ns wit h ot her Me dical Pr o d ucts a n d ot her F or ms of I nteracti o n:  
 
Si nce s yste mic a bs or pti o n of dicl ofe nac fr o m t o pi cal a p plicati o n is ver y l o w, i nteracti o ns 
are u nli kel y. 
 
Pre g na nc y & Lactati o n:  
 
T here are i ns uffi cie nt dat a o n t he use of dicl ofe nac i n pre g n a nt w o me n. Dicl ofe nac s h o ul d 
be use d d uri n g t he first t w o tri mesters of pre g na n c y o nl y if t he e x pect e d b e nefit j ustifies 
t he p ote ntial ris k t o t he f oet us. As with ot her N S AI Ds, use of dicl ofe nac d uri n g t he t hir d 
tri mester of pre g n a nc y is c o ntrai n dicate d o wi n g t o t he p ossi bilit y of uteri ne i nertia, fet al 
re nal i m pair me nt wit h s u bse q ue nt oli g o h y dra m ni os a n d/ or pre m at ure cl os ur e of t he d u ct us 
arteri os us  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 0  of 7 0  
 
 
It is n ot k no w n w het her t o pical dicl ofe nac is e x crete d i n breast mil k. Dicl ofe nac s h o ul d 
o nl y be use d d uri n g lactati o n if t he e x pecte d be nefit j ustifies t he p ote ntial ris k t o t he ne w -
b or n. If t here are c o m pelli n g reas o ns f or usi n g it, it s h o ul d n ot be a p plie d t o t he b reasts, 
n or s h o ul d it be use d at a hi g her d osa ge or f or a l o n ger peri o d of ti me t ha n rec o m me n de d  
 
A bilit y t o perf or m tas ks t hat re q uire J u d g e me nt, M ot or or C o g niti ve S kills:  
 
T o pical a p plicati o n of di cl ofe nac has n o i nfl ue n ce o n t he a bilit y t o dri ve a n d u se 
mac hi nes.  
 
A d verse Reacti o ns:  
 
A d verse reacti o ns are ta b ulate d bel o w b y S yste m Or ga n Class a n d fre q ue n c y. T he 
f oll o wi n g c o n ve nti o n has bee n utilise d f or t he cl assificati o n of u n desira ble effects: ver y 
c o m m o n ( ≥ 1/ 1 0) c o m m o n ( ≥ 1/ 1 0 0 t o < 1/ 1 0); u nc o m m o n ( ≥ 1/ 1, 0 0 0 t o < 1/ 1 0 0); rare 
( ≥ 1/ 1 0, 0 0 0 t o < 1/ 1, 0 0 0); ver y rare ( < 1/ 1 0, 0 0 0), n ot k n o w n (ca n n ot be esti mate d fr o m 
a vaila ble data).  
 
Wit hi n eac h fre q ue n c y gr o u pi n g, a d verse reacti o ns are prese nte d i n or d er of decreasi n g 
seri o us ness. 
 
T a bl e 1 1 -2  
A d v er s e R e a cti o n Fr e q u e n c y  
 
Me d D R A S O C  
A d verse Re a cti o n  
Fre q ue nc y  
I nfecti o n a n d i nfestati o n  
Ras h p ust ular  
Ver y rare  
I m m u ne s yste m dis or ders 
A n gi oe de ma, h y perse nsiti vit y (i ncl u di n g urticaria)  
Ver y rare  
Res pirat or y, t h oracic a n d 
me diasti nal dis or ders  
Ast h ma  
Ver y rare  
S ki n a n d s u bc uta ne o us tiss ue 
dis or ders  
Der matitis (i ncl u di n g c o ntact der matitis), ras h, 
er yt he ma, ecze ma, pr urit us.  
C o m m o n  
Der matitis b ull o us  
Rare  
P h ot ose nsiti vit y reacti o n  
Ver y rare  
 
O ver d osa g e:  
 
T he l o w s yste mic a bs or pti o n of t o pical di cl ofe n ac re n ders o ver d ose u nli kel y. H o we ver 
u n desira ble effects, si milar t o t h ose o bser ve d f oll o wi n g a n o ver d ose of dicl ofe nac ta blets, 
ca n be e x pecte d if t o pical dicl ofe nac is i n geste d. I n t he e ve nt of acci de ntal i n gesti o n, 
res ulti n g i n si g nifica nt s yste mic a d verse effects, ge neral t hera pe utic meas ures n or mall y 
a d o pte d t o tr eat p ois o ni n g wit h n o n -ster oi d al a nti-i nfla m mat or y me dici nes s h o ul d be use d. 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 1  of 7 0  
 
1 1. 9. 2  
B e n efit s  
Partici pati n g i n t his cli nical st u d y offers patie nts se veral si g nifica nt be nefits:  
E n ha nce d U n dersta n di n g of Real -W orl d Effecti ve ness:  
Real W orl d E vi de nce ( R W E) st u dies, s uc h as t his o ne, pr o vi de val ua ble i nsi g hts i nt o h o w 
a pr o d uct perf or ms i n e ver y da y s etti n gs, reflecti n g a m ore acc urate pict ure of its 
effecti ve ness i n a di vers e p o p ulati o n. T his st u d y ai ms t o e val uate t he real -life i m pact of 
usi n g V oltare n gel ( dicl of e nac) o n f u ncti o nal m o bilit y a n d q ualit y of life, e ns uri n g t hat t he 
fi n di n gs are hi g hl y rele v a nt t o t he t y pical c o ns u mer base. 
O bjecti ve Meas ure me nt of Be nefits:  
T he st u d y will g o be y o n d s u bjecti ve assess me nts of be nefits i n t he fiel d of O A a n d Pai n. 
Utilisi n g researc h -gra d e weara ble de vi ces ( Acti gra p h), t he st u d y will meas ure c h a n ges i n 
f u ncti o nal m o bilit y a n d q ualit y of life as pects. T his o bjecti ve data c ollecti o n all o ws f or 
precise 
m o nit ori n g of t he patie nt's pr o gress, pr o vi di n g a clear a n d q ua ntifia ble 
u n dersta n di n g of h o w V oltare n gel i nfl ue nces dail y acti vities a n d o verall well -bei n g.  
C o m pre he nsi ve Data C ollecti o n:  
T he st u d y c o m bi nes b ot h o bjecti ve a n d s u bjecti ve assess me nts t o offer a h olistic vie w of 
t he be nefits of usi n g V oltare n gel. T his d ual a p pr oac h e ns ures a t h or o u g h e val uati o n, 
ca pt uri n g t he n ua nce d w a ys i n w hic h t he gel i m pr o ves f u ncti o nal m o bilit y a n d q ualit y of 
life, be y o n d j ust pai n reli ef. 
Pers o nalise d Healt h I nsi g hts:  
Patie nts will recei ve d etaile d fee d bac k o n t h eir m o bilit y a n d q ualit y of life, deri ve d fr o m 
b ot h t he weara ble d e vice data a n d s u bjecti ve re p orts. T his pers o nalize d i nf or mati o n ca n 
hel p patie nts better u n dersta n d t heir c o n diti o n a n d t he i m pact of t he tr eat me nt, e na bli n g 
m ore i nf or me d dis c ussi o ns wit h healt hcare pr o vi d ers.  
C o ntri b uti o n t o Me dical K n o wle d ge:  
B y partici pati n g i n t his st u d y, patie nts c o ntri b ute t o a br oa der u n dersta n di n g of h o w t o pical 
dicl ofe nac ca n be n efit i n di vi d uals wit h oste oart hritis a n d ot her c o n diti o ns ca usi n g pai n a n d 
i m paire d m o bilit y. T he fi n di n gs fr o m t his st u d y c o ul d i nf or m f ut ure treat me nt g ui deli nes 
a n d i m pr o ve care str ate gi es f or ot hers wit h si milar c o n diti o ns.  
P ote ntial f or I m pr o ve d Q ualit y of Life:  
Gi ve n t he esta blis he d be nefits of dicl ofe n ac i n pai n relief a n d t he p ot e ntial f or e n ha n ce d 
m o bilit y a n d dail y f u ncti o ni n g, patie nts i n t his st u d y 
ma y e x perie nce s u bsta ntial 
i m pr o ve me nts i n t heir q ualit y of life. I m pr o v e d m o bilit y ca n lea d t o i ncrease d a bilit y t o 
e n ga ge i n p h ysical acti vities, better slee p, e n ha n ce d m o o d, a n d greater partici pati o n i n 
dail y acti vities, w hic h c ollecti vel y c o ntri b ute t o o verall well -b ei n g.  
Safet y a n d M o nit ori n g:  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 2  of 7 0  
 
Partici pa nts i n t his st u d y will be cl osel y m o nit ore d, e ns uri n g a n y a d v erse effects are 
pr o m ptl y a d dresse d. T his le vel of atte n ti o n ca n pr o vi de patie nts wit h a se nse of sec urit y 
a n d i m me diate s u p p ort, e n ha nci n g t he o verall treat me nt e x perie n ce.  
Partici pati o n i n t his st u d y n ot o nl y offers p ote ntial direct b e nefits t o t he p atie nts i n ter ms 
of i m pr o ve d m o bilit y a n d q ualit y of life b u t als o c o ntri b utes t o t he a d v a nce m e nt of me dical 
k n o wle d ge a n d t he p ot e ntial t o be nefit f ut ure patie nts wit h si milar c o n diti o ns. T he 
c o m pre he nsi ve a n d p ers o nalise d i nsi g hts gai ne d t hr o u g h t his st u d y ca n e m p o wer patie nts 
a n d e n ha n ce t heir tr eat m e nt j o ur ne y.  
1 1. 9. 3  
Ri s k s/ B e n efit s E v al u ati o n  
 
Dicl ofe nac is a well -esta blis he d N S AI D t hat has a nal gesic a n d a nti -i nfla m mat or y 
acti vities. T o pical dicl ofe nac h as a wi d e a n d l o n g -sta n di n g use f or t h e s y m pt o matic 
treat me nt of ac ute a n d c hr o nic m usc ul os keletal c o n diti o ns, i nclu di n g  mil d  oste oart hritis  of 
t he k nee a n d fi n gers.  
I n t he E ur o pea n Ec o n o mic Area ( E E A), dicl ofe nac diet h yla mi ne 1. 1 6 % gel a n d 2. 3 2 % gel 
( V oltare n E m ul gel), w ere res pecti vel y first re gistere d i n 1 9 8 5 i n S witzerla n d a n d R o ma nia, 
a n d i n 2 0 1 1 i n P ort u gal. Si n ce t he n, ma n y t o pical dicl ofe nac me dici n es, i ncl u di n g gels, 
s pra ys, a n d patc h es, ha v e bee n re gistere d i n t he E E A c o u ntries. F urt her m ore, dicl ofe n ac 
s o di u m 1 % gel has bee n a p pr o ve d i n t he U S si nce 2 0 0 7 f or prescri pti o n use a n d si nce 2 0 2 0 
f or o ver-t he-c o u nt er use f or t he te m p orar y pai n r elief of oste oart hritis. 
T he de gree of sci e ntific a n d cli nical i nterest i n t he use  of dicl ofe n ac diet h yla mi ne is 
reflecte d i n t he wealt h of st u dies a n d p u blicati o ns, as well as t he c o h ere n ce of t he scie ntific 
a n d cli nical asse ss me nts. T he t o pical a p plicati o n of dicl ofe nac ac hie ves t hera pe uticall y 
effecti ve c o n ce ntrati o ns i n t he tar get tiss ues, w hilst mi ni mizi n g s yste mic e x p os ure. 
Dicl ofe nac prefere ntiall y distri b utes a n d persists i n dee p i nfla me d tiss ues, s uc h as t he 
j oi nts. P har mac o ki netic st u dies ha ve als o de m o nstrate d t hat dicl ofe nac, w he n a p plie d 
t o picall y, pe netr ates t he s ki n barrier t o reac h s oft tiss ues, j oi nts, a n d t he s y n o vial fl ui d i n 
s ufficie ntl y hi g h c o nce ntrati o n t o e xert l ocal t hera pe utic acti vit y.  
T o mi ni mise t he  ris ks f or t he partici pati n g s u bjects, i ncl usi o n a n d e xcl usi o n criteria h a ve 
bee n caref ull y select e d c o nsi deri n g t he a p pr o ve d safet y pr o d uct i nf or mati o n of V oltare n 
gel. T he st u d y is a l o w -i nter ve nti o nal cli nical trial, a n d t he pr o d uct will be use d as per t h e 
a p pr o ve d i n dicati o ns a n d p os ol o g y.  
D uri n g t he st u d y, t he s u bjects will be m o nit ore d f or a n y d eteri or ati o n i n ge neral well -
bei n g, a n d t he y will be as ke d t o re p ort a n y a d verse e ve nts, w het her t he y o cc ur d uri n g t he 
st u d y. 
As s ufficie nt i nf or mati o n a b o ut t he I n vesti gati o nal Me dici nal Pr o d uct is alrea d y a vaila ble, 
n o s pecial safet y i n vesti gati o ns will be carrie d o ut d uri n g t he cli nical trial.   
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 3  of 7 0  
 
I n s u m mar y, re g ul ar c h ec ks ( 3 visits) will be ta ke n t o miti gate p ote ntial ris ks a n d t o e ns ure 
a de q uate s afet y of t h e  s u bjects partici pati n g i n t his cli nical trial.  
After c o nsi derati o n of t he ris ks a n d be n efits, t he perf or ma n ce of t he cli nical trial is 
c o nsi dere d et hicall y j ustifia ble, as t he e x pecte d f ut ure t hera pe utic be nefits of t he I M P 
a p pear t o b e greater t ha n t he ris ks t o t he s u bjects. 
1 2  
D A T A M A N A G E M E N T  
As use d i n t his pr ot oc ol, t he ter m e C R F is u n d erst o o d t o refer t o eit her a p a 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 d ata c ollecti o n met h o d.  
F or t his st u d y, s u bject d ata will be e ntere d i nt o a n e C R F, usi n g a v ali date d s yste m. Dat a 
relati n g t o S A Es, pre g na nc y a n d i nci de nts will als o be c ollecte d. 
T he i n vesti gat or is res p o nsi ble f or v erif yi n g t h at data e ntri es are acc urat e a n d c orrect b y 
p h ysicall y or electr o ni call y si g ni n g t he e C R F.  
T he s o urce d o c u me nts (e. g., h os pital rec or ds, cli nical a n d office c harts, la b orat or y n otes, 
me m ora n da, s u bj ect diaries, q uesti o n nair es, e v al uati o n c hec klists, dis pe nsi n g rec or ds, 
rec or de d dat a fr o m a ut o mate d i nstr u me nts) w hic h c o ntai n t he s o urce of d ata rec or de d i n 
t he e C R F s h o ul d be s pecifie d.  T he e C R F or e -Dair y  ca n be use d as a s o urce d oc u me nt at 
t he discreti o n of data m a na ge me nt. 
Eac h s u bject will be assi g ne d a n d i d e ntifie d b y a u ni q ue Scree ni n g S u bject N u m ber. A n y 
refere nce ma de t o a n i n di vi d ual s u bject wit hi n t he st u d y m ust be d o ne usi n g t heir u ni q ue 
Scree ni n g S u bject N u m b er.  
1 2. 1  
C a s e R e p ort F or m  
F or eac h s u bject w h o has gi ve n i nf or me d c o nse nt/asse nt t he e C R F m ust be c o m plete d a n d 
si g ne d b y t he i n vesti gat or or a ut h orize d desi g nee t o certif y t hat t he d ata are c o m plete a n d 
c orrect.  T h e i n vesti gat or m ust mai ntai n acc urate d oc u me nt ati o n (s o urce d ata) t hat 
s u p p orts t he i nf or mati o n e ntere d i n t he e C R F. 
Ma na ge me nt of cli nical d ata will be perf or me d i n acc or da n ce wit h T hir d Part y Bi ostatistics 
a n d Data Ma na g e me nt ( B D M) Ve n d or a p plica bl e sta n dar ds a n d d ata cl ea ni n g pr oce d ures 
wit h o versi g ht b y Hale o n t o e ns ure i nte grit y of t he data, f or e xa m ple, t o re m o ve err ors a n d 
i nc o nsiste ncies i n t he dat a.  
T o pr otect t he pri v ac 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 f ull birt h date) is t o be rec or de d i n t he e C R F or as part of t he q uer y te xt.  
All e C R F pa ges s h o ul d b e c o m plete d d uri n g a s u bject assess me nt w he n t he e C R F has bee n 
desi g nate d as t he s o urce.  Data t hat is s o urce d else w here s h o ul d be e ntere d i nt o t he e C R F 
i n a n a gree d u p o n ti mefra me bet wee n t he I n v esti gat or a n d S p o ns or.   
Hale o n will o btai n a n d retai n all e C R Fs a n d ass ociate d st u d y d ata as a p plica ble at t h e 
c o m pleti o n of t he st u d y.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 4  of 7 0  
 
1 2. 2  
D at a H a n dli n g  
D oc u me ntati o n of al l 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 alit 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 perf or me d i n t he Electr o nic Data Ca pt ure ( E D C) 
S yste m, a n d it will i ncl u de rati o nale f or c h a n ges. T he E D C s yste m has a n a u dit trail, w hic h 
will pr o vi de a c o m plete rec or d of t he c h a n ges a n d c orrecti o ns e n d orse d b y t he i n vesti gat or.  
A d verse e ve nts will be c o de d usi n g 
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A) a n d a n y c o nc o mita nt me dicati ons t er ms (if a p plica bl e) usi n g a n i nter nal 
vali date d me dicati o n dicti o nar y.   
1 2. 2. 1  
D at a Q u eri e s  
Pr o gra m me d e dit c h ec ks will be ge nerate d a ut o maticall y, as t he d ata are b ei n g e ntere d i nt o 
t he s yste m. Re p orts a n d listi n gs o n t he e C R F data will als o be r u n, i n a d diti o n t o t he q ueries 
alrea d y pr o gra m me d a n d ge nerate d b y t h e s yste m, t o raise ma n ual q ueries as nee de d f or 
site clarificati o n or c orrecti o n. T he Cli nical Dicti o nar y De vel o p me nt a n d Ma na ge me nt 
Gr o u p will raise q ueries as nee de d o n safet y dat a t o c o de t he te r ms ( A Es a n d Dr u gs or 
c o nc o mita nt me dicati o n) a p pr o priatel y.  
T he st u d y m o nit or will perf or m o n g oi n g re vie w t he of t he e 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 e C R F b y a ut h orise d site pers o n nel 
are acc urate, c o m pl ete, a n d verifia ble fr o m s o urce d oc u me nts; t hat t he safet y a n d ri g hts of 
partici pa nts are bei n g pr otecte d; a n d t hat t h e st u d y is bei n g c o n d ucte d i n acc or da nce wit h 
t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y a gree me nts, I C H G C P, a n d all 
a p plica ble re g ulat or y re q uire me nts. 
A n y q ueries will be ge nerate d i n t he E D C S yste m t o t he i n vesti gat or or desi g nee, e na bli n g 
t he err ors t o be a d dress e d i n parallel wit h Data Ma na ge me nt re vie w. T h e st u d y m o nit or 
ca n als o r u n re p orts a n d listi n gs o n t he e C R Fs, t o rais e m a n ual q u eries as nee de d f or site 
clarificati o n or c orrecti o n.  
1 2. 3  
Pr o c e s si n g P ati e nt/ S u bj e ct R e p ort e d O ut c o m e s a n d D at a 
C oll e cti o n fr o m I nt er n et of M e di c al T hi n g s  
Electr o nic Patie nt re p orte d o utc o me (e P R O) data will be c ollecte d usi n g electr o nic de vices 
a n d tra nsferre d electr o nicall y t o C R O a n d Hale o n. 
All e P R O s o urce d ata 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 m o 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 ntial A Es or c o nc o mita nt me dicati o ns 
re p orte d o n t hese d o c u m e nts are disc usse d wit h t he s u bject a n d tra ns cri be d acc uratel y t o 
t he e C R F a n d/ or D M S. e P R Os t hat are classe d as s o urce d ata will be retai ne d b y t he 
i n vesti gat or a n d tr ue/certifie d c o pies 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 mitant me dicati o ns c ollecte d as e P R O will be re vie we d a n d 
tra nscri be d t o t he e C R F b y a me m ber of t h e st u d y tea m. 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 5  of 7 0  
 
T o pr otect t he pri vac y of s u bjects, n o pers o nal i nf or mati o n (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 e P R O t hat will be f or war de d t o Hale o n or 
 
1 3  
S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A A N A L Y S E S  
1 3. 1  
S a m pl e Si z e D et er mi n ati o n  
S ufficie nt i n di vi d uals will be scree ne d t o e nr ol a p pr o xi matel y 1 9 5 s u bjects ass u mi n g a n 
esti mate d 2 5 % dr o p o ut rate. It is belie ve d t hat f or t his st u d y 1 4 7 c o m plete d s u bjects are 
dee me d s uffi cie nt t o o bser ve a n i m pr o ve me nt i n Q o L.  
T here were n o pre vi o us si milar st u dies meas uri n g M V P A c o u ple d wit h dail y use of a 
dicl ofe nac gel. T h us, t h e effect siz e was c h ose n b ase d o n literat ure re vie w t o d etect e ve n 
mil d i m pr o ve me nt i n Q o L fact ors: “ A n effect m a g nit u de bet wee n 0. 2 a n d 0. 5 i n dicates 
mil d i m pr o ve me nt, bet wee n 0. 5 a n d 0. 8 i n dicates m o derate i m pr o ve me nt, a n d greater t ha n 
0. 8 i n dicates c o nsi dera ble i m pr o ve me nt i n s y m pt o ms a n d Q o L.” T h e sa m ple si ze was 
base d o n a si g nifica nce le vel ( α) = 0. 0 5, P o wer ( 1 -β) = 8 0 %, a n d a sta n dar di ze d effect siz e 
of 0. 2 5  
Literat ure re vie w als o i n dicate d t hat Q o L sc ores are n ot n or mall y distri b ute d. S u bjects wit h 
w orse b aseli ne s y m pt o ms s h o we d lar ger i m pr o ve me nt i n Q o L s c ores. T heref ore, a t w o -
si de d n o n-para metric Wil c o x o n Si g ne d Ra n k test calc ulati o n was perf or me d.  
Usi n g t he a b o v e p ara met ers, w e o btai n a s a m ple size N = 1 9 5 t o retai n t he re q uire d 1 4 7 
c o m plete d s u bjects. T heref ore, it has bee n deter mi ne d t hat 1 9 5 eli gi b le s u bjects will be 
recr uite d f or t he trial, wit h a n a ntici pate d 1 4 7 st u d y s u bjects e x pecte d t o s uccessf ull y 
c o m plete t he st u d y.  
1 3. 2  
P o p ul ati o n s f or A n al y si s  
•  T he e nr olle d p o p ulati o n will i ncl u de all s u bjects w h o meet t he i ncl usi o n/e xcl usi o n 
criteria.  
•  T he safet y p o p ulati o n will i ncl u de all s u bjects w h o use st u d y pr o d uct at least o nce. 
Safet y p o p ulati o n will be use d of safet y varia bles.  
•  T he m o difie d I nte nt -T o -Treat ( mI T T) p o p ulati o n will i ncl u de all s u bjects w h o use 
st u d y pr o d uct at least o nce a n d h a ve d ata fr o m at least o ne p ost b aseli ne Q o L 
q uesti o n naire t o s u p p ort at least o ne of t he  sec o n d ar y e n d p oi nt assess me nts. Q o L a n d 
e P R O data will be s u m marize d usi n g t he mI T T p o p ulati o n o nl y . 
1 3. 3  
St ati sti c al A n al y s e s  
A d diti o nal details of t he pr o p ose d statistical a nal ysis will be d oc u me nte d i n t he statistical 
a nal ysis pla n ( S A P), w hic h will be writte n f oll o wi n g fi nalizati o n of t he pr ot oc ol a n d pri or 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 6  of 7 0  
 
t o st u d y a nal ysis. T his secti o n is a s u m mar y of t he pla n ne d statistical a nal ys es of t he m ost 
i m p orta nt e n d p oi nts i ncl udi n g pri mar y a n d ke y sec o n dar y e n d p oi nts.  
All data e xtracte d fr o m Acti gra p h a n d s u bjecti ve assess me nts ma y u n der g o vis ualisati o n, 
a n d gra p hs will be pl otte d w here ver feasi ble. F or i nsta nce, d ata p ertai ni n g t o b ot h t he d ail y 
a vera g e n u m ber of ste ps ta ke n a n d t he d ail y a v era ge n u m ber of st airs cli m be d/ desce n d e d 
will be pres e nte d i n sets of c harts, gra p hs, a n d heat ma ps. T his a p pr oac h ai ms t o e na ble a 
m ore t h or o u g h a nal ysis, f osteri n g a c o m pr e he nsi ve u n dersta n di n g of i ntricate patter ns, 
tre n ds, a n d relati o ns hi ps e m be d de d i n t he d ataset. F urt her i nf or mati o n will be pr o vi de d i n 
t he statistical a nal ysis pla n ( S A P). 
1 3. 3. 1  
Pri m ar y A n al y si s  
  
T otal st u d y d urati o n is 2 8 da ys, wit h pri mar y a nal ysis perf or me d p ost baseli ne ( baseli ne is 
fr o m Da y -7 t o Da y 0). F or pri mar y a nal y sis, a vera ge mi n utes of M V P A o n Da y 7 will be 
calc ulate d o ver all n o n -missi n g da ys bet wee n st u d y da y 1 ( pr o d uct us a ge) t hr o u g h 7, 
i ncl usi ve.   
A vera g e mi n utes of M V P A o n Da y 1 4 will be calc ulat e d o ver all n o n -missi n g da ys 
bet wee n st u d y d a y 8 t hr o u g h 1 4, i n cl usi ve. A vera ge mi n utes of M V P A o n Da y 2 1 will b e 
calc ulate d o ver all n o n -missi n g da ys bet wee n st u d y da y 1 5 t hr o u g h 2 1, i ncl usi ve. A n y da ys 
be y o n d da y 2 1 will be e x cl u de d fr o m all s u m maries a n d a nal ys es a n d will o nl y be prese nt 
i n liste d data. 
A  Mi xe d M o d el wit h Re peate d M eas ures ( M M R M) will be use d t o a nal yse t he c h a n ge 
fr o m bas eli ne i n 
M V P A a vera g e mi n utes as t he res p o nse v aria ble. S u bjects will be 
i ncl u de d as a ra n d o m effect, a n d ti me p oi nt will b e treate d as a re peat e d m eas ure wit hi n 
eac h s u bject. If da t a are f o u n d t o be n o n-n or mal, a n a p pr o pri ate n o n -para metric test will 
be perf or me d. If t he para meter f or t he i nterce pt ( wit h c o m p o u n d s y m metr y  str uct ure 
bet wee n visits) is f o u n d t o be statisticall y si g nifica nt ( p -val ue < 0. 0 5), t he n t he i n di vi d ual 
ti me p oints ( wit h u nstr uct ure d c o varia nce str uct ure bet wee n visits) will be a d de d as a fi xe d 
effect a n d a dj uste d me a ns f or eac h ti me p oi nt will be prese nt e d . P-val ues a n d 9 5 % 
c o nfi de nce i nter vals ( CIs) f or t he mea n c ha n ge fr o m baseli ne i n M V P A will be o btai ne d 
a n d prese nt e d f or eac h ti me p oi nt. Ot her t ha n t he gl o bal test f or a n o verall c ha n ge fr o m 
baseli ne (i.e., i nterce pt), t here will be n o ot her a dj ust me nt f or m ulti plicit y.  
1 3. 3. 2  
S e c o n d ar y A n al y si s  
F or t he sec o n d ar y o bj ecti ve, f u ncti o nal m o bilit y as meas ure d t hr o u g h wear a bles a n d P R O, 
pai n i nte nsit y assesse d t hr o u g h N R S ( dail y assess me nt), acti vit y -relate d pai n a n d stiff ness 
as meas ure d i n t he W O M A C s u bscales f or c o m p osite pai n a n d c o m p osite stiff ness will be 
a nal yse d usi n g t he sa m e M M R M as i n t he pri mar y o bjecti ve w here t he last o bser ve d dail y 
val ue u p t o Da y 0 will be use d as t he bas eli ne val u e.  
C orrelati o ns of q ualit y of life will als o be pr o vi de d as it pertai ns t o t he f oll o wi n g:  
•  Slee p/alert ness: Kar oli ns ka Slee pi ness Scale assesse d 1 x/ da y.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 7  of 7 0  
 
•  Healt h -relate d q ualit y of life: E Q-5 D -5 L.  
•  C ha n ge i n t he n u m ber of st u d y s u bjects re p orti n g t hat t he y feel m ore i n c o ntr ol of 
t heir art hritis pai n bef ore a n d after V oltare n us e. 
1 3. 3. 3  
S af et y A n al y si s( e s)  
All A Es will be c o d e d usi n g Me d D R A. A Es will be cat e g orize d as rel ate d, pr o ba ble, 
u nli ke l y, or u nrelat e d b y res p o nsi ble a ut h orit y pri or t o data base l oc k. T he n u m ber of 
A Es/ S A Es a n d n u m ber of s u bjects wit h A Es/ S A Es will be liste d a n d ta b ulate d.  
1 3. 3. 4  
E x pl or at or y A n al y si s( e s)  
F or t he e x pl orat or y e n d p oi nts, c orrelati o ns bet wee n pai n relief, m o bilit y, a n d q ualit y of 
life i n dices will be meas ure d t hr o u g h o ut t he trial. A d diti o nall y, t he use of c o nc o mita nt 
me dicati o ns a n d a n y c ha n ges i n use of pai n relief me dicati o ns will be rec or de d t hr o u g h o ut 
t he trial. 
Ti me -t o-pai n relief will als o be meas ure d  after use of t he test pr o d uct; t his will be 
meas ure d as t he ela ps e d ti me fr o m test pr o d uct use t o ac hie vi n g s ufficie nt p ai n relief t o 
st o p usi n g t he pr o d uct a n d will be e val uate d usi n g Ka pla n-Mei er c ur ves.  
1 3. 3. 5  
E x cl u si o n of D at a fr o m A n al y si s  
A n y reas o ns f or e x cl usi o n fr o m a n a n al ysis p o p ulati o n will be liste d, if a p plica ble.  
1 3. 3. 6  
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  
A ge a n d ot her c o nti n u o us de m o gra p hic a n d baseli ne varia bl es will be s u m marize d usi n g 
descri pti ve statistics s uc h as mea n, ra n g e, me di a n a n d sta n dar d d e viati o n. Ge n der a n d ot her 
cate g oric al de m o gra p hi c a n d baseli ne vari a bles will be s u m marize d usi n g fre q ue nc y 
c o u nts a n d perce nta g es f or t he safet y a n d mI T T p o p ulati o ns.  
1 2. 3. 6  
St u d y Dr u g/ Pr o d u ct C o m pli a n c e a n d U s e of Ot h er T h er a pi e s  
1 3. 3. 6. 1  St u d y  Dr u g/ Pr o d u ct C o m pli a n c e  
C o m plia nce a n d pr o d uct use will be m o nit ore d t hr o u g h o ut t he st u d y via e Diar y a n d d ata 
tra nsfers fr o m Acti gra p h b y rele va nt st u d y pers o n nel ( Site Staff, C R O a n d S p o ns or st u d y 
tea m).  
St u d y pr o d uct c o m plia nce will be t a b ulate d a n d s u m marize d f or t he s afet y p o p ulati o n. 
S u m maries will i ncl u de a si m ple yes/ n o fre q ue n c y (a n d perce nt) c o u nt at eac h ti me p oi nt.  
1 3. 3. 6. 2  Pri or a n d C o n c o mit a nt M e di c ati o n s  
C o nc o mita nt me dicati o ns ta ke n d uri n g t he st u d y will be liste d f or t he safet y p o p ulati o n.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 8  of 7 0  
 
1 3. 3. 7  
H a n dli n g of Dr o p o ut s a n d Mi s si n g D at a  
Missi n g data d ue t o ge n eral dr o p o ut/ wit h dra wals will be assesse d o n a n o n g oi n g basis 
d uri n g t he st u d y. A n y f urt her se nsiti vit y a nal ys es nee d e d d ue t o missi n g data will be 
re vie we d at t he ti me of data re vie w. A d diti o nal details will be pr o vi de d i n t he data 
ma na ge me nt pla n a n d re p orti n g a n d statistical a nal ysis pla n.  
1 3. 3. 8  
I nt eri m A n al y si s  
N o i nteri m a nal ysis is pla n ne d f or t his st u d y.  
1 4  
S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S  
1 4. 1  
Q u alit y C o ntr ol  
I n acc or da n ce wit h a p pli ca ble re g ulati o ns i ncl u di n g G C P, a n d Hale o n pr oce d ures, Hale o n 
or desi g nee (i.e., 
) m o nit ors will c o ntact t he site pri or t o t he start of t he st u d y 
t o re vie w wit h t he site st aff t he pr ot oc ol, st u d y re q uire me nts, a n d t heir res p o nsi bilities t o 
satisf y re g ulat or y, et hical, a n d Hale o n re q uire m e nts.  
W he n re vie wi n g data c ollecti o n pr oce d ures, t he disc ussi o n will i ncl u de i de ntificati o n, 
a gree m e nt, a n d d oc u m e ntati o n of data ite ms f or w hic h t he e C R F will ser ve as t he s o urce 
d oc u me nt.  
Hale o n or desi g n ee will m o nit or t he st u d y a n d site  acti vit y t o verif y t hat t h e:  
•  Data are a ut he ntic, acc urate, a n d c o m plete.  
•  Safet y a n d ri g hts of s u bjects are b ei n g pr otecte d.  
•  St u d y is c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y 
ot her st u d y a gree me nts, G C P, a n d all a p plica ble re g ulat or y re q uir e me nts.  
T he e xte nt a n d nat ur e of m o nit ori n g will be descri be d i n a writte n m o nit ori n g pla n o n file 
at Hale o n. T h e i n vesti gat or ( or desi g ne e) a grees t o all o w t he m o nit or direct access t o all 
rele va nt d oc u m e nts a n d a grees t o c o-o p erate wit h t he m o nit or t o e ns ure t hat a n y pr o ble ms 
detecte d d uri n g t hes e m o nit ori n g visits are res ol ve d.  
1 4. 2  
Q u alit y A s s ur a n c e  
T o e ns ure c o m plia nce wit h G C P a n d all a p plica bl e re g ulat or y re q uir e me nts, Hale o n ma y 
c o n d uct a q ualit y ass ura n ce assess me nt a n d/ or a u dit of t he site rec or ds, a n d t he re g ulat or y 
a ge ncies ma y c o n d u ct a re g ulat or y i ns pecti o n at a n y ti me d uri n g or after c o m pleti o n of t he 
st u d y.  
I n t he e ve nt of a n assess me nt, a u dit or i ns p ecti o n, t he i n vesti gat or (a n d i nstit uti o n) m ust 
a gree t o gra nt t he a d vis or(s), a u dit or(s) a n d i ns pect or(s) direct access t o all rele va nt 
d oc u me nts a n d t o all ocat e t heir ti me a n d t he ti me of t heir staff t o disc uss t he c o n d uct of 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 5 9  of 7 0  
 
t he st u d y, a n y fi n di n gs/rele va nt iss ues a n d t o i m ple me nt a n y c orrecti ve a n d/ or pre ve nt ati ve 
acti ons t o a d dress a n y fi n di n gs/iss ues i de ntifie d.  
T he i n vesti gat or will n otif y Hale o n   or its a ge nts i m me diatel y of a n y re g ulat or y i ns pecti o n 
n otificati o n i n relati o n t o t he st u d y. F urt her m ore, t he i n vesti gat or will c o o perat e wit h 
Hale o n or its a ge nts t o pre pa re t he st u d y site f or t he i ns pecti o n a n d will all o w Hale o n or 
its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n. T he i n vesti gat or will 
pr o m ptl y a p pl y c o pies of t he i ns pecti o n fi n di n g t o Hale o n or its a ge nt. B ef ore res p o nse 
s u b missi o n t o t he re g ulat or y a ut h orit y, t he i n vesti gat or will pr o vi de Hale o n or its a g e nts 
wit h a n o p p ort u nit y t o re vie w a n d c o m me nt o n r es p o nses t o a n y s uc h fi n di n gs.  
T he s p o ns or will be a vail a ble t o hel p i n vesti gat ors pre pare f or a n i ns pecti o n.  
1 4. 3  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s  
1 4. 3. 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 v esti gat or t o h a 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 a n d/ or asse nt d oc u me nts, i n vesti gat or 
br oc h ure/safet y state me n t (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 ret ai ne d i n t he 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 w ar de d t o Hal e 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 o c ol are ma de.  
T he o nl y circ u msta nce i n w hic h a n a me n d me nt ma y be i nitiate d pri or t o I R B/ 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 v e nt, t he i n v esti gat or m ust n otif y t he I R B/ E C a n d Hal e o n i n writi n g i m me diatel y 
after t he i m ple me ntati o n.  
1 4. 3. 2  
Et hi c al C o n d u ct of t h e St u d y  
T he st u d y will be c o n d ucte d i n acc or da n ce wit h t he pr ot oc ol a n d le gal a n d re g ulat or y 
req uire me nts. T he st u d y will be c o n d ucte d i n c o m plia nce wit h t he E U Cli nical Trial 
Re g ulati o n 5 3 6/ 2 0 1 4, as well as t he ge neral pri nci ples set f ort h i n t he I nter n ati o nal Et hical 
G ui deli nes f or Bi o me dical Researc h I n v ol vi n g H u ma n S u bjects ( C o u ncil f or I nter nat i o nal 
Or ga nizati o ns of Me dic al Scie nces 2 0 0 2), I nt er nati o nal Et hical G ui deli nes f or Healt h -
Relate d Researc h I n v ol vi n g H u ma ns ( C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces, 2 0 1 6) , g ui deli nes f or G C P (I C H 1 9 9 6 a n d re visi o n 2), a n d t he Declarat i o n of 
Helsi n ki ( W orl d Me dic al Ass ociati o n 2 0 1 3).  
1 4. 3. 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 p ers o nal data a n d will n ot i ncl u de s u bject 
na mes or ot her i d e ntifia ble data i n a n y re p orts, p u blicati o ns, or ot her discl os ures, e x ce pt 
w he re re q uire d b y la ws.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 6 0  of 7 0  
 
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 her a ut h orize d parties, s u bject 
na mes, a d dress es, a n d ot her i de ntifia ble data will be re place d b y n u merical c o des base d o n 
a n u m beri n g s yste m pr o vi de d b y Hale o n i n or der 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 bject’s n u merical c o d e t o his or her act ual i de ntit y.  I n cas e of data tra 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 vac y la ws.  
1 4. 3. 4  
S u bj e ct R e cr uit m e nt  
A d vertise me nts a p pr o ve d b y I R Bs/ E Cs a n d i n vesti gat or data bases ma y be use d as 
recr uit me nt pr oce d ures.  Use of et hics c o m mittee a p pr o ve d ge n eric, pre -s cree ni n g 
q uesti o n naire t o assess basic s u bject c h aracteristics t o deter mi ne ge neral eli gi bilit y f or t his 
st u d y is all o we d.  T his g e neric q u esti o n naire m a y be use d b y sites as a p h o ne scri pt a n d/ or 
t o re vie w i nter nal data bases t o i de ntif y s u bjects.   
Hale o n  will ha v e a n o p p ort u nit y t o re vie w a n d a p pr o ve t h e c o nte nt of a n y st u d y 
recr uit me nt materials directe d t o p ote ntial st u d y s u bjects bef ore s uc h materials are us e d.  
1 4. 3. 5  
R e p orti n g of S af et y I s s u e s a n d S eri o u s Br e a c h e s of t h e Pr ot o c ol 
or I C H G C P  
Wit hi n Hale o n  a seri o us breac h is defi n e d as a breac h li kel y t o affect t o a si g nifica nt de gree 
t he safet y a n d ri g hts of a s u bject or t he relia bilit y a n d r o b ust ness of t he dat a ge nerate d i n 
Hale o n  -s p o ns or e d h u ma n s u bject researc h st u dies.  
I n t he e ve nt of a n y pr o hi biti o n or restricti o n i m p ose d (i.e., cli nical h ol d) b y a n a p plica ble 
c o m pete nt a ut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat 
mi g ht i nfl ue nce t he e val u ati o n of t he be n efits a n d ris ks of t h e 
i n vesti gatio nal pr o d uct, Hale o n s h o ul d be i nf or m e d i m me diatel y.  
I n a d diti o n, t he i n vesti gat or will i nf or m Hale o n i m me diatel y of a n y ur ge nt safet y meas ures 
ta ke n b y t he i n vesti gat or t o pr otect t he st u d y s u bjects a gai nst a n y i m me diate hazar d, a n d 
of a n y s eri o us breac h es of t his pr ot oc ol, of I C H G C P or of t he E U Cli nical Trial Re g ulati o n 
5 3 6/ 2 0 1 4 t hat t he i n vesti gat or bec o mes a ware of.  
I n c o m plia nce wit h Article 5 2 of t he E U Cli nical Trial Re g ulati o n 5 3 6/ 2 0 1 4, Hale o n will 
n otif y t he me m ber states c o ncer ns at t he ti me of t he breac h t hr o u g h t he E U p ortal wit h o ut 
u n d ue dela y b ut n ot later t ha n se ve n da ys of bec o mi n g a ware of t hat breac h.  
1 4. 4  
P o sti n g of I nf or m ati o n o n P u bli cl y A v ail a bl e Cli ni c al Tri al 
R e gi st er s  
St u d y i nf or mati o n fr o m t his pr ot oc ol will be p oste d o n p u blicl y a vaila bl e cli nical trial 
re gisters bef ore e nr ol m e nt of s u bjects be gi ns i n acc or da n ce wit h a p plica ble Hale o n 
pr ocesses.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 6 1  of 7 0  
 
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 hel p a d va n ce 
me dical scie nce or i m pr o ve patie nt/s u bject care acc or di n g t o l ocal re g ulat or y re q uire me nts. 
T his hel ps e ns ure t he dat a pr o vi de d b y st u d y partici pa nts are use d t o ma xi m u m effect i n 
t he creati o n of k n o wle d ge a n d u n derst a n di n g.  
1 4. 5  
Pr o vi si o n of St u d y R e s ult s t o I n v e sti g at or s  
W here re q uir e d b y a p plica ble re g ulat or y re q uire me nts, a n i n vesti gat or si g nat or y will be 
i de ntifie d f or t he a p pr o val of t he cli nical st u d y re p ort.  T he i n vesti gat or will be pr o vi de d 
reas o na bl e access t o statistical ta bles, fi g ures, a n d rele va nt re p orts a n d will ha ve t he 
o p p ort u nit y t o re vie w t he c o m plete st u d y res ults at a Hal e o n  site or ot her m ut uall y 
a greea ble l ocati o n.  
Hale o n  will als o pr o vi de t he i n vesti gat or wit h t he f ull s u m mar y of t he st u d y res ults.  T h e 
i n vesti gat or is e nc o ura g e d t o s hare t he s u m mar y res ults wit h t he st u d y s u bjects, as 
a p pr o priate.  
T he pr oce d ures a n d ti mi n g f or p u blic discl os ure of t he res ults s u m mar y a n d f or 
de vel o p me nt of a ma n us cri pt f or p u blicati o n will be i n acc or da nce wit h s p o ns or p olic y  a n d 
as per t he c o u ntr y s pecifi c re g ulat or y re q uir e me nts f or discl os ure . 
A ma n uscri pt will be pr o gresse d f or p u blicati o n i n t he scie ntific literat ure if t he res ults 
pr o vi de i m p orta nt scie ntific or me dical k n o wle d ge. A d diti o nall y, acc or da nce wit h t he E U 
Cli nical Trial Re g ulati o n 5 3 6/ 2 0 1 4 A n ne x I V (t he p u blicati o n p olic y of t he trial data) t he 
data will be u pl oa de d t o t he C TI S d ata base wit hi n o ne year after e n d of tri al.  
1 4. 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 o r m ust mai ntai n all site st u d y rec or ds (e xce pt 
f or t h ose re q uir e d b y l ocal 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 ocati o n.   
T he rec or ds (st u d y/ site master file) m ust be mai ntai ne d t o all o w eas y a n d ti mel y retrie val, 
w he n nee de d (e . g., f or a Hale o n a u dit or re g ulat or y i ns pecti o n) a n d m ust be a vaila ble f or 
re vie w i n c o nj u ncti o n wit h assess me nt of t he facilit y, s u p p orti n g s yste ms, a n d rele va nt site 
staff. 
W here per mitte d b y l ocal la ws/re g ulati o ns or i nstit uti o nal p olic y, s o me or all t hese rec or ds 
ca n be mai ntai ne d i n a f or mat ot her t ha n har d c o p y (e. g., micr ofic he, sca n n e 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 e ns ure t hat all re pr o d ucti o ns are le gi ble a n d are a tr u e a n d  acc urat e 
c o p y of t he ori gi nal a n d meet accessi bilit y a n d retrie val sta n dar ds, i ncl u di n g re -ge n erati n g 
a har d c o p y, if re q uir e d.  F urt her m ore, t h e i n vesti g at or m ust e ns ure t h ere is a n acce pt a ble 
bac k -u p of t hes e re pr o d ucti o ns a n d t hat a n acce pta ble q ualit y  c o ntr ol pr ocess e xists f or 
ma ki n g t hese re pr o d ucti o ns.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 6 2  of 7 0  
 
T he i n vesti gat or m ust ass ure t hat t he s u bject’s a n o n y mit y will be mai ntai ne d.  O n e C R Fs 
or ot her d oc u me nts s u b mitte d t o Hale o n, s u bjects s h o ul d n ot be i de ntifie d b y t heir na mes 
or i nitials, b ut b y a n i de ntificati o n c o de. T he i n vesti gat or s h o ul d kee p a se parat e l o g of 
s u bjects’ c o des, na mes a n d a d dresses.  D oc u me nts n ot f or s u b missi o n t o Hale o n, e. g. 
s u bjects’ writte n c o nse nt f or ms, s h o ul d be mai ntai ne d b y t he i n vesti gat or i n strict 
c o nfi de nce.  
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C F, pertai ni n g t o t he c o n d uct of t his st u d y m ust 
be retai ne d b y t he i n v esti gat or as per t he si g n e d c o ntract ual a gree me nt, fr o m t he iss ue of 
t he fi nal Cli nical St u d y Re p ort ( C S R) or e q ui val e nt s u m mar y, u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. T he mi ni m u m rete nti o n ti me will 
meet t he stri ctest sta n d ar d a p plica ble t o t hat site f or t h e st u d y, as di ctate d b y a n y 
i nstit uti o nal re q uire me nts or l ocal la ws or re g ulati o ns, Hale o n sta n dar ds/ pr oce d ures, 
a n d/ or i nstit uti o nal re q uire me nts.   
N o st u d y d oc u me nt s h o ul d be destr o ye d wit h o ut a pri or writte n a gree me nt b et wee n Hale o n  
a n d t he i n vesti gat or. T he i n vesti gat or m ust n otif y Hale o n  of a n y c ha n g es i n t he arc hi v al 
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 tr a nsfer of 
o w ners hi p of t he rec or ds i n t he e ve nt t h e i n vesti gat or is n o l o n ger ass ociat e d wit h t he site.  
Acc or di n g t o t he P O L -0 0 0 -3 0 0 Hale o n Gl o bal R ec or ds Rete nti o n Sc he d ule, Hale o n a n d 
t he i n vesti gat or s hall arc hi ve t he c o nte nt of t he cli nical trial master file f or at least 3 0 years 
after t he e n d of t he cli nical trial.  
1 4. 7  
C o n diti o n s f or T er mi n ati n g t h e St u d y  
Pre mat ure ter mi nati o n of t his st u d y ma y occ ur beca use of a re g ulat or y a ut h orit y decisi o n,  
c ha n ge i n o pi ni o n of t he I R B/ E C, or st u d y pr o d uct safet y pr o ble ms, or at t he discreti o n of 
Hale o n.  I n a d diti o n, H ale o n  ret ai ns t he ri g ht t o disc o nti n ue de vel o p me nt of pr o d uct at a n y 
ti me. F or m ultice ntre st u dies (if a p plica ble), t his ca n occ ur at o ne or m or e or at all sites.    
If a st u d y is pre mat urel y ter mi nate d, Hal e o n will pr o m ptl y n otif y t he i n vesti gat or.  After 
n otificati o n, t he i n vesti gat or m ust pr o m ptl y c o ntact all partici pati n g s u bj ects a n d s h o ul d 
ass ure a p pr o priate t hera p y/ f oll o w -u p f or t he s u bj ects.  As directe d b y Hal e o n, all st u d y 
materials m ust be c ollecte d a n d all e C R F’s c o m plete d t o t he greatest e xte nt p ossi ble.  
W here re q uire d b y t he a p plica ble re g ul at or y re q uire me nts, Hale o n s h o ul d i nf or m t he 
re g ulat or y a ut h orit y(ies) a n d t he i n vesti gat or s h o ul d pr o m ptl y i nf or m t he I R B/ E C a n d 
pr o vi de t he I R B/ E C a det aile d writte n e x pla nati o n of t he ter mi nati o n or s us pe nsi o n.  
If t he I R B/ E C ter mi nates or s us pe n ds its a p pr o val/fa v o ura bl e o pi ni o n of a st u d y, t h e 
i n vesti gat or s h o ul d pr o m ptl y n otif y t he Hale o n a n d pr o vi de Hale o n  wit h a detaile d writte n 
e x pla nati o n of t he ter mi nati o n or s us pe nsi o n.  
U p o n c o m pleti o n or pre mat ure disc o nti n uati o n of t he st u d y, t he Hale o n m o nit or will 
c o n d uct site cl os ure acti vities wit h t he i n vesti gat or or site staff, as a p pr o priate,  i n 
acc or da nce wit h a p plica ble re g ulati o ns i ncl u di n g G C P, a n d Hale o n  Sta n dar d O perati n g 
Pr oce d ures.  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 6 3  of 7 0  
 
1 5  
R E F E R E N C E S  
 
[ Alt ma n R D, Bart h el H R ( 2 0 1 1)] T o pical T h era pies f or Oste oart hritis. Dr u gs 2 0 1 1; 7 1 
( 1 0): 1 2 5 9-1 2 7 9.  
[ Ba n n ur u R R, Osa ni M C, Va ys br ot E E, et al (2 0 1 9)]  O A R SI g ui deli nes f or t he n o n -
s ur gical ma na ge me nt of k nee, hi p, a n d p ol yartic ular oste oart hritis. Oste oart hritis a n d 
Cartila ge 2 7 ( 2 0 1 9) 1 5 7 8 -1 5 8 9.  
[ Bart hel H R, Has el w o o d D, L o n gle y S, 3r d, et al ( 2 0 0 9)] Ra n d o mize d c o ntr olle d trial of 
dicl ofe nac s o di u m gel i n k nee oste oart hritis. Se mi n Art hritis R he u m; 3 9( 3): 2 0 3 -1 2.  
[ da C osta B R, Pereir a T V, Saa dat P, R u d nic ki M, Is ka n der S M, B o d mer N S, et al ( 2 0 2 1)]. 
Effecti ve n ess a n d s afet y of n o n -ster oi dal a nti-i nfla m mat or y dr u gs a n d o pi oi d treat me nt f or 
k nee a n d hi p oste oart hritis: net w or k meta -a n al ysis. B MJ. 2 0 2 1 Oct 1 2; 3 7 5: n 2 3 2 1.  
[ Ha ge n M a n d Ba ker M ( 2 0 1 7)] S ki n pe netrati o n a n d tiss ue per meati o n after t o pical 
a d mi nistrati o n of dicl ofe nac. C urr Me d R es O pi n; 3 3( 9): 1 6 2 3 -3 4.  
[Je vse var D S, S h ores P B, M ulle n K, et al ( 2 0 1 8)] Mi xe d Treat me nt C o m paris o ns f or 
N o ns ur gical Treat me nt of K nee Ost e oart hritis: A Net w or k Met a -a n al ysis. J A m Aca d 
Ort h o p S ur g; 2 6( 9): 3 2 5 -3 6.  
[J or da n K M, Ar de n N K, D o hert y M, et al ( 2 0 0 3)] E U L A R Rec o m m e n d ati o ns 2 0 0 3: a n 
e vi de nce -base d a p pr oac h t o t he ma na ge me nt of k n ee oste oart hritis: Re p ort of a Tas k F orce 
of t he Sta n di n g C o m mittee f or I nter n ati o nal Cli nical St u dies I ncl u di n g T h era pe utic Trials 
( E S CI SI T). A n n R he u m Dis; 6 2( 1 2): 1 1 4 5-5 5.  
[ K olasi ns ki 
S L, 
Ne o gi 
T, 
H oc h ber g 
M C 
( 2 0 1 9)]  
A meri ca n 
C olle ge 
of 
R he u mat ol o g y/ Art hritis F o u n dati o n G ui deli ne f or t he Ma na ge m e nt of Oste oart hritis of t he 
Ha n d, Hi p, a n d K n ee. Art hritis & R he u mat ol o g y; 7 2( 2): 2 2 0 -2 3 3  
[ Kl o p pe n b ur g 
M, Kr o o n F P, Bla nc o FJ, et al ( 2 0 1 9)] 2 0 1 8 u p date of t he E U L A R 
rec o m me n dati o ns f or t he ma na ge me nt of ha n d oste oart hritis. A n n R he u m Dis; 7 8( 1): 1 6-
2 4.  
[ O’ Brie n C, D u d a J, Kit as G, et al ( 2 0 2 0)] Meas ure me nt of s e de ntar y ti me a n d p h ysical 
acti vit y i n r he u mat oi d art hritis: a n Acti Gra p h a n d acti v P A L ™ val i dati o n st u d y. R he u mat ol 
I nt. 2 0 2 0 Se p; 4 0( 9): 1 5 0 9-1 5 1 8   
[ va n 
Walse m A, Pa n d hi S, Ni x o n R M, et al ( 2 0 1 9)] Relati ve b e nefit -ris k c o m pari n g 
dicl ofe nac t o ot h er tra diti o nal n o n -ster oi dal a nti-i nfla m mat or y dr u gs a n d c y cl o o x y ge nase-
2 i n hi bit ors i n patie nts wit h oste oart hritis or r he u m at oi d art hritis: a net w or k meta -a nal ysis. 
Art hritis Res T her; 1 9( 1) 6 6  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of 
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 6 4  of 7 0  
 
1 6  
A P P E N DI CI E S  
1 6. 1  
A B B R E VI A TI O N S  
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y b e use d i n t he pr ot oc ol.  
T a bl e 1 6 . 1 
A b br e vi ati o n s  
 
A b br e vi ati o n  
T er m  
A C R  
A m eri c a n C oll e g e of R h e u m at ol o g y  
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  
C O X  
C y cl o o x y g e n a s e  
CI  
C o nfi d e n c e I nt er v al s  
C R F  
C a s e r e p ort f or m  
E C  
Et hi c s c o m mitt e e  
e C R F  
El e ctr o ni c C a s e R e p ort F or m  
e P R O  
El e ctr o ni c P ati e nt r e p ort e d o ut c o m e  
E u dr a C T  
E ur o p e a n Cli ni c al Tri al s D at a b a s e  
E U  
E ur o p e a n U ni o n  
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  
h C G  
h u m a n c h ori o ni c g o n a d otr o pi n  
H SI  
H u m a n S u bj e ct I nf or m ati o n  
I B 
I n v e sti g at or’ s br o c h ur e 
I C 
I nf or m e d C o n s e nt 
I C F 
I nf or m e d C o n s e nt F or m 
I C H 
I nt er n ati o n al C o nf er e n c e o n H ar m o ni s ati o n 
I D 
I d e ntifi c ati o n 
I E C 
I n d e p e n d e nt Et hi c s C o m mitt e e 
I R B 
I n stit uti o n al r e vi e w b o ar d 
I R C 
I nt er n al r e vi e w c o m mitt e e 
M e d D R A  
M e di c al Di cti o n ar y f or R e g ul at or y A cti viti e s  
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  
mI T T  
m o difi e d I nt e nt -T o -Tr e at  
M V P A  
M o d er at e a n d Vi g or o u s P h y si c al A cti vit y  
N/ A  
N ot a p pli c a bl e  
N S AI D( s)  
N o n -st er oi d al a nti -i nfl a m m at or y dr u g s 
O A  
O st e o art hriti s  
O A R SI  
O st e o art hriti s R e s e ar c h S o ci et y I nt er n ati o n al  
Q C  
Q u alit y c o ntr ol  
Q o L  
Q u alit y of Lif e  
R W E  
R e al W orl d E vi d e n c e  
S A E  
S eri o u s a d v er s e e v e nt  
S A P  
St ati sti c al A n al y si s Pl a n  
S O P  
St a n d ar d o p er ati n g pr o c e d ur e  
W O M A C  
W e st er n O nt ari o a n d M c M a st er U ni v er siti e s Art hriti s I n d e x  
U S  
U nit e d St at e s ( Of A m eri c a)  
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
 
Pr ot oc ol N u m ber: 3 0 0 1 2 8  
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of  
Hale o n  
Cli nical Pr ot oc ol Te m plate, T M F -1 8 7 8 2 1, v 1 1. 0.  Pare nt S O P: 
 
Pa ge 6 5  of 7 0  
 
 
1 6. 2  
S T U D Y Q U E S TI O N N AI R E S  
1 6. 2. 1  
W e st er n O nt ari o a n d M c M a st er U ni v er siti e s Art hriti s I n d e x 
( W O M A C) 5-p oi nt Li k ert s c al e e x a m pl e  
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0. 0 
Pa ge 6 6  of 7 0  
 
1 6. 2. 2  
K ar oli n s k a Sl e e pi n e s s S c al e E x a m pl e  
 
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0. 0 
Pa ge 6 7  of 7 0  
 
1 6. 2. 3  
S elf -R e p ort e d P ai n N u m eri c al R ati n g S c al e a n d Vi s u al A n al o g u e 
S c al e E x a m pl e s  
 
N u merical Rati n g Sca le:  
 
 
Vis ual A nal o g ue Scale:  
 
 
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0. 0 
Pa ge 6 8  of 7 0  
 
1 6. 2. 4  
E Q -5 D -5 L Q u alit y of Lif e Q u e sti o n n air e e x a m pl e  
 
 
 
 
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0. 0 
Pa ge 6 9  of 7 0  
 
1 6. 3. 1  
E n d of t h e st u d y q u e sti o n s  
 
•  H o w w o ul d y o u r ate y o ur s atisf acti o n wit h t he V olt are n Gel y o u use d ?  
Ver y Satisfie d   
Satisfie d  
Ne utral  
Dissatisfie d   
Ver y Dissatisfie d   
Please e x plai n w h y y o u c h ose Ver y Satisfie d/ Satisfie d/ Ne utral/ Dissatisfie d/ Ver y 
Dissatisfie d?  
 
•  Will y o u c o nsi der usi n g V olt are n Gel f or O A k nee p ai n a g ai n ?  
Yes  
N o  
Please e x plai n w h y y o u w o ul d/ w o ul d n ot use t his pr o d uct a gai n.  
 
After ta ki n g V oltare n Art hritis Pai n Relie vi n g gel:  
 
•  I fi n d less disc o mf ort asce n di n g a n d desce n di n g stairs:  
 
Str o n gl y A gree  
A gree  
Ne utral  
Disa gree  
Str o n gl y Disa gree  
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

H A L E O N  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber:  3 0 0 1 2 8  
 
 
Pr o pert y of Hal e o n - C o nfi de ntial   
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of Hale o n  
 Cli nical Pr ot oc ol Te m plate v 1 0. 0 
Pa ge 7 0  of 7 0  
 
1 6. 4  
A C TI G R A P H I N F O R M A TI O N  
Acti gra p h is I S O -1 3 4 8 5: 2 0 1 6 certifie d, a n d t he weara bl e tec h n ol o g y is F D A 5 1 0( k) cleare d 
Class II me dical de vices i n t he U. S. a n d a d here t o re g ulat or y sta n dar ds w orl d wi de. F urt her 
i nf or mati o n o n Acti gra p h certificati o n ca n be f o u n d i n t he f oll o wi n g li n ks:  
•  htt ps://t heacti gra p h.c o m/c o m plia nce  
•  htt ps:// w w w.access data.f da. g o v/scri pts/c dr h/cf d ocs/cf p m n/ p m n.cf m?I D = K 1 8 1 0 7 7  
 
I nf or mati o n o n h o w t o trai n vi de os a n d fre q ue ntl y as ke d q uesti o ns ca n be f o u n d o n Acti gra p h 
t ut orial part of t he we bsit e: htt ps://t heacti gra p h.c o m/t ut or ials  
 
 
3 0 0 1 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
C CI

Si g nat ure Pa ge f or  3 0 0 1 2 8 T M F- 2 5 0 9 9 0 v 4. 0
Si g nat ure Pa ge f or T M F- 2 5 0 9 9 0 v 4. 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 2 8 Pr ot oc ol R W E St u d y E val uati n g t he Effects of V oltare n use o n M o bilit y a n d Q O L 0 8 J ul 2 0 2 4 | T M F- 2 5 0 9 9 0 | 4. 0
P P D
P P D