A Randomized, Multi-center, Evaluator-blinded, No-treatment Controlled Study to Evaluate the Efficacy and Safety of Restylane Perlane Lidocaine for Correction of Midface Volume Deficit and/or Midface Contour Deficiency
Phase: NA
Conditions: Midface Volume Deficit
Sponsor: Galderma R&D

1( 6 2)
A r a n d o miz e d, m ulti -c e nt er, e v al u at or-bli n d e d, n o -tr e at m e nt c o ntr oll e d st u d y t o e v al u at e 
t h e effic ac y a n d s af et y of R est yl a n e P erl a n e Li d oc ai n e f or c orr ecti o n of Mi df ac e V ol u m e 
D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y
St u dy pr o d uct :
R est yl a n e P erl a n e Li d oc ai n e
Cli nic al Tri al N u m b er ( C T N):
4 3 C H 1 5 0 7
C o -or di n ati n g I nv esti g at or 
S p o ns or:
Q- M e d A B
S e mi n ari e g at a n 2 1
S E -7 5 2 2 8 U p ps al a , S w e d e n
T el e p h o n e: + 4 6 1 8 4 7 4 9 0 0 0
F acsi mil e:   + 4 6 1 8 4 7 4 9 0 0 1
C o nfi d e nti alit y St at e m e nt
T his st u d y pr ot oc ol c o nt ai ns c o nfi d e nti al i nf or m ati o n b el o n gi n g t o Q -M e d A B. Exc e pt as m a y 
b e ot h er wis e a gr e e d t o i n writi n g, b y acc e pti n g or r e vi e wi n g t h es e m at eri als, y o u a gr e e t o h ol d 
s uc h i nf or m ati o n i n c o nfi d e nc e a n d n eit h er discl os e it t o a n y t hir d p arti es ( exc e pt w h er e 
r e q uir e d b y a p plic a bl e l a w) n or us e it f or a n y ot h er p ur p os e t h a n i n r el ati o n t o t h e cli nic al 
st u d y d escri b e d h er ei n.
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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4. 0
 
 
 
Pri nt date:
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P P D

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S u m m ar y of C h a n g es i n Cli nic al St u d y Pr ot oc ol 4 3 C H 1 5 0 7 fr o m V ersi o n 3 . 0 t o V ersi o n 4. 0
A d d e d t ext is writt e n i n b ol d a n d d el et e d t ext is writt e n as stri k et hr o u g h.
S ecti o n i n t h e 
cli nic al st u d y 
pr ot oc ol
R ati o n al f or c h a n g es
D escri pti o n of c h a n g es
I nv esti g at ors 
a n d St u d y 
A d mi nistr ativ e 
Str uct ur e
R e w or di n g 
St u d y Dir ect or
Cli nic al Pr oj ect M a n a g er
S p o ns or 
Si g n at ur es
R e w or di n g
St u d y Dir ect or
Cli nic al Pr oj ect M a n a g er
S y n o psis -
S af et y 
Ass ess m e nt :
Cl arific ati o n
I nf or m ati o n o n A Es c a n als o b e o bt ai n e d fr o m l a b or at or y 
t est r e p ort, si g ns a n d s y m pt o ms d et ect e d d uri n g e ac h 
ex a mi n ati o n, o bs er v ati o ns b y t h e st u d y p ers o n n el, 
 s p o nt a n e o us r e p orts fr o m t h e s u bj ects.
S ecti o n 4. 7 
Sc h e d ul e of 
ev e nts
L a b or at or y t ests ar e 
a d d e d at 4 w e e ks visit 
aft er i niti al tr e at m e nt
acc or di n g t o E C 
s u g g esti o n
F or d et ails of t h e c h a n g e pl e as e r ef er t o T a bl e 1 a n d t a bl e 
2.
S ecti o n 4. 8. 1. 3
4 W ( ± 3 d) aft er 
r a n d o miz ati o n 
F oll o w -
u p/ O pti o n al 
T o uc h -u p
L a b or at or y t ests ar e 
a d d e d at 4 w e e ks visit 
aft er i niti al tr e at m e nt 
acc or di n g t o E C 
s u g g esti o n
S ecti o n 4. 8. 1. 3   4 W ( ± 3 d) aft er r a n d o miz ati o n F oll o w -
u p/ O pti o n al T o uc h -u p

La b or at or y 
t ests ( h a e m at ol o g y a n d s er u m 
c h e mistr y)
S ecti o n 4. 8. 2. 6
4 W ( ± 3 d) aft er 
6 M tr e at m e nt 
F oll o w -
u p/ O pti o n al 
T o uc h -u p
Cl arific ati o n
Pr oc e d ur es ar e t h e s a m e as 4 W aft er r a n d o miz ati o n visit 
f or Gr o u p A a n d Tr e at m e nt Gr o u p , e xc e pt t h e e xtr a s et 
of p h ot o gr a p hs . ( D et ails pl e as e s e e s ecti o n 4. 8. 1. 3)
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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4. 0
 
 
 
Pri nt date:
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C CI

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Section 8.2
Laboratory 
assessment
Laboratory tests are 
added at 4 weeks visit 
after initial treatment 
according to EC 
suggestion
Laboratory samples will be taken at the screening visit 
(day -21 to day 1) for all subjects. In Group A and 
Treatment Group, it will also be taken at 4 weeks visit 
after initial treatment, 6 months visit after last 
treatment or at early termination if termination occurs 
before 6 months visit after last treatment. In control 
group, it will be taken at 6 months visit before treatment, 
4 weeks visits after 6M treatment and also be taken at 
final visit or early termination.
Subject 
information 
and informed 
consent form
Updates required: 
Yes  
   No  
Electronic case 
report form 
(eCRF)
Updates required:
Yes  
   No 
Title 
Doc id  
43CH1507 Perlane Lido midface study protocol
MA-30843
 
Effective date: 
 
Version: 
Effective
2016-09-07 11:57
4.0
Print date:
2023-04-18 09:19

4( 6 2)
I n v esti g at ors a n d St u d y A d mi nistrat i ve Str uct ur e
C o -or di n ati n g I nv esti g at or
S p o ns or
Q- M e d A B
S e mi n ari e g at a n 2 1
S E -7 5 2 2 8  U p ps al a, S w e d e n
T el e p h o n e:
+ 4 6 1 8 4 7 4 9 0 0 0
F acsi mil e:
+ 4 6 1 8 4 7 4 9 0 0 1
M e dic al Ex p ert
Cli nic al Pr oj ect M a n a g er
St u d y St atistici a n
C o ntr act R es e arc h Or g a niz ati o n
( C R O)
F urt h er d et ails o n all p artici p ati n g I n v esti g at ors a n d t h e c o m pl et e a d mi nistr ati v e str uct ur e of t h e st u d y 
ar e f o u n d i n t h e st u d y fil e s. N ot e t h at a d mi nistr ativ e c h a n g es ar e t o b e d oc u m e nt e d i n t h e st u dy fil es 
wit h o ut r e q uiri n g a cli nic al st u dy pr ot oc ol ( CS P) a m e n d m e nt.
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
P P D
P P D
P P D
P P D

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S p o ns or Si g n at ur e s
T h e C S P is el ectr o nic all y si g n e d i n t h e d oc u m e nt m a n a g e m e nt s yst e m wit hi n t h e Q -
M e d A B q u alit y m a n a g e m e nt s yst e m b y t h e r e pr es e nt ati v es list e d b el o w.
,   
Q- M e d
A B
El ectr o nic all y si g n e d i n t h e d oc u m e nt 
m a n a g e m e nt s yst e m wit hi n Q -M e d 
q u alit y m a n a g e m e nt s yst e m
S p o ns or ’s M e dic al E x p ert, Q- M e d
A B
El ectr o nic all y si g n e d i n t h e d oc u m e nt 
m a n a g e m e nt s yst e m wit hi n Q -M e d 
q u alit y m a n a g e m e nt s yst e m
Cli nic al Pr oj ect M a n a g er , Q-M e d A B
El ectr o nic all y si g n e d i n t h e d oc u m e nt 
m a n a g e m e nt s yst e m wit hi n Q -M e d 
q u alit y m a n a g e m e nt s yst e m
St u d y St atistici a n, Q- M e d
A B
El ectr o nic all y si g n e d i n t h e d oc u m e nt 
m a n a g e m e nt s yst e m wit hi n Q - M e d q u alit y 
m a n a g e m e nt s yst e m 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
P P D
P P D
P P D
P P D
P P D

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Signed Agreement of the Clinical Study Protocol
CTN:                                                      43CH1507
Title of the CSP:
A randomized, multi-center, evaluator-blinded, no-
treatment controlled study to evaluate the efficacy and 
safety of Restylane Perlane Lidocaine for correction of 
Midface Volume Deficit and/or Midface Contour Deficiency
I, the undersigned, have read and understand the protocol specified above, and agree on 
the contents. The study protocol, the Clinical Trial Agreement and the additional 
information given in the Instruction For Use for Restylane Perlane Lidocaine will serve as a 
basis for co-operation in this study.
Principal Investigator
Printed name 
Signature
Date
Study site
Title 
Doc id  
43CH1507 Perlane Lido midface study protocol
MA-30843
 
Effective date: 
 
Version: 
Effective
2016-09-07 11:57
4.0
Print date:
2023-04-18 09:19

7( 6 2)
S y n o psis
Titl e of st u d y:
A r a n d o miz e d, m ulti -c e nt er, e v al u at or-bli n d e d, n o -tr e at m e nt c o ntr oll e d st u d y t o 
e v al u at e t h e effic ac y a n d s af et y of R est yl a n e P erl a n e Li d oc ai n e f or c orr ecti o n of 
Mi df ac e V ol u m e D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y 
Cli nic al Tri al N u m b er:  
4 3 C H 1 5 0 7
C o u ntri es i n v ol v e d, 
n u m b er of 
sit es/c o u ntr y, n u m b er 
of s u bj ects:
T h e st u d y will b e c o n d uct e d at a p pr oxi m at el y 5 sit es i n C hi n a. 
Gr o u p A:
U p t o 2 0 s u bj ects ( 2 first tr e at e d s u bj ects p er Tr e ati n g I n v esti g at or) will b e 
e nr oll e d as gr o u p A. T h es e s u bj ects wil l all r ec ei v e tr e at m e nt wit h R est yl a n e 
P erl a n e Li d oc ai n e ( P erl a n e -Li d o).
Gr o u p B:
E v al u at or tr e at m e nt -bl i n d gr o u p wit h a p pr oxi m at el y 1 48 s u bj ects will b e 
r a n d o miz e d i n a 3: 1 r ati o t o tr e at m e nt gr o u p or n o-tr e at m e nt c o ntr ol gr o u p, i. e., 
1 1 1 s u bj ects assi g ne d t o t h e Tr e at m e nt Gr o u p a n d 3 7 s u bj ects assi g n e d t o t h e 
C o ntr ol Gr o u p.
C o -or di n ati n g 
I n v esti g at or: 
Pri m ar y o bj ecti v e:
T h e pri m ar y o bj ectiv e is t o d e m o nstr at e s u p eri orit y of P erl a n e -Li d o r el ativ e t o 
n o -tr e at m e nt i n t h e tr e at m e nt of Mi df ac e v ol u m e D eficit a n d/ or Mi df ac e 
C o nt o ur D efici e nc y b y c o m p ari n g t h e p erc e nt r es p o n d ers, d efi n e d b y at l e ast 1 
p oi nt i m pr o v e m e nt fr o m b as e li n e o n t h e M M V S o n b ot h si d es of t h e f ac e, as 
m e as ur e d b y bli n d e d e v al u at or at 6 m o nt hs .
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
P P D
C CI

8( 6 2)
S af et y o bj ecti v es:
T h e s af et y o bj ecti v es ar e:

T o e v al u at e t h e s af et y of P erl a n e -Li d o d uri n g t h e w h ol e st u d y b y 
c oll ecti n g A d v ers e E v e nts ( A Es).
St u d y D esi g n:
T his is a r a n d o miz e d, e v al u at or -bli n d e d, n o -tr e at m e nt c o ntr oll e d st u d y i n 
s u bj ects wit h Mi df ac e V ol u m e D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y. 
S u bj ects will b e scr e e n e d f or eli gi bilit y wit hi n 2 1 d a ys pri or t o B as eli n e. T h e first 2 
eli gi bl e s u bj ects f or e ac h Tr e ati n g I nv esti g at or will r ec eiv e tr e at m e nt as Gr o u p A, 
B ef or e st art of e nr ol m e nt i nt o Gr o u p B, t h e i nj ecti o n t ec h ni q u e will b e e v al u at e d 
by t h e S p o ns or a n d p erf or m e d w h e n t h e s u bj ects i n Gr o u p A f or e ac h sit e h a v e 
r ec ei v e d t h eir first tr e at m e nt. If tr e at m e nts ar e f o u n d t o b e c orr ectl y p erf or m e d, 
n o f urt h er tr ai ni n g is n e e d e d, t h er e ar e n o o utst a n di n g q u esti o ns r e g ar di n g t h e 
i nj ecti o n t ec h ni q ue a n d n o ot h er c orr ecti v e acti o ns ar e i d e ntifi e d, t h e e nr ol m e nt 
i n Gr o u p B c a n st art f or t h at sit e. S u bj ects i n gr o u p B will b e r a n d o miz e d eit h er t o 
t h e Tr e at m e nt Gr o u p or t h e C o ntr ol Gr o u p i n a 3: 1 r ati o.
S u m m ari es of t h e r es ults f or Gr o u p A a n d B will b e d o n e s e p ar at el y i n t h e st u d y 
r e p ort.
Tr e at m e nt 
E ac h s u bj ect assi g n e d t o Gr o u p A or t h e T r e at m e nt G r o u p i n Gr o u p B will r ec ei v e 
a n i niti al tr e at m e nt o n D a y 1. A t o uc h -u p tr e at m e nt m a y b e p erf or m e d 4 w e e ks 
aft er t h e i niti al tr e at m e nt if o pti m al mi df ac e a u g m e nt ati o n h as n ot b e e n 
o bt ai n e d. O pti m al mi df ac e a u g m e nt ati o n is d efi n e d as t h e b est p ossi bl e a est h etic 
r es ult t h at c a n b e o bt ai n e d f or a n i n di vi d u al st u d y p artici p a nt, as a gr e e d u p o n b y 
t h e tr e ati n g i n v esti g at or a n d s u bj ect. 
S u bj ects assi g n e d t o t h e C o ntr ol Gr o u p i n Gr o u p B will n ot r ec ei v e tr e at m e nt at 
b as eli n e b ut will r et ur n f or r o uti n e f oll o w -u p f or 1 2 m o nt hs. At m o nt h 6 visit, 
s u bj ects i n C o ntr ol G r o u p will b e off er e d a tr e at m e nt a n d a n o pti o n al t o uc h -u p 
tr e at m e nt. 
E v al u ati o n of eff ectiv e n ess
Mi df ac e f ull n ess will b e ass ess e d usi n g a s e p ar at e f o ur -gr a d e M M V S wit h p h ot o
g ui d es f or t h e ri g ht a n d l eft si d e 
 by
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
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C CI
C CI
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9( 6 2)
t h e bli n d e d ev al u at or at scr e e ni n g, b as eli n e , , 6,  
 m o nt hs i n G r o u p A 
a n d T r e at m e nt G r o u p, a n d at scr e e ni n g, b as eli n e,
6 m o nt hs,  
 
 i n C o ntr ol G r o u p. 
E v al u at i o n of s af et y
I nf or m ati o n r e g ar di n g A Es will b e c oll ect e d c o nti n u o usl y d uri n g t h e st u d y. 
I ncl usi o n crit eri a: 
T h e s u bj ect m ust m e et t h e f oll o wi n g crit eri a t o b e eli gi bl e f or t h e st u d y:
1.
Si g n e d a n d d at e d i nf or m e d c o ns e nt t o p artici p at e i n t h e st u d y
2.
M e n or w o m e n a g e d 1 8 y e ars of a g e or ol d er of C hi n es e ori gi n
3.
S u bj ects willi n g t o a bst ai n fr o m a ny ot h er f aci al pl astic s ur gic al or 
c os m etic pr oc e d ur es b el o w t h e l ev el of t h e l o w er or bit al ri m f or t h e 
d ur ati o n of t h e st u d y ( e. g., l as er or c h e mic al r es urf aci n g, n e e dli n g, 
f ac elift, r a di ofr e q u e nc y etc.).
4.
S u bj ects s e e ki n g a u g m e nt ati o n t h er a p y f or t h e mi df ac e
5.
M M V S sc or e of 2, 3 or 4 o n e ac h si d e of t h e f ac e as ass ess e d by t h e 
bli n d e d e v al u at or 
E xcl usi o n crit eri a:
T h e pr es e nc e of a n y of t h e f oll o wi n g excl usi o n crit eri a will excl u d e a s u bj ect fr o m 
e nr ol m e nt i n t h e st u d y:
1.
K n o w n/ pr e vi o us all er g y or h y p ers e nsiti vit y t o a n y i nj ect a bl e H A g el.
2.
K n o w n/ pr e vi o us all er g y or h y p ers e nsitivit y t o l oc al a n a est h etics, e. g. 
li d oc ai n e or ot h er a mi d e-t y p e a n a est h etics 
3.
Hist or y of s e v er e or m ulti pl e all er gi es m a nif est e d b y a n a p h yl axis 
4.
Pr e vi o us tiss u e r e vit aliz ati o n tr e at m e nt wit h l as er or li g ht, m es ot h er a p y, 
r a di ofr e q u e nc y, 
ultr as o u n d, 
cr y ot h er a p y, 
c h e mic al 
p e eli n g 
or 
d er m a br asi o n i n t h e mi df ac e wit hi n 6 m o nt hs b ef or e tr e at m e nt
5.
Pr e vi o us 
s ur g er y (i ncl u di n g a est h etic 
f aci al s ur gic al t h er a p y or 
li p os ucti o n) or t att o o i n t h e ar e a t o b e tr e at e d 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI
C CI
C CI
C CI
C CI
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10(62)
6.
Previous tissue augmentation therapy or contouring with any permanent 
(non-biodegradable) or semi-permanent filler, autologous fat, lifting 
threads or permanent implant below the level of the lower orbital rim. 
7.
Previous use of any hyaluronic acid based or collagen based 
biodegradable facial tissue augmentation therapy below the level of the 
lower orbital rim within 12 months before treatment.
8.
Previous use of any neurotoxin below the level of the lower orbital rim 
within 9 months before treatment.
9.
History of radiation or cancerous or pre-cancerous lesions (e.g. actinic 
keratosis) in the area to be treated
10. Scars or deformities, active skin disease, inflammation or related 
conditions, such as infection, perioral dermatitis, seborrheic eczema, 
rosacea, acne psoriasis and herpes zoster near or in the area to be 
treated.
11. Subjects with a dental or oral status on visual inspection that in the 
opinion of the Investigator would make the subject unsuitable for 
inclusion, or Subjects with dental, oral or sinus surgery within past 12 
months prior to the treatment visit or planned surgery, including dental 
implants, during the study period.
12. Ongoing infection in mouth or dentals
13. Chronic infection in head and neck region
14. Tendency for edema, puffiness or swelling in the area to be treated 
15. History of or active autoimmune disease or connective tissue diseases 
such as systemic lupus erythematosus, rheumatoid  arthritis, 
polymyositis, dermatomyositis or localized or systemic scleroderma. 
16. Tendency to form keloids, hypertrophic scars, or any other healing 
disorder
17. History of bleeding disorders or treatment with anticoagulants or 
inhibitors of platelet aggregation (e.g. aspirin or other non-steroid anti-
inflammatory drugs (NSAIDs), Omega-3, or vitamin E within 2 weeks 
before treatment 
18. Treatment 
with 
chemotherapy, 
immunosuppressive 
agents, 
immunomodulatory therapy (e.g. monoclonal antibodies), systemic or 
topical (facial) corticosteroids within 3 months  before treatment 
(inhaled corticoids are allowed)
19. Treatment with topical (facial) retinoids within 3 months or systemic 
retinoids within 6 months before treatment.
20. The presence of moderate or severe abnormal rating for midface 
symmetry, i.e. more than 1 grade difference in MMVS score between 
each side of the face.
21. Any medical condition that in the opinion of the Investigator would make 
the subject unsuitable for inclusion (e.g. a chronic, relapsing or 
hereditary disease that may affect the general condition or may require 
Title 
Doc id  
43CH1507 Perlane Lido midface study protocol
MA-30843
 
Effective date: 
 
Version: 
Effective
2016-09-07 11:57
4.0
Print date:
2023-04-18 09:19

1 1 ( 6 2)
fr e q u e nt m e dic al tr e at m e nt, a n y a b n or m al scr e e ni n g l a b or at or y v al u e or 
E C G, or ps yc hi atric dis or d ers).
2 2. Ot h er c o n diti o n pr ev e nti n g t h e s u bj ect fr o m e nt eri n g t h e st u d y i n t h e 
I n v esti g at or’s o pi ni o n, e. g. s u bj ects n ot li k ely t o a v oi d ot h er f aci al 
c os m etic tr e at m e nts, s u bj ects a ntici p at e d t o b e u nr eli a bl e, u n av ail a bl e 
or i nc a p a bl e of u n d erst a n di n g t h e st u d y ass ess m e nts or h avi n g 
u nr e alistic ex p ect ati o ns of t h e tr e at m e nt r es ult
2 3. W o m e n w h o ar e pr e g n a nt or br e ast f e e di n g, or W o m a n of c hil d b e ari n g 
p ot e nti al w h o ar e n ot pr actici n g a d e q u at e c o ntr ac e pti o n or pl a n ni n g t o 
b ec o m e pr e g n a nt d uri n g t h e st u d y p eri o d.
2 4. I nt e nti o n t o c h a n g e a si g nific a nt a m o u nt of w ei g ht (≥2 B MI) d uri n g t h e 
st u d y p eri o d
2 5. St u d y sit e p ers o n n e l, cl os e r el ativ es of t h e st u d y sit e p ers o n n el ( e. g. 
p ar e nts, c hil dr e n, si bli n gs, or s p o us e), e m pl o y e es, or cl os e r el ativ es of 
e m pl o y e es at t h e S p o ns or c o m p a n y 
2 6. P artici p ati o n i n a n y ot h er cli nic al st u d y wit hi n 3 0 d a ys b ef or e tr e at m e nt 
I n v esti g ati o n al 
pr o d uct, 
d os e a n d m o d e of 
a d mi nistr ati o n:
P erl a n e -Li d o c o nsists of st a biliz e d h y al ur o nic aci d of n o n-a ni m al ori gi n at a 
c o nc e ntr ati o n of 2 0 m g/ mL, i n p h os p h at e b uff er e d s ali n e wit h li d oc ai n e 
h y dr oc hl ori d e 3 m g/ ml. T h e st u d y pr o d uct is s u p p li e d i n st eril e 1 mL s yri n g es.  A 
2 9 G t hi n w all e d ( T W) × ½” n e e dl e will b e us e d f or i nj ecti o n.
P erl a n e -Li d o s h o ul d b e i nj ect e d i nt o s u bc ut a n e o us t o s u pr a p eri ost e al l a y er i n t h e 
mi df ac e. 
P erl a n e -Li d o will b e a d mi nist er e d i nf eri or t o t h e m axill ar y pr o mi n e nce, s u p eri or 
t o t h e pl a n e of n as al al a e, i ncl u di n g t h e ar e a fr o m t h e l at er al c a nt h us t o t h e 
m e di al c a nt h us a n d l at er al t o t h e n os e o n t h e s u bj ect’s ri g ht a n d l eft si d es. 
I n v esti g at ors will b e i nstr uct e d t o us e t h e a m o u nt of d er m al fill er n ec ess ar y t o 
ac hi e v e a n o pti m al a est h etic r es ult. 
T h e i nj ecti o n pr oc e d ur e s h o ul d strictl y f oll o w r ul es of as e ptic s ur gic al t ec h ni q u e 
(r ef er t o t h e P erl a n e- Li d o I F U f or d et ails).
D ef ects s h o ul d b e f ull y c orr ect e d, b ut n ot o v erc orr ect e d.  T h e i nj ecti o n sit e 
s h o ul d b e m ass a g e d t o c o nf or m t o t h e c o nt o ur of t h e s urr o u n di n g tiss u es .
It is r ec o m m e n d e d t h at t h e d os e s h o ul d n ot exc e e d 4 mL (i. e., ri g ht a n d l eft 
mi df ac e c o m bi n e d) f or a tr e at m e nt s essi o n, i. e., i niti al tr e at m e nt or t o uc h-u p 
tr e at m e nt r es p ecti v el y.
R ef er e nc e t h er a p y, 
d os e a n d m o d e of 
a d mi nistr ati o n:
N ot a p plic a bl e.
D ur ati o n of tr e at m e nt 
a n d f oll o w -u p: 
T h e t ot al d ur ati o n f or e ac h s u bj ect will b e a p pr oxi m at el y 1 4 m o nt hs .
Effic ac y Ass ess m e nt: 
M e dicis Mi df ac e V ol u m e Sc al e ( M M V S) :
M M V S is a 4 -gr a d e sc al e ass ess es t h e f ull n ess of t h e mi df ac e fr o m F airl y F ull ( 1) 
t o S u bst a nti al L oss of F ull n ess ( 4) as d escri b e d b el o w.  T h e bli n d e d e v al u at or 
 
 will r at e t h e s u bj ect’s ri g ht a n d l eft mi df ac e f or s e v erit y of 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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1 2 ( 6 2)
v ol u m e d efici e nc y usi n g t h e M M V S at all a p plic a bl e st u d y visits . 
M M V S
1
F airl y f ull mi df ac e
2
Mil d l oss of f ull n ess i n mi df ac e ar e a
3
M o d er at e l oss of f ull n ess wit h sli g ht h oll o wi n g b el o w m al ar 
pr o mi n e nc e
4
S u bst a nti al l oss of f ull n ess i n t h e mi df ac e ar e a, cl e arl y a p p ar e nt 
h oll o wi n g b el o w m al ar pr o mi n e nc e
S af et y Ass ess m e nt:
A E will b e gi n t o b e c oll ect e d aft er I C F si g n e d. E ac h s u bj ect will b e q u esti o n e d 
a b o ut A Es at e ac h cli nic al visit f oll o wi n g t h e scr e e ni n g visit. T h e q u esti o n as k e d 
will b e “ Si nc e y o ur l ast cli nic al visit h av e y o u h a d a ny h e alt h pr o bl e ms ?” 
I nf or m ati o n o n A Es c a n als o b e o bt ai n e d fr o m l a b or at or y t est r e p ort, si g ns a n d 
s y m pt o ms d et ect e d d uri n g e ac h ex a mi n ati o n, o bs er v ati o ns b y t h e st u d y 
p ers o n n el, 
 s p o nt a n e o us r e p orts fr o m t h e s u bj ects.
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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St atistic al M et h o ds: 
All s u m m ari es will b e d o n e s e p ar at el y f or Gr o u p A a n d B. F or st atistic al i nf er e nc e, 
o nl y Gr o u p B will b e us e d.
Pri m ar y a n al ysis
T h e p erc e nt r es p o n d ers ( a r es p o n d er will b e d efi n e d as a s u bj ect wit h at l e ast 1 
gr a d e i m pr o v e m e nt fr o m b as eli n e M M V S f or t h e ri g ht a n d l eft si d es of t h e f ac e 
c o m bi n e d) will b e c alc ul at e d f or e ac h tr e at m e nt gr o u p at M o nt h 6 b as e d o n t h e 
bli n d e d e v al u at or's ass ess m e nt. 
 
 
 
 
 
 
 
 
S af et y
 
A d v ers e e v e nt i nci d e nc es will b e 
s u m m ariz e d b y M e d D R A s yst e m or g a n cl ass ( S O C) a n d pr ef err e d t er m ( P T).
S a m pl e siz e
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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4. 0
 
 
 
Pri nt date:
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Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
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A b br e vi ati o ns a n d d efi niti o ns of t er ms 
A E
A d v ers e E v e nt 
Bli n d e d E v al u at or
A n ev al u at or r es p o nsi bl e f or i n d e p e n d e nt ev al u ati o n of tr e at m e nt 
r es ult(s). T h e e v al u at or m ust n ot b e i n v ol v e d i n t h e tr e at m e nt of t h e 
s u bj ect.
C F D A
C hi n a F o o d a n d Dr u g A d mi nistr ati o n
C o -or di n ati n g 
I nv esti g at or
A n I n v esti g at or assi g n e d t h e r es p o nsi bilit y f or t h e c o or di n ati o n of 
I n v esti g at ors at diff er e nt c e nt ers p artici p ati n g i n a m ultic e nt er st u d y
C S P
Cli nic al St u d y Pr ot oc ol
C T A
Cli nic al Tri al A gr e e m e nt
C T N
Cli nic al tri al n u m b er
C V
C urric ul u m vit a e
D evic e d efici e nc y
I n a d e q u ac y of a m e dic al d e vic e wit h r es p ect t o its i d e ntit y, q u alit y, 
d ur a bilit y, r eli a bilit y, s af et y or p erf or m a nc e (i ncl u d es m alf u ncti o ns, us e 
err ors, a n d i n a d e q u at e l a b elli n g)
D M P
D at a m a n a g e m e nt pl a n
E C G
El ectr oc ar di o gr a p h
e C R F
El ectr o nic C as e R e p ort F or m
F A S
F ull A n al ysis S et
G
G a u g e
G C P
G o o d Cli nic al Pr actic e
H A
H y al ur o nic aci d
I C F
I nf or m e d C o ns e nt F or m
I C H
I nt er n ati o n al C o nf er e nc e o n H ar m o nis ati o n 
I E C
I n d e p e n d e nt Et hics C o m mitt e e
I F U
I nstr ucti o ns f or Us e
I nv esti g ati o n al 
pr o d uct
M e dic al d e vic e b ei n g ass ess e d f or s af et y or p erf or m a nc e i n a st u d y. 
“I n v esti g ati o n al pr o d uct” is t h e s a m e as “st u d y d e vic e”, “i n v esti g ati o n al 
d e vic e”, or “i nv esti g ati o n al m e dic al d evic e”.
I nstit uti o n
A n y p u blic or pri v at e e ntit y or a g e nc y or m e dic al or d e nt al f acilit y w h er e 
cli nic al st u di es ar e c o n d uct e d.
I nv esti g at or
T h e Pri nci p al I n v esti g at or or ot h er q u alifi e d p ers o n, i. e. s u b -I n v esti g at or, 
d esi g n at e d a n d s u p er vis e d b y t h e Pri nci p al I n v esti g at or at a st u d y sit e t o 
p erf or m critic al st u d y -r el at e d pr oc e d ur es a n d/ or m a k e i m p ort a nt st u d y-
r el at e d d ecisi o ns as s p ecifi e d o n t h e d el e g ati o n l o g. 
I nv esti g at or Fil e
Ess e nti al d oc u m e nts r el ati n g t o a cli nic al st u d y as d efi n e d i n G C P 
g ui d a nc e d oc u m e nt a n d m ai nt ai n e d b y t h e I n v esti g at or.
M e d D R A
M M V S
M e dic al Dicti o n ar y f or R e g ul at or y Acti viti es
M e dicis Mi df ac e V ol u m e Sc al e
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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16(62)
NSAIDs
non-steroid anti-inflammatory drugs
PI 
Principal Investigator
PP
Per protocol
QA
Quality assurance
RA
Regulatory authority
Perlane-Lido
Restylane Perlane Lidocaine
PT
Preferred term
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SDV
Source data verification
SOC
System organ class 
Sponsor file
Essential documents relating to a clinical study as defined in applicable 
GCP guidance document and maintained by the Sponsor.
U-HCG
Urinary human chorionic gonadotropin
WHO
World Health Organization
Title 
Doc id  
43CH1507 Perlane Lido midface study protocol
MA-30843
 
Effective date: 
 
Version: 
Effective
2016-09-07 11:57
4.0
Print date:
2023-04-18 09:19

1 7 ( 6 2)
Ta bl e of C o nt e nts
S U M M A R Y O F C H A N G E S I N CLI NI C AL S T U D Y P R O T O C OL 4 3 C H 1 5 0 7 F R O M V E R SI O N 3. 0 T O 
V E R SI O N 4. 0
2
I N V E S TI G A T O R S A N D S TU D Y A D MI NI S T R A TI V E S T R U C T U R E
4
S P O N S O R SI G N A T U R E S
5
SI G N E D A G R E E M E N T O F T H E CLI NI C AL S T U D Y P R O T O C OL
6
S Y N O P SI S
7
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 5
T A BL E O F C O N T E N T S
1 7
1
E T HI C AL C O N SI D E R A TI O N S
2 0
2
B A C K G R O U N D I N F O R M A TI O N
2 0
2. 1
I n dic ati o n a n d p o p ul ati o n d escri pti o n
2 0
2. 2
I nv esti g ati o n al pr o d uct d escri pti o n
2 0
2. 3
R ef er e nc e pr o d uct d escri pti o n
2 1
2. 4
Pr evi o us ex p eri e nc e
2 1
2. 4. 1
N o n -Cli nic al D oc u m e nt ati o n
2 1
2. 4. 2
Cli nic al D oc u m e nt ati o n
2 1
2. 5
St u d y r ati o n al e
2 2
2. 6
J ustific ati o n f or t h e d esi g n of t h e st u d y
2 2
2. 7
Ris k a n d b e n efits
2 2
3
O BJ E C TI V E S A N D E N D P OI N T S
2 3
3. 1
Pri m ar y o bj ecti v e a n d e n d p oi nt
2 3
3. 3
S af et y o bj ecti v es a n d e n d p oi nts
2 4
4
D E SI G N O F T H E S T U D Y
2 4
4. 1
G e n er al O utli n e
2 4
4. 2
N u m b er of S u bj ects
2 6
4. 3
D ur ati o n of S u bj ect P artici p ati o n
2 6
4. 4
R a n d o miz ati o n a n d bli n di n g
2 6
4. 4. 1
R a n d o mi zati o n
2 6
4. 4. 2
Bli n di n g
2 6
4. 4. 3
E m er g e ncy u n bli n di n g
2 6
4. 5
M e dic al hist or y
2 6
4. 6
C o nc o mit a nt M e dic ati o n, Tr e at m e nt, a n d Pr oc e d ur e
2 6
4. 7
Sc h e d ul e of e v e nts
2 8
4. 8
Visits
3 1
4. 8. 1
Visits f or Gr o u p A a n d Tr e at m e nt Gr o u p
3 1
4. 8. 2
Visits f or C o ntr ol Gr o u p
3 2
5
S U BJ E C T S
3 4
5. 1
S u bj ect i nf or m ati o n a n d i nf or m e d c o ns e nt
3 4
5. 2
I ncl usi o n Crit eri a
3 5
5. 3
Excl usi o n Crit eri a
3 5
5. 4
Scr e e ni n g a n d S u bj ect N u m b ers
3 7
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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1 8 ( 6 2)
5. 5
Wit h dr a w al of S u bj ects
3 7
6
S T U D Y P R O D U C T S
3 8
6. 1
I nv esti g ati o n al Pr o d uct
3 8
6. 2
R ef er e nc e Pr o d uct
3 8
6. 3
A d diti o n al Pr o d ucts a n d M at eri al
3 8
6. 4
P ac k a gi n g, L a b elli n g a n d St or a g e
3 8
6. 5
Pr o d uct acc o u nt a b ility
3 8
6. 6
Tr e at m e nt
3 9
6. 6. 1
Tr e at m e nt Pr oc e d ur e
3 9
6. 6. 2
Tr e at m e nt r e gi m e n ( d os e)
4 1
6. 6. 3
P ost -tr e at m e nt C ar e
4 1
6. 6. 4
P ost -tri al pr ovisi o ns
4 1
6. 6. 5
El ectr o nic c as e r e p ort f or m r ec or di n gs
4 1
6. 6. 6
Tr e at m e nt c o m pli a nc e
4 1
7
E F FI C A C Y A S S E S S M E N T S
4 1
7. 1
G e n er al i nf or m ati o n
4 1
7. 2
M e dicis Mi df ac e V ol u m e Sc al e ( M M V S)
4 2
8
S A F E T Y A S S E S S M E N T S
4 5
8. 2
L a b or at or y ass ess m e nt
4 5
8. 3
E C G -scr e e ni n g
4 6
8. 4
A dv ers e E v e nts
4 6
8. 4. 1
D efi niti o n of A dv ers e Ev e nts
4 6
8. 4. 2
D efi niti o n of S eri o us A dv ers e Ev e nt
4 6
8. 4. 3 
R ec or di n g I nstr ucti o ns
4 6
8. 4. 4
R e p orti n g of A dv ers e Ev e nts
4 8
8. 4. 5
R e p ort i n g of S eri o us A dv ers e Ev e nts
4 8
8. 4. 6
F oll o w -u p of U nr es olv e d Ev e nts aft er st u dy t er mi n ati o n
5 0
8. 4. 7
Pr e g n a ncy
5 0
8. 4. 8
A ntici p at e d A dv ers e Ev e nts
5 0
8. 5
D evic e D efici e nci es
5 0
8. 5. 1
D efi niti o n of D evic e D efici e ncy
5 0
8. 5. 2 
R ec or di n g I nstr ucti o ns
5 1
8. 5. 3
R e p orti n g D evic e D efici e ncy
5 1
9
D A T A H A N DLI N G A N D M A N A G E M E N T
5 1
9. 1
D at a m a n a g e m e nt
5 1
9. 2
El ectr o nic c as e r e p ort f or ms
5 2
9. 2. 1
D at a e ntry
5 2
9. 2. 2
T h e q u ery pr oc ess
5 2
9. 2. 3
Us er i d e ntific ati o n
5 3
9. 2. 4
A u dit tr ail
5 3
9. 3
S o urc e d oc u m e nts
5 3
9. 4
R ec or d k e e pi n g a n d acc ess t o s o urc e d at a
5 3
9. 5
D oc u m e nt a n d d at a r et e nti o n
5 4
1 0
S T A TI S TI C AL M E T H O D S
5 4
1 0. 1
G e n er al
5 4
1 0. 2
A n al ysis P o p ul ati o ns
5 5
1 0. 3
D e m o gr a p hics, b as eli n e ass ess m e nts, a n d s u bj ect c h ar act eristics
5 5
1 0. 4
Effic ac y A n al ysis
5 5
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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4. 0
 
 
 
Pri nt date:
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1 9 ( 6 2)
1 0. 5
S af et y A n al ysis
5 6
1 0. 6
H a n dli n g of Missi n g D at a
5 6
1 0. 7
I nt eri m A n al ysis
5 7
1 0. 8
D at a m o nit ori n g c o m mitt e e
5 7
1 0. 9
Wit h dr a w als a n d d e vi ati o ns
5 7
1 0. 1 0
S a m pl e Siz e
5 7
1 1
P R O T E C TI O N O F P E R S O N AL D A T A
5 7
1 2
Q U ALI T Y C O N T R OL A N D Q U ALI T Y A S S U R A N C E
5 8
1 2. 1
Q u alit y c o ntr ol
5 8
1 2. 2
Q u alit y ass ur a nc e
5 8
1 2. 3
C h a n g es t o t h e cli nic al st u d y pr ot oc ol
5 9
1 3
FI N A N CI N G, I N D E M NI FI C A TI O N, A N D I N S U R A N C E
5 9
1 4
P U BLI C A TI O N P OLI C Y
5 9
1 5
S U S P E N SI O N O R P R E M A T U R E T E R MI N A TI O N
5 9
1 6
R E F E R E N C E S
6 1
1 7
A P P E N DI C E S
6 2
List of T a bl es
T a bl e 1. Sc h e d ul e of E v e nts f or Gr o u p A a n d Tr e at m e nt G r o u p ............................................2 8
Gr o u p A a n d Tr e at m e nt G r o u p................................................................................................2 8
T a bl e 2. Sc h e d ul e of E v e nts f or C o ntr ol G r o u p ......................................................................2 9
T a bl e 3 . M e dicis Mi df ac e V ol u m e Sc al e .................................................................................4 2
List of Fi g ur es
Fi g ur e 1.  Fl o w c h art … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … … . 25
Fi g ur e 2. Tr e at m e nt Ar e a ...… … … … … … … … … … … … … … … … … … … … … … … …. … … … . …… … … … .… … … 4 0
List of A p p e n dic es
A p p e n dix 1
D ecl ar ati o n of H elsi n ki 
A p p e n dix 2
P h ot o g ui d e f or M e dicis Mi df ac e V ol u m e Sc al e
A p p e n dix 3    E U I F U of R est yl a n e P erl a n e Li d oc ai n e
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

20(62)
1
Ethical Considerations
1.1 Statement of ethical compliance
The study shall be conducted in compliance with the Clinical Trial Agreement (CTA), the 
Clinical Study Protocol (CSP), applicable Good Clinical Practice (GCP), and applicable regional 
or national regulations. The international standard for clinical study of medical devices for 
human subjects, ISO14155:2011 shall be followed. The International Conference on 
Harmonisation (ICH) guideline for GCP (E6) shall be followed as applicable for medical 
device. The study shall be conducted in accordance with the ethical principles that have 
their origin in the Declaration of Helsinki (Appendix 1).
1.2 Application to independent ethics committee and/or regulatory authorities
It is the responsibility of the Principal Investigator (PI) to obtain approval of the 
CSP/CSP amendment(s) from the independent ethics committee (IEC). The study shall not 
begin until the required favourable opinion from the IEC has been obtained. The PI shall file 
all correspondence with the IEC in the Investigator file and copies of IEC approvals shall be 
forwarded to the Sponsor. Any additional requirements imposed by the IEC or regulatory 
authorities (RA) shall be followed. 
The collection, access to, processing, and transfer of protected health information or 
sensitive personal data shall be carried out in accordance with applicable rules and 
regulations.
2
Background Information
2.1
Indication and population description
Restylane Perlane Lidocaine (Perlane-Lido) has been approved in the United States, Europe 
and several countries worldwide as a medical device for facial tissue augmentation. In 
Europe, the label recommends the product to be used for shaping the contours of the face, 
the correction of folds and for lip enhancement.
2.2
Investigational product description 
Among the different materials used as raw materials in injectable fillers for aesthetic use, 
sodium hyaluronate, also denoted hyaluronic acid (HA) when found in vivo and hereinafter 
referred to as HA, is the most frequently used 1. Hyaluronic acid is a naturally occurring 
polysaccharide found in all vertebrates and in some bacteria 1, 2. 
The chemical structure of HA is very simple with repeating disaccharide units of glucuronic 
acid and N-acetylglucosamine. As the chemical structure of HA is identical in all species and 
tissues, it is non-allergenic.
To eliminate the risk for contamination, the HA used in the manufacture of Galderma’s HA 
gels is of non-animal source, biosynthesised from Streptococcus species of bacteria.
Title 
Doc id  
43CH1507 Perlane Lido midface study protocol
MA-30843
 
Effective date: 
 
Version: 
Effective
2016-09-07 11:57
4.0
Print date:
2023-04-18 09:19

2 1 ( 6 2)
D uri n g m a n uf act uri n g, 
cr oss-li n ks ar e i ntr o d uc e d b et w e e n t h e H A c h ai ns usi n g t h e 
N A S H A ( T M) t ec h n ol o g y i n or d er t o o bt ai n a g el n et w or k. As a r es ult, t h e d ur ati o n of t h e g el i n 
t h e b o d y is s e v er al m o nt hs, as c o m p ar e d t o o nl y a f e w d a ys f or a s ol uti o n of n ati v e H A.
P erl a n e -Li d o als o c o nsists of li d oc ai n e h y dr oc hl ori d e 3 m g/ ml.
2. 3
R ef er e nc e pr o d uct d escri pti o n
N ot a p plic a bl e.
2. 4
Pr e vi o us e x p eri e nc e
2. 4. 1
N o n -Cli nic al D oc u m e nt ati o n
I n or d er t o e ns ur e bi ol o gic al s af et y a n d t o f ulfill t h e d e m a n ds of t h e I S O 1 0 9 9 3 ( Bi ol o gic al 
E v al u ati o n of M e dic al d e vic es), 
s e v er al bi oc o m p ati bilit y st u di es e v al u ati n g c yt ot oxicit y, 
s e nsitiz ati o n, irrit ati o n, g e n ot oxicit y, g e n er al t oxicit y a n d l oc al eff ec ts aft er i m pl a nt ati o n 
h a v e b e e n p erf or m e d o n N A S H A g el pr o d ucts of diff er e nt g el p articl e siz e. T h e c o ncl usi o n 
fr o m t h es e st u di es h as b e e n t h at t h e pr o d ucts ar e w ell t ol er at e d wit h o ut a n y si g ns of 
t oxicit y.
I n a d diti o n, hist ol o gic al e v al u ati o ns aft er s u bc ut a n e o us i nj ecti o ns of R est yl a n e P erl a n e i n 
r ats h a v e b e e n p erf or m e d
3. At t h e t er mi n ati o n of t h e st u dy, ei g ht m o nt hs p ost i nj ecti o n, 
R est yl a n e P erl a n e still r e m ai n e d i d e ntifi a bl e b y hist ol o g y. T h e i m pl a nts w er e s urr o u n d e d by 
a u nif or ml y t hi n c a ps ul e wit h
o nl y mi ni m al 
c ell i nfiltr ati o n, c o nfir mi n g t h at R estyl a n e 
P erl a n e is hi g hl y bi oc o m p ati bl e.
2. 4. 2
Cli nic al D oc u m e nt ati o n
Exc e pt f or n as ol a bi al f ol ds tr e at m e nt,4, 5 P erl a n e -Li d o als o h as b e e n pr ov e n s af e a n d 
effic aci o us
f or c h e e k a u g m e nt ati o n a n d c orr ecti o n of a g e -r el at e d mi df ac e 
c o nt o ur 
d efici e nci es i n a cli nic al tri al6 ( M A-1 4 0 0 -0 5) p erf or m e d i n U S . P erl a n e -Li d o is a p pr ov e d 
u n d er t h e br a n d n a m e R est yl a n e ® L yft wit h Li d oc ai n e i n U S.
T h e st u d y w as a n e v al u at or -bli n d e d, n o tr e at m e nt c o ntr oll e d st u dy of 2 0 0 s u bj ects w h o
w er e r a n d o miz e d i n a 3: 1 r ati o t o r ec ei v e P erl a n e -Li d o i n t h e mi df ac e or n o tr e at m e nt at
b as eli n e. T h e pri m ar y eff ecti v e n ess o bj ecti v e w as t o i d e ntif y if P erl a n e -Li d o w as m or e 
eff ecti v e i n mi df ac e 
a u g m e nt ati o n t h a n n o tr e at m e nt as d et er mi n e d by t h e bli n d e d 
e v al u at or’s ass ess m e nt of mi df ac e f ull n ess usi n g t h e M e dicis Mi df ac e V ol u m e Sc al e (M M V S )
at M o nt h 2 f oll o wi n g b as eli n e/ D a y 0. 
I n t h e P erl a n e -Li d o gr o u p, 8 8. 7 % ( 1 3 3/ 1 5 0 s u bj ects) w er e M M V S r es p o n d ers i n t h e ri g ht a n d 
l eft mi df ac e c o m bi n e d. I n t h e n o tr e at m e nt gr o u p at M o nt h 2, t h e pr o p orti o n of M M V S 
r es p o n d ers fr o m b as eli n e w as 1 6. 0 % ( 8/ 5 0 s u bj ects). T h e diff er e nc e i n t h e pr o p orti o n of 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

2 2 ( 6 2)
M M V S r es p o n d ers fr o m b as eli n e f or ri g ht a n d l eft mi df ac e c o m bi n e d, b et w e e n t h e P erl a n e -
Li d o a n d n o tr e at m e nt gr o u ps, w as st atistic all y si g nific a nt ( p < 0. 0 0 1) i n f a v or of P erl a n e -Li d o
tr e at m e nt; t h er ef or e, t h e pri m ar y eff ecti v e n ess ass ess m e nt w as m et.
T h e pr o p orti o n of M M V S r es p o n d ers w as als o st atistic all y si g nific a nt at all ot h er e v al u ati o n 
ti m e p oi nts t hr o u g h M o nt h 1 2 f or b ot h t h e bli n d e d e v al u at or 
, 
as o utli n e d i n t h e s ec o n d ar y o bj ecti v es.
T h e st u d y als o i n dic at es t h at t h e s af et y pr ofil e of P erl a n e -Li d o is m ai nt ai n e d. T h e m aj orit y of 
e v e nts w er e mil d , c o nsi d er e d t ol er a bl e a n d r es ol v e d i n 2 – 7 d a ys. Br uisi n g t e n d e d t o h a v e a 
l o n g er d ur ati o n wit h t h e m aj orit y of s u bj ects r es ol vi n g b et w e e n 8 a n d 1 4 d a ys. T w o s u bj ects 
( 1 %, 2/ 1 9 9) r e p ort e d f o ur s eri o us a d v ers e ev e nts ( S A Es) t h at w er e c o nsi d er e d t o b e r el ate d 
t o t h e d e vic e a n d/ or t h e pr oc e d ur e. O n e s u bj ect r e p ort e d i m pl a nt sit e i nfl a m m ati o n (l at e 
o ns et i nfl a m m at or y r e acti o ns) i n b ot h c h e e ks at s e p ar at e ti m es. T h e s ec o n d s u bj ect 
ex p eri e nc e d i m pl a nt sit e h e m at o m as i n t h e ri g ht c h e e k a n d i m pl a nt sit e i nf ecti o n/a bsc ess. 
Tr e at m e nt of 
t h e S A Es i ncl u d e d N S AI Ds, 
a nti bi otics, i ncisi o n a n d dr ai n a g e 
a n d, 
h y al ur o ni d as e. All e v e nts r es ol v e d. 
P ost m ar k et s ur v eill a nc e d at a f or P erl a n e -L als o s u p p ort t h at t h e A E pr ofil e is acc e pt a bl e.
2. 5
St u d y r ati o n al e
By Jul y 2 0 1 5, P erl a n e -Li d o h as b e e n a p pr o v e d i n 5 2 c o u ntri es/r e gi o ns, i ncl u di n g U S, E U, 
H o n g K o n g, K or e a, I n di a, etc. 
Gi v e n t h e a ntici p at e d l o w l e v el or tr a nsi e nt a n d acc e pt a bl e ris k, t h e ris k/ b e n efit ass ess m e nt 
of t h e us e of P erl a n e -Li d o f or t h e c orr ecti o n of mi df ac e v ol u m e d eficit a p p e ars t o off er a 
s u bst a nti al cli nic al b e n efit at r e as o n a bl e ris k. T his st u d y ai ms t o ev al u at e t h e effic ac y a n d 
s af et y of P erl a n e -Li d o f or Mi df ac e v ol u m e D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y i n a 
C hi n es e p o p ul ati o n. 
O nl y st u d y i n v esti g at ors q u alifi e d b y e d uc ati o n a n d ex p eri e nc e, a n d w h o ar e s kill e d i n t h e 
us e of d er m al fill ers fr o m t h eir cli nic al pr actic e a n d p artici p ati o n i n cli nic al r es e arc h, will b e 
c h os e n i n or d er t o ass ur e pr o p er d e vic e i m pl a nt ati o n a n d m a n a g e m e nt of st u d y ris k.
2. 6
J ustific ati o n f or t h e d esi g n of t h e st u d y
T h e p ur p os e of t his st u d y is t o d e m o nstr at e s u p eri orit y of P erl a n e -Li d o r el ati v e t o n o -
tr e at m e nt i n t h e tr e at m e nt of Mi df ac e v ol u m e D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y b y 
c o m p ari n g t h e p erc e nt r es p o n d ers, d efi n e d b y at l e ast 1 p oi nt i m pr o v e m e nt fr o m b as eli n e 
o n t h e M M V S 
o n b ot h si d es of t h e f ac e, at 6 m o nt hs . Ev al u ati o n wit h st a n d ar diz e d
e v al u ati o n t o ols will b e us e d i n t h e st u dy. T h e M M V S 
w as us e d i n t h e P erl a n e -Li d o 
r e gistr ati o n cli nic al tri al f or mi df ac e a u g m e nt ati o n i n U S a n d acc e pt e d b y F D A.
2. 7
Ris k a n d b e n efits
Aft er t h e i nj ecti o n of P erl a n e -Li d o, s o m e c o m m o n i nj ecti o n-r el at e d r e acti o ns mi g ht occ ur. 
T h es e r e acti o ns i ncl u d e er yt h e m a, s w elli n g, p ai n, itc hi n g, br uisi n g or t e n d er n ess at t h e 
i m pl a nt sit e. T y pic all y r es ol uti o n is s p o nt a n e o us wit hi n a f e w ( 2-7) d ays aft er i nj ecti o n i nt o 
t h e s ki n.
R ar e c as es of h y p ers e nsiti vit y h a v e b e e n r e p ort e d aft er tr e at m e nt wit h P erl a n e -Li d o. T h er e 
m a y b e a n i ncr e as e d ris k f or t h es e e v e nts i n s u bj ects wit h h y p ers e nsiti vit y t o a ny i n gr e di e nt 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

2 3 ( 6 2)
of st u d y pr o d ucts . T o mi ni mis e t his ris k, s u bj ects wit h h y p ers e nsiti vit y t o a ny i n gr e di e nt of 
st u d y pr o d ucts s h all b e excl u d e d fr o m t h e st u d y.
T h er e is a ris k t h at t h e s u bj ect will n ot g ai n t h e f ull a est h etic c orr ecti o n of Mi df ac e v ol u m e 
D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y . T h er e is als o a ris k f or d e v el o p m e nt of p al p a bl e 
l u m ps or dis pl ac e m e nt of t h e i nj ect e d P erl a n e -Li d o I nfl a m m ati o n or i nf ecti o n h as b e e n 
r e p ort e d i n a f e w c as es aft er P erl a n e -Li d o tr e at m e nt. T h er e m a y b e ris k of br uisi n g a n d/ or 
d a m a gi n g b o d y str uct ur es s uch as n er v es or bl o o d v ess els c o n n ect e d t o t h e i nj ecti o n sit e, 
h o w e v er t h es e ris ks ar e mi n or. 
Gi v e n
t h e a ntici p at e d l o w l e v el of
tr a nsi en t a n d acc e p t abl e
a d v ers e e v e nts (A E)
i n
c o n n ecti o n wit h t h e i nj ecti o n, t h e ris k-b e n ef it ass e ss me nt of t h e us e of P erl a n e Li d oc ai n e
f or tr e at m e nt of Mi df ac e v ol u m e D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y a p p e ars t o o ff er
a cli nic al b e n efit at r e as o n a bl e ris k.
3
O bj ecti v es a n d E n d p oi nts
3. 1
Pri m ar y o bj ecti v e a n d e n d p oi nt
T h e pri m ar y o bj ecti v e is t o d e m o nstr at e s u p eri orit y of P erl a n e -Li d o r el ati v e t o n o -tr e at m e nt 
i n t h e tr e at m e nt of Mi df ac e 
v ol u m e D eficit a n d/ or Mi df ac e 
C o nt o ur D efici e nc y by 
c o m p ari n g t h e p erc e nt r es p o n d ers, d efi n e d b y at l e ast 1 p oi nt i m pr o v e m e nt fr o m b as eli n e 
o n t h e M M V S o n b ot h si d es of t h e f ac e, as m e as ur e d b y bli n d e d e v al u at or at 6 m o nt hs .
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

2 4 ( 6 2)
3. 3
S af et y o bj ecti v es a n d e n d p oi nts
T h e s af et y o bj ecti v es a n d e n d p oi nts ar e:

T o e v al u at e t h e s af et y of P erl a n e -Li d o d uri n g t h e w h ol e st u d y b y c oll ecti n g A d v ers e 
E v e nts ( A Es).
4
D esi g n of t h e St u d y
4. 1
G e n er al O utli n e
T his is a r a n d o miz e d, e v al u at or -bli n d e d, n o -tr e at m e nt c o ntr oll e d st u dy i n s u bj ects wit h 
Mi df ac e V ol u m e D eficit a n d/ or Mi df ac e C o nt o ur D efici e nc y. 
S u bj ects will b e scr e e n e d f or eli gi bilit y wit hi n 2 1 d a ys pri or t o B as eli n e. T h e first 2 eli gi bl e 
s u bj ects f or e ac h Tr e ati n g I n v esti g at or will r ec eiv e tr e at m e nt as Gr o u p A. B ef or e st art of 
e nr ol m e nt i nt o Gr o u p B, t h e i nj ecti o n t ec h ni q u e will b e ev al u at e d by t h e S p o ns or a n d 
p erf or m e d w h e n t h e s u bj ects i n Gr o u p A f or e ac h sit e h a v e r ec ei v e d t h eir first tr e at m e nt. If 
tr e at m e nts ar e f o u n d t o b e c orr ectl y p e rf or m e d, n o f urt h er tr ai ni n g is n e e d e d, t h er e ar e n o 
o utst a n di n g q u esti o ns r e g ar di n g t h e i nj ecti o n t ec h ni q u e a n d n o ot h er c orr ecti v e acti o ns ar e 
i d e ntifi e d, t h e e nr ol m e nt i n Gr o u p B c a n st art f or t h at sit e. S u bj ects i n gr o u p B will b e 
r a n d o miz e d eit h er t o t h e Tr e at m e nt Gr o u p or t h e C o ntr ol Gr o u p i n a 3: 1 r ati o.
S u m m ari es of t h e r es ults f or Gr o u p A a n d B will b e d o n e s e p ar at el y i n t h e st u d y r e p ort.
Tr e at m e nt 
E ac h s u bj ect assi g n e d t o Gr o u p A or t h e T r e at m e nt G r o u p i n Gr o u p B will r ec eiv e a n i niti al 
tr e at m e nt o n D a y 1. A t o uc h-u p tr e at m e nt m ay b e p erf or m e d 4 w e e ks aft er t h e i niti al 
tr e at m e nt if o pti m al mi df ac e 
a u g m e nt ati o n h as n ot b e e n o bt ai n e d. O pti m al mi df ac e 
a u g m e nt ati o n is d efi n e d as t h e b est p ossi bl e a est h etic r es ult t h at c a n b e o bt ai n e d f or a n 
i n di vi d u al st u d y p artici p a nt, as a gr e e d u p o n b y t h e tr e ati n g i n v esti g at or a n d s u bj ect. 
S u bj ects assi g n e d t o t h e C o ntr ol Gr o u p i n Gr o u p B will n ot r ec ei v e tr e at m e nt at b as eli n e b ut 
will r et ur n f or r o uti n e f oll o w-u p f or 1 2 m o nt hs. At m o nt h 6 visit, s u bj ects i n c o ntr ol gr o u p 
will b e off er e d a tr e at m e nt a n d a n o pti o n al t o uc h- u p tr e at m e nt. 
E v al u ati o n of eff ecti v e n ess
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI

2 5 ( 6 2)
Mi df ac e f ull n ess will b e ass ess e d usi n g a s e p ar at e f o ur-gr a d e M M V S wit h p h ot o g ui d es f or 
t h e ri g ht a n d l eft si d e 
 b y t h e bli n d e d e v al u at or , 
at scr e e ni n g, b as eli n e ,
, 6, 
m o nt hs
i n G r o u p A a n d T r e at m e nt G r o u p, a n d at 
scr e e ni n g, b as eli n e, 
6 m o nt hs, 
 
i n C o ntr ol G r o u p.  
E v al u ati o n of s af et y
I nf or m ati o n r e g ar di n g A Es will b e c oll ect e d c o nti n u o usl y d uri n g t h e st u dy. 
 
 
 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI
C CI
C CI
C CI
C CI
C CI
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26(62)
4.2
Number of Subjects
The study will be performed at approximately 5 sites in China and approximately 168
subjects will be enrolled. 
4.3
Duration of Subject Participation
The total duration for each subject will be approximately 14 months.
4.4
Randomization and blinding
4.4.1 Randomization
Approximately 148 subjects will be randomized in a 3:1 ratio to treatment with Perlane-Lido 
or to no treatment. Before starting the study, a computer generated randomization list will 
be prepared under the supervision of a designated statistician. 
Each subject will be assigned a subject number as they arrive for the treatment visit. For 
group B, randomization will be assigned via the eCRF system.  At the time for randomization, 
the subject’s initials, date of randomization, subject number, randomized treatment, and 
the signature of the Investigator must be documented in a randomization log.  The 
treatment information will be kept by the Treating Investigator during the study not to be 
disclosed to the Blinded Evaluator.
4.4.2 Blinding
Only the evaluator will be blinded, both treating investigator and subjects will be open-
labelled.
The Blinded Evaluator shall not be allowed to retrieve study supplies or to be present during 
opening of the study supplies or injections. The Treating Investigator is not allowed to 
discuss treatments with the blinded evaluator or the subjects. All documents with 
information on study products shall be kept in a separate binder not available to the blinded 
evaluator.
4.4.3 Emergency unblinding
Not applicable as the Treating Investigator is unblinded.
4.5
Medical history
History of surgical events and medical conditions that are judged as relevant by the 
Investigator shall be documented in the eCRF using medical terminology.
4.6
Concomitant Medication, Treatment, and Procedure
Except as noted below, concomitant medications or other treatments or procedures may be
utilized when the PI or his/her authorized designee considers it medically necessary.
Information regarding any use of concomitant medications, including over-the-counter
medications administered during the study is to be recorded in the eCRF. The generic name
or the trade name of all concomitant medication or a description of the procedure and the
reason for its use shall be documented in the eCRF.
Title 
Doc id  
43CH1507 Perlane Lido midface study protocol
MA-30843
 
Effective date: 
 
Version: 
Effective
2016-09-07 11:57
4.0
Print date:
2023-04-18 09:19

27(62)
The following medications, treatments, and procedures are restricted or prohibited during 
the study:

Anticoagulants or inhibitors of platelet aggregation (e.g. aspirin or other non-
steroidal anti-inflammatory drugs [NSAIDs]), Omega-3, or Vitamin E should not be 
used within two weeks before treatment to avoid increased bruising or bleeding at
injection sites.

Lidocaine should be used with caution in patients receiving other local anesthetics or
agents structurally related to amide-type local anesthetics e.g., certain 
antiarrhythmics, since the systemic toxic effects can be additive.

Concomitant treatment with chemotherapy, immunosuppressive agents,
immunomodulatory therapy (e.g., monoclonal antibodies) is prohibited.

Long term concomitant treatment with systemic or topical (facial) corticosteroids is
prohibited (inhaled corticoids are allowed). Corticosteroids should be used with
caution and should be adjudged as necessary by the Investigator.

Use of systemic or topical (facial) retinoic acid is prohibited.

Facial tissue augmenting therapy, contouring or revitalization treatment with fillers, 
lifting threads, permanent implant, mesotherapy, radiofrequency, ultrasound, 
cryotherapy, fat-injection, neurotoxin, laser or light treatment, chemical peeling or
dermabrasion are prohibited.

Planned surgery including aesthetic facial surgical therapy or facial liposuction, sinus
surgery or dental root surgery, or tattoo in the area to be treated is prohibited.

Participation in any other clinical study is prohibited
If a subject has used any of the above prohibited medications or performed any of the 
above prohibited procedures, a protocol deviation will be documented. The subject should 
continue in the study for the scheduled follow-up visits.
Title 
Doc id  
43CH1507 Perlane Lido midface study protocol
MA-30843
 
Effective date: 
 
Version: 
Effective
2016-09-07 11:57
4.0
Print date:
2023-04-18 09:19

2 8 ( 6 2)
4. 7
Sc h e d ul e of e v e nts
T a bl e 1. Sc h e d ul e of E v e nts f or Gr o u p A a n d Tr e at m e nt G r o u p
Gr o u p A a n d Tr e at m e nt G r o u p
Scr e e ni n g a
B as eli n e a/ 
I niti al 
tr e at m e nt
F oll o w -u p 
/ O pti o n al 
T o uc h -u p 
F oll o w -u p b
F oll o w -u p
Fi n al visit
/ E arl y t er mi n ati o n 
D- 2 1 t o D 1
D 1
4 W ( ± 3 d) aft er 
r a n d o miz ati o n
4 W ( ± 3 d) aft er 
t o uc h-u p 
3 M ( ± 1 w), 6M ( ± 1 w) a n d 
9 M ( ± 2 w) aft er l ast 
tr e at m e nt
1 2 M ( ± 2 w) aft er l ast 
tr e at m e nt
I nf or m e d c o ns e nt
X
H ei g h t, D e m o gr a p h y
X
W ei g ht
X
X
X
X
X
X
M e dic al hist or y & c o nc urr e nt 
dis e as es
X
X
C o nc o mit a nt 
m e dic ati o n/ pr oc e d ur es
X
X
X
X
X
X
Vit al si g ns
X c
L a b or at or y t ests
X
X
X e
X f
E C G
X
Pr e g n a nc y t est
X c
X c
X
I ncl usi o n a n d Excl usi o n crit eri a
X
X
R a n d o miz ati o n
X
Tr e at m e nt
X
X
M M V S ( Bli n d e d E v al u at or) 
X
X c
X
X
P h ot o gr a p h y
X c
X c, d
X
X
X
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
Versi o n :
Effecti ve  date:
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

2 9 ( 6 2)
D e vic e d efici e nci es
X
X
Ass ess m e nt of A E
X
X
X
X
X
X
St u d y t er mi n ati o n
X
a)
Scr e e ni n g visit a n d b as eli n e visit c a n b e c o m bi n e d t o o n e visit if f e asi bl e.
b)
O nl y f or s u bj ect r ec ei v e t o uc h -u p tr e at m e nt.
c)
Pri or t o tr e at m e nt, if tr e at p erf or m e d.
e)
O nl y p erf or m e d at 6 M.
f)
O nl y p erf or m e d at e arl y t er mi n ati o n if t er mi n ati o n occ urs b ef or e 6 m o nt hs visit aft er l ast tr e at m e nt
T a bl e 2 . Sc h e d ul e of E v e nts f or C o ntr ol G r o u p
C o ntr ol G r o u p
A cti vit y 
Scr e e ni n g 
a
B as eli n e 
a
F oll o w -u p
F oll o w -
u p
F oll o w -u p 
/ Tr e at m e nt
F oll o w -u p 
/ O pti o n al 
T o uc h -u p 
F oll o w -u p b
F oll o w -u p
Fi n al visit
/ E arl y 
t er mi n ati o n 
D- 2 1 t o 1
D 1
4 W ( ± 3 d) 
aft er 
r a n d o miz at
i o n
3 M ( ± 1 w)
aft er 
r a n d o miz a
ti o n  
6 M ( ± 1 w)
aft er 
r a n d o miz ati
o n
4 W ( ± 3 d)
aft er 6 M 
tr e at m e nt
4 W ( ± 3 d)
aft er t o uc h -u p
3 M ( ± 1 w) 
aft er l ast 
tr e at m e nt
6 M ( ± 1 w) 
aft er l ast tr e at m e nt
I nf or m e d c o ns e nt
X
H ei g ht , D e m o gr a p h y
X
W ei g ht
X 
X 
X 
X 
X
X
X
X
X
M e dic al hist or y & 
c o nc urr e nt dis e as es
X 
X
C o nc o mit a nt 
m e dic ati o n/ pr oc e d ur es
X 
X 
X 
X 
X
X
X
X
X
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
Versi o n :
Effecti ve  date:
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI

3 0 ( 6 2)
Vit al si g ns
X
X c
L a b or at or y t ests
X
X c
X
X
E C G
X
Pr e g n a nc y t est
X
X c
X c
X
I ncl usi o n a n d Excl usi o n 
crit eri a
X 
X
R a n d o miz ati o n
X
Tr e at m e nt
X
X
M M V S ( Bli n d e d E v al u at or) 
X 
X
X 
X c
X
X
P h ot o gr a p h y
X 
X d
X 
X c
X c
X
X
X
D e vic e d efici e nci es
X
X
Ass ess m e nt of A E
X 
X 
X 
X 
X
X
X
X
X
St u d y t er mi n ati o n
X
a)
Scr e e ni n g visit a n d b as eli n e visit c a n b e c o m bi n e d t o o n e visit if f e asi bl e.
b)
O nl y f or s u bj ect r ec ei v e t o uc h - u p tr e at m e nt.
c)
Pri or t o tr e at m e nt, if tr e at p erf or m e d.
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
Versi o n :
Effecti ve  date:
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI
C CI

3 1 ( 6 2)
4. 8
Visits
4. 8. 1 Visits f or Gr o u p A a n d Tr e at m e nt G r o u p
4. 8. 1. 1
Scr e e ni n g ( D-2 1 t o D1)

I nf orm e d c o ns e nt

D e m o gr a p h y (I niti als, D at e of birt h , G e n d er a n d Et h nic ori gi n )

H ei g ht a n d W ei g ht

Scr e e ni n g l a b or at or y t ests ( h a e m at ol o g y a n d s er u m c h e mistr y)

E C G

I ncl usi o na n d exc lusi o n crit eri a

M M V S ( b y Bli n d e d E v al u at or
)

M e dic al hist o ry/c o nc urr e nt dis e as es

C o nc o m it a ntm e dic ati o ns a n d tr e at m e nts

A E d uri n g t h e visit
4. 8. 1. 2
B as eli n e ( D1)

W ei g ht

M e dic al hist o ry/c o nc urr e nt dis e as es

Vit al si g ns ( p uls e r at e, bl o o d pr ess ur e, r es pir at or y r at e, axill ar y t e m p er at ur e)

I ncl usi o na n d exc lusi o n crit eri a

Pr e g n a nc y t est f or c hil d b e ari n g p ot e nti al w o m e n

P h ot o gr a p h y (b ef or e i nj ecti o n)

R a n d o miz ati o n 

M M V S ( b y Bli n d e d E v al u at or
)

T r e at m e nt


C o nc o m it a ntm e dic ati o ns a n d tr e at m e nts

D e vic e d efici e nci es

A E si nc e l ast visit
4. 8. 1. 3
4 W ( ± 3 d) aft er r a n d o miz ati o n F oll o w -u p/ O pti o n al T o uc h -u p

W ei g ht

P h ot o gr a p h y ( b ef or e i nj ecti o n )



Pr e g n a nc y t est f or c hil d b e ari n g p ot e nti al w o m e n

Tr e at m e nt ( o pti o n al)



C o nc o mit a nt m e dic ati o ns a n d tr e at m e nts 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI
C CI
C CI
C CI
C CI

3 2 ( 6 2)

D e vic e d efici e nci es

A E si nc e l ast visit

La b or at or y t ests ( h a e m at ol o g y a n d s er u m c h e mistr y)
4. 8. 1. 4
4 W (±3 d) aft er t o uc h -u p F oll o w -u p ( o nly f or s u bj ects w h o r ec eiv e d t o uc h -u p)

W ei g ht

P h ot o gr a p h y




C o nc o mit a nt m e dic ati o ns a n d tr e at m e nts 

A E si nc e l ast visit
4. 8. 1. 5
3 M ( ± 1 w), 6M ( ± 1 w) a n d 9M ( ± 2 w) aft er l ast tr e at m e nt F oll o w -u p

W ei g ht

P h ot o gr a p h y

M M V S ( b y Bli n d e d E v al u at or
)



C o nc o mit a nt m e dic ati o ns a n d tr e at m e nts 

A E si nc e l ast visit

La b or at or y t ests (O nl y p erf or m e d at 6 M)
4. 8. 1. 6
1 2 M ( ± 2 w) aft er l ast tr e at m e nt Fi n al visit or E arly t er mi n ati o n

W ei g ht

P h ot o gr a p h y 

M M V S ( b y Bli n d e d E v al u at or
)



Pr e g n a nc y t est f or c hil d b e ari n g p ot e nti al w o m e n

C o nc o mit a nt m e dic ati o ns a n d tr e at m e nts 

A E si nc e l ast visit

La b or at or y t ests (O nl y p erf or m e d at e arl y t er mi n ati o n if t er mi n ati o n occ urs b ef or e 6 
m o nt hs visit aft er l ast tr e at m e nt )

St u d y t er mi n ati o n
4. 8. 2 Visits f or C o ntr ol G r o u p
4. 8. 2. 1
Scr e e ni n g ( D -2 1 t o D 1)
Pr oc e d ur es ar e t h e s a m e as Scr e e ni n g visit f or G r o u p A a n d T r e at m e nt G r o u p. ( D et ails 
pl e as e s e e s ecti o n 4. 8. 1. 1)
4. 8. 2. 2
B as eli n e ( D 1)

W ei g ht
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI
C CI
C CI
C CI

3 3 ( 6 2)

M e dic al hist o ry/c o nc urr e nt dis e as es

Vit al si g ns ( p uls e r at e, bl o o d pr ess ur e, r es pir at or y r at e, axill ar y t e m p er at ur e)

I ncl usi o na n d exc lusi o n crit eri a

Pr e g n a nc y t est f or c hil d b e ari n g p ot e nti al w o m e n

P h ot o gr a p h y 

R a n d o miz ati o n 

M M V S ( b y Bli n d e d E v al u at or
)

C o nc o m it a ntm e dic ati o ns a n d tr e at m e nts

A E si nc e l ast visit
4. 8. 2. 3
4 W ( ±3 d ) aft er r a n d o miz ati o n F oll o w -u p 

W ei g ht

P h ot o gr a p h y
 



C o nc o mit a nt m e dic ati o ns a n d tr e at m e nts 

A E si nc e l ast visit
4. 8. 2. 4
3 M ( ± 1 w) aft er r a n d o miz ati o n F oll o w -u p
Pr oc e d ur es ar e t h e s a m e as 3 M aft er l ast tr e at m e nt f or G r o u p A a n d T r e at m e nt G r o u p. 
( D et ails pl e as e s e e s ecti o n 4. 8. 1.5)
4. 8. 2. 5
6 M ( ± 1 w) aft er r a n d o miz ati o n F oll o w -u p / tr e at m e nt

W ei g ht

Vit al si g ns ( p uls e r at e, bl o o d pr ess ur e, r es pir at or y r at e, axill ar y t e m p er at ur e)

l a b or at or y t ests ( h a e m at ol o g y a n d s er u m c h e mistr y)

Pr e g n a nc y t est f or c hil d b e ari n g p ot e nti al w o m e n

M M V S ( b y Bli n d e d E v al u at or
)

P h ot o gr a p h y ( b ef or e i nj ecti o n )



Tr e at m e nt


C o nc o m it a ntm e dic ati o ns a n d tr e at m e nts

D e vic e d efici e nci es

A E si nc e l ast visit
4. 8. 2. 6
4 W ( ± 3 d) aft er 6 M tr e at m e nt F oll o w -u p/ O pti o n al T o uc h -u p
Pr oc e d ur es ar e t h e s a m e as 4 W aft er r a n d o miz ati o n visit f or G r o u p A a n d T r e at m e nt G r o u p, 
. ( D et ails pl e as e s e e s ecti o n 4. 8. 1.3)
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI
C CI
C CI
C CI
C CI
C CI

3 4 ( 6 2)
4. 8. 2. 7
4 W (± 3 d) aft er t o uc h- u p F oll o w -u p ( o nly f or s u bj ects w h o r ec eiv e t o uc h -u p) 
Pr oc e d ur es ar e t h e s a m e as 4 W aft er t o uc h -u p visit f or G r o u p A a n d T r e at m e nt G r o u p. 
( D et ails pl e as e s e e s ecti o n 4. 8. 1.4)
4. 8. 2. 8
3 M ( ± 1 w) aft er l ast tr e at m e nt F oll o w -u p
Pr oc e d ur es ar e t h e s a m e as 3 M aft er l ast tr e at m e nt visit f or G r o u p A a n d T r e at m e nt G r o u p. 
( D et ails pl e as e s e e s ecti o n 4. 8. 1.5)
4. 8. 2. 9
6 M ( ± 1 w) aft er l ast tr e at m e nt Fi n al visit / e arly t er mi n ati o n 

W ei g ht

P h ot o gr a p h y 

M M V S ( b y Bli n d e d E v al u at or
)



Pr e g n a nc y t est f or c hil d b e ari n g p ot e nti al w o m e n

l a b or at or y t ests ( h a e m at ol o g y a n d s er u m c h e mistr y)

C o nc o mit a nt m e dic ati o ns a n d tr e at m e nts 

A E si nc e l ast visit

St u d y t er mi n ati o n
5
S u bj ects
5. 1
S u bj ect i nf or m ati o n a n d i nf or m e d c o ns e nt
T h e PI or his/ h er a ut h oris e d d esi g n e e m ust al w a ys us e t h e I E C -a p pr o v e d s u bj ect i nf or m ati o n 
a n d I nf or m e d C o ns e nt F or m a n d it m ust n ot b e c h a n g e d wit h o ut pri or disc ussi o n wit h t h e 
S p o ns or a n d a p pr o v al fr o m t h e a p plic a bl e I E C.
It is t h e r es p o nsi bilit y of t h e PI or his/ h er a ut h oris e d d esi g n e e t o gi v e e ac h s u bj ect pri or t o 
i ncl usi o n i n t h e st u d y, f ull a n d a d e q u at e v er b al a n d writt e n i nf or m ati o n r e g ar di n g all as p ects 
of t h e cli nic al st u d y t h at ar e r el e v a nt t o t h e s u bj ect’s d ecisi o n t o p artici p at e t hr o u g h o ut t h e 
st u d y, e. g. ex pl ai n t h e p ur p os e a n d pr oc e d ur es of t h e st u dy, t h e d ur ati o n a n d n u m b er of 
ex p ect e d p artici p a nts, p ossi bl e ris ks i n v ol v e d, a n d t h e o pi ni o n of t h e I E C. T h e s u bj ect s h all 
b e i nf or m e d t h at t h e p artici p ati o n is c o nfi d e nti al a n d v ol u nt ar y a n d t h at t h e s u bj ect h as t h e 
ri g ht t o wit h dr a w fr o m t h e st u d y at a n y ti m e, wit h o ut a ny eff ect o n his/ h er f ut ur e m e dic al 
car e, tr e at m e nt or b e n efits t o w hic h t h e s u bj ect is ot h er wis e e ntitl e d. T h e i nf or m ati o n
s h all b e pr o vi d e d i n a l a n g u a g e cl e arl y a n d f ull y u n d er st a n d a bl e t o t h e s u bj ect. T h e s u bj ect
s h all b e giv e n s uffici e nt ti m e t o r e a d a n d u n d erst a n d t h e I nf or m e d C o ns e nt F or m a n d t o 
c o nsi d er p artici p ati o n i n t h e st u d y. B ef or e a n y st u d y-r el at e d acti viti es ar e p erf or m e d, t h e 
I nf or m e d C o ns e nt F or m s h all b e p ers o n all y si g n e d a n d d at e d b y t h e s u bj ect a n d t h e PI or 
his/ h er a ut h oris e d d esi g n e e r es p o nsi bl e f or c o n d ucti n g t h e i nf or m e d c o ns e nt pr oc ess. T h e 
c o ns e nt i ncl u d es i nf or m ati o n t h at d at a will 
b e c oll ect e d, r ec or d e d, pr oc ess e d, a n d 
tr a nsf err e d t o c o u ntri es o utsi d e C hi n a. T h e d at a will n ot c o nt ai n a n y i nf or m ati o n t h at ca n b e 
us e d t o i d e ntif y a n y s u bj ect.
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI

35(62)
All signed Informed Consent Forms shall be filed in the Investigator file. The subject shall be 
provided with a copy of the signed and dated Informed Consent Form and any other written 
information.
The Investigator shall ensure that important new information is provided to new and 
existing subjects throughout the study
5.2
Inclusion Criteria
The subject must meet the following criteria to be eligible for the study:
1. Signed and dated informed consent to participate in the study
2. Men or women aged 18 years of age or older of Chinese origin
3. Subjects willing to abstain from any other facial plastic surgical or cosmetic 
procedures below the level of the lower orbital rim for the duration of the study 
(e.g., laser or chemical resurfacing, needling, facelift, radiofrequency etc.).
4. Subjects seeking augmentation therapy for the midface
5. MMVS score of 2, 3 or 4 on each side of the face as assessed by the blinded 
evaluator
5.3
Exclusion Criteria
The presence of any of the following exclusion criteria will exclude a subject from enrolment 
in the study:
1. Known/previous allergy or hypersensitivity to any injectable HA gel.
2. Known/previous allergy or hypersensitivity to local anaesthetics, e.g. lidocaine or 
other amide-type anaesthetics 
3. History of severe or multiple allergies manifested by anaphylaxis 
4. Previous tissue revitalization treatment with laser or light, mesotherapy, 
radiofrequency, ultrasound, cryotherapy, chemical peeling or dermabrasion in the 
midface within 6 months before treatment
5. Previous surgery (including aesthetic facial surgical therapy or liposuction) or tattoo 
in the area to be treated 
6. Previous tissue augmentation therapy or contouring with any permanent (non-
biodegradable) or semi-permanent filler, autologous fat, lifting threads or 
permanent implant below the level of the lower orbital rim. 
7. Previous use of any hyaluronic acid based or collagen based biodegradable facial 
tissue augmentation therapy below the level of the lower orbital rim within 12 
months before treatment.
8. Previous use of any neurotoxin below the level of the lower orbital rim within 9
months before treatment.
9. History of radiation or cancerous or pre-cancerous lesions (e.g. actinic keratosis) in 
the area to be treated
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10. Scars or deformities, active skin disease, inflammation or related conditions, such as 
infection, perioral dermatitis, seborrheic eczema, rosacea, acne psoriasis and herpes 
zoster near or in the area to be treated.
11. Subjects with a dental or oral status on visual inspection that in the opinion of the 
Investigator would make the subject unsuitable for inclusion, or Subjects with 
dental, oral or sinus surgery within past 12 months prior to the treatment visit or 
planned surgery, including dental implants, during the study period.
12. Ongoing infection in mouth or dentals
13. Chronic infection in head and neck region
14. Tendency for edema, puffiness or swelling in the area to be treated 
15. History of or active autoimmune disease or connective tissue diseases such as 
systemic lupus erythematosus, rheumatoid  arthritis, polymyositis, dermatomyositis 
or localized or systemic scleroderma. 
16. Tendency to form keloids, hypertrophic scars, or any other healing disorder
17. History of bleeding disorders or treatment with anticoagulants or inhibitors of 
platelet aggregation (e.g. aspirin or other non-steroid anti-inflammatory drugs 
(NSAIDs), Omega-3, or vitamin E within 2 weeks before treatment 
18. Treatment with chemotherapy, immunosuppressive agents, immunomodulatory 
therapy (e.g. monoclonal antibodies), systemic or topical (facial) corticosteroids 
within 3 months  before treatment (inhaled corticoids are allowed)
19. Treatment with topical (facial) retinoids within 3 months or systemic retinoids 
within 6 months before treatment.
20. The presence of moderate or severe abnormal rating for midface symmetry, i.e. 
more than 1 grade difference in MMVS score between each side of the face.
21. Any medical condition that in the opinion of the Investigator would make the 
subject unsuitable for inclusion (e.g. a chronic, relapsing or hereditary disease that 
may affect the general condition or may require frequent medical treatment, any 
abnormal screening laboratory value or ECG, or psychiatric disorders).
22. Other condition preventing the subject from entering the study in the Investigator’s 
opinion, e.g. subjects not likely to avoid other facial cosmetic treatments, subjects 
anticipated to be unreliable, unavailable or incapable of understanding the study 
assessments or having unrealistic expectations of the treatment result
23. Women who are pregnant or breast feeding, or Woman of childbearing potential 
who are not practicing adequate contraception or planning to become pregnant 
during the study period.
24. Intention to change a significant amount of weight (≥2 BMI) during the study period
25. Study site personnel, close relatives of the study site personnel (e.g. parents, 
children, siblings, or spouse), employees, or close relatives of employees at the 
Sponsor company 
26. Participation in any other clinical study within 30 days before treatment.
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5.4
Screening and Subject Numbers
Each screened subject will be assigned a screening number consisting of “S” and the site 
number followed by a consecutive number starting with 01 at each site, e.g. S101, S102.The
screening number shall be listed on a subject screening and inclusion log. 
A “screening failure” is defined as a subject who does not fulfil the eligibility criteria. For 
screening failures, the eCRF screening visit shall be completed to an extent that makes it 
clear which assessments have been made and the reason why the subject did not fulfil the 
eligibility criteria. The reason for excluding a subject from entering the study shall also be 
specified in the subject screening and inclusion log. 
When the Investigator has confirmed that all inclusion criteria and no exclusion criteria are 
met, each enrolled subject will be assigned a subject number by the eCRF consisting of the 
site number followed by a consecutive number starting with 01 at each site, e.g. 101, 102.
The subject number, subject name, and other information sufficient to link the eCRF to the 
medical records (e.g. national identification number, chart number, etc.) shall be recorded 
on a subject identification list. The subject identification list shall only be available at the site, 
both throughout and after the study.
5.5
Withdrawal of Subjects
Each subject shall be advised in the Informed Consent Form that the subject has the right to 
withdraw from the study at any time, for any reason, without prejudice. Subjects may also 
be discontinued from this study if the Investigator determines that it is in the subject’s best 
interest to do so, and may be withdrawn at the Investigator's discretion at any time.
The withdrawal criteria are:

Medical reasons: If the subject suffers from a medical condition that in the judgement 
of the Investigator makes it medically necessary to withdraw the subject. The specific 
rationale for Investigator-initiated withdrawal of a subject for medical reasons shall 
document the specific condition for withdrawing the subject.

Withdrawal of informed consent: A subject can withdraw their consent to participate 
in the study at their own request or be withdrawn from participation in the study at 
the request of their legally authorised representative at any time for any reason.

Lost to follow-up: If a subject does not return for a scheduled visit, reasonable effort 
shall be made to contact that subject, e.g. call three times at different hours and leave 
messages if applicable before declaring the subject lost to follow-up.

Other: Examples of other reasons for withdrawal may be failure to comply with 
protocol requirements or to complete the protocol-specified evaluations.
The reason and date for withdrawal shall be documented in the eCRF. When possible, an 
explanatory comment shall be added in the study termination module/pages to further 
explain the reason for withdrawal. If withdrawal of a subject occurs during a regular study 
visit, the eCRF for that specific visit shall be completed as far as possible together with the 
study termination eCRF module. 
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If withdrawal of a subject occurs between regular study visits the subject should when 
possible (irrespective of the reason for withdrawal) be scheduled for a termination visit. In 
these cases the eCRF for the early termination visit should be completed. The subject will 
need to follow the same requirements for the final visit.
If a subject is withdrawn from the study, all data collected until the time of withdrawal will 
be used in the analyses.
A withdrawn or discontinued subject must not be replaced or re-entered into the study.
If an AE which, according to the Investigator’s assessment, is related to the use of any of the 
study products and is still ongoing at the time of the withdrawal, such events shall be 
followed-up after the last study visit until resolved, assessed as chronic or stable, or for at 
least three months.
6
Study Products 
6.1
Investigational Product 
Perlane-Lido consists of stabilized hyaluronic acid of non-animal origin at a concentration of 
20 mg/mL, in phosphate buffered saline with lidocaine hydrochloride 3 mg/ml. The study 
product is supplied in sterile 1 mL syringes.  A 29G thin walled (TW) × ½” needle will be used 
for injection.
6.2
Reference Product
Not applicable.
6.3
Additional Products and Material
The study product is supplied in sterile 1 mL syringes.  A 29G thin walled (TW) × ½” needle 
will be used for injection.Any other materials will be supplied by the site.
6.4
Packaging, Labelling and Storage
Restylane Perlane Lidocaine is manufactured by Q-Med AB, Uppsala, Sweden who will 
supply the study products. Restylane Perlane Lidocaine will be used for the study.
The syringes are labelled with name of the product, name of the manufacturer (Q-Med AB). 
The syringes in its blister are packed in a carton. The carton will be labelled in local 
language, specifying the protocol number, lot number, expiry date and that the product is to 
be used for clinical studies exclusively.
The study products should be stored at a temperature up to 25oC and protected from 
sunlight and freezing. Opened syringes should not be re-used. Accountability will be 
performed as specified in section 6.5.
6.5
Product accountability
The study product will be released to the PI or his/her authorised designee after study 
approvals have been received from the IEC and the CTA has been signed by all parties.
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The PI must ensure that the study product is kept in a secure location, with access limited to 
those authorised by the PI.
The study product must be traceable from the manufacturer to its use in subjects until 
return or disposal. It is therefore important that the PI maintains accurate product 
accountability records, i.e. documentation of the physical location of all study product, 
deliveries, and return of study product between the Sponsor or a third-party vendor and the 
PI, and documentation of administration of product to the subject. A shipping record shall 
be kept of all study products received from the Sponsor; including the product name, date 
received, batch number, expiration date, and amount received. In addition, dispensing logs 
shall be maintained including the product name, dispense date, the number of syringes 
used, the number of syringes left in stock, and the subject receiving study product. A log for 
accountability procedure is provided by the Sponsor. 
When the study is completed, all unused or expired study product at each study site shall be 
returned to the Sponsor or a third-party vendor for destruction. Any malfunctioning study 
products shall be reported as described in Section 8.5.3.
Product deliberately or accidentally destroyed during shipment or at a study site shall be 
accounted for and documented. Used syringes, disposable needle, and any opened unused 
material must be discarded immediately after the treatment session and must not be 
reused due to risk for contamination of the unused material and the associated risks 
including infections according to standard procedures at the site. Disposal of hazardous 
material, i.e. syringes and needles must conform to applicable laws and regulations. The 
study product must not be used outside the study.
6.6
Treatment 
6.6.1
Treatment Procedure
The subjects will be informed about the indications, expected result, precautions and 
potential AEs.
Local anesthetics (topical, infiltrative, or regional blocks) before the treatment will be used 
at the discretion of the treating Investigator. Injection procedures are associated with a risk 
of infection. Aseptic technique and standard practice to prevent cross-infections should be 
observed at all times including the use of disposable gloves during the injection procedure. 
The subject should not wear make-up on the day of treatment, if make-up was already 
applied this must be completely removed prior to any injection. The treatment site should 
be thoroughly cleaned at least twice with a suitable antiseptic solution.
To avoid breakage of the needle, no attempt to bend or otherwise manipulate it before or 
during treatment is recommended. Before injecting, the air should be removed by pressing 
the rod carefully until a small droplet is visible at the tip of the needle. Aspiration prior to 
injection in order to avoid accidental intravascular injection is recommended. Injection 
should stop just before the needle is pulled out from the skin to prevent material from 
leaking out from the injection site. Excessive pressure must not be applied at any time
during injection. If resistance is encountered the needle should be partially withdrawn and 
repositioned or fully withdrawn and checked for function.
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Perlane-Lido should be injected into subcutaneous to supraperiosteal layer in the midface. 
Perlane-Lido will be administered inferior to the maxillary prominence, superior to the plane 
of nasal alae, including the area from the lateral canthus to the medial canthus and lateral 
to the nose on the subject’s right and left sides (Figure 2). If Perlane-Lido is injected too 
superficially this may result in visible lumps and/or bluish discoloration. Investigators will be 
instructed to use the amount of dermal filler necessary to achieve an optimal aesthetic 
result. A touch-up treatment may be performed 4 weeks after the initial treatment if 
optimal midface augmentation has not been obtained. Defects should be fully corrected, 
but not overcorrected.
Care should be taken to avoid intramuscular injection. This can often be recognized by an
increased force of injection required compared to subcutaneous injection. Care should also 
be taken to avoid excess deposition of material into individual areas. After each injection, 
the area should be observed to assess the degree of enhancement and the uniformity of the 
implant. The area should be gently palpated to ensure an even deposition of the implant. 
Palpated “skip areas” should be treated with additional implant material or by gentle 
massage/kneading of the area until a uniform implant is palpable.
Figure 2. Injection Area
Information regarding the local anaesthetic used, injection technique, depth of injection and 
volume used per side will be recorded.
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4 1 ( 6 2)
6. 6. 2
Tr e at m e nt r e gi m e n ( d os e)
It is r ec o m m e n d e d t h at t h e d os e s h o ul d n ot exc e e d 4 mL (ri g ht a n d l eft mi df ac e c o m bi n e d)
f or a tr e at m e nt s essi o n, i. e., i niti al tr e at m e nt or t o uc h-u p tr e at m e nt r es p ectiv el y.
6. 6. 3
P ost -tr e at m e nt C ar e 
Ic e i n a p pr o pri at e p ac k a gi n g c a n b e a p pli e d o n t h e tr e at m e nt sit e f or a s h ort p eri o d t o
r e d uc e s w elli n g a n d disc o mf ort.
Aft er t h e i nj ecti o n, s o m e c o m m o n i nj ecti o n-r el at e d r e acti o ns mi g ht occ ur. T h es e r e acti o ns 
i ncl u d e er yt h e m a, s w elli n g, p ai n, itc hi n g, br uisi n g or t e n d er n ess at t h e i m pl a nt sit e. T y pic all y 
r es ol uti o n is s p o nt a n e o us wit hi n a f e w ( 2-7) d ays . T h e p ati e nt m ust av oi d ex p osi n g t h e 
tr e at e d ar e a t o h e at (s u n b at hi n g, s a u n a, st e a m b at hs, etc.) or extr e m e c ol d l e ast u ntil a ny 
i niti al s w elli n g a n d er yt h e m a h as r es olv e d. I n or d er t o pr e v e nt i nf ecti o ns, t h e p ati e nt s h o ul d 
a v oi d t o uc hi n g t h e tr e at e d ar e a a n d n o cr e a ms or c os m etics s h o ul d b e a p pli e d b ef or e t h e 
s ki n h as h e al e d c o m pl et el y.
6. 6. 4
P ost -tri al pr o visi o ns 
Aft er t h e st u d y is fi n alis e d Q -M e d A B will n ot s u p pl y a n y m or e tr e at m e nts t o t h e s u bj ects, 
e v e n if t h e r es ult d o es n ot p ersist.
6. 6. 5
El ectr o nic c as e r e p ort f or m r ec or di n gs
T h e f oll o wi n g d et ails of e ac h i nj ecti o n ar e t o b e r ec or d e d i n t h e e C R F: 

D at e f or a d mi nistr ati o n

L ot n u m b er 

L oc al a n a est h etic us e d ( pr o d uct n a m e, v ol u m e i nj ect e d/ a m o u nt a p pli e d, a n d 
c o nc e ntr ati o n)

A d mi nist er e d v ol u m e p er si d e

I nj ecti o n t ec h ni q u e p er si d e

D e pt h of i nj ecti o n p er si d e

P ost -tr e at m e nt c ar e ( m ass a g e, ic e p ac k, etc )
I n a d diti o n, a n y t ec h nic al pr o bl e ms ( d e vic e d efici e nci es) or cli nic al c o m plic ati o ns ( A Es) 
ass oci at e d wit h t h e i nj ecti o n will b e r ec or d e d i n t h e e C R F.
6. 6. 6
Tr e at m e nt c o m pli a nc e
T h e tr e at m e nt is a n i m pl a nt a d mi nist er e d b y t h e Tr e ati n g In v esti g at or a n d t h e d et ails of t h e 
a d mi nistr ati o n ar e r ec or d e d i n t h e e C R F . N o ot h er m e as ur e m e nts of tr e at m e nt c o m pli a nc e 
will b e m a d e.
7
Ef fic ac y Ass ess m e nts
7. 1
G e n er al i nf or m ati o n
T h e m et h o ds f or c oll ecti n g effic ac y d at a i ncl u d e ass ess m e nt of M M V S
7( S ecti o n 7. 2), 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI

4 2 ( 6 2)
. A d escri pti o n of t h e l a b or at or y ass ess m e nts is giv e n i n S ecti o n 
8. 2 a n d t h e E C G ass ess m e nt i n S ecti o n 8. 3.
Ass ess m e nts will b e p erf or m e d by 
 t h e bli n d e d
e v al u at or, as d escri b e d i n t h e r es p ecti v e s ecti o n. T o a v oi d i nt er-o bs erv er v ari a bilit y, ev ery 
eff ort s h o ul d b e m a d e t o e ns ur e t h at pr ef er a bl y t h e s a m e i n di vi d u al w h o m a d e t h e i niti al 
b as eli n e d et er mi n ati o ns c o m pl et es all c orr es p o n di n g f oll o w-u p e v al u ati o ns. If it is n ot
p ossi bl e t o us e t h e s a m e e v al u at or /
t o f oll o w t h e s u bj ect, e v al u ati o ns s h o ul d b e 
o v erl a p p e d ( ex a mi n e t h e s u bj ect t o g et h er a n d disc uss fi n di n gs) f or at l e ast 1 visit.
7. 2
M e dicis Mi df ac e V ol u m e Sc al e ( M M V S)
M M V S 
is a 4- gr a d e sc al e ass ess es t h e f ull n ess of t h e mi df ac e fr o m F airl y F ull ( 1) t o 
S u bst a nti al L oss of F ull n ess ( 4) as d escri b e d b el o w . A v ali d ati o n st u d y c o ncl u d e d t h at t h e 
acc ur ac y of t his ass ess m e nt t o ol w as acc e pt a bl e f or us e i n ass essi n g c orr ecti o n of mi df ac e 
v ol u m e l oss a n d/ or c o nt o ur d efici e nc y [L or e nc 2 0 1 2] . T h e bli n d e d e v al u at or will r at e t h e 
s u bj ect’s ri g ht a n d l eft mi df ac e f or s e v erit y of v ol u m e d efici e nc y usi n g t h e M M V S 
at 
scr e e ni n g, b as eli n e , , 6, 
 m o nt hs
i n G r o u p A a n d T r e at m e nt G r o u p; a n d at 
scr e e ni n g, b as eli n e,
6 m o nt hs, 
i n C o ntr ol G r o u p. 
 
. T h e bli n d e d e v al u at or 
 will c o n d uct t h eir M M V S 
ass ess m e nts usi n g a p h ot o gr a p hic sc al e ( A p p e n dix 2). 
T a bl e 3 . M e dicis Mi df ac e V ol u m e Sc al e
M M V S
1
F airl y f ull mi df ac e
2
Mil d l oss of f ull n ess i n mi df ac e ar e a
3  
M o d er at e l oss of f ull n ess wit h sli g ht h oll o wi n g b el o w m al ar 
pr o mi n e nc e
4
S u bst a nti al l oss of f ull n ess i n t h e mi df ac e ar e a, cl e arl y 
a p p ar e nt h oll o wi n g b el o w m al ar pr o mi n e nc e
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

4 3 ( 6 2)
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

4 4 ( 6 2)
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

4 5 ( 6 2)
8
S af et y A ss ess m e nts
8. 2
L a b or at or y ass ess m e nt
L a b or at or y s a m pl es will b e t a k e n at t h e scr e e ni n g visit ( d a y -2 1 t o d a y 1) f or all s u bj ects. I n 
Gr o u p A a n d Tr e at m e nt Gr o u p, it will als o b e t a k e n at 4 w e e ks visit aft er i niti al tr e at m e nt, 6 
m o nt hs visit aft er l ast tr e at m e nt or at e arl y t er mi n ati o n if t er mi n ati o n occ urs b ef or e 6 
m o nt hs visit aft er l ast tr e at m e nt. I n c o ntr ol gr o u p, it will b e t a k e n at 6 m o nt hs visit b ef or e 
tr e at m e nt, 4 w e e ks visits aft er 6 M tr e at m e nt a n d als o b e t a k e n at fi nal visit or e arly 
t er mi n ati o n.
T h e f oll o wi n g l a b or at or y ass ess m e nts will b e p erf or m e d:

H a e m at ol o g y: h a e m o gl o bi n, r e d bl o o d c ells, w hit e bl o o d c ells, diff er e nti al c o u nt a n d 
pl at el et c o u nt .

S er u m c h e mistry: r e n al f u ncti o n t ests (cr e ati ni n e a n d B U N) ; a n d liv er f u ncti o n t ests 
( as p art at e a mi n o tr a nsf er as e (A S A T), al a ni n e a mi n o tr a nsf er as e ( AL A T) t ot al bilir u bi n , 
dir ect bilir u bi n a n d i n dir ect bilir u bi n ).

Uri n e: ( U-H C G) Pr e g n a nc y t est f or w o m e n of c hil d b e ari n g p ot e nti al ( pr e g n a nc y t est 
will b e p erf or m e d pri or t o tr e at m e nt a n d at t h e st u d y c o m pl eti o n, i n all w o m e n of 
c hil d b e ari n g p ot e nti al).
Ot h er l a b or at or y t est mi g ht b e p erf or m e d at t h e discr eti o n of t h e i n v esti g at or. All 
l a b or at or y ass a ys will b e p erf or m e d at a l oc al l a b or at or y. R ef er e nc e r a n g es will b e s u p pli e d 
b y t h e l a b or at or y a n d us e d b y t h e I n v esti g at or t o ass ess t h e l a b or at or y d at a f or cli nic al 
si g nific a nc e a n d o ut of r a n g e p at h ol o gic al c h a n g es. 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI

46(62)
The results of the hematology and serum chemistry will only be used for safety assessment 
by investigator and will not be collected in the eCRF. The pregnancy test for women of 
childbearing potential will be recorded in the eCRF.
8.3
ECG-screening
ECG will be taken at the screening visit (day -21 to day 1) and assessed by investigator for 
clinical significance. The results of ECG will only be used for screening purposes by the 
investigator and will not be collected in the eCRF.
8.4
Adverse Events
8.4.1
Definition of Adverse Events
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons*, 
whether or not related to the study product. 
This definition includes:

events related to the investigational product or the reference product

events related to the procedures involved
. *For users or other persons, this definition is restricted to events related to the investigational product
8.4.2
Definition of Serious Adverse Event 
A serious adverse event (SAE) is an AE that:
a) led to death,
b) led to serious deterioration in the health of the subject, that either resulted in
1. a life-threatening** illness or injury, or
2. a permanent impairment of a body structure or body function, or
3. in-patient or prolonged hospitalisation***, or
4. medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
c) led to foetal distress, foetal death, or a congenital abnormality or birth defect
In cases of doubt, whether an AE fulfils a serious criterion or not, there should be a 
predisposition to report as a SAE rather than not report as such (see section 8.4.4).
**The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at risk 
of death at the time of the event; it does not refer to an event which hypothetically might have caused death if 
it were more severe. (Source: ICH-E2A clinical safety data management: definitions and standards for 
expedited reporting).
*** Planned hospitalisation for a pre-existing condition, or a procedure required by the CSP, without serious 
deterioration in health, is not considered a SAE. (Source: ISO14155:2011).
8.4.3
Recording Instructions
AE will begin to be collected after ICF signed. Each subject will be questioned about AEs at 
each clinical visit following the screening visit. The question asked will be "Since your last 
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cli nic al visit h a v e y o u h a d a n y h e alt h pr o bl e ms ?" Inf or m ati o n o n A Es c a n als o b e o bt ai n e d 
fr o m si g ns a n d s y m pt o ms d et ect e d d uri n g e ac h ex a mi n ati o n or fr o m a l a b or at or y t est, 
o bs er v ati o ns by t h e st u d y p ers o n n el , 
 s p o nt a n e o us r e p orts fr o m t h e 
s u bj ects. 
W h e n a n A E is r el at e d t o a d e vic e d efici e nc y (r ef er t o s ecti o n 8. 5 ), i ncl u di n g t ec h nic al d e vic e 
m alf u ncti o n, t h e A E s h all b e r ec or d e d o n t h e A E m o d ul e i n t h e e C R F a n d t h e t ec h nic al 
c o m pl ai nt s h all b e r e p ort e d s e p ar at el y o n t h e cli nic al st u d y c o m pl ai nt f or m.
I n v esti g at ors, or ot h er st u d y p ers o n n el, will r ec or d all A Es i n t h e e C R F, i ncl u di n g :

E v e nt t er m (r ec or d e d i n st a n d ar d m e dic al t er mi n ol o g y a n d a v oi di n g a b br e vi ati o ns),

D escri pti o n of e v e nt a n d a ff ect e d ar e a (if a p plic a bl e),

St art d at e ( First d a y wit h s y m pt o ms)

St o p d at e (L ast d a y wit h s y m pt o ms)

I nt e nsit y ( mil d, m o d er at e or s e v er e acc or di n g t o d efi niti o n i n s ecti o n 8. 4 . 3. 1)

S eri o us n ess (s eri o us or n ot s eri o us, acc or di n g t o d efi niti o n i n s ecti o n 8. 4. 2 )

C a us al r el ati o ns hi p t o st u d y pr o d uct a n d st u d y pr o d uct i nj ecti o n pr oc e d ur e ( y es or 
n o)

Acti o n t a k e n ( n o n e, m e dic ati o n tr e at m e nt, n o n -p h ar m ac ol o gic al tr e at m e nt or o t h er 
pr oc e d ur es/ t ests, s u bj ect wit h dr a w n)

O utc o m e of t h e A E (o n g oi n g, r ec ov er e d, r ec o v er e d wit h s e q u ele , d e at h, chr o nic / 
st a bl e, n ot r ec o v er e d at st u d y e n d)
T h e A E m o d ul e i n t h e e C R F m ust b e si g n e d a n d d at e d b y t h e In v esti g at or .
8. 4. 3. 1
I nt e nsit y
F or e ac h r e p ort e d A E , t h e i nt e nsit y will b e r ec or d e d. T h e f oll o wi n g d efi niti o ns of i nt e nsit y 
ar e t o b e us e d:
Mil d :
A mil d A E m e a ns a w ar e n ess of s y m pt o ms or si g ns, b ut e asil y t ol er at e d 
( acc e pt a bl e).
M o d er at e:
A m o d er at e A E m e a ns e n o u g h disc o mf ort t o i nt erf er e wit h us u al acti vit y 
( dist ur bi n g).
S e v er e:
A s e v er e A E m e a ns i nc a p acit y t o w or k or t o d o us u al acti vit y 
( u n acc e pt a bl e).
If t h e i nt e nsit y c h a n g es o v er ti m e t h e m axi m u m i nt e nsit y of t h e A E s h o ul d b e r ec or d e d.
8. 4. 3. 2
C a us al R el ati o ns hi p a n d S eri o us n ess
E ac h A E , s eri o us as w ell as n o n -s eri o us, will b e ass ess e d b y t h e In v esti g at or f or c a us al 
r el ati o ns hi p wit h t h e st u d y pr o d uct a n d its us e (t h e i nj ecti o n pr oc e d ur e) a n d f or s eri o us n ess
( y es or n o) of t h e e v e nt . 
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A two-point scale (Yes or No) will be used for causality assessments. The Investigators shall 
be asked to indicate a response to each of the following questions in the eCRF:

“Do you consider that there is a reasonable possibility that the event may have been 
caused by the study product?” and 

“Do you consider that there is a reasonable possibility that the event may have been 
caused by the study product injection procedure?”
If any of these questions is answered Yes, the AE is considered related. 
Each AE will also be assessed for causal relationship and seriousness by the Sponsor, in 
order to fulfil regulatory requirements. 
8.4.4
Reporting of Adverse Events
AE reporting on each subject will start after the ICF has been signed. The reporting will 
continue during each follow-up visit (including telephone contacts and extra visits between 
planned visits) until the last scheduled visit in the study.
All AEs, non-serious as well as serious, are to be reported as an AE in the eCRF.
8.4.5
Reporting of Serious Adverse Events
After aware of any SAE, the Investigator shall report it to his/her administrative department 
of medical device clinical trials under the clinical trial institution, which in turn shall notify 
the Sponsor Representative in writing. This initial report can be made via fax or e-mail or 
submitted via the eCRF.
In case of difficulty to obtain all the required information within 24 hours, an initial report 
can be submitted, with the following information as a minimum, irrespective of whether 
some of it is regarded as preliminary:

CTN
Subject identification (age, gender, subject number)
AE description
date when AE occurred
date when AE became serious
Name of PI and original reporter (if other than Investigator)
Name of study product
Treatment specification
The Investigator will assure completeness of the SAE information and the supporting 
documentation.
Follow-up information and data missing in the initial SAE reporting shall be gathered as soon 
as possible and reported to the Sponsor via Sponsor’s representative immediately but not 
later than 24 hours of awareness of the new data. Complete and adequate information on 
each SAE is required. All attempts to obtain this information, including dates for follow-up 
activities, must be documented by the Investigator.
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S u p p orti n g d oc u m e nt ati o n t o b e pr o vi d e d wit h t h e S A E r e p ort:

C o nc o mit a nt M e dic ati o n F or m /list

C o nc o mit a nt Pr oc e d ur e / Tr e at m e nt F or m /list

A E F or m /list

M e dic al Hist or y F or m /list

A n y ot h er r el e v a nt s u p p orti n g d oc u m e nt ati o n ( e. g. h os pit al n ot es, d e at h c ertific at e, 
a ut o ps y r e p orts etc.)
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
S p o ns or’s r e pr es e nt ati v e ( C R O)
F a x n u m b er f or S A E r e p orti n g:             
E- m ail f or S A E r e p orti n g:
P h o n e n u m b er f or S A E r e p orti n g:        
S urf ac e m ail f or S A E r e p orti n g:
            
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _
E- m ail a d dr ess will b e pr e -pr o gr a m m e d i n t h e e C R F s yst e m.
F or n o n -ur g e nt c o m pl e m e nt ar y i nf or m ati o n n ot p ossi bl e t o s e n d b y e - m ail or f ax, pl e as e us e 
s urf ac e m ail.
T h e S A E f or m m ust b e si g n e d a n d d at e d b y t h e I n v esti g at or. If t h e i niti al 2 4 -h o ur S A E r e p ort 
d o es n ot c o nt ai n f ull i nf or m ati o n or if it is m a d e wit h o ut usi n g t h e S A E f or m t h e f ully 
c o m pl et e d a n d si g n e d S A E f or m t o t h e S p o ns or’s r e pr es e nt ati v e will als o b e m a d e i n t h e 
e C R F s yst e m. If t h er e ar e diffic ulti es acc essi n g t h e e C R F, t h e f oll o w u p r e p ort c o ul d b e s e nt 
t o t h e S p o ns or’s r e pr es e nt ati v e vi a e m ail or f ax, pl e as e al ert t h e C R O vi a t el e p h o n e, if 
a p plic a bl e. A c o p y of t h e f ull y c o m pl et e d S A E f or m s hall b e k e pt at t h e sit e.
I n a d diti o n, acc or di n g t o n ati o n al r e g ul ati o ns, th e a d mi nistr ati v e d e p art m e nt of m e dic al 
d e vic e cli nic al tri als s h o ul d, wit hi n 2 4 h o urs, d eli v er a writt e n r e p ort t o t h e c orr es p o n di n g 
Et hics C o m mitt e e a n d t h e l oc al f o o d a n d dr u g a d mi nistr ati v e d e p art m e nt of pr ovi nc e, 
a ut o n o m o us r e gi o n a n d m u nici p alit y at t h e pl ac e w h er e t h e cli nic al tri al i nstit uti o n l oc at es. 
I n c as e of a d e at h i nci d e nt, t h e cli nic al tri al i nstit uti o ns a n d i n v esti g at ors s h o ul d f ur nish t h e 
Et hics C o m mitt e e a n d t h e S p o ns or R e pr es e nt ati v e wit h all r e q uir e d m at eri als.
T h e S p o ns or R e pr es e nt ati v e is r es p o nsi bl e f or, wit hi n fiv e ( 5) b usi n ess d ays u p o n b ei n g 
i nf or m e d, r e p orti n g a n y S A E or d e vic e d ef ect wit h t h e li k eli h o o d of S A E t o t h e f o o d a n d dr u g 
a d mi nistr ati v e d e p art m e nt w h er e it h as b e e n r e gist er e d a n d t h e c o m p et e nt a ut h oriti es of 
h e alt h a n d f a mil y pl a n ni n g at t h e s a m e l ev el; m e a n w hil e, t h e S p o ns or s h o ul d n otif y ot h er 
cli nic al tri al i nstit uti o ns a n d i n v esti g at ors p artici p ati n g i n t h e cli nic al tri al, a n d pr o m ptl y 
r e p ort it t o t h e Et hics C o m mitt e e of t h e i n v ol v e d cli nic al tri al i nstit uti o ns vi a t h e 
a d mi nistr ati v e d e p art m e nt of m e dic al d e vic e cli nic al tri als acc or di n g t o n ati o n al r e g ul ati o ns.
Title  
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8.4.6
Follow-up of Unresolved Events after study termination
All serious as well as non-serious AEs with a causal relationship to the study product or 
treatment procedure and ongoing at study end, shall be followed up after the subject's 
participation in the study is over. Such events shall be followed-up after the last study visit
until resolved, assessed as chronic or stable, or for at least three months. Final outcome 
after study end should be reported on an AE Follow-up module in the eCRF.
8.4.7
Pregnancy
Pregnancy itself is not regarded as an AE.
If there is a pregnancy during the study period the subject must continue to be followed 
within the study and the outcome of pregnancy must be reported even if the expected date 
of delivery occurs after study completion.
A pregnancy confirmed during the study period must be reported by the Investigator on a 
pregnancy report form immediately upon acknowledge be submitted to the Sponsor 
according to contact details specified in section 8.4.5. The report can be prospective or 
retrospective. Follow-up shall be conducted to obtain outcome information on all 
prospective reports. 
Cases that led to foetal distress, foetal death or a congenital abnormality or birth defect are 
to be regarded as SAEs and shall be reported on the exposure in utero report form to the 
Sponsor immediately but no later than 24 hours after the Investigators awareness. These 
events shall be handled as SAEs during data processing. Other complications during the 
pregnancy that are related to the pregnant woman and fulfils any serious criteria, such as 
pre-eclampsia requiring hospitalisation, shall be reported and handled as SAEs. Elective 
abortions without complications will not be reported as AEs.
8.4.8
Anticipated Adverse Events
After the injection some common injection-related reactions might occur with both 
products. These reactions include bruising, erythema, swelling, pain, tenderness and itching
at the injections site. Typically these reactions start on the day of treatment and resolve
spontaneous within a few (2-7) days after injection, as observed in the Chinese clinical study 
for Restylane and in consistent with international results for both products.
Refer to the Restylane Perlane Lidocaine IFU (See Appendix 3).
8.5
Device Deficiencies
8.5.1
Definition of Device Deficiency
A device deficiency is defined as an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety* or performance.
Note: Device deficiencies include malfunctions, use errors, and inadequate labelling.
*Inadequacy of device safety refers to properties of the device which could have or have led to an AE. 
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8.5.2
Recording Instructions
When a device deficiency is discovered the Clinical Study Complaint Form in the eCRF will be 
completed by the Investigator. The type of complaint shall be described and injury to the 
subject or user or unintended exposure to study product shall be reported as applicable. If 
an injury has occurred, an AE module or a SAE Form should be completed following 
instructions in section 8.4. If no SAE was experienced as a result of the device deficiency the 
Investigator shall assess whether or not the device deficiency could have led to an SAE if:

Suitable action had not been taken,

Intervention had not been made or,

Circumstances had been less fortunate
The Sponsor will also make the same assessment in the Clinical Study Complaint Form. 
8.5.3
Reporting Device Deficiency
The Investigator will complete the Clinical Study Complaint Form to the Sponsor using the 
contact details specified in section 8.4.5. A device deficiency that led to a SAE and any 
device deficiency that could have led to a SAE shall be reported within 24 hours after the 
Investigator’s awareness in accordance to section 8.4.5.
In order to fulfil regulatory reporting requirements, all deficiencies with the study product 
must be assessed by both the Investigator and the Sponsor to determine if it could have led 
to a SAE.
If an SAE has resulted from a device deficiency or if either the Investigator or the Sponsor 
assesses that the device deficiency could have led to an SAE the event will be reported in 
accordance with Regulatory requirements, as applicable.
The deficient study product shall be kept, if applicable, by the study site until the QA
complaints group has confirmed whether the product shall be returned to Sponsor for 
further study or if it can be destroyed at the study site.
9
Data Handling and Management 
9.1
Data management
Data management based on GCP refers to the activities defined to achieve safe routines to 
enter clinical data information into a database, efficiently and avoiding errors. The data 
management routine includes procedures for handling eCRFs, database set-up and 
management, data entry and verification, data validation, and documentation of the 
performed activities including information of discrepancies in the process. The data 
management process will be described in detail in the data management plan (DMP).
The database, the data entry screens and program will be designed in accordance with the 
CSP. Data validation will be performed by computerised logical checks and manual review. 
Drugs and events will be coded in accordance with World Health Organization (WHO) Drug 
and medical dictionary for regulatory activities (MedDRA) dictionaries as specified in the 
DMP. Safety data (SAE) in the clinical database will be reconciled against the data in the 
safety database.
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When all efforts have been made to ensure that the data recorded in the eCRFs and entered 
in the database is as correct and complete as possible, the clinical database will be locked. 
Study data will be transferred to SAS datasets which thereafter will be write-protected. 
Statistical analyses will be generated in SAS using data from the locked datasets.
9.2
Electronic case report forms 
An eCRF is required and shall be completed electronically for each screened subject 
(screening visit) and included subjects (subsequent visits). 
The eCRF includes password protection and internal quality checks, such as automatic range 
checks, to identify data that appear inconsistent, incomplete, or inaccurate. Study data will 
be transcribed directly from the source documents, which are to be defined at each site 
before inclusion of the first subject.
Authorised study site personnel designated by the PI shall complete data collection. 
Appropriate training and security measures shall be completed with all authorised study site 
personnel prior to the study being initiated and any data being entered into the system for 
any subject.
The study data is the sole property of the Sponsor and shall not be made available in any 
form to third parties without written permission from the Sponsor. At the end of the study, 
electronic data are kept at the Sponsor and a copy (provided by the vendor) at the study site 
as part of the Investigator file.
Any delegation of collection of data shall be specified in a signature and delegation log.
9.2.1
Data entry
All data shall be entered in English. The eCRFs should always reflect the latest observations 
on the subjects participating in the study. Therefore, the eCRFs shall be completed within 5 
working days after the subject’s visit. The subject’s identity must always remain confidential, 
i.e. the name and address of the subjects must not be registered in the eCRFs or in the 
database. The Investigator must verify that all data entries in the eCRFs are accurate and 
correct. If some assessments are not done, or if certain information is not available, not 
applicable or unknown, the Investigator shall indicate this in the eCRF. The Investigator shall 
electronically sign off the study data. By signing, the Investigator takes responsibility for the 
accuracy, completeness, and legibility of the data reported to the Sponsor in the eCRF.
9.2.2
The query process
The monitor shall review the eCRFs and evaluate them for completeness and consistency by 
100%. Each eCRF shall be compared with the respective source documents to ensure that 
there are no discrepancies between critical data. All entries, corrections, and alterations 
shall be made by the PI or his/her authorised designee. The monitor cannot enter data in 
the eCRFs. Once study data have been submitted to the central server via the eCRF, 
corrections to the data fields will be audit trailed, meaning that the reason for change, the 
name of the person who made the change, together with time and date will be logged. 
Roles and rights of the site personnel responsible for entering study data into the eCRF shall 
be determined in advance. If discrepant data is detected during review of the data, either by 
the Sponsor or its representatives, the responsible data manager or monitor shall raise a 
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query in the electronic data capture application. The query shall state the question or data 
to be changed and shall be resolved in the system by the PI or his/her authorised designee. 
The appropriate study site personnel shall answer the queries in the eCRF. This will be audit 
trailed by the electronic data capture application meaning that the name of study site 
personnel, time, and date is logged.
9.2.3
User identification
Electronic CRF records will be automatically appended with the identification of the creator, 
by means of their unique User ID. Specified records shall be electronically signed by the 
Investigator to document his/her review of the data and acknowledgement that the data 
are accurate. This will be facilitated by means of the Investigator’s unique User ID and 
password; date and time stamps will be added automatically at time of electronic signature. 
If an entry in an eCRF requires change, the correction shall be made in accordance with the 
relevant software procedures. 
9.2.4
Audit trail
All changes will be fully recorded in a protected audit trail and a reason for the change shall 
be stated. Once all data have been entered, verified, and validated, the database will be 
locked.
9.3
Source documents
The eCRF is essentially considered a data entry form and does not constitute the original (or 
source) medical records unless otherwise specified. Source documents are all documents 
used by the Investigator or hospital that relate to the subject’s medical history, that verifies 
the existence of the subject, the inclusion and exclusion criteria, and all records covering the 
subject’s participation in the study. They include photographs, memoranda, material 
dispensing records, subject files, etc.
The PI is responsible for maintaining source documents. These shall be made available for 
inspection by the monitor at each monitoring visit. The Investigator must submit a 
completed eCRF for each subject for whom signed informed consent has been collected. All 
supportive documentation submitted with the eCRF, such as photographs, should be clearly 
identified with the subject number. Any personal information, including name, shall be 
removed or rendered illegible to preserve individual confidentiality.
9.4
Record keeping and access to source data
The PI/institution shall permit study-related monitoring, audits and IEC review and shall 
provide direct access to the source data/medical record including the identity of all 
participating subjects (sufficient information to link records, i.e. eCRF, medical records, 
original signed Informed Consent Forms and detailed records of study product 
accountability). The records should be retained by the PI as required by local legislation and 
international guidelines. Any transfer of responsibility for storage of the records shall be 
documented and the Sponsor should be informed in writing.
The Sponsor shall verify that each subject has consented in writing to direct access to the 
original medical record/source data (by the use of written subject information and signed 
informed consent). The data recorded in the eCRFs shall be checked for consistency with the 
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s o urc e d oc u m e nts/ m e dic al r ec or d b y t h e m o nit or 
d uri n g m o nit ori n g 
(s o urc e d at a 
v erific ati o n; S D V). I n or d er t o b e a bl e t o p erf or m S D V, i nf or m ati o n a b o ut e ac h s u bj ect’s 
p artici p ati o n i n t h e st u d y h as t o b e d et ail e d i n t h e m e dic al r ec or d. 
T h e s o urc e d at a l oc ati o n l o g s p ecifi es w h at d at a t h at s h o ul d b e a v ail a bl e i n t h e m e dic al 
r ec or d. T h e s o urc e d at a l oc ati o n l o g s h o ul d als o s p ecif y t h e d at a f or w hic h t h e e C R F s erv es 
as t h e s o urc e. S uc h d at a o nl y n e e d t o b e r ec or d e d i n t h e e C R F a n d ar e t y pic all y ass oci at e d 
wit h st u d y-s p ecific pr oc e d ur es a n d n ot wit h n or m al cli nic al c ar e pr actic e. F or t his t y p e of 
st u d y d at a t h e I n v esti g at or w o ul d n ot b e ex p ect e d t o d u plic at e t h e i nf or m ati o n i nt o t h e 
m e di c al r ec or d.
9. 5
D oc u m e nt a n d d at a r et e nti o n
All r ec or ds p ert ai ni n g t o t h e c o n d uct of t h e st u d y, i ncl u di n g si g n e d e C R Fs, I nf or m e d C o ns e nt 
F or ms, st u d y pr o d uct acc o u nt a bilit y r ec or ds, s o urc e d oc u m e nts, a n d ot h er st u dy 
d oc u m e nt ati o n m ust b e r et ai n e d aft er st u dy co m pl eti o n acc or di n g t o n ati o n al l e gisl ati o n 
a n d t h e C T A. S p o ns or will i nf or m t h e sit es as t o w h e n t h es e d oc u m e nts n o l o n g er n e e ds t o 
b e r et ai n e d. M e as ur es s h o ul d b e t a k e n t o pr e v e nt acci d e nt al or pr e m at ur e d estr ucti o n of 
t h es e d oc u m e nts ( e. g. pr ot ecti o n a g ai nst d a m a g e a n d u n a ut h oris e d acc ess, pr ef er a bl y by 
st or a g e i n a fir e-pr o of c a bi n et). R ef er t o t h e C T A.
Aft er st u d y c o m pl eti o n a n d d at a b as e l oc k, a s ec urit y s e al e d C D wit h el ectr o nic st u dy d at a 
s h all b e pr o vi d e d b y t h e e C R F v e n d or f or arc hi vi n g.
It is t h e PI’s r es p o nsi bilit y t o i nf or m Q -M e d A B i n writi n g if t h e I n v esti g at or fil e is m o v e d or if 
t h e r es p o nsi bilit y f or t h e d oc u m e nts is tr a nsf err e d t o s o m e o n e els e
1 0 St atistic al M et h o ds
1 0. 1
G e n er al
A c o m pr e h e nsi v e St atistic al A n al ysis Pl a n ( S A P) wit h d et ail e d d escri pti o n of all st atistic al 
a n al ys es will b e writt e n a n d fi n aliz e d pri or t o d at a b as e l oc k ( D BL). All s u m m ari es f or Gr o u p 
A a n d B will b e d o n e s e p ar at el y. F or gr o u p A, o nl y d escri pti v e st atistics will b e us e d. All 
st atistic al a n al ys es, i ncl u di n g s u m m ar y t a bl es a n d d at a listi n gs, will b e p erf or m e d usi n g t h e 
S A S ® s yst e m ( v ersi o n 9). 
C o nti n u o us v ari a bl es will b e s u m m aris e d usi n g st a n d ar d st atistic al m e as ur es, s uc h as m e a n, 
m e di a n, st a n d ar d d e vi at i o n, mi ni m u m a n d m axi m u m v al u es. C at e g oric al v ari a bl es will b e 
pr es e nt e d i n fr e q u e nc y t a bl es wit h n u m b er a n d p erc e nt of o bs er v ati o ns f or e ac h l e v el.
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
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Versi o n: 
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 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
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5 5 ( 6 2)
1 0. 2
A n al ysis P o p ul ati o ns
T h e f oll o wi n g p o p ul ati o ns will b e d efi n e d:

S af et y
I ncl u d es all s u bj ects i n Gr o u p B w h o w er e tr e at e d wit h 
P erl a n e -Li d o or r a n d o miz e d t o n o-tr e at m e nt gr o u p. 
S u bj ects ar e a n al yz e d b as e d o n t h e as tr e at e d pri nci pl e.

F ull A n al ysis S et ( F A S)
I ncl u d es all s u bj ects i n Gr o u p B w h o w er e tr e at e d wit h 
P erl a n e -Li d o or r a n d o miz e d t o n o-tr e at m e nt gr o u p. 
S u bj ects ar e a n al yz e d acc or di n g t o t h e r a n d o mis ati o n 
assi g n m e nt.

P er Pr ot oc ol ( P P) 
I ncl u des all s u bj ects i n F A S t h at c o m pl y t o t h e pr ot oc ol 
pr oc e d ur es wit h n o d e vi ati o ns t h at c a n aff ect t h e 
e v al u ati o n of t h e pri m ar y v ari a bl e.
T h e F A S p o p ul ati o n is t h e pri m ar y p o p ul ati o n f or all effic ac y a n al ys es. All s af et y a n al ys es will 
b e b as e d o n t h e S af et y p o p ul ati o n.
1 0. 3
D e m o gr a p hics, b as eli n e ass ess m e nts, a n d s u bj ect c h ar act eristics
D e m o gr a p hic e n d p oi nts a n d s u bj ect c h ar act eristics will b e pr es e nt e d b y st u d y pr o d uct usi n g 
d escri pti v e st atistics.
1 0. 4
Effic ac y A n al ysi s
Pri m ary a n alysis
T h e p erc e nt r es p o n d ers ( a r es p o n d er will b e d efi n e d as a s u bj ect wit h at l e ast 1 gr a d e 
i m pr o v e m e nt fr o m b as eli n e M M V S f or t h e ri g ht a n d l eft si d es of t h e f ac e c o m bi n e d) will b e 
c alc ul at e d f or e ac h tr e at m e nt gr o u p at M o nt h 
6 b as e d o n t h e bli n d e d ev al u at or's 
ass ess m e nt. 
 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
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C CI
C CI

5 6 ( 6 2)
1 0. 5
S af et y A n al ysis
 
 A 
si mil ar s u m m ar y will als o b e pr es e nt e d b y s e v erit y. A gr a p h will b e g e n er at e d t o ill ustr at e 
t h e i nci d e nc e o v er ti m e. D at a fr o m t h e P erl a n e -L gr o u p will b e p o ol e d wit h t h e n o-
tr e at m e nt gr o u p.
All A Es will b e c o d e d acc or di n g t o M e d D R A. 
All A Es will b e s u m m aris e d by s yst e m or g a n cl ass ( S O C), pr ef err e d t er m ( P T) a n d tr e at m e nt. 
Si nc e t h e n o -tr e at m e nt c o ntr ol gr o u p will r ec eiv e tr e at m e nt at t h e m o nt h 6 visit, o nl y A Es 
occ urr i n g u p u ntil t h at ti m e p oi nt will b e i ncl u d e d i n t his pr es e nt ati o n , f or b ot h gr o u ps . 
F urt h er m or e, all A Es will als o b e s u m m aris e d b y S O C a n d P T usi n g t h e P erl a n e -L gr o u p f or
t h e w h ol e st u d y p eri o d , a n d als o usi n g t h e n o -tr e at m e nt gr o u p f or t h e st u d y p eri o d 
f oll o wi n g t h eir tr e at m e nt at M o nt h 6 .
R el at e d A Es will b e s u m m aris e d by S O C, P T a n d i nt e nsit y. I n a d diti o n, f or r el at e d A Es t h e 
n u m b er of d a ys t o o ns et a n d t h e d ur ati o n of e v e nt will b e s u m m aris e d by S O C a n d P T usi n g 
m e a n, S D, mi n, m ax a n d m e di a n. Acti o n t a k e n f or r el at e d A Es will als o b e s u m m aris e d. D at a 
fr o m t h e P erl a n e-L gr o u p will b e p o ol e d wit h t h e n o-tr e at m e nt gr o u p.
S eri o us A Es will b e list e d. 
N o n r el at e d A Es will b e s u m m aris e d b y S O C, P T, a n d i nt e nsit y. T his will b e d o n e as d escri b e d 
f or all A Es, i. e. b as e d o n t h e f oll o wi n g s u bs ets of d at a: first 6 m o nt hs f oll o wi n g tr e at m e nt b y 
tr e at m e nt, t h e P erl a n e -L gr o u p f or t h e w h ol e st u d y, a n d t h e n o -tr e at m e nt gr o u p f or t h e 
p eri o d f oll o wi n g t h eir tr e at m e n t. 
1 0. 6
H a n dli n g of Missi n g D at a
N u m b er of missi n g v al u es will b e s u m m ariz e d a n d r e p ort e d as a p pr o pri at e. T h e b as eli n e 
o bs er v ati o n c arri e d f or w ar d ( B O C F) m et h o d will b e us e d as t h e pri m ar y m et h o d t o h a n dl e 
missi n g d at a o n M M V S u p t o t h e M o nt h 6 visit i n t h e F A S a n al ysis s et. T his str at e g y is a 
c o ns er v ati v e a p pr o ac h as it tr e ats s u bj ects wit h missi n g
d at a as n o n -r es p o n d ers. I m p act of 
missi n g d at a o n t h e pri m ar y a n al ysis f or M o nt h 6 e n d p oi nt will b e e v al u at e d by p erf or mi n g 
s e nsiti vit y a n al ysis b as e d o n t h e P P p o p ul ati o n. I n a d diti o n, missi n g d at a f or t h e pri m ary 
a n al ysis will als o b e h a n dl e d usi n g t h e m ulti pl e i m p ut ati o n m et h o d . 
All ot h er e n d p oi nts will b e a n al yz e d o n a v ail a bl e d at a, i. e. n o i m p ut ati o ns will b e d o n e.
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
C CI
C CI

5 7 ( 6 2)
1 0. 7
I nt eri m A n al ysis
N o i nt eri m a n al ysis is pl a n n e d.
1 0. 8
D at a m o nit ori n g c o m mitt e e
N ot a p plic a bl e f or t his st u d y .
1 0. 9
Wit h dr a w als a n d d e vi ati o ns
All wit h dr a w n s u bj ects will b e list e d i n di vi d u all y, i ncl u di n g at l e ast s u bj ect n u m b er, d at e a n d 
r e as o n f or wit h dr a w al, a n d l ast visit p erf or m e d.
S u bj ects wit h C S P d e vi ati o ns will b e list e d i n di vi d u all y, i ncl u di n g s u bj ect n u m b er a n d 
o bs er v e d d e vi ati o n. D e p e n di n g o n t h e s eri o us n ess of t h e d e vi ati o n, s u bj ect mi g ht b e 
excl u d e d fr o m t h e P P p o p ul ati o n, w hic h s hall b e d oc u m e nt e d pr i ort o D BL .
D e vi ati o ns fr o m t h e st atistic al pl a n will b e d oc u m e nt e d i n pr ot oc ol D e vi ati o n l o g.
1 0. 1 0 S a m pl e Siz e
1 1 Pr ot ecti o n of p ers o n al d at a
F or t h e p ur p os es of t h e st u d y, S p o ns or will b e c o nsi d er e d t h e d at a c o ntr oll er, a n d 
I nstit uti o n a n d PI will b ot h b e c o nsi d er e d d at a pr oc ess ors.
All pr oc essi n g of p ers o n al d at a m ust b e c arri e d o ut i n acc or d a nc e wit h n ati o n al l e gisl ati o n 
c o nc er ni n g t h e pr ot ecti o n of p ers o n al d at a. T h e I nstit uti o n a n d t h e PI ar e r es p o nsi bl e f or 
c o m pl yi n g wit h all r e q uir e m e nts p urs u a nt t o n ati o n al l e gisl ati o n i n t h e c o u ntr y i n w hic h t h e 
I nstit uti o n a n d t he PI ar e l oc at e d. T h e S p o ns or will e ns ur e t h at all r e q uir e m e nts ar e 
c o m pli e d wit h f or d at a pr oc essi n g, w hic h is c arri e d o ut i n S w e d e n b y t h e S p o ns or.
T h e I nf or m e d C o ns e nt F or m s h all c o nt ai n i nf or m ati o n a b o ut w h at p ers o n al d at a t o b e 
c oll ect e d i n t h e st u d y a n d t h at t his will b e k e pt c o nfi d e nti al. T h e pr o vi d e d i nf or m ati o n s h all 
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
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4. 0
 
 
 
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58(62)
be sufficient to enable all subjects to give their consent not only to the participation in the 
study, but also to the processing of personal data. Such information includes information 
regarding the purposes of the collecting, processing, data transfer to countries outside 
China, and the length of time during which personal data will be stored. The subject shall 
have the right of access to stored personal data, and the right to correction of incorrect 
information. If a subject decides to terminate the study prematurely, data collected before 
withdraw of consent will be used in the evaluation of the study, however no new data may 
be collected. Authorised representatives from the Sponsoror a RA may visit the study site to 
perform audits/inspections, including source data verification, i.e. comparing data in the 
subjects’ medical records and the eCRF. Data and information shall be handled strictly 
confidential.
12 Quality Control and Quality Assurance
12.1 Quality control
On-site monitoring of the study will be arranged by the Sponsor according to GCP guidelines 
to verify that the rights and well-being of the subjects are protected, the reported data are 
accurate, complete, verifiable from source documents, and that the conduct of the study 
complies with the approved CSP, subsequent amendment(s), GCP and the applicable 
regulatory requirements. 
Any CSP deviation shall be reported in the eCRF, which shall be verified, discussed, and 
collected, by the monitor and appropriate corrective and preventive actions shall be taken. 
The PI is responsible for promptly reporting any deviations from the CSP that affects the 
rights, safety or well-being of the subject or the scientific integrity of the study, including 
those which occur under emergency circumstances, to the Sponsor as well as the IEC if 
required by national regulations. Deviations shall be reviewed to determine the need to 
amend the CSP or to terminate the study. Handling of CSP deviations shall be performed as 
described in the monitoring manual.
12.2 Quality assurance
The study site may be subject to quality assurance audit by the Sponsor as well as inspection 
by appropriate RA. It is important that the PI and other relevant study site personnel are 
available during the monitoring visits, possible audits, and inspections, and that sufficient 
time is devoted to the monitoring process.
Each participating member of the study site team shall provide a curriculum vitae (CV) or 
equivalent that demonstrates their qualifications to conduct the study. The CV shall give 
name, date and place of birth, address and place of work, and shall show the training, 
appointments and, for the PI, any other information that confirms the suitability of the PI to 
be responsible for the study. 
It is the responsibility of the PI to ensure that all personnel involved in the study are fully 
informed of all relevant aspects of the study, including detailed knowledge of and training in 
all procedures to be followed. All Investigators and other responsible persons shall be listed 
together with their function in the study on the signature and delegation log.
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12.3 Changes to the clinical study protocol
The PI and other site personnel involved in the study must not implement any deviation 
from or changes to the CSP without agreement with the Sponsor and prior review and 
documented approval from the IEC, except where necessary to eliminate an immediate 
hazard to the subjects. All changes to the final CSP must be documented in a written 
protocol amendment. However, administrative changes are to be documented in the 
Sponsor file without requiring a protocol amendment.
13 Financing, Indemnification, and Insurance
The CTA outlines the compensation and payment terms of the study. The CTA must be 
signed before the first subject is screened in the study. If there are differences between the 
CTA and the CSP regarding certain rights and obligations, the CTA is the prevailing 
document. Q-Med AB’s obligations in this clinical study are covered by Galderma’s global 
general liability program. An insurance certificate will be provided upon request. The 
institution/PI is obligated to maintain insurance coverage for their obligations in the clinical 
study according to the CTA.
14 Publication Policy
The PI’s, institutions, and Q-Med AB’s obligations regarding intellectual property rights, 
confidentiality, and publications are described in detail in the CTA.
The aim is to submit the results of this study for publication in the public database 
ClinicalTrials.gov and to a medical journal for a first joint publication of the results. Everyone 
who is to be listed as an author of the results of this multicentre study shall have made a 
substantial, direct, intellectual contribution to the work. Authorship will be based on (1) 
substantial contributions to the conception or design of the work; or the acquisition, 
analysis, or interpretation of data for the work; and (2) drafting the work or revising it 
critically for important intellectual content; and (3) final approval of the version to be 
published; and (4) agreement to be accountable for all aspects of the work in ensuring that 
questions related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved*. Conditions 1, 2, 3, and 4 must all be met in order to be 
designated as author. Those who do not meet all four criteria should be acknowledged. 
Among the authors that fulfil the above mentioned criteria, one author will be appointed by 
Q-Med AB to take primary responsibility for the overall work as primary author.
*Defining the role of authors and contributors, compiled by the International Committee of 
Medical Journal Editors (ICMJE) (http://www.icmje.org). 
15 Suspension or Premature Termination
The Sponsor will suspend or terminate the study when so instructed by the IEC or if it is 
judged that the subjects are subjected to unreasonable risks, or for valid scientific or 
administrative reasons. 
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The Sponsor may also decide to close a single study site due to unsatisfactory subject 
enrolment or non-compliance with the CSP, GCP, or applicable regulatory requirements.
In the event of premature termination, Q-Med AB will provide information on the handling 
of currently enrolled subjects who have not completed the study
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16 References
1.
Monheit GD, Coleman KM. Hyaluronic acid fillers. Dermatol 2006 May-Jun; 19(3):141-50.
2.
Gold M. The science and art of hyaluronic acid dermal filler use in esthetic applications. J 
Cosmet Dermatol 2009 Dec; 8(4):301-7.
3.
Fernandez-Cossio S and Castano-Oreja MT. Biocompatibility of two novel dermal fillers: 
histological evaluation of implants of a hyaluronic acid filler and a polyacrylamide filler. Plast 
Reconstr Surg. 2006 May; 117(6):1789-96.
4.
Heden P, Fagrell D, Jernbeck J, Rylander R, Samuelson U, Sellman G, Stark B. Injection of 
stabilized hyaluronic acid-based gel of non-animal origin for the correction of nasolabial 
folds: comparison with and without lidocaine. Dermatol Surg. 2010;36:775-781.
5.
Brandt F, Bank D, Cross SL, Weiss R. A lidocaine-containing formulation of large-gel particle 
hyaluronic acid alleviates pain. Dermatol Surg. 2010 Nov;36 Suppl 3:1876-85.
6.
Instructions for Use Restylane Lyft with Lidocaine in US. Available from URL: 
http://www.galdermausa.com/IFU/Restylane_Lyft_IFU.pdf?_ga=1.42582114.610718906.145
4326093.
Assessed 2016-03-29.
7.
Lorenc ZP, Bank D, Kane M, Lin X, Smith S. Validation of a Four Point Photographic Scale for 
the Assessment of Midface Volume Loss and/or Contour Deficiency. Plast Reconstr Surg 
2012 Dec;130(6):1330-6.
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17 Appendices
Appendix 1
Declaration of Helsinki 
Appendix 2
Photo guide for MMVS
Appendix 3    EU IFU of Restylane Perlane Lidocaine
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Appendix 1
Declaration of Helsinki
1(5)
WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving
Human Subjects
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and amended by the:
29th WMA General Assembly, Tokyo, Japan, October 1975
35th WMA General Assembly, Venice, Italy, October 1983
41st WMA General Assembly, Hong Kong, September 1989
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996
52nd WMA General Assembly, Edinburgh, Scotland, October 2000
53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added)
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added)
59th WMA General Assembly, Seoul, Republic of Korea, October 2008
64th WMA General Assembly, Fortaleza, Brazil, October 2013
Preamble
1.
The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of
ethical principles for medical research involving human subjects, including research on identifiable 
human material and data.
The Declaration is intended to be read as a whole and each of its constituent paragraphs should be
applied with consideration of all other relevant paragraphs.
2.
Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. The
WMA encourages others who are involved in medical research involving human subjects to adopt 
these principles.
General Principles
3.
The Declaration of Geneva of the WMA binds the physician with the words, “The health of my patient
will be my first consideration,” and the International Code of Medical Ethics declares that, “A 
physician shall act in the patient's best interest when providing medical care.”
4.
It is the duty of the physician to promote and safeguard the health, well-being and rights of patients,
including those who are involved in medical research. The physician's knowledge and conscience are 
dedicated to the fulfilment of this duty.
5.
Medical progress is based on research that ultimately must include studies involving human subjects.
6.
The primary purpose of medical research involving human subjects is to understand the causes,
development and effects of diseases and improve preventive, diagnostic and therapeutic 
interventions (methods, procedures and treatments). Even the best proven interventions must be 
evaluated continually through research for their safety, effectiveness, efficiency, accessibility and 
quality.
7.
Medical research is subject to ethical standards that promote and ensure respect for all human 
subjects and protect their health and rights.
8.
While the primary purpose of medical research is to generate new knowledge, this goal can never 
take precedence over the rights and interests of individual research subjects.
9.
It is the duty of physicians who are involved in medical research to protect the life, health, dignity,
integrity, right to self-determination, privacy, and confidentiality of personal information of research 
subjects. The responsibility for the protection of research subjects must always rest with the physician 
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Appendix 1
Declaration of Helsinki
2(5)
or other health care professionals and never with the research subjects, even though they have given 
consent.
10. Physicians must consider the ethical, legal and regulatory norms and standards for research involving
human subjects in their own countries as well as applicable international norms and standards. No 
national or international ethical, legal or regulatory requirement should reduce or eliminate any of 
the protections for research subjects set forth in this Declaration.
11. Medical research should be conducted in a manner that minimises possible harm to the environment.
12. Medical research involving human subjects must be conducted only by individuals with the 
appropriate ethics and scientific education, training and qualifications. Research on patients or 
healthy volunteers requires the supervision of a competent and appropriately qualified physician or 
other health care professional.
13. Groups that are underrepresented in medical research should be provided appropriate access to
participation in research.
14. Physicians who combine medical research with medical care should involve their patients in research
only to the extent that this is justified by its potential preventive, diagnostic or therapeutic value and 
if the physician has good reason to believe that participation in the research study will not adversely 
affect the health of the patients who serve as research subjects.
15. Appropriate compensation and treatment for subjects who are harmed as a result of participating in
research must be ensured.
Risks, Burdens and Benefits
16. In medical practice and in medical research, most interventions involve risks and burdens. Medical 
research involving human subjects may only be conducted if the importance of the objective
outweighs the risks and burdens to the research subjects.
17. All medical research involving human subjects must be preceded by careful assessment of predictable
risks and burdens to the individuals and groups involved in the research in comparison with 
foreseeable benefits to them and to other individuals or groups affected by the condition under 
investigation.
Measures to minimise the risks must be implemented. The risks must be continuously monitored,
assessed and documented by the researcher.
18. Physicians may not be involved in a research study involving human subjects unless they are confident
that the risks have been adequately assessed and can be satisfactorily managed.
When the risks are found to outweigh the potential benefits or when there is conclusive proof of
definitive outcomes, physicians must assess whether to continue, modify or immediately stop the 
study.
Vulnerable Groups and Individuals
19. Some groups and individuals are particularly vulnerable and may have an increased likelihood of 
being wronged or of incurring additional harm.
All vulnerable groups and individuals should receive specifically considered protection.
20. Medical research with a vulnerable group is only justified if the research is responsive to the health 
needs or priorities of this group and the research cannot be carried out in a non-vulnerable group. In 
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Appendix 1
Declaration of Helsinki
3(5)
addition, this group should stand to benefit from the knowledge, practices or interventions that result 
from the research.
Scientific Requirements and Research Protocols
21. Medical research involving human subjects must conform to generally accepted scientific principles, 
be based on a thorough knowledge of the scientific literature, other relevant sources of information, 
and adequate laboratory and, as appropriate, animal experimentation. The welfare of animals used 
for research must be respected.
22. The design and performance of each research study involving human subjects must be clearly 
described and justified in a research protocol.
The protocol should contain a statement of the ethical considerations involved and should indicate 
how the principles in this Declaration have been addressed. The protocol should include information 
regarding funding, sponsors, institutional affiliations, potential conflicts of interest, incentives for 
subjects and information regarding provisions for treating and/or compensating subjects who are 
harmed as a consequence of participation in the research study.
In clinical trials, the protocol must also describe appropriate arrangements for post-trial provisions.
Research Ethics Committees
23. The research protocol must be submitted for consideration, comment, guidance and approval to the
concerned research ethics committee before the study begins. This committee must be transparent in 
its functioning, must be independent of the researcher, the sponsor and any other undue influence 
and must be duly qualified. It must take into consideration the laws and regulations of the country or 
countries in which the research is to be performed as well as applicable international norms and 
standards but these must not be allowed to reduce or eliminate any of the protections for research 
subjects set forth in this Declaration.
The committee must have the right to monitor ongoing studies. The researcher must provide 
monitoring information to the committee, especially information about any serious adverse events. 
No amendment to the protocol may be made without consideration and approval by the committee. 
After the end of the study, the researchers must submit a final report to the committee containing a 
summary of the study’s findings and conclusions.
Privacy and Confidentiality
24. Every precaution must be taken to protect the privacy of research subjects and the confidentiality of 
their personal information.
Informed Consent
25. Participation by individuals capable of giving informed consent as subjects in medical research must 
be voluntary. Although it may be appropriate to consult family members or community leaders, no 
individual capable of giving informed consent may be enrolled in a research study unless he or she 
freely agrees.
26. In medical research involving human subjects capable of giving informed consent, each potential 
subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts 
of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of 
the study and the discomfort it may entail, post-study provisions and any other relevant aspects of 
the study. The potential subject must be informed of the right to refuse to participate in the study or 
to withdraw consent to participate at any time without reprisal. Special attention should be given to 
the specific information needs of individual potential subjects as well as to the methods used to 
deliver the information.
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Appendix 1
Declaration of Helsinki
4(5)
After ensuring that the potential subject has understood the information, the physician or another
appropriately qualified individual must then seek the potential subject’s freely-given informed 
consent, preferably in writing. If the consent cannot be expressed in writing, the non-written consent 
must be formally documented and witnessed.
All medical research subjects should be given the option of being informed about the general 
outcome and results of the study.
27. When seeking informed consent for participation in a research study the physician must be 
particularly cautious if the potential subject is in a dependent relationship with the physician or may 
consent under duress. In such situations the informed consent must be sought by an appropriately 
qualified individual who is completely independent of this relationship.
28. For a potential research subject who is incapable of giving informed consent, the physician must seek
informed consent from the legally authorised representative. These individuals must not be included 
in a research study that has no likelihood of benefit for them unless it is intended to promote the 
health of the group represented by the potential subject, the research cannot instead be performed 
with persons capable of providing informed consent, and the research entails only minimal risk and 
minimal burden.
29. When a potential research subject who is deemed incapable of giving informed consent is able to give
assent to decisions about participation in research, the physician must seek that assent in addition to 
the consent of the legally authorised representative. The potential subject’s dissent should be 
respected.
30. Research involving subjects who are physically or mentally incapable of giving consent, for example,
unconscious patients, may be done only if the physical or mental condition that prevents giving 
informed consent is a necessary characteristic of the research group. In such circumstances the 
physician must seek informed consent from the legally authorised representative. If no such 
representative is available and if the research cannot be delayed, the study may proceed without 
informed consent provided that the specific reasons for involving subjects with a condition that 
renders them unable to give informed consent have been stated in the research protocol and the 
study has been approved by a research ethics committee. Consent to remain in the research must be 
obtained as soon as possible from the subject or a legally authorised representative.
31. The physician must fully inform the patient which aspects of their care are related to the research. 
The refusal of a patient to participate in a study or the patient’s decision to withdraw from the study 
must never adversely affect the patient-physician relationship.
32. For medical research using identifiable human material or data, such as research on material or data
contained in biobanks or similar repositories, physicians must seek informed consent for its collection, 
storage and/or reuse. There may be exceptional situations where consent would be impossible or 
impracticable to obtain for such research. In such situations the research may be done only after 
consideration and approval of a research ethics committee.
Use of Placebo
33. The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of 
the best proven intervention(s), except in the following circumstances:
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or
Where for compelling and scientifically sound methodological reasons the use of any intervention less
effective than the best proven one, the use of placebo, or no intervention is necessary to determine 
the efficacy or safety of an intervention
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Appendix 1
Declaration of Helsinki
5(5)
and the patients who receive any intervention less effective than the best proven one, placebo, or no
intervention will not be subject to additional risks of serious or irreversible harm as a result of not 
receiving the best proven intervention.
Extreme care must be taken to avoid abuse of this option.
Post-Trial Provisions
34. In advance of a clinical trial, sponsors, researchers and host country governments should make
provisions for post-trial access for all participants who still need an intervention identified as 
beneficial in the trial. This information must also be disclosed to participants during the informed 
consent process.
Research Registration and Publication and Dissemination of Results
35. Every research study involving human subjects must be registered in a publicly accessible database
before recruitment of the first subject.
36. Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to the
publication and dissemination of the results of research. Researchers have a duty to make publicly 
available the results of their research on human subjects and are accountable for the completeness 
and accuracy of their reports. All parties should adhere to accepted guidelines for ethical reporting. 
Negative and inconclusive as well as positive results must be published or otherwise made publicly 
available. Sources of funding, institutional affiliations and conflicts of interest must be declared in the 
publication. Reports of research not in accordance with the principles of this Declaration should not 
be accepted for publication.
Unproven Interventions in Clinical Practice
37. In the treatment of an individual patient, where proven interventions do not exist or other known
interventions have been ineffective, the physician, after seeking expert advice, with informed consent 
from the patient or a legally authorised representative, may use an unproven intervention if in the 
physician's judgement it offers hope of saving life, re-establishing health or alleviating suffering. This 
intervention should subsequently be made the object of research, designed to evaluate its safety and 
efficacy. In all cases, new information must be recorded and, where appropriate, made publicly 
available.
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A p pe n di x 2
P h ot o g ui de f or M M V S 
1( 1)
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
Versi o n :
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
1(9)
Composition
Hyaluronic acid, stabilized
20 mg/mL
Lidocaine hydrochloride
3 mg/mL
Phosphate buffered saline
q.s.
Description
Restylane Perlane Lidocaine is a sterile, transparent, biodegradable gel of stabilized 
hyaluronic acid of non-animal origin with the addition of 0.3% lidocaine hydrochloride. It is 
supplied in a glass syringe. The contents of the syringe are sterilized using moist heat. The 
product is for single use only. Disposable 29G TW (thin-walled) needles sterilized using 
ethylene oxide are provided. To ensure traceability the patient record label (part of the 
syringe label) should be attached to patient records.
Intended Use
This product is intended to be used for facial tissue augmentation. It is recommended to be 
used for shaping the contours of the face, the correction of folds and for lip enhancement. It 
should be injected into the deep layer of the dermis and/or the surface layer of the subcutis or 
in the submucosal level of the lip. For facial areas with limited soft tissue support and soft 
tissue cover, e.g. the periorbital region, injection into the subcutaneous fatty tissue or 
supraperiostal administration are recommended. The addition of lidocaine provides a pain 
relieving effect during treatment.
Before the first treatment session, it is recommended to contact your local Galderma 
representative or Restylane distributor for more information about injection techniques and 
training opportunities. This product is only intended to be administered by authorized 
personnel in accordance with local legislation.
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
2(9)
Mode of action 
This product is a filler that adds volume to the tissue, thereby restoring the skin contours or 
enhancing the lips to the desired level of correction. The volume and the lifting capacity 
originate from the ability of stabilized hyaluronic acid to bind water. 
Warning

Do not use in patients with known hypersensitivity to lidocaine or to amide-type local 
anaesthetics. 

Do not inject intramuscularly or intravascularly. As for other injectable medical 
devices, inadvertent injection into blood vessels could potentially lead to vascular 
occlusion, ischemia and necrosis. Aspiration prior to injection is recommended.

If the overlying skin turns a whitish colour (blanching), the injection should be 
stopped immediately and the area massaged until it returns to a normal colour. 

Do not use in patients with bleeding disorders or in patients who are taking 
thrombolytics or anticoagulants.

Do not resterilize.

Do not mix with other products prior to injection of the device.
Precautions
General considerations relevant to injectable medical devices

Injection procedures are associated with a risk of infection. Aseptic technique and 
standard practice to prevent cross-infections are to be observed. 

Special caution should be exercised when treating areas in close proximity to 
permanent implant.

Knowledge of the anatomy of treatment site and special caution are required in order 
to avoid perforation or compression of vessels, nerves and other vulnerable structures.

Special caution should be exercised when treating areas with limited collateral 
circulation, due to increased risk of ischemia.

Special caution should be exercised in treating facial areas with limited soft tissue 
support or soft tissue cover, such as the periorbital area, to avoid formation of 
palpable lumps.

Patients with pre-existing pigmented dark lower eye lid circles, thin skin and pre-
existing tendency toward edema formation are not suitable candidates for treatment of 
the lower periorbital region.
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
3(9)

Do not use where there is active disease, such as inflammation, infection or tumours, 
in or near the intended treatment site.

Injection procedures can lead to reactivation of latent or subclinical herpes viral 
infections.

Patients who are using substances that affect platelet function, such as aspirin and 
non-steroidal anti-inflammatory drugs may, as with any injection, experience 
increased bruising or bleeding at injection sites.

Patients with unattainable expectations are not suitable candidates for treatment.

Do not use the product if package is damaged.
Specific considerations relevant to the use of this product

Do not inject this product into an area where an implant other than hyaluronic acid 
has been placed.

If the product is injected too superficially this may result in visible lumps and/or 
bluish discoloration.

Patients should avoid excessive sun or extreme cold at least until any initial swelling 
and redness has resolved. 

If laser treatment, chemical peeling or any other procedure based on active dermal 
response is performed after treatment with this product there is a theoretical risk of 
eliciting an inflammatory reaction at the implant site. This also applies if the product 
is administered before the skin has healed completely after such a procedure. 

This product has not been tested in pregnant or breastfeeding women or in children.

Considerations should be given to the total dose of lidocaine administered if dental 
block or topical administration of lidocaine is used concurrently. High doses of 
lidocaine (more than 400 mg) can cause acute toxic reactions manifesting as 
symptoms affecting the central nervous system and cardiac conduction.

Lidocaine should be used with caution in patients receiving other local anaesthetics or 
agents structurally related to amide-type local anaesthetics e.g., certain anti-
arrhythmics, since the systemic toxic effects can be additive. 

Lidocaine should be used cautiously in patients with epilepsy, impaired cardiac 
conduction, severely impaired hepatic function or severe renal dysfunction.
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
4(9)

Peribulbar injections of local anaesthetics carry a low risk of persistent ocular muscle 
dysfunction.
Adverse events 
Anticipated injection-related reactions
Injection-related reactions might occur. These reactions include bruising, erythema, itching, 
swelling, pain or tenderness at the implant site. Typically resolution is spontaneous within a 
few days after injection into the skin, and within one week after injection of the lips.
Post marketing adverse event reporting
The following post marketing adverse events have been reported (non-exhaustive list). The 
frequency of reporting is based on the number of estimated treatments performed with the 
Restylane fillers range of products.
1/1 000 – 1/10 000
Swelling
1/10 000 – 1/50 000
Bruising, discoloration, erythema, infection, inflammation,  
ischemia/necrosis, mass, pain/tenderness, papules/nodules
1/50 000 – 1/100 000
Hypersensitivity, induration, neurological symptoms such as 
paresthesia, pruritus, short duration of effect
<1/100 000
Abscess, acne, angioedema, atrophy/scarring, blisters, capillary 
disorders such as telangiectasia, dermatitis, device dislocation, 
fistula, granuloma, rash, reactivation of herpes infection, urticaria, 
visual disturbance
Vascular compromise may occur due to an inadvertent intravascular injection or as a result of 
vascular compression associated with implantation of any injectable product. This may 
manifest as blanching, discoloration, necrosis or ulceration at the implant site or in the area 
supplied by the blood vessels affected; or rarely as ischemic events in other organs due to 
embolisation. Isolated rare cases of ischemic events affecting the eye leading to visual loss, 
and the brain resulting in cerebral infarction, following facial aesthetic treatments have been 
reported.
Isolated rare cases of ischemia/necrosis affecting the nose have been reported after injection, 
especially in patients who had prior rhinoplasty.
Symptoms of inflammation at the implant site commencing either shortly after injection or 
after a delay of up to several weeks have been reported. In case of unexplained inflammatory 
reactions infections should be excluded and treated if necessary since inadequately treated 
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
5(9)
infections may progress into complications such as abscess formation. Treatment using only 
oral corticosteroids without concurrent antibiotic treatment is not recommended.
The prolonged use of any medication, e.g., corticosteroids or antibiotics in treatment of 
adverse events has to be carefully assessed, since this may carry a risk for the patient. In case 
of persistent or recurrent inflammatory symptoms, consider removal of the product by 
aspiration/drainage, extrusion or enzymatic degradation (use of hyaluronidase has been 
described in scientific publications). Before any removal procedure is performed, the 
swelling may be reduced by using, e.g., NSAID for 2-7 days or a short course of 
corticosteroids for less than 7 days, in order to more easily palpate any remaining product.
Post inflammatory pigmentation changes have been observed in clinical studies in people 
with dark skin (Fitzpatrick Type IV-VI).
For patients who have experienced clinically significant reactions, a decision for retreatment 
should take into consideration the cause and significance of previous reactions.
For reporting of adverse events contact your local Galderma representative or distributor for 
this product.
Performance
In a controlled multicenter study with Restylane Perlane for the correction of nasolabial folds 
75% of the subjects maintained a clinically significant improvement 6 months after treatment.
In a randomized controlled 12 months follow-up study, Restylane Perlane with lidocaine was 
comparable to Restylane Perlane alone in terms of esthetic efficacy.
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
6(9)
Needle
Disposable sterile 29G TW (thin-walled) needles are provided. In case a replacement needle 
is required a 27G needle should be used.
Alternatively, a sterile blunt cannula 23-25G can be used. The size and the length of the 
cannula will affect the force needed to extrude the gel. If a thinner cannula is used the 
resistance during injection may be too high resulting in an increased risk for leakage or
separation of the cannula and syringe. The same considerations are applicable for needles.
Assembly of needle to syringe
Use the thumb and forefinger to hold firmly around both the glass syringe and the luer-lock 
adapter. Grasp the needle shield (or hub if using cannula) with the other hand. To facilitate 
proper fastening, both push and rotate firmly. See picture. Strict aseptic technique must be 
followed.
Improper assembly may result in separation of the needle and syringe during injection.
Treatment procedure

The patient shall be informed about the indications, expected result, precautions and 
potential adverse events. The patient’s need for additional pain relief should be 
assessed. For lip augmentation, anaesthesia through a nerve block can be used. 

Clean the treatment site thoroughly with a suitable antiseptic solution.

To avoid breakage of the needle or cannula, do not attempt to bend or otherwise 
manipulate it before or during treatment..

Before injecting, remove the air by pressing the rod carefully until a small droplet is 
visible at the tip of the needle.

When using a needle, aspiration prior to injection is recommended. Inject slowly 
while pulling the needle backwards.

Injection should stop just before the needle is pulled out from the skin to prevent 
material from leaking out from the injection site. 

As an alternative to the needle, a blunt cannula can be used. After preparation as 
described above, an entry point is made in the skin, e.g. with a sharp needle of 
appropriate size. Inject slowly. During injection, it is recommended to keep the side 
hole of the cannula facing downwards, away from the skin surface, to ensure that the 
flow of the gel is maintained at the correct tissue depth.

Do not apply excessive pressure to the syringe at any time. Presence of scar tissue 
may impede advancement of the cannula/needle. If resistance is encountered the 
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
7(9)
cannula/needle should be partially withdrawn and repositioned or fully withdrawn and 
checked for function.

It is recommended to change needle/cannula for each new treatment site.

At each treatment session a maximum dosage of 2 mL per treatment site is 
recommended. 

Defects should be fully corrected, but not overcorrected, at each treatment session.

The correction site should be massaged to conform to the contour of the surrounding 
tissues.

If there is pronounced skin laxity, it is recommended that the product be injected on 
two or more separate occasions.

After the first treatment, additional implantations of the product may be necessary to 
achieve the desired level of correction. Periodic follow-up injections help sustain the 
desired degree of correction. 
The syringe, disposable needle/blunt cannula and any unused material must be discarded 
immediately after the treatment session and must not be reused due to risk for contamination 
of the unused material and the associated risks including infections. Disposal should be in 
accordance with accepted medical practice and applicable national, local or institutional 
guidelines. 
Shelf life and Storage
The expiry date is indicated on package. Store up to 25° C. Protect from freezing and 
sunlight. 
Manufacturer
Q-Med AB, Seminariegatan 21, SE-752 28 Uppsala, Sweden
Phone +46(0)18 474 90 00, Fax +46(0)18 474 90 01
www.q-med.com, e-mail: info.q-med@galderma.com
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
8(9)
Symbols on packaging
Do not use if package is damaged.
CE-marked according to MDD 93/42/EEC;
0344 is the Notified Body number for Restylane Perlane Lidocaine.
CE-marked according to MDD 93/42/EEC;
0197 is the Notified Body number for the co-packed needle(s)
Restylane and NASHA are trademarks owned by Galderma S.A. 
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Appendix 3
EU IFU of Restylane Perlane Lidocaine
9(9)
Picture included in the Instructions for Use
Use the thumb and forefinger to hold firmly around both the glass syringe and the luer-
lock adapter. Grasp the needle shield (or hub if using cannula) with the other hand. To 
facilitate proper fastening, both push and rotate firmly
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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
2 0 1 6- 0 9- 0 7 1 0: 1 6
J u stifi c ati o n
A p pr o v e d b y O w n er
2 0 1 6- 0 9- 0 7 1 1: 0 1
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
2 0 1 6- 0 9- 0 7 1 1: 4 7
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
2 0 1 6- 0 9- 0 7 1 1: 5 7
J u stifi c ati o n
A p pr o v e d b y Pr oj e ct M a n a g er
Title  
D o c i d  
4 3 C H 1 5 0 7 Perl a ne Li d o mi df ace st u d y pr ot oc ol
M A- 3 0 8 4 3
 
 
 
 
Effecti ve dat e: 
 
Versi o n: 
Eff e cti v e
 2 0 1 6- 0 9- 0 7 1 1: 5 7
4. 0
 
 
 
Pri nt date:
 2 0 2 3- 0 4- 1 8 0 9: 1 9
P P D
P P D
P P D
P P D