A Phase IV, Randomized, Interventional, Study to Assess Subject Treatment Session Perception and Investigator Treatment Experience of Alluzience and Vacuum-Dried Botulinum Neurotoxin Type A for Aesthetic Use
Phase: PHASE4
Conditions: Glabellar Frown Lines
Sponsor: Galderma R&D

C O N FI D E N TI A L 
Pa ge 1 of 7 1
C LI NI C A L S T U D Y P R O T O C O L
P R O T O C O L N U M B E R: 0 5 P F 2 0 0 5
C O N FI D E N TI A L
T his d oc u me nt c o nt ai ns c o nfi de nti al, pr o priet ar y i nf or m ati o n
All t he i nf or mati o n pr o vi de d t o t he I n vesti gat or a n d his/ her staff a n d all data o btai ne d t hr o u g h t his 
Q- Me d A B cli nical st u d y pr ot oc ol are c o nfi de ntial. Q- Me d A B, part of t he Gal der ma Gr o u p , is t he 
o w ner of all i nf or mati o n i ncl u de d i n t his pr ot oc ol as S p o n s or a n d t he S p o ns or reser ves all pr o prietar y 
ri g hts. N o i nf or mati o n ma y  be discl ose d t o a n y thir d part y wit h o ut pri or writte n c o nse nt fr o m 
Q- M e d A B .
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 2 of 7 1
TI T L E P A G E
A P hase I V, Ra n d o mize d, I nter ve nti o nal, St u d y  t o Assess S u bject Treat me nt Sessi o n Perce pti o n 
a n d I n vesti gat or Treat me nt E x perie nce of All uzie nce a n d Vac u u m-Drie d B ot uli n u m Ne ur ot o xi n 
T y pe A f or Aest hetic Use
S h ort title:
S t u d y c o m pari n g T reat me nt wit h A ll uzie nce vs R ec o nstit ute d t o xi n
S T A R
C li nic al Tri al N u m ber ( CT N ): 0 5 P F 2 0 0 5
P h ase : P hase I V, p ost -mar ket st u d y
S P O N S O R:
Q- Me d A B, part of t he Gal der ma Gr o u p
Se mi narie gata n 2 1
S E -7 5 2 2 8 U p psala, S we de n
Tele p h o ne: + 4 6 1 8 4 7 4 9 0 0 0
S A F E T Y :
F or safet y questi o ns, t he Safet y e-mail (dr u gsafet y p v @a d va nce dcli nical.c o m ) or Me dical M o nit or
s h o ul d be c o ntacte d usi n g t he c o ntact i nf or mati o n pr o vi de d i n t he I nvesti gat or’s site file. Seri o us 
a d verse e ve nt s ( S A Es) a n d pre g na nc y  re p ort f or ms s h o ul d be s u b mitte d as descri be d i n Secti o ns 
7. 2. 1. 2. 2 a n d 7. 2. 1. 2. 3 .
M E DI C A L
M O NI T O R:
F or a n y me dical q uesti o ns relate d t o t he cli nical st u d y pr ot oc ol ( C S P), t he Me dical M o nit or
s h o ul d 
be c o ntacte d usi n g t he c o ntact i nf or mati o n pr o vi de d i n t he I nvesti gat or’s site f ile.
T his cli nical st u d y shall be perf or me d i n c o m plia nce wit h t he cli nical trial a gree me nt ( C T A), t he 
cli nical st u d y pr ot oc ol, I nter nati o nal C o u ncil f or Har m o nizati o n (I CH)- G o o d Cli nical Practice 
( G C P),1 a n d a p plica ble re gi o nal a n d nati o nal re g ulati o ns. T he st u d y shall be c o n d ucte d i n 
acc or da nce wit h t he et hical pri nci ples t hat ha ve t heir ori gi n i n t he Declarati o n of Helsi n ki .
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 of 7 1
S T U D Y A D MI NI S T R A TI V E S T R U C T U R E
S p o ns or c o ntact :
, Sr. Cli nical Pr oject Ma na ger
Tele p h o ne:
E- mail: 
Me dical M o nit or:
C o ntact details pr o vi de d i n t he I nvesti gat or’s site file
E- mail f or S A E a n d Pre g na nc y  Re p orti n g: dr u gsafet y p v @a d va nce dcli nical.c o m
E- mail f or P Q C Re p orti n g:
dr u gsafet y p v @a d va nce dcli nical.c o m
F urt her details o n all partici pati n g I n vesti gat ors a n d t he c o m plete a d mi nistrati ve str uct ure of t he 
st u d y are f o u n d i n t he st u d y files. N ote t hat a d mi nistrati ve c ha n ges are t o be d oc u me nte d i n t he st u d y 
files wit h o ut re q uiri n g a C S P a me n d me nt.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
P P D
P P D
P P D
P P D

C O N FI D E N TI A L 
Pa ge 4 of 7 1
T a ble of C o nte nts
TI T L E P A G E .................................................................................................................................................. 2
S T U D Y A D MI NI S T R A TI V E S T R U C T U R E .............................................................................................. 3
C LI N I C A L S T U D Y S C H E M A TI C A N D F L O W C H A R T ...................................................................... 1 5
S C H E D U L E O F A S S E S S M E N T S .............................................................................................................. 1 7
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S ........................................................... 1 8
1.
B A C K G R O U N D A N D R A TI O N A L E ........................................................................................ 2 1
1. 1
Me dic al B ac k gr o u n d a n d S h ort R ati o n ale f or t he Cli nic al St u d y ............................................ 2 1
1. 2
I n vesti g ati o n al Pr o d uct Pr ofile .................................................................................................... 2 2
1. 2. 1
Dr u g Pr ofile ..............................................................................................................................2 2
................................................................................. 2 2
1. 2. 3
Cli nic al D oc u me nt ati o n ........................................................................................................... 2 3
1. 3
R ati o n ale f or St u d y Desi g n, D oses a n d C o ntr ol Gr o u p ............................................................. 2 5
1. 4
Ris k/ Be nefit Assess me nt ............................................................................................................... 2 5
2.
C LI NI C A L S T U D Y O B J E C TI V E S, E N D P OI N T S, A N D C LI NI C A L 
H Y P O T H E SI S ...............................................................................................................................2 6
2. 1
Cli nic al St u d y O bjecti ves ............................................................................................................. 2 6
2. 1. 1
Pri m ar y O bjecti ves a n d E n d p oi nts ........................................................................................ 2 6
2. 1. 2
Sec o n d ar y Effic ac y O bjecti ve a n d E n d p oi nts ....................................................................... 2 6
................................................................. 2 7
2. 1. 4
S afet y O bjecti ves a n d E n d p oi nts ............................................................................................ 2 7
3.
O V E R A L L C LI NI C A L S T U D Y D E S C RI P TI O N ..................................................................... 2 8
4.
C LI NI C A L S T U D Y D U R A TI O N A N D T E R MI N A TI O N ....................................................... 2 8
5.
S E L E C TI O N A N D DI S P O SI TI O N O F C LI NI C A L S T U D Y P O P U L A TI O N ....................... 2 9
5. 1
N u m ber of S u bjects ....................................................................................................................... 2 9
5. 2
Cli nic al St u d y P o p ul ati o n C h ar acteristics .................................................................................. 2 9
5. 2. 1
I ncl usi o n Criteri a ..................................................................................................................... 2 9
5. 2. 2
E xcl usi o n Criteri a .................................................................................................................... 3 0
5. 3
Me dic al Hist or y ............................................................................................................................. 3 1
5. 4
Pre vi o us a n d C o nc o mit a nt T her a pies ......................................................................................... 3 1
5. 4. 1
Defi niti o n .................................................................................................................................. 3 1
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI
C CI

C O N FI D E N TI A L 
Pa ge 5 of 7 1
5. 4. 2
C ate g ories ................................................................................................................................. 3 1
5. 4. 3
Rec or di n g .................................................................................................................................. 3 2
5. 4. 4
A ut h orize d C o nc o mit a nt T her a pies ....................................................................................... 3 2
5. 4. 5
Pr o hi bite d C o nc o mit a nt T her a pies ........................................................................................ 3 2
5. 5
Pr oce d ures/ Re as o ns f or S u bject Disc o nti n u ati o n ...................................................................... 3 3
6.
C LI NI C A L S U P P LI E S ................................................................................................................ 3 4
6. 1
Cli nic al S u p pl y I de ntific ati o n a n d Use ........................................................................................ 3 4
6. 1. 1
All uzie nce .................................................................................................................................. 3 4
6. 1. 2
P o w der B o N T - A....................................................................................................................... 3 4
6. 1. 3
St u d y Pr o d ucts Descri pti o n .................................................................................................... 3 5
6. 1. 4
S u bject I de ntific ati o n N u m ber ...............................................................................................3 5
6. 1. 5
Met h o d of Tre at me nt Assi g n me nt .......................................................................................... 3 6
6. 1. 6
R a n d o miz ati o n N u m ber .......................................................................................................... 3 6
6. 1. 7
I nstr ucti o ns f or Use a n d A d mi nistr ati o n ............................................................................... 3 6
6. 1. 7. 1
Tre at me nt Pr oce d ure ......................................................................................................... 3 6
6. 1. 7. 2
Tre at me nt Re gi me n ............................................................................................................ 3 7
6. 2
St u d y Pr o d ucts P ac k a gi n g a n d L a beli n g .................................................................................... 3 7
6. 3
S u p plies M a n a ge me nt ................................................................................................................... 3 8
6. 3. 1
Acc o u nt a bilit y .......................................................................................................................... 3 8
6. 3. 2
St or a ge of t he St u d y Pr o d ucts ................................................................................................ 3 8
6. 3. 3
Dis pe nsi n g a n d Ret ur n ............................................................................................................ 3 8
6. 3. 4
Tre at me nt C o m pli a nce M a n a ge me nt a n d Rec or d ................................................................ 3 8
6. 3. 5
D ose M o dific ati o n .................................................................................................................... 3 9
6. 3. 6
Pr o d uct Q u alit y C o m pl ai nts ................................................................................................... 3 9
6. 4
Bli n di n g .......................................................................................................................................... 3 9
7.
C LI NI C A L S T U D Y A S S E S S M E N T ........................................................................................... 3 9
7. 1
Effic ac y Assess me nts ..................................................................................................................... 3 9
7. 1. 1
Rec o nstit uti o n/ Pre p ar ati o n Q uesti o n n aire ............................................................................ 3 9
7. 1. 2
I n vesti g at or Tre at me nt Sessi o n Q uesti o n n aire ..................................................................... 3 9
.... 3 9
.... 4 0
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 6 of 7 1
...................... 4 0
...................... 4 0
7. 2
S afet y Assess me nts ........................................................................................................................ 4 1
7. 2. 1
A d verse E ve nts ( A E) ................................................................................................................ 4 1
7. 2. 1. 1
Defi niti o ns ............................................................................................................................ 4 1
7. 2. 1. 1. 1
A dverse Eve nts ( A E) ........................................................................................................ 4 1
7. 2. 1. 1. 2
Tre at me nt E mer ge nt A dverse Eve nt ( T E A E) ................................................................... 4 2
7. 2. 1. 1. 3
Seri o us A dverse Eve nts ( S A E) ......................................................................................... 4 2
7. 2. 1. 1. 4
U nex pecte d A dv erse Dr u g Re acti o n ................................................................................ 4 3
7. 2. 1. 1. 5
A dverse Eve nt ( A E) Re p orti n g Peri o d ............................................................................. 4 3
7. 2. 1. 1. 6
Severity ............................................................................................................................ 4 3
7. 2. 1. 1. 7
Rel a ti o ns hi p t o t he St u dy Pr o d uct a n d/ or Cli nic al St u dy Pr oce d ure.............................. 4 3
7. 2. 1. 2
Re p orti n g Pr oce d ures ......................................................................................................... 4 4
7. 2. 1. 2. 1
Pr oce d ures f or Re p orti n g A dverse Eve nts ( A E) ..............................................................4 4
7. 2. 1. 2. 2
Pr oce d ure f or Re p orti n g a Seri o us A dverse Eve nt ( S A E) ............................................... 4 5
7. 2. 1. 2. 3
Pr oce d ures f or Re p orti n g Pre g n a nci es ........................................................................... 4 6
7. 3
Ot her Assess me nts ........................................................................................................................ 4 7
7. 3. 1
P h ot o gr a p h y ............................................................................................................................. 4 7
7. 3. 2
Pre g n a nc y Test......................................................................................................................... 4 7
7. 4
A p pr o pri ate ness of Me as ure me nts ..............................................................................................4 7
8.
C LI NI C A L S T U D Y VI SI T S D E S C RI P TI O N S A N D P R O C E D U R E S ................................... 4 7
8. 1
Descri pti o n of Cli nic al St u d y Visits ............................................................................................. 4 7
8. 1. 1
Scree ni n g, Visit 1 ( D a y -2 1 t o D a y 0) ...................................................................................... 4 8
8. 1. 2
B aseli ne/ Tre at me nt, Visit 2 ( D a y 0) ........................................................................................ 4 8
8. 1. 3
M o nt h 1 ( ± 7 d a ys), F oll o w -u p visit a n d E n d of St u d y Visit f or p o w der B o N T -A 
tre at me nt gr o u p, Visit 3 .......................................................................................................... 4 9
8. 1. 4
M o nt h 3, 5 a n d 6 ( ± 7 d a ys), F oll o w -u p visits a n d E n d of St u d y Visit/ E arl y 
Ter mi n ati o n Visit f or All uzie nce tre at me nt gr o u p, Visit 4, 5 a n d 6 .................................... 5 0
8. 2
U nsc he d ule d Visits ........................................................................................................................ 5 0
8. 3
S u bject I nstr ucti o ns ...................................................................................................................... 5 0
9.
S T A TI S TI C A L M E T H O D S P L A N N E D .................................................................................... 5 1
9. 1
St atistic al a n d A n al ytic al Pl a ns ................................................................................................... 5 1
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 7 of 7 1
9. 1. 1
P o p ul ati o ns A n al yze d a n d E v al u a bilit y ................................................................................. 5 1
9. 1. 1. 1
F ull A n al ysis Set ( F A S) Effic ac y P o p ul ati o n .................................................................... 5 1
9. 1. 1. 2
Per -pr ot oc ol ( P P) Effic ac y P o p ul ati o n .............................................................................. 5 1
9. 1. 1. 3
S afet y P o p ul ati o n ................................................................................................................ 5 1
9. 1. 1. 4
I m p ut ati o n of Missi n g D at a ...............................................................................................5 1
9. 1. 2
D at a Prese nt ati o n a n d Gr a p hics ............................................................................................. 5 1
9. 1. 2. 1
S u b gr o u p A n al ysis .............................................................................................................. 5 2
9. 1. 2. 2
S afet y A n al ysis .................................................................................................................... 5 2
9. 1. 2. 3
Effic ac y A n al ysis ................................................................................................................. 5 2
9. 1. 3  
Wi t h dr a w als a n d De vi ati o ns................................................................................................... 5 2
9. 1. 4
I nfere nti al St atistic al A n al yses ...............................................................................................5 3
9. 2
S a m ple Size Deter mi n ati o n .......................................................................................................... 5 3
9. 2. 1
I nteri m A n al ysis ....................................................................................................................... 5 3
1 0.
T R AI NI N G / M O NI T O RI N G / D A T A M A N A G E M E N T / Q U A LI T Y 
A S S U R A N C E ................................................................................................................................ 5 3
1 0. 1
Pers o n nel Tr ai ni n g ........................................................................................................................ 5 3
1 0. 2
Cli nic al M o nit ori n g ....................................................................................................................... 5 3
1 0. 3
D at a M a n a ge me nt ......................................................................................................................... 5 4
1 0. 4
Q u alit y Ass ur a nce/ A u dit/I ns pecti o n ........................................................................................... 5 4
1 0. 5
C h a n ges i n Cli nic al St u d y C o n d uct/ A me n d me nts ..................................................................... 5 5
1 0. 5. 1
Cli nic al St u d y C o n d uct ............................................................................................................ 5 5
1 0. 5. 2
A me n d me nts ............................................................................................................................. 5 5
1 1.
E T HI C S A N D G E N E R A L C LI NI C A L S T U D Y C O N D U C T C O N SI D E R A TI O N S ............. 5 5
1 1. 1
I n de pe n de nt Et hics C o m mittee (I E C) a n d Re g ul at or y A ut h orities ( R A) ................................ 5 5
1 1. 2
Et hic al C o n d uct of t he Cli nic al St u d y ......................................................................................... 5 6
1 1. 3
S u bject I nf or m ati o n a n d C o nse nt ...............................................................................................5 6
1 1. 4
Pr otecti o n of Pers o n al D at a ......................................................................................................... 5 6
1 1. 5
C o ntr act u al Re q uire me nts ........................................................................................................... 5 7
1 1. 6
D at a C ollecti o n a n d Arc hi vi n g ..................................................................................................... 5 7
1 1. 6. 1
D at a C ollecti o n ......................................................................................................................... 5 7
1 1. 6. 2
S o urce D oc u me nt ati o n ............................................................................................................. 5 7
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 8 of 7 1
1 1. 6. 3
Arc hi ves .................................................................................................................................... 5 7
1 1. 7
I ns ur a nce ....................................................................................................................................... 5 8
1 1. 8
P u blic ati o n P olic y .......................................................................................................................... 5 8
1 2.
LI T E R A T U R E R E F E R E N C E LI S T ................................................................................................ 5 9
1 3.
S U M M A R Y O F C H A N G E S ............................................................................................................. 6 0
1 4.
A P P E N DI C E S .................................................................................................................................... 6 1
A p pe n di x 1
Pre p ar ati o n of All uzie nce a n d Rec o nstit uti o n of p o w der B o N T - A................................ 6 1
A p pe n di x 2
I n vesti g at or Tre at me nt Sessi o n Q uesti o n n aire (f or All uzie nce o nl y) ............................ 6 4
........................... 6 5
........................... 6 6
........................... 6 7
........................... 6 8
SI G N E D A G R E E M E N T O F T H E C LI NI C A L S T U D Y P R O T O C O L ( C S P) ....................................... 7 1
List of T a bles
Ta ble 1
Cli nical St u d y Sc he matic ........................................................................................................... 1 5
Ta ble 2
Sc he d ule of Assess me nts ........................................................................................................... 1 7
T a ble 3: 
I nvesti gat or Li ve Assess me nt at Ma xi m u m Fr o w n – Res p o n der Rate ( %) at differe nt 
ti me p oi nts.................................................................................................................................. 2 3
Ta ble 4: 
Patie nt Self -Assess m e nt – Res p o n der Rate ( %) at differe nt ti me p oi nts ................................... 2 4
Ta ble 5
Descri pti o n a n d Usa ge of t he St u d y Pr o d ucts ............................................................................ 3 5
List of Fi g ures
Fi g ure 1 
St u d y Fl o w C hart ....................................................................................................................... 1 6
Fi g ure 2
I njecti o n Sites f or Treati n g Gla bellar Li nes ............................................................................... 3 7
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 9 of 7 1
S T U D Y S Y N O P SI S
Cli nic al St u d y Title:
A P hase I V, Ra n d o mize d, I nter ve nti o nal, St u d y  to Assess 
S u bject
Treat me nt Sessi o n Perce pti o n a n d I n vesti gat or 
Treat me nt E x perie nce of All uzie nce a n d Vac u u m -Drie d 
B ot uli n u m Ne ur ot o xi n T y pe A f or Aest hetic Use
S h ort Title: 
S t u d y c o m pari n g T reat me nt wit h A ll uzie nce vs 
R ec o nstit ute d t o xi n (S T A R )
Cli nic al Tri al N u m ber:
0 5 P F 2 0 0 5
C o u ntries I n v ol ve d a n d Pl a n ne d 
N u m ber of St u d y Sites :
C o u ntries: Ger ma n y a n d t he U nite d Ki n g d o m
N o. of st u d y sites: u p t o 1 0 sites
Cli nic al St u d y Desi g n:
T his is a P hase I V, o pe n -la bel, ra n d o mize d, i nter ve nti o nal, 
t w o-ar me d, 
m ulti -ce ntre 
st u d y t o i n vesti gate s u bject 
treat me nt perce pti o n a n d I n vesti gat or treat me nt e x perie nce 
w he n 
usi n g 
All uzie nce 
or 
vac u u m -drie d 
b ot uli n u m 
ne ur ot o xi n t ype A ( p o w der B o N T -A) f or treat me nt of 
gla bellar li nes ( G L).
A p pr o xi matel y  15 0 s u bjects will be ra n d o mize d t o eit her 
All uzie nce or p o w der B o N T -A treat me nt i n a 
 rati o. It is 
esti mate d t hat ar o u n d 1 7 0 s u bjects will be scree ne d t o o btai n 
t he n u m ber of ra n d o mize d s u bjects nee de d f or t he st u d y.
R a n d o mizati o n will be stratifie d b y st u d y site.
T he st u d y co nsists of si x v isits; scree ni n g, treat me nt a n d f o ur 
f oll o w-u p visits 1, 3, 5 a n d 6 m o nt hs after treat me nt, s u bjects 
ra n d o mize d t o be treate d wit h p o w der B o N T-A will o nl y  b e 
f oll o we d f or 1 m o nt h. T he scree ni n g visit a n d t he treat me nt 
visit mi g ht be c o n d ucte d at t he sa me d a y. T he I nvesti gat or 
a n d s u bject will after t he treat me nt fill i n q uesti o n naires 
a b o ut h o w t he y percei ve d t he treat me nt sessi o n a n d t he 
I n vesti gat or will 
als o a ns wer q uesti o n naires re gar di n g 
treat me nt details, rec o nstit uti o n 
of 
t he use d
st u d y 
pr o d uct . 
A d verse e ve nts ( A Es) will be c ollecte d fr o m treat me nt u ntil 
t he e n d of t he s u bject’s partici pati o n . A n y relate d, 
u nres ol ve d A E will be f oll o we d u ntil res ol uti o n f or u p t o 
3 m o nt hs after t he st u d y or u ntil c o nsi dere d sta ble.
T ot al N u m ber of S u bjects 
( Pl a n ne d): 
A p pr o xi matel y  15 0 s u bjects will be ra n d o mize d t o eit her 
All uzie nce or p o w der B o N T -A treat me nt i n a 
 rati o, 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI
C CI
C CI
C CI
C CI

C O N FI D E N TI A L 
Pa ge 1 0 of 7 1
gi vi n g a t otal of 1 0 0 s u bjects ra n d o mize d t o All uzie nce a n d 
5 0 s u bjects t o p o w der B o N T- A treat me nt gr o u ps.
Pri m ar y O bjecti ve a n d E n d p oi nt
T o e valuate ti me nee de d t o pre pare All uzie nce a n d p o w der 
B o N T -A.
o
Ti me t o pre pare st u d y pr o d uct acc or di n g t o pr ot oc ol 
(A p pe n di x 1 ).
Sec o n d ar y Effic ac y O bjecti ves a n d 
E n d p oi nts:  
1.
T o e val uate pre parati o n/rec o nstit uti o n e x perie nce of 
All uzie nce a n d p o w der B o N T -A.
o
Pr o p orti o n of st u d y pr o d ucts pre pare d b y t he 
i n vesti gat ors i n fr o nt of t he patie nts.
o
Pr o p orti o n of a ns wers wit hi n eac h a ns wer o pti o n 
(str o n gly a gree, a gree, neit her a gree n or 
disa gree, disa gree a n d str o n gl y disa gree ) t o 
q uesti o n c o m pari n g All uzie nce pre parati o n vs. 
p o w der B o N T -A rec o nstit uti o n wit h re gar ds t o 
tec h nical iss ues/ pr o ble ms.
o
Pr o p orti o n of treat me nt sessi o ns w here t he 
I n vesti gat or a ns wers t hat he/s he ha ve 
e x perie nce d iss ues wit h p o w der B o N T -A 
rec o nstit uti o n.
Q uesti o n naire t o be use d is a vaila ble i n A p pe n di x 1 .
2.
T o descri be I n vesti gat or treat me nt e x perie nce w he n 
usi n g All uzie nce f or t he treat me nt of G L.
o
Pr o p orti o n of a ns wers wit hi n eac h a ns wer o pti o n 
(str o n gly a gree, a gree, neit her a gree n or 
disa gree, disa gree a n d str o n gl y disa gree ) f or 
eac h q uesti o n s pecifie d i n t he In vesti gat or 
Treat me nt Sessi o n Q uesti o n naire ( A p p e n di x 2)
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 1 1 of 7 1
S afet y O bjecti ves a n d E n d p oi nts:
T he safet y o bjecti ve is t o e val uate t he safet y o f a si n gle d ose 
of All uzie nce f or t he treat me nt of m o derate t o se vere G L.
o
I nci de nce, ca usalit y, se verit y, a n d d urati o n of 
A Es c ollecte d d uri n g t he st u d y .
Cli nic al St u d y D ur ati o n:
T he pla n ne d d urati o n of recr uit me nt (fr o m first s u bject first 
visit
[ F S F V] t o
last s u bject first
visit
[L S F V ]) is 
a p pr o xi matel y 3 m o nt h s.
T he pla n ne d cli nical st u d y durati o n fr o m F S F V t o last 
s u bject last visit [ LS L V] is a p pr o xi matel y  9 m o nt hs.
I ncl usi o n Criteri a:
1.
Fe male 1 8 t o < 6 5 years of a ge.
2.
M o derate t o se vere G L at ma xi m u m fr o w n as assesse d 
b y  t he I n vesti gat or.
3.
Fe male 
of 
n o n- c hil d beari n g 
p ote ntial 
(i.e., 
p ost me n o pa usal [a bse nce of me nstr ual blee di n g f or 1 
ye ar pri or t o scree ni n g, wit h o ut 
a n y ot her me dical 
reas o n], or has u n der g o ne h y sterect o my or bilateral 
o o p h orect o m y). O R Fe male of c hil d beari n g p ote n tial 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI
C CI

C O N FI D E N TI A L 
Pa ge 1 2 of 7 1
wit h a ne gati ve uri ne pre g na nc y  test at scree ni n g a n d 
baseli ne, a n d a grees t o use a hi g hl y effecti ve a n d 
a p pr o ve d c o ntrace pti ve met h o d f or t he d urati o n of t he 
st u d y. A hi g hl y effecti ve met h o d of c o ntrace pti o n is 
defi ne d as:

Bilateral t u bal li gati o n;

C o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) 
oral, i ntra va gi nal or tra ns der mal c o ntrace pti ves t hat 
i n hi bit o v ulati o n as t he pri mar y m o de of acti o n, o n a 
sta ble d ose f or at least 2 8 da y s pri or t o scree ni n g 
visit; 

H or m o nal 
or c o p per i ntra uteri ne de vice (I U D) 
i nserte d at least 2 8 da ys pri or t o Da y 1;

Part ner vasect o mize d f or at least t hree m o nt hs pri or 
t o scree ni n g visit;

Pr o gest o ge n -o nl y oral, i njecta ble or i m pla nta ble 
c o ntrace pti ves t hat i n hi bit o v ulati o n as t he pri mar y 
m o de of acti o n, o n a sta ble d ose f or at least 2 8 d a y s 
pri or t o scree ni n g visit; or

Strict a bsti ne nce (i.e., refrai ni n g fr o m heter ose x ual 
i nterc o urse f or t he e ntire d urati o n of t he s u bject's 
partici pati o n i n t he st u d y).
4.
Ti me a n d a bilit y to c o m plete t he st u d y an d c o m pl y wit h 
i nstr ucti o ns.
5.
U n dersta n ds 
t he st u d y re q uire me nts a n d si g ne d t he 
i nf or me d c o nse nt f or m (I C F).
6.
S u bjects w h o ha ve pla n ne d t o u n der g o aest hetic facial 
treat me nt wit h p o w der t o xi n at t he st u d y site.
7.
Pre vi o us use of a n y a p pr o ve d b ot uli n u m t o xi n i n facial 
areas.
E xcl usi o n Criteri a:
1.
Pre vi o us use of a n y b ot uli n u m t o xi n i n facial area wit hi n 
6 m o nt hs pri or t o st u d y  treat me nt.
2.
Fe male w h o is pre g na nt, breast fee di n g, or i nte n ds t o 
c o ncei ve a c hil d d uri n g t he st u d y .
3.
K n o w n aller g y or h y perse nsiti vit y  to a n y c o m p o ne nt of 
t he st u d y pr o d uct or a n y b ot uli n u m t o xi n ser ot y p e.
4.
A n y  kn o w n c o ntrai n dicati o n s uc h as
s u bject wit h 
blee di n g 
dis or der 
or 
s u bject 
c urre ntl y 
usi n g 
a ntic oa g ula nts .
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 1 3 of 7 1
5.
Pre vi o us 
use of a n y h y al ur o nic aci d s oft tiss ue 
a u g me ntati o n t hera p y i n t he treate d area wit hi n 3 m o nt hs 
bef ore baseli ne.
6.
Pre vi o us s oft tiss ue a u g me ntati o n wit h a n y per ma ne nt 
( n o n-bi o de gra da ble s uc h as silic o ne, p ol y acr yla mi de, 
etc) or se mi-per ma ne nt (i.e., calci u m h y dr o x yl a patite, 
p ol y - L-Lactic aci d or p ol y m et h y l-met hacr y late) pr o d uct; 
lifti n g t hrea ds, or a ut ol o g o us fat i n t he treat me nt area.
7.
S u bject has a n y pri or or c urre nt ps yc hiatric ill ness (e. g. 
Ps y c h osis, de pressi o n, a n xiet y), alc o h ol or dr u g a b use, or 
is ta ki n g a nti de pressa nt, a n xi ol ytic, or a nti ps yc h otic 
me dicati o n 
t hat, i n t he I nvesti gat or's o pi ni o n,
c o ul d 
affect t he s u bject's safet y an d/ or partici pati o n i n t he 
st u d y.
8.
Ot her c o nc urre nt me dical c o n diti o ns, t hera py,  or ot her 
c o n diti o n t hat, i n t he I n vesti gat or's o pi ni o n, w o ul d 
i nterfere wit h t he e val uati o n of t he st u d y me dicati o n, 
safety or efficac y, a n d/ or p ut t he s u bject at ris k if he/s he 
partici pates i n t he st u d y.
9.
Partici pati o n i n a n i n vesti gati o nal de vice or dr u g st u d y 
wit hi n 3 0 da y s pri or t o st u d y treat me nt or pla ns t o e nr oll 
i n a n y ot her i n vesti gati o nal st u d y d uri n g partici pati o n i n 
t his st u d y.
1 0. St u d y site pers o n nel, cl ose relati ves of t he st u d y site 
pers o n nel (e. g. pare nts, c hil dre n, si bli n gs, or s p o use), 
e m pl o yees or cl ose relati ves of e m pl o yees at t he S p o ns or 
c o m pa n y. 
Tre at me nt gr o u ps

All uzie nce

p o w der B o N T - A (B O T O X ®/ Vista bel ® )
1 5 0 s u bjects will be ra n d o mize d t o eit her All uzie nce or 
p o w der B o N T -A treat me nt i n a  
 rati o.
All uzie nce:
All uzie nce is a n a b o b ot uli n u m ne ur ot o xi n t ype A, s u p plie d 
as a sterile, b uffere d s ol uti o n f or i njecti o n. Eac h vial c o ntai ns 
1 2 5 S pe y w o o d u nits (s. U) i n 0. 6 2 5 m L
of s ol uti o n, i.e. 
2 0 0 s.U/ m L .
Stre n gt h/ C o nce ntr ati o n:
1 0 U/ 0. 0 5 m L per i njecti o n p oi nt. I n t otal 5 0 s.U i n 0. 2 5 m L
f or 5 i njecti o n p oi nts.
B O T O X ®/ Vist a bel ® :
B O T O X ®/ Vista bel ® is a b ot uli n u m t o xi n t ype A , s u p plie d 
i n a sterile, vac u u m-drie d f or m. T he vial, c o ntai ni n g 5 0 U, is 
rec o nstit ute d wit h 1. 2 5 m L of sterile, 0. 9 % s o di u m c hl ori de 
bef ore st u d y treat me nt. 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 1 4 of 7 1
Stre n gt h/ C o nce ntr ati o n:
4 U/ 0. 1 m L per i njecti o n p oi nt. I n total 2 0 U i n 0. 5 m L f or 
5 i njecti o n p oi nts.
Tre at me nt are a/I n dic ati o n:
Gla bellar li nes
Tre at me nt re gi me n a n d i njecti o n 
pr oce d ure:
Si n gle treat me nt at t he baseli ne visit, wit h eit her All uzie nce 
or p o w der B o N T - A a d mi nistere d acc or di n g t o eac h pr o d ucts 
S m P C.
St atistic al Met h o d:
 
 
 
 
 
 
S a m ple Size:
T he sa m ple size of a p pr o xi matel y  1 5 0 s u bjects, 1 0 0 s u bjects 
i n t he All uzie nce treat me nt gr o u p a n d 5 0 i n t he p o w der 
B o N T -A treat me nt gr o u p, is n ot base d o n a statistical 
calc ulati o n. T he selecte d n u m ber of s u bjects is re gar de d as 
s ufficie nt f or a n e val uati o n of t he st u die d e n d p oi nts b y usi n g 
descri pti ve statistics.
I nteri m A n al ysis:
N o i nteri m a nal ys is will be perf or me d.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 1 5 of 7 1
C LI N I CA L S T U D Y S C H E M A TI C A N D F L O W C H A R T
T a ble 1  
Cli nic al St u d y Sc he m atic
S cr e e ni n g

B a s eli n e/ R a n d o mi z ati o n t o Tr e at m e nt

Gr o u p 1
Gr o u p 2
n = 1 0 0
n = 5 0
Tr e at m e nt 
5 0 s. U of All u zi e n c e i n G L
2 0 U of p o w d er B o N T -A i n G L
Tr e at m e nt Fr e q u e n c y
Si n gl e t r e at m e nt at B a s eli n e

F oll o w - Up Vi sit s
Gr o u p 1
1, 3 , 5- a n d 6-m o nt h s F U vi sit s
Gr o u p 2
1- m o nt h F U vi sit
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 1 6 of 7 1
Fi g ure 1
St u d y Fl o w C h art
M o nt h 1
(7 da ys)
Visit 3: Fi nal St u d y Visit/ 
Earl y Ter mi nati o n
Da y 0
Visit 2: O btai n Baseli ne Data a n d 
C o nfir m Eli gi bilit y
Ra n d o mizati o n a n d Treat me nt
( 
 [ All uzie nce t o p o w der B o N T-A] )
Gr o u p 1
All uzie nce 5 0 u nits
( 1 0 0 s u bjects)
M o nt h
5
(7 da ys)
Scree n Fail ures
Visit 1: I nf or me d C o nse nt a n d Scree ni n g
Gr o u p 2
p o w der B o N T -A 2 0 u nits 
( 5 0 s u bjects)
Da y - 2 1 t o Da y 0
Visit 3:
P ost -treat me nt F oll o w-u p 
Visit
M o nt h 3
(7 da ys)
Visit 4: P ost -treat me nt 
F oll o w -u p Visit
M o nt h 6
(7 da ys)
Visit 6: Fi nal St u d y Visit/ 
Earl y Ter mi nati o n
Visit 5: P ost -treat me nt 
F oll o w -u p Visit
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 1 7 of 7 1
S C H E D U L E O F A S S E S S M E N T S
T a ble 2
Sc he d ule of Assess me nts
1 m o nt h = 4 wee ks/ 2 8 da ys
V isit wi n d o ws are calc ulate d fr o m Baseli ne / Visit 2 if n ot ot her wise 
s pecifie d.
Visit 1
Gr o u p 1 a n d 2
Visit 2
Gr o u p 1 a n d 2
Visit 3 /
Gr o u p 1
E o S Gr o u p 2
Visit 4
Gr o u p 1
Visit 5
Gr o u p 1
Visit 6 /E T
E o S Gr o u p 1
Scree ni n g 1
Treat me nt/
Baseli ne 1
( wit hi n 3 wee ks after 
scree ni n g)
1- M o nt h 
F oll o w -u p
( ± 7 da ys)
3- M o nt h 
F oll o w -u p
( ± 7 da ys)
5- M o nt h 
F oll o w -u p
( ± 7 da ys)
6- M o nt h 
F oll o w -u p
( ± 7 da ys)
I nf or me d C o nse nt
X
( X)2
D e m o gra p hic Data i ncl u di n g, me dical hist or y & c o n -
c urre nt diseases, pre vi o us facial treat me nts/ pr oce d ures
X
( X)2
I ncl usi o n / E xcl usi o n Criteria
X
X
A d verse E ve nts 3
X
X
X
X
X
C o nc o mita nt Me dicati o n/ Pr oce d ures 
X
X
X
X
X
X
Uri ne Pre g na nc y Test 4
X
X
P h ot o gra p h y
X
X
X
X
Ra n d o mizati o n
X
Treat me nt
X
E n d of st u d y 5
X
Gr o u p 2, p o w der B o N T- A
X
Gr o u p 1, All uzie nce
I n vesti g at or Assess me nts
Rec o nstit uti o n/ Pre parati o n Q uesti o n naire
X
I n vesti gat or Treat me nt Sessi o n Q uesti o n naire6
X
1.
Scree ni n g a n d treat me nt/ baseli ne visits c a n be perf or me d at t he sa me da y
2.
O nl y t o be c o n d ucte d if n o scree ni n g visit has bee n perf or me d. C ha n ges t o me dical hist or y s h o ul d be as ke d f or if t he scree ni n g a n d baseli ne visits are n ot perf or me d o n t he sa me da y.
3.
A Es are c ollecte d fr o m treat me nt t o t he e n d of t he s u bject’s partici pati o n, for details h o w t o f oll o w -u p o n g oi n g A Es at t he last visit se e secti o n 7. 2. 1. 1. 5 . 
4.
O nl y f or w o m e n of c hil d beari n g p ote ntial
5.
S u bjects i n t he p o w der B o N T -A treat me nt gr o u p will be f oll o we d 1 m o nt h a n d s u bjects i n t he All uzie nce treat me nt gr o u p will be f oll o we d f or 6 m o nt hs. 
6.
O nl y f or All uzie nce -treate d s u bjects
7.
O nl y t o be c o m plete d o nce f or eac h T reati n g I n vesti gat or, per st u d y pro d uct , after all e nr olle d s u bjects ha ve c o m plete d Visit 2.
8.
Pe rf or me d pre-treat me nt
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
Versi o n :
Effecti ve  date:
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 1 8 of 7 1
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S
A b brevi ati o n / Ter m
Defi niti o n
A E 
A d verse E ve nt
All uzie nce
B ot uli n u m Ne ur ot o xi n T y pe A
hae ma g gl uti ni n c o m ple x s ol uti o n 
rea dy f or i njecti o n (i n vesti gati o nal pr o d uct)
B o N T
B ot uli n u m Ne ur ot o xi n
B o N T - A
B ot uli n u m Ne ur ot o xi n T y p e A
B o N T - A-H A C
B ot uli n u m Ne ur ot o xi n T y pe A hae ma g gl uti ni n c o m ple x
C
De grees Celsi us
C R A
Cli nical Researc h Ass ociate
C S P
Cli nical St u d y  Pr ot oc ol
C T A
Cli nical Trial A gree me nt
C T N
Cli nical Trial N u m ber
D M P
Data Ma na ge me nt Pla n
e C R F
Electr o nic Case Re p ort F or m
E D C
Electr o nic Data Ca pt ure
e. g. 
F or E xa m ple ( Lati n: e xe m pli gratia)
E T
Earl y Ter mi nati o n
E U
E ur o pea n U ni o n
F A S
F ull A nal ys is Set
F S F V
First S u bject First Visit (first s u bject scree ne d, i.e., w h o si g ns t he 
i nf or me d c o nse nt f or m)
G C P 
G o o d Cli nical Practice 
G L
Gla bellar Li nes
H S A
H u ma n Ser u m Al b u mi n
I CF
I nf or me d C o nse nt F or m
I C H
I nter nati o nal C o u ncil f or Har m o niz ati o n 
i.e. 
T hat is ( Lati n: i d est)
I E C
I n de pe n de nt Et hics C o m mittee
I M P
I n vesti gati o nal Me dici nal Pr o d uct
I n vesti gat or
T he Pri nci pal I nvesti gat or ( PI) or ot her q ualifie d pers o n, i.e., s u b-
I n vesti gat or, desi g nate d a n d s u per vise d b y  the PI  at a st u d y site t o 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 1 9 of 7 1
A b brevi ati o n / Ter m
Defi niti o n
perf or m critical st u d y -relate d pr oce d ures or t o ma ke i m p orta nt st u d y-
relate d decisi o ns as s pecifie d o n t he si g nat ure a n d dele gati o n l o g.
I n vesti gat or’s site file
Esse ntial d oc u me nts relati n g t o a cli nical st u d y as defi ne d i n 
a p plica ble G C P 
g ui da nce d oc u me nt (s) a n d mai ntai ne d 
b y  the 
I n vesti gat or.
I n vesti gati o nal p r o d uct
A p har mace utical f or m of a n acti ve i n gre die nt bei n g teste d i n a cli nical 
st u d y, i ncl u di n g a pr o d uct wit h a mar keti n g a ut h orizati o n w he n use d 
or asse m ble d (f or m ulate d or pac ka ge d) i n a wa y differe nt fr o m t he 
a p pr o ve d f or m, or w he n use d f or a n u na p pr o ve d i n dicati o n, or w he n 
use d t o gai n f urt her i nf or mati o n a b o ut a n a p pr o ve d use.
I UD
I ntra uteri ne De vice
k g
Kil o gra m
L S F V
Last S u bject First Visit (last s u bject scree ne d, i.e., w h o si g ns t he 
i nf or me d c o nse nt f or m)
L S L V
Last S u bject Last Visit (last s u bject w h o c o m plete d his/ her last cli nical 
st u d y visit)
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
m g
Milli gra m
m L
Milliliter
N or n
N u m ber
N/ A
N ot A p plica ble
Na Cl
S o di u m c hl ori de
o na b ot uli n u mt o xi n A
U S A N na me f or B O T O X ® / Vista bel®
PI
Pri nci pal I n vesti gat or; q ualifie d pers o n res p o nsi ble f or c o n d ucti n g t he 
st u d y at a st u dy site .
P P
Per- Pr ot oc ol
P Q C
Pr o d uct Q ualit y  C o m plai nt
R A
Re g ulat or y  A ut h orit y
Refere nce pr o d uct
A n i n vesti gati o nal or mar kete d 
pr o d uct (i.e., acti ve c o ntr ol), or 
place b o, use d as a c o m parat or i n a cli nical st u d y.
s. U
S pe y w o o d u nit
S A E
Seri o us A d verse E ve nt
S A P
Statistical A nal y sis Pla n
S m P C
S u m mar y  of P r o d uct C haracteristics
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 2 0 of 7 1
A b brevi ati o n / Ter m
Defi niti o n
S O P
Sta n dar d O perati n g Pr oce d ure
S pe y w o o d u nit
T o xi n p ote nc y  meas ure me nt u nit
S p o ns or file
Esse ntial d oc u me nts relati n g t o a cli nical st u d y as defi ne d i n 
a p plica ble G C P g ui da nce d oc u me nt (s) a n d mai ntai ne d b y  the S p o ns o r.
St u d y  files
T he I n vesti gat or site file a n d S p o ns or file
St u d y  p r o d ucts
T he i n vesti gati o nal pr o d uct a n d t he refere nce pr o d uct u n der st u d y .
St u d y  sites
T he l ocati o n(s) w here 
t he st u d y-relate d acti vities are act uall y 
c o n d ucte d.
S U S A R
S us pecte d U ne x pecte d Seri o us A d verse Reacti o ns
T E A E
Treat me nt E mer ge nt A d verse E ve nt
U
U nits
B O T O X ® /Vista bel ®
o na b ot uli n u mt o xi n A, 
B ot uli n u m 
T o xi n 
T y pe 
A 
f or injecti o n
(refere nce pr o d uct)
W H O
W orl d Healt h Or ga nizati o n
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 2 1 of 7 1
1. 
B A C K G R O U N D A N D R A TI O N A L E
1. 1
Me dic al B ac k gr o u n d a n d S h ort R ati o n ale f or t he C li nic al St u d y
O ver t he last fe w deca des, as t he a gi n g p o p ulati o n c o nti n ues t o gr o w, t here has bee n a n i ncreasi n g 
de ma n d f or c os metic pr oce d ures t o re verse t he a p peara nce of a d va nci n g a ge, partic ularl y  in t he 
facial area.
T his i ncreasi n g pre occ u pati o n wit h p h y sical a p peara nce has le d t o t he de vel o p me nt of ma n y 
differe nt pr o d ucts a n d pr oce d ures, s uc h as s ur ger y, res urfaci n g of vari o us t ypes, a n d t he use of 
filli n g a ge nts. 
W hile n o ne of t hese met h o ds are e ntirel y ris k fr ee, c o nti n u o us researc h is necessar y t o pr o vi de t he 
safest a n d m ost effecti ve met h o ds f or treat me nt of t he a gi n g face. Alt h o u g h t here are fi ve fact ors 
t hat i nter pla y in t he pr o d ucti o n of w hat is k n o w n as t he a gi n g face 2, t here are pri marily t w o fact ors 
i nteracti n g t o pr o d uce t he m ore si g nifica nt li nes a n d f ol ds, as o p p ose d t o wri n kles: t he s ki n a n d t he 
u n derl yi n g m uscles. 
Ma n y  thera pies ha ve e v ol ve d t o treat wri n kles a n d t he s ki n fact ors of t he li nes a n d f ol ds, a m o n g 
t he m are vari o us t ypes of res urfaci n g, der mat ol o gic pr o d ucts a n d i njecti o ns f or s oft tiss ue 
a u g me ntati o n. 
T he use of Cl ostri di u m b ot uli n u m t o xi n t y pe A ( B o N T -A) has bee n s h o w n t o a meli orate li nes a n d 
f ol ds b y  te m p oraril y paral ysi n g s pecific m uscle gr o u ps. Ma n y st u dies re gar di n g t he aest hetic use 
of B o N T -A ha ve n o w bee n p u blis he d i n t he peer re vie we d me dical literat ure 3 , 4 , 5 , 6 , 7 , 8 , 9 , 1 0 , 1 1 , 1 2. 
M ore 
rece ntly, Cl ostri di u m b ot uli n u m t o xi n (B o N T) pr o d ucts ha ve bee n a p pr o ve d f or t he 
i m pr o ve me nt i n t he a p peara nce of gla bellar li nes i n a n u m b er of c o u ntries i n t he E ur o pea n U ni o n
( E U) a n d i n t he U nite d States of A merica. Base d o n b ot h cli nical o bser vati o n a n d o bjecti ve 
meas ure me nt of gla bellar f ol ds, B o N T -A, i n l o w d oses, has bee n s h o w n t o s u p press t he m usc ular 
acti vit y of t he gla bellar area b y te m p orar y rela xati o n of t he pr ocer us a n d c orr u gat or m uscle c o m ple x. 
B o N T -A is a p ote nt ne ur ot o xi n is olate d fr o m t he bacteri u m Cl ostri di u m b ot uli n u m, a Gra m p ositi ve, 
s p ore f or mi n g a naer o be. B o N T -A, a si n gle c hai n pr otei n ( m olec ular wei g ht ~ 1 5 0, 0 0 0 Dalt o ns [ Da]), 
is o ne of se ve n differe nt ser ot y pes (classe d t y pe A t hr o u g h G) of B o N T pr o d uce d b y  t his or ga nis m. 
Pr otei ns e n d o ge n o us t o t he bacteri u m clea ve t he si n gle c hai n pr otei n, res ulti n g i n a dic hai n 
ne ur ot o xi n c o ntai ni n g a li g ht c hai n ( m olec ular wei g ht ~ 5 0 , 0 0 0 Da) a n d a hea v y c hai n ( m olec ular 
wei g ht ~ 1 0 0, 0 0 0 Da) t hat re mai n li n ke d b y  an i nter c hai n dis ulfi de a n d n o nc o vale nt b o n ds. B o N T -A 
acts selecti vely o n peri p heral c h oli ner gic ner ve e n di n gs, i n hi biti n g acet yl c h oli ne release, effecti vel y 
bl oc ki n g si g nal tra ns missi o n fr o m ner ve t o m uscle 
a n d i n d uci n g a te m p orar y, partial 
c he m o de ner vati o n of t he i njecte d m uscle.
M ost a p pr o ve d B o N T -A pre parati o ns i n E ur o pe a n d N ort h A merica re q uire rec o nstit uti o n a n d t his 
is ass ociate d wit h se veral c halle n ges.
Healt hcare pr ofessi o nals m ust
s pe n d ti me o n pre parati o n ,
err ors ma y occ ur i n t he dil uti o n w hic h c o ul d res ult i n u n der or o ver -d osi n g, m ore waste t ha n nee de d 
is pr o d uce d w hic h m a y  ha ve ec o n o mic i m pacts a n d t he varia bilit y  of d osi n g is i ncrease d. T heref ore ,
a rea dy- t o-use li q ui d f or m ulati o n of B o N T -A will
facilitate a n d sta n dar dize i njecti o n practice, 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 2 2 of 7 1
e ns uri n g t hat a p pr o priate d oses a n d c o nce ntrati o ns are a d mi nistere d a n d t h us pre ve nti n g 
rec o nstit uti o n err ors1 3.
All uzie nce is a n o vel B o N T t ype- A 1 pr o d uce d as a li q ui d f or m ulati o n , wit h rece ntly gra nte d mar ket 
a ut h orizati o n i n t he st u d y partici pati n g c o u ntries . T his st u d y see ks t o e val uate s u bject treat me nt 
sessi o n perce pti o n a n d I n vesti gat or treat me nt e x perie nce w he n usi n g All uzie nce a n d p o w der 
B o N T -A.
1. 2
I n vesti g ati o n al Pr o d uct Pr ofile
1. 2. 1
Dr u g P r ofile
All uzie nce is a n i njecta ble li q ui d f or m of B o N T -A hae ma g gl uti ni n c om ple x (B o N T - A-H A C) 
s u p plie d i n a glass vial. T he acti ve B o N T - A-H A C is t he sa me as prese nt i n t he pre vi o usl y mar kete d 
pr o d uct D y s p ort ® 5 0 0 u nits ( U), 3 0 0 U a n d 1 2 5 U (t he latter stre n gt h a p pr o ve d as Azzal ure ® i n 
E ur o pe) .
T he c urre ntl y mar kete d freeze-drie d pre parati o ns of B o N T - A-H A C pr o d ucts are f or m ulate d wit h 
lact ose ( b ul ki n g a ge nt) a n d h u ma n ser u m al b u mi n ( H S A) i n a glass vial. T he p ote ntial ris k of i nfecti o
us diseases d ue t o t he tra ns missi o n of i nfecti ve a ge nts ca n n ot be t otall y excl u de d w he n H S A a n d 
ot her plas ma -deri ve d pr o d ucts are use d i n t he ma n ufact ure a n d f or m ulati o n of me dici nal pr o d ucts 1 4.
T he de vel o p me nt of s u bstit utes f or plas ma -deri ve d H S A as a n e xci pie nt f or me dici nal pr o d ucts is 
e nc o ura ge d b y  the E ur o pea n Me dici nes A ge nc y  as descri be d i n t he N ote f or G ui da nce o n Plas ma -
Der i ve d Me dici nal 
Pr o d ucts C P M P/ B W P/ 3 2 8/ 9 9 1 5. 
 
 
 
 
1. 2. 2
Fi n di n gs fr o m Pre - Cli nic al St u dies
St u dies o n ac ute t o xicit y, c hr o nic t o xicit y an d l ocal t olera nce at t he i njecti o n site s h o we d n o u n us ual
a d verse l ocal or s ys te mic effects at cli nically rele va nt d ose le vels 1 6.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI
C CI

C O N FI D E N TI A L 
Pa ge 2 3 of 7 1
1. 2. 3
Cli nic al D oc u me nt ati o n
A p o ole d t otal of 3 7 2 patie nts wit h m o derate t o se vere gla bellar li nes were treate d i n 2 pi v otal trials, 
2 5 0 at t he rec o m me n de d d ose of 5 0 s. U, a n d 1 2 2 wit h place b o1 6.
T he maj orit y  of patie nts s u bjecti vel y re p orte d a n effect wit hi n 2 t o 3 da y s, i ncl u di n g 2 3 % of patie nts 
wit hi n 1 da y . T he pr o p orti o n of res p o n ders by i n vesti gat or assess me nt was statisticall y si gnifica ntl y 
hi g her f or patie nts treate d wit h All uzie nce 1 m o nt h after i njecti o n c o m pare d t o place b o (t he pri mar y  
e n d p oi nt) as well as at all ot her ti me p oi nts fr o m 8 da y s u p t o 6 m o nt hs (Ta ble 3 ). 
T a ble 3 : I n vesti g at or Li ve Assess me nt at M a xi m u m Fr o w n – Res p o n der R ate ( %) at differe nt 
ti me p oi nts
Visit after i njecti o n
All uzie nce 
( N = 2 5 0)
Pl ace b o
( N = 1 2 2)
8 da ys
8 0. 0 %
2. 5 %
1 m o nt h
8 7. 6 %
2. 5 %
2 m o nt hs
7 6. 8 %
1. 7 %
3 m o nt hs
5 7. 6 %
1. 7 %
4 m o nt hs
3 6. 3 %
1. 8 %
5 m o nt hs
1 7. 5 %
0. 9 %
6 m o nt hs
1 0. 0 %
0. 9 %
N ote: A res p o n der is defi ne d as ha vi n g a se verit y gra de of m o derate or se vere at baseli ne a n d a se verit y gra de of n o ne 
or mi l d at a gi ve n visit. Res p o n der rates, t he pri mar y efficac y e n d p oi nt at Da y  29, was statisticall y si g nifica ntl y differe nt 
t o place b o ( p < 0. 0 0 0 1). Res p o n der rates at ot her ti me p oi nts were n o mi nall y differe nt t o place b o ( p-val ues ra n gi n g fr o m 
≤ 0. 0 0 0 1 t o 0. 0 0 0 8) at all ti me p oi nts). 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 2 4 of 7 1
T he pr o p orti o n of res p o n ders acc or di n g t o t he patie nt self-assess me nt was hi g her f or patie nts treate d 
wit h All uzie nce c o m pare d t o place b o at all ti me p oi nts fr o m 8 da y s u p t o 6 m o nt hs (Ta ble 4 ). 
T a ble 4 : P atie nt Self -Assess me nt – Res p o n der R ate ( %) at differe nt ti me p oi nts
Visit after i njecti o n
All uzie nce 
( N = 2 5 0)
Pl ace b o
( N = 1 2 2)
8 da ys
6 6. 0 %
4. 9 %
1 m o nt h
7 6. 8 %
5. 7 %
2 m o nt hs
7 2. 4 %
2. 5 %
3 m o nt hs
4 8. 8 %
3. 4 %
4 m o nt hs
3 2. 7 %
4. 3 %
5 m o nt hs
2 3. 1 %
4. 3 %
6 m o nt hs
1 5. 1 %
2. 6 %
N ote: A res p o n der is defi ne d as ha vi n g a se verit y gra de of m o derate or se vere at baseli ne a n d a se verit y gra de of n o ne 
or m il d at a gi v e n visit . Res p o n der rates were statisticall y si g nifica ntl y differe nt t o place b o wit h p ≤ 0. 0 0 0 1 at all ti m e 
p oi nts .
Patie nts’ le vel of satisfacti o n 1 m o nt h f oll o wi n g i njecti o n s h o we d t hat 8 5. 2 % of t he patie nts 
recei vi n g All uzie nce were eit her satisfie d or very satisfie d c o m pare d t o 9 % f or place b o patie nts.
Aest hetic a n d ps yc h ol o gical i m pr o ve me nt was o bser ve d usi n g Face -Q scales. F or t he facial 
a p peara nce o verall scale ( w hic h i nc or p orates s u bject rati n gs f or facial bala nce, e n d - of-d a y  
a p peara nce, facial fres h ne ss, reste d l o o k, a p peara nce w he n wa ki n g u p a n d a p peara nce u n der bri g ht 
li g hts) a n d t he ps yc h ol o gical well bei n g scale ( w hic h i nc or p orates s u bject rati n gs o n feeli n g o k a y , 
self-acce pta nce, c o mf ort wit h self, feeli n g g o o d, self-li ki n g, feeli n g ha p p y,  feeli n g attracti ve, a n d 
feeli n g c o nfi de nt), o ne m o nt h after i njecti o n, s u bjects treate d wit h All uzie nce s h o we d i m pr o ve me nt 
i n t he sc ore f or eac h of t hese scales c o m pare d t o s u bjects w h o were treate d wit h place b o (n o mi nal 
p < 0. 0 0 0 1).
A t otal of 5 9 5 patie nts recei ve d u p t o 5 treat me nt c ycles of All uzie nce i n a 1 2 m o nt hs l o n g-ter m 
o pe n -la bel p hase III st u d y. Efficac y was mai ntai ne d o ver t he 1 2 m o nt hs peri o d, b y  t he i n vesti gat or 
assess me nt, t he patie nt assess me nt, patie nt satisfacti o n a n d F A C E - Q q uesti o n naires.
T he pr o p orti o n of res p o n ders at ma xi m u m fr o w n, deter mi ne d b y  t he i n vesti gat or 1 m o nt h after t he 
i njecti o n, was mai ntai ne d 
o ver re peate d i njecti o n c ycles ( bet wee n 8 2. 2 % a n d 8 7. 8 %). T he 
c orres p o n di n g pr o p orti o ns 3 m o nt hs after i njecti o n ra n ge d bet wee n 4 5. 3 % a n d 5 6. 8 % acr oss t he 
5 treat me nt c ycles.
Patie nts ( 5 9 5 i n t otal) recei vi n g All uzie nce o ver a 1 2 m o nt hs peri o d were teste d f or a nti b o d y 
f or mati o n. N o patie nts teste d p ositi ve f or t o xi n-ne utralisi n g a nti b o dies.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 2 5 of 7 1
1. 3
R ati o n ale f or S t u d y D esi g n, D oses a n d C o ntr ol Gr o u p
T he p ur p ose of t his st u d y is t o assess s u bject treat me nt sessi o n perce pti o n a n d I nvesti gat or treat me nt 
e x perie nce w he n usi n g All uzie nce a n d p o w der B o N T -A. B ot h t he i n vesti gati o nal dr u g, All uzie nce 
a n d t he c o m parat or, B O T O X ® / Vista bel® (p o w der B o N T -A) are a p pr ove d i n t he E U/ E E A t o treat 
g la bellar li nes. It is belie ve d t hat a rea dy t o use s ol uti o n, s uc h as All uzie nce, mi g ht be a d va nta ge o us 
c o m pare d t o a vac u u m drie d p o w der, t hat nee ds t o be rec o nstit ute d bef ore use, w he n use d i n a 
cli nical setti n g. T his st u d y an d its assess me nts are t heref ore ai me d at e val uati n g h o w t he s u bjects 
a n d I n vesti gat or e x perie nces t he treat me nt sessi o n a n d t he ha n dli n g of t he st u d y  pr o d uct.  
 
 
 
 
T he c h ose n d ose of 2 0 U f or p o w der B o N T - A was base d o n t he d ose rec o m me n de d b y  the 
ma n ufact urer 1 7. N ote t hat t he u nits f or p o w der B o N T - A are s pecific t o t he pre parati o n a n d are n ot 
i nterc ha n gea ble wit h ot her pre parati o ns of B o N T-A pr o d ucts.
T he d ose c h ose n f or All uzie nce is b ase d o n t he e val uati o n of res ults f or t he differe nt d ose le vels 
st u die d t o date i n t he cli nical pr o gra m, w here t he S p o ns or has c o ncl u de d t hat a 5 0 s. U d ose offers 
a n a p pr o priate bala nce bet wee n efficac y , d urati o n of effect, a n d safet y. 5 0 s. U is t he a p pr o ve d d ose 
f or All uzie nce f or t he treat me nt of G L as per t he S u m mar y  of Pr o d ucts C haracteristics 1 6.
1. 4
Ris k/ Be nefit A ssess me nt
B ot h st u d y pr o d ucts i n vesti gate d i n t his trial are o n t he mar ket i n t he partici pati n g c o u ntries a n d are 
c o nsi dere d safe f or use i n h u ma ns. 
A maj orit y of a d verse reacti o ns re p orte d wit h All uzie nce i n cli nical trials were of mil d t o m o derate 
i nte nsit y an d re versi ble. T he m ost fre q ue ntly re p orte d a d verse reacti o ns were hea dac he a n d i njecti o n 
site reacti o ns. T he i nci de nce of a d verse reacti o ns te n de d t o decrease wit h re peate d treat me nts.
A d verse effects p ossi bl y  relate d t o t he s prea d of t o xi n effect dista nt fr o m t he site of a d mi nistrati o n 
ha ve bee n v er y  rarel y re p orte d wit h b ot uli n u m t o xi n (e xcessi ve m uscle wea k ness, d y s p ha gia, 
as pirati o n p ne u m o nia wit h fatal o utc o mes i n s o me cases). Detaile d a d verse reacti o n i nf or mati o n ca n 
be f o u n d i n t he All uzie nce S u m mar y  of Pr o d ucts C haracteristics 1 6.
A d verse reacti o ns ca use d b y  B O T O X ® /Vista bel ® are si milar t o t he e x pecte d ad verse reacti o ns liste d 
a b o ve f or All uzie nce as b ot h dr u gs are B o N T -A deri vati ves. Detaile d a d verse reacti o n i nf or mat i o n 
ca n be f o u n d i n t he B O T O X ® /Vista bel ® S u m mar y of Pr o d ucts C haracteristics 1 7. 
T he d ose a d mi nistere d are acc or di n g t o t he prescri bi n g i nf or mati o n f or t he st u d y pr o d ucts i n t he 
E U/ E E A . T heref ore, t he ris ks ass ociate d wit h partici pati o n i n t his st u d y are c o nsi dere d acce pta ble 
c o m pare d t o t he a ntici pate d hi g h de gree of s u bject satisfacti o n wit h treat me nt a n d t he treat me nt 
re gi me n.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
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C O N FI D E N TI A L 
Pa ge 2 6 of 7 1
2.
C LI NI C A L S T U D Y O B J E C TI V E S , E N D P OI N T S, A N D C LI NI C A L H Y P O T H E SI S
2. 1
Cli nic al St u d y O bjecti ves
T he o bjecti ve of t he st u d y is t o assess, s u bject treat me nt sessi o n perce pti o n a n d I n vesti gat or 
treat me nt e x perie nce w he n u si n g All uzie nce a n d p o w der B o N T -A. A d diti o nall y , efficac y an d safet y 
of a si n gle d ose of All uzie nce , f or t he treat me nt of m o derate t o se vere G L, will be e val uate d d uri n g 
a 6-m o nt h f oll o w -u p peri o d. 
2. 1. 1
Pri m ar y O bjecti ves a n d E n d p oi nts
T he pri mar y  objecti ve of t his st u d y is t o e val uate t he ti me nee de d t o pre pare All uzie nce a n d p o w der 
B o N T - A acc or di n g t o pr ot oc ol (A p pe n di x 1 ).
2. 1. 2
Sec o n d ar y Effic ac y O bjecti ve a n d E n d p oi nts
1.
O bjecti ve: 
T o e val uate pre parati o n/rec o nstit uti o n e x perie nce of All uzie nce 
a n d p o w der 
B o N T -A.
E n d p oi nts: 
o
Pr o p orti o n of st u d y  pr o d ucts pre pare d by t he i n vesti gat ors i n fr o nt of t he patie nts.
o
Pr o p orti o n of a ns wers wit hi n eac h a ns wer o pti o n ( str o n gly a gree, a gree, neit her a gree 
n or disa gree, disa gree a n d str o n gl y disa gree ) t o q uesti o n c o m pari n g All uzie nce 
pre parati o n vs. p o w der B o N T- A rec o nstit uti o n wit h re gar ds t o tec h nical 
iss ues/ pr o ble ms.
o
Pr o p orti o n of treat me nt sessi o ns w here t he I n vesti gat or a ns wers t hat he/s he ha ve 
e x perie nce d iss ues wit h p o w der B o N T -A rec o nstit uti o n .   
See A p pe n di x 1 (Rec o nstit uti o n/ Pre parati o n of All uzie nce a n d p o w der B o N T -A) f or details.
2.
O bjecti ve : T o descri be I n vesti gat or treat me nt e x perie nce w he n usi n g All uzie nce f or t he 
treat me nt of G L.
E n d p oi nts: 

Pr o p orti o n of a ns wers wit hi n eac h a ns wer o pti o n (str o n gl y agree, a gree, neit her a gree n or 
disa gree, disa gree a n d str o n gly disa gree ) f or eac h q uesti o n s pecifie d i n t he I n vesti gat or 
Treat me nt Sessi o n Q uesti o n na ire (A p pe n di x 2 )
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
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C O N FI D E N TI A L 
Pa ge 2 7 of 7 1
2. 1. 4
S afet y O bjecti ves a n d E n d p oi nts
T he safety o bjecti ve is t o e val uate t he safety of a si n gle d ose of All uzie nce f or t he treat me nt of 
m o derate t o se vere G L .
E n d p oi nts :

I nci de nce, ca usalit y, se verit y, a n d d urati o n of A Es c ollecte d d uri n g t he st u d y.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 2 8 of 7 1
3.
O V E R A L L C LI NI C A L S T U D Y D E S C RI P TI O N
T his is a n, o pe n-la bel, ra n d o mize d, i nter ve nti o nal, t w o-ar me d, m ulti -ce ntre st u d y to i n vesti gate 
s u bject treat me nt perce pti o n a n d I n vesti gat or treat me nt e x perie nce w he n usi n g All uzie nce or 
vac u u m -drie d b ot uli n u m ne ur ot o xi n t y pe A ( p o w der B o N T -A) f or treat me nt of G L.
A p pr o xi matel y  1 5 0 s u bjects will be ra n d o mize d t o eit her All uzie nce or p o w der B o N T-A treat me nt 
i n a  
 rati o. Ra n d o mizati o n will be stratifie d b y st u d y site. It is esti mate d t hat ar o u n d 1 7 0 s u bjects 
will be scree ne d t o o btai n t he n u m ber of ra n d o mize d s u bjects nee de d f or t he st u d y.
T he st u d y  co nsists of si x visits; scree ni n g, treat me nt a n d f o ur f oll o w -u p visits 1, 3, 5 a n d 6 m o nt hs 
after treat me nt, s u bjects ra n d o mize d t o be treate d wit h p o w der B o N T -A will o nl y  be f oll o we d f or 
1- m o nt h (see Ta ble 1 a n d Fi g ure 1 ). T he scree ni n g visit a n d t he treat me nt visit mi g ht be c o n d ucte d 
at t he sa me d a y . T he I n vesti gat or a n d 
 will after t he treat me nt a ns wer q uesti o n naires a b o ut 
h o w t he y percei ve d t he treat me nt sessi o n a n d t he I n vesti gat or will als o a ns wer q uesti o n naires 
re gar di n g treat me nt details, rec o nstituti o n a n d 
 of t he 
use d st u d y pr o d uct . 
.
A d verse e ve nts ( A Es) will be c ollecte d fr o m treat me nt u ntil t he f oll o w- u p visit. A n y  relate d, 
u nres ol ve d A E will be f oll o we d u ntil res ol uti o n f or u p t o 3 m o nt hs after t he st u d y or u ntil c o nsi dere d 
sta ble.
Ef ficac y assessme nts will i ncl u de ( Secti o n 7. 1 ):

I n vesti gat or Assess me nts:
o
Rec o nstit uti o n/ Pre parati o n Q uesti o n naire
o
I n vesti gat or Treat me nt Sessi o n Q uesti o n naire 
Safet y  assess me nts will i ncl u de ( Secti o n 7. 2 ):

A Es

Pre g na nc y  test
T he selecti o n criteria f or t he st u d y po p ulati o n are descri be d i n Secti o n 5 . Detaile d i nf or mati o n a b o ut 
t he st u d y tas ks f or eac h st u d y visit is o utli ne d i n Secti o n 8 a n d i n Ta ble 2 . T he treat me nt pr oce d ure 
is pr o vi de d i n Secti o n 6. 1. 7. 1 .
4.
C LI NI C A L S T U D Y D U R A TI O N A N D T E R MI N A TI O N
T he pla n ne d d urati o n of recr uit me nt (fr o m first s u bject first visit [ F S F V] t o last s u bject first v isit 
[ LS F V]) is a p pr o xi matel y  3 m o nt hs.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI
C CI
C CI
C CI
C CI

C O N FI D E N TI A L 
Pa ge 2 9 of 7 1
T he pla n ne d cli nical st u d y durati o n fr o m F S F V t o last s u bject last visit (L S L V) is a p pr o xi matel y 
9 m o nt hs.
Cli nical st u d y partici pati o n is a p pr o xi matel y 6. 5 m o nt hs f or s u bjects i n t he All uzie nce treat me nt 
gr o u p a n d 1. 5 m o nt hs f or s u bjects i n t he p o w der B o N T -A treat me nt gr o u p, i ncl u di n g t he scree ni n g, 
treat me nt, a n d f oll o w-u p peri o ds .
T he S p o ns or ma y  deci de t o pre mat urel y ter mi nate or s us pe n d t he partici pati o n of a partic ular cli nical 
st u d y site (e. g., d ue t o lac k of s u bject e nr oll me nt or n o n- c o m plia nce wit h cli nical st u d y pr ot oc ol
( C S P), re g ulati o n, or G C P) or pre mat urely s us pe n d t he cli nical st u dy (e. g., f or safety, st u d y pr o d uct
q ualit y , re g ulat or y, efficac y, or l o gistical reas o ns) at a n y ti me wit h a p pr o priate n otificati o n.
5. 
S E L E C TI O N A N D DI S P O SI TI O N O F C LI NI C A L S T U D Y P O P U L A TI O N
5. 1
N u m ber of S u bjects
As a scree n fail ure rate of a p pr o xi matel y 1 0 % is antici pate d, a p pr o xi matel y 1 7 0 s u bjects will be 
scree ne d i n or der t o e nr oll a p pr o xi matel y 1 5 0 s u bjects i n a 
rati o t o 5 0 s. U of All uzie nce (N = 1 0 0)
or 2 0 U p o w der B o N T -A ( N = 5 0). It is e x pecte d t hat eac h site will recr uit a si milar n u m ber of 
s u bjects (a p pr o xi matel y 1 0 t o 2 0 s u bjects) .
5. 2
Cli nic al St u d y P o p ul ati o n C h ar acteristics
I n or der t o be eli gi ble f or t he cli nical st u d y, s u bjects m ust f ulfill all of t he f oll o wi n g criteria. T hese 
criteria are a p plica ble at b ot h scree ni n g a n d baseli ne u nless ot her wise s pecifie d ( n ote t hat 
1 m o nt h = 4 wee ks/ 2 8 da ys ).
5. 2. 1
I ncl usi o n C riteri a
S u bjects m ust meet all t he f oll o wi n g criteria t o be eli gi ble f or t he st u d y:
1.
Fe male 1 8 t o < 6 5 years of a ge .
2.
M o derate t o se vere G L at ma xi m u m fr o w n as assesse d b y  t he I n vesti gat or.
3.
Fe male of n o n- c hil d beari n g p ote ntial (i.e., p ost me n o pa usal [a bse nce of me nstr ual blee di n g f or 
1 y ear pri or t o scree ni n g, wit h o ut a n y  ot her me dical reas o n], or has u n der g o ne h ysterect o m y or 
bilateral o o p h orect o m y ).
O R 
Fe male of c hil d beari n g p ote ntial wit h a ne gat i ve uri ne pre g na nc y test at scree ni n g a n d baseli ne 
a n d a grees t o use a hi g hl y  effecti ve a n d a p pr o ve d c o ntrace pti ve met h o d f or t he d urati o n of t he 
st u d y. A hi g hly effecti ve met h o d of c o ntrace pti o n is defi ne d as:
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 3 0 of 7 1

Bilateral t u bal li gati o n;

C o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) oral, i ntra va gi nal or tra ns der mal 
c o ntrace pti ves t hat i n hi bit o v ulati o n as t he pri mar y m o de of acti o n, o n a sta ble d ose 
f or at least 2 8 da ys pri or t o scree ni n g visit; 

H or m o nal or c o p per I U D i nserte d at least 2 8 da y s pri or t o Da y  1;

Part ner vasect o mize d f or at least t hree m o nt hs pri or t o scree ni n g visit;

Pr o gest o ge n - o nly o ral, i njecta ble or i m pla nta ble c o ntrace pti ves t hat i n hi bit o v ulati o n 
as t he pri mar y m o de of acti o n, o n a sta ble d ose f or at least 2 8 da y s pri or t o scree ni n g 
v isit; or

Strict a bsti ne nce (i.e., refrai ni n g fr o m heter ose x ual i nterc o urse f or t he e ntire d urati o n 
of t he s u bject's partici pati o n i n t he st u d y ).
4.
Ti me a n d a bilit y  t o c o m plete t he st u d y a n d c o m pl y wit h i nstr ucti o ns.
5.
U n dersta n ds t he st u d y re q uire me nts a n d si g ne d t he i nf or me d c o nse nt f or m (I C F).
6.
S u bjects w h o ha ve pla n ne d t o u n der g o aest hetic facial treat me nt wit h p o w der t o xi n at t he st u d y 
site.
7.
Pre vi o us use of a n y a p pr o ve d b ot uli n u m t o xi n i n facial areas.
5. 2. 2
E xcl usi o n Criteri a
T he prese nce of a n y of t he f oll o wi n g e xcl usi o n criteria e xcl u des a s u bject fr o m e nr oll me nt i n t he 
st u d y: 
1.
Pre vi o us use of a n y b ot uli n u m t o xi n i n facial area wit hi n 6 m o nt hs pri or t o st u d y treat me nt.
2.
Fe male w h o is pre g na nt, breast fee di n g, or i nte n ds t o c o n cei ve a c hil d d uri n g t he st u d y.
3.
K n o w n aller g y or h y perse nsiti vit y  to a n y c o m p o ne nt of t he i n vesti gati o nal pr o d uct or a n y 
b ot uli n u m t o xi n ser ot y p e.
4.
A n y  kn o w n c o ntrai n dicati o n s uc h as s u bject wit h blee di n g dis or der or s u bject c urre ntl y usi n g 
a ntic oa g ula nts.
5.
Pre vi o us use of a n y  h yal ur o nic aci d s oft tiss ue a u g me ntati o n t hera p y i n t he treate d area wit hi n 
3 m o nt hs bef ore baseli ne.
6.
Pre vi o us s oft tiss ue a u g me ntati o n wit h a n y per ma ne nt ( n o n-bi o de gra da ble s uc h as silic o ne, 
p ol y acr yla mi de, etc) or se mi- per ma ne nt (i.e., calci u m h y dr o x y la patite, p ol y - L-Lactic aci d or 
p ol y met h y l-met hacr y late) pr o d uct; lifti n g t hrea ds, or a ut ol o g o us fat i n t he treat me nt area.
7.
S u bject has a n y pri or or c urre nt ps yc hiatric ill ness (e. g. Ps y c h osis, de pressi o n, a n xiet y), alc o h ol 
or dr u g a b use, or is ta ki n g a nti de pressa nt, a n xi ol ytic, or a nti ps yc h otic me dicati o n t hat, i n t he 
I n vesti gat or's o pi ni o n, c o ul d affect t he s u bject's safet y a n d/ or partici pati o n i n t he st u d y.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 1 of 7 1
8.
Ot her c o nc urre nt me dical c o n diti o ns, t hera p y, or ot her c o n diti o n t hat, i n t he I n vesti gat or's 
o pi ni o n, w o ul d i nterfere wit h t he e val uati o n of t he st u d y  me dicati o n, safet y or efficac y, a n d/ or 
p ut t he s u bject at ris k if he/s he partici pates i n t he st u d y .
9.
Partici pati o n i n a n i n vesti gati o nal de vice or dr u g st u d y  wit hi n 3 0 da ys pri or t o st u d y treat me nt 
or pla ns t o e nr oll i n a n y ot her i n vesti gati o nal st u d y d uri n g partici pati o n i n t his st u d y .
1 0. St u d y  site pers o n nel, cl ose relati ves of t he st u d y site pers o n nel (e. g. pare nts, c hil dre n, si bli n gs, 
or s p o use), e m pl o ye es or cl ose relati ves of e m pl o y ees at t he S p o ns or c o m pa n y.
5. 3
Me dic al Hist or y
Rele va nt hist or y  of s ur gical e ve nts a n d me dical c o n diti o ns s hall be d oc u me nte d i n t he s u bject’s 
st u d y file a n d electr o nic case re p ort f or m (e C R F) usi n g me dical ter mi n ol o g y .
5. 4
Pre vi o us a n d C o nc o mit a nt T her a pies
5. 4. 1
Defi niti o n
Pre vi o us t hera pies are defi ne d as t hera pies t hat ha ve bee n st o p pe d wit hi n 4 wee ks prece di n g t he 
scree ni n g visit or wit hi n ti mefra mes s pecifie d i n t he i ncl usi o n/excl usi o n criteria .
C o nc o mita nt t hera pies are defi ne d as f oll o ws:

a n y e xisti n g t hera pies o n g oi n g at t he ti me of t he scree ni n g visit,

a n y cha n ges t o e xisti n g t hera pies (s uc h as c ha n ges i n d ose or f or m ulati o n) d uri n g t he c o urse 
of t he cli nical st u d y, or

a n y ne w t hera pies recei ve d b y t he s u bject si nce t he scree ni n g visit.
5. 4. 2
C ate g ories
T he f oll o wi n g t w o cate g ories are t o be c o nsi dere d f or pre vi o us a n d c o nc o mita nt t hera pies: 

Dr u gs , i ncl u di n g, b ut n ot li mite d t o, prescri pti o n, o ver t he c o u nter, birt h c o ntr ol 
pills/ patc hes/ h or m o nal de vices, vita mi ns, her bal me dici nes/s u p ple me nts, a n d h o me o pat hic 
pre parati o ns.

Me dical a n d s ur gical pr oce d ures , incl u di n g , b ut n ot li mite d t o, laser/ra diati o n pr oce d ures, 
der mal fillers (area of treat me nt s h o ul d be i n dicate d), X- r a ys, s ur geries, ot her facial 
pr oce d ures, a n d t o ot h e xtracti o ns.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 2 of 7 1
5. 4. 3
Rec or di n g
Pre vi o us a n d c o nc o mita nt t hera pies are t o be rec or de d i n t he s u bject’s s o urce d oc u me nts a n d e C R Fs.
C o nc o mita nt t hera pies are t o be re vie we d at eac h visit a n d u p date d i n t he s o urce d oc u me nts a n d 
e C R Fs as nee de d . 
A n y  ne w c o nc o mita nt t hera py or m o dificati o n of a n e xisti n g thera p y ma y be li n ke d t o a n A E. A 
c orres p o n di n g A E for m s h o ul d be c o m plete d t o acc o u nt f or t he c ha n ge i n t hera py, e xce pt i n s o me 
cases s uc h as t hera p y use d f or pr o p h yl a xis, d ose m o dificati o n f or a c hr o nic c o n diti o n, etc.
5. 4. 4
A ut h orize d C o nc o mit a nt T her a pies
U nless liste d bel o w u n der pr o hi b ite d c o nc o mita nt t hera pies (Secti o n 5. 4. 5 ), all c o nc o mita nt 
t hera pies are a ut h orize d.
5. 4. 5
Pr o hi bite d C o nc o mit a n t T her a pies
T he f oll o wi n g t hera pies are pr o hi bite d si nce t he y ma y interfere wit h t he efficac y an d/ or safety 
assess me nt of t he st u d y pr o d uct s:

B o N T of a n y  ser oty p e.

A n y  ot her i n vesti gati o nal ne w dr u g or de vice.

A n y  a bs or ba ble (te m p orar y) or n o n-a bs or ba ble (per ma ne nt) material i n t he treat me nt area.

Facial aest hetic pr oce d ures (e. g., a blati ve s ki n res urfaci n g, laser treat me nt, micr o nee dli n g , 
p h ot o d y na mic t hera p y, tatt o oi n g or c he mical peel) or a n y ot her pr oce d ures i n t he treat me nt
area.

F acial s ur ger y or e ye s ur ger y (i ncl u di n g L A SI K pr oce d ure).

Me dicati o ns t hat affect ne ur o m usc ular tra ns missi o n s uc h as c urare -li ke de p olarizi n g a ge nts, 
li nc osa mi des, p ol ym y xi ns, a ntic h oli nesterases a n d a mi n o gl yc osi de a nti bi otics.
If a pr o hi bite d t hera p y is necessar y f or t he best cli nical i nterest of t he s u bject or d ue t o safety reas o ns, 
t he Me dical M o nit or
s h o ul d be n otifie d , if ti me per mits, t o disc uss p ossi ble alter nati ves pri or t o 
a d mi nistrati o n of a pr o hi bite d t hera p y ( c o ntact i nf or mati o n f or t he Me dical M o nit or pr o vi de d i n t he 
I n vesti gat or’s site file).
If a s u bject recei ves a pr o hi bite d t hera py d ur i n g t he cli nical st u d y, t he Me dical M o nit or
s h o ul d be 
n otifie d t o disc uss t he s u bject’s c o nti n uati o n i n t he cli nical st u d y (c o ntact i nf or mati o n f or t he 
Me dical M o nit or pr o vi de d i n t he I nvesti gat or’s site file). If p ossi ble, the s u bject s h o ul d c o nti n ue i n 
t he st u d y f or t he sc he d ule d f oll o w-u p visits.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 3 of 7 1
5. 5
Pr oce d ures/ Re as o ns f or S u bject D isc o nti n u ati o n
A n I n vesti gat or m a y  deci de t o disc o nti n ue a s u bject fr o m t he cli nical st u d y f or me dical or safety 
reas o ns.
Alt h o u g h t he i m p orta nce of c o m pleti n g t he e ntire cli nical st u d y s h o ul d be e x plai ne d t o t he s u bject 
b y  t he cli nical st u d y pers o n nel, a n y  s u bject is free t o disc o nti n ue partici pati o n i n t his cli nical st u d y
at a n y ti me a n d f or w hate ver reas o n, s pecifie d or u ns pecifie d, a n d wit h o ut a n y prej u dice. N o 
c o nstrai nts are t o be i m p ose d o n t he s u bject, a n d w he n a p pr o priate, a s u bject m a y  be treate d wit h 
ot her c o n v e nti o nal t hera p y w he n cli nically i n dicate d. 
W he n a s u bject d oes n ot c o m plete t he cli nical st u d y, s/he will be f ull y  assesse d if s uc h assess me nt 
is p ossi ble. T he pr oce d ures desi g nate d f or t he M o nt h
1 ( p o w der B o N T -A treat me nt gr o u p) or t he 
M o nt h 6 ( All uzie nce treat me nt gr o u p) / Earl y Ter mi nati o n ( E T) visit s h o ul d be c o m plete d f or all 
s u bjects disc o nti n ui n g t he cli nical st u d y a n d t he a p pr o priate e C R F s h o ul d be c o m plete d.
All disc o nti n uati o ns a n d t he reas o n f or disc o nti n uati o n are t o be d oc u me nte d b y t he I n vesti gat or o n 
t he e C R F e xit for m. F or disc o nti n uati o n d ue t o a n A E, t he A E for m is t o be c o m plete d. T he 
I n vesti gat or s h o ul d als o e ns ure t hat t he s u bject recei ves s uita ble t hera py f or t he A E.
P ote ntial reas o ns f or disc o nti n uati o n are liste d bel o w:

A d verse E ve nt:
C o m plete a n A E f or m.

Wit h dra wal b y  
S u bject:
I ncl u des c o nse nt wit h dra wal, s u bject rel ocati o n, sc he d ule c o nflicts, etc.  
E x plai n t he reas o n f or wit h dra wal i n t he c o m me nt secti o n of t he e C R F
exit f or m.

L ost t o 
F oll o w - u p:
C o nfir me d b y  e. g., calli n g t hree ti mes at differe nt h o urs a n d lea vi n g
messa ges , if a p plica ble, bef ore declari n g t he s u bject l ost t o f oll o w- u p. 
E x plai n i n t he c o m me nt secti o n of t he e C R F exit f or m.

Ot her:
T his cate g or y is t o be use d f or a s u bject w h o disc o nti n ues d ue t o a 
reas o n ot her t ha n as s pecifie d i n t he pre defi ne d cate g ories a b o ve.  
E x plai n t he reas o n f or disc o nti n uati o n i n t he c o m me nt secti o n of t he 
e C R F exit f or m.
A s u bject w h o has bee n ra n d o mize d a n d assi g ne d a kit n u m ber/ra n d o mizati o n n u m ber ca n n ot be 
re place d b y  an ot her s u bject if he/s he disc o nti n ues t he cli nical st u d y f or a n y reas o n. A d diti o nal 
s u bjects m a y
be e nr olle d (ra n d o mize d/assi g ne d t o treat me nt) i n or der t o attai n t he n u m ber of 
e val ua ble s u bjects. U n der n o circ u msta nces s hall s u bjects be e nr olle d m ore t ha n o nce.
Pre g na n cies occ urri n g d uri n g t he scree ni n g peri o d are c o nsi dere d scree n fail ures; t he y sh o ul d be 
rec or de d as s uc h i n t he e C R F a n d n o pre g na nc y f or m is t o be c o m plete d.
F or a pre g na nc y  occ urri n g after t he scree ni n g peri o d , f oll o w t he pr oce d ures descri be d i n 
Secti o n 7. 2. 1. 2. 3 . T he s u bject m a y  re mai n i n t he st u d y, b ut n o i n vasi ve pr oce d ure s h o ul d be 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 4 of 7 1
c o n d ucted. T he S p o ns or m a y  als o deci de t o pre mat urel y ter mi nate or s us pe n d a s u bject’s 
partici pati o n i n t he cli nical st u d y.
6.
C LI NI C A L S U P P LI E S
6. 1
Cli nic al S u p pl y I de ntific ati o n a n d U se
At t he baseli ne visit, eac h s u bject will recei ve a si n gle treat me nt di vi de d e q uall y  a m o n g 5 i njecti o n 
p oi nts ( 0. 1 m L  per i njecti o n p oi nt) i n t he gla bellar re gi o n wit h eit her All uzie nce or p o w der B o N T - A
acc or di n g t o his or her ra n d o mizati o n assi g n me nt. F or details re gar di n g t he treat me nt pr oce d ure, 
refer t o Secti o n 6. 1. 7. 1 .
6. 1. 1
All uzie nce
T he i n vesti gati o nal pr o d uct All uzie nce will be s u p plie d as a li q ui d i n a vial c o ntai ni n g 1 2 5 s.U of 
All uzie nce at a c o nce ntrati o n of 2 0 0 U/ m L . T he dr u g pr o d uct s h o ul d be st ore d at t he rec o m me n de d 
te m perat ure ( bet wee n + 2° C a n d + 8° C) s h o ul d n ot be fr oze n. Kee p vials i n t he o uter cart o n i n or der 
t o pr otect fr o m li g ht. Eac h vial c o ntai ns 0. 6 2 5 m L of d eli vera ble v ol u me of s ol uti o n. A v ol u me of 
0. 2 5 m L, c o ntai ni n g 5 0 s.U of All uzie nce, will be wit h dra w n fr o m t he vial i nt o a s yri n ge f or s u bject 
a d mi nistrati o n.
Details of t he dr u g c o m p ositi o n a n d e xci pie nts are pr o vi de d i n t he c urre nt S m P C f or All uzie nce 1 6.5 9
6. 1. 2
P o w der B o N T - A
T he refere nce pr o d uct o na b ot uli n u mt o xi n A / p o w der B o N T - A will be s u p plie d i n a sterile vial 
c o ntai ni n g 5 0 U of vac u u m -drie d B o N T T y pe A . T he dr u g c o m p ositi o n , a n d h o w t o rec o nstit ute t he 
refere nce pr o d uct bef ore i njecti o n, is pr o vi de d i n t he S m P C 1 7.
T he u n o pe ne d vial a n d rec o nstit ute d s ol uti o n s h o ul d be st ore d at t he rec o m me n de d te m perat ure 
( bet wee n + 2° C a n d + 8° C). T he refere nce pr o d uct s h o ul d n ot be fr oze n.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 5 of 7 1
6. 1. 3
St u d y Pr o d uct s Descri pti o n
T a ble 5
Descri pti o n a n d U s a ge of t he S t u d y Pr o d ucts
I n vesti g ati o n al pr o d uct
Refere nce pr o d uct
N a me of dr u g s u bst a nce 
A b o b ot uli n u mt o xi n A
O na b ot uli n u mt o xi n A
N a me of i n vesti g ati o n al 
pr o d uct / refere nce pr o d uct 
All uzie nce
B O T O X ®/ Vista bel ®
P h ar m ace utic al f o r m
S ol uti o n f or i njecti o n
Vac u u m -drie d p o w der
C o nce ntr ati o n
2 0 0 s.U/ m L, eac h vial c o ntai ns 1 2 5 s. U i n 
0. 6 2 5 m L of s ol uti o n rea d y f or use,
1 0 U/ 0, 0 5 m L per i njecti o n p oi nt
5 0 U/ vial
Dil ute d i n 0. 9 % s o di u m c hl ori de bef ore 
use t o 4 U/ 0. 1 m L per i njecti o n p oi nt
B uffer c o m p ositi o n
N/ A
P ac k a gi n g
Glass vial
Glass vial
Rec o nstit uti o n
N/ A
1. 2 5 m L ( 0. 9 % Na Cl s ol uti o n )
St or a ge c o n diti o ns
2- 8º C 
2- 8º C 
D os a ge
5 0 s.U
0. 2 5 m L t otal
0. 0 5 m L per i njecti o n p oi nt
2 0 U
0. 5 m L t otal
0. 1 m L per i njecti o n p oi nt
R o ute
I ntra m usc ular i njecti o n
I ntra m usc ular i njecti o n
D ose re gi me n 
Si n gle treat me nt at baseli ne visit 
Si n gle treat me nt at baseli ne visit
L oc ati o n of tre ate d are a
Gla bellar re gi o n
Gla bellar re gi o n
6. 1. 4
S u bject I de ntific ati o n N u m ber 
Eac h st u d y partici pa nt w h o has si g ne d t he I C F will be assi g ne d a scree ni n g n u m ber d uri n g t he 
scree ni n g visit. U p o n ra n d o mizati o n, a s u bject is c o nsi dere d e nr olle d a n d will be assi g ne d a s u bject 
n u m ber w hic h will be use d f or t he d urati o n of t he st u d y for all d oc u me ntati o n a n d disc ussi o n. T he 
s u bject n u m bers s hall be all ocate d i n asce n di n g se q ue ntial or der f or eac h st u d y site. If a s u bject is 
dee me d i neli gi ble f or st u d y partici pati o n, t he reas o n f or scree n fail ure s h o ul d be s pecifie d. A scree n 
fail ure ca n n ot be re -scree ne d.
A l o g/listi n g s h o ul d be mai ntai ne d b y  eac h site f or all s u bjects w h o ha ve si g ne d t he I CF. T here 
s h o ul d be sufficie nt i nf or mati o n t o li n k t he e C R F t o a st u d y su bject’s so urce d oc u me nts a n d me dical 
rec or ds.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 3 6 of 7 1
6. 1. 5
Met h o d of T re at me nt A ssi g n me nt
Bef ore starti n g t he st u d y, a ra n d o mizati o n list stratifie d b y  st u d y site will be ge nerate d b y  a 
statisticia n i n de pe n de nt fr o m t he st u dy. W he n t he I n vesti gat or has c o nfir me d s u bject eli gi bilit y, t he
s u bject will be all ocate d a st u d y pr o d uct wit hi n t he electr o nic we b res p o nse s yste m. 
6. 1. 6  
R a n d o miz ati o n N u m ber
Eli gi ble s u bjects will be all ocate d a ra n d o mizati o n n u m ber a n d w hic h treat me nt t o gi ve t he s u bject 
wit hi n t he electr o nic we b res p o nse s yste m (e. g. t he e C R F). T he ra n d o mizati o n n u m ber will n ot be 
pre -pri nte d o n t he st u d y pr o d uct, h o we ver, t he vial use d f or t he treat me nt will ha ve t o be mar ke d 
wit h t he s u bject’s ra n d o mizati o n n u m ber f or acc o u nta bilit y  of st u d y pr o d uct.
R a n d o mizati o n n u m ber will be all ocate d i n asce n di n g se q ue ntial or der , wit hi n eac h site, t o eac h 
eli gi ble s u bject.
6. 1. 7
I nstr ucti o ns f or U se a n d A d m i nistr ati o n
I n this st u d y, All uzie nce ( 5 0 s.U) will be c o m pare d t o refere nce pr o d uct p o w der B o N T - A ( 2 0 U)
a d mi nistere d acc or di n g t o eac h pr o d ucts S m P C 1 6 , 1 7.
All uzie nce is s u p plie d as a li q ui d i n a b uffere d s ol uti o n. P o w der B o N T -A is s u p plie d as a w hite a n d 
dr y  su bsta nce t hat is rec o nstit ute d i n sterile Na Cl s ol uti o n (sali ne) bef ore use . F or a descri pti o n of 
t he st u d y pr o d ucts, see Secti o n 6. 1. 3 .
B ot h All uzie nce a n d t he sali ne use d f or rec o nstit uti n g p o w der B o N T -A s h o ul d be all o we d t o 
e q uili brate t o r o o m te m perat ure f or 1 5 - 3 0 mi n bef ore i njecti o n. T he pre parati o n of t he s yri n ge wit h 
All uzie nce a n d t he rec o nstit uti o n of p o w der B o N T -A m ust be perf or me d i n t he sa me r o o m a n d i n 
fr o nt of t he s u bject b y  t he T reati n g I n vesti gat or.
T he i njecti o n pr oce d ure is i de ntical f or b ot h treat me nt gr o u ps . I n a d diti o n t o be i n g trai ne d i n t he 
a d mi nistrati o n tec h ni q ue pri or t o st u d y initiati o n, all T reati n g In vesti gat ors will
nee d t o ha ve 
pre vi o us e x perie nce wit h B o N T - A pr o d ucts f or t he st u die d i ndicati o n .
T he ha n dli n g of acci de ntl y d ama ge d or s pille d st u d y pro d uct s are descri be d i n t he Mater ial Safet y 
Data S heet s.
6. 1. 7. 1
Tre at me nt Pr oce d ure
Pri or t o i njecti o n, t he treat me nt area s h o ul d be clea ne d wit h a s uita ble a ntise ptic s ol uti o n. A n 
a p pr o priatel y size d s yri n ge a n d nee dle s h o ul d be use d t o a d mi nister t he treat me nt. T he nee dle size 
( ga u ge) use d b y t he I n vesti gat or i n t he st u dy s h o ul d be c ollecte d.
Treat me nt of t he gl a bellar re gi o n wit h All uzie nce or p o w der B o N T -A is a d mi nistere d as a n 
i ntra m usc ular i njecti o n, gi ve n as 0. 0 5 m L per i njecti o n p oi nt f or All uzie nce ( 0. 2 5 m L i n t otal), a n d 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 7 of 7 1
gi ve n as 0. 1 m L per i njecti o n p oi nt f or p o w der B o N T -A ( 0. 5 m L i n t otal), usi n g a n a p pr o priatel y 
size d s yri n ge a n d nee dle.
T he 5 i njecti o n sites i ncl u de 2 i njecti o ns i nt o eac h c orr u gat or s u percilii m uscle, a n d 1 i njecti o n i nt o 
t he pr ocer us m uscle. Bef ore i njecti o n, place t he t h u m b or i n de x fi n ger firml y bel o w t he or bital ri m 
i n or der t o pre ve nt e xtra vasati o n bel o w t he or bital ri m. T he nee dle be vel s h o ul d be p oi nte d u p war d 
a n d me diall y  duri n g t he i njecti o n. I n or der t o re d uce t he ris k of pt osis, a v oi d i njecti o ns near t he 
le vat or pal pe brae s u peri oris m uscle, partic ularl y i n patie nts wit h lar ger br o w -de press or c o m ple xes 
( de press or s u percilii). I njecti o ns s h o ul d be ma de i nt o t he ce ntral part of t he c orr u gat or m uscle, at 
least 1 c m a b o ve t he or bital ri m. T he rec o m me n de d i njecti o n p oi nts f or G Ls are s h o w n bel o w i n
Fi g ure 2.
Fi g ure 2
I njecti o n Sites f or Tre ati n g Gl a bell ar Li nes
6. 1. 7. 2
Tre at me nt Re gi me n
Eac h s u bject will recei ve a si n gle treat me nt wit h 5 0 s.U All uzie nce , 2 0 U of p o w der B o N T -A at t he 
baseli ne visit. T he t otal i njecti o n v ol u me f or All uzie nce is 0. 2 5 m L  in 5 i njecti o n p oi nts, i.e. 0. 0 5 m L
( 1 0 s.U) per i njecti o n p oi nt. T he t otal i njecti o n v ol u me f or p o w der B o N T -A is 0. 5 m L i n 5 i njecti o n 
p oi nts, i.e. 0. 1 m L ( 4 U) per i njecti o n p oi nt. 
6. 2
St u d y Pr o d ucts P ac k a gi n g a n d L a beli n g
All uzie nce a n d o na b ot uli n u mt o xi n A are ma n ufact ure d u n der ase ptic c o n diti o ns a n d s u p plie d i n a 
glass vial, cl ose d wit h a r u b ber st o p per a n d seale d wit h a n al u mi n u m o ver seal. T he st u d y pr o d ucts 
s h o ul d be tra ns p orte d a n d st ore d at 2- 8º C (see Ta ble 5 ).
T he la be ls will be pri nte d i n E n glis h a n d/ or l ocal la n g ua ge c o ntai n i n g t he i nf or mati o n re q ueste d b y 
G o o d Ma n ufact uri n g Practice a n d l ocal re g ulati o ns, a n d at a mi ni m u m , will i ncl u de t he p r ot oc ol 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 3 8 of 7 1
n u m ber, st ora ge c o n diti o ns, a n d a n i n vesti gati o nal test article disclai mer (e. g., f or cli nical trial use 
o nl y ).
6. 3
S u p plies M a n a ge me nt
6. 3. 1
Acc o u nt a bilit y
U p o n recei pt of t he st u d y pr o d uct s, t he I n vesti gat or or desi g n ee will mai ntai n acc urate rec or ds of
st u d y pr o d uct deli ver y  to t he cli nical st u d y site, t he i n ve nt or y at t he cli nical st u d y site, t he use b y  
eac h s u bject, t he rec o nciliati o n of all st u d y pr o d uct s recei ve d fr o m t he S p o ns or’s desi g nee, a n d t he 
ret ur n t o t he S p o ns or’s desi g nee for dis p osal of u n use d st u d y  pr o d uct s.
All st u d y  pr o d uct s se nt t o t he In vesti gat or/I nstit uti o n will be acc o u nte d f or a n d n o u na ut h orize d use 
is per mitte d. A Cli nical Researc h Ass ociate ( C R A )/ m o nit or will assess a n d verif y  acc o u nta bilit y of 
t he st u d y pr o d ucts.
6. 3. 2
St or a ge of t he S t u d y Pr o d uct s
T he s t u d y pr o d uct s m ust be st ore d i n a safe a n d sec ure area wit h restricte d access, u n der t he st ora ge 
c o n diti o ns s pecifie d b y  t he S p o ns or (see Ta ble 5 ). T he st ora ge te m perat ure will be rec or de d a n d ke pt 
at t he st u d y site. 
6. 3. 3
Dis pe nsi n g a n d R et ur n 
All st u d y pr o d ucts m ust be i n ve nt orie d a n d a rec or d of t he dis pe nsi n g f or eac h s u bject m ust be 
ap pr o priatel y d oc u me nte d . A n y  dis pe nsi n g err ors m ust be re p orte d t o t he S p o ns or a n d pr o perl y 
d oc u me nte d.
I n t he e ve nt of earl y ter mi nati o n/s us pe nsi o n of t he cli nical st u d y, a ra pi d recall of st u d y pr o d uct s 
will be i nitiate d. 
All use d st u d y pr o d ucts a n d/ or s u p plies will be destr o y e d at t he st u d y site. Destr ucti o n will occ ur 
acc or di n g t o a p plica ble re g ulati o ns a n d t he site’s dr u g destr ucti o n S ta n dar d O perati n g P r oce d ure 
( S O P). U n use d or e x pire d st u d y pr o d uct will be ret ur ne d f or destr ucti o n t o t he S p o ns or 
re prese ntati ve at ti me p oi nts a p pr o ve d by t he S p o ns or.
6. 3. 4
Tre at me nt C o m pli a nce M a n a ge me nt a n d R ec or d
T he treat me nt is a n i njecti o n a d mi nistere d b y  the In vesti gat or. Details of t he i njecti o n pr oce d ure will 
be rec or de d i n t he e C R F a n d s u bject s o urce d oc u me nts . N o ot her meas ure me nts of treat me nt 
c o m plia nce will be ma de.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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5. 0
 
Pri nt date:
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C O N FI D E N TI A L 
Pa ge 3 9 of 7 1
6. 3. 5
D ose M o dific ati o n 
D ose m o dificati o ns are n ot per mitte d.
6. 3. 6
Pr o d uct Q u alit y C o m pl ai nts
Pr o d uct Q ualit y  Co m plai nts ( P Q Cs) s h o ul d be re p orte d usi n g t he e- mail liste d i n t he st u d y 
a d mi nistrati ve str uct ure o n pa ge 3 . A P Q C is a n e xter nal j u d ge me nt pres u mi n g a q ualit y  defect or
q ualit y  iss ue f or a pr o d uct relati n g t o its prese ntati o n or use a n d is i de ntifie d b y  a su bject, 
practiti o ner , I nvesti gat or site pers o n nel, distri b ut or, or a n y o ne else i n v ol ve d i n cli nical s u p plies
ha n dli n g. E xa m ples ma y i ncl u de , b ut are n ot li mite d t o , a p peara nce iss ues, o d or, da ma ge d st o p pers, 
l o w fills, a n d f orei g n matter i n t he pr o d uct. T hese c o m plai nts ma y or m ay n ot re prese nt a p ote ntial 
ris k t o t he s u bject. A P Q C f or m m ust be c o m plete d b y t he st u d y site pers o n nel a n d f or war de d t o t he 
S p o ns or or desi g nee wit hi n 2 4 h o urs of a ware ness. A n y  affecte d st u d y pr o d uct s h o ul d be 
q uara nti ne d, a n d n ot use d, u ntil f urt her n otice b y t he S p o ns or.
A d diti o nal c o ntact details are pr o vi de d i n t he I n vesti gat or’s site file.
6. 4
Bli n di n g
N ot a p plica ble – o pe n -la bel st u d y.
7.
C LI NI C A L S T U D Y A S S E S S M E N T
7. 1
Effic ac y A ssess me nts
7. 1. 1
Rec o nstit uti o n/ Pre p ar ati o n Q uesti o n n aire
T he Rec o nstit uti o n a n d Pre pa rati o n Q uesti o n naire
(A p pe n di x 1 ) s h o ul d be c o m plete d b y  the 
Treati n g I n vesti gat or after t he s u bject has bee n treate d at Visit 2 ( Baseli ne). T he q uesti o n naire is 
di vi de d i nt o t w o treat me nt s pecific parts, o ne f or All uzie nce a n d o ne f or p o w der B o N T -A.
7. 1. 2
I n vesti g at or Tre at me nt Sessi o n Q uesti o n n aire
T he I n vesti gat or Treat me nt Sessi o n Q uesti o n naire (A p pe n di x 2 ) s h o ul d be c o m plete d b y  the 
Treati n g I n vesti gat or after t he s u bject has bee n treate d at Visit 2 ( baseli ne). T he q uesti o n naire s h o ul d 
o nl y  be c o m plete d f or All uzie nce treate d s u bjects.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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5. 0
 
Pri nt date:
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C CI

C O N FI D E N TI A L 
Pa ge 4 0 of 7 1
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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Pri nt date:
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C CI

C O N FI D E N TI A L 
Pa ge 4 1 of 7 1
7. 2
S afet y A ssess me nts
7. 2. 1
A d verse E ve nts ( A E)
A Es are t o be m o nit ore d t hr o u g h o ut t he c o urse of t he cli nical st u d y fr o m treat me nt (see sc he d ule of 
assess me nts i n Ta ble 2 ). All A Es are t o be re p orte d o n t he A E f or m i n t he e C R F wit h c o m plete 
i nf or mati o n as re q uire d. 
If A Es occ ur, t he mai n c o ncer n s hall be t he safety of t he s u bjects. At t he ti me of t he I C F si g nat ure, 
eac h s u bject m ust be pr o vi de d wit h t he na me a n d p h o ne n u m ber of cli nical st u d y site pers o n nel f or 
re p orti n g A Es a n d me dical e mer ge ncies.
At eac h f oll o w-u p visit, t he I nvesti gat or ( or s u b-I n vesti gat or) will q uesti o n t he s u bject a b o ut A Es 
usi n g a n o pe n n o n- pers uasi ve q uesti o n t o elicit re p orti n g of A Es, f or e xa m ple, “ Ha ve y o u n otice d 
a n y c ha n ge i n y o ur healt h si nce t he last visit?” A d diti o nal q uesti o ni n g a n d e xa mi nati o n will t he n be 
perf or me d as a p pr o priate.
7. 2. 1. 1
Defi niti o ns
7. 2. 1. 1. 1
A dverse E ve nts (A E )
Acc or di n g t o I CH E 2 A 1 9, a n A E is a n y unt o war d me dical occ urre nce i n a patie nt or a cli nical 
i n vesti gati o n s u bject a d mi nistere d a p har mace utical pr o d uct a n d w hic h d oes n ot necessaril y ha ve a 
ca usal relati o ns hi p wit h t his treat me nt. A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n 
(i ncl u di n g a n a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease te m p orall y ass ociate d wit h t he use 
of a me dici nal (i n vesti gati onal) pr o d uct, w het her or n ot relate d t o t he me dici nal (in vesti gati o nal) 
pr o d uct.
T h us, a n y  ne w si g n, sy m pt o m or disease, or a n y cli nicall y si g nifica nt w orse ni n g o f a n e xisti n g si g n, 
s ym pt o m or disease (i ncl u di n g ne w e pis o des of a c hr o nic disease [e. g., h a y fe ver, aller g y]) c o m pare d 
t o t he c o n diti o n at t he first visit, s h o ul d be c o nsi dere d a n A E. Lac k of efficac y  is n ot c o nsi dere d a n 
A E.
N otes:

T here s h o ul d be a n atte m pt t o re p ort a dia g n osis rat her t ha n t he si g ns, s y m pt o ms or a b n or mal 
la b orat or y val ues ass ociate d wit h t he re p ort of a n A E. H o we ver, a dia g n osis s h o ul d be re p orte d 
o nl y  if, i n t he In vesti gat or’s j u d g me nt, it is relati vel y  certai n. Ot her wise, s y m pt o ms, si g ns, or 
la b orat or y val ues s h o ul d be use d t o descri be t he A E.

Pre g n a nc y is n ot t o be c o nsi dere d a n A E; h o we ver, it is a n i m p orta nt me dical e ve nt t hat m ust 
be m o nit ore d as descri be d i n Secti o n 7. 2. 1. 2. 3 .
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI

C O N FI D E N TI A L 
Pa ge 4 2 of 7 1

T he effects of all B o N T pr o d ucts ma y  s prea d fr o m t he area of i njecti o n t o pr o d uce sy m pt o ms 
c o nsiste nt wit h B o N T effects. T hese s ym pt o ms ha ve bee n re p orte d h o urs t o wee ks after 
i njecti o n. Re m ote s prea d of t o xi n t hat affects s wall o wi n g a n d breat hi n g ca n be life t hreate ni n g, 
a n d t here ha ve bee n re p orts of deat h. T he ris k of s y m pt o ms is i ncrease d i n s u bjects w h o ha ve 
u n derl y i n g c o n diti o ns (e. g., dis or ders of t he ne ur o m usc ular j u ncti o n) t hat w o ul d pre dis p ose 
t he m t o t hese sy m pt o ms. B o N T is c o ntrai n dicate d i n i n di vi d uals wit h k n o w n h y perse nsiti vit y 
t o a n y B o N T pre parati o n or t o a n y of t he c o m p o ne nts i n t he f or m ulati o n. 
7. 2. 1. 1. 2
Tre at me nt E mer ge nt A dverse Eve nt ( T E A E)
A T E A E is a n e ve nt t hat e mer ges d uri n g or after treat me nt, ha vi n g bee n a bse nt pre -treat me nt, or 
w orse ns relati ve t o t he pre- treat me nt state.
7. 2. 1. 1. 3
Seri o us A dverse E ve nts ( S A E)
A S A E is a n y u nt o war d me dical occ urre nce t hat at a n y  d ose:

Res ults i n deat h,

Is life-t hreate ni n g,

Re q uires i n - patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n,

Res ults i n persiste nt or si g nifica nt disa bilit y /i nca pacit y

Is a c o n ge nital a n o maly/ birt h defect , or

I m p orta nt me dical e ve nts t hat ma y  not res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n ma y  be c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical j u d g me nt, 
t he y ma y je o par dize t he safety o f t he s u bject, a n d ma y  re q uire me dical or s ur gical i nter ve nti o n 
t o pre ve nt o ne of t he o utc omes liste d i n t his defi niti o n. E xa m ples of s u c h e ve nts are i nte nsi ve 
treat me nt i n a n e mer ge nc y ro o m or at h o me f or aller gic br o nc h os pas m, bl o o d d y scrasia, or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n.
N ote: T he ter m “life-t hreate ni n g” refers t o a n e ve nt i n w hic h t he s u bject was at ris k of deat h at t he 
ti me of t he e ve nt; it d oes n ot refer t o a n e ve nt w hic h h y p ot heticall y mi g ht ha ve ca use d deat h if it 
were m ore se vere.
If t he s u bject has ha d t o sta y for a ni g ht i n t he h os pital , i n-patie nt h os pitalizati o n is c o nsi dere d t o 
ha ve occ urre d . T he criteri o n f or pr ol o n gati o n of h os pitalizati o n is als o defi ne d as an e xtra ni g ht at 
t he h os pital. H os pitalizati o n ma y  not c o nstit ute s ufficie nt gr o u n ds t o be c o nsi dere d as a n S A E if it 
is s olel y for t he p ur p ose of dia g n ostic test(s) (e ve n if relate d t o a n A E), electi ve h os pitalizati o n f or 
a n i nter ve nti o n t hat was alrea d y pla n ne d bef ore s u bject e nr ol me nt i n t he cli nical st u d y, a d missi o n 
t o a da y -care facilit y, s ocial a d missi o n (e. g., if t he s u bject has n o place t o slee p), or a d mi nistrati ve 
a d missi o n (e. g., f or a y earl y e xa mi nati o n).
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
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C O N FI D E N TI A L 
Pa ge 4 3 of 7 1
7. 2. 1. 1. 4
U nex pecte d A dverse D r u g R e acti o n
A n u ne x pecte d a d verse dr u g reacti o n is defi ne d as a n a d verse reacti o n, t he nat ure or se verity of 
w hic h is n ot c o nsiste nt wit h t he a p plica ble st u d y  pr o d uct i nf or mati o n (e. g., S m P C ).
7. 2. 1. 1. 5
A dverse E ve nt ( A E) R e porti n g P eri o d
T he cli nical st u d y peri o d d uri n g w hic h A Es m ust be re p orte d is t he peri o d fr o m w he n t he s u bject is 
treate d wit h st u dy pr o d uct t o t he e n d of t he s u bject’s partici pati o n.
T he S p o ns or s h o ul d be i nf or me d if t he I n vesti gat or bec o mes a ware of a n y u n us ual safet y 
i nf or mati o n or a n y safet y inf or mati o n t hat a p pears t o be dr u g -relate d i n v ol vi n g a s u bject w h o has 
partici pate d i n a cli nical st u d y, e ve n after a s u bject has c o m plete d t he cli nical st u d y.  
7. 2. 1. 1. 6
Severity
Se verit y  is a cli nical deter mi nati o n of t he i nte nsit y of a n A E a n d n ot t he se verit y of a disease.
T he I n vesti gat or is t o classif y t he i nte nsit y of A Es usi n g t he f oll o win g defi niti o ns as a g ui deli ne. F or 
t his classificati o n, t he I nvesti gat or will ta ke i nt o acc o u nt t he p ossi ble ra n ge of t he i nte nsity of t he 
e ve nt a n d re p ort t he gra de of i nte nsit y whic h is m ost a p pr o priate acc or di n g t o his / her me dical 
j u d g me nt.
Mil d
A ware ness of si g ns or s y m pt o m, b ut easil y  t olerate d.
M o der ate
Disc o mf ort, e n o u g h t o ca use i nte rfere nce wit h us ual acti vit y.
Se vere
I nca pacitati n g wit h i na bilit y t o w or k or perf or m us ual acti vit y.
7. 2. 1. 1. 7
Rel ati o ns hi p t o t he S t u dy Pr o d uct a n d/ or C li nic al St u dy P r oce d ure
T he I nvesti gat or is t o deter mi ne w het her t here is a reas o na ble ca usal relati o ns hi p bet wee n t he 
occ urre nce of t he A E a n d e x p os ure t o t he st u d y  pr o d uct a n d/ or cli nical st u d y pr oce d ure .
Me dical j u d g me nt s h o ul d be use d t o deter mi ne t he relati o ns hi p, c o nsi deri n g all rele va nt fact ors 
i ncl u di n g t he patter n of reacti o n, te m p oral relati o ns hi ps, rele va nt me dical hist or y, a n d c o nf o u n di n g 
fact ors s uc h as c o-me dicati o n or c o nc urre nt diseases.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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Pri nt date:
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C O N FI D E N TI A L 
Pa ge 4 4 of 7 1
T he e x pressi o n “reas o na ble ca usal relati o ns hi p” is mea nt t o c o n ve y  i n ge neral t hat t here are facts or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p (I C H E 2 A, Secti o n III A 1).
T he relati o ns hi p assess me nt f or a n A E is t o be c o m plete d usi n g t he f oll o wi n g defi niti o ns as a 
g ui deli ne:
Re as o n a ble P ossi bilit y: Acc or di n g t o t he re p orti n g I n vesti gat or, t here is a reas o na ble p ossi bilit y  
(i.e., s u g gesti ve e vi de nce or ar g u me nts) t hat t here is a ca usal relati o ns hi p irres pecti ve of t he d ose 
a d mi nistere d bet wee n:

T he st u d y  pr o d uct a n d t he A E .

T he cli nical st u d y pr ot oc ol pr oce d ure (e. g., br uisi n g or mar ks fr o m bl o o d dra ws, i njecti o n 
relate d tra u ma, etc.) a n d t he A E .
A t w o -p oi nt scale ( Yes or N o res p o nse) s hall be use d f or t he ca usalit y assess me nt. T he I n vesti gat or 
s hall be as ke d t o i n dicate a res p o nse t o eac h of t he f oll o wi n g q uesti o ns i n t he e C R F:

“ D o y o u c o nsi der t hat t here is a reas o na ble p ossi bilit y that t he e ve nt ma y ha ve be e n ca use d b y 
t he st u d y pr o d uct?”, a n d 

“ D o y o u c o nsi der t hat t here is a reas o na ble p ossi bilit y that t he e ve nt ma y ha ve bee n ca use d b y 
t he st u d y pr o d uct i njecti o n pr oce d ure?”
If t he a ns wer is “ Yes” t o eit her of t hese q uesti o ns, t he A E is c o nsi dere d relate d.
N o Re as o n a ble P ossi bilit y: N o s u g gesti ve e vi de nce or ar g u me nts ca n be i de ntifie d re gar di n g a 
ca usal relati o ns hi p bet wee n t he st u d y  pr o d uct or t he cli nical st u d y pr ot oc ol pr oce d ure a n d t he A E.
7. 2. 1. 2
Re p orti n g P r oce d ures
7. 2. 1. 2. 1
Pr oce d ures f or R e p orti n g A dverse Eve nts (A E)
T he c ollecti o n of A Es is fr o m t he ti me t hat a s u bject is treate d t o t he e n d of t he s u bject’s 
partici pati o n .
At eac h f oll o w- u p visit, t he I nvesti gat or ( or s u b-I n vesti gat or) will q uesti o n t he s u bject a b o ut A Es 
usi n g a n o pe n n o n- pers uasi ve q uesti o n t o elicit re p orti n g of A Es, f or e xa m ple, “ Ha ve y o u n otice d 
a n y cha n ge i n y o u r healt h si nce t he last visit?”. Directe d q uesti o ni n g a n d e xa mi nati o n will t he n be 
perf or me d as a p pr o priate. 
A n y  A E occ urri n g d uri n g t he A E re p orti n g peri o d, w het her it is relate d t o t he st u d y pr o d uct or n ot, 
will be rec or de d i m me diatel y in t he s o urce d oc u me nt, a n d descri be d o n t he A E f or m i n t he e C R F
al o n g wit h t he date of o nset, se verit y , relati o ns hi p t o t he stu d y  pr o d uct , acti o n ta ke n, a n d o utc o me, 
wit h o ut o mitti n g a n y req ueste d a n d k n o w n i nf or mati o n. A d diti o nal i nf or mati o n will be re q uested 
u n der certai n circ u msta nces. 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
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Pri nt date:
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C O N FI D E N TI A L 
Pa ge 4 5 of 7 1
At st u d y en d, A Es assesse d as relate d t o t he treat me nt or st u d y pr oce d ure will be m o nit ore d u ntil 
t he y are res ol ve d or ha ve reac he d a sta ble c o n diti o n. Ot her A Es will be m o nit ore d u ntil t he last visit 
if t he y are n ot res ol ve d or sta ble. 
T he I n vesti gat or will mai ntai n all perti ne nt me dical rec or ds i n t he s u bject’s st u d y file. If necessar y
a n d a ppr o ve d b y  th e s u bject or t heir le gal healt h care re prese ntati ve, t he I n vesti gat or m a y c o ntact t he 
s u bject’s pers o nal p h ysicia n or ot her healt h care pr o vi der(s) t o o btai n f urt her details.
F or S A Es (see Secti o n 7. 2. 1. 2. 2 ) a n d pre g na ncies (see Secti o n 7. 2. 1. 2. 3 ), t he S p o ns or is t o be 
inf or me d i m me diatel y by e-mail. T he e ve nt m ust be re p orte d t o t he Safet y e-mail wit hi n 2 4 h o urs 
of recei pt of t he i nf or mati o n (c o ntact details i n Secti o n 7. 2. 1. 2. 2 ).
7. 2. 1. 2. 2
Pr oce d ure f or R e p orti n g a Seri o us A dverse Eve nt ( S A E)
F or a n S A E occ urri n g d uri n g t he cli nical st u d y, re gar dless of w het her it is related t o t he treat me nt 
or n ot, a n d w het her it i s e x pecte d or n ot, t he I n vesti gat or m ust d o t he f oll o wi n g:
1.
Ta ke pr o m pt a n d a p pr o priate me dical acti o n, if necessar y. T he safet y of t he s u bject is t he first 
pri orit y .
2. 
E ns ure t hat t he e ve nt is classifie d as a n S A E ( Secti o n 7. 2. 1. 1. 3 ).
3.
C o m plete t he A E f or m pr o vi de d i n t he e C R F as full y  as p ossi ble.
Pri nt a n d c o m plete t he S A E f or m. T he c o m plete d f or m, acc o m pa nie d b y  an y  ot her rele va nt 
i nf or mati o n or a n o n ymize d me dical rec or ds (e. g., la b orat or y test res ults), is se nt wit hi n 
2 4 h o urs of recei pt of t he i nf or mati o n t o t he Safet y  e-mail
liste d bel o w . T he de m o gra p hics, 
me dical hist or y , dr u gs /thera pies f or m, me dical a n d s ur gical pr oce d ures f or m, a n d A E pa ges 
of t he e C R F m ust be c o m plete d a n d a vaila ble f or re vie w i n t he electr o nic d ata ca pt ure ( E D C) 
s yste m at t he ti me of t he re p ort.
4.
I m me diatel y se n d t he c o m plete d S A E re p ort f or m t o t he Safet y  e-mail a n d disc uss f urt her 
acti o ns t o be ta ke n.
E- mail: dr u gsafet y p v @a d va nce dcli nical. c o m
A d diti o nal c o ntact details are pr o vi de d i n t he I n vesti gat or’s site file.
5.
M o nit or a n d rec or d t he pr o gress of t he e ve nt u ntil it is res ol ve d or has reac he d a cli nicall y 
sta ble o utc o me, wit h or wit h o ut se q uelae. F or all a d diti o nal f oll o w- u p e val uati o ns, se n d all 
f oll o w- u p i nf or mati o n a b o ut t he S A E t o t he Safet y  e-mail
wit hi n 2 4 h o urs of receipt of t he 
u p date d i nf or mati o n. S A Es will be m o nit ore d u ntil t he I n vesti gat or a n d S p o ns or a gree t hat t he 
e ve nt is satisfact oril y res ol ve d.
6.
O btai n a n d m ai ntai n all perti ne nt me dical rec or ds a n d i nf or mati o n re gar di n g t he S A E i n t he 
s u bject’s st u d y file.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 4 6 of 7 1
7.
I nf or m t he S p o ns or of t he fi nal o utc o me of t he e ve nt. Se n d a f oll o w- u p S A E f or m, w he n
a p pr o priate, t o t he Safety e-mail .
8.
Pr o m pt n otificati o n of S A Es b y t he In vesti gat or t o t he S p o ns or is esse ntial t o e ns ure t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities are met re gar di n g t he safety of t he s u bjects. T he 
S p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y ( R A) a n d ot her 
re g ulat or y age ncies a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n. T he S p o ns or
will c o m pl y  wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g t o R as, 
I n de pe n de nt Et hics C o m mittees (IE C s), a n d In vesti gat ors. I nvesti gat or safety re p orts are 
pre pare d f or S us pecte d U ne x pecte d Seri o us A d verse Reacti o ns ( S U S A Rs) acc or di n g t o l ocal 
re g ulat or y re q uire me nts a n d t he S p o ns or ’s p olic y , a n d are f or war de d t o In vesti gat ors as 
necessar y . A n In vesti gat or w h o recei ves a n In vesti gat or safety re p ort descri bi n g S A E(s) or 
ot her s pecific safet y i nf or mati o n (e. g., s u m mar y or listi n g of S A Es) fr o m t he S p o ns or will file 
it wit h t he In vesti gat ors Br oc h ure a n d will n otif y t he IE C , if a p pr o priate, acc or di n g t o l ocal 
re q uire me nts.
9.
C o m pl y  with t he a p plica ble re g ulat or y  re q uire me nt(s) relate d t o t he re p orti n g of S A Es t o t he 
IE C .
7. 2. 1. 2. 3
Pr oce d ures f or R e p orti n g P re g n a ncies
A n y  pre g na nc y occ urri n g d uri n g t he cli nical st u dy, w here t he fet us c o ul d ha ve bee n e x p ose d t o st u d y 
pr o d uct , m ust be m o nit ore d u ntil its o utc o me i n or der t o e ns ure t he c o m plete c ollecti o n of safety 
data.
S u bjects w h o ha ve a p ositi ve pre g na nc y  test d uri n g t he scree ni n g peri o d are c o nsi dere d scree n 
fail ures a n d are rec or de d as s uc h i n t he e C R F, a n d n o pre g na nc y f or m is t o be c o m plete d.
If a s u bject bec o mes pre g na nt after recei vi n g st u d y me dicati o n , t he I nvesti gat or is t o d o t he 
f oll o wi n g:
1.
T he s u bject d oes n ot nee d t o be wit h dra w n fr o m t he cli nical st u d y, i.e., s he m a y  co nti n ue t o 
atte n d t he pla n ne d st u d y visits, b ut n o i n vasi ve pr oce d ure s h o ul d be c o n d ucte d (e. g., n o sa m ple
s h o ul d be ta ke n f or la b testi n g).
2.
C o m plete t he Pre g na nc y  Re p ort Part A as f ull y as p ossi ble. S e n d t he f or m wit hi n 2 4 h o urs of 
recei pt of t he i nf or mati o n t o t he Safet y  e-mail (liste d i n Secti o n 7. 2. 1. 2. 2 ).
3.
M o nit or a n d rec or d t he pr o g ress of t he pre g na nc y  until its o utc o me. If necessar y  a n d a p pr o ve d 
b y  th e s u bject or t heir le gal healt h care re prese ntati ve, c o ntact t he s u bject’s re g ular p h y sicia n
( ge neral practiti o ner or g y nec ol o gist ) or h os pital staff t o o btai n f urt her det ails a n d as k f or 
re g ular f oll o w-u p i nf or mati o n.
4.
At t he o utc o me of t he pre g na nc y , c o m plete t he Pre g na nc y  Re p ort Part B. F or all a d diti o nal 
e val uati o ns, se n d t he f oll o w-u p i nf or mati o n t o t he Safet y e-mail wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n. If t he s u bject ca n n o l o n ger be reac he d (l ost t o f oll o w-u p), d oc u me ntati o n of 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 4 7 of 7 1
t he n o n -res p o nse/atte m pte d c o ntact c o nsisti n g of , e. g. calli n g t hree ti mes at differe nt h o urs 
an d lea v i n g messa ges , is re q uire d.
5.
If t he pre g na nc y  lea ds t o a n a b orti o n (electi ve a b orti o n, s p o nta ne o us a b orti o n or t hera pe utic 
a b orti o n), i n uter o deat h or c o n ge nital a n o mal y, f oll o w t he pr oce d ure f or declarati o n of a n 
S A E (see Secti o n 7. 2. 1. 2. 2 ).
7. 3
Ot her Assess me nts
7. 3. 1
P h ot o gr a p h y
Sta n dar dize d di gital p h ot o gra p hs will be ta ke n of t he s u bject’s gla bellar re gi o n a n d t he f ull face at 
Visit 2 ( baseli ne , pri or t o treat me nt) , Visit 3, 4 a n d 6 .
Eac h In vesti gat or ( or desi g nee) will ta ke p h ot o gra p hs usi n g t he site’s ca mera e q ui p me nt, c o n diti o ns, 
a n d setti n gs. Detaile d i nstr ucti o ns f or p h ot o gra p h y  will be pr o vi de d i n a se parate p h ot o gra p h y 
ma n ual.
7. 3. 2
Pre g n a nc y Test
F or fe males of c hil d beari n g p ote ntial , a uri ne pre g na nc y test will be perf or me d pri or t o treat me nt at 
scree ni n g a n d baseli ne ( pri or t o treat me nt). A ne gati ve pre g na nc y  test is re q uire d f or st u d y incl usi o n. 
T he res ult will be d oc u me nte d. Pre g na ncies d uri n g t he st u d y sh o ul d be re p orte d as descr i be d i n 
Secti o n 7. 2. 1. 2. 3.
7. 4
A p pr o pri ate ness of M e as ure me nts
T he t ype of efficac y an d safety meas ure me nts
c h ose n f or t his st u d y ha ve bee n use d i n pre vi o us 
cli nical st u dies a n d are c onsi dere d t o be a de q uate meas ure me nts t hat are wi del y
rec o g nize d as 
relia ble, acc urate, a n d rele va nt f or t he tar get i n dicati o n a n d st u d y o bjecti ve.
8.
C LI NI C A L S T U D Y VI SI T S D E S C RI P TI O N S A N D P R O C E D U R E S
8. 1
Descri pti o n of C li nic al St u d y V isits
F or a n o ver vie w of t he sc he d ule of assess me nts f or eac h st u d y  visit, please refer t o Ta ble 2 .
A writte n, si g ne d I CF m ust be o btai ne d pri or t o perf or mi n g a n y cli nical st u d y-relate d e val uati o ns 
a n d/ or pr oce d ures. T he s u bject m ust be pr o vi de d wit h a f ull y co m plete d, date d a n d si g ne d c o p y of 
t he IC F .
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 4 8 of 7 1
8. 1. 1
Scree ni n g , Visit 1 (D a y -2 1 t o D a y 0)
T he scree ni n g a n d baseli ne visits m a y  be perf or me d o n t he sa me d a y ; h o we ver, a ma xi m u m of 
2 1 da y s is all o we d bet wee n t he scree ni n g a n d baseli ne visits. 
At t he scree ni n g visit, t he I n vesti gat or or desi g nee will:
1.
Re vie w a n d e x plai n t he nat ure of t he st u d y t o t he s u bject , partic ularl y t he pr o hi bite d acti vities 
a n d c o nstrai nts (e. g., restricti o ns f or ot her aest hetic treat me nts a n d t he use of t o pical a n d 
s yste mic me dicati o ns, see Secti o n 5. 4. 5 ).
2.
O btai n t he si g ne d a n d date d I CF , a n d pr o vi de t he s u bject wit h a f ully c o m plete d, date d a n d 
si g ne d c o py of t he I C F .
3.
C ollect i nf or mati o n re gar di n g de m o gra p hics (i.e., date of birt h, ge n der, race, et h nicit y, hei g ht, 
a n d 
wei g ht) ,
rele va nt me dical 
hist or y
a n d
c o nc urre nt 
diseases, 
pre vi o us 
facial 
treat me nts/ pr oce d ures (i ncl u di n g t o xi n naï ve/ n o n -t o xi n naï ve), pre vi o us me dicati o ns a n d 
pr oce d ures, a n d c o nc o mita nt me dicati o ns a n d pr oce d ures (see Ta ble 2 ).
4.
If t he s u bject is a fe male of c hil d beari n g p ote ntial, c ollect uri ne f or pre g na nc y  test a n d 
d oc u me nt t he test res ult (see Secti o n 7. 3. 2 ). A ne gati ve res ult is re q uire d f or st u d y i ncl usi o n.
5.
I n vesti gat or assi g ns a scree ni n g n u m ber t o all s u bjects, re vie ws t he i ncl usi o n/e xcl usi o n criteria
( Secti o ns 5. 2. 1 a n d 5. 2. 2 ), a n d c o nfir m s w het her or n ot t he s u bject meets st u d y eli gi bilit y
re q uire me nts. 
If yes, sc he d ule t he baseli ne visit.
If n o, d oc u me nt t he s u bject as a scree n fail ure.
8. 1. 2
B aseli ne / Tre at me nt, Visit 2 (D a y 0 )
If t he scree ni n g a n d baseli ne visits are perf or me d o n t he sa me d a y , t he st u d y assess me nts t hat are 
c o m m o n t o b ot h 
st u d y 
visits will 
o nl y  
be perf or me d 
o nce 
(i.e., A E, 
c o nc o mita nt 
t hera pies/ pr oce d ures, U P T, i ncl usi o n/e xcl usi o n re vie w). A ma xi m u m o f 2 1 da y s is all o we d bet wee n 
t he scree ni n g a n d baseli ne visits. 
At t he b aseli ne visit, t he I n vesti gat or or desi g nee (N ote: t he tre ati n g i nvesti g at or m ust perf or m b ot h 
t he rec o nstit uti o n/ pre p ar ati o n a n d t he tre at me nt) will:
1.
As k t he s u bject a b o ut a n y cha n ge s i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or 
c ha n ge d) si nce t he pre vi o us 
visit. 
Rec or d 
c ha n ges
i n c o nc o mita nt 
t hera pies/ pr oce d ures as a p pr o priate ( Secti o n 5. 4 ).
2.
If t he s u bject is a fe male of c hil d beari n g p ote ntial, c ollect uri ne f or pre g na nc y  test a n d 
d oc u me nt t he test res ult (see Secti o n 7. 3. 2 ). A ne gati ve res ult is re q uire d f or st u d y i ncl usi o n.
3.
I n vesti gat or re vie ws t he i ncl usio n/e xcl usi o n criteria (Secti o n 5. 2. 1 a n d 5. 2. 2 ), a n d c o nfir m 
w het her or n ot t he s u bject meets st u d y eli gi bilit y re q uire me nts. 
If yes, e nr oll/ra n d o mize t he s u bject i n t he cli nical st u d y. Pr ocee d t o t he ne xt ste ps.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 4 9 of 7 1
If n o, d oc u me nt t he s u bject as a scree n fail ure.
4.
F or s u bjects w h o meet all eli gi bilit y re q uire me nts, the I n vesti gat or will recei ve n otificati o n of 
t he s u bject’s ra n d o mizati o n assi g n me nt.
5.
Ta ke s u bject p h ot o gra p hs (see Secti o n 7. 3. 1 ) f or f ut ure G AI S assess me nts acc or di n g t o 
se parate p h ot o gra p h y ma n ual. If t he s u bject is weari n g ma ke -u p, i nstr uct t he s u bject t o re m o ve 
it pri or t o ta ki n g t he p h ot o gra p hs.
6.
Ma ke s ure t o e q uili brate All uzie nce , or t he sali ne use d f or rec o nstit uti o n of p o w der B o N T - A,
f or 3 0 mi n t o r o o m te m perat ure bef ore i njecti o n.
7.
As k t he s u bject t o c o m plete t he S u bject Satisfacti o n Q uesti o n naire ( A p pe n di x 6 ). N ote: m ust 
be perf or me d bef ore treat me nt.
8.
T he I n vesti gat or s h o ul d pre pare St u d y  Pr o d uct acc or di n g t o t he assi g ne d treat me nt i n t he 
sa me r o o m a n d i n fr o nt o f t he s u bject ( Secti o n 6. 1. 7 ).
9.
Pri or t o i njecti o n, clea n t he s u bject’s treat me nt area wit h a s uita ble a ntise ptic s ol uti o n .
1 0.
T he I n vesti gat or will a d mi nister treat me nt. See Secti o n 6. 1. 7. 1 f or i njecti o n tec h ni q ue a n d 
treat me nt pr oce d ure re q uire me nts.
1 1.
As k t he s u bject a b o ut a n y Aes e x perie nce d , i n c o n necti o n t o, a n d after t he treat me nt. Rec or d 
Aes, as a p pr o priate, o n t he c orres p o n di n g e C R F f or m(s).
1 2.
Rec or d p ost -treat me nt c o nc o mita nt t hera pies/ pr oce d ures .
1 3.
As k t he s u bject t o c o m plete t he S u bject Treat me nt Sessi o n Q uesti o n naire ( A p pe n di x 4 ).
1 4.
C o m plete t he R ec o nstit uti o n / Pre parati o n Q uesti o n naire
(A p pe n di x 1 ) a n d t he I nvesti gat or 
Treat me nt Sessi o n Q uesti o n naire ( A p pe n di x 2 ).
1 5.
Sc he d ule t he ne xt visit (M o nt h
1 ± 7 da y s).
8. 1. 3
M o nt h 1 ( ± 7 d a y s), F oll o w -u p visit a n d E n d of St u d y Visit f or p o w der B o N T -A 
tre at me nt gr o u p, Visit 3
T he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut Ae s usi n g a n o pe n -e n de d q uesti o n, s uc h as “H ave y o u n otice d a ny 
c h a n ge i n y o ur he alt h si nce t he l ast visit ?” Rec or d all Aes as a p pr o priate ( Secti o n 7. 2. 1 ).
2.
As k t he s u bject a b o ut a n y cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (ad de d, 
re m o ve d or 
c ha n ge d) si nce t he pre vi o us 
visit. 
Rec or d 
c ha n ges
i n c o nc o mita nt 
t hera pies/ pr oce d ures as a p pr o priate ( Secti o n 5. 4 ).
3.
Ta ke s u bject p h ot o gra p hs (see Secti o n 7. 3. 1 ).
4.
F or p o w der B o N T -A treate d s u bjects: 

E xit t he s u bject fr o m t he st u d y .
5. 
F or All uzie nce treat me nt gr o u p s u bjects:
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 0 of 7 1

Sc he d ule t he ne xt visit ( M o nt h 2
± 7 da y s).
8. 1. 4
M o nt h 
3, 5 a n d 6 ( ± 7 d a ys) , F oll o w -u p visits a n d E n d of St u d y Visit/ E arl y 
Ter mi n ati o n Visit f or All uzie nce tre atme nt gr o u p , Visit 4, 5 a n d 6
T he I n vesti gat or or desi g nee will:
1.
As k t he s u bject a b o ut A es usi n g a n o pe n -e n de d q uesti o n, s uc h as “Ha ve y o u n otice d a n y 
c ha n ge i n y o ur healt h si nce t he last visit? ” Rec or d all Aes as a p pr o priate ( Secti o n 7. 2. 1 ).
2.
As k t he s u bject a b o ut a n y cha n ges i n his/ her c o nc o mita nt t hera pies/ pr oce d ures (a d de d, 
re m o ve d or 
c ha n ge d) si nce t he pre vi o us 
visit. 
Rec or d 
c han ges
i n c o nc o mita nt 
t hera pies/ pr oce d ures as a p pr o priate ( Secti o n 5. 4 ).
3.
Ta ke s u bject p h ot o gra p hs (see Secti o n 7. 3. 1 ) ( o nl y visit 4 a n d 6).
4.
5.
6.
Sc he d ule t he ne xt visit M o nt h 5 ( ± 7 d a y s), O R M o nt h 6 ( ± 7 d a y s), O R c o m plete t he e n d of 
st u d y f or m at visit m o nt h 6 ( Visit 6), de pe n di n g o n c urre nt visit. 
7.
E xit t he s u bject fr o m t he st u d y .
8. 2
U nsc he d ule d Visits
W he n necessar y , u nsc he d ule d visits ma y  be c o n d ucte d, i n partic ular if a n A E occ urs a n d nee ds t o 
be assesse d a n d/ or treate d.
8. 3
S u bject I nstr ucti o ns
S u bjects will be a d vise d t hat a n y facial ma ke - u p will nee d t o be re m o ve d bef ore ta ki n g t he st u d y 
p h ot o gra p hs. 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI
C CI
C CI

C O N FI D E N TI A L 
Pa ge 5 1 of 7 1
9.
S T A TI S TI C A L M E T H O D S P L A N N E D
9. 1
St atistic al a n d A n al ytic al P l a ns
A Statistical A nal y sis Pla n ( S A P) will be de vel o pe d as a se parate d oc u me nt. T he S A P will c o ntai n 
a detaile d a n d tec h nical descri pti o n re gar di n g s pecific data co n ve nti o ns, calc ulati o ns a n d t he 
statistical pr oce d ures t hat will be use d t o perf or m t he a nal yses t hat are s pecifie d i n t he secti o ns 
bel o w. T he S A P will be fi nalize d pri or t o data base l oc k .
A n y  c ha n ges ma de t o t he fi nalize d S A P will be d oc u me nte d i n t he Cli nical St u d y  Re p ort.
9. 1. 1
P o p ul ati o ns A n al yze d a n d E v al u a bilit y 
T he statistica l a nalys es will be perf or me d base d o n t he f oll o wi n g s u bject p o p ulati o ns.
9. 1. 1. 1
F ull A n alysis Set ( F A S ) Effic acy P o p ul ati o n
T he F A S i ncl u des all ra n d o mize d a n d treate d s u bjects. F A S will be use d f or all efficac y eval uati o ns.
9. 1. 1. 2
Per -pr ot oc ol ( P P) Effic acy P o p ul ati o n
T he Per Pr ot oc ol ( P P) p o p ulati o n is a s u bset of t he s u bjects i n t he F A S p o p ulati o n w h o c o m plete t he 
M o nt h 1 visit a n d ha ve n o pr ot oc ol de viati o ns c o nsi dere d t o ha ve a s u bsta ntial i m pact o n t he pri mar y 
efficac y outc o me. T he pri mar y  efficac y e n d p oi nt will be e val uate d usi n g t he P P p o p ulati o n if t he P P 
p o p ulati o n c o nsists of less t ha n 9 5 % of t he F A S p o p ulati o n.
9. 1. 1. 3
S afety P o p ul ati o n
T he safety p o p ulati o n i ncl u des all s u bjects w h o were a d mi nistere d st u d y pr o d uct (i.e., All uzie nce or 
p o w der B o N T - A). Safety a nal ys is will be perf or me d base d o n t he Safet y p o p ulati o n.
9. 1. 1. 4
I m p ut ati o n of M issi n g D at a
N o i m p utati o n of missi n g data will be perf or me d, i.e. a nal yz es will be perf or me d o n o bser ve d cases 
( O C). T he n u m ber of missi n g val ues will be s u m marize d a n d re p orte d as a p pr o priate.
9. 1. 2
D at a P rese nt ati o n a n d G r a p hics
All statistical a nal ys es, i ncl u di n g s u m mar y ta bles a n d data listi n gs, will be perf or me d usi n g t he 
S A S ® s yste m ( Versi o n 9 . 4 or hi g her).
All efficac y, safety a n d baseli ne c haracteristics varia bles will be prese nte d usi n g de scri pti ve 
statistics wit hi n eac h treat me nt gr o u p, a n d gra p hs as a p pr o priate. C o nti n u o us data will be 
s u m marize d usi n g n ( n u m ber of o bser vati o ns), mea n, sta n dar d de viati o n, me dia n, mi ni m u m a n d 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 2 of 7 1
ma xi m u m val ue, w hile cate g orical data will be prese nte d b y n a n d perce nta ges. All data will als o be 
liste d i n s u bject data listi n gs.
S u bject dis p ositi o n, c o m pleti o n a n d disc o nti n uati o n b y  st u d y visit, pr ot oc ol de viati o ns, 
de m o gra p hics a n d baseli ne c haracteristics, me dical hist or y , me dical a n d s ur gical pr oce d ures, a n d 
p ri or a n d c o nc o mita nt me dicati o ns will be s u m marize d b y  treat me nt gr o u p.
9. 1. 2. 1
S u b gr o u p A n alysis
N o s u b gr o u p a nal yz es will be perf or me d.
9. 1. 2. 2
S afety A n alysis
A d verse E ve nts ( A E) will be s u m marize d b y  nu m ber of s u bjects a n d n u m ber of e ve nts per treat me nt 
gr o u p. Ae s will be s u m marize d b y  ca usalit y, s yste m or ga n class , preferre d ter m a n d ma xi m u m 
i nte nsit y. All relate d Aes will als o be s u m marize d b y ti me t o o nset, d urati o n a n d acti o n ta ke n.
Ae s occ urri n g bef ore treat me nt will o nl y be pr o vi de d i n s u bject data listi n gs.
9. 1. 2. 3
Effic acy A n alysis
All efficac y  a nal ysis will be perf or me d descri pti vel y b y treat me nt gr o u p (if a p plica ble). 
T he I n vesti gat or Treat me nt Sessi o n Q uesti o n naire, 
 
 will be pr ese nte d b y  cate g or y an d als o b y  usi n g t hree 
cate g ories ( Str o n gl y a gree/ A gree, Neit her a gree n or disa gree , a n d Disa gree/ Str o n gl y disa gree). 
 
 
 
9. 1. 3  
Wit h dr a w als a n d De vi ati o ns
All wit h dra w n s u bjects will be liste d i n di vi d uall y, i ncl u di n g at least s u bject n u m ber, date a n d reas o n 
f or wit h dra wal, a n d last visit perf or me d.
S u bjects wit h C S P de viati o ns will be liste d i n di vi d uall y, i ncl u di n g s u bject n u m ber a n d o bser ve d 
de viati o n. T he y  will als o be s u m marize d i n t otal ( b y treat me nt gr o u p a n d o verall) as well as b y  st u d y 
site. De pe n di n g o n t he seri o us ness of t he de viati o n, t he s u bject mi g ht be e xcl u de d fr o m t he P P 
p o p ulati o n, w hic h s hall be d oc u me nte d pri or t o data base l oc k.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7
C CI
C CI
C CI

C O N FI D E N TI A L 
Pa ge 5 3 of 7 1
9. 1. 4
I nfere nti al S t atistic al A n al yses
N o i nfere ntial statistics will be perf or me d.
9. 2
S a m ple S ize D eter mi n ati o n
T he sa m ple size of a p pr o xi matel y  1 5 0 s u bjects, 1 0 0 s u bjects i n t he All uzie nce treat me nt gr o u p a n d 
5 0 i n t he p o w der B o N T -A treat me nt gr o u p, is n ot base d o n a statistical calc ulati o n. T he selecte d 
n u m ber of s u bjects is re gar de d as s ufficie nt f or a n e val uati o n of t he st u die d e n d p oi nts b y  usi n g 
descri pti ve statistics.
9. 2. 1 
I nteri m A n al ysis
N o i nteri m a nal ys is will be perf or me d .
1 0.
T R AI NI N G / M O NI T O RI N G / D A T A M A N A G E M E N T / Q U A LI T Y A S S U R A N C E
1 0. 1
Pers o n nel T r ai ni n g
In vesti gat ors a n d ot her res p o nsi ble pers o ns s h o ul d be liste d t o get her wit h t heir f u ncti o n o n t he 
si g nat ure a n d dele gati o n l o g. St u d y  staff s hall pr o vi de a c urric ul u m vitae or e q ui vale nt, as 
a p pr o priate.
It is t he res p o nsi bilit y of the Pri nci pal I n vesti gat or (PI ) t o e ns ure t hat all pers o n nel i n v ol ve d i n t he 
st u d y are f ully i nf or me d re gar di n g all rele va nt as pects of t he st u d y, i ncl u di n g detaile d k n o wle d ge of 
a n d d oc u me n te d trai ni n g i n all pr oce d ures t o be f oll o we d.
1 0. 2
Cli nic al M o nit ori n g
T he c o n d uct of t he cli nical st u d y will be cl osel y m o nit ore d b y  re prese ntati ves of t he S p o ns or t o 
verif y  that t he ri g hts a n d well -bei n g of t he s u bjects are pr otecte d; t he re p orte d data are acc urate, 
c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; a n d t o verif y  ad here nce t o t he C S P , I CH G C P 
g u i deli nes, nati o nal re g ulati o ns, a n d a p plica ble S O Ps. 
T he I n vesti gat or will all o w t he C R O/ S p o ns or re prese ntati ves t o ha ve direct access t o all cli nical 
st u d y rec or ds, case re p ort f or ms ( C R Fs), c orres p o n di n g s u bject me dical rec or ds, st u d y pr o d uct s,
dis pe nsi n g rec or ds, a n d a n y ot her d oc u me nts c o nsi dere d as s o urce d oc u me ntati o n. A d diti o nall y , t he 
C R O/ S p o ns or re prese ntati ve is t o ha ve access t o t he st u d y pr o d uct st ora ge area a n d cli nical st u d y
facilities. T he I n vesti gat or als o a grees t o assist t he C R O/ S p o ns or re prese ntati ve w he n re q uire d.
C S P de viati o ns s hall be re p orte d, verifie d b y  the m o nit or , a n d a p pr o priate c orrecti ve a n d pre ve nti ve 
acti o ns s hall be ta ke n. T he PI  is res p o nsi ble f or pr o m ptl y  re p orti n g a n y de viati o ns fr o m t he C S P t hat 
affects t he ri g hts, safety o r well -bei n g of t he s u bject or t he scie ntific i nte grit y of t he st u d y, i ncl u di n g 
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 4 of 7 1
t h ose w hic h occ ur u n der e mer ge nc y circ u msta nces, t o t he S p o ns or as well as t he I E C if re q uire d b y 
nati o nal re g ulati o ns. De viati o ns s hall be re vie we d t o deter mi ne t he nee d t o a me n d t he C S P or t o 
ter mi nate t he st u d y. Ha n dli n g of C S P de viati o ns s hall be perf or me d as descri be d i n t he m o nit ori n g 
ma n ual. 
1 0. 3  
D at a M a n a ge me nt
Data ma na ge me nt base d o n G C P refers t o t he acti vities t hat e ns ure sec ure a n d r o b ust r o uti nes f or 
efficie ntl y e nteri n g cli nical data i nt o a data base. T he data ma na ge me nt r o uti nes i ncl u de pr oce d ures 
f or data base set- u p a n d ma na ge me nt, data e ntr y an d verificati o n, data vali dati o n, a n d d oc u me ntati o n 
of t he perf or me d acti vities a n d a n y discre pa ncies i n t he pr ocess. T he data ma na ge me nt pr ocess will
be descri be d i n detail i n t he Data Ma na ge me nt P la n ( D M P).
T he data base a n d data e ntr y scree ns will be desi g ne d i n acc or da nce wit h C S P a n d eC R F 
s pecificati o ns. T he E D C s yste m is c o m plia nt wit h re g ulat or y re q uire me nts f or s oft ware vali dati o n. 
Data vali dati o n will be perf or me d b y  co m p uterize d l o gical c h ec ks a n d ma n ual re vie w. Dr u gs a n d 
e ve nts will be c o de d i n acc or da nce wit h t he W orl d Healt h Or ga nizati o n ( W H O) Dr u g data base a n d 
t he Me dical Dicti o nar y  for Re g ulat or y  Acti vities ( Me d D R A) as s pecifie d i n t he D M P. Safet y  data 
( S A E, a n d if a p plica ble, Aes of special i nterest) i n t he cli nical data base will be rec o ncile d a gai nst 
t he data i n t he safety data base.
W he n all eff orts ha ve bee n ma de t o e ns ure t hat t he data rec or de d i n t he e C R Fs a n d e ntere d i n t o t he 
data base are as c orrect a n d c o m plete as p ossi ble, t he cli nical data base will be l oc ke d. St u d y  data will 
be tra nsferre d t o S A S datasets, w hic h t hereafter will be write -pr otecte d. Statistical a nal ys es will be 
ge nerate d i n S A S usi n g data fr o m t he l oc ke d datasets.
1 0. 4
Q u alit y Ass ur a nce/ A u dit /I ns pecti o n
T he cli nical stu d y is c o n d ucte d u n der t he s p o ns ors hi p of t he S p o ns or i n c o m plia nce wit h t he 
a p plica ble i nter nati o nal a n d l ocal re g ulat or y  re q uire me nts as well as a p plica ble I C H g ui deli nes a n d 
i n acc or da nce wit h t he S O Ps f or cli nical st u d y c o n d uct a n d m o nit ori n g fr o m t he S p o ns or a n d/ or 
C R O .
A u dits of cli nical st u d y sites m a y  be c o n d ucte d b y  the C R O/ S p o ns or re prese ntati ves, a n d i ns pecti o n 
ma y  be perf or me d b y  R A i ns pect orates or a n I E C bef ore, d uri n g or after t he cli nical st u d y. For a u dits 
perf or me d b y  or o n be half of t he S p o ns or , a u dit certificate(s) will be pr o vi de d b y  Qualit y  Ass ura nce.
T he I n vesti gat or will allo w a n d assist t he C R O/ S p o ns or re prese ntati ves, I E C a n d re g ulat or y age ncies
t o ha ve direct access t o all re q ueste d cli nical st u d y-relate d rec or ds.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 5 of 7 1
1 0. 5
C h a n ges i n C li nic al St u d y C o n d uct/ A me n d me nts
1 0. 5. 1
Cli nic al St u d y C o n d uct
Wit h t he e xce pti o n of eli mi nati n g a n i m me diate hazar d t o a s u bject, t he I n vesti gat or s h o ul d n ot 
de viate fr o m t he C S P or i m ple me nt a n y c ha n ges wit h o ut writte n a p pr o val fr o m t he S p o ns or a n d 
pri or re vie w a n d d oc u me nte d a p pr o val/fa v ora ble o pi ni o n fr o m t he I E C of a pr ot oc ol a me n d me nt.
C ha n ges t hat i n v ol ve o nl y  lo gistical or a d mi nistrati ve c ha n ges t o t he C S P are a ut h orize d. T he 
I n vesti gat or s h o ul d d oc u me nt a n d e x plai n a n y de viati o n fr o m t he C S P .
1 0. 5. 2
A m e n d me nts
T he S p o ns or m a y  mo dif y  the C S P at a n y ti me f or et hical, me dical, or scie ntific reas o ns. A n y 
a me n d me nts will be ha n dle d acc or di n g t o a p plica ble l ocal re g ulati o ns.
T he S p o ns or d oes n ot ha ve t o n otif y  no n- s u bsta ntial a me n d me nts t o t he c o m pete nt a ut h orities or
I E Cs. H o we ver, n o n- s u bsta ntial a me n d me nts s h o ul d be rec or de d a n d detaile d i n s u bse q ue nt 
s u b missi o ns, e. g., i n t he s u bse q ue nt n otificati o n of a s u bsta ntial a me n d me nt.
1 1.
E T HI C S A N D G E N E R A L C LI NI C A L S T U D Y C O N D U C T C O N SI D E R A TI O N S
1 1. 1
I n de pe n de nt Et hics C o m mittee (I EC) a n d Re g ul at or y A ut h orities ( R A)
T his C S P a n d all a p plica ble a me n d me nts will be re vie we d a n d a p pr o ve d b y  t he a p pr o priate I E C. It 
is t he res p o nsi bilit y of the PI  to o btai n a p pr o val of t he C S P/ C S P a me n d me nt(s) fr o m t he I E C. T he 
st u d y shall n ot be gi n u ntil t he re q uire d fa v ora ble o pi ni o n fr o m t he I EC has bee n o btai ne d. T he PI 
s hall file all c orres p o n de nce wit h t he I E C i n t he I n vesti gat or file a n d pr o vi de c o pies of I E C a p pr o vals 
t o t he S p o ns or as re q uire d. A n y a d diti o nal re q uire me nts i m p ose d b y  the I E C or R A shall be 
f oll o we d. 
T his st u d y re q uires a p plicati o n f or a p pr o val fr o m t he R A. T he st u d y will n ot be starte d u ntil t he 
S p o ns or has recei ve d writte n a p pr o val or u ntil t he stat ut or y waiti n g peri o d fr o m t he a p pr o priate 
a ut h orit y has ela pse d. T he S p o ns or will pr o vi de t he PI  wit h a c o p y of t he rele va nt R A a p pr o val 
d oc u me ntati o n .
T he c ollecti o n, access t o, pr ocessi n g, a n d tra nsfer of pr otecte d healt h i nf or mati o n or se nsiti ve 
pers o nal data s hall be carrie d o ut i n acc or da nce wit h a p plica ble r ules a n d re g ulati o ns .
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 6 of 7 1
1 1. 2
Et hic al C o n d uct of t he Cli nic al St u d y
T his cli nical st u d y will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol , t he H E L SI N KI declarati o n 
( 1 9 6 4) a nd its s u bse q ue nt a me n d me nts, I CH G C P, nati o nal re g ulati o ns, a n d i n c o m plia nce wit h 
ot her a p plica ble re g ulat or y req uire me nts. 
1 1. 3
S u bject Inf or m ati o n a n d C o nse nt
All s u bjects w h o partici pate i n t his cli nical st u d y are re q uire d t o be f ull y i nf or me d a b o ut t he cli nical 
st u d y i n acc or da nce wit h G C P g ui deli nes, nati o nal re g ulati o ns a n d g ui deli nes , a n d i n acc orda nce 
wit h l ocal re q uire me nts. 
T he I C F, a p pr o ve d b y  an I E C, will be full y  ex plai ne d t o t he s u bject. T he s u bject m ust a gree t o p h ot o 
c o nse nt i n or der t o partici pate i n t he cli nical st u d y. 
Pri or t o e nr ol lme nt i nt o t he cli nical st u d y, t he s u bject a n d t he PI or desi g nee m ust si gn a n d date t he 
c o nse nt f or m(s). T he I n vesti gat or is res p o nsi ble f or mai ntai ni n g eac h s u bject’s c o nse nt f or m(s) i n 
t he I n vesti gat or’s S ite F ile a n d pr o vi di n g eac h s u bject wit h a c o p y of t he si g ne d a n d date d c o nse nt 
f or m(s).
1 1. 4
Pr otecti o n of Pers o n al D at a
F or t he p ur p oses of t he st u d y , t he S p o ns or is c o nsi dere d t he data c o ntr oller, a n d t he I nstit uti o n a n d 
PI  are b ot h c o nsi dere d t o be data pr ocess ors.
All pr ocessi n g of pers o nal data m ust be carrie d o ut i n acc or da nce wit h nati o nal le gislati o n 
c o ncer ni n g the pr otecti o n of pers o nal data. T he I nstit uti o n a n d PI  are res p o nsi ble f or c o m pl yi n g wit h 
all re q uire me nts p urs ua nt t o nati o nal le gislati o n i n t he c o u ntr y in w hic h t he I nstit uti o n a n d PI  are 
l ocate d. T he S p o ns or will e ns ure t hat all re q uire me nts are c o m plie d wit h f or data pr ocessi n g, w hic h 
is carrie d o ut i n S we de n b y t he S p o ns or. I nstit uti o n a n d PI are a ware of, a n d will o btai n t he re q uire d 
a p pr o vals pri or t o t he tra nsfer of se nsiti ve pers o nal data w hic h is s u bject t o pre -a p pr o val, pri or t o 
t he tra nsfer of s uc h data o utsi de E ur o pe .
T he I CF s hall c o ntai n i nf or mati o n a b o ut w hic h pers o nal data will be c ollecte d i n t he st u d y  a n d t hat 
t he data will be ke pt c o nfi de ntial. T he pr o vi de d i nf or mati o n s hall be s ufficie nt t o e na ble all s u bjects 
t o gi ve t heir c o nse nt n ot o nl y  t o t he partici pati o n i n t he st u dy, b ut als o t o t he pr ocessi n g of pers o nal 
data. S uc h i nf or mati o n i ncl u des i nf or mati o n re gar di n g t he p ur p oses of data c ollecti o n pr ocessi n g, 
data tra nsfer t o c o u ntries o utsi de of E ur o pe , a n d t he le n gt h of ti me d uri n g w hi c h t he pers o nal data 
will be st ore d. T he s u bject s hall ha ve t he ri g ht t o access t he st ore d pers o nal data, a n d t he ri g ht t o 
c orrect a n y i nc orrect or o bs olete i nf or mati o n. If a s u bject deci des t o ter mi nate t he st u d y pre mat urely, 
data c ollecte d bef ore wit h dra w n c o nse nt will be use d i n t he e val uati o n of t he st u d y, h o we ver n o ne w 
data ma y be c ollecte d. A ut h orize d re prese ntati ves fr o m t he S p o ns or or a R A ma y visit t he st u d y site 
t o perf or m a u dits/i ns pecti o ns, i ncl u di n g s o urce data verificati o n, i.e., c o m pari n g da ta i n t he s u bjects’ 
me dical rec or ds a n d t he e C R F. Data a n d i nf or mati o n s hall be ha n dle d strictl y  c o nfi de ntial.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 7 of 7 1
1 1. 5
C o ntr act u al R e q uire me nts
T he cli nical trial a gree me nt ( C T A) o utli nes t he c o m pe nsati o n a n d pa y me nt ter ms of t he st u d y . T he 
C T A m ust be si g ne d bef o re t he first s u bject is scree ne d i n t he st u d y. If t here are differe nces bet wee n 
t he C T A a n d t he C S P re gar di n g certai n ri g hts a n d o bli gati o ns, t he C T A is t he pre vaili n g d oc u me nt. 
1 1. 6
D at a C ollecti o n a n d A rc hi vi n g
1 1. 6. 1
D at a C ollecti o n
T he I n vesti gat or m ust mai ntai n all re q uire d rec or ds f or all s u bjects. T he data f or t his cli nical st u d y
will be rec or de d i n t he s u bject’s s o urce d oc u me nts a n d i n t he e C R Fs. All data s h o ul d be rec or de d in 
t he eC R Fs c o m pletel y a n d pr o m ptl y.
1 1. 6. 2
S o urce D oc u me nt ati o n
T he e C R F is c o nsi dere d a data e ntr y for m a n d d oes n ot c o nstit ute t he ori gi nal ( or s o urce) me dical 
rec or ds u nless ot her wise s pecifie d. S o urce d oc u me nts are all d oc u me nts use d by t he I n vesti gat or or 
h os pital t hat relate t o t he s u bject’s me dical hist or y , verif y i n g t he e xiste nce of t he s u bject, t he 
i ncl usi o n a n d e xcl usi o n criteria, a n d all rec or ds c o veri n g t he s u bject’s partici pati o n i n t he st u d y . 
T he s o urce data l ocati o n l o g s pecifies w hat data t hat s hall be a vaila ble i n t he me dical rec or d. T he 
s o urce data l ocati o n l o g s hall als o s pecif y the data f or w hic h t he e C R F ser ves as t he s o urce. S uc h 
data o nl y  nee d t o be rec or de d i n t he e C R F a n d are t ypicall y  ass ociate d wit h st u d y-s pecific 
pr oce d ures a n d n ot wit h n or mal cli nical care practice. F or t his t ype of st u d y data t he I n vesti gat or 
w o ul d n ot be e x pecte d t o d u plicate t he i nf or mati o n i nt o t he me dical rec or d. 
T he PI  is res p o nsi ble f or mai ntai ni n g a de q uate s o urce d oc u me ntati o n . S o urce data s h o ul d be 
attri b uta ble, le gi ble, c o nte m p ora ne o us, ori gi nal, acc urate, a n d c o m plete. C ha n ges t o s o urce data 
s h o ul d be tracea ble, i.e., wit h o ut o bsc uri n g t he ori gi nal data e ntr y an d wit h a n e x pla nati o n if 
necessar y .
S o urce d oc u me nts s hall be ma de a vaila ble f or i ns pecti o n b y t he m o nit or at eac h m o nit ori n g visit , as 
well as d uri n g a u dits a n d/ or i ns pecti o ns.
1 1. 6. 3
Arc hi ves
All perti ne nt data, sa m ples, p h ot o gra p hs, c orres p o n de nce, a n d re p orts, t he ori gi nal or a me n de d C S P , 
a n d all ot her material 
relati n g t o t he cli nical st u d y will 
be mai ntai ne d 
sec urely i n t he 
S p o ns or/ C R O/I n vesti gat or/I nstit uti o n arc hi ves f or t he le gall y re q uire d d urati o n f or arc hi vi n g.
T he I n vesti gat or/I nstit uti o n s h o ul d mai ntai n t he esse ntial cli nical st u d y d oc u me nts acc or di n g t o t he 
a p plica ble re g ulat or y re q uire me nts.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 8 of 7 1
T he I nvesti gat or/I nstit uti o n s h o ul d ta ke meas ures t o pre ve nt acci de ntal or pre mat ure destr ucti o n of 
t hese d oc u me nts.
If t he PI retires, rel ocates, or wit h dra ws fr o m t he res p o nsi bilit y of kee pi n g t he cli nical st u d y rec or ds 
f or a n y reas o n, c ust o d y m ust be tra nsferre d t o a pers o n w h o will acce pt t he res p o nsi bilit y. T he 
S p o ns or/ C R O m ust be n ot ifie d i n writi n g of t he na me a n d a d dress of t he ne w c ust o dia n.
1 1. 7
I ns ur a nce
Q -Me d
A B’s o bli gati o ns i n t his cli nical st u d y are c o vere d b y  Gal der ma’s gl o bal ge neral lia bilit y 
pr o gra m. A n i ns ura nce certificate will be pr o vi de d u p o n re q uest. T he i nstit uti o n/ PI is o bli gate d t o 
mai ntai n i ns ura nce c o vera ge f or t heir o bli gati o ns i n t he cli nical st u d y  acc or di n g t o t he C T A.
1 1. 8
P u blic ati o n P olic y
T he 
o bli gati o n of t he I nstit uti o n/ PI a n d S p o ns or re gar di n g i ntellect ual pr o pert y ri g hts, 
c o nfi de ntialit y, a n d p u blicati o ns are descri be d i n detail i n t he C T A.
T he ai m is t o s u b mit t he res ults of t his st u d y for p u blicati o n i n t he p u blic data base 
(htt p:// w w w.cli nicaltrials. g o v ) a n d t o a peer -re vie we d me dical j o ur nal f or p u blicati o n . Eac h pers o n
liste d as a n a ut h or of t he res ults of t his m ultice nter st u d y shall ha ve ma de a s u bsta ntial, direct, a n d 
i ntellect ual c o ntri b uti o n t o t he w or k. A ut h ors hi p will be base d o n: ( 1) s u bsta ntial c o ntri b uti o ns t o 
t he c o nce pti o n or desi g n of t he w or k; or t he ac q uisiti o n, a nal ysis, or i nter pretati o n of data f or t he 
w or k;
( 2) drafti n g t he w or k or re visi n g it criticall y for i m porta nt i ntellect ual c o nte nt; ( 3) fi nal 
a p pr o val of t he versi o n t o be p u blis he d; a n d ( 4) a gree me nt t o be acc o u nta ble f or all as pects of t he 
w or k i n e ns uri n g t hat q uesti o ns relate d t o t he acc urac y or i nte grit y of a n y part of t he w or k are 
a p pr o priatel y i n vesti gate d a n d res ol ve d.a C o n diti o ns 1, 2, 3, a n d 4 m ust al l be met i n or der t o b e  
desi g nate d as a n a ut h or. T h ose w h o d o n ot meet all f o ur cr iteria will be ac k n o wle d ge d. A m o n g t he 
a ut h ors t hat f ulfill t he a b o ve-me nti o ne d criteria, o ne a ut h or will be a p p oi nte d b y  the S p o ns or t o ta ke 
pr i mar y res p o nsi bilit y f or t he o verall w or k as pri mar y a ut h or.
                                                
a Defi ni n g t he r ole of a ut h ors a n d c o ntri b ut ors, c o m pile d b y t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors 
(I C MJ E) (htt p:// w w w.ic mje. or g ).
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 5 9 of 7 1
1 2.
LI T E R A T U R E R E F E R E N C E LI S T
1.
I C H E 6 ( R 2): I nter nati on al C o nf er e n c e o n H ar m o nis ati o n Tri p artit e G ui d eli n e:  G ui deli ne f or G o o d 
Cli ni c al Pr a cti c e, 2 0 1 6. 
2.
Els o n M L. E v al u ati o n a n d tr e at m e nt of t h e a gi n g f a c e. I n: Els o n M L, E d. E v al u ati o n a n d 
Tr e at m e nt of t h e A gi n g F a c e. N e w Y or k: S pri n g er V erl a g, 1 9 9 5; 1 -9.
3.
L o w e NJ. B ot uli n u m t y p e A f or f a ci al r ej u v e n ati o n. U S A a n d U K p ers p e cti v es. D er m at ol S ur g 
1 9 9 8; 2 4: 2 1 6 -2 1 8. 
4.
G u errissi J, S ar kissi a n P. L o c al i nj e cti o n i nt o mi m eti c m us cl es of b ot uli n u m t o xi n A f or t h e 
tr e at m e nt of f a ci al li n es. A n n Pl ast S ur g 1 9 9 7; 3 9( 5): 4 4 7- 45 3.
5.
F ost er, J A, B ar n h orst D, P a p a y F, et al. T h e us e of b ot uli n u m A t o xi n t o a m eli or at e f a ci al ki n eti c 
fr o w n li n es. O p ht h al m ol o g y 1 9 9 6; 1 0 3( 4): 6 1 8-6 2 2.
6.
G u y ur o n B, H u d dl est o n S W. A est h eti c i n di c ati o ns f or b ot uli n u m t o xi n i nj e cti o n. Pl ast R e c o nstr 
S ur g 1 9 9 4; 9 3( 5): 9 1 3 -9 1 8.
7.
Blit z er A, Bri n M F, K e e n M A, A vi v J E. B ot uli n u m t o xi n f or t h e tr e at m e nt of h y p erf u n cti o n al 
li n es of t h e f a c e. Ar c h Ot ol ar y n g ol H e a d N e c k S ur g 1 9 9 3; 1 1 9( 9): 1 0 1 8-1 0 2 2.
8.
C arr ut h ers J D, C arr ut h ers J A. Tr e at m e nt of gl a b ell ar fr o w n li n es wit h C. b ot u li n u m A e x ot o xi n. J 
D er m at ol S ur g O n c ol 1 9 9 2; 1 8( 1): 1 7 -2 1. 
9.
F a gi e n S. B ot o x f or t h e tr e at m e nt of d y n a mi c a n d h y p er ki n eti c f a ci al li n es a n d f urr o ws: 
A dj u n cti v e Us e i n F a ci al A est h eti c S ur g er y. Pl ast R e c o nstr S ur g 1 9 9 9; 1 0 3( 2): 7 0 1 -7 1 3.
1 0. R a mir e z A L, R e e c k J, M a a s C S. B ot uli n u m t o xi n t y p e B ( M y o Bl o c) i n t h e m a n a g e m e nt of 
h y p er ki n eti c f a ci al li n es. Ot ol ar y n g ol H e a d N e c k S ur g 2 0 0 2; 1 2 6( 5): 4 5 9 -4 6 7.
1 1. Ki m EJ, R a mir e z A L, R e e c k J B, M a as C S. T h e r ol e of b ot uli n u m t o xi n t y p e B ( M y o bl o c) i n t h e 
tr e at m e nt of h y p er ki n eti c f a ci al li n es. Pl ast R e c o nstr S ur g 2 0 0 3; 1 1 2( 5): 8 8 S 9 3 S; dis c ussi o n 9 4 S-
9 7 S.
1 2. C arr ut h ers J A, L o w e NJ, M e nt er M A, et al. B O T O X Gl a b ell ar Li n es I St u d y Gr o u p. A 
m ulti c e nt er, d o u bl e bli n d, r a n d o mi z e d, pl a c e b o c o ntr oll e d st u d y of t h e effi c a c y a n d s af et y of 
b ot uli n u m t o xi n t y p e A i n t h e tr e at m e nt of gl a b ell ar li n es. J A m A c a d D er m at ol 2 0 0 2; 4 6( 6): 8 4 0 -
8 4 9.
1 3. As c h er B, K est e m o nt P, B oi n e a u D, B o d o k h I, St ei n A, H e c k m a n n M, D e n d orf er M, P a vi ci c T, 
V olt e a u M, Ts e A, Pi c a ut P, R z a n y B. Li q ui d F or m ul ati o n of A b o b ot uli n u mt o xi n A E x hi bits a 
F a v or a bl e Effi c a c y a n d S af et y Pr ofil e i n M o d er at e t o S e v er e Gl a b ell ar Li n es: A R a n d o mi z e d, 
D o u bl e -Bli n d, Pl a c e b o - a n d A cti v e C o m p ar at or -C o ntr oll e d Tri al. A est h et S ur g J. 2 0 1 8 F e b 
1 7; 3 8( 2): 1 8 3 -1 9 1. D oi: 1 0. 1 0 9 3/ asj/sj w 2 7 2. P MI D: 2 8 2 0 0 0 0 2.
1 4. E ur o p e a n M e di ci n es A g e n c y, G ui d eli n e o n pl as m a -d eri v e d m e di ci n al pr o d u cts. 
E M A/ C H M P/ B W P/ 7 0 6 2 7 1/ 2 0 1 0.
1 5. E ur o p e a n M e di ci n es A g e n c y, N ot e f or g ui d a n c e o n d e v el o p m e nt p h ar m a c e uti cs f or 
bi ot e c h n ol o gi c al a n d bi ol o gi c al pr o d u cts. C P M P/ B W P/ 3 2 8/ 9 9.
1 6. S u m m ar y of Pr o d u ct C h ar a ct eristi c All u zi e n c e, 2 0 0 S p e y w o o d u nits/ ml, s ol uti o n f or i nj e cti o n, 
r e visi o n 2 0 2 1-0 6 -1 0
1 7. S u m m ar y of Pr o d u ct C h ar a ct eristi c :
Vist a b el ® , 4 All er g a n U nits/ 0. 1 ml, P o w d er f or s ol uti o n f or i nj e cti o n, r e visi o n 2 4/ 0 9/ 2 0 1 8.
B O T O X ®, 5 0 All er g a n U nits, P o w d er f or s ol uti o n f or i nj e cti o n, r e visi o n 2 1 /1 2 / 2 02 0.
1 8. G o o d M a n uf a ct uri n g Pr a cti c es, A n n e x 1 3.
1 9. I C H E 2 A: I nt er n ati o n al C o nf er e n c e o n H ar m o nis ati o n Tri p artit e G ui d eli n e:  Cli ni c al S af et y D at a 
M a n a g e m e nt: D efi niti o ns a n d St a n d ar ds f or E x p e dit e d R e p orti n g. 1 9 9 4
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 6 0 of 7 1
1 3.
S U M M A R Y O F C H A N G E S
Secti o n i n t he cli nic al
st u d y pr ot oc ol
R ati o n al f or c h a n ges
Descri pti o n of c h a n ges
S y n o psis
As per re q uest fr o m E C n o 
i nteri m a nal ysis will be 
perf or me d.
Re m o ve d p ossi bilit y  t o 
perf or m a n i nteri m a nal ysis 
bef ore st u d y c o m pleti o n.
7. 2. 1. 2. 2 Pr oce d ure f or 
Re p orti n g a Seri o us 
A d verse E ve nt ( S A E)
U p date d t o matc h t he S A E 
re p orti n g pr ocess.
A d de d “ Pri nt a n d c o m plete t he 
S A E f or m” u n der b ullet 3.
9. 2. 1 I nteri m A nal ys is
As per re q uest fr o m E C n o 
i nteri m a nal ysis will be 
perf or me d.
Re m o ve d p ossi bilit y  t o 
perf or m a n i nteri m a nal ysis 
bef ore st u d y c o m pleti o n.
A p pe n di x 4, 5 a n d 6
Re q uest fr o m E C t o re m o ve 
si g nat ure r o w f or s u bject 
q uesti o n naires t o pr otect 
pse u d o -a n o n y m isati o n.
Re m o ve d si g nat ure r o w.
N ote: Mi n or c orrecti o ns a n d e dit orial c ha n ges are n ot liste d a b o ve.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 6 1 of 7 1
1 4.
A P P E N DI C E S
A p pe n di x 1
Pre p ar ati o n of All uzie nce a n d Rec o nstit uti o n of p o w der B o N T - A
All uzie nce Pre p ar ati o n Q uesti o n n aire
Ti me f or st u d y  pr o d uct t o e q uili brate t o r o o m 
te m perat ure
(N ote: s h o ul d be 1 5 – 3 0 mi n acc or di n g t o C S P )
M M: S S
H o w l o n g di d it ta ke t o pre pare t he pr o d uct t o 
ha ve it rea d y f or i njecti o n?
Ti me fr o m o pe ni n g t he o uter b ox t o h avi n g a syri n ge 
re a dy f or use.
M M: S S
Di d y o u pre pare t he pr o d uct i n fr o nt of t he s u bject?
Yes
☐N o
☐
I di d n ot e x perie nce a ny t ec h nical iss ues/ pr o ble ms w he n usi n g a rea d y t o use pr o d uct as 
c o m pare d t o a pr o d uct t o be rec o nstit ute d
Str o n gl y a gree
A gree
Neit her a gree n or 
disa gree
Disa gree
Str o n gl y disa gree
☐
☐
☐
☐
☐
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 6 2 of 7 1
B O T O X/ Vist a bel Rec o nstit uti o n Q uesti o n n aire
N O T E: Rec o nstit uti o n i nf or m ati o n c a n be f o u n d o n t he ne xt p a ge.
Ti me f or s ol ve nt t o e q uili brate t o r o o m te m perat ure 
(N ote: s h o ul d be 1 5 – 3 0 mi n acc or di n g t o C S P )
M M: S S
H o w l o n g di d it ta ke t o pre pare t he pr o d uct t o 
ha ve it rea d y f or i njecti o n?
Ti me fr o m o pe ni n g t he o uter b ox t o h avi n g a syri n ge 
re a dy f or use.
M M: S S
Di d y o u rec o nstit ute i n fr o nt of t he s u bject?
Yes
☐N o
☐
A n y  pr o d uct pr o ble ms ass ociate d wit h t he rec o nstit uti o n?
Yes
☐N o
☐
If “ Yes” a b o ve:
☐  Wr o n g fi nal c o nce ntrati o n ( U/ m L ) 
☐  Wr o n g c o nce ntrati o n of Na Cl use d/ wr o n g dil ue nt use d
☐  Vac u u m n ot p ulli n g t he s ol ve nt i nt o t he vial
☐  Di ffic ulties t o i nsert t he nee dle i nt o t he vial
☐  Particles i n s ol uti o n
☐  B u b ble/ F oa m f or mati o n
☐  Waste of pr o d uct
Ot her, please descri be:
_ _ _ _ _ _ _
Ha ve y o u e ver ha d a n y iss ue s t o rec o nstit ute t he p o w der B o N T - A i n t he past ?
Yes
☐N o
☐
If “ Yes” a b o ve:
☐Wr o n g fi nal c o nce ntrati o n ( U/ m L ) 
☐Wr o n g c o nce ntrati o n of Na Cl use d/ wr o n g dil utie nt use d
☐
Va c u u m n ot p ull i n g t he s ol ve nt i nt o t he vial
☐  Di ffic ulties t o i nsert t he nee dle i nt o t he vial
☐
Particles i n s ol uti o n
☐
B u b ble / F oa m f or mati o n
☐Waste of pr o d uct
Ot her, please descri be:
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 6 3 of 7 1
Re me m ber t o f oll o w t he rec o nstit uti o n descri pti o n i n t he s u m mar y of pr o d uct c haracteristics (see 
list bel o w), a n y de viati o n (e. g. re m o vi n g t he r u b ber ca p s h o ul d be rec or de d as a pr ot oc ol 
de viati o n).

Rec o nstit uti o n s h o ul d be perf or me d i n acc or da nce wit h g o o d practices r ules, partic ularl y 
f or t he res pect of ase psis. 

B O T O X ®/ VI S T A B E L ® has t o be rec o nstit ute d wit h sterile u n preser ve d n or mal sali ne 
s ol uti o n ( 0. 9 % s o di u m c hl ori de s ol uti o n f or i njecti o n). As per t he dil uti o n ta ble bel o w, t he 
re q ueste d a m o u nt of sterile u n preser ve d n or mal sali ne s ol uti o n ( 0. 9 % s o di u m c hl ori de 
s ol uti o n f or i njecti o n) has t o be dra w n u p i nt o a s yri n ge i n or der t o o btai n a rec o nstit ute d 
s ol uti o n at a c o nce ntrati o n of 4 U nits/ 0. 1 m L
Vi al si z e
Vi al si z e
A m o u nt of s ol v e nt a d d e d (st eril e
A m o u nt of s ol v e nt a d d e d (st eril e u n pr es er v e d n or m al s ali n e 
u n pr es er v e d n or m al s ali n e 
s ol uti o n ( 0. 9 %
s ol uti o n ( 0. 9 % s o di u m c hl ori d e s ol uti o n f or i nj e cti o n))
s o di u m c hl ori d e s ol uti o n f or i nj e cti o n))
R es ul
R es ul ti n g d os e
ti n g d os e
( U nits p er 0. 1 
( U nits p er 0. 1 m L
m L )
5 0 U nits
1. 2 5 m L
4. 0 U nits

T o a v oi d B O T O X ®/ VI S T A B E L ® de nat urati o n, t he s ol uti o n is pre pare d b y  i njecti n g t he 
s ol ve nt sl o wl y i nt o t he vial a n d by ge ntl y r otati n g t he vial a v oi di n g b u b ble f or mati o n.

T he vial has t o be discar de d if t he vac u u m d oes n ot p ull t he s ol ve nt i nt o t he vial.
O nce rec o nstit ute d, t he s ol uti o n s h o ul d be vis uall y ins pecte d pri or t o use. O nl y  clear, c ol o urless t o 
sli g htl y yell o w s ol uti o n wit h o ut particles s h o ul d be use d.
Title  
D o c i d  
0 5 P F 2 0 0 5 Cli nic al St u d y Pr ot oc ol - S T A R
M A- 4 8 4 4 1
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 2 1- 1 2- 0 1 1 7: 3 9
5. 0
 
Pri nt date:
 2 0 2 1- 1 2- 0 6 0 9: 4 7

C O N FI D E N TI A L 
Pa ge 6 4 of 7 1
A p pe n di x 2
I n vesti g at or Tre at me nt Sessi o n Q uesti o n n aire ( for All uzie nce o nl y)
N O T E: 
T o be a ns were d f or All uzie nce o nl y
Str o n gl y 
a gree
A gree
Neit her 
a gree n or 
disa gree
Disa gree
Str o n gl y 
disa gree
1.
I prefer t o utilize a rea d y t o use pr o d uct as 
c o m pare d t o a pr o d uct t o be rec o nstit ute d

 
 
 

2.
I c o ul d de dicate m ore ti me t o e x plai n t he treat me nt 
pr oce d ure i n usi n g a rea d y t o use pr o d uct as 
c o m pare d t o a pr o d uct t o be rec o nstit ute d
 
 
 
 

3.
I c o ul d sa ve ti me o n t he rec o nstit uti o n a n d i njecti o n 
pr oce d ure t o d o s o met hi n g else
 
 
 
 

4.
I felt m ore rela xe d/less stresse d i n n ot ha vi n g t o 
rec o nstit ute t he pr o d uct t o be i njecte d
 
 
 
 

5.
I feel m ore sec ure w he n I ha ve a pre-dil ute d 
s ol uti o n a n d d o n’t ha ve t o rec o nstit ute t he pr o d uct 
m yself
 
 
 
 

6.
I ha ve a g o o d feeli n g a b o ut i njecti n g a m o der n a n d 
i n n o vati ve pr o d uct as c o m pare d t o t he rec o nstit ute d 
pr o d uct
 
 
 
 

7.
I feel I a m m ore precise i n m y i njecti o n wit h a rea d y 
t o use pr o d uct c o m pare d t o a pr o d uct t o be 
rec o nstit ute d
 
 
 
 

8.
I li ke t o pr o p ose ne w i n n o vati ve treat me nt wit h 
li q ui d rea d y t o use pr o d uct t o m y patie nt
 
 
 
 

9.
I pr o d uce d s u bsta ntiall y less waste of n o n-t o xi n 
material (s yri n ges, nee dles, sali ne etc.) usi n g rea d y -
t o-use pr o d uct as c o m pare d t o t he rec o nstit ute d 
pr o d uct
 
 
 
 

1 0.
W he n I use a rea d y t o use t o xi n I s pe n d less 
materials f or i njecti o n  
 
 
 
 

1 1.
I belie ve t hat t he use of rea d y t o use t o xi n is better 
f or t he e n vir o n me nt as I pr o d uce less waste
 
 
 
 

1 2.
I feel m ore c o nfi de nt w he n i njecti n g a pr o d uct free 
fr o m a ni mal a n d h u ma n e xci pie nts
 
 
 
 

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SI G N E D A G R E E M E N T O F T H E C LI NI C A L S T U D Y P R O T O C O L ( C S P)
C T N:
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C S P title:
A P hase I V, Ra n d o mize d, I nter ve nti o nal, St u d y  to Assess S u bject 
Treat me nt Sessi o n Perce pti o n a n d I nvesti gat or Treat me nt E x perie nce 
of All uzie nce a n d Vac u u m -Drie d B ot uli n u m Ne ur ot o xi n T y pe A f or 
Aest hetic Use
I, t he u n dersi g ne d, ha ve rea d a n d u n dersta n d t he C S P s pecifie d a b o ve, a n d a gree o n t he c o nte nts. 
T he C S P, t he cli nical trial a gree me nt ( C T A) a n d t he a d diti o nal i nf or mati o n gi ve n i n t he S m P C will 
ser ve as a basis f or c o-o perati o n i n t his st u d y .
Pri nci p al I n vesti g at or
Pri nte d na me 
Si g nat ure
Date
St u d y site
Title  
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Si g n p a g e: 1 of 1
S I G N A T U R E S PA G E
D at e
Si g n e d b y
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J u stifi c ati o n
A p pr o v e d b y T e c h ni c al E x p ert
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J u stifi c ati o n
A p pr o v e d b y T e c h ni c al E x p ert
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J u stifi c ati o n
A p pr o v e d b y T e c h ni c al E x p ert
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J u stifi c ati o n
C o m pil e d b y
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J u stifi c ati o n
A p pr o v e d b y 
Title  
D o c i d  
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P P D
P P D
P P D
P P D
P P D
P P D