A Multicenter, Double-blind, Randomized, Controlled Study of the Safety and Effectiveness of PN40082 for Lip Augmentation
Conditions: Lip Augmentation
Sponsor: Prollenium Medical Technologies Inc.



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1   
S Y N O P SI S   
Titl e  of  St u d y:  A  M ulti c e nt er,  D o u bl e- bli n d,  R a n d o mi z e d,  C o ntr oll e d  St u d y  of t h e  S af et y  a n d 
Eff e cti v e n ess  of  P N 4 0 0 8 2  f or  Li p A u g m e nt ati o n   
N a m e  of  S p o ns o r:  Pr oll e ni u m  M e di c al  T e c h n ol o gi es I n c. 
N a m e  of  Fi nis h e d  P r o d u ct:  P N 4 0 0 8 2  
D e vi c e  C o m p ositi o n:  H y al ur o ni c  a ci d  g el  wit h li d o c ai n e ( 0. 3 %  w/ w) 
O bj e cti v es:  T o  c o m p ar e t h e s af et y  a n d  effi c a c y  pr ofil e  of  P N 4 0 0 8 2  v ers us  R est yl a n e  Sil k  
I nj e ct a bl e  G el wit h  0. 3 % li d o c ai n e ( R est yl a n e  Sil k)  f or li p  a u g m e nt ati o n. 
St u d y  D esi g n:  T his is  a  d o u bl e- bli n d, r a n d o mi z e d,  c o ntr oll e d,  m ulti c e nt er  cli ni c al st u d y  of 
su bj e cts s e e ki n g li p  a u g m e nt ati o n.  S u bj e cts  m e eti n g i n cl usi o n/ e x cl usi o n  crit eri a  will  b e 
r a n d o mi z e d  1: 1 t o tr e at m e nt  wit h  eit h er P N 4 0 0 8 2  or  R est yl a n e  Sil k .  T h e  E v al u ati n g I n v esti g at or 
will  b e  bli n d e d t o t h e tr e at m e nt. I nj e cti o ns  of t h e st u d y  d e vi c e  will  b e  p erf or m e d  b y  a n  u n bli n d e d 
Tr e ati n g I n v esti g at or.   
At  e a c h  visit, t h e  bli n d e d  E v al u ati n g I n v esti g at or  e v al u ati o ns  a n d s u bj e ct  e v al u ati o ns  of t h e 
tr e at e d  ar e as  will  b e  p erf or m e d  a n d r e c or d e d. Visits   a n d t el e p h o n e  c o nt a cts will  o c c ur  at:  
Visit  1 /  W e e k  0 ( D a y  1)  –  b as eli n e  a n d tr e at m e nt  
  -D a y  3  ( ± 2  d a ys) - S af et y f oll o w - u p t el e p h o n e  c all 
  - D a y  1 4 ( ± 2  d a ys) –  S af et y f oll o w - u p t el e p h o n e  c all 
Visit  2 /  D a y  2 8 ( ± 2  d a ys)  / M o nt h  1  –  i nt eri m  visit (t o u c h-u p if  n e c ess ar y)  
  -D a y  3 3  ( ± 2  d a ys)  – S af et y f oll o w - u p t el ep h o n e  c all  (f or s u bj e cts  wit h t o u c h- u p 
tr e at m e nt 
  -D a y  4 4  ( ± 2  d a ys)  – S af et y f oll o w - u p t el e p h o n e  c all (f or s u bj e cts  wit h t o u c h- u p 
tr e at m e nt) 
Visit  3 /  D a y  5 6 ( ± 4  d a ys) /  M o nt h  2  –  i nt eri m  visit 
Visit  4  / D a y  8 4 ( ± 4  d a ys) /  M o nt h  3  –  i nt eri m  visit 
  - D a y  1 1 2 ( ± 4  d a ys) /  M o nt h  4  – S af et y f oll o w - u p t el e p h o n e  c all 
  - D a y  1 4 0 ( ± 4  d a ys) /  M o nt h  5  – S af et y f oll o w - u p t el e p h o n e  c all 
Visit  5  / D a y  1 6 8 ( ± 7  d a ys) /  M o nt h  6  –  E n d  of  St u d y  ( E O S) Visit .  All s u bj e cts  will 
u n d er g o t h e  c o ns e nt  pr o c e d ur e f or  t h e  o p e n-l ab el  r etr e at m e nt  pr ot o c ol. 
E v al u ati o ns i n cl u d e: 
Li p  F ull n ess  Gr a di n g  S c al e ( L F G S)  ( O v er all li p f ull n ess  c o nsi d eri n g  b ot h li ps 
t o g et h er, f ull n ess  of t h e  u p p er li p  a n d f ull n ess  of t h e l o w er li p) 
P eri or al  li n es  at r est se v erit y  sc al e ( P O L)  ( O v er all  p eri or al li n es  at r est s e v erit y 
c o nsi d eri n g  b ot h li ps t o g et h er,  p eri or al li n es  at r est s e v erit y  of t h e  u p p er li p  a n d 
p eri or al li n es  at r est s e v erit y  of t h e l o w er li p)  
P ati e nt  Gl o b al  A est h eti c I m pr o v e m e nt ( p G AI)  

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I n v esti g at or  Gl o b al  A est h eti c I m pr o v e m e nt (i G AI) 
S af et y  will  b e  ass ess e d  b y  m o nit ori n g  a d v ers e  e v e nts ( A Es)  at  all st u d y  visits  
Ot h er  S af et y  E v al u ati o ns i n cl u d e: 
                Li p  F u n cti o n  
                 Li p  S e ns ati o n 
                 Li p  T e xt ur e 
                Li p  Fir m n ess  
                Li p  S y m m etr y  
Li p  M o v e m e nt/ F u n cti o n 
Ot h er  e v al u ati o ns i n cl u d e: 
I n v esti g at or  E as e  of  Us e  Ass ess m e nt 
S w elli n g  Ass ess m e nt   
S u bj e ct  S atisf a cti o n  wit h  Li ps  Ass ess m e nt  
N u m b e r  of  St u d y  C e nt e rs:  A p pr o xi m at el y  7  sit es i n t h e  U nit e d  St at es  
D u r ati o n  of  P a rti ci p ati o n:  S u bj e cts  will  p arti ci p at e i n t h e st u d y f or  a p pr o xi m at el y  6  m o nt hs 
fr o m t h e ti m e t h e y si g n t h e i nf or m e d  c o ns e nt f or m (I C F) t hr o u g h t h e E O S  visit . 
D u r ati o n  of  St u d y:  T h e st u d y  will r e q uir e  a p pr o xi m at el y  2 0  m o nt hs fr o m t h e first s u bj e ct 
si gni n g t h e I C F t o t h e  M o nt h  6  E O S  visit f or t h e  l ast s u bj e ct 
N u m b e r  of  S u bj e cts:  A p pr o xi m at el y  1 5 8 s u bj e cts  will  b e r a n d o mi z e d 
I n cl usi o n  C rit e ri a:  
1.   M e n  or  n o n- pr e g n a nt  or  n o n- br e astf e e di n g  w o m e n   o v er  2 1 y e ars  of  a g e  
2.   If f e m al e  a n d  of  c hil d b e ari n g  p ot e nti al, a  n e g ati v e  uri n e  pr e g n a n c y t est  at  B as eli n e 
( D a y  1)  a n d t h e s u bj e ct  a gr e es t o  us e  a d e q u at e  c o ntr a c e pti o n  d uri n g t h e st u d y  p eri o d 
3.   H as  a n  o v er all  s c or e  of  v er y t hi n,  or  t hi n  o n t h e  L FG S ,  as  a gr e e d  u p o n  b y t h e  Tr e ati n g 
a n d  E v al u ati n g I n v esti g at ors,  a n d  d esir es  at l e ast  a  1- p oi nt i m pr o v e m e nt i n  o v er all  L F G S 
s c or e;  O R  
H as  a  Fit z p atri c k s ki n  p h ot ot y p e  I V,  V  or  VI  a n d  h as  a n L F G S  s c or e  of t hi c k  or f ull,  as 
a gr e e d  u p o n  b y t h e  Tr e ati n g  a n d  E v al u ati n g I n v esti g at ors,  a n d  d esir es  tr e at m e nt t o t h e 
v er mili o n  b o d y  of  1  or  b ot h li ps 
4.   Willi n g t o  gi v e  writt e n i nf or m e d  c o ns e nt  
E x cl usi o n  C rit e ri a:   
1.   W o m e n  w h o  ar e  pr e g n a nt, l a ct ati n g,  or  pl a n ni n g  a  pr e g n a n c y 
2.   Hist or y  of  all er g y ,  a n a p h yl a xis or  h y p ers e nsiti vit y t o i nj e ct a bl e  h y al ur o ni c  a ci d  pr o d u cts, 
l o c al  a n est h eti cs  of t h e  a mi d e t y p e s u c h  as li d o c ai n e, or t o l at e x ,  or is  pl a n ni n g t o  u n d er g o 
d es e nsiti z ati o n t h er a p y  d uri n g t h e st u d y 

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3.   H as li p t att o os,  pi er ci n gs, f a ci al  h air,  or s c ars t h at  w o ul d i nt erf er e  wit h  vis u ali z ati o n  of 
t h e li ps  a n d  p eri or al  ar e a for t h e  eff e cti v e n ess  ass ess m e nts  
4.   H as  a b n or m al li p f u n cti o n,  wit h i n a bilit y t o  eff e cti v el y si p  w at er t hr o u g h  a str a w  
5.   H as  a b n or m al li p s e ns ati o n,  wit h i n a bilit y t o f e el  a  0. 4 G  m o n ofil a m e nt  or  a  c ott o n  wis p  at 
a n y sit e  o n t h e li p  
6.   H as  m o d er at e  or s e v er e  a b n o r m al li p  as y m m etr y 
7.   H as  a n y  m ass f or m ati o n  o n t h e li p  
8.   H as  d e nt ur es  or  a n y  d e vi c e  c o v eri n g  all  or  p art  of t h e  u p p er  p al at e,  a n d/ or s e v er e 
m al o c cl usi o n  or  d e nt of a ci al  or  m a xill of a ci al  d ef or miti es  as j u d g e d  b y t h e  Tr e ati n g 
I n v esti g at or.  S u bj e cts  pl a n ni n g t o  u n d er g o  e xt e nsi v e  d e nt al  pr o c e d ur es s u c h as  d e nt al 
i m pl a nts,  m ulti pl e t o ot h  e xtr a cti o ns,  or  or al s ur g er y s h o ul d  n ot  p arti ci p at e.  Mi n or  d e nt al 
pr o c e d ur es s u c h  as t e et h  cl e a ni n g  a n d  r e p air  of  c ari es  ar e  n ot  e x cl usi o n ar y 
9.   H as  u n d er g o n e f a ci al  pl asti c s ur g er y  or  r e c ei v e d  p er m a n e nt f a ci al i m pl a nts ( e. g., 
p ol y m et h yl m et h a cr yl at e, sili c o n e,  p ol yt etr afl u or o et h yl e n e ,  p ol y a cr yl a mi d e, lifti n g 
t hr e a ds)  a n y w h er e i n t h e f a c e  or  n e c k,  or is  pl a n ni n g t o  b e i m pl a nt e d  wit h  a n y  of t h es e 
pr o d u cts  d uri n g t h e st u d y 
1 0.  H as  u n d er g o n e s e m i-p er m a n e nt  d er m al fill er tr e at m e nt ( e. g.,  c al ci u m  h y dr o x yl a p atit e, 
p ol y- L-l a cti c  a ci d) i n t h e l o w er f a c e ( b el o w t h e  or bit al ri m)  wit hi n  1 2  m o nt hs  b ef or e 
e nr oll m e nt  or is  pl a n ni n g t o  u n d er g o s u c h tr e at m e nt  d uri n g t h e st u d y 
1 1.  H as  u n d er g o n e f a ci al tiss u e  a u g m e nt ati o n  wit h f at i nj e cti o ns,  b ot uli n u m t o xi n i nj e cti o ns 
i n t h e l o w er f a c e ( b el o w t h e  or bit al ri m),  m es ot h er a p y,  or  c os m eti c  pr o c e d ur es i n t h e f a c e 
or  n e c k ( e. g., f a c e-lift, l as er,  p h ot o- m o d ul ati o n, i nt e ns e  p uls e d li g ht, r a di o fr e q u e n c y, 
d er m a br asi o n,  m o d er at e  or  gr e at er  d e pt h  c h e mi c al  p e el,  mi cr o n e e dli n g,  or  ot h er  a bl ati v e 
pr o c e d ur es)  wit hi n  9  m o nt hs  b ef or e  e nr oll m e nt  or is  pl a n ni n g t o  u n d er g o  a n y  of t h es e 
pr o c e d ur es  d uri n g t h e st u d y 
1 2.  H as  us e d  A N Y li p filli n g  a g e nts  wit hi n  1 2  m o nt hs  of st u d y  e nr oll m e nt ( h y al ur o ni c  a ci d 
pr o d u cts,  c oll a g e n- b as e d  pr o d u cts , et c. ) 
1 3.  H as  us e d  a n y li p  pl u m pi n g  pr o d u cts  or  d e vi c es  wit hi n  1 0  d a ys  b ef or e  e nr oll m e nt  or is 
pl a n ni n g t o  us e s u c h  pr o d u cts  d uri n g t h e st u d y 
1 4.  H as  b e g u n  usi n g  a n y  o v er-t h e- c o u nt er  ( O T C)  or  pr es cri pti o n  or al  or t o pi c al  a nti- wri n kl e 
pr o d u cts f or t h e li ps  or  ar o u n d t h e  m o ut h  wit hi n  9 0  d a ys  b ef or e  e nr oll m e nt  or is  pl a n ni n g 
t o  b e gi n  usi n g s u c h  pr o d u cts  d uri n g t h e st u d y ( S u bj e cts  w h o  h a v e  b e e n  o n  a st a bl e 
r e gi m e n  of s u c h  pr o d u cts f or  at l e ast  9 0  d a ys  ar e  eli gi bl e f or t h e st u d y  a n d  m ust  c o nti n u e 
t h eir r e gi m e n t hr o u g h o ut t h e st u d y.) 
1 5.  Is  o n  a n  o n g oi n g r e gi m e n  of  a nti c o a g ul ati o n t h er a p y ( e. g.,  w arf ari n), t hr o m b ol yti cs,  or 
i n hi bit ors  of  pl at el et  a g gr e g ati o n  or  n o nst er oi d al  a nti-i nfl a m m at or y  dr u gs (N S AI Ds,  e. g., 
as piri n, i b u pr of e n)  or  ot h er s u bst a n c es  k n o w n t o i n cr e as e  c o a g ul ati o n ti m e ( e. g.,  h er b al 
s u p pl e m e nts  wit h  g arli c  or  gi n g k o)  wit hi n  1 0  d a ys  of  u n d er g oi n g st u d y  d e vi c e i nj e cti o ns. 
S u bj e cts  w h o  will  wit h h ol d s u c h t h er a p y f or  1 0  d a ys  b ef or e  A N D  aft er  a n y i nj e cti o n 
s essi o n m a y  p arti ci p at e  

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1 6.  H as  a  h ist or y  or  pr es e n c e  of  bl e e di n g  dis or d ers 
1 7.  H as  us e d s yst e mi c  c or tic ost er oi ds  or i m m u n os u p pr essi v e  m e di c ati o ns  wit hi n  3 0  d a ys 
pri or t o tr e at m e nt  
1 8.  Is  o n  a  c o n c urr e nt r e gi m e n  of li d o c ai n e  or str u ct ur all y r el at e d l o c al  a n est h eti cs ( e. g., 
b u pi v a c ai n e)  
1 9.  H as  a n  a cti v e i nfl a m m ati o n  (s ki n  er u pti o ns s u c h  as  c ysts,  pi m pl es, r as h es,  or  hi v es), 
i nf e cti o n,  c a n c er o us  or  pr e c a n c er o us l esi o n,  or  u n h e al e d  w o u n d  o n t h e f a c e 
2 0.   H as  a  h ist or y  of  k n o w n s us c e pti bilit y t o  k el oi d f or m ati o n  or  h y p ertr o p hi c s c ars 
2 1.  H a s  p or p h yri a 
2 2.  H as  a cti v e  h er p es l a bi alis l esi o ns  at t h e ti m e  of i nj e cti o ns.  S u bj e cts  wit h  a  hist or y  of 
h er p es l a bi alis  w h o  h a v e  h a d f o ur ( 4)  or  m or e  o ut br e a ks i n t h e  1 2  m o nt hs  pri or t o 
e nr oll m e nt  ar e  als o  e x cl u d e d  e v e n i n t h e  a bs e n c e  of l esi o ns  at t h e  b as eli n e  visit  
2 3.  H as i m p air e d  c ar di a c  c o n d u cti o n, s e v er el y i m p air e d  h e p ati c f u n cti o n,  or s e v er e r e n al 
d ysf u n cti o n t h at, i n t h e  o pi ni o n  of t h e i n v esti g at or,  w o ul d  pl a c e t h e m  at ris k  of  ass o ci at e d 
c o m pli c ati o ns fr o m t h es e ill n ess es  d uri n g t h e  c o urs e  of t h e st u d y 
2 4.  H as  a n y  u n c o ntr oll e d  dis e as e, i. e.,  a  c o n diti o n t h at  h as  n ot  b e e n  a p pr o pri at el y  di a g n os e d, 
e v al u at e d ,  a n d r ec ei v e d  m e di c all y  a p pr o pri at e tr e at m e nt  or  c ar e 
2 5.  H as s e v er e  c ar di o v as c ul ar  dis e as e ; e x a m pl es i n cl u d e  b ut  ar e  n ot li mit e d t o  N e w  Y or k  
H e art  Ass o ci ati o n  h e art f ail ur e  cl assifi c ati o n III  or I V,  u nst a bl e  a n gi n a,  a n d  i nt er n al 
p a c e m a k ers.  P ot e nti al s u bj e cts  wit h  o t h er si g nifi c a nt  c ar di o v as c ul ar  dis e as es s h o ul d  b e 
dis c uss e d  wit h t h e  M e di c al  M o nit or  b ef or e  e nr olli n g 
St u d y  D e vi c e s 
T est  d e vi c e : P N 4 0 0 8 2:  a  cl e ar,  c ol orl ess  g el i n  1. 0  m L  pr e- fill e d s yri n g es  wit h  2 5 m g/ m L  of 
st a bili z e d  h y al ur o ni c  a ci d  a n d li d o c ai n e  0. 3 %  w/ w  
C o m p a r at o r  d e vi c e : R est yl a n e  Sil k : a  cl e ar,  c ol orl ess  g el i n  1. 0  m L  pr e- fill e d s yri n g es 
f or m ul at e d t o  a  c o n c e ntr ati o n  of  2 0 m g/ m L  of st a bili z e d  h y al ur o ni c  a ci d  a n d li d o c ai n e  0. 3 %  w/ w 
St atisti c al  M et h o ds  
S a m pl e  Si z e  D et e r mi n ati o n :  
A t ot al  of  1 5 8  s u bj e cts  will  b e r a n d o mi z e d .  
A n al ysis  P o p ul ati o ns: 
I nt e nt-t o-tr e at (I T T/s af et y)  p o p ul ati o n:  All r a n d o mi z e d s u bj e cts  w h o r e c ei v e d st u d y  d e vi c e  
M o difi e d i nt e nt- t o-tr e at ( mI T T):  All r a n d o mi z e d s u bj e cts  w h o  m et t h e i n cl usi o n/ e x cl usi o n 
crit eri a,  w er e r a n d o mi z e d,  a n d  r e c ei v e d st u d y  d e vi c e 
P er - pr ot o c ol ( P P): All r a n d o mi z e d s u bj e cts  w h o  m et  all i n cl usi o n/ e x cl usi o n  crit eri a; r e c ei v e d 
st u d y  d e vi c e,  c o m pl et e d  Visit 5  wit hi n t h e s p e cifi e d  wi n d o w;  h a d  L F G S  s c or e  b y t h e  Bli n d e d 
E v al u ati n g I n v esti g at or  at  Visit  3/ M o nt h  2  wit hi n t h e s p e cifi e d  visit  wi n d o w ,  a n d  h a d  n o 
si g nifi c a nt  pr ot o c ol  vi ol ati o ns t h at  w o ul d  aff e ct t h e tr e at m e nt  e v al u ati o n  

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Effi c a c y  a n al ys es  will  b e  p erf or m e d  o n t h e  mI T T  a n d  P P  p o p ul ati o ns ,  wit h  P P  as t h e  pri m ar y 
p o p ul ati o n  a n d  mI T T s u p p orti v e.  
S af et y  a n al ys es  will  b e  p erf or m e d  o n t h e I T T  p o p ul ati o n. 
Effi c a c y  A n al ysis: 
T h e  pri m ar y  effi c a c y  e n d p oi nt is  c h a n g e fr o m  b as eli n e t o  M o nt h  2 i n  o v er all li p f ull n ess  b as e d 
o n t h e  Bli n d e d  E v al u ati n g I n v esti g at or  a ss ess m e nt  usi n g t h e  L F G S . If t h e l o w er li mit  of t h e 9 5 % 
c o nfi d e n c e i nt er v al ( CI)  f or ( P N 4 0 0 8 2  mi n us R est yl a n e  Sil k)  wit h r es p e ct t o t h e  pri m ar y 
e n d p oi nt is  a b o v e  a  pr e- s p e cifi e d  NI li mit - 0. 5 0,  P N 4 0 0 8 2  will b e  c l ai m e d n o n-i nf eri or t o t h e 
R est yl a n e  Sil k .   
S e c o n d ar y  a n al ysis  i n cl u d e  
•   p er c e nt  of s u bj e cts  wit h  tr e at m e nt s u c c ess (r es p o n d er: o v er all  L F G S   b as e d  o n t h e  Bli n d e d 
E v al u ati n g I n v esti g at or  Ass ess m e nt )  at Visit  3/ M o nt h  2  w h er e r es p o n d er  is  d efi n e d  as  a 
s u bj e ct  wit h at l e ast  a  1 - gr a d e i n cr e as e fr o m  b as eli n e  o n t h e  L F G S  p ost  a u g m e nt ati o n,  
•   p er c e nt  of  r es p o n d ers o v er all   o n t h e  P O L s e v erit y s c al e at  Visit  4/ M o nt h  3  ( d efi n e d  as  a 
s u bj e ct  d e m o nstr ati n g  ≥  1 - p oi nt i m pr o v e m e nt, i. e.,  d e cr e as e i n s e v erit y, fr o m  b as eli n e), 
•   c h a n g e fr o m  b as eli n e  t o Visit  4/ M o nt h  3 i n  o v er all  L F G S  b as e d  o n t h e  Bli n d e d 
E v al u ati n g I n v esti g at or  Ass ess m e nt , 
•   c h a n g e fr o m  b as eli n e t o  Visit  5/ M o nt h  6 i n  o v er all  L F G S    b as e d  o n t h e  Bli n d e d 
E v al u ati n g I n v esti g at or  Ass ess m e nt.  
Ot h er  effi c a c y  a n al ysis  i n cl u d e  
•   p G AI , i G AI,  a n d  S w elli n g  Ass ess m e nt at  e a c h s c h e d ul e d  visit , 
•   p er c e nt  of s u bj e cts  wit h  tr e at m e nt s u c c ess (r es p o n d er:  u p p er li ps, l o w er li ps  L F G S)  at 
Visit  3/ M o nt h  2  w h er e r es p o n d er is  d efi n e d  as  a s u bj e ct  wit h  at l e ast  a  1- gr a d e i n cr e as e 
fr o m  b as eli n e  o n t h e  L F G S  p ost  a u g m e nt ati o n, 
•   p er c e nt  of r es p o n d ers ( u p p er li ps, l o w er li ps)  o n t h e  P O L s e v erit y s c al e  at  Visit  4/ M o nt h 
3 ( d efi n e d  as  a s u bj e ct  d e m o nstr ati n g  ≥  1 - p oi nt i m pr o v e m e nt, i. e.,  d e cr e as e i n s e v erit y, 
fr o m  b as eli n e), 
•   satisf a cti o n  wit h  li ps  V A S  at  e a c h s c h e d ul e d  visit, 
•   c h a n g e fr o m  b as eli n e t o  Visit  4/ M o nt h  3  a n d  Visit  5/ M o nt h  6 i n  u p p er li ps, l o w er li ps 
L F G S . 
S af et y  A n al ysis: 
A d v ers e  e v e nts  will  b e  c o d e d t o s yst e m  or g a n  cl ass  a n d  pr ef err e d t er ms  usi n g t h e  M e di c al 
Di cti o n ar y f or  R e g ul at or y  A cti viti es ( M e d D R A,  V ersi o n  2 0  or  hi g h er). 
Fr e q u e n c y  a n d  p er c e nt a g e  of s u bj e cts r e p orti n g  tr e at m e nt-e m er g e nt  a d v ers e  e v e nts ( T E A Es)  will 
b e t a b ul at e d f or  e a c h tr e at m e nt  b y  pr ef err e d t er ms  a n d f urt h er  b y s e v erit y  a n d r el ati o ns hi p t o 
st u d y d e vi c e. I n s u m m ari es  of s e v erit y  a n d r el ati o ns hi p, s u bj e cts r e p orti n g  m or e t h a n  o n e  e v e nt 
i n  a tr e at m e nt  ar m t h at  ar e  m a p p e d t o t h e s a m e  pr ef err e d t er m  will  b e  c o u nt e d  o nl y  o n c e i n t h at 
tr e at m e nt  ar m  u n d er t h e str o n g est s e v erit y a n d r el ati o ns hi p , r es p e cti v el y.  I n  a d diti o n,  vis u al 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol  
 
0 2 O C T 2 0 1 8  
 
8 
 
r el at e d  T E A Es  will  b e s u m m ari z e d s e p ar at el y f or  e a c h tr e at m e nt  b y  pr ef err e d t er m. 
S af et y  a n al ys es  will  b e  c o n d u ct e d  usi n g t h e I T T  p o p ul ati o n. 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol  
 
0 2 O C T 2 0 1 8  
 
9 
 
2   
S C H E D U L E  O F  A C TI VI TI E S  
Visit  N u m b e r ( M o nt h)  
Visit  1  
( W e e k  0) 
P h o n e 
C o nt a cts  
Visit  2  
( M o  1) 
P h o n e 
C o nt a cts a 
Visit  3  
( M o  2) 
Visit  4  
( M o  3) 
P h o n e 
C o nt a cts  
Visit  5  
( M o  6) E n d  of 
St u d y/ E a rl y 
T e r mi n ati o n  
U ns c h e d 
Visit  
S c h e d ul e d  D a y(s)  
D a y  1  
D a y  3  &  
D a y  1 4  
D a y  2 8  
D a y  3 3  &  
D a y  4 4  
D a y  5 6   
D a y  8 4  
D a y  1 1 2  & 
D a y  1 4 0  
D a y  1 6 8   b 
S c h e d uli n g  Wi n d o w  
n o n e   
±  2  d a ys   ±  2  d a ys   ±  2  d a ys   
±  4  d a ys   ±  4  d a ys   
±  4  d a ys   
±  7  d a ys   
 
I nf or m e d  c o ns e nt 
X  
  
  
 
 
 
 
 
 
M e di c al  hist or y/  d e m o gr a p hi c s  
X  
  
  
 
 
 
 
 
 
A b br e vi at e d  P h ysi c al  e x a mi n ati o n (i n cl u di n g 
vit al si g ns)  
X  
  
  
 
 
 
 
 
 
Visi o n  e v al u ati o ns ( S n ell e n  vis u al 
a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds, 
o c ul ar  m otilit y )d 
X 
  
X  
  
X  
X  
X 
X  
X c 
Pri or/ C o n c o mit a nt  M e di c ati o n/ 
Tr e at m e nt  
X   
X  
X  
X  
X  
X  
X 
X 
X 
I n cl usi o n/ e x cl usi o n  crit eri a r e vi e w 
X  
  
  
 
 
 
 
 
 
Uri n e  pr e g n a n c y t est  e 
X  
  
  
 
 
 
 
 
 
Fit z p atri c k  S ki n  T y p e  
X  
  
  
  
  
  
 
 
 
Li p  F ull n ess  Gr a di n g  S c al e  ( L F G S) ( O v er all, 
u p p er li p  a n d l o w er li p)  
X   
  
X  
  
X  
X 
 
X  
X c 
P eri or al  li n es at r est s e v erit y  sc al e ( P O L)  
( O v er all,  u p p er li p  a n d l o w er li p) 
X 
  
X  
  
X  
X 
 
X  
X c 
R a n d o mi z ati o n  
X  
  
  
 
 
 
 
 
 
Tr e at m e nt  wit h  st u d y  d e vi c e  
X  
  
X a  
 
 
 
 
 
 
I n v e sti g at or  E as e  of  Us e Ass e ss m e nt  
X  
 
X a  
 
 
 
 
 
 
E v al u ati o n f or t o u c h -u p  
 
 
X   
 
 
 
 
 
 
P ati e nt  G AI ( p G AI)  
 
  
X   
  
X   
X   
 
X   
X c 
S w elli n g  Ass e ss m e nt  
 
  
X   
  
X   
X   
 
X   
X c 
I n v e sti g at or  G AI (i G AI) 
 
  
X   
  
X   
X   
 
X   
X c 
S u bj e ct  S atisf a cti o n  wit h  Li ps  
 
  
X   
  
X   
X   
 
X   
X c 
Li p  F u n cti o n  ( pri or t o i nj e cti o ns) 
X  
  
X   
  
X   
X   
 
X   
X c  
Li p  S e ns ati o n  ( pri or t o i nj e cti o ns) 
X  
  
X   
  
X   
X   
 
X   
X c  
Li p  T e xt ur e ( pri or t o i nj e cti o ns)  
X  
  
X   
  
X   
X   
 
X   
X c  
Li p  Fir m n e ss ( pri or t o i nj e cti o ns)  
X  
  
X   
  
X   
X   
 
X   
X c  

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol  
 
0 2 O C T 2 0 1 8  
 
1 0  
 
Li p  S y m m etr y ( pri or t o i nj e cti o ns)  
X  
  
X   
  
X   
X   
 
X   
X c  
Li p  M o v e m e nt/ F u n cti o n  
X  
  
X   
  
X   
X   
 
X   
X c  
A d v ers e  e v e nt  ass ess m e nt  
X   
X   
X   
X   
X   
X   
X   
X   
X  
Tr e at m e nt  q u esti o n  
 
  
  
  
  
  
 
X   
 
S u bj e ct  Di ar y  
Dis p e ns e  
 
C oll e ct/ 
dis p e ns e f  
 
C oll e ct f   
 
 
 
 
N ot e:  T h e ti mi n g  of  e a c h  visit is r el ati v e t o  D a y  1,  w hi c h is  d efi n e d  as t h e  d a y t h e s u bj e ct is r a n d o mi z e d  a n d  first tr e at e d. 
a.  F or s u bj e cts  w h o  h a v e  t o u c h-u p tr e at m e nt  at  Visit  2  
b.   All s u bj e cts  will r e c ei v e  a f oll o w -u p  p h o n e  c all  at  1 2  m o nt hs  aft er first tr e at m e nt . 
c.   If/ as  n e e d e d 
d.   p erf or m e d  pri or t o  a n y tr e at m e nt  a n d r e p e at e d  3 0  mi n ut es f oll o wi n g  a n y tr e at m e nt  a n d  all f oll o w -u p  visits.  
e.   F or  w o m e n  of  c hil d b e ari n g  p ot e nti al, t o  b e  c o m pl et e d  pri or t o  e nr oll m e nt.   
f.   Dis p e ns e/ c oll e ct  di ar y  o nl y if t o u c h  u p is  p erf or m e d 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 1  
 
3   
T A B L E  O F  C O N T E N T S  
SI G N A T U R E  P A G E  ...................................................................................................................... 2 
1  
S Y N O P SI S  ............................................................................................................................... 3 
2  
S C H E D U L E  O F  A C TI VI TI E S  .............................................................................................. 9 
3  
T A B L E  O F  C O N T E N T S  ...................................................................................................... 1 1 
List  of  T a bl es  .............................................................................................................................. 1 3 
List  of  Fi g ur es  ............................................................................................................................. 1 4 
4  
LI S T  O F  A B B R E VI A TI O N S  A N D  D E FI NI TI O N S  O F  T E R M S  .................................... 1 5 
5  
I N T R O D U C TI O N ................................................................................................................. 1 6 
5. 1  
B a c k gr o u n d ....................................................................................................................... 1 6  
5. 2  
R ati o n al e f or t h e  St u d y  a n d  St u d y  D esi g n ........................................................................ 1 6  
6  
S T U D Y  O B J E C TI V E S  ......................................................................................................... 1 6 
7  
I N V E S TI G A TI O N A L  P L A N  ............................................................................................... 1 6 
7. 1  
O v er all  St u d y  D esi g n  ........................................................................................................ 1 6 
7. 2  
B e gi n ni n g  a n d  E n d  of  St u d y ............................................................................................. 1 7  
7. 3  
St u d y  P o p ul ati o n ............................................................................................................... 1 7  
7. 3. 1  I n cl usi o n  Crit eri a ......................................................................................................... 1 7 
7. 3. 2  E x cl usi o n  Crit eri a  ........................................................................................................ 1 8 
7. 3. 3  S u bj e ct  Wit h dr a w al  Crit eri a  ........................................................................................ 1 9 
7. 3. 4  R e pl a c e m e nt  of  S u bj e cts  ............................................................................................. 2 0 
7. 4  
Tr e at m e nts  ......................................................................................................................... 2 0 
7. 4. 1  D os a g e  a n d  F or m ul ati o ns ............................................................................................ 2 0  
7. 4. 2  R a n d o mi z ati o n ............................................................................................................ 2 0  
7. 4. 3  St u d y  D e vi c e  A d mi nistr ati o n  ...................................................................................... 2 0 
7. 4. 4  Bli n di n g  of  St u d y  D e vi c e ............................................................................................ 2 2  
7. 4. 5  M et h o d  of  P a c k a gi n g,  L a b eli n g,  St or a g e,  a n d  Dis p e nsi n g ......................................... 2 2  
7. 4. 6  St u d y  D e vi c e  A c c o u nt a bilit y  ...................................................................................... 2 3 
7. 4. 7  Pri or  a n d  C o n c o mit a nt  M e di c ati o ns ............................................................................ 2 3  
7. 4. 7. 1  
Pr e c a uti o ns  .......................................................................................................... 2 3 
7. 4. 7. 2  
M e di c ati o ns  a n d  Tr e at m e nts  Pr o hi bit e d  B ef or e  St u d y  E ntr y  a n d  D uri n g t h e  St u d y
 ............................................................................................................................. 2 3 
7. 4. 7. 3  
C o n c o mit a nt  M e di c ati o ns  a n d  Tr e at m e nts  All o w e d  D uri n g t h e  St u d y .............. 2 4  
7. 4. 8  Ass ess m e nt  of  C o m pli a n c e ......................................................................................... 2 4  
7. 5  
St u d y  S c h e d ul e .................................................................................................................. 2 4  
7. 6  
St u d y  Pr o c e d ur es  .............................................................................................................. 2 4 
7. 6. 1  St u d y  R ol es ................................................................................................................. 2 4  
7. 6. 2  St u d y I niti ati o n  ............................................................................................................ 2 5 
7. 6. 3  Writt e n I nf or m e d  C o ns e nt ........................................................................................... 2 5  
7. 6. 4  Si g nifi c a nt  M e di c al  Hist or y/ D e m o gr a p hi c I nf or m ati o n  ............................................. 2 5 
7. 6. 5  P h ysi c al  E x a mi n ati o n (I n cl u di n g  Vit al  Si g ns)  ............................................................ 2 5 
7. 6. 6  Visi o n  E v al u ati o ns ...................................................................................................... 2 6  
7. 6. 7  Pri or  a n d  C o n c o mit a nt  M e di c ati o n/ Tr e at m e nt  R e vi e w  .............................................. 2 6 
7. 6. 8  Uri n e  Pr e g n a n c y  T est  a n d  A c c e pt a bl e  C o ntr a c e pti v e  M et h o ds  .................................. 2 6 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 2  
 
7. 6. 9  Li p  F ull n ess  Gr a di n g  S c al e  ......................................................................................... 2 6 
7. 6. 1 0  P eri or al  Li n es  at  R est  S e v erit y  S c al e  .......................................................................... 2 6 
7. 6. 1 1  R e vi e w I n cl usi o n/ E x cl usi o n  Crit eri a  .......................................................................... 2 6 
7. 6. 1 2  E v al u ati o n f or  T o u c h- u p ............................................................................................. 2 7  
7. 6. 1 3  P ati e nt  Gl o b al  A est h eti c I m pr o v e m e nt ( p G AI)  S c or e  ................................................ 2 7 
7. 6. 1 4  I n v esti g at or  Gl o b al  A est h eti c Im pr o v e m e nt (i G AI)  S c or e  ......................................... 2 7 
7. 6. 1 5  I n v esti g at or  E as e  of  Us e  Ass ess m e nt .......................................................................... 2 7 
7. 6. 1 6  S w elli n g  Ass ess m e nt  ................................................................................................... 2 7 
7. 6. 1 7  Li p  F u n cti o n  E v al u ati o n .............................................................................................. 2 8  
7. 6. 1 8  Li p  S e ns ati o n  E v al u ati o n ............................................................................................ 2 8  
7. 6. 1 9  Li p  T e xt ur e  E v al u ati o n  ............................................................................................... 2 8 
7. 6. 2 0  Li p  Fir m n ess  E v al u ati o n ............................................................................................. 2 9  
7. 6. 2 1  Li p  S y m m etr y  E v al u ati o n  ........................................................................................... 2 9 
7. 6. 2 2  Li p  M o v e m e nt/ F u n cti o n .............................................................................................. 3 0  
7. 6. 2 3  S u bj e ct  S atisf a cti o n  wit h  Li ps ( Vis u al  A n al o g  S c al e)  ................................................ 3 0 
7. 6. 2 4  S u bj e ct  Di ar y  C ar d  ...................................................................................................... 3 0 
7. 6. 2 5  A d v ers e  E v e nts  a n d  S eri o us  A d v ers e  E v e nts  Ass ess m e nt .......................................... 3 0  
7. 6. 2 6  Tr e at m e nt  Q u esti o n  ..................................................................................................... 3 0 
7. 7  
Visit -S p e cifi c  Pr o c e d ur es  .................................................................................................. 3 0 
7. 7. 1  Visit  1/ D a y  1:  B as eli n e  a n d  Tr e at m e nt  ....................................................................... 3 0 
7. 7. 2  T el e p h o n e  C o nt a cts  o n  D a y  3  a n d  D a y  1 4 ( ±  2  d a ys) ................................................. 3 1  
7. 7. 3  Visit  2/ D a y  2 8 ( ±  2  d a ys): I nt eri m  Visit  at  M o nt h  1  wit h   P ossi bl e  T o u c h-u p  Tr e at m e nt
  3 1 
7. 7. 4  T el e p h o n e  C o nt a cts  o n  D a y  3 3  a n d  D a y  4 4 ( ± 2  d a ys) f or  S u bj e cts  wit h  T o u c h- u p 
Tr e at m e nt  .................................................................................................................... 3 2 
7. 7. 5  Visit  3/ D a y  5 6 ( ±  4  d a ys)  a n d  Visit  4/ D a y  8 4 ( ±  4  d a ys): I nt eri m  Visits  at  M o nt h   2  a n d 
M o nt h  3 ....................................................................................................................... 3 2  
7. 7. 6  T el e p h o n e  C o nt a cts  o n  D a y  1 1 2 ( M o nt h  4)  a n d  D a y  1 4 0 ( M o nt h  5)  ± 4  d a ys ............ 3 3  
7. 7. 7  Visit  5/ D a y  1 6 8 ( ±  7  d a ys):  M o nt h  6  E n d  of  St u d y  Visit/ E arl y  T er mi n ati o n ............. 3 3  
7. 7. 8  U ns c h e d ul e d  Visit ....................................................................................................... 3 3  
7. 8  
Effi c a c y  A n al ysis  .............................................................................................................. 3 4 
7. 8. 1  Pri m ar y  Effi c a c y  E n d p oi nt .......................................................................................... 3 4  
7. 8. 2  S e c o n d ar y  Effi c a c y  A n al ysis  ...................................................................................... 3 4 
7. 8. 3  Ot h er  Effi c a c y  A n al ysis  .............................................................................................. 3 4 
7. 9  
Ass ess m e nt  of  S af et y  ........................................................................................................ 3 5 
7. 9. 1  S af et y  A n al ysis  ............................................................................................................ 3 5 
7. 9. 2  Ot h er  S af et y  E v al u ati o ns  ............................................................................................. 3 5 
7. 9. 3  D efi niti o ns  of  T er ms  ................................................................................................... 3 5 
7. 9. 3. 1  
A d v ers e  E v e nt  ..................................................................................................... 3 5 
7. 9. 3. 2  
S us p e ct e d  A d v ers e  R e a cti o n  ............................................................................... 3 5 
7. 9. 3. 3  
U n e x p e ct e d  A d v ers e  E v e nt ................................................................................. 3 5  
7. 9. 3. 4  
A d v ers e  E v e nts  of  S p e ci al I nt er est  ..................................................................... 3 5 
7. 9. 3. 5  
S eri o us  A d v ers e  E v e nt ........................................................................................ 3 6  
7. 9. 3. 6  
Pl a n n e d  H os pit ali z ati o n  ...................................................................................... 3 6 
7. 9. 4  Pr e g n a n c y  .................................................................................................................... 3 6 
7. 9. 5  M o nit ori n g  A d v ers e  E v e nts ........................................................................................ 3 7  
7. 9. 6  Ass ess m e nt  of  A d v ers e  E v e nts ................................................................................... 3 7  
7. 9. 6. 1  
Ass ess m e nt  of  S e v erit y  ....................................................................................... 3 7 
7. 9. 6. 2  
Ass ess m e nt  of  C a us alit y  ..................................................................................... 3 7 
7. 9. 6. 3  
R ef er e n c e  S af et y I nf or m ati o n f or  Ass essi n g  E x p e ct e d n ess  of  A d v ers e  E v e nts  . 3 7 
7. 9. 7  R e p orti n g  S af et y  O bs er v ati o ns ................................................................................... 3 7  

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 3  
 
7. 9. 8  Di ar y  Ass ess m e nts  ...................................................................................................... 3 9 
7. 9. 9  Crit eri a f or  E arl y  T er mi n ati o n  of t h e  St u d y  ................................................................ 3 9 
7. 9. 1 0  Wit h dr a w al,  Tr e at m e nt I nt err u pti o n,  a n d  U n bli n di n g  of  Bli n d e d  Tr e at m e nt  D u e t o 
S af et y  O bs er v ati o ns  .................................................................................................... 3 9 
7. 9. 1 0. 1  Wit h dr a w al  .......................................................................................................... 3 9 
7. 9. 1 0. 2  U n bli n di n g  Tr e at m e nt f or  a  S u bj e ct  D uri n g t h e  St u d y ....................................... 3 9  
8  
S T A TI S TI C A L  M E T H O D S  ................................................................................................ 4 0 
8. 1  
A n al ysis  P o p ul ati o ns ......................................................................................................... 4 0  
8. 2  
Effi c a c y  A n al ysis  .............................................................................................................. 4 0 
8. 3  
I nt eri m  A n al ysis ................................................................................................................ 4 1 
8. 4  
S af et y  A n al ys es  ................................................................................................................. 4 1 
8. 5  
S a m pl e  Si z e  D et er mi n ati o n  ............................................................................................... 4 1 
9  
E T HI C S  .................................................................................................................................. 4 2 
9. 1  
I nf or m e d  C o ns e nt .............................................................................................................. 4 2 
9. 2  
I nstit uti o n al  R e vi e w  B o ar d (I R B) ..................................................................................... 4 2 
9. 3  
S u bj e ct  C o nfi d e nti alit y  ..................................................................................................... 4 2 
9. 4  
St u d y  R e gistr ati o n  ............................................................................................................. 4 2 
1 0  D A T A  H A N D LI N G  A N D  R E C O R D K E E PI N G  ................................................................ 4 3 
1 0. 1  Sit e  R e g ul at or y  D o c u m e nts  R e q uir e d f or I niti ati o n  ......................................................... 4 3 
1 0. 2  M ai nt e n a n c e  a n d  R et e nti o n  of  R e c or ds ............................................................................ 4 3  
1 0. 2. 1  C as e  R e p ort  F or ms ( C R Fs)  ......................................................................................... 4 3 
1 0. 2. 2  Pri m ar y  S o ur c e  D o c u m e nts  ......................................................................................... 4 4 
1 0. 3  St u d y  M o nit ori n g .............................................................................................................. 4 4  
1 0. 4  A u dits  a n d I ns p e cti o ns ...................................................................................................... 4 5  
1 0. 5  M o difi c ati o ns t o t h e  Pr ot o c ol ............................................................................................ 4 5  
1 0. 6  C o m pl eti o n  of t h e  St u d y ................................................................................................... 4 5  
1 1  C O N FI D E N TI A LI T Y,  U S E  O F I N F O R M A TI O N,  A N D  P U B LI C A TI O N  .................... 4 5 
1 2  LI S T  O F  R E F E R E N C E S  ..................................................................................................... 4 6 
1 3  I N VE S TI G A T O R  A G R E E M E N T  ...................................................................................... 4 7 
1 4  A P P E N DI X  1  ......................................................................................................................... 4 8 
P N 4 0 0 8 2 I N S T R U C TI O N S  F O R  U S E ....................................................................................... 5 0 
R E S T Y L A N E ®  SI L K I N S T R U C TI O N S  F O R  U S E  ................................................................. 5 4 
 
 
List  of  T a bl es  
T a bl e   1. 
Fit z p atri c k  Cl assifi c ati o n  S c al e .............................................................................. 2 5 
T a bl e  2.  
Li p  T e xt ur e  S c ori n g  Crit eri a  .................................................................................. 2 8 
T a bl e  3.  
Li p  Fir m n ess  S c ori n g  Crit eri a  ................................................................................ 2 9 
T a bl e  4.  
Li p  S y m m etr y  S c ori n g  Crit eri a  .............................................................................. 2 9 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 4  
 
List  of  Fi g u r es  
Fi g ur e   1. 
Vis u al  A n al o g  S c al e f or  S u bj e ct  S atisf a cti o n  ........................................................ 3 0 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 5  
 
4   
LI S T  O F  A B B R E VI A TI O N S  A N D  D E FI NI TI O N S  O F  T E R M S  
 
T er m  
D efi niti o n  
A E  
a d v ers e  e v e nt  
C F R  
C o d e  of  F e d er al  R e g ul ati o ns 
CI  
c o nfi d e n c e i nt er v al  
C R A  
Cli ni c al  R es e ar c h  Ass o ci at e  
C R F  
c as e r e p ort f or m ,  p a p er  or  el e ctr o ni c 
D C F  
d at a  c orr e cti o n f or m  
E O S  
e n d  of st u d y  
F D A  
F o o d  a n d  Dr u g  A d mi nistr ati o n 
G C P  
G o o d  Cli ni c al  Pr a cti c e  
I C F 
inf 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 u n cil f or H ar m o nis ati o n 
iG AI  
I n v esti g at or  Gl o b al  A est h eti c I m pr o v e m e nt 
I R B 
Instit uti o n al  R e vi e w  B o ar d  
I T T 
i nt e nt-t o-tr e at 
I U D 
i ntr a ut eri n e  d e vi c e 
L F G S  
Li p  F ull n ess  Gr a di n g  S c al e 
M e d D R A  
M e di c al  Di cti o n ar y f or  R e g ul at or y  A cti viti es  
m I T T 
m o difi e d i nt e nt -t o-tr e at 
N S AI D  
n o nst er oi d al  a nti-i nfl a m m at or y  dr u g 
O T C  
o v er -t h e- c o u nt er 
p G AI  
P ati e nt  Gl o b al  A est h eti c I m pr o v e m e nt 
PI  
pri n ci p al i n v esti g at or  
P O L  
p eri or al  li n es at r est  
P P  
p er- pr ot o c ol 
S A E  
s eri o us  a d v ers e  e v e nt 
S A R  
s us p e ct e d  a d v ers e r e a cti o n 
T E A E  
tr e at m e nt-e m er g e nt  a d v ers e  e v e nt  
V A S  
vis u al  a n al o g s c al e  

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 6  
 
5   
IN T R O D U C TI O N  
5. 1   
B a c k g r o u n d 
P N 4 0 0 8 2  is  a st a bili z e d  h y al ur o ni c  a ci d  d er m al fill er  wit h li d o c ai n e. R est yl a n e  Sil k  I nj e ct a bl e  G el  wit h 
0. 3 % li d o c ai n e ( h er e aft er r ef err e d t o  as  R est yl a n e  Sil k)  is a st a bi li z e d h y al ur o ni c  a ci d  d er m al fill er  wit h 
li d o c ai n e t h at is  c o m m er ci all y  a v ail a bl e f or s u b m u c os al i m pl a nt ati o n f or li p  a u g m e nt ati o n  a n d  d er m al 
i m pl a nt ati o n f or  c orr e cti o n  of  p eri or al r h yti ds i n  a d ults  o v er t h e  a g e  of  2 1 y e ars .  T h e  p ur p os e  of t his 
st u d y is t o  c o m p ar e t h e  effi c a c y  a n d s af et y  of  P N 4 0 0 8 2  a n d  R est yl a n e  Sil k  f or li p  a u g m e nt ati o n. 
5. 2   
R ati o n al e  f o r t h e  St u d y  a n d  St u d y  D esi g n 
T o  b e  e nr oll e d i n t h e st u d y s u bj e cts  w h o  h a v e  a  Li p  F ull n ess  Gr a di n g  S c al e ( L F G S) s c or e  of  v er y t hi n, 
t hi n,  or  m o d er at el y t hi c k m ust  b e s e e ki n g  at l e ast  a  1 - p oi nt i m pr o v e m e nt i n t h eir  o v er all  L F GS s c or e  a n d 
s u bj e cts  w h o  h a v e  a n  L F G S s c or e  of  t hi c k  or f ull m ust  b e s e e ki n g  tr e at m e nt t o t h e  v er mili o n  b o d y  of  1 
f or  b ot h li ps.  S u bj e cts  will  b e r a n d o mi z e d  1: 1 t o tr e at m e nt  wit h  eit h er P N 4 0 0 8 2  or  R est yl a n e  Sil k . All 
s u bj e cts  will  b e f oll o w e d f or  effi c a c y  a n d s af et y f or  6  m o nt hs.  All s u bj e cts  will  b e  e v al u at e d f or 
r etr e at m e nt  a n d  u n d er g o  c o ns e nt  pr o c e d ur e f or t h e s u bs e q u e nt  o p e n-l a b el r etr e at m e nt  pr ot o c ol. 
6   
S T U D Y  O B J E C TI V E S  
T o  c o m p ar e t h e s af et y  a n d  effi c a c y  pr ofil e  of  P N 4 0 0 8 2  v ers us  R est yl a n e  Sil k  f or li p  a u g m e nt ati o n. 
7   
IN V E S TI G A TI O N A L  P L A N  
7. 1   
O v e r all  St u d y  D esi g n 
T his is  a  d o u bl e- bli n d, r a n d o mi z e d,  c o ntr oll e d,  m ulti c e nt er  cli ni c al st u d y  of s u bj e cts s e e ki n g li p 
a u g m e nt ati o n.  S u bj e cts  m e eti n g i n cl usi o n/ e x cl usi o n  crit eri a  will  b e r a n d o mi z e d  1 : 1 t o tr e at m e nt  wit h 
eit h er  P N 4 0 0 8 2  or  R est yl a n e  Sil k .  T h e  E v al u ati n g I n v estig at or  will  b e  bli n d e d t o t h e tr e at m e nt. 
I nj e cti o ns  of t h e st u d y  d e vi c e  will  b e  p erf or m e d  b y  a n  u n bli n d e d  Tr e ati n g I n v esti g at or.  
At  e a c h  visit, t h e  bli n d e d  E v al u ati n g I n v esti g at or  e v al u ati o ns  a n d s u bj e ct  e v al u ati o ns  of t h e tr e at e d  ar e as 
will  b e  p erf or m e d  a n d r e c or d e d.  Visits  a n d t el e p h o n e  c o nt a cts  will  o c c ur  at:  
Visit  1 /  W e e k  0 ( D a y  1)  –  b as eli n e  a n d tr e at m e nt  
  -D a y  3  ( ± 2  d a ys) - S af et y f oll o w - u p t el e p h o n e  c all 
  - D a y  1 4 ( ± 2  d a ys) –  S af et y f oll o w - u p t el e p h o n e  c all 
Visit  2 /  D a y  2 8 ( ± 2  d a ys) /  M o nt h  1  –  i nt eri m  visit (t o u c h-u p if  n e c ess ar y)  
  -D a y  3 3  ( ± 2  d a ys)  – S af et y f oll o w - u p t el e p h o n e  c all (f or s u bj e cts  wit h t o u c h-u p tr e at m e nt)  
  - D a y  4 4 ( ± 2  d a ys) –  S af et y f oll o w - u p t el e p h o n e  c all (f or s u bj e cts  wit h t o u c h-u p tr e at m e nt)  
Visit  3 /  D a y  5 6  ( ± 4  d a ys) / M o nt h  2  –  i nt eri m  visit 
Visit  4  / D a y  8 4 ( ± 4  d a ys) /  M o nt h  3  –  i nt eri m  visit 
  - D a y  1 1 2 ( ± 4  d a ys) /  M o nt h  4  – S af et y f oll o w - u p t el e p h o n e  c all 
  - D a y  1 4 0 ( ± 4  d a ys) /  M o nt h  5  – S af et y f oll o w - u p t el e p h o n e  c all 
Visit   5 / D a y  1 6 8 ( ± 7  d a ys) /  M o nt h  6  –  E n d  of  St u d y  ( E O S) Visit.  All  s u bj e cts will  b e 
e v al u at e d f or r etr e at m e nt  a n d  u n d er g o t h e  c o ns e nt  pr o c e d ur e f or t h e s u bs e q u e nt  o p e n- l a b el 
r etr e at m e nt pr ot o c ol. 
E ffi c a c y v al u ati o ns i n cl u d e: 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 7  
 
Li p  F ull n ess  Gr a di n g  S c al e ( L F G S)  ( O v er all li p f ull n ess  c o nsi d eri n g  b ot h li ps t o g et h er, 
f ull n ess  of t h e  u p p er li p  a n d f ull n ess  of t h e l o w er li p) 
P eri or al  li n es  at r est se v erit y  sc al e ( P O L)  ( O v er all  p eri or al li n es  at r est s e v erit y  c o nsi d eri n g 
b ot h li ps t o g et h er,  p eri or al li n es  at r est s e v erit y  of t h e  u p p er li p  a n d  p eri or al li n es  at r est 
s e v erit y  of t h e l o w er li p) 
P ati e nt  Gl o b al  A est h eti c I m pr o v e m e nt ( p G AI)  
I n v esti g at or  Gl o b al  A est h eti c I m pr o v e m e nt (i G AI) 
S af et y  will  b e  ass ess e d  b y  m o nit ori n g  a d v ers e  e v e nts ( A Es)  at  all st u d y  visits .   A d v ers e  E v e nts  of 
S p e ci al I nt er est,  a n y  c h a n g es i n  visi o n  a n d  a n y  e v e nts  attri b ut a bl e t o  a n  e m b oli c  or is c h e mi c  c a us e (i. e., 
s ki n i nf ar cti o n)  will  b e  m o nit or e d.   Ot h er  S af et y  e v al u ati o ns i n cl u d e li p f u n cti o n,  li p s e ns ati o n, li p 
t e xt ur e, li p fir m n ess, li p s y m m etr y,  a n d li p  m o v e m e nt/f u n cti o n.   Ot h er  e v al u ati o ns i n cl u d e I n v esti g at or 
E as e  of  Us e  Ass ess m e nt ,  S w elli n g  Ass ess m e nt,  a n d  S u bj e ct  S atisf a cti o n  wit h  Li ps  Ass ess m e nt. 
7. 2   
B e gi n ni n g  a n d  E n d  of  St u d y  
A s u bj e ct is  c o nsi d er e d t o  b e  e nr oll e d i n t h e st u d y  w h e n  h e/s h e  h as  pr o vi d e d  writt e n i nf or m e d  c o ns e nt 
a n d  h as  b e e n r a n d o mi z e d t o tr e at m e nt. 
A s u bj e ct is  c o nsi d er e d t o  h a v e  c o m pl et e d t h e st u d y  aft er  h e/s h e  h as  c o m pl et e d  Visit  5/  M o nt h  6. 
A s u bj e ct is  c o nsi d er e d t o  h a v e  wit h dr a w n  aft er  h e/s h e  h as  wit h dr a w n  c o ns e nt  or  h as  b e e n  wit h dr a w n 
u n d er t h e  c o n diti o ns s p e cifi e d i n  S e cti o n  7. 3. 3 . 
A s u bj e ct is  c o nsi d er e d t o  h a v e  b e e n l ost t o f oll o w- u p if  h e/s h e  c a n n ot  b e  c o nt a ct e d  b y t h e i n v esti g at or. 
T h e i n v esti g at or  will  d o c u m e nt  eff orts t o  att e m pt t o r e a c h t h e s u bj e ct  at l e ast  t wi c e  b y t el e p h o n e  a n d  will 
s e n d  a  c ertifi e d l ett er  b ef or e  c o nsi d eri n g t h e s u bj e ct l ost t o f oll o w - u p.  T h e  e n d  of  p arti ci p ati o n f or  a 
s u bj e ct l ost t o f oll o w-u p is  d o c u m e nt e d  as t h e  d at e  of t h e  c ertifi e d l ett er.  
E a c h s u bj e ct  will  b e  m o nit or e d f or t h e  o c c urr e n c e  of  A Es, i n cl u di n g s eri o us  a d v ers e  e v e nts ( S A Es), 
i m m e di at el y  aft er tr e at m e nt i niti ati o n. E a c h s u bj e ct  will  b e f oll o w e d f or s af et y  m o nit ori n g  u ntil  h e/s h e is 
dis c h ar g e d fr o m t h e st u d y. 
F oll o w- u p  pr o c e d ur es r el at e d t o  pr e g n a n c y,  A Es,  or  S A Es  m a y  c o nti n u e  b e y o n d t h e  e n d  of t h e st u d y. 
E a c h s u bj e ct  will  p arti ci p at e i n t h e st u d y f or  a p pr o xi m at el y  6  m o nt hs .  Aft er  d et er mi n ati o n  of  eli gi bilit y 
at  Visit  1/ D a y  1,  e a c h s u bj e ct  will  b e tr e at e d  wit h  P N 4 0 0 8 2  or  R est yl a n e  Sil k. 
It is  a nti ci p at e d t h at t h e  d ur ati o n  of t his st u d y  will  b e 2 0  m o nt hs  fr o m t h e first s u bj e ct si g ni n g t h e I C F t o 
t h e  M o nt h  6  E O S  visit l ast s u bj e ct. 
At t h e  e n d  of st u d y  visit t h e s u bj e cts  w h o  h a v e  c o m pl et e d  Visit  5/ M o nt h  6  wit hi n  wi n d o w  will  b e i n vit e d 
t o  p arti ci p at e i n  a n  o p e n-l a b el r etr e at m e nt stu d y,  P R O  2 0 1 8- 0 3. 
7. 3   
St u d y  P o p ul ati o n  
A p pr o xi m at el y  1 5 8  h e alt h y  m al es  a n d f e m al es  o v er   2 1 y e ars  of  a g e s e e ki n g  li p  a u g m e nt ati o n will  b e 
s el e ct e d t o  p arti ci p at e i n t h e st u d y.  
7. 3. 1   I n cl usi o n  C rit e ri a  
S u bj e ct s m ust  m e et  all  of 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.   M e n  or  n o n- pr e g n a nt  or  n o n- br e astf e e di n g  w o m e n   o v er  2 1 y e ars  of  a g e  
2.   If f e m al e  a n d  of  c hil d b e ari n g  p ot e nti al,  a  n e g ati v e  uri n e  pr e g n a n c y t est  at  B as eli n e ( D a y  1)  a n d 
t h e s u bj e ct  a gr e es t o  us e  a d e q u at e  c o ntr a c e pti o n  d uri n g t h e st u d y  p eri o d 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
1 8  
 
3.   H as  a n  o v er all  s c or e  of  v er y t hi n   or t hi n  o n t h e  L F G S,  as  a gr e e d  u p o n  b y t h e  Tr e ati n g  a n d 
E v al u ati n g I n v esti g at ors,  a n d  d esir es  at l e ast  a  1- p oi nt i m pr o v e m e nt i n  o v er all  L F G S s c or e;  O R 
H as  a  Fit z p atri c k s ki n  p h ot ot y p e  I V, V  or  VI  a n d  h as  a n  L F G S s c or e  of t hi c k  or f ull,  as  a gr e e d 
u p o n  b y t h e  Tr e ati n g  a n d  E v al u ati n g I n v esti g at ors,  a n d  d esir es tr e at m e nt t o t h e  v er mili o n  b o d y  of 
1  or  b ot h li ps 
4.   Willi n g t o  gi v e  writt e n i nf or m e d  c o ns e nt  
7. 3. 2   E x cl usi o n  C rit e ri a  
S u bj e cts  w h o  m e et  a n y  of t h e f oll o wi n g  crit eri a  will  b e  e x cl u d e d fr o m t h e st u d y: 
1.   W o m e n  w h o  ar e  pr e g n a nt, l a ct ati n g,  or  pl a n ni n g  a  pr e g n a n c y 
2.   Hist or y  of  all er g y ,  a n a p h yl a xis or  h y p ers e nsiti vit y t o i nj e ct a bl e  h y al ur o ni c  a ci d  pr o d u cts, l o c al 
a n est h eti cs  of t h e  a mi d e t y p e s u c h  as li d o c ai n e,  or t o l at e x,  or is  pl a n ni n g t o  u n d er g o 
d es e nsiti z ati o n t h er a p y  d uri n g t h e st u d y 
3.   H as li p t att o os,  pi er ci n gs, f a ci al  h air,  or s c ars t h at  w o ul d i nt erf er e  wit h  vis u ali z ati o n  of t h e li ps 
a n d  p eri or al  ar e a f or t h e  eff e cti v e n ess  ass ess m e nts  
4.   H as  a b n o r m al li p f u n cti o n,  wit h i n a bilit y t o  eff e cti v el y si p  w at er t hr o u g h  a str a w 
5.   H as  a b n or m al li p s e ns ati o n,  wit h i n a bilit y t o f e el  a  0. 4 G  m o n ofil a m e nt  or  a  c ott o n  wis p  at  a n y 
sit e  o n t h e li p 
6.   H as  m o d er at e  or s e v er e  a b n or m al li p  as y m m etr y  
7.   H as  a n y  m ass f or m ati o n  o n t h e li p  
8.   H as  d e nt ur es  or  a n y  d e vi c e  c o v eri n g  all  or  p art  of t h e  u p p er  p al at e,  a n d/ or s e v er e  m al o c cl usi o n  or 
d e nt of a ci al  or  m a xill of a ci al  d ef or miti es  as j u d g e d  b y t h e  Tr e ati n g I n v esti g at or .  S u bj e cts  pl a n ni n g 
t o  u n d er g o  e xt e nsi v e  d e nt al  pr o c e d ur es s u c h  as d e nt al i m pl a nts,  m ulti pl e t o ot h  e xtr a cti o ns , or 
or al s ur g er y s h o ul d  n ot  p arti ci p at e.  Mi n or  d e nt al  pr o c e d ur es s u c h  as t e et h  cl e a ni n g  a n d  r e p air  of 
c ari es  ar e  n ot  e x cl usi o n ar y  
9.   H as  u n d er g o n e f a ci al  pl asti c s ur g er y  or r e c ei v e d  p er m a n e nt f a ci al i m pl a nts ( e. g., 
p ol y m et h yl m et h a cr yl at e, sili c o n e,  p ol yt etr afl u or o et h yl e n e ,  p ol y a cr yl a mi d e, lifti n g t hr e a ds) 
a n y w h er e i n t h e f a c e  or  n e c k,  or is  pl a n ni n g t o  b e i m pl a nt e d  wit h  a n y  of t h es e  pr o d u cts  d uri n g 
t h e st u d y 
1 0.  H as  u n d er g o n e s e mi -p er m a n e nt  d er m al fill er tr e at m e nt ( e. g.,  c al ci u m  h y dr o x yl a p atit e,  p ol y - L-
l a cti c  a ci d) i n t h e l o w er f a c e ( b el o w t h e  or bit al ri m)  wit hi n  1 2  m o nt hs  b ef or e  e nr oll m e nt  or is 
pl a n ni n g t o  u n d er g o s u c h tr e at m e nt  d uri n g t h e st u d y 
1 1.  H as  u n d er g o n e f a ci al tiss u e  a u g m e nt ati o n  wit h f at i nj e cti o ns,  b ot uli n u m t o xi n i nj e cti o ns i n t h e 
l o w er f a c e ( b el o w t h e  or bit al ri m),  m es ot h er a p y,  or  c os m eti c  pr o c e d ur es i n t h e f a c e  or  n e c k ( e. g., 
f a c e-lift, l as er,  p h ot o- m o d ul ati o n, i nt e ns e  p uls e d li g ht, r a di o fr e q u e n c y,  d er m a br asi o n,  m o d er at e 
or  gr e at er  d e pt h  c h e mi c al  p e el,  mi cr o n e e dli n g,  or  ot h er  a bl ati v e  pr o c e d ur es)  wit hi n  9  m o nt hs 
b ef or e  e nr oll m e nt  or is  pl a n ni n g t o  u n d er g o  a n y  of t h es e  pr o c e d ur es  d uri n g t h e st u d y 
1 2.  H as  us e d  A N Y li p filli n g  a g e nts  wit hi n  1 2  m o nt hs  of st u d y  e nr oll m e nt ( h y al ur o ni c  a ci d  pr o d u cts, 
c oll a g e n - b as e d  pr o d ucts , et c. ) 
1 3.  H as  us e d  a n y li p  pl u m pi n g  pr o d u cts  or  d e vi c es  wit hi n  1 0  d a ys  b ef or e  e nr oll m e nt  or is  pl a n ni n g t o 
us e s u c h  pr o d u cts  d uri n g t h e st u d y 
1 4.  H as  b e g u n  usi n g  a n y  o v er-t h e- c o u nt er ( O T C)  or  pr es cri pti o n  or al  or t o pi c al  a nti- wri n kl e  pr o d u cts 
f or t h e li ps  or  ar o u n d t h e  m o ut h  wit hi n  9 0  d a ys  b ef or e  e nr oll m e nt  or is  pl a n ni n g t o  b e gi n  usi n g 

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s u c h  pr o d u cts  d uri n g t h e st u d y ( S u bj e cts  w h o  h a v e  b e e n  o n  a  st a bl e r e gi m e n  of s u c h  pr o d u cts f or 
at l e ast  9 0  d a ys  ar e  eli gi bl e f or t h e st u d y  a n d  m ust  c o nti n u e t h eir r e gi m e n t hr o u g h o ut t h e st u d y.) 
1 5.  Is  o n  a n  o n g oi n g r e gi m e n  of  a nti c o a g ul ati o n t h er a p y ( e. g.,  w arf ari n), t hr o m b ol yti cs,  or i n hi bit ors 
of  pl at el et  a g gr e g ati o n   or  n o nst er oi d al  a nti-i nfl a m m at or y  dr u gs ( N S AI Ds,  e. g.,  as piri n, 
i b u pr of e n)  or  ot h er s u bst a n c es  k n o w n t o i n cr e as e  c o a g ul ati o n ti m e ( e. g.,  h er b al s u p pl e m e nts  wit h 
g arli c  or  gi n g k o)  wit hi n  1 0  d a ys  of  u n d er g oi n g st u d y  d e vi c e i nj e cti o ns.  S u bj e cts  w h o  will 
wit h h ol d s u c h t h er a p y f or  1 0  d a ys  b ef or e  A N D  aft er  a n y i nj e cti o n s essi o n  m a y  p arti ci p at e  
1 6.  H as  a  hist or y  or  pr es e n c e  of  bl e e di n g  dis or d ers 
1 7.  H as  us e d s yst e mi c  c orti c o st er oi ds  or i m m u n os u p pr essi v e  m e di c ati o ns  wit hi n  3 0  d a ys  pri or t o 
tr e at m e nt  
1 8.  Is  o n  a  c o n c urr e nt r e gi m e n  of li d o c ai n e  or str u ct ur all y r el at e d l o c al  a n est h eti cs ( e. g.,  b u pi v a c ai n e) 
1 9.  H as  a n  a cti v e i nfl a m m ati o n  (s ki n  er u pti o ns s u c h  as  c ysts,  pi m pl es, r as h es,  or  hi v es), i nf e cti o n, 
c a n c er o us  or  pr e c a n c er o us l esi o n,  or  u n h e al e d  w o u n d  o n t h e f a c e 
2 0.  H as  a  hist or y  of  k n o w n s us c e pti bilit y t o  k el oi d f or m ati o n  or  h y p ertr o p hi c s c ars 
2 1.  H as  p or p h yri a 
2 2.  H as  a cti v e  h er p es l a bi alis  l esi o ns  at t h e ti m e  of i nj e cti o ns.  S u bj e cts  wit h  a  hist or y  of  h er p es 
l a bi alis  w h o  h a v e  h a d f o ur ( 4)  or  m or e  o ut br e a ks i n t h e  1 2  m o nt hs  pri or t o  e nr oll m e nt  ar e  als o 
e x cl u d e d  e v e n i n t h e  a bs e n c e  of l esi o ns  at t h e  b as eli n e  visit  
2 3.  H as i m p air e d  c ar di a c  c o n d u cti o n, s e v er el y i m p air e d  h e p ati c f u n cti o n,  or s e v er e r e n al  d ysf u n cti o n 
t h at, i n t h e  o pi ni o n  of t h e i n v esti g at or,  w o ul d  pl a c e t h e m  at ris k  of  ass o ci at e d  c o m pli c ati o ns fr o m 
t h es e ill n ess es  d uri n g t h e  c o urs e  of t h e st u d y 
2 4.  H as  a n y  u n c o ntr oll e d  dis e as e, i. e.,  a  c o n diti o n t h at  h as  n ot  b e e n  a p pr o pri at el y  di a g n os e d, 
e v al u at e d , a n d r e c ei v e d  m e di c all y  a p pr o pri at e tr e at m e nt  or  c ar e  
2 5.  H as s e v er e  c ar di o v as c ul ar  dis e as e ; e x a m pl es i n cl u d e  b ut  ar e  n ot li mit e d t o  N e w  Y or k  H e art 
Ass o ci ati o n  h e art f ail ur e  cl assifi c ati o n III   or I V,  u nst a bl e  a n gi n a,  a n d i nt er n al  p a c e m a k ers. 
P ot e nti al s u bj e cts  wit h  ot h er si g nifi c a nt  c ar di o v as c ul ar  dis e as es s h o ul d  b e  dis c uss e d  wit h t h e 
M e di c al  M o nit or  b ef or e  e nr olli n g 
7. 3. 3   S u bj e ct  Wit h d r a w al  C rit e ri a  
A s u bj e ct  m a y  wit h dr a w fr o m t h e st u d y  at  a n y ti m e  f or  a n y r e as o n. 
A s u bj e ct  will  b e  wit h dr a w n fr o m t h e st u d y if  his/ h er s af et y  or  w ell - b ei n g is  d et er mi n e d t o  b e  at ris k. 
Wit h dr a w al  will  b e  m a d e  at t h e  dis cr eti o n  of t h e i n v esti g at or  or  at t h e s u bj e ct’s r e q u est.  
A s u bj e ct  m ust  wit h dr a w fr o m t h e st u d y f or  a n y  of t h e f oll o wi n g r e as o ns: 
•   T h e s u bj e ct  or l e g al r e pr es e nt ati v e  wit h dr a ws  c o ns e nt 
•   T h e s u bj e ct’s  st u d y  d e vi c e assi g n m e nt  is  u n bli n d e d 
•   T h er e is  a si g nifi c a nt  pr ot o c ol  vi ol ati o n  as  d et er mi n e d  b y t h e  S p o ns or  or  m e di c al  m o nit or. 
A s u bj e ct  m a y  b e  wit h dr a w n fr o m t h e st u d y f or  a n y  of t h e f oll o wi n g r e as o ns: 
•   L ost t o f oll o w- u p 
•   I n v esti g at or  dis cr eti o n 
Wit h dr a w al is  p er m a n e nt;  aft er  a s u bj e ct  h as  b e e n  wit h dr a w n,  h e/s h e  will  n ot  b e  all o w e d t o  e nr oll  a g ai n. 

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If  a s u bj e ct is  wit h dr a w n fr o m t h e st u d y f or  a n y r e as o n, t h e E O S   or  E arl y  T er mi n ati o n  pr o c e d ur es ( Visit 
5/ M o nt h  6) s h o ul d  b e  c o m pl et e d  a n d  a n y  o utst a n di n g  d at a  a n d s u bj e ct  di ari es s h o ul d  b e  c oll e ct e d.  D at a, 
i n cl u di n g t h e  d at e  a n d  pri m ar y r e as o n f or  wit h dr a w al,  m ust  b e  d o c u m e nt e d  o n t h e E O S  c as e r e p ort f or m 
( C R F)  a n d s o ur c e  d o c u m e nt. 
If  a s u bj e ct  wit h dr a ws fr o m t h e st u d y  at  a n y ti m e  d u e t o  a n  A E, t h e r e as o n f or  wit h dr a w al, t h e  n at ur e  of 
t h e  A E,  a n d its  cli ni c al  c o urs e  m ust  b e f ull y  d o c u m e nt e d.  T h e i n v esti g at or  m ust stri v e t o f oll o w t h e 
s u bj e ct  u ntil t h e  A E  h as r es ol v e d,  b e c o m e  cli ni c all y i nsi g nifi c a nt, is st a bili z e d,  or t h e s u bj e ct is l ost t o 
f oll o w- u p.  F or  a n y  S A E, f oll o w t h e pr o c e d ur es  pr o vi d e d i n  S e cti o n  7. 9. 7 . 
7. 3. 4   R e pl a c e m e nt  of  S u bj e cts  
A s u bj e ct  w h o  wit h dr a ws  fr o m t h e st u d y  will  n ot  b e r e pl a ce d.   
7. 4   
T r e at m e nts  
T h e i n v esti g at or  will t a k e r es p o nsi bilit y  f or  a n d will  t a k e  all st e ps t o  m ai nt ai n  a p pr o pri at e r e c or ds  a n d 
e ns ur e  a p pr o pri at e s u p pl y,  h a n dli n g, st or a g e,  distri b uti o n,  a n d  us e  of st u d y  m at eri als i n  a c c or d a n c e  wit h 
t h e  pr ot o c ol  a n d  a n y  a p pli c a bl e l a ws  a n d r e g ul ati o ns. 
7. 4. 1   D os a g e  a n d  F o r m ul ati o ns 
T h e  f oll o wi n g st u d y  d e vi c es  will  b e us e d i n t h e st u d y  a n d  pr o vi d e d  b y t h e  S p o ns or: 
T est  d e vi c e : P N 4 0 0 8 2  ( m a n uf a ct ur e d  b y Pr oll e ni u m  M e di c al  T e c h n ol o gi es) is  a  cl e ar,  c ol orl ess  g el i n 
1. 0  m L  pr e- fill e d s yri n g es  wit h  2 5 m g/ m L  of st a bili z e d  h y al ur o ni c  a ci d   a n d li d o c ai n e  0. 3 % w/ w . 
C o m p a r at o r  d e vi c e : R est yl a n e  Sil k  (m a n uf a ct ur e d  b y  Q- M e d  A B  f or  M e di cis –  A  Di visi o n  of  V al e a nt 
P h ar m a c e uti c als  C or p or ati o n  N ort h  A m eri c a,  L L C  ) is a  cl e ar,  c ol orl ess  g el i n  1. 0  m L  pr e -fill e d s yri n g es 
f or m ul at e d t o  a  c o n c e ntr ati o n  of  2 0 m g/ m L  of st a bili z e d  h y al ur o ni c  a ci d   a n d li d o c ai n e  0. 3 %  w/ w.  
7. 4. 2   R a n d o mi z ati o n 
S u bj e cts  w h o s atisf y  all  of t h e  eli gi bilit y  crit eri a   will  b e r a n d o mi z e d i n  a 1 : 1 r ati o t o tr e at m e nt  wit h 
P N 4 0 0 8 2  or  R est yl a n e  Sil k .  R a n d o mi z ati o n  will  b e  p erf or m e d  a c c or di n g t o  a  c o m p ut er-g e n er at e d 
r a n d o mi z ati o n s c h e m e t h at  will  b e  g e n er at e d  a n d  m ai nt ai n e d  b y  a n i n d e p e n d e nt t hir d  p art y.  A s e al e d 
c o p y  of t h e r a n d o mi z ati o n s c h e m e s h o ul d  b e r et ai n e d  at  e a c h sit e  a n d s h o ul d  b e  a v ail a bl e t o r e g ul at or y 
a ut h oriti es  at t h e ti m e  of sit e i ns p e cti o n t o  all o w f or  v erifi c ati o n  of t h e tr e at m e nt i d e ntit y f or  e a c h 
s u bj e ct. 
A  u ni q u e s u bj e ct  n u m b er  will  b e  assi g n e d t o  e a c h s u bj e ct.  E a c h sit e  will r e c ei v e t h e r a n d o mi z ati o n 
s c h e m e.  E a c h  eli gi bl e s u bj e ct  will  b e  assi g n e d  a  u ni q u e r a n d o mi z ati o n  c o d e  n u m b er i n  as c e n di n g  or d er. 
7. 4. 3   St u d y  D e vi c e  A d mi nist r ati o n   
S u bj e cts  ar e  p h ysi c all y  m as k e d ( bli n df ol d e d) j ust  pri or t o  a n d  d uri n g  all i nj e cti o n  pr o c e d ur es t o  pr e v e nt 
o bs er v ati o n  of t h e s yri n g es  c o nt ai ni n g st u d y  d e vi c e.  A n y  u n bli n d e d i n v esti g at ors  a n d  st aff s h o ul d  b e 
r e mi n d e d  N O T t o  dis c uss t h e tr e at m e nt i n t h e  pr es e n c e  of t h e s u bj e ct. 
T h e s u bj e ct  s h o ul d  b e  p ositi o n e d i n  a s e at e d  p ositi o n  a n d  m a y  b e r e cli n e d t o  as  m u c h  as  4 5°. 
A n y  m a k e u p s h o ul d  b e r e m o v e d  wit h  a  g e ntl e  cl e a ns er  or  a s p e cifi c  m a k e u p r e m o v er  pr o d u ct (s u c h  as 
N e utr o g e n a  Cl e a nsi n g  M a k e u p  R e m o v er  F a ci al  Wi p es) . 
T h e  n o n- v er milli o n  ar e as  of t h e  u p p er  a n d l o w er li ps s h o ul d  b e  pr e p ar e d  b y  g e ntl e  w as hi n g  wit h  a 
s ur gi c al s cr u b  pr o d u ct ( C hl or h e xi di n e ,  T e c h ni c ar e, et c .). 
T o  pr e p ar e t h e s yri n g es f or  us e, t h e i n v esti g at or s h o ul d  att a c h  o n e  of t h e  n e e dl es  i n cl u d e d i n t h e s u bj e ct 
st u d y  d e vi c e  kit i n  a fir m  m a n n er.  T h e  pl u n g er s h o ul d  b e  g e ntl y  d e pr ess e d t o  e x pr ess  a n y  u n w a nt e d  air 

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u ntil  a s m all  dr o pl et  of i m pl a nt  m at eri al  a p p e ars  at t h e ti p  of t h e  n e e dl e.   
St u d y  d e vi c e  is  a d mi nist er e d  usi n g o nl y  a  n e e dl e  pr o vi d e d i n t h e s u bj e ct st u d y  d e vi c e  kit.  T h e  n e e dl e is 
i ns ert e d  at  a n  a p pr o xi m at e  a n gl e  of  3 0°  p ar all el t o t h e s urf a c e  of t h e s ki n  or li p.  F or r h yti ds, st u d y  d e vi c e 
s h o ul d  b e i nj e ct e d i nt o t h e  mi d- t o- d e e p  d er mis.  St u d y d e vi c e  s h o ul d  b e i nj e ct e d i nt o t h e s u b m u c os al 
l a y er f or li p  a u g m e nt ati o n; c ar e s h o ul d  b e t a k e n t o  a v oi d i ntr a m us c ul ar i nj e cti o n. If st u d y  d e vi c e  is 
i nj e ct e d t o o s u p erfi ci all y t his  m a y r es ult i n  visi bl e l u m ps  a n d/ or  bl uis h  dis c ol or ati o n. 
I nj e ct st u d y d e vi c e  a p pl yi n g li g ht t o  m o d er at e,  e v e n  pr ess ur e  o n t h e  pl u n g er.  A v oi d i nj e cti n g  q ui c kl y  as 
r a pi d i nj e cti o n  c a n r es ult i n i n cr e as e d  p ai n. It is i m p ort a nt t h at t h e i nj e cti o n is st o p p e d j ust  b ef or e t h e 
n e e dl e is  p ull e d  o ut  of t h e s ki n t o  pr e v e nt  m at eri al fr o m l e a ki n g  o ut  or  b ei n g  t o o s u p erfi ci all y i m pl a nt e d 
i nt o t h e s ki n. 
O nl y  c orr e ct  or  a u g m e nt t o  1 0 0 %  of t h e  d esir e d  v ol u m e  eff e ct.  D o  n ot  o v er c orr e ct  or  o v erfill.  
T h e  n e e dl e  m a y  b e r e pl a c e d  as  n e e d e d t o  e ns ur e s u bj e ct  c o mf ort.  O nl y  n e e dl es  pr o vi d e d i n t h e s u bj e ct 
st u d y  d e vi c e  kit  m a y  b e  us e d.  B ef or e  n e e dl e r e pl a c e m e nt, t h e  pl u n g er s h o ul d  b e  wit h dr a w n sli g htl y  a n d 
o n c e t h e  n e e dl e  h as  b e e n r e pl a c e d, t h e  pl u n g er r e - a d v a n c e d t o  e ns ur e t h at t h e  n e w  n e e dl e is  pr efill e d 
wit h i m pl a nt  m at eri al  pri or t o r est arti n g i nj e cti o ns.  
T y pi c al  us a g e f or  e a c h tr e at m e nt s essi o n is s p e cifi c t o t h e sit e  as  w ell  as t h e   a m o u nt  of  a u g m e nt ati o n  or 
r h yti ds  c orr e cti o n  d esir e d.  B as e d  o n  U. S.  cli ni c al st u di es, t h e  m a xi m u m  v ol u m e  all o w e d  p er tr e at m e nt is 
1. 5  m L  p er li p ( 1. 5 f or  u p p er,  1. 5 f or l o w er)  a n d  1. 0  m L f or  p eri or al r h yti d  c orr e cti o n.  T h us, t h e 
m a xi m u m  a m o u nt t h at  c a n  b e   us e d  at  o n e tr e at m e nt s essi o n is  4. 0  ml. 
A m o u nts  of  m at eri al i nj e ct e d s h o ul d  b e r e c or d e d s e p ar at el y f or t h e  u p p er li p, l o w er li p  a n d  p eri or al 
ar e as.  
I N J E C TI O N  T E C H NI Q U E S  
1.   St u d y  d e vi c e  c a n  b e i nj e ct e d  b y  a  n u m b er  of  diff er e nt t e c h ni q u es t h at  d e p e n d  o n  t h e tr e ati n g 
i n v esti g at or’s  e x p eri e n c e  a n d  pr ef er e n c e  a n d s u bj e ct c h ar a ct eristi cs.  
2.   S e ri al  p u n ct u r e  i n v ol v es  m ulti pl e,  cl os el y s p a c e d i nj e cti o ns  al o n g  wri n kl es, f ol ds,  or t h e 
v er milli o n  b or d er.  Alt h o u g h s eri al  p u n ct ur e  all o ws  pr e cis e  pl a c e m e nt  of t h e fill er, it  pr o d u c es 
m ulti pl e  p u n ct ur e  w o u n ds t h at  m a y  b e  u n d esir a bl e t o s o m e  s u bj e cts. 
3.   Li n e a r t h r e a di n g (i n cl u d es  r et r o g r a d e  a n d  a nt e g r a d e)  is  a c c o m plis h e d  b y f ull y i ns erti n g t h e 
n e e dl e i nt o t h e  c e nt er  of t h e  ar e a t o  b e  c orr e ct e d  or  a u g m e nt e d  a n d i nj e cti n g t h e f ill er  al o n g t h e 
tr a c k  as  a  “t hr e a d. ”  Alt h o u g h t hr e a di n g is  m ost  c o m m o nl y  pr a cti c e d  aft er t h e  n e e dl e  h as  b e e n 
f ull y i ns ert e d  a n d is  b ei n g  wit h dr a w n, it  c a n  als o  b e  p erf or m e d  w hil e  a d v a n ci n g t h e  n e e dl e - 
a nt e gr a d e t e c h ni q u e).  T o  a u g m e nt  t h e li p, t h e r etr o gr ad e li n e ar t hr e a di n g t e c h ni q u e is t h e  m ost 
a d vis a bl e.  
4.   S eri al t hr e a di n g is  a t e c h ni q u e t h at  utili z es  el e m e nts  of  b ot h  a p pr o a c h es.    
N ot e!  T h e  c orr e ct i nj e cti o n t e c h ni q u e is  cr u ci al f or t h e fi n al r es ult  of t h e tr e at m e nt.  
5.   T h e f oll o wi n g t e c h ni q u es s h o ul d  b e  a v oi d e d  as t h e y  m a y r es ult i n  a n i n cr e as e i n s h ort- t er m 
e pis o d es  of  br uisi n g, s w elli n g, r e d n ess,  p ai n,  or t e n d er n ess  at t h e i nj e cti o n sit e: 
•  Diss e cti o n  of t h e s u b- e pi d er m al  pl a n e  wit h l at er al  m o v e m e nt  of t h e  n e e dl e  – 
“f a n ni n g ”  
•  R a pi d fl o w r at e ( >   0. 3  m L/ mi n) of i m pl a nt  m at eri al i nj e cti o n  
•  Hi g h i nj e cti o n  v ol u m es  
•  T h e  us e  of  n e e dl es  ot h er t h a n  o n es  pr o vi d e d i n t h e s u bj e ct st u d y  d e vi c e  kit 
6.   T h e  us e  of  c a n n ul as is  pr o hi bit e d. 

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7.   W h e n t h e i nj e cti o n is  c o m pl et e d, t h e tr e at e d sit e s h o ul d  b e  g e ntl y   m ass a g e d s o t h at it  c o nf or ms 
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.  M ass a gi n g t h at s u bst a nti all y  d ef or ms t h e li ps  or  c a us es 
bl a n c hi n g  of  c o m pr ess e d tiss u es is  e x c essi v e  a n d s h o ul d  b e  a v oi d e d  e x c e pt  as  d es cri b e d  b el o w. 
8.    If  e x c essi v e  m at eri al is i m pl a nt e d  or irr e g ul arl y i m pl a nt e d,  m ass a g e t h e  ar e a s o m e w h at  m or e 
fir ml y t h a n f or t h e  us u al i m pl a nt ati o n  pr o c e d ur e t o  o bt ai n  o pti m al r es ults. 
9.   If  bl a n c hi n g  of t h e tiss u es is  o bs er v e d  d uri n g  or  dir e ctl y  aft er i nj e cti o n a n d  b e c o m es  a  c o n c er n, 
t h e  ar e a  m a y  b e  g e ntl y  m ass a g e d. If  bl a n c hi n g  p ersists, c o nt a ct t h e  M e di c al  M o nit or . 
1 0.   T h e li ps s h o ul d  b e  a u g m e nt e d t o  a c hi e v e t h e  m a xi m u m  d esir a bl e   a p p e ar a n c e f or  b ot h t h e 
tr e ati n g i n v esti g at or  a n d t h e s u bj e ct.  S u bj e cts s h o ul d  b e  pr o vi d e d  a s m all  h a n d  mirr or t o  o bs er v e 
t h e r es ults  a n d f urt h er i nj e cti o ns  c o n d u ct e d  u ntil  m a xi m u m  b e n efit  h as  b e e n  o bt ai n e d.  C ar e 
s h o ul d  b e t a k e n t o  e ns ur e t h at t h e li ps  ar e s y m m etri c fr o m ri g ht t o l eft  a n d t h at t h e  u p p er  a n d 
l o w er li ps  h a v e r el ati v e  pr o p orti o n alit y.  
1 1.   T h e  p eri or al  ar e a s h o ul d  b e  c orr e ct e d  A F T E R t h e  u p p er  a n d l o w er li ps  h a v e  b e e n  c orr e ct e d. 
S o m e  c orr e cti o n  of  p eri or al r h yti ds  m a y  o c c ur  wit h li p  a u g m e nt ati o n, t h us it is  b est t o  a d dr ess 
a n y r e m ai ni n g  p eri or al  c orr e cti o n  n e e ds  aft er t h e li p i nj e cti o ns  h a v e  b e e n  c o m pl et e d.   
1 2.   If t h e tr e at e d  are a is s w oll e n  dir e ctl y  aft er t h e i nj e cti o n,  a n i c e  p a c k  c a n  b e  a p pli e d  o n t h e sit e f or 
a s h ort  p eri o d  if t h e i n v esti g at or  d e e ms it  a p pr o pri at e. I c e s h o ul d  b e  us e d  wit h  c a uti o n if t h e  ar e a 
is still  n u m b fr o m  a n est h eti c t o  a v oi d t h er m al i nj ur y. 
1 3.   S u bj e cts  s h o ul d  b e  e n c o ur a g e d t o  a v oi d  a r e c u m b e nt  p ositi o n f or s e v er al  h o urs  aft er i nj e cti o ns t o 
r e d u c e s w elli n g.  T h e  us e  of i c e,  c ol d  p a c ks  or  ot h er t h er a pi es t o r e d u c e s w elli n g s h o ul d  o nl y  b e 
p erf or m e d  at i nstr u cti o n  of t h e i n v esti g at or.  T h e s u bj e ct s h o ul d  b e i n str u ct e d t o  c o nt a ct t h e sit e if 
s u bst a nti al s w elli n g  o c c ur s. 
7. 4. 4   Bli n di n g  of  St u d y  D e vi c e  
I nj e cti o ns  of t h e st u d y  d e vi c e  ar e  p erf or m e d  b y t h e  u n bli n d e d Tr e ati n g I n v esti g at or .  T h e  bli n d e d 
E v al u ati n g I n v esti g at or  is  n ot  all o w e d t o r etri e v e st u d y s u p pli es  or t o  b e  pr es e nt  d uri n g  o p e ni n g  of t h e 
st u d y s u p pli es  or  d uri n g t h e i nj e cti o ns.  T h e  Tr e ati n g I n v esti g at or  is  n ot t o  h a v e  a n y  dis c ussi o n  wit h t h e 
E v al u ati n g I n v esti g at or  or s u bj e cts r e g ar di n g t h e tr e at m e nts.  
S u bj e cts  ar e  bli n d e d t o tr e at m e nt  assi g n m e nt.  S u bj e cts  ar e  p h ysi c all y  m as k e d ( bli n df ol d e d) j ust  pri or t o 
a n d  d uri n g  all i nj e cti o n  pr o c e d ur es t o  pr e v e nt  o bs er v ati o n  of t h e s yri n g es  c o nt ai ni n g  st u d y  d e vi c e. 
S u bj e cts, i n v esti g at ors, t h e  S p o ns or’s st aff  c o n d u cti n g t h e st u d y,  a n d  m e m b ers  of t h e  a d mi nistr ati v e 
t e a m  will  n ot  h a v e  a c c ess t o i n di vi d u al s u bj e cts’ tr e at m e nt  assi g n m e nts. I n t h e  e v e nt  of  a n  e m er g e n c y 
t h at r e q uir es  br e a ki n g  of t h e st u d y  bli n d, t h e r a n d o mi z ati o n  c o d e  will  b e  m ai nt ai n e d  b y  e a c h i n v esti g at or 
t h at  c a n  b e  o p e n e d t o r e v e al t h e st u d y  d e vi c e. 
S e e  S e c ti o n 7. 9. 1 0. 2  f or  a  d es cri pti o n  of t h e  m et h o d  of  u n bli n di n g  a s u bj e ct  d uri n g t h e st u d y if s u c h 
a cti o n is  w arr a nt e d.  
At  Visit  5, s u bj e cts  a n d  bli n d e d  e v al u ati n g i n v esti g at ors  will  b e  as k e d  w hi c h tr e at m e nt t h e y t h o u g ht  w as 
a d mi nist er e d   as  a  w a y  of  e v al u ati n g t h e  bli n di n g. 
7. 4. 5   M et h o d  of  P a c k a gi n g,  L a b eli n g,  St o r a g e,  a n d  Dis p e nsi n g 
F or  P N 4 0 0 8 2,  o n e  1. 0  m L s yri n g e  is  p a c k a g e d  al o n g  wit h t w o fi n e-g a u g e  n e e dl es ( 3 0 G) i n  a n  e as y - o p e n 
tr a y.  E a c h s yri n g e is  e q ui p p e d  wit h a  L u er - L o k  as  w ell  as  a  c ust o m fi n g er  gri p  a n d  pl u n g er r o d.  Th e 
s yri n g es  c o nt ai n  a  p e el a bl e l a b el t o  b e  pl a c e d  o n t h e s u bj e ct r e c or d f or tr a c ki n g  p ur p os es.  T w o tr a ys  ar e  
p a c k a g e d i n  a  c art o n.  A l a b el t h at i n cl u d es t h e  pr ot o c ol  n u m b er  a n d  S p o ns or  n a m e  will  b e  att a c h e d t o 
e a c h  c art o n .  

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R est yl a n e  Sil k  st u d y  d e vi c e  will  b e s u p pli e d  b y  Pr oll e ni u m i n t h e  c o m m er ci al  p a c k a gi n g. I n v esti g at ors 
will  b e i nstr u ct e d t o f oll o w i nstr u cti o ns r e g ar di n g st or a g e i n  a c c or d a n c e  wit h t h e st u d y  d e vi c e’s 
Dir e cti o ns  f or  Us e. 
All  stu d y  d e vi c e  will  b e st or e d i n  a  cli m at e -c o ntr oll e d, li mit e d  a c c ess  ar e a.  
T h e i n v esti g at or  a gr e es t o st or e  a n d  a d mi nist er t h e  st u d y  d e vi c e o nl y  at t h e sit e(s) list e d  o n  F or m  F D A 
1 5 7 2 ( or i n v esti g at or  a gr e e m e nt/st at e m e nt).  T h e i n v esti g at or, s u b-i n v esti g at or(s),  or  q u alifi e d  d esi g n e es 
als o  a gr e e t h at t h e  st u d y  d e vi c e  will  b e  a d mi nist er e d  o nl y t o s u bj e cts  w h o  h a v e  pr o vi d e d  writt e n 
i nf or m e d  c o ns e nt  a n d  h a v e  m et  all  e ntr y  crit eri a. St u d y  d e vi c e   m a y  n ot  b e  us e d f or  a n y  p ur p os e  ot h er 
t h a n  as st at e d i n t h e  pr ot o c ol. 
7. 4. 6   St u d y  D e vi c e  A c c o u nt a bilit y  
St u d y  d e vi c e  will  b e  a v ail a bl e  o n sit e f or  e a c h s u bj e ct.  R e c ei pt  of st u d y  d e vi c e   will  b e  d o c u m e nt e d  a n d 
c o nfir m e d  vi a t h e I n v esti g ati o n al  Pr o d u ct  R e c ei pt  F or m.  All  st u d y  d e vi c e m ust  b e  k e pt i n  a l o c k e d  ar e a 
wit h  a c c ess r estri ct e d t o  d esi g n at e d st u d y  p ers o n n el i n  a  cli m at e- c o ntr oll e d, li mit e d  a c c ess  ar e a.  T h e 
a d mi nistr ati o n  of  st u d y  d e vi c e will  b e r e c or d e d  o n t h e  St u d y  D e vi c e   Dis p e nsi n g  L o g.  T h e sit e  m o nit or 
will  p eri o di c all y  c h e c k t h e s u p pl y  of  st u d y  d e vi c e h el d  b y t h e i n v esti g at or  or  p h ar m a cist t o  e ns ur e 
a c c o u nt a bilit y.  At st u d y  c o n cl usi o n,  all  u n us e d  P N 4 0 0 8 2 st u d y  d e vi c e  will  b e r et ur n e d t o t h e  S p o ns or 
a n d  d o c u m e nt e d  usi n g t h e I n v esti g ati o n al  Pr o d u ct  R et ur n  F or m. 
I n v e nt or y r e c or ds  m ust  b e r e a dil y  a v ail a bl e f or i ns p e cti o n  b y t h e st u d y  m o nit or  a n d/ or  a u dit or,  a n d  o p e n 
t o i ns p e cti o n  b y r e g ul at or y  a ut h oriti es  at  a n y ti m e. 
7. 4. 7   P ri o r  a n d  C o n c o mit a nt  M e di c ati o ns  
All  m e di c ati o ns  a n d  ot h er tr e at m e nts t a k e n  b y t h e s u bj e ct  wit hi n  6  m o nt hs  b ef or e  Visit  1/ D a y  1  a n d 
d uri n g t h e st u d y  ar e t o  b e r e c or d e d  o n t h e  C R F  usi n g t h eir  g e n eri c  n a m e, if  k n o w n,  wit h t h e 
c orr es p o n di n g i n di c ati o n.  T h e  m e di c ati o ns t o  b e r e c or d e d i n cl u d e  pr es cri pti o n  a n d  O T C  m e di c ati o ns  a n d 
di et ar y s u p pl e m e nts.  All  m e di c ati o ns t a k e n  o n  a r e g ul ar  b asis, i n cl u di n g  vit a mi ns,  as piri n,  a n d 
a c et a mi n o p h e n, s h o ul d  b e r e c or d e d  pri or t o first  us e  of t h e st u d y  d e vi c e . 
T h e  us e  of  a n y  c o n c o mit a nt  m e di c ati o n  m ust r el at e  t o t h e s u bj e ct’s  d o c u m e nt e d  m e di c al  hist or y, 
pr o p h yl a xis,  or  a n  A E. 
7. 4. 7. 1   
P r e c a uti o ns  
S u bj e cts s h o ul d  b e  gi v e n t h e f oll o wi n g  a d diti o n al i nstr u cti o ns: 
•   S u bj e ct s h o ul d  mi ni mi z e  or  a v oi d  e x c essi v e  n at ur al  or  artifi ci al s u nli g ht  e x p os ur e  a n d  e xtr e m e 
c ol d  w e at h er  
•   S u bj e cts s h o ul d  a v oi d  e pil ati o n, l as er,  m e c h a ni c al  or  c h e mi c al  p e eli n g  pr o c e d ur es  d uri n g t h e 
st u d y 
7. 4. 7. 2   
M e di c ati o ns  a n d  T r e at m e nts  P r o hi bit e d  B ef o r e  St u d y  E nt r y  a n d  D u ri n g t h e  St u d y  
T h e  m e di c ati o ns  pr o hi bit e d  pri or t o  Visit  1/ D a y  1  ar e list e d i n t h e  e x cl usi o n  crit eri a ( S e cti o n  7. 3. 2 ). 
S u bj e cts  will  b e  a d vis e d t o  a v oi d t h e f oll o wi n g f or t h e  d ur ati o n  of t h e st u d y: 
•   F a ci al  pl asti c s ur g er y  or  p er m a n e nt f a ci al i m pl a nts ( e. g.,  p ol y m et h yl m et h a cr yl at e, sili c o n e, 
p ol yt etr afl u or o et h yl e n e ,  p ol y a cr yl a mi d e, lifti n g t hr e a ds)  a n y w h er e i n t h e f a c e  or  n e c k 
•   S e mi -p er m a n e nt  d er m al fill er tr e at m e nt ( e. g.,  c al ci u m  h y dr o x yl a p atit e,  p ol y - L-l a cti c  a ci d) i n t h e 
l o w er f a c e ( b el o w t h e  orbit al ri m)  
•   Ot h er  h y al ur o ni c  a ci d  fill er  m at eri als  or  c oll a g e n-b as e d fill er  m at eri als  b el o w t h e  or bit al ri m  

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•   F a ci al tiss u e  a u g m e nt ati o n  wit h f at i nj e cti o ns,  b ot uli n u m t o xi n i nj e cti o ns i n t h e l o w er f a c e 
( b el o w t h e  or bit al ri m),  m es ot h er a p y,  or  c os m eti c  pr o c e d ur es i n t h e f a c e  or  n e c k ( e. g., f a c e-lift, 
l as er,  p h ot o- m o d ul ati o n, i nt e ns e  p uls e d li g ht, r a di o fr e q u e n c y,  der m a br asi o n,  m o d er at e  or  gr e at er 
d e pt h  c h e mi c al  p e el,  mi cr o n e e dli n g,  or  ot h er  a bl ati v e  pr o c e d ur es) 
•   Us e  of  a n y li p  pl u m pi n g  pr o d u cts  or  d e vi c es 
•   Us e  of  a n y  O T C  or  pr es cri pti o n,  or al  or t o pi c al,  a nti- wri n kl e  pr o d u cts f or t h e li ps  or  ar o u n d t h e 
m o ut h ( S u bj e cts  w h o  h a v e  b e e n  o n  a r e gi m e n  of s u c h  pr o d u cts f or  at l e ast  9 0  d a ys  ar e  eli gi bl e f or 
t h e st u d y  a n d  m ust  c o nti n u e t h eir r e gi m e n t hr o u g h o ut t h e st u d y.) 
7. 4. 7. 3   
C o n c o mit a nt  M e di c ati o ns  a n d  T r e at m e nts  All o w e d  D u ri n g t h e  St u d y  
P er mitt e d  m e di c ati o ns/tr e at m e nts i n cl u d e  a n y  c o n c o mit a nt  m e di c ati o n/tr e at m e nt  n ot list e d i n t h e 
e x cl usi o n  crit eri a ( S e cti o n  7. 3. 2 ). 
7. 4. 8   Ass ess m e nt  of  C o m pli a n c e  
A d mi nistr ati o n  of t h e  st u d y  d e vi c e  b y t h e i n v esti g at or is  d o c u m e nt e d  o n t h e  C R F. 
7. 5   
St u d y  S c h e d ul e  
T h e  visit- b y - visit s c h e d ul e  of st u d y  a cti viti es is  pr o vi d e d i n S e cti o n  2 . T h e ti mi n g  of  e a c h  visit is r el ati v e 
t o  D a y  1,  w hi c h is  d efi n e d  as t h e  d a y t h e s u bj e ct is r a n d o mi z e d  a n d first tr e at e d. 
All  visits s h o ul d  b e  p erf or m e d  wit hi n t h e  wi n d o ws s p e cifi e d  o n t h e  s c h e d ul e  of st u d y  a cti viti es .  E v er y 
att e m pt s h o ul d  b e  m a d e t o  h a v e  e a c h s u bj e ct  att e n d  e a c h  visit  as s c h e d ul e d. If  a s u bj e ct is  u n a bl e t o 
att e n d  a  visit  wit hi n t h e s p e cifi e d  wi n d o w t h e  visit s h o ul d  b e s c h e d ul e d  as  cl os el y  as  p ossi bl e t o t h e 
a p pli c a bl e  wi n d o w. 
7. 6   
St u d y  P r o c e d u r es  
T h e s c h e d ul e  of st u d y  a cti viti es  s u m m ari z es t h e st u d y  pr o c e d ur es t o  b e  p erf or m e d  at  e a c h  visit. 
I n di vi d u al st u d y  pr o c e d ur es  ar e  d es cri b e d  b el o w. 
All  cli ni c al  ass ess m e nts ( L F G S,  P O L , i G AI, li p f u n cti o n, li p s e ns ati o n, li p t e xt ur e, li p fir m n ess, li p 
s y m m etr y,  a n d li p  m o v e m e nt/f u n cti o n e v al u ati o ns)  m ust  b e  c o n d u ct e d  b y  q u alifi e d i n v esti g at ors list e d 
o n t h e  F or m  F D A  1 5 7 2  w h o  h a v e  b e e n  d el e g at e d t h es e t as ks  b y t h e  pri n ci p al i n v esti g at or ( PI).  T h e  PI 
m a y  d el e g at e t his t as k   o nl y t o  p h ysi ci a ns,  p h ysi ci a n  assist a nts,  or  n urs e  pr a ctiti o n ers  w h o  h a ve 
d o c u m e nt e d tr ai ni n g f or t his  pr ot o c ol  a n d  p ast  e x p eri e n c e  c o n d u cti n g t h e  ass ess m e nt.  
T h e  L F G S,  P O L, i G AI , li p f u n cti o n, li p s e ns ati o n, li p t e xt ur e, li p fir m n ess, li p s y m m etr y,  a n d li p 
m o v e m e nt/f u n cti o n  e v al u ati o ns  ar e t o  b e  p erf or m e d  b y  a r es e ar c h t e a m  m e m b er  w h o  d o es  n ot  p arti ci p at e 
i n tr e at m e nt  a n d  w h o is  bli n d e d t o t h e tr e at m e nt  assi g n m e nt ( bli n d e d  E v al u ati n g I n v esti g at or). 
T o  mi ni mi z e  v ari a bilit y  of  e v al u ati o ns, t h e s a m e i n v esti g at or/s u b -i n v esti g at or s h o ul d  p erf or m t h es e 
ass ess m e nts f or  a n y  gi v e n s u bj e ct  a n d  a nti ci p at e  e v al u ati n g t h e s u bj e ct  at  e a c h  visit, t o t h e  e xt e nt 
p ossi bl e. 
7. 6. 1   St u d y  R ol es  
E a c h sit e  will  d esi g n at e  at l e ast  o n e   Tr e ati n g I n v esti g at or  a n d  at l e ast  o n e  bli n d e d  E v al u ati n g 
I n v esti g at or. I n  a d diti o n,  o n e  or  m or e  m e m b ers  of t h e st u d y sit e st aff  m a y  b e  d esi g n at e d  as  u n bli n d e d f or 
t h e  p ur p os es  of  assisti n g i n t h e  m a n a g e m e nt  of st u d y  d e vi c e us e.  A n y st u d y st aff  d esi g n at e d  as 
u n bli n d e d s h o ul d  h a v e  n o  dir e ct  c o nt a ct  wit h s u bj e cts  a n d  m a y  n ot  p erf or m  a n y s u bj e ct  e v al u ati o ns, 
ass ess m e nts  or  m e as ur e m e nts (i n cl u di n g  vit al si g ns,  q u esti o n n air es,  et c. ).  D esi g n ati o n  of  u n bli n d e d 
st u d y st aff  will  b e r e c or d e d i n t h e  D el e g ati o n  of  A ut h oriti es  L o g f or m.  

P R O  2 0 1 8 -0 2  
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T h e  Tr e ati n g I n v esti g at or  will  b e r es p o nsi bl e f or  c o n d u cti n g t h e i nj e cti o ns,  e ns uri n g t h at t h e  c orr e ct 
r a n do mi z e d st u d y  d e vi c e is  a d mi nist er e d i n  a c c or d a n c e  wit h t h e  pr ot o c ol  a n d  ot h er st u d y i nstr u cti o ns. 
T h e  T r e ati n g I n v esti g at or will  ass ess s u bj e cts  a n d  d et er mi n e t h e  n e e d f or t o u c h - u p i nj e cti o ns.  A n y  A Es 
br o u g ht t o t h e  att e nti o n  of t h e  Tr e ati n g I n v esti g at or  will  b e f or w ar d e d t o t h e  bli n d e d  E v al u ati n g 
I n v esti g at or f or fi n al  a dj u di c ati o n  a n d  d o c u m e nt ati o n. 
T h e  bli n d e d  E v al u ati n g  I n v esti g at or  will  b e r es p o nsi bl e f or  assi g ni n g  gr a d es f or t h e  v ari o us  p ar a m et ers 
( L F G S,  P O L, i G AI, li p f u n cti o n, li p s e ns ati o n et c. ). T h e  bli n d e d  E v al u ati n g I n v esti g at or  w ill  b e 
r es p o nsi bl e f or r e c or di n g  A Es  a n d  d et er mi ni n g t h eir s e v erit y  a n d r el ati o ns hi p t o t h e st u d y  d e vi c e  or t h e 
i nj e cti o n  pr o c e d ur e. 
7. 6. 2   St u d y I niti ati o n  
T h e i n v esti g ati o n al st aff  m a y  n ot  e nr oll  a n y s u bj e cts  pri or t o  c o m pl eti o n  of  a sit e i niti ati o n  visit.  T his 
visit  will i n cl u d e,  b ut is  n ot li mit e d t o,  a n i n v e nt or y  of st u d y s u p pli es (if  pr es e nt)  a n d  a  d et ail e d r e vi e w 
of t h e  pr ot o c ol,  C R Fs,  a n d t h e i n v esti g at or’s r es p o nsi biliti es  as  o utli n e d  o n  F or m  F D A  1 5 7 2. 
7. 6. 3   W ritt e n I nf o r m e d  C o ns e nt  
T h e st u d y  p ers o n n el  will r e vi e w t h e I C F  wit h  e a c h s u bj e ct  a n d  gi v e t h e s u bj e ct  a n  o p p ort u nit y t o  h a v e  all 
q u esti o ns  a ns w er e d  b ef or e  pr o c e e di n g  wit h  a n y st u d y  pr o c e d ur es.  A  c o p y  of t h e si g n e d I C F  will  b e 
gi v e n t o  e v er y s u bj e ct  a n d t h e  ori gi n al  will   b e  m ai nt ai n e d  wit h t h e s u bj e ct’s r e c or ds. 
7. 6. 4   Si g nifi c a nt  M e di c al  Hist o r y / D e m o g r a p hi c I nf o r m ati o n 
M e di c al  hist or y  a n d  d e m o gr a p hi c i nf or m ati o n  will  b e  o bt ai n e d  at  Visit  1/ D a y  1.  T h e  m e di c al  hist or y  will 
i n cl u d e  a  c o m pl et e r e vi e w  of  all  c urr e nt  dis e as es  a n d t h eir r es p e cti v e  d ur ati o ns  a n d tr e at m e nts. 
D e m o gr a p hi c i nf or m ati o n  will i n cl u d e  d at e  of  birt h, s e x  at  birt h , r a c e,  et h ni cit y,  a n d  Fit z p atri c k s ki n t y p e 
(T a bl e   1).  
 
T a bl e  1.  
Fit z p at ri c k  Cl assifi c ati o n  S c al e  
S ki n  T y p e   
S ki n  C ol o r  
C h a r a ct e risti cs  
I 
W hit e;  v er y f air; r e d  or  bl o n d  h air;  bl u e  e y es; fr e c kl e s   
Al w a ys  b ur ns,  n e v er t a ns  
II 
W hit e; f air; r e d  or  bl o n d  h air;  bl u e,  h a z el,  or  gr e e n  
e y es  
Us u all y  b ur ns, t a ns  wit h  diffi c ult y  
III 
Cr e a m  w hit e; f air  wit h  a n y  e y e  or  h air  c ol or;  v er y 
c o m m o n  
S o m eti m es  mil d  b ur n,  gr a d u all y t a ns  
I V 
Br o w n; t y pi c al  M e dit err a n e a n  C a u c asi a n  s ki n   
R ar el y  b ur ns, t a ns  wit h  e as e  
V  
D ar k  Br o w n;  mi d -e ast er n s ki n t y p es  
v er y r ar el y  b ur ns, t a ns  v er y  e a sil y  
VI  
Bl a c k  
N e v er  b ur ns, t a ns  v er y  e a sil y  
 
7. 6. 5   P h ysi c al  E x a mi n ati o n (I n cl u di n g  Vit al  Si g ns)  
A n  a b br e vi at e d  p h ysi c al  e x a mi n ati o n i n cl u di n g  h ei g ht,  w ei g ht,  a n d  vit al si g ns  will  b e r e c or d e d.  Vit al 
si g ns  will i n cl u d e sitti n g  bl o o d  pr ess ur e, t e m p er at ur e,  h e art r at e,  a n d r es pir at or y r at e.  T his  p h ysi c al 
e x a mi n ati o n  will  b e  p erf or m e d  at  Visit  1/ D a y  1 t o  d et er mi n e t h at t h e s u bj e ct is  h e alt h y  e n o u g h t o 
p arti ci p at e i n t h e st u d y.  

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7. 6. 6   Visi o n  E v al u ati o ns  
S u bj e cts  will  b e  ass ess e d  wit h  S n el l e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  a n d  o c ul ar  m otilit y  b y 
a tr ai n e d  e v al u at or.   T h es e  ass ess m e nts  will  b e  p erf or m e d  pri or t o  a n y tr e at m e nt.   T h es e  ass ess m e nts  will 
als o  b e r e p e at e d  3 0  mi n ut es f oll o wi n g  a n y tr e at m e nt  a n d  at  all f oll o w - u p  visits. 
7. 6. 7   P ri o r  a n d  C o n c o mit a nt  M e di c ati o n/ T r e at m e nt  R e vi e w  
Pri or  m e di c ati o ns/tr e at m e nts, i n cl u di n g t h e  n e c ess ar y  w as h o ut ti m es,  a n d  c o n c o mit a nt  m e di c ati o ns 
(i n cl u di n g  pr es cri pti o n,  O T C,  a n d  di et ar y s u p pl e m e nts t a k e n  a n d  ot h er tr e at m e nts  a n d  c os m eti c  pr o d u cts 
us e d  b y t h e s u bj e ct ) will  b e r e vi e w e d  wit h t h e s u bj e ct.  A r e c or d  of  pri or  m e di c ati o ns/tr e at m e nts t a k e n  or 
us e d  b y t h e s u bj e ct  wit hi n  6  m o nt hs  b ef or e si g ni n g t h e I C F  a n d  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts  will 
b e  o bt ai n e d  at  Visit  1/ D a y  1.  C o n c o mit a nt  m e di c at i o ns  or tr e at m e nts  will  b e r e vi e w e d  wit h t h e s u bj e ct  at 
e a c h st u d y  visit  a n d t el e p h o n e  c o nt a ct . 
7. 6. 8   U ri n e  P r e g n a n c y  T est  a n d  A c c e pt a bl e  C o nt r a c e pti v e  M et h o ds  
W o m e n  of  c hil d b e ari n g  p ot e nti al, i n  a d diti o n t o  h a vi n g  a  n e g ati v e  uri n e  pr e g n a n c y t est  at  Visit  1/  D a y  1, 
m ust  b e  willi n g t o  us e  a n  a c c e pt a bl e f or m  of  birt h  c o ntr ol  d uri n g t h e st u d y.  T h e f oll o wi n g  ar e  c o nsi d er e d 
a c c e pt a bl e  m et h o ds  of  birt h  c o ntr ol f or t h e  p ur p os e  of t his st u d y:  or al  c o ntr a c e pti v es,  c o ntr a c e pti v e 
p at c h es,  c o ntr a c e pti v e i m pl a nt,  v a gi n al  c o ntr a c e pti v e,  d o u bl e  b arri er  m et h o ds ( e. g.,  c o n d o m  a n d 
s p er mi ci d e),  c o ntr a c e pti v e i nj e cti o n ( D e p o- Pr o v er a ® ), I U D,  h or m o n al I U D ( Mir e n a® ),  a n d  a bsti n e n c e 
wit h  a  d o c u m e nt e d s e c o n d  a c c e pt a bl e  m et h o d  of  birt h  c o ntr ol if t h e s u bj e ct  b e c o m es s e x u all y  a cti v e. 
S u bj e cts  e nt eri n g t h e st u d y  w h o  ar e  o n  h or m o n al  c o ntr a c e pti v es  m ust  h a v e  b e e n  o n t h e  m et h o d f or  at 
l e ast  9 0  d a ys  pri or t o t h e st u d y  a n d  c o nti n u e t h e  m et h o d f or t h e  d ur ati o n  of t h e st u d y.  S u bj e cts  w h o  h a d 
us e d  h or m o n al  c o ntr a c e pti o n  a n d st o p p e d  m ust  h a v e st o p p e d  n o l ess t h a n  9 0  d a ys  pri or t o  Visit  1/ D a y  1. 
7. 6. 9   Li p  F ull n ess  G r a di n g  S c al e   
T h e  L F G S  is  a  5- p oi nt  p h ot o n u m eri c r ati n g s c al e t h at  w as  d e v el o p e d t o  o bj e cti v el y  q u a ntif y t h e  3-
di m e nsi o n al f ull n ess  of t h e li p.  T h e s c al e r ati n gs  ar e  0 f or  v er y t hi n,  1 f or t hi n,  2 f or  m o d er at el y t hi c k,  3 
f or t hi c k,  a n d  4 f or f ull ( C arr ut h ers  et  al,  2 0 0 8). P h ot o gr a p hs ill ustr ati n g t h e r ati n gs  will  b e  pr o vi d e d t o 
e a c h sit e.  T h e  ass ess m e nt s  of  o v er all li p f ull n ess  c o nsi d eri n g  b ot h li ps t o g et h er, f ull n ess  of t h e  u p p er li p 
a n d f ull n ess  of t h e l o w er li p  will  b e  p erf or m e d  b y t h e  Tr e ati n g I n v esti g at or  at  Visit  1  a n d  b y t h e  bli n d e d 
E v al u ati n g I n v esti g at or  at  e a c h st u d y  visit . 
7. 6. 1 0   P e ri o r al  Li n es  at  R est  S e v e rit y  S c al e  
T h e  P O L is  a  4 - p oi nt r ati n g s c al e  w hi c h  c orr es p o n ds t o t h e  m ost s e v er e  p eri or al li n e  attri b ut e  w h e n t h e 
s u bj e ct’s  m o ut h is  at r est  wit h t h e f oll o wi n g r ati n gs  ( C o h e n  et  al,  2 0 1 4):  
0.   N o n e  =  a  m o ut h  wit h  n o  p eri or al li n es 
1.   Mil d  =  a  m o ut h  wit h  a f e w s h all o w  p eri or al li n es  
2.   M o d er at e  =  a  m o ut h  wit h s o m e  m o d er at e li n es  
3.   S e v er e  =  a  m o ut h  wit h  m a n y  d e e p li n es  or  cr e vi c es  
T h e  ass ess m e nt s  of o v er all  p eri or al li n es  at r est s e v erit y  c o nsi d eri n g  b ot h li ps t o g et h er,  p eri or al li n es  at 
r est s e v erit y  of t h e  u p p er li p  a n d  p eri or al li n es  at r est s e v erit y  of t h e l o w er li p  will  b e  p erf or m e d  b y t h e 
Tr e ati n g I n v esti g at or  at  Visit  1  a n d  b y t h e  bli n d e d  E v al u ati n g I n v esti g at or  at  e a c h st u d y  visit.  
7. 6. 1 1   R e vi e w  I n cl usi o n/ E x cl usi o n  C rit e ri a  
T h e i n cl usi o n  a n d  e x cl usi o n  crit eri a  will  b e r e vi e w e d  b y t h e i n v esti g at or  or  q u alifi e d  d esi g n e e t o  e ns ur e 
t h at t h e s u bj e ct  q u alifi es f or t h e st u d y. 

P R O  2 0 1 8 -0 2  
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0 2 O C T 2 0 1 8  
2 7  
 
7. 6. 1 2   E v al u ati o n f o r  T o u c h -u p  
T h e  Tr e ati n g  I n v esti g at or  will  e v al u at e t h e s u bj e ct  at  Visit 2  a n d  d et er mi n e i n  c o ns ult ati o n  wit h t h e 
s u bj e ct t h e  n e e d f or  a t o u c h- u p tr e at m e nt.   
7. 6. 1 3   P ati e nt  Gl o b al  A est h eti c I m p r o v e m e nt ( p G AI)  S c o r e  
T h e  p G AI s c or e is  a  5 -p oi nt s c al e  wit h t h e f oll o wi n g  c at e g ori es:  
1.  W ors e  –  t h e  a p p e ar a n c e is  w ors e t h a n t h e ori gi n al  c o n diti o n.  
2.  N o  c h a n g e  –  t h e  a p p e ar a n c e is t h e s a m e  as t h e  ori gi n al  c o n diti o n. 
3.   I m pr o v e d  –  o b vi o us i m pr o v e m e nt i n  a p p e ar a n c e fr o m t h e i niti al  c o n diti o n.  A t o u c h- u p  mi g ht 
f urt h er i m pr o v e t h e r es ult. 
4.    M u c h i m pr o v e d  –  m ar k e d i m pr o v e m e nt i n  a p p e ar a n c e fr o m t h e i niti al  c o n diti o n,  b ut  n ot 
c o m pl et el y  o pti m al.  A t o u c h - u p  mi g ht sli g htl y i m pr o v e t h e r es ult 
5.    V er y  m u c h i m pr o v e d  –  o pti m al  c os m eti c r es ult.  
T h e  p G AI s c or e  will  b e r e c or d e d  b y t h e  bli n d e d  E v al u ati n g I n v esti g at or  at  Visit s  2,  3,  4,  a n d  5.  S u bj e cts 
will  b e  as k e d t h e  q u esti o n  “ H o w  w o ul d  y o u r at e i m pr o v e m e nt i n  y o ur  a p p e ar a n c e  c o m p ar e d t o  y o ur 
i niti al  c o n diti o n  usi n g t h e s c al e  b el o w ? ” 
7. 6. 1 4   I n v esti g at o r  Gl o b al  A est h eti c I m p r o v e m e nt (i G AI)  S c o r e  
T h e i G AI s c or e is  a  5 -p oi nt s c al e  wit h t h e f oll o wi n g  c at e g ori es:  
1.  W ors e  – t h e  a p p e ar a n c e is  w ors e t h a n t h e  ori gi n al  c o n diti o n. 
2.  N o  c h a n g e  –  t h e  a p p e ar a n c e is t h e s a m e  as t h e  ori gi n al  c o n diti o n. 
3.   I m pr o v e d  –  o b vi o us i m pr o v e m e nt i n  a p p e ar a n c e fr o m t h e i niti al  c o n diti o n.  A t o u c h- u p  mi g ht 
f urt h er i m pr o v e t h e r esult. 
4.    M u c h i m pr o v e d  –  m ar k e d i m pr o v e m e nt i n  a p p e ar a n c e fr o m t h e i niti al  c o n diti o n,  b ut  n ot 
c o m pl et el y  o pti m al.  A t o u c h - u p  mi g ht sli g htl y i m pr o v e t h e r es ult. 
5.    V er y  m u c h i m pr o v e d  –  o pti m al  c os m eti c r es ult.  
T h e i G AI s c or e  will  b e  ass ess e d  b y t h e  Bli n d e d  E v al u ati n g I n v esti g at or  at  Visits  2,  3,  4,  a n d  5.  
7. 6. 1 5   I n v esti g at o r  E as e  of  Us e  Ass ess m e nt  
T h e  Tr e ati n g  I n v esti g at or  will  ass ess  o v er all  e as e  of  us e  b y t h e  d e vi c e  b y  cir cli n g t h e  a p pr o pri at e  n u m b er 
o n t h e  n u m eri c al  rati n g  s c al e fr o m  0  b ei n g  n ot  e as y t o  1 0  b ei n g m ost  e as y  at  Visit  1/ D a y   1 a n d f or 
s u bj e cts  w h o  h a v e t o u c h- u p tr e at m e nt  at  Visit  2/ M o nt h  1. 
7. 6. 1 6   S w elli n g  Ass ess m e nt  
S w elli n g  will  ass ess e d  b y t h e  Bli n d e d  E v al u ati n g I n v esti g at or  at  Visits  2,  3,  4,  a n d  5  usi n g t h e  5- p oi nt 
s c al e  wit h t h e  c at e g ori es t h at f oll o w . T h e   bli n d e d  E v al u ati n g I n v esti g at or s h o ul d  e x a mi n e  b ot h  u p p er 
a n d l o w er li p si m ult a n e o usl y  a n d r e c all t h e  d e gr e e  of  a u g m e nt ati o n  ori gi n all y  pr o vi d e d f or  c o m p aris o n. 
T h e s u bj e ct s h o ul d  n ot  b e s p e cifi c all y  q u esti o n e d r e g ar di n g s w elli n g  b ut if t h e  s u bj e ct s po nt a n e o usl y 
r e p orts it, s u c h i nf or m ati o n  c a n  b e  us e d t o  assist i n s el e cti o n  of  a  gr a d e f or s w elli n g. 
0:  N o n e  –  N o s w elli n g  n oti c e a bl e.  Li ps  a p p e ar t h e s a m e  as  w h e n  ori gi n all y  a u g m e nt e d.  A n y li p 
e nl ar g e m e nt is  d u e t o t h e i m pl a nt e d  pr o d u ct  o nl y. 
1:  Mi ni m al  –  Sli g ht  e nl ar g e m e nt  of  eit h er li p  b e y o n d t h e  ori gi n all y  pr o vi d e d  a u g m e nt ati o n.  M a y 
or  m a y  n ot  b e  n oti c e a bl e t o t h e s u bj e ct  b ut is  n oti c e a bl e  t o t h e i n v esti g at or. 

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2:  Mil d  –  S o m e  e nl ar g e m e nt  of  eit h er li p  b e y o n d t h e  ori gi n al  a u g m e nt ati o n t h at is  e asil y 
n oti c e a bl e  t o t h e s u bj e ct,  b ut t h e li ps  d o  n ot  a p p e ar  a b n or m all y l ar g e. 
3:  M o d er at e  –  Si g nifi c a nt  e nl ar g e m e nt  of  eit h er li p  b e y o n d t h e  ori gi n al  a u g m e nt ati o n.  Eit h er li p 
a p p e ars  a b n or m all y l ar g e.  
4:  S e v er e  –  A n y  d e gr e e  of s w elli n g t h at s u bst a nti all y i nt erf er es  wit h li p f u n cti o n s u c h  as  c h a n g es 
i n s p e e c h  or  diffi c ult y  e ati n g  or  dri n ki n g. 
 
7. 6. 1 7   Li p  F u n cti o n  E v al u ati o n  
S u bj e cts’ li p f u n cti o n  will  b e  ass ess e d  b y t h e  Bli n d e d  E v al u ati n g  I n v esti g at or b y t h eir  a b ilit y t o si p 
li q ui d t hr o u g h  a str a w pri or t o  a n y i nj e cti o ns  a n d  at  all f oll o w - u p  visits. 
7. 6. 1 8   Li p  S e ns ati o n  E v al u ati o n 
S u bj e cts’ li p s e ns ati o n  will  b e  ass ess e d  b y t h e  Bli n d e d  E v al u ati n g I n v esti g at or  a n d  t est e d  vi a:  1) t h e 
m o n ofil a m e nt t est (i. e.,  a s u bj e ct’s  a b ilit y t o f e el t h e s e ns ati o n  of  a  0. 4 G  m o n ofil a m e nt  at t hr e e  p oi nts  o n 
t h e  u p p er li p  a n d t hr e e  p oi nts  o n t h e l o w er li p  a n d  2) t h e  c ott o n  wis p t est (i. e.,  a s u bj e ct’s  a bilit y t o f e el 
t h e s e ns ati o n  of  a  c ott o n  wis p  at t hr e e  p oi nts  o n t h e  u p p er li p  a n d t hr e e  p oi nts  o n t h e l o w er li p) pri or t o 
a n y i nj e cti o ns  a n d  at  all f oll o w - u p  visits. 
7. 6. 1 9   Li p  T e xt u r e  E v al u ati o n 
S u bj e cts’ li p t e xt ur e  will  b e  ass ess e d  b y t h e  Bli n d e d  E v al u ati n g I n v esti g at or  as  n or m al  or  a b n or m al  pri or 
t o  a n y i nj e cti o n  a n d  at  all f oll o w- u p  visits. 
T a bl e  2.  
Li p  T e xt u r e  S c o ri n g  C rit e ri a  
N or m al   
 
A b n or m al   
 
 
Mil d  
M o d er at e   
S e v er e  
T e xt ur e  of t h e li p is 
e v e n  wit h o ut  visi bl e 
u n d ul ati o ns  or 
e x c essi v e  c o ars e n ess 
b e y o n d t h at  e x p e ct e d 
f or st at e d  a g e 
T h e li p s h o ws  a si n gl e 
ar e a  of t e xt ur al 
irr e g ul arit y ( a s m all 
p a p ul e,  ar e a  of  e x c ess 
s m o ot h n ess, f o c al 
a bs e n c e  of 
p er p e n di c ul ar li n es) 
c a n   b e  vis u ali z e d  o nl y 
wit h  cl os e i ns p e cti o n  
T h e li p s h o ws  m or e 
t h a n  o n e  ar e a  of 
t e xt ur al irr e g ul arit y ( a 
s m all  p a p ul e,  ar e a  of 
e x c ess s m o ot h n ess, 
f o c al  a bs e n c e  of 
p er p e n di c ul ar li n es) 
c a n   b e  vis u ali z e d  o nl y 
wit h  cl os e i ns p e cti o n. 
Or  
T h e li p s h o ws  o n e 
ar e a  of t e xt ur al 
irr e g ul arit y (l ess t h a n 
¼  of t h e li p  ar e a)  at  a 
c o n v ers ati o n al 
dist a n c e.  
T h e li p  s h o ws t w o  or 
m or e  ar e as  of  t e xt ur al 
irr e g ul arit y ( a s m all 
p a p ul e,  ar e a  of  e x c ess 
s m o ot h n ess, f o c al 
a bs e n c e  of 
p er p e n di c ul ar li n es) 
c a n  b e  vis u ali z e d  at  a 
c o n v ers ati o n al 
dist a n c e.  
Or  
T h e li p s h o ws  o n e 
ar e a  of t e xt ur al 
irr e g ul arit y ( m or e 
t h a n  ¼ of t h e li p  ar e a) 
at  c o n v ers ati o n al 
dist a n c e  
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
2 9  
 
7. 6. 2 0   Li p  Fi r m n ess  E v al u ati o n 
S u bj e cts’ li p fir m n ess  will  b e  ass ess e d  b y t h e  Bli n d e d  E v al u ati n g I n v esti g at or  as  n or m al  or  a b n or m al 
pri or t o  a n y i nj e cti o n  a n d  at  all f oll o w - u p  visits. 
T a bl e  3.  
Li p  Fi r m n ess  S c o ri n g  C rit e ri a  
N or m al   
 
A b n or m al   
 
 
Mil d  
M o d er at e   
S e v er e  
Li p is s u p pl e  w h e n 
c o m pr ess e d l at er all y 
a n d s urf a c e  dist ort e d  
r e a dil y  wit h  mi ni m al 
pr ess ur e.   Pr ess ur e 
wit h  a  n arr o w 
di a m et er i nstr u m e nt 
( c ott o n-ti p p e d 
a p pli c at or, t o ot h pi c k, 
et c)  c a us e s a f o c al 
d e pr essi o n i n t h e 
s urf a c e  of t h e li p.  
U p o n  p al p ati o n, li p  is 
a bs e nt  of  a b n or m al 
str u ct ur es s u c h  as 
s c ars  or l u m ps; 
n or m al  pr o d u ct f e el 
wit h o ut  b ei n g  visi bl e. 
Li p is sli g htl y fir m 
wit h l at er al 
c o m pr essi o n  or 
r e q uir e d sli g htl y 
gr e at er t h a n  n or m al 
pr ess ur e t o  dist ort t h e 
s urf a c e.   U p o n 
p al p ati o n,  a n 
a b n or m al str u ct ur e 
s u c h  as  a s c ar  or l u m p 
is f elt,  b ut is  n ot 
visi bl e.  
Li p is fir m  wit h l at er al 
c o m pr essi o n  or 
r e q uir es disti n ctl y 
gr e at er t h a n  n or m al 
pr ess ur e t o  dist ort t h e 
s urf a c e  or  pr ess ur e 
wit h  a  n a rr o w 
di a m et er i nstr u m e nt 
( c ott o n-ti p p e d 
a p pli c at or  or 
t o ot h pi c k)  c a us es a 
br o a d er  d e pr essi o n i n 
t h e s urf a c e  of t h e li p.  
U p o n  p al p ati o n,  a n 
a b n or m al str u ct ur e 
s u c h  as  a s c ar  or l u m p 
is f elt  a n d is visi bl e.  
Li p is  v er y fir m  wit h 
l at er al  c o m pr essi o n  or 
r e q uir es si g nifi c a ntl y 
gr e at er t h a n  n or m al 
pr ess ur e t o  dist ort  t h e 
s urf a c e.   U p o n 
p al pit ati o n,  a n 
a b n or m al str u ct ur e 
s u c h  as  a s c ar  or l u m p 
is f elt  a n d is  vis u all y 
distr a cti n g.  
 
7. 6. 2 1   Li p  S y m m et r y  E v al u ati o n 
S u bj e cts’ li p s y m m etr y   will  b e  ass ess e d  b y t h e  Bli n d e d  E v al u ati n g I n v esti g at or  as  n or m al  or  a b n or m al 
pri or t o  a n y i nj e cti o n  a n d  at  all f oll o w - u p  visits. 
T a bl e  4.  
Li p  S y m m et r y  S c o ri n g  C rit e ri a  
N or m al   
 
A b n or m al   
 
 
Mil d  
M o d er at e   
S e v er e  
O n e si d e  of t h e li p 
b al a n c e d  or  mirr or e d 
t h e  ot h er si d e 
O n e si d e  of t h e li p 
s h o ws  a  1  m m  or l ess 
diff er e n c e i n  h ei g ht  or 
a  1  m m  or l ess 
diff er e n c e i n t h e 
l e n gt h  of t h e 
v er mili o n  at r e p os e. 
O n e si d e  of t h e li p 
s h o ws  a  1. 1  m m t o  2 
m m  diff er e n c e i n 
h ei g ht  or  a  1. 1 t o  2 
m m  diff er e n c e i n t h e 
l e n gt h  of t h e 
v er mili o n  at r e p os e    
O n e si d e  of t h e li p 
s h o ws  a  gr e at er t h a n  2 
m m  diff er e n c e i n t h e 
h ei g ht  or  a  gr e at er 
t h a n  2  m m  diff er e n c e 
i n t h e l e n gt h  of t h e 
v er mili o n  at r e p os e. 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
3 0  
 
7. 6. 2 2   Li p  M o v e m e nt/ F u n cti o n  
Li p  m o v e m e nt/f u n cti o n  will  b e  e v al u at e d  b y t h e  Bli n d e d  E v al u ati n g  I n v esti g at or  as  n or m al  or  a b n or m al 
pri or t o  a n y i nj e cti o n  a n d  at  all f oll o w - u p  visits  as t h e s u bj e ct’s  a bilit y t o  p u c k er li ps,  bl o wi n g  a n d 
pr o n u n ci ati o n  of  w or ds t h at  b e gi n  wit h t h e l ett er  “ W ” s u c h  as  w at er,  w or k,  w e e k  a n d  wi n d.  
7. 6. 2 3   S u bj e ct  S atisf a cti o n  wit h  Li ps  ( Vis u al  A n al o g  S c al e) 
S u bj e cts  will  b e  as k e d t o  ass ess t h eir  o v er all s atisf a cti o n  wit h t h eir li ps  at  Visits  2,  3,  4 ,  a n d  5  usi n g  a 
1 0 0- m m  V A S s c al e fr o m  0  =  V er y  U ns atisfi e d t o  1 0 0  =  V er y  S atisfi e d ( Fi g ur e  1 ).   
Fi g u r e   1.    
Vis u al  A n al o g  S c al e f o r  S u bj e ct  S atisf a cti o n 
 
   
   
  V er y      
   
   
   
   
   
   
 V er y   
   
          U ns atisfi e d    
   
   
   
   
   
          S atisfi e d  
7. 6. 2 4   S u bj e ct  Di a r y  C a r d  
A  di ar y  c ar d  will   b e  dis p e ns e d t o  e a c h  e nr oll e d s u bj e ct  at  Visit  1/ D a y  1.  T h e s u bj e ct  will  b e i nstr u ct e d t o 
c o m pl et e t h e  di ar y  c ar d s t o r e c or d  a n y  A Es  e x p eri e n c e d  d uri n g t h e 2  w e e ks  aft er r e c ei vi n g  t h e i niti al 
tr e at m e nt  a n d t h e t o u c h  u p tr e at m e nt.  T h e  di ar y  c ar ds will  b e  c oll e ct e d  at  Visit  2/ M o nt h  1  a n d  Visit 
3/ M o nt h  2 if t o u c h  u p tr e at m e nt  w as  gi v e n.  A  n e w  di ar y  c ar d  will  b e  dis p e ns e d  at  Visit  2/ M o nt h  1  if 
t o u c h  u p tr e at m e nt is  gi v e n. 
7. 6. 2 5   A d v e rs e  E v e nts   a n d S e ri o us  A d v e rs e  E v e nts  Ass ess m e nt  
S e e  S e cti o n  7. 9  f or i nstr u cti o ns  o n t h e  ass ess m e nt  a n d r e p orti n g  of  A Es  a n d  S A Es  a n d  S e cti o n 7. 9. 7  f or 
i nstr u cti o ns  o n r e p orti n g  S A Es t o t h e  S p o ns or  or  d esi g n e e. 
7. 6. 2 6   T r e at m e nt  Q u esti o n  
At  Visit  5  or  e arl y t er mi n ati o n, s u bj e cts  a n d  bli n d e d  e v al u ati n g i n v esti g at ors  will  b e  as k e d t o i d e ntif y 
w hi c h tr e at m e nt t h e y t h o u g ht  h a d  b e e n  a d mi nist er e d . 
7. 7   
Visit -S p e cifi c  P r o c e d u r es  
T h e f oll o wi n g s e cti o ns  o utli n e t h e  pr o c e d ur es r e q uir e d  at  e a c h  visit. 
7. 7. 1   Visit  1/ D a y  1:  B as eli n e  a n d  T r e at m e nt 
•   O bt ai n  writt e n i nf or m e d  c o ns e nt  
•   O bt ai n  m e di c al  hist or y  a n d  d e m o gr a p hi c i nf or m ati o n, i n cl u di n g  Fit z p atri c k s ki n t y p e 
cl assifi c ati o n   
•   P erf or m  a b br e vi at e d  p h ysi c al  e x a mi n ati o n, i n cl u di n g  h ei g ht,  w ei g ht,  a n d  vit al si g ns 
(t e m p er at ur e,  h e art r at e,  bl o o d  pr ess ur e,  a n d r es pir at or y r at e)  
•   Visi o n  E v al u ati o n ( S n ell e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  o c ul ar  m otilit y) 
•   O bt ai n/r e c or d  pri or  a n d  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts   
•   P erf or m  uri n e  pr e g n a n c y t est f or  all  w o m e n  of  c hil d b e ari n g  p ot e nti al  
•   L F G S  ass ess m e nt   
•   P O L  ass ess m e nt  

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
3 1  
 
•   Li p f u n cti o n  e v al u ati o n  pri or t o  tr e at m e nt  a d mi nistr ati o n 
•   Li p s e ns ati o n  e v al u ati o n  pri or t o  tr e at m e nt  a d mi nistr ati o n 
•   Li p t e xt ur e  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n  
•   Li p fir m n ess  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n  
•   Li p s y m m etr y  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n  
•   Li p  m o v e m e nt/f u n cti o n  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n  
•   E v al u at e i n cl usi o n/ e x cl usi o n  crit eri a  
•   R a n d o mi z ati o n  
•   Tr e at m e nt  a d mi nistr ati o n   
•   Visi o n  E v al u ati o n ( S n ell e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  o c ul ar  m otilit y)  3 0 
mi n ut es  aft er tr e at m e nt  
•   I n v esti g at or  E as e  of  Us e  ass ess m e nt  
•   Ass ess  A Es  
•   Dis p e ns e s u bj e ct  di ar y  c ar d   
•   S c h e d ul e  n e xt  visit 
•   C o m pl et e  C R Fs   
7. 7. 2   T el e p h o n e  C o nt a cts  o n  D a y  3  a n d  D a y  1 4 ( ±  2  d a ys) 
•   Ass ess  A Es  
•   Ass ess  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts  
•   C o nfir m  a d h er e n c e t o  pr o hi bit e d tr e at m e nts/ m e di c ati o ns  
7. 7. 3   Visit  2/ D a y  2 8  ( ±  2  d a ys): I nt e ri m  Visit at  M o nt h  1  wit h  P ossi bl e  T o u c h -u p  T r e at m e nt  
•   L F G S  ass ess m e nt s  
•   P O L  ass ess m e nt s 
•   p G AI  ass ess m e nt  
•   i G AI  ass ess m e nt 
•   Li p f u n cti o n  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n if  a p pli c a bl e  
•   Li p s e ns ati o n  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr at i o n if  a p pli c a bl e 
•   Li p t e xt ur e  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n  if  a p pli c a bl e 
•   Li p fir m n ess  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n  if  a p pli c a bl e 
•   Li p s y m m etr y  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n  if  a p pli c a bl e 
•   Li p  m o v e m e nt/f u n cti o n  e v al u ati o n  pri or t o tr e at m e nt  a d mi nistr ati o n if  a p pli c a bl e  
•   Visi o n  E v al u ati o n ( S n ell e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  o c ul ar  m otilit y) 
•   S w elli n g  Ass ess m e nt  
•   S u bj e ct s atisf a cti o n  wit h li ps ( V A S)  

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
3 2  
 
•   Tr e at m e nt  a d mi nistr ati o n if t o u c h - u p is  n e e d e d (at  Tr e ati n g I n v esti g at or ’s  dis cr eti o n) 
•   Visi o n  E v al u ati o n ( S n ell e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  o c ul ar  m otilit y)  3 0 
mi n ut es  aft er tr e at m e nt if  a p pli c a bl e  
•   I n v esti g at or  E as e  of Us e  ass ess m e nt  if  a p pli c a bl e  
•   Ass ess  A Es  
•   Ass ess  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts   
•   C oll e ct s u bj e ct  di ar y  c ar d  
•   Dis p e ns e  n e w s u bj e ct  di ar y  c ar d  if t o u c h  u p tr e at m e nt is  gi v e n   
•   S c h e d ul e  n e xt  visit 
•   C o m pl et e  C R Fs   
7. 7. 4   T el e p h o n e  C o nt a cts  o n  D a y  3 3  a n d  D a y  4 4  ( ±2  d a ys)  f o r  S u bj e cts  wit h  T o u c h-u p  T r e at m e nt  
•   Ass ess  A Es  
•   Ass ess  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts   
•   C o nfir m  a d h er e n c e t o  pr o hi bit e d tr e at m e nts/ m e di c ati o ns   
7. 7. 5   Visit  3/ D a y  5 6 ( ±  4  d a ys)  a n d  Visit  4/ D a y  8 4 ( ±  4  d a ys): I nt e ri m  Visits  at  M o nt h  2  a n d 
M o nt h   3 
•   L F G S  as s ess m e nts  
•   P O L  ass ess m e nt s 
•   p G AI  ass ess m e nt  
•   i G AI  ass ess m e nt 
•   Li p f u n cti o n  e v al u ati o n 
•   Li p s e ns ati o n  e v al u ati o n 
•   Li p t e xt ur e  e v al u ati o n  
•   Li p fir m n ess  e v al u ati o n  
•   Li p s y m m etr y  e v al u ati o n  
•   Li p  m o v e m e nt/f u n cti o n  e v al u ati o n 
•   Visi o n  E v al u ati o n ( S n ell e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  o c ul ar  m otilit y)  
•   Ass ess  A Es  
•   S w elli n g  Ass ess m e nt  
•   Ass ess  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts   
•   S u bj e ct s atisf a cti o n  wit h li ps  ( V A S) 
•   C oll e ct s u bj e ct  di ar y  c ar d  at  Visit  3 if  dis p e ns e d  at  Visit  2  
•   S c h e d ul e  n e xt  visit 
•   C o m pl et e  C R Fs   

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
3 3  
 
7. 7. 6   T el e p h o n e  C o nt a cts  o n  D a y  1 1 2 ( M o nt h  4)  a n d  D a y  1 4 0 ( M o nt h  5)  ± 4  d a ys  
•   Ass ess  A Es  
•   Ass ess  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts  
•   C o nfir m  a d h er e n c e t o  pr o hi bit e d tr e at m e nts/ m e di c ati o ns  
7. 7. 7   Visit  5/ D a y  1 6 8 ( ±  7  d a ys):  M o nt h  6  E n d  of  St u d y  Visit/ E a rl y  T e r mi n ati o n  
•   L F G S  ass ess m e nt s  
•   P O L  ass ess m e nt s 
•   p G AI  ass ess m e nt  
•   i G AI  ass ess m e nt 
•   Li p f u n cti o n  e v al u ati o n 
•   Li p s e ns ati o n  e v al u ati o n 
•   Li p t e xt ur e  e v al u ati o n  
•   Li p fir m n ess  e v al u ati o n  
•   Li p s y m m etr y  e v al u ati o n  
•   Li p  m o v e m e nt/f u n cti o n  e v al u ati o n 
•   Visi o n  E v al u ati o n ( S n ell e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  o c ul ar  m otilit y)  
•   Ass ess  A Es  
•   S w elli n g  Ass ess m e nt  
•   Ass ess  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts   
•   S u bj e ct s atisf a cti o n  wit h li ps  ( V A S) 
•   Tr e at m e nt  q u esti o n  
•   O bt ai n  writt e n  c o ns e nt f or  o p e n- l a b el r etr e at m e nt  pr ot o c ol 
•   C o m pl et e  C R Fs   
All  s u bj e cts  will  b e  e v al u at e d f or r etr e at m e nt  a n d  u n d er g o  c o ns e nt  pr o c e d ur e f or t h e s u bs e q u e nt  o p e n-
l a b el r etr e at m e nt  pr ot o c ol.  
7. 7. 8   U ns c h e d ul e d  Visit  
A n  u ns c h e d ul e d  visit is  all o w e d  at  a n y ti m e if i n t h e i n v esti g at or’s  o pi ni o n it is  w arr a nt e d.  T h e f oll o wi n g 
pr o c e d ur es  m a y  b e  p erf or m e d  at t h e  U ns c h e d ul e d  Visit if r e q uir e d.  
•   L F G S  ass ess m e nt s  
•   P O L  ass ess m e nt s 
•   p G AI  ass ess m e nt  
•   i G AI  ass ess m e nt 
•   Li p f u n cti o n  e v al u ati o n 
•   Li p s e ns ati o n  e v al u ati o n 

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•   Li p t e xt ur e  e v al u ati o n  
•   Li p fir m n ess  e v al u ati o n  
•   Li p s y m m etr y  e v al u ati o n  
•   Li p  m o v e m e nt/f u n cti o n  e v al u ati o n  
•   Visi o n  E v al u ati o n ( S n ell e n  vis u al  a c uit y,  c o nfr o nt ati o n al  vis u al fi el ds,  o c ul ar  m otilit y) 
•   Ass ess  A Es  
•   S w elli n g  Ass ess m e nt  
•   S u bj e ct  S atisf a cti o n  wit h li ps ( V A S)  
•   Ass ess  c o n c o mit a nt  m e di c ati o ns/tr e at m e nts   
•   C o m pl et e  C R Fs   
7. 8   
Effi c a c y  A n al ysis 
7. 8. 1   P ri m a r y  Effi c a c y  E n d p oi nt 
T h e  pri m ar y  effi c a c y  e n d p oi nt is  c h a n g e fr o m  B as eli n e t o  M o nt h  2 i n  o v er all li p f ull n ess  b as e d  o n t h e 
Bli n d e d  E v al u ati n g I n v esti g at or  ass ess m e nt  usi n g t h e  L F G S.  T h e  L F G S  is  a  v ali d at e d s c al e ( C arr ut h ers 
et  al,  2 0 0 8 ).   
7. 8. 2   S e c o n d a r y  Effi c a c y  A n al ysis 
S e c o n d ar y  a n al ysis  i n cl u d e  
•   p er c e nt  of s u bj e cts  wit h tr e at m e nt s u c c ess (r es p o n d er:  o v er all  L F G S   b as e d  o n t h e  Bli n d e d 
E v al u ati n g I n v esti g at or  Ass ess m e nt )  at  Visit  3/ M o nt h  2  w h er e r es p o n d er is  d efi n e d  as  a s u bj e ct 
wit h  at l e ast  a  1 -gr a d e i n cr e as e fr o m  b as eli n e  o n t h e  L F G S  p ost  a u g m e nt ati o n,   
•   p er c e nt  of r es p o n d ers  o v er all  o n t h e  P O L s e v erit y s c al e  at  Visit  4/ M o nt h  3 ( d efi n e d  as  a s u bj e ct 
d e m o nstr ati n g  ≥  1 - p oi nt i m pr o v e m e nt, i. e.,  d e cr e as e i n s e v erit y, fr o m  b as eli n e), 
•   c h a n g e  fr o m  b as eli n e t o Visit  4/ M o nt h  3 i n  o v er all  L F G S  b as e d  o n t h e  Bli n d e d  E v al u ati n g 
I n v esti g at or  Ass ess m e nt 
•   c h a n g e fr o m  b as eli n e t o  Visit  5/ M o nt h  6 i n  o v er all  L F G S    b as e d  o n t h e  Bli n d e d  E v al u ati n g 
I n v esti g at or  Ass ess m e nt. 
 
7. 8. 3   Ot h e r  Effi c a c y  A n al ysis 
Ot h er  effi c a c y  a n al ysis  i n cl u d e  
•   p G AI, i G AI,  a n d  S w elli n g  Ass ess m e nt  at  e a c h s c h e d ul e d  visit, 
•   p er c e nt  of s u bj e cts  wit h tr e at m e nt s u c c ess (r es p o n d er:  u p p er li ps, l o w er li ps  L F G S)  at  Visit 
3/ M o nt h  2  w h er e r es p o n d er is  d efi n e d  as  a s u bj e ct  wit h  at l e ast  a  1- gr a d e i n cr e as e fr o m  b as eli n e 
o n t h e  L F G S  p ost  a u g m e nt ati o n 
•   p er c e nt  of r es p o n d ers ( u p p er li ps, l o w er li ps)  o n t h e  P O L s e v erit y s c al e  at  Visit  4/ M o nt h  3 
( d efi n e d  as  a s u bj e ct  d e m o nstr ati n g ≥  1 - p oi nt i m pr o v e m e nt, i. e.,  d e cr e as e i n s e v erit y, fr o m 
b as eli n e ), 
•   s atisf a cti o n  wit h li ps  V A S  at  e a c h s c h e d ul e d  visit, 

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•  
c h a n g e fr o m  b as eli n e t o  Visit  4/ M o nt h  3  a n d  Visit  5/ M o nt h  6 i n  u p p er li ps, l o w er li ps  L F G S.  
   
7. 9   
Ass ess m e nt  of  S af et y  
7. 9. 1   S af et y  A n al ysis 
S af et y  of t h e  st u d y  d e vi c es  will  b e  c o m p ar e d  b y  e v al u ati n g t h e  n at ur e, s e v erit y,  a n d fr e q u e n c y  of 
tr e at m e nt-e m er g e nt  a d v ers e  e v e nts ( T E A Es).  All  A Es t h at  o c c ur  d uri n g t h e st u d y  will  b e r e c or d e d 
w h et h er  or  n ot t h e y  ar e  c o nsi d er e d t o  b e r el at e d t o tr e at m e nt.  A  d es cri pti o n  of t h e  A E  will  b e r e c or d e d 
wit h t h e  d at e  of  o ns et,  d at e  of r es ol uti o n, s e v erit y  of t h e  A E, r el ati o ns hi p t o t h e st u d y  d e vi c e,  a cti o n 
t a k e n,  a n d t h e  o ut c o m e. 
7. 9. 2   Ot h e r  S af et y  E v al u ati o ns 
Li p f u n cti o n,  li p s e ns ati o n, li p t e xt ur e, li p fir m n ess, li p s y m m etr y  a n d li p  m o v e m e nt/f u n cti o n will  b e 
ass ess e d  pri or t o  a n y i nj e cti o ns  a n d  at  all f oll o w- u p  visits.  
7. 9. 3   D efi niti o n s of  T e r ms  
7. 9. 3. 1   
A d v e rs e  E v e nt  
A n  A E is  d efi n e d  as  a n y  u nt o w ar d  m e di c al  o c c urr e n c e  ass o ci at e d  wit h t h e  us e  of  a  dr u g/ d e vi c e  i n 
h u m a ns,  w h et h er  or  n ot  c o nsi d er e d  dr u g/ d e vi c e-r el at e d ( 2 1  C o d e  of  F e d er al  R e g ul ati o ns [ C F R ] 
3 1 2. 3 2  ( a)  a n d  8 0 3).  A n  A E  c a n t h er ef or e  b e  a n y  u nf a v or a bl e  a n d  u ni nt e n d e d si g n (i n cl u di n g  a n 
a b n or m al l a b or at or y fi n di n g, f or  e x a m pl e), s y m pt o m,  or  dis e as e t e m p or all y  ass o ci at e d  wit h t h e  us e  of  a 
dr u g / d e vi c e,  wit h o ut  a n y j u d g m e nt  a b o ut  c a us alit y. 
E x p e ct e d  a d v ers e  e v e nts  ar e  d efi n e d  as t h e  e v e nts t h at  a p p e ar e d  at i nj e cti o n sit e s u bs e q u e nt t o t h e first 
i nj e cti o n.  E x p e ct e d  a d v ers e  e v e nts  m a y i n cl u d e  b ut  ar e  n ot li mit e d t o  br uisi n g, s w elli n g,  er yt h e m a, 
e d e m a, i nfl a m m ati o n  at i nj e cti o n sit e.  
7. 9. 3. 2   
S us p e ct e d  A d v e rs e  R e a cti o n  
A s us p e ct e d  a d v ers e r e a cti o n ( S A R) is  d efi n e d  as  a n y  A E f or  w hi c h t h er e is r e as o n a bl e  p ossi bilit y t h at 
t h e  dr u g/ d e vi c e  c a us e d t h e  A E ( 2 1  C F R  3 1 2. 3 2 ( a)). 
7. 9. 3. 3   
U n e x p e ct e d  A d v e rs e  E v e nt  
A n  A E  or  S A R is  c o nsi d er e d  u n e x p e ct e d if it is  n ot  c o nsist e nt  wit h t h e ris k i nf or m ati o n  d es cri b e d i n t h e 
l a b eli n g f or t h e st u d y  d e vi c es. 
7. 9. 3. 4   
A d v e rs e  E v e nts  of  S p e ci al I nt e r est  
C ert ai n  e v e nts  will r e q uir e  m or e  d et ail e d  a n d ti m el y r e p orti n g.  T h es e i n cl u d e:  
-  a n y  c h a n g es i n  visi o n 
-  a n y  e v e nts  attri b ut a bl e t o  a n  e m b oli c  or is c h e mi c  c a us e (i. e. , s ki n i nf ar cti o n) 
-  A n y i n ci d e n c e  of  a n  e v e nt  d u e t o  a n  e m b oli c  or is c h e mi c  c a us e  or  vis u al  dist ur b a n c es (i n cl u di n g, 
b ut  n ot li mit e d t o,  a n y l oss  of  visi o n,  bl urr y  visi o n,  d o u bl e  visi o n,  p ai n i n  or  ar o u n d  e y e,  bli n d 
s p ot  or s h a d o w i n t h e  vis u al fi el d, tr o u bl e  m o vi n g  e y es,  et c.)  M U S T  b e i m m e di at el y r e p ort e d t o 
t h e  M e di c al  M o nit or  b y  p h o n e,  e m ail  or f a x.  T h e i n v esti g at or/ c o or di n at or  m ust  c o m pl et e  t h e  A E 
s o ur c e/ C R F  p a g e  a n d  e m ail  or  f a x it t o t h e  M e di c al m o nit or  as s o o n  as  p ossi bl e  aft er t h e 
i n v esti g at or  or  c o or di n at or  h as  b e c o m e  a w ar e  of its  o c c urr e n c e.  T h es e r e p orts  will i n cl u d e t h e 
d e pt h  of i nj e cti o n, t h e i nj e cti o n  v ol u m e, t h e s y m pt o ms t h at  w er e  o bs er v e d, t h e ti m e t o  o ns et, ti m e 

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t o r es ol uti o n  a n d  a n y i nt er v e nti o ns t h at  w er e i m pl e m e nt e d.   T h e  S p o ns or  will  n otif y t h e  F D A 
wit hi n  1 0  w or ki n g  d a ys. 
I n t h e  e v e nt  of  bli n d n ess  or  a n y  o p ht h al mi c si g ns  or s y m pt o ms, s u bj e cts will  u n d er g o  i m m e di at e 
e v al u ati o n  b y  a r eti n a s p e ci alist.  
R ef er t o  A p p e n di x  1 f or first  ai d  pr ot o c ol.  
7. 9. 3. 5   
S e ri o us  A d v e rs e  E v e nt  
A n  S A E is  d efi n e d  as  a n y  A E  or  S A R t h at, i n t h e  vi e w  of t h e i n v esti g at or  or  S p o ns or, r es ults i n  a n y  of 
t h e f oll o wi n g  o ut c o m es ( 2 1  C F R  3 1 2. 3 2 ( a)): 
•   D e at h  
•   Lif e -t hr e at e ni n g  A E ( N ot e: t h e t er m  “lif e-t hr e at e ni n g ”  as  us e d  h er e r ef ers t o  a n  e v e nt t h at i n t h e 
vi e w  of t h e i n v esti g at or  or  S p o ns or  pl a c es t h e s u bj e ct  at i m m e di at e ris k  of  d e at h  at t h e ti m e  of t h e 
e v e nt; it  d o es  n ot i n cl u d e  a n  A E  or  S A E t h at,  h a d it  o c c urr e d i n  a  m or e s e v er e f or m,  mi g ht  h a v e 
c a us e d  d e at h [ 2 1  C F R  3 1 2. 3 2( a)]) 
•   I n p ati e nt  h os pit ali z ati o n  or  pr ol o n g ati o n  of  e xisti n g  h os pit ali z ati o n.  S e e  e x cl usi o n t o  S A E 
r e p orti n g  b el o w  u n d er  Pl a n n e d  H os pit ali z ati o n. 
•   P ersist e nt  or si g nifi c a nt i n c a p a cit y  or s u bst a nti al  disr u pti o n  of t h e  a bilit y t o  c o n d u ct  n or m al lif e 
f u n cti o ns 
•   C o n g e nit al  a n o m al y/ birt h  d ef e ct 
•   R e q uir e d i nt er v e nti o n t o  pr e v e nt  p er m a n e nt i m p air m e nt/ d a m a g e 
•   A n y  “ ot h er ” i m p ort a nt  m e di c al  e v e nt.  I m p ort a nt  m e di c al  e v e nts t h at  m a y  n ot r es ult i n  d e at h,  b e 
lif e-t hr e at e ni n g,  or r e q uir e  h os pit ali z ati o n  m a y  b e  c o nsi d er e d s eri o us  w h e n,  b as e d  u p o n 
a p pr o pri at e  m e di c al j u d g m e nt, t h e y  m a y j e o p ar di z e t h e s u bj e ct  a n d  m a y r e q uir e  m e di c al  or 
s ur gi c al i nt er v e nti o n t o  pr e v e nt  o n e  of t h e  o ut c o m es list e d i n t his  d efi niti o n.  E x a m pl es  of s u c h 
m e di c al  e v e nts i n cl u d e  all er gi c  br o n c h os p as m r e q uiri n g i nt e nsi v e tr e at m e nt i n  a n  e m er g e n c y 
r o o m  or  at  h o m e,  bl o o d  d ys cr asi as  or  c o n v ulsi o ns t h at  d o  n ot r es ult i n i n p ati e nt  h os pit ali z ati o n, 
or t h e  d e v el o p m e nt  of  dr u g  d e p e n d e n c y  or  dr u g  a b us e. 
7. 9. 3. 6   
Pl a n n e d  H os pit ali z ati o n  
A  h os pit ali z ati o n  pl a n n e d  b y t h e s u bj e ct  pri or t o si g ni n g t h e I C F is  c o nsi d er e d  a t h er a p e uti c i nt er v e nti o n 
a n d  n ot t h e r es ult  of  a  n e w  S A E  a n d s h o ul d  b e r e c or d e d  as  m e di c al  hist or y. If t h e  pl a n n e d  h os pit ali z ati o n 
or  pr o c e d ur e  o c c urs  as  pl a n n e d, t h e r e c or d i n t h e s u bj e ct’s  m e di c al  hist or y is  c o nsi d er e d  c o m pl et e. 
H o w e v er, if t h e  e v e nt/ c o n diti o n  w ors e ns  d uri n g t h e st u d y, it  m ust  b e r e p ort e d  as  a n  A E. 
7. 9. 4   P r e g n a n c y  
Pr e g n a n ci es  o c c urri n g  aft er  a d mi nistr ati o n  of  st u d y  d e vi c e r e q uir e i m m e di at e r e p orti n g.  T h e y  m ust  b e 
r e p ort e d  wit hi n  2 4  h o urs aft er t h e i n v esti g at or  h as  b e c o m e  a w ar e  of t h e  pr e g n a n c y.   A  pr e g n a n c y r e p ort 
will  b e  c o m pl et e d  a n d s e nt  b y f a x t o  t h e S p o ns or  or  d esi g n e e  wit hi n  2 4  h o urs  of  b e c o mi n g  a w ar e  of t h e 
pr e g n a n c y.  T h e i n v esti g at or  will  c oll e ct f oll o w - u p i nf or m ati o n r e g ar di n g t h e  o ut c o m e  of t h e  pr e g n a n c y 
a n d  a n y  p ost n at al s e q u el a e i n t h e i nf a nt t h at  m ust  als o  b e r e p ort e d t o t h e  S p o ns or  or  d esi g n e e.   U p o n 
a w ar e n ess  of t h e  o ut c o m e  of t h e  pr e g n a n c y, t h e  Pri n ci p al I n v esti g at or   or  d esi g n e e  m ust f or w ar d  a 
f oll o w- u p  Pr e g n a n c y  R e p ort  wit h  a n y r el e v a nt i nf or m ati o n t o t h e S p o ns or  or  d esi g n e e .  
If t h e  o ut c o m e  of t h e  pr e g n a n c y  m e ets t h e  crit eri a f or i m m e di at e  cl assifi c ati o n  of  a n  S A E ( e. g., 
s p o nt a n e o us  a b orti o n, still birt h,  n e o n at al  d e at h,  or  c o n g e nit al  a n o m al y), t h e i n v esti g at or  will r e p ort t h e 

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e v e nt  b y  f a xi n g  a  c o m pl et e d  S A E r e p ort f or m t o t h e S p o ns or  or  d esi g n e e  wit hi n  2 4  h o urs  of  b ei n g 
n otifi e d  of t h e  pr e g n a n c y r e p ort. 
T h e s u bj e ct s h o ul d i m m e di at el y  b e  wit h dr a w n fr o m t h e st u d y. 
7. 9. 5   M o nit o ri n g  A d v e rs e  E v e nts   
E a c h s u bj e ct  will  b e  m o nit or e d f or t h e  o c c urr e n c e  of  A Es, i n cl u di n g  S A Es, i m m e di at el y  aft er tr e at m e nt 
i niti ati o n.  E a c h s u bj e ct  will  b e f oll o w e d f or s af et y  m o nit ori n g  u ntil  dis c h ar g e d fr o m t his st u d y.  F oll o w-
u p  pr o c e d ur es r el at e d t o  pr e g n a n c y  or  A Es  or  S A Es  m a y  c o nti n u e  b e y o n d t h e  e n d  of t h e st u d y. 
S u bj e cts  will  b e  q u esti o n e d  a n d/ or  e x a mi n e d  b y t h e i n v esti g at or  or  a  q u alifi e d  d esi g n e e f or  o c c urr e n c e  of 
A Es t hr o u g h o ut t h e st u d y.  T h e  pr es e n c e  or  a bs e n c e  of s p e cifi c  A Es s h o ul d  n ot  b e  eli cit e d fr o m s u bj e cts. 
I n  a d diti o n, s u bj e cts  will  b e i nstr u ct e d t o r e c or d  A Es  o n t h e s u bj e ct  di ar y  c ar d  d uri n g t h e  2  w e e ks  aft er 
tr e at m e nt.  S u bj e cts  h a vi n g  A Es  will  b e  m o nit or e d  wit h r el e v a nt  cli ni c al  ass ess m e nts  a n d l a b or at or y t ests, 
as  d et er mi n e d  b y t h e i n v esti g at or.  
A Es,  a cti o ns t a k e n  as  a r es ult  of  A Es,  a n d f oll o w- u p r es ults  m ust  b e r e c or d e d  o n t h e  C R F,  as  w ell  as i n 
t h e s u bj e ct’s s o ur c e  d o c u m e nt ati o n. 
F or  all  A Es t h at r e q uir e t h e s u bj e ct t o  b e  wit h dr a w n fr o m t h e st u d y  a n d  S A Es, r el e v a nt  cli ni c al 
ass ess m e n ts  will  b e r e p e at e d  as  cli ni c all y  a p pr o pri at e  u ntil fi n al r es ol uti o n  or st a bili z ati o n  of t h e 
e v e nt(s).  
7. 9. 6   Ass ess m e nt  of  A d v e rs e  E v e nts  
7. 9. 6. 1   
Ass ess m e nt  of  S e v e rit y  
S e v erit y  of  A Es  will  b e  gr a d e d  a c c or di n g t o t h e f oll o wi n g  d efi niti o ns: 
Mil d : A E t h at  w as  e asil y t ol e rat e d  
M o d er at e : A E s uffi ci e ntl y  dis c o mf orti n g t o i nt erf er e  wit h  d ail y  a cti vit y  
S e v er e : A E t h at  pr e v e nt e d  n or m al  d ail y  a cti viti es  
7. 9. 6. 2   
Ass ess m e nt  of  C a us alit y  
A  m e di c all y  q u alifi e d i n v esti g at or  m ust  ass ess t h e r el ati o ns hi p  of  a n y  A E (i n cl u di n g  S A Es) t o t h e  us e  of  
t h e st u d y  d e vi c e  as  u nli k el y r el at e d,  p ossi bl y r el at e d,  or  pr o b a bl y r el at e d  b as e d  o n  a v ail a bl e i nf or m ati o n, 
usi n g t h e  f oll o wi n g  g ui d eli n es:  
U nli k el y r el at e d :  n o t e m p or al  ass o ci ati o n,  or t h e  c a us e  of t h e  e v e nt  h as  b e e n i d e ntifi e d,  or t h e 
st u d y  d e vi c e c a n n ot  b e i m pli c at e d   b as e d  o n  a v ail a bl e i nf or m ati o n 
P ossi bl y r el at e d : t e m p or al  ass o ci ati o n  b ut  ot h er  eti ol o gi es  ar e li k el y t o  b e t h e  c a us e;  h o w e v er, 
i n v ol v e m e nt  of t h e st u d y  d e vi c e  c a n n ot  b e  e x cl u d e d  b as e d o n  a v ail a bl e i nf or m ati o n  
Pr o b a bl y r el at e d : t e m p or al ass o ci ati o n,  ot h er  eti ol o gi es  ar e  p ossi bl e,  b ut  u nli k el y  b as e d  o n 
a v ail a bl e i nf or m ati o n  
7. 9. 6. 3   
R ef e r e n c e  S af et y I nf o r m ati o n f o r  Ass ess i n g E x p e ct e d n ess  of  A d v e rs e  E v e nts  
T h e  ref er e n c e  saf et y  inf or m ati o n f or  ass essi n g t h e  e x p e ct e d n ess  of  a n  A E  f or t h e st u d y d e vi c e  i n t his 
st u d y is t h e P N 4 0 0 8 2 I nstr u cti o ns f or  Us e   a n d t h e R est yl a n e ®   Sil k I nstr u cti o ns f or  Us e. 
7. 9. 7   R e p o rti n g  S af et y  O bs e r v ati o ns 
A n y  S A E ,  w h et h er  d e e m e d  d e vi c e-r el at e d  or  n ot,  m ust  b e r e p ort e d t o t h e  S p o ns or  or  d esi g n e e b y 
t el e p h o n e,  e m ail or f a x   as s o o n  as  p ossi bl e  aft er t h e i n v esti g at or  or  c o or di n at or  h as  b e c o m e  a w ar e  of its 

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(i n cl u di n g  all  d e at hs)  m ust  als o  b e r e p ort e d t o t h e I nstit uti o n al  R e vi e w  B o ar d (I R B)  b y t h e i n v esti g at or 
a c c or di n g t o I R B r e p orti n g r e q uir e m e nts  a n d  d o c u m e nt ati o n  of t his r e p ort s e nt t o t h e  S p o ns or  or 
d esi g n e e. 
T h e i n v esti g at or  m ust  pr o vi d e  a f oll o w- u p  writt e n r e p ort  wit hi n  5  c al e n d ar  d a ys  of r e p orti n g t h e  e v e nt t o 
t h e  m e di c al  m o nit or.  T h e  writt e n r e p ort  m ust  c o nt ai n  a f ull  d es cri pti o n  of t h e  e v e nt  a n d  a n y s e q u el a e. 
S u bj e cts  w h o  h a v e  h a d  a n  S A E  m us t  b e f oll o w e d  cli ni c all y  u ntil  all  p ar a m et ers (i n cl u di n g l a b or at or y) 
h a v e  eit h er r et ur n e d t o  n or m al  or  ar e st a bili z e d.  
7. 9. 8   Di a r y  Ass ess m e nts  
Di ari es  will  b e r e vi e w e d  b y t h e  Tr e ati n g I n v esti g at or  a n d/ or  u n bli n d e d st aff  e a c h ti m e t h e y  ar e r et ur n e d 
b y  a s u bj e ct.  E ntri es  will  b e r e vi e w e d f or  c o m pl et e n ess  a n d  m e di c al  a c c ur a c y.  A n y  di ar y  e v e nts list e d  b y 
t h e s u bj e ct  as  p ersisti n g  b e y o n d t h e fi n al r e c or di n g  d a y  of t h e  di ar y  will  b e  e v al u at e d  b y t h e  Tr e ati n g 
I n v esti g at or at t h e  n e xt  visit   a n d  m a y  b e r e c or d e d  as  a n A E   at t h e  dis cr eti o n  of t h e i n v esti g at or. 
7. 9. 9   C rit e ri a f o r  E a rl y  T e r mi n ati o n  of t h e  St u d y  
T h e tri al  m a y  b e t er mi n at e d  b e c a us e  of s af et y  c o n c er ns.   W h er e t er mi n ati o n is  d e e m e d  a p pr o pri at e, t h er e 
will  b e ti m el y  c o m m u ni c ati o n  wit h t h e  F D A i n  a c c or d a n c e  wit h t h e r e g ul ati o n ( 2 1  C F R  8 1 2. 1 5 0 
( d e vi c es)).   T h e s p o ns or,  Pr oll e ni u m  M e di c al  T e c h n ol o gi es,  will i niti at e  dis c ussi o n  as s o o n  as  p ossi bl e 
a b o ut t h e  a p pr o pri at e  c o urs e  of  a cti o n f or t h e tri al i n  q u esti o n  a n d f or t h e i n v esti g ati o n al  pr o d u ct.   T h er e 
will  b e i m m e di at e f ol l o w  u p  b y t h e  c o m p a n y t o i n v esti g at e  a n y  p ot e nti al s af et y  c o n c er n. 
I n t h e  e v e nt  of  a  v as c ul ar  e m b oli c  e v e nt l e a di n g t o s ki n  n e cr osis,  visi o n l oss,  or str o k e,  e nr oll m e nt  a n d 
tr e at m e nt  at t h e i n v esti g ati o n al sit e  will  b e s us p e n d e d  a n d  a r o ot  c a us e i n v esti g ati o n  will  b e  c o n d u ct e d t o 
d et er mi n e t h e  c a us e  of t h e  e m b oli c  e v e nt  a n d  w h et h er t h e  o ut c o m e  w as  a nti ci p at e d (t h e i n v esti g at or  di d 
n ot  pr o p erl y f oll o w t h e tr e at m e nt  S O P)  or  u n a nti ci p at e d (t h e i n v esti g at or  di d  pr o p erl y f oll o w t h e 
tr e at m e nt  S O P).  If t h e l att er sit u ati o n is  o bs er v e d, t h e  e ntir e st u d y  will  b e i m m e di at el y s us p e n d e d  a n d 
n o  p ati e nts  will  b e  e nr oll e d  u ntil t h e  e v e nt  c a n  b e  pr o p erl y  c h ar a ct eri z e d  a n d  a n  a p pr o pri at e tr e at m e nt 
str at e g y t o  a v oi d t his  u n a nti ci p at e d  e v e nt  c a n  b e  d e vis e d.  
 
7. 9. 1 0   Wit h d r a w al,  T r e at m e nt I nt e r r u pti o n,  a n d  U n bli n di n g  of  Bli n d e d  T r e at m e nt  D u e t o  S af et y 
O bs e r v ati o ns 
7. 9. 1 0. 1   Wit h d r a w al 
S e e  S e cti o n  7. 3. 3  f or t h e  crit eri a f or wit h dr a wi n g  a s u bj e ct.  If a s u bj e ct  is wit h dr a w n  fr o m t h e st u d y, t h e 
a cti viti es s p e cifi e d f o r Visit  5/ M o nt h  6  o n  t h e s c h e d ul e  of st u d y  a cti viti es ( S e cti o n  2 ) s ho ul d  b e 
c o m pl et e d if  p ossi bl e. 
7. 9. 1 0. 2   U n bli n di n g  T r e at m e nt f o r  a  S u bj e ct  D u ri n g t h e  St u d y  
U n bli n di n g  b y t h e i n v esti g at or s h o ul d  o c c ur  o nl y i n t h e  e v e nt  of  a n  A E  or  S A E f or  w hi c h it is  n e c ess ar y 
t o  k n o w t h e st u d y tr e at m e nt t o  d et er mi n e  a n  a p pr o pri at e  c o urs e  of t h er a p y f or t h e s u bj e ct. I n t h e  e v e nt  of 
a n  e m er g e n c y t h at r e q uir es  br e a ki n g  of t h e st u d y  bli n d, t h e I n v esti g at or  c a n  u n bli n d t h e s u bj e ct  wit h o ut 
pri or  c o nt a ct  wit h t h e  M e di c al  M o nit or  alt h o u g h t h e I n v esti g at or  will i m m e di at el y  n otif y t h e  M e di c al 
M o nit or  a c c o m p a ni e d  b y  a  writt e n  e x pl a n ati o n  of t h e r e as o n  w h y t h e  bli n d  w as  br o k e n.  I n t h e  e v e nt  of 
a n  e m er g e n c y t h at r e q uir es  br e a ki n g  of t h e st u d y  bli n d, t h e r a n d o mi z ati o n  c o d e  will  b e  m ai nt ai n e d  b y 
e a c h  u n bli n d e d  Tr e ati n g I n v esti g at or t h at  c a n  b e  o p e n e d t o r e v e al t h e st u d y  d e vi c e t o t h e  a p pli c a bl e st aff.  
I n t h e  e v e nt t h e  u n bli n d e d  Tr e ati n g I n v esti g at or is  n ot  a v ail a bl e, t h e sit e s h o ul d  d esi g n at e  a n ot h er 
u n bli n d e d st aff  m e m b er  n ot i n v ol v e d i n t h e st u d y  c o n d u ct t o  a c c ess t h e r a n d o mi z ati o n  c o d e f or t h at 

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s u bj e ct.   N ot e t his  c a n  b e  d o n e  WI T H O U T i nf or mi n g t h e  bli n d e d  E v al u ati n g I n v esti g at or  a n d t h us 
m ai nt ai ni n g t h e st u d y  bli n d.  If  u n bli n di n g  o c c urs, t h e s u bj e ct  m ust  b e  wit h dr a w n fr o m t h e st u d y. 
8   
S T A TI S TI C A L  M E T H O D S  
Pri or t o t h e  d at a b as e l o c k,  a  d et ail e d, fi n ali z e d  St atisti c al  A n al ysis  Pl a n  will  b e  c o m pl et e d  a n d  pl a c e d  o n 
fil e. T h e  St atisti c al  A n al ysis  Pl a n  will  c o nt ai n  a  m or e  c o m pr e h e nsi v e  e x pl a n ati o n  t h a n t h at  pr o vi d e d  h er e 
of t h e  m et h o d ol o g y  us e d i n t h e st atisti c al  a n al ys es ,  as  w ell  as t h e r ul es  a n d  d at a  h a n dli n g  c o n v e nti o ns 
us e d t o  p erf or m t h e  a n al ys es  a n d t h e  pr o c e d ur e  us e d  t o a c c o u nt f or  missi n g  d at a.  
8. 1   
A n al ysis  P o p ul ati o ns 
I nt e nt-t o-tr e at (I T T) (s af et y)  p o p ul ati o n: All r a n d o mi z e d s u bj e cts  w h o r e c ei v e d  st u d y  d e vi c e  
M o difi e d i nt e nt- t o-tr e at ( mI T T):  All r a n d o mi z e d s u bj e cts  w h o  m et t h e i n cl usi o n/ e x cl usi o n  crit eri a,  w er e 
r a n d o mi z e d,  a n d r e c ei v e d st u d y  d e vi c e 
P er - pr ot o c ol ( P P): All r a n d o mi z e d s u bj e cts  w h o  m et  all i n cl usi o n/ e x cl usi o n  crit eri a; r e c ei v e d  st u d y 
d e vi c e ,  c o m pl et e d  Visit 5  wit hi n t h e s p e cifi e d  wi n d o w;  h a d  L F G S  s c or e  b y t h e  Bli n d e d  E v al u ati n g 
I n v esti g at or  at  Visit  3/ M o nt h  2 wit hi n t h e s p e cifi e d  visit  wi n d o w ,  a n d  h a d  n o si g nifi c a nt  pr ot o c ol 
vi ol ati o ns t h at  w o ul d  aff e ct t h e tr e at m e nt  e v al u ati o n  
Effi c a c y  a n al ys es  will  b e  p erf or m e d  o n t h e  mI T T  a n d  P P  p o p ul ati o ns,  wit h  P P  as t h e  pri m ar y  p o p ul ati o n 
a n d  mI T T s u p p orti v e.  
S af et y  a n al ys es  will  b e  p erf or m e d  o n t h e I T T  p o p ul ati o n. 
8. 2   
Effi c a c y  A n al ysis 
T h e  pri m ar y  effi c a c y  e n d p oi nt is  c h a n g e fr o m  b as eli n e t o  M o nt h  2 i n  o v er all li p f ull n ess  b as e d  o n t h e 
Bli n d e d  E v al u ati n g I n v esti g at or  ass ess m e nt  usi n g t h e  L F G S.  A  9 5 %  c o nfi d e n c e i nt er v al ( CI)  will  b e 
c o nstr u ct e d  f or t h e  diff er e n c e  b et w e e n  P N 4 0 0 8 2  a n d R est y l a n e  Sil k (i. e.  P N 4 0 0 8 2  mi n us R est yl a n e  Sil k)  
wit h r es p e ct t o t h e  pri m ar y  e n d p oi nt.  If t h e l o w er li mit  of t his  9 5 %  CI is  a b o v e  a  pr e -s p e cifi e d  NI li mit -
0. 5 0,  P N 4 0 0 8 2  will  b e  c l ai m e d n o n- i nf eri or t o R est yl a n e  Sil k . 
T h e  p ri m ar y e n d p oi nt  will  als o  b e  a n al y z e d f or t h e f oll o wi n g t w o s u bs ets  of s u bj e cts: ( 1) s u bj e cts t h at 
h a v e i nj e cti o n  o n  o n e li p  o nl y,  a n d ( 2) s u bj e cts t h at  h a v e i nj e cti o ns  o n  b ot h li ps. 
   
S e c o n d ar y  a n al ysis  i n cl u d e  
•   p er c e nt  of s u bj e cts  wit h tr e at m e nt s u c c ess (r es p o n d er:  o v er all  L F G S   b as e d  o n t h e  Bli n d e d 
E v al u ati n g I n v esti g at or  Ass ess m e nt )  at  Visit  3/ M o nt h  2  w h er e r es p o n d er is  d efi n e d  as  a s u bj e ct 
wit h  at l e ast  a  1 -gr a d e i n cr e as e fr o m  b as eli n e  o n t h e  L F G S  p ost  a u g m e nt ati o n,   
•   p er c e nt  of r es p o n d ers  o v er all  o n t h e  P O L s e v erit y s c al e  at  V isit  4/M o nt h  3 ( d efi n e d  as  a s u bj e ct 
d e m o nstr ati n g  ≥  1 - p oi nt i m pr o v e m e nt, i. e.,  d e cr e as e i n s e v erit y, fr o m  b as eli n e), 
•   c h a n g e fr o m  b as eli n e t o  Visit  4/ M o nt h  3 i n  o v er all  L F G S  b as e d  o n t h e  Bli n d e d  E v al u ati n g 
I n v esti g at or  Ass ess m e nt 
•   c h a n g e fr o m  b as eli n e t o  Vi sit  5/M o nt h  6 i n  o v er all  L F G S    b as e d  o n t h e  Bli n d e d  E v al u ati n g 
I n v esti g at or  Ass ess m e nt. 
 
F or t his  n o n-i nf eri orit y st u d y, t h e  n ull  h y p ot h esis t o  b e t est e d f or  all t h e s e c o n d ar y  e n d p oi nts is t h at t h er e is 
n o  diff er e n c e  b et w e e n t h e t w o  pr o d u cts,  a n d  all st atisti c al  c o m p aris o ns f or t h es e  e n d p oi nts  will  b e  c o nsi d er e d 
d es cri pti v e ( n o n-i nf er e nti al). T h es e s e c o n d ar y  v ari a bl es  will  b e s u m m ari z e d  wit h  d es cri pti v e st atisti cs f or 

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e a c h tr e at m e nt  ar m  a n d  a  9 5 %  CI f or t h e  diff er e n c e  b et w e e n tr e at m e nts.  F or t h e  pr o p orti o n  v ari a bl es, t h e 
9 5 %  CI f or tr e at m e nt  diff er e n c e  will  b e  c al c ul at e d  usi n g t h e  W al d’s  m et h o d,  wit h s u bj e cts  p o ol e d fr o m 
all st u d y sit es.   F or t h e  c h a n g e  v ari a bl es, t h e  9 5 %  CI f or tr e at m e nt  diff er e n c e  will  b e  d eri v e d  usi n g 
A N C O V A  wit h f a ct ors  of tr e at m e nt  a n d  sit e,  a n d t h e  c orr es p o n di n g  b as eli n e  v al u e f or t h e  e n d p oi nt  as 
c o v ari at e.  
 
Ot h er  effi c a c y  a n al ysis i n cl u d e  
•   p G AI, i G AI,  a n d  S w elli n g  Ass ess m e nt  at  e a c h s c h e d ul e d  visit, 
•   p er c e nt  of s u bj e cts  wit h tr e at m e nt s u c c ess (r es p o n d er:  u p p er li ps, l o w er li ps  L F G S)  at  Visit 
3/ M o nt h  2  w h er e r es p o n d er is  d efi n e d  as  a s u bj e ct  wit h  at l e ast  a  1- gr a d e i n cr e as e fr o m  b as eli n e 
o n t h e  L F G S  p ost  a u g m e nt ati o n, 
•   p er c e nt  of r es p o n d ers ( u p p er li ps, l o w er li ps)  o n t h e  P O L s e v erit y s c al e  at  Visit  4/ M o nt h  3 
( d efi n e d  as  a s u bj e ct  d e m o nstrati n g  ≥  1 - p oi nt i m pr o v e m e nt, i. e.,  d e cr e as e i n s e v erit y, fr o m 
b as eli n e ), 
•   s atisf a cti o n  wit h li ps  V A S  at  e a c h s c h e d ul e d  visit , 
•   c h a n g e fr o m  b as eli n e t o  Visit  4/ M o nt h  3  a n d  Visit  5/ M o nt h  6 i n  u p p er li ps, l o w er li ps  L F G S.  
All  ot h er  effi c a c y  e n d p oi nts  will  b e  s u m m ari z e d  b y tr e at m e nt  ar m  usi n g  d es cri pti v e st atisti cs.   
8. 3   
I nt e ri m  A n al ysis 
N o f or m al i nt eri m  a n al ysis is  pl a n n e d.   
8. 4   
S af et y  A n al ys es 
A d v ers e  e v e nts  will  b e  c o d e d t o s yst e m  or g a n  cl ass  a n d  pr ef err e d t er ms  usi n g t h e  M e di c al  Di cti o n ar y f or 
R e g ul at or y  A cti viti e s ( M e d D R A,  V ersi o n  2 0  or  hi g h er).  
Fr e q u e n c y  a n d  p er c e nt a g e  of s u bj e cts r e p orti n g tr e at m e nt- e m er g e nt  a d v ers e  e v e nts ( T E A Es)  will  b e 
t a b ul at e d f or  e a c h tr e at m e nt  b y  pr ef err e d t er ms  a n d f urt h er  b y s e v erit y  a n d r el ati o ns hi p t o st u d y  d e vi c e. 
I n s u m m ari es  of s e verit y   a n d r el ati o ns hi p, s u bj e cts r e p orti n g  m or e t h a n  o n e  e v e nt i n  a tr e at m e nt  ar m t h at 
ar e  m a p p e d t o t h e s a m e  pr ef err e d t er m  will  b e  c o u nt e d  o nl y  o n c e i n t h at tr e at m e nt  ar m  u n d er t h e 
str o n g est s e v erit y  a n d r el ati o ns hi p, r es p e cti v el y.  I n  a d diti o n,  vis u al rel at e d  T E A Es  will  b e s u m m ari z e d 
s e p ar at el y f or  e a c h tr e at m e nt  b y  pr ef err e d t er m.  
Ass ess m e nt r es ults  of li p f u n cti o n , li p s e nsiti vit y, li p t e xt ur e, li p fir m n ess, li p s y m m etr y,  a n d li p 
m o v e m e nt/f u n cti o n  will  b e s u m m ari z e d  wit h fr e q u e n c y  a n d  p er c e nt a g e f or  e a c h s c h e d ul e d  visit.  
S af et y  a n al ys es  will  b e  c o n d u ct e d  usi n g t h e I T T  p o p ul ati o n. 
8. 5   
S a m pl e  Si z e  D et e r mi n ati o n  
F or t h e  P R O  2 0 1 8- 0 2 st u d y, t h e  pri m ar y  v ari a bl e is  c h a n g e fr o m  b as eli n e t o  M o nt h  3 i n  L F G S.   T h e 
s a m pl e si z e  w as  d et er mi n e d  b as e d  o n ( 1)  b ot h  P N 4 0 0 8 2  a n d  R est yl a n e  Sil k  h a vi n g  a n  e q u al  m e a n  v al u e 
wit h  a   c o m m o n st a n d ar d  d e vi ati o n of  0. 8 5  f or  c h a n g e fr o m  b as eli n e i n  L FG S,  a n d  ( 2) t h e  n o n-i nf eri orit y 
li mit of  - 0. 5 0.  T h e t est: c o ntr ol r ati o  of  1: 1 r es ults i n  1 2 6 ( 6 3: 6 3) P P  s u bj e cts  at  9 0 %  p o w er.  Ass u mi n g 
8 0 %  of r a n d o mi z e d s u bj e cts  m e et t h e  P P   crit eri a,  a t ot al  of  1 5 8 ( 7 9: 7 9) s u bj e cts  will  b e r a n d o mi z e d t o 
o bt ai n  1 2 6 ( 6 3: 6 3)  P P  s u bj e cts. 

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E T HI C S  
9. 1   
I nf o r m e d  C o ns e nt  
T h e  pri n ci pl es  of i nf or m e d  c o ns e nt,  a c c or di n g t o  F o o d  a n d  Dr u g  A d mi nistr ati o n ( F D A) r e g ul ati o ns  a n d 
I nt er n ati o n al  C o u n cil  o n  H ar m o ni z ati o n (I C H)  g ui d eli n es  o n  G C P,  will  b e f oll o w e d.  A  c o p y  of t h e 
pr o p os e d I C F  m ust  b e s u b mitt e d  wit h t h e  pr ot o c ol t o t h e I R B f or  a p pr o v al. 
T h e i nf or m e d  c o ns e nt  pr o c ess  m ust  b e  c o n d u ct e d  a n d t h e I C F  m ust  b e si g n e d  b ef or e  e a c h s u bj e ct 
u n d er g o es  a n y  Visit  1  pr o c e d ur es t h at  ar e  p erf or m e d s ol el y f or t h e  p ur p os e  of  d et er mi ni n g  eli gi bilit y f or 
t h e st u d y, i n  c o m pli a n c e  wit h  2 1  C F R  P art  5 0.  E a c h s u bj e ct’s si g n e d I C F  m ust  b e  k e pt o n fil e  b y t h e 
i n v esti g at or f or i ns p e cti o n  b y r e g ul at or y  a ut h oriti es  at  a n y ti m e.  A  c o p y  of t h e si g n e d I C F  will  b e  gi v e n 
t o t h e s u bj e ct.  A  n ot ati o n  will  b e  m a d e i n t h e s u bj e ct’s  m e di c al r e c or d i n di c ati n g t h e  d at e  a n d ti m e 
i nf or m e d  c o ns e nt  w as  o bt ai n e d. 
9. 2   
I nstit uti o n al  R e vi e w  B o a r d (I R B) 
T h e st u d y  pr ot o c ol  a n d I C F  m ust  b e  a p pr o v e d i n  writi n g  b y  a n  a p pr o pri at e I R B  as  d efi n e d  b y  F D A 
r e g ul ati o ns  a n d  ot h er  a p pli c a bl e r e q uir e m e nts  pri or t o  e nr oll m e nt  of  a n y st u d y s u bj e cts. 
A n y  c h a n g es t o t h e  pr ot o c ol  or  a  c h a n g e  of  i n v esti g at or  a p pr o v e d  b y t h e  S p o ns or  m ust  als o  b e  a p pr o v e d 
b y t h e sit e’s I R B  a n d  d o c u m e nt ati o n  of t h at  a p pr o v al  pr o vi d e d t o t h e  S p o ns or  or  d esi g n e e.  R e c or ds  of 
t h e I R B r e vi e w  a n d  a p pr o v al  of  all  d o c u m e nts  p ert ai ni n g t o t his st u d y  m ust  b e  k e pt  o n fil e  b y th e 
i n v esti g at or  a n d  ar e s u bj e ct t o i ns p e cti o n  b y r e g ul at or y  a ut h oriti es  d uri n g  or  aft er  c o m pl eti o n  of t h e 
st u d y.  S A Es  m ust  als o  b e r e p ort e d t o t h e I R B. 
P eri o di c st at us r e p orts  m ust  b e s u b mitt e d t o t h e I R B  at l e ast  a n n u all y,  as  w ell  as  n otifi c ati o n  of 
c o m pl eti o n  of t h e st u d y  a n d  a fi n al r e p ort  wit hi n  1  m o nt h  of st u d y  c o m pl eti o n  or t er mi n ati o n.  A  c o p y  of 
all r e p orts s u b mitt e d t o t h e I R B  m ust  b e s e nt t o t h e   S p o ns or or  d esi g n e e.  
T h e i n v esti g at or  will  e ns ur e t h at  a n I R B t h at  c o m pli es  wit h t h e r e q uir e m e nts s et f o rt h i n  2 1  C F R  P art  5 6 
will  b e r es p o nsi bl e f or t h e i niti al  a n d  c o nti n ui n g r e vi e w  a n d  a p pr o v al  of t h e st u d y. 
9. 3   
S u bj e ct  C o nfi d e nti alit y  
All s u bj e ct  d at a  will  b e i d e ntifi e d  o nl y  b y  a s u bj e ct i d e ntifi c ati o n  n u m b er  a n d s u bj e ct i niti als.  H o w e v er, 
i n  c o m pli a n c e  wit h f e d er al  g ui d eli n es r e g ar di n g t h e  m o nit ori n g  of  cli ni c al st u di es  a n d i n f ulfill m e nt  of 
his/ h er  o bli g ati o ns t o t h e  S p o ns or , t h e i n v esti g at or  m ust  p er mit t h e st u d y  m o nit or,  S p o ns or 
r e pr es e nt ati v e  or  a u dit or,  a n d/ or  F D A r e pr es e nt ati v e  or  ot h er r e g ul at or y  a ut h orit y t o r e vi e w t h e  p orti o n 
of t h e s u bj e ct’s  m e di c al r e c or d t h at is  dir e ctl y r el at e d t o t h e st u d y.  T his s h all i n cl u d e  all st u d y -r el e v a nt 
d o c u m e nt ati o n i n cl u di n g  m e di c al  hist or y t o  v erif y  eli gi bilit y,  a d missi o n/ dis c h ar g e s u m m ari es f or 
h os pit al st a ys  o c c urri n g  w hil e t h e s u bj e ct is  e nr oll e d i n t h e st u d y,  a n d  a ut o ps y r e p orts if  a  d e at h  o c c urs 
d uri n g t h e st u d y. 
As  p art  of t h e r e q uir e d  c o nt e nt  of i nf or m e d  c o ns e nt,  e a c h s u bj e ct  m ust  b e i nf or m e d t h at  his  or  h er 
m e di c al  c h art  m a y  b e r e vi e w e d  b y t h e   S p o ns or, t h e  S p o ns or’s  a ut h ori z e d r e pr es e nt ati v es,  F D A  or  ot h er 
r e g ul at or y  a ut h orit y. If  a c c ess t o t h e  m e di c al r e c or d r e q uir es  a s e p ar at e  w ai v er  or  a ut h ori z ati o n, it is t h e 
i n v esti g at or’s r es p o nsi bilit y t o  o bt ai n s u c h  p er missi o n fr o m t h e s u bj e ct i n  writi n g  b ef or e t h e s u bj e ct is 
e nt er e d i nt o t h e st u d y. 
9. 4   
St u d y  R e gist r ati o n 
T h e  st u d y will  b e r e gist er e d  b y t h e   S p o ns or  o n  a n  a p pr o pri at e fr e e  p u bli c  w e b sit e s u c h  as 
cli ni c altri als. g o v,  w hi c h is  a s er vi c e  of t h e  U nit e d  St at es  N ati o n al I nstit ut es  of  H e alt h.  

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1 0. 1   
Sit e  R e g ul at o r y  D o c u m e nts  R e q ui r e d f o r I niti ati o n  
T h e   S p o ns or  or  d esi g n e e  will r e c ei v e t h e f oll o wi n g  d o c u m e nts  pri or t o t h e i niti ati o n  of t h e st u d y: 
•   C o m pl et e d, si g n e d  F or m  F D A  1 5 7 2 
•   C urr e nt  c urri c ul a  vit a e, si g n e d  a n d  d at e d, f or t h e  pri n ci p al i n v esti g at or  ( PI) a n d  c o -i n v esti g at ors 
n a m e d  o n  F or m  F D A  1 5 7 2  
•   C urr e nt li c e ns e(s)  of t h e  PI  a n d  c o -i n v esti g at ors  n a m e d  o n F or m  F D A   1 5 7 2 
•   D o c u m e nt ati o n  of I R B  a p pr o v al  of t h e st u d y  pr ot o c ol, i n v esti g at or,  a n d  I C F 
•   C urr e nt I R B  m e m b ers hi p list  
•   A  c o p y  of t h e  pr ot o c ol si g n at ur e  p a g e si g n e d  b y t h e  PI  
•   Ori gi n al  N o n - dis cl os ur e  A gr e e m e nts f or t h e PI  a n d  c o -i n v esti g at ors  n a m e d  o n F or m  F D A   1 5 7 2 
•   D e b ar m e nt  C ertifi c ati o n f or t h e  PI  a n d  c o -i n v esti g at ors  n a m e d  o n F or m  F D A  1 5 7 2 
•   Fi n a n ci al  Dis cl os ur e  St at e m e nt f or  all i n di vi d u als  n a m e d   o n F or m  F D A  1 5 7 2 
1 0. 2   
M ai nt e n a n c e  a n d  R et e nti o n  of  R e c o r ds  
T h e st u d y  will  b e  c o n d u ct e d  a c c or di n g t o  G C P   as  o utli n e d i n I C H  g ui d eli n es  b y t h e F D A . It is t h e 
r es p o nsi bilit y  of t h e i n v esti g at or t o  m ai nt ai n  a  c o m pr e h e nsi v e  a n d  c e ntr ali z e d fili n g s yst e m  of  all 
r el e v a nt  d o c u m e nt ati o n. I n v esti g at ors  will  b e i nstr u ct e d t o r et ai n  all st u d y r e c or ds r e q uir e d  b y t h e 
S p o ns or  a n d  t h e r e g ul ati o ns i n  a s e c ur e  a n d s af e f a cilit y  wit h li mit e d  a c c ess.  R e g ul ati o ns r e q uir e 
r et e nti o n f or  a  p eri o d  of  at l e ast  2  y e ars  aft er m ar k eti n g  a p pr o v al  a n d  n otifi c ati o n fr o m t h e  S p o ns or. 
T h es e r e g ul at or y  d o c u m e nts s h o ul d  b e r et ai n e d f or  a l o n g er  p eri o d if r e q uir e d  b y l o c al r e g ul at or y 
a ut h oriti es.   
T h es e r e c or ds i n cl u d e  d o c u m e nts  p ert ai ni n g t o t h e r e c ei pt  a n d r et ur n  of st u d y  d e vi c e , I R B, inf or m e d 
c o ns e nt, s o ur c e  d o c u m e nts,  a n d  fi n al si g n e d C R Fs .  N o  d o c u m e nts s h all  b e tr a nsf err e d fr o m t h e sit e  or 
d estr o y e d  wit h o ut first  n otif yi n g t h e   S p o ns or. 
1 0. 2. 1   C as e  R e p o rt  F o r ms ( C R F s)  
C R Fs f or i n di vi d u al s u bj e cts  will  b e  pr o vi d e d  b y t h e  S p o ns or  or  d e si g n e e. C R Fs  m ust  b e l e gi bl e  a n d 
c o m pl et e.   C R Fs f or t his st u d y  will  b e  m ai nt ai n e d i n  a st u d y  bi n d er  a n d  d at a r e c or d e d  o n  2-p art  N C R 
p a p er.  O n e  c o p y  will  b e  k e pt  b y t h e i n v esti g at or  a n d t h e  ot h er  c o p y  will  b e  c oll e ct e d  b y t h e st u d y 
m o nit or.  All f or ms s h o ul d  b e  c o m pl et e d  usi n g  a  bl a c k  b all p oi nt  p e n.  Err ors s h o ul d  b e li n e d  o ut,  b ut  n ot 
o blit er at e d,   a n d t h e  c orr e cti o n i ns ert e d, i niti al e d,  a n d  d at e d  b y  d esi g n at e d st u d y  p ers o n n el. F urt h er  d at a 
c orr e cti o ns  will  b e  p erf or m e d  o n s p e ci al  “ d at a  c orr e cti o n  for ms ” ( D C F s) t h at  will  b e pr o vi d e d t o t h e 
i n v esti g at or i n  c as e  of  err o n e o us  or  u n cl e ar  d at a.  Th e i n v esti g at or  will  m a k e t h e  c orr e cti o n  o n t h e  D C F 
a n d si g n t h e  D C F.  T h e  ori gi n al  will  b e  s e nt t o t h e st u d y  m o nit or  a n d  a  c o p y  r et ai n e d  wit h t h e  C R Fs. 
A  C R F  m ust  b e  c o m pl et e d  a n d si g n e d  b y t h e i n v esti g at or f or  e a c h s u bj e ct  e nr oll e d, i n cl u di n g t h os e 
wit h dr a w n  fr o m t h e st u d y f or  a n y r e as o n. T h e r e as o n f or  wit h dr a w al   m ust  b e  n ot e d  o n a s u bj e ct’s  st u d y 
t er min ati o n f or m. 
C R Fs  m ust  b e  k e pt  c urr e nt t o r efl e ct t h e s u bj e ct’s st at us  at  e a c h  p h as e  d uri n g t h e  c o urs e  of t h e st u d y.  
S u bj e cts  ar e  n ot t o  b e i d e ntifi e d  o n  C R Fs  b y  n a m e;  a p pr o pri at el y  c o d e d i d e ntifi c ati o n  a n d t h e s u bj e ct’s 
i niti als  m ust  b e  us e d. T h e i n v esti g at or  m ust  k e e p  a s e p ar at e l o g  of t h e s u bj e cts ’ n a m e s  a n d  a d dr ess es. 
S o ur c e  d o c u m e nts s u c h  as t h e  cli ni c  c h art  ar e t o  b e  m ai nt ai n e d s e p ar at el y fr o m t h e  C R F  t o  all o w  d at a 
v erifi c ati o n.  B e c a us e  of t h e  p ot e nti al f or  err ors, i n a c c ur a ci es,  a n d ill e gi bilit y i n tr a ns cri bi n g  d at a  o nt o 

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C R Fs ,  ori gi n als  of l a b or at or y  a n d  ot h er t est r es ults  m ust  b e  k e pt  o n fil e  wit h t h e s u bj e ct’s C R F . C R Fs , 
s o ur c e  d o c u m e nts,  a n d  c o pi es  of t est r es ults  m ust  b e  a v ail a bl e  at  all ti m es f or i ns p e cti o n  b y t h e st u d y 
m o nit or.  T h e f oll o wi n g s h o ul d  als o  b e  a v ail a bl e f or r e vi e w: 
•   S u bj e ct  S cr e e ni n g  L o g,  w hi c h s h o ul d r efl e ct t h e r e as o n  a n y s u bj e ct s cr e e n e d f or t h e s t u d y  w as 
f o u n d t o  b e i n eli gi bl e 
•   D el e g ati o n  of  A ut h orit y  L o g ,  w hi c h  will list  all sit e  p ers o n n el  wit h t h eir r es p o nsi biliti es as 
d el e g at e d  b y t h e  PI  a n d  t h eir si g n at ur es. T his l o g  will  b e  m ai nt ai n e d  at t h e sit e t hr o u g h o ut t h e 
st u d y 
•   M o nit ori n g  L o g ,  w hi c h  will list t h e  d at e  a n d  p ur p os e  of  all  m o nit ori n g  visits  b y t h e  S p o ns or or 
d esi g n e e 
•   E nr oll m e nt  L o g , w hi c h  will  list s u bj e ct i niti als  a n d st art  a n d  e n d  d at es f or  all  e nr oll e d s u bj e cts  
•   Pr o d u ct  I n ve nt or y/ P a c ki n g  Sli p,  w hi c h  will list  t h e t ot al  a m o u nt  of st u d y  d e vi c e s hi p p e d t o t h e 
sit e  a n d r e c ei v e d  a n d  si g n e d f or  b y t h e i n v esti g at or 
•   St u d y  D e vi c e  Dis p e nsi n g  L o g , w hi c h  will list  t h e l ot  n u m b er  a n d t ot al  a m o u nt  of st u d y  d e vi c e 
us e d f or  e a c h  s u bj e ct 
•   I C F,  w hi c h  m ust  b e  a v ail a bl e f or  e a c h s u bj e ct  a n d  b e  v erifi e d f or  pr o p er  d o c u m e nt ati o n 
•   All  c orr es p o n d e n c e 
1 0. 2. 2   P ri m a r y  S o u r c e  D o c u m e nts  
T h e i n v esti g at or  m ust  m ai nt ai n  pri m ar y s o ur c e  d o c u m e nts s u p p orti n g si g nifi c a nt  d at a f or  e a c h s u bj e ct’s 
m e di c al  n ot es.  T h es e  d o c u m e nts,  w hi c h  ar e  c o nsi d er e d  “s o ur c e  d at a , ” s h o ul d i n cl u d e  d o c u m e nt ati o n  of: 
•   D e m o gr a p hi c i nf or m ati o n 
•   E vi d e n c e s u p p orti n g t h e  i n di c ati o n f or  whi c h t h e s u bj e ct is  b ei n g st u di e d 
•   G e n er al i nf or m ati o n s u p p orti n g t h e s u bj e ct’s  p arti ci p ati o n i n t h e st u d y 
•   G e n er al  hi st or y  a n d  p h ysi c al fi n di n gs 
•   H os pit ali z ati o n  or  E m er g e n c y  R o o m r e c or ds (if  a p pli c a bl e) 
•   E a c h st u d y  visit  b y  d at e, i n cl u di n g  a n y r el e v a nt fi n di n gs/ n ot es  b y t h e i n v esti g at or(s),  o c c urr e n c e 
( or l a c k)  of A Es ,  a n d  c h a n g es i n  m e di c ati o n  us a g e 
•   A n y  a d diti o n al  visits   d uri n g t h e st u d y 
•   A n y r el e v a nt t el e p h o n e  c o n v ers ati o ns  wit h t h e s u bj e ct r e g ar di n g t h e st u d y  or  p ossi bl e  A Es  
•   A n  ori gi n al, si g n e d  I C F f or st u d y  p arti ci p ati o n 
T h e i n v esti g at or  m ust  als o r et ai n  all s u bj e ct -s p e cifi c  pri nt o uts/r e p orts  of t ests  a n d  pr o c e d ur es  p erf or m e d 
as  a r e q uir e m e nt  of t h e st u d y.  D uri n g  m o nit ori n g  visits t h e  m o nit or  will  v ali d at e  C R F  e ntri es   a g ai nst 
t h es e  d at a s o ur c es. 
1 0. 3   
St u d y  M o nit o ri n g  
T h e   S p o ns or  or  d esi g n e e  will  b e r es p o nsi bl e f or  m o nit ori n g t h e st u d y  a c c or di n g t o  G C P  a n d  a p pli c a bl e 
r e g ul ati o ns.  T h e st u d y  will  b e  m o nit or e d  b y  a  Cli ni c al  R es e ar c h  Ass o ci at e ( C R A) i n  c o m pli a n c e  wit h 
G C P, I C H  g ui d eli n es,  a n d  a p pli c a bl e r e g ul ati o ns.  T h e i n v esti g at or  will  b e  visit e d  b y  a  C R A  pri or t o t h e 
st u d y  a n d  at r e g ul ar i nt er v als  d uri n g t h e  c o urs e  of t h e st u d y.  T h es e  visits  ar e t o  v erif y  a d h er e n c e t o t h e 
pr ot o c ol.  T h e  C R A  will r e vi e w t h e I C Fs  a n d  v erif y  C R F  e ntri es  b y  c o m p ari n g t h e m  wit h t h e s o ur c e 
d o c u m e nts ( h os pit al/ cli ni c/ offi c e r e c or ds) t h at  will  b e  m a d e  a v ail a bl e f or t his  p ur p os e.  T h e  C R A  will 
r e vi e w t h e  m ai nt e n a n c e  of r e g ul at or y  d o c u m e nt ati o n  a n d  pr o d u ct  a c c o u nt a bilit y.  T h e  m o nit or  will 
r e vi e w t h e  pr o gr ess  of t h e st u d y  wit h t h e i n v esti g at or  a n d  ot h er sit e  p ers o n n el  o n  a r e g ul ar  b asis.  C R Fs 
m a y  b e  c oll e ct e d  d uri n g t h es e  visits.  At t h e  e n d  of t h e st u d y,  a  cl os e o ut  m o nit ori n g  visit  will  b e 

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Pr ot o c ol   
0 2 O C T 2 0 1 8  
4 5  
 
p erf or m e d.  M o nit ori n g  visits  will  b e  arr a n g e d  wit h sit e  p ers o n n el i n  a d v a n c e  at  a  m ut u all y  a c c e pt a bl e 
ti m e.  S uffi ci e nt ti m e  m ust  b e  all o w e d  b y t h e sit e  p ers o n n el f or t h e  m o nit ori n g  of  C R Fs  a n d r el e v a nt 
s o ur c e  d o c u m e nts.  T h e  c o or di n at or  a n d/ or i n v esti g at or s h o ul d  b e  a v ail a bl e t o  a ns w er  q u esti o ns  or 
r es ol v e  d at a  cl arifi c ati o ns.  A d e q u at e ti m e  a n d s p a c e f or t h es e  visits s h o ul d  b e  m a d e  a v ail a bl e  b y t h e 
i n v esti g at or  a n d st u d y st aff. 
1 0. 4   
A u dits  a n d I ns p e cti o ns  
D uri n g t h e  c o urs e  of t h e st u d y  a n d/ or  aft er it  h as  b e e n  c o m pl et e d,  1  or  m or e sit e s  m a y  b e  a u dit e d  b y 
a ut h ori z e d r e pr es e nt ati v es  of t h e  S p o ns or.  T h e  p ur p os e  of t h e  a u dit is t o  d et er mi n e  w h et h er  or  n ot t h e 
st u d y is  b ei n g  c o n d u ct e d  a n d  m o nit or e d i n  c o m pli a n c e  wit h r e c o g ni z e d  G C P/I C H  g ui d eli n es  a n d 
r e g ul ati o ns. 
A d diti o n all y, t h e st u d y  m a y  b e i ns p e ct e d  b y r e g ul at or y  a ut h oriti es . T h es e i ns p e cti o ns  m a y t a k e  pl a c e  at 
a n y ti m e  d uri n g   or  aft er  c o m pl eti o n  of t h e st u d y  a n d  ar e  b as e d  o n l o c al r e g ul ati o ns. 
1 0. 5   
M o difi c ati o ns t o t h e  P r ot o c ol 
T h e  pr o c e d ur es  d efi n e d i n t h e  pr ot o c ol  a n d  C R Fs  will  b e  c ar ef ull y r e vi e w e d t o  e ns ur e t h at  all  p arti es 
i n v ol v e d  wit h t h e st u d y f ull y  u n d erst a n d t h e  pr ot o c ol.  T o  e ns ur e t h e  v ali dit y  of t h e  d at a,  n o  d e vi ati o ns 
fr o m t h e  pr ot o c ol (wit h  mi ni m al  e x c e pti o ns ) m a y  b e  m a d e  u nl ess t h e iss u e is  br o a d  e n o u g h t o  w arr a nt 
r e visi o n  of t h e  pr ot o c ol.  S u c h r e visi o ns  m ust  b e s u b mitt e d t o  a n d  h a v e  d o c u m e nt e d  a p pr o v al fr o m t h e 
S p o ns or  a n d I R B  pri or t o i m pl e m e nt ati o n.   T h e  o nl y  cir c u mst a n c e i n  w hi c h  a n  a m e n d m e nt  m a y  b e 
i niti at e d  wit h o ut pri or I R B  a p pr o v al is t o  eli mi n at e  a n  a p p ar e nt i m m e di at e  h a z ar d  t o  a s u bj e ct  or 
s u bj e cts. I n s u c h  a  c as e,  ho w e v er, t h e i n v esti g at or  m ust  n otif y t h e  S p o ns or  i m m e di at el y  a n d t h e I R B 
wit hi n  5  w or ki n g  d a ys  aft er i m pl e m e nt ati o n.  
1 0. 6   
C o m pl eti o n  of t h e  St u d y  
T h e i n v esti g at or is r e q uir e d t o f or w ar d  C R Fs  a n d  all  ot h er r el e v a nt  d at a  a n d r e c or ds t o t h e  S p o ns or  or 
d esi g n e e.  T h e i n v esti g at or  will  c o m pl et e  a n d r e p ort (s u b missi o n  of  C R Fs)  his/ h er st u d y i n s atisf a ct or y 
c o m pli a n c e  wit h t h e  pr ot o c ol  as s o o n  as  p ossi bl e  aft er t h e  c o m pl eti o n  of t h e st u d y. 
T h e i n v esti g at or  m ust s u b mit  a fi n al r e p ort t o t h e I R B  a n d t h e  S p o ns or  wit hi n  1  m o nt h  of st u d y 
c o m pl eti o n  or  e arl y  t er mi n ati o n. 
1 1   
C O N FI D E N TI A LI T Y,  U S E  O F I N F O R M A TI O N,  A N D  P U B LI C A TI O N  
All i nf or m ati o n r el at e d t o t his st u d y t h at is  s up pli e d  b y t h e  S p o ns or  a n d  n ot  pr e vi o usl y  p u blis h e d is 
c o nsi d er e d  c o nfi d e nti al i nf or m ati o n.  T his i nf or m ati o n i n cl u d es  b ut is  n ot li mit e d t o  d at a,  m at eri als 
( pr ot o c ol, C R Fs ),  e q ui p m e nt,  e x p eri e n c e ( w h et h er  of  a s ci e ntifi c, t e c h ni c al,  e n gi n e eri n g,  o p er ati o n al,  or 
c o m m er ci al  n at ur e),  d esi g ns, s p e cifi c ati o ns,  k n o w- h o w,  pr o d u ct  us es,  pr o c ess es, f or m ul a e,  c osts, 
fi n a n ci al  d at a,  m ar k eti n g  pl a ns  a n d  dir e ct s elli n g s yst e ms,  c ust o m er lists, a n d t e c h ni c al  a n d  c o m m er ci al 
i nf or m ati o n r el ati n g t o  c ust o m ers  or  b usi n ess  pr oj e cti o ns  us e d  b y t h e  S p o ns or i n its  b usi n ess. A n y  d at a, 
i n v e nti o ns,  or  dis c o v eri es  c oll e ct e d  or  d e v el o p e d  as  a r es ult  of t his st u d y ar e   c o nsi d er e d  c o nfi d e nti al. 
T his  c o nfi d e nti al i nf or m ati o n s h all r e m ai n t h e s ol e  pr o p ert y  of t h e  S p o ns or, s h all  n ot  b e  dis cl os e d t o  a n y 
u n a ut h ori z e d  p ers o n  or  us e d i n  a n y  u n a ut h ori z e d  m a n n er  wit h o ut  writt e n  c o ns e nt  of t h e  S p o ns or,  a n d 
s h all  n ot  b e  us e d  e x c e pt i n t h e  p erf or m a n c e  of t h e st u d y. 
T h e i nf or m ati o n  d e v el o p e d  d uri n g t h e  c o urs e  of t his st u d y is  als o  c o nsi d er e d  c o nfi d e nti al  a n d  will  b e 
us e d  b y t h e  S p o ns or i n t h e  d e v el o p m e nt  of t h e  st u d y  m e di c ati o n.  T h e i nf or m ati o n  m a y  b e  dis cl os e d  as 
d e e m e d  n e c ess ar y  b y t h e   S p o ns or.  T o  all o w t h e  us e  of t h e i nf or m ati o n  d eri v e d fr o m t his st u d y, t h e 
i n v esti g at or is  o bli g e d t o  pr o vi d e t h e  S p o ns or wit h  c o m pl et e t est r es ults  a n d  all  d at a  d e v el o p e d i n t h e 
st u d y.  T h e i nf or m ati o n  o bt ai n e d  d uri n g t his st u d y  m a y  b e  m a d e  a v ail a bl e t o  ot h er i n v esti g at ors  w h o  ar e 
c o n d u cti n g si mil ar st u di es.  

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
4 6  
 
T h e i n v esti g at or s h all  n ot  m a k e  a n y  p u bli c ati o n r el at e d t o t his  st u d y  wit h o ut t h e  e x pr ess  writt e n 
p er missi o n  of t h e  S p o ns or.  If t h e i n v esti g at or w a nts  t o  p u blis h  or  pr es e nt t h e r es ults  of t his st u d y, h e  or 
s h e  a gr e es t o  pr o vi d e t h e  S p o ns or  wit h  a n  a bstr a ct,  m a n us cri pt,  a n d/ or  pr es e nt ati o n f or r e vi e w  6 0  d a ys 
pri or t o s u b missi o n f or  p u bli c ati o n  or  pr es e nt ati o n.  T h e   S p o ns or r et ai ns t h e ri g ht t o  d el et e  c o nfi d e nti al 
i nf or m ati o n  a n d t o  o bj e ct t o s u g g est e d  p u bli c ati o n/ pr es e nt ati o n a n d/ or its ti mi n g ( at t h e   S p o ns or’s s ol e 
dis cr eti o n). 
1 2   
LI S T  O F  R E F E R E N C E S  
C arr ut h ers  A,  C arr ut h ers J,  H ar d as  B,  et  al.  A  v ali d at e d li p f ull n ess  gr a di n g s c al e.  D er m at ol  S ur g. 
2 0 0 8; 3 4  S u p pl  2:  S 1 6 1- S 1 6 6. 
C o h e n J L,  T h o m as J,  P ar a d k ar  D,  et  al.  A n i nt err at er  a n d i ntr ar at er r el i a bilit y st u d y  of  3  p h ot o gr a p hi c 
s c al es f or t h e  cl assifi c ati o n  of  p eri or al  a est h eti c fi g ur es.  D er m at ol  S ur g.  2 0 1 4; 4 0: 6 6 3- 6 7 0. 
W olt ers  K l u w er  H e alt h, I n c.   R est or ati o n  of  Vis u al  L oss  wit h  R etr o b ul b ar  H y al ur o ni d as e I nj e cti o n  Aft er 
H y al ur o ni c  A ci d  Fill er.   D e r m at ol  S ur g  2 0 1 8; 4 4: 4 3 5- 4 4 6. 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
4 7  
 
1 3   
I N V E S TI G A T O R  A G R E E M E N T  
 
P r ot o c ol  N u m b e r:   
P R O  2 0 1 8- 0 2 
P r ot o c ol  Titl e:  
A  M ulti c e nt er,  D o u bl e- bli n d,  R a n d o mi z e d,  C o ntr oll e d  St u d y  of t h e  S af et y 
a n d  Eff e cti v e n ess  of  P N 4 0 0 8 2 f or  Li p  A u g m e nt ati o n 
 
I  h a v e  c ar ef ull y r e a d  a n d u n d erst a n d t h e f or e g oi n g  pr ot o c ol  a n d  a gr e e t h at it  c o nt ai ns  all t h e  n e c ess ar y 
i nf or m ati o n f or  c o n d u cti n g t his st u d y s af el y. I  will  c o n d u ct t his st u d y i n stri ct  a c c or d a n c e  wit h t his 
pr ot o c ol, I C H  g ui d eli n es f or  G o o d  Cli ni c al  Pr a cti c e, t h e  C o d e  of  F e d er al  R e g ul ati o ns, t h e  H e alt h 
I ns ur a n c e  P ort a bilit y  a n d  A c c o u nt a bilit y  A ct ( HI P A A),  a n d l o c al r e g ul at or y  g ui d eli n es. I  will  e ns ur e t h at 
t h e r e q uir e m e nts f or  o bt ai ni n g i nf or m e d  c o ns e nt  ar e  m et. I  will  att e m pt t o  c o m pl et e t h e st u d y  wit hi n t h e 
ti m e  d esi g n at e d. I  will  e ns ur e t h at t h e ri g hts, s af et y,  a n d  w elf ar e  of s u bj e cts  u n d er  m y  c ar e  ar e  pr ot e ct e d. 
I  will  e ns ur e  c o ntr ol  of t h e  d e vi c es  u n d er i n v esti g ati o n i n t his st u d y. I  will s u p er vis e  all t esti n g  of t h e 
d e vi c es i n v ol vi n g  h u m a n s u bj e cts. I  will  pr o vi d e  c o pi es  of t h e  pr ot o c ol  a n d  all  ot h er st u d y- r el at e d 
i nf or m ati o n s u p pli e d  b y t h e s p o ns or t o  all  p ers o n n el r es p o nsi bl e t o  m e  w h o  p arti ci p at e i n t h e st u d y. I 
will  dis c uss t his i nf or m ati o n  wit h t h e m t o  ass ur e t h at t h e y  ar e  a d e q u at el y i nf or m e d r e g ar di n g t h e  d e vi c e 
a n d  c o n d u ct  of t h e st u d y. I  a gr e e t o  k e e p r e c or ds  o n  all s u bj e ct i nf or m ati o n ( c as e r e p ort f or ms, s hi p m e nt 
a n d  d e vi c e r et ur n f or ms,  a n d  all  ot h er i nf or m ati o n  c oll e ct e d  d uri n g t h e st u d y)  a n d  d e vi c e  dis p ositi o n i n 
a c c or d a n c e  wit h  F D A r e g ul ati o ns. I  will  n ot  e nr oll  a n y s u bj e cts i nt o t his  pr ot o c ol  u ntil I R B  a p pr o v al  a n d 
s p o ns or  a p pr o v al  ar e  o bt ai n e d. 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
I n v esti g at or  N a m e ( Pri nt) 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _              _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
I n v esti g at or  Si g n at ur e                                                          D at e   
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
4 8  
 
1 4   
A P P E N DI X  1  
Fill er  First  Ai d  Pr ot o c ol   ( W olt ers  Kl u w er  H e alt h, I n c,  2 0 1 8) 
M at e ri als t h at  a r e  n e e d e d  o n -sit e: 
•   H y al ur o ni d as e ( H yl e n e x ) 
•   As piri n  3 2 5 m g 
•   Nitr o gl y c eri n  p ast e  
P r o vi d e t h e f oll o wi n g  c o nt a cts  t o s u bj e cts  a n d t h es e  c o nt a cts  als o  p ost e d  o n-sit e f o r  e as y  r ef e r e n c e:  
•  
O p ht h al m ol o gist  “ o n  c all ”  
•  
Cl os est  E R  wit h str o k e  m a n a g e m e nt  c a p a bilit y  wit h  dir e cti o ns t o  E R  
P r e p a r ati o n: 
- 
T h e  a b o v e  m at eri als s h o ul d  b e  g at h er e d  a n d l a b el e d f or  e m er g e n c y  us e  o nl y (t o  e ns u r e t h e y  ar e 
a v ail a bl e s h o ul d  a n  ur g e nt sit u ati o n  aris e).  
- 
St aff s h o ul d  b e  e d u c at e d r e g ar di n g t h e  ur g e nt  n at ur e  of s u c h  a n  e v e nt  a n d t h e l o c ati o n  of  all 
m at eri als  a n d  c o nt a ct i nf or m ati o n.  
- 
I n v esti g at ors  m a y  wis h t o f a mili ari z e t h e ms el v es  wit h t h e r etr o b ul bar i nj e cti o n t e c h ni q u e  vi a 
lit er at ur e  or  o n li n e tr ai ni n g.   
It is  criti c al t o r e c o g ni z e  a n y i ntr a v as c ul ar  e v e nts  d uri n g i nj e cti o ns  a n d  a ct  q ui c kl y t o  m a xi mi z e 
li k eli h o o d  of r e v ers al.  As s o o n  as  a n i ntr a v as c ul ar is r e c o g ni z e d, st o p  a n y f u rt h e r i nj e cti o ns . 
If  a s ki n i nf a r cti o n is i d e ntifi e d: 
•   A p pl y  nitr o gl y c eri n  p ast e   –  a p pl y li b er all y t o t h e  aff e ct e d  ar e a  a n d  m ass a g e i n  g e ntl y,  e x p e ct 
h e a d a c h e  c o m pl ai nt fr o m s u bj e ct  b ut  d o  n ot  wit h h ol d t h e tr e at m e nt. 
•   M ass a g e  ar e a  t o  h el p  pr o m ot e d  bl o o d fl o w 
•   Dis p e ns e  As piri n  3 2 5  m g -  H a v e  p ati e nt  c h e w t his  or t h e  as piri n  m a y  b e  pl a c e d s u bli n g u all y  f or 
m a xi m u m r a pi d  a bs or pti o n 
•   If  bl a n c hi n g  p ersists,  c o nsi d er i nfiltr ati o n  wit h  h y al ur o ni d as e 
o   I nfiltr at e i n t h e  ar e a  w h er e  m at eri al  w as  b ei n g i nj e ct e d –  t his  m a y  all o w  h y al ur o ni d as e to 
e nt er t h e s a m e  v ess el t h at  w as i n a d v ert e ntl y  c a n n ul at e d.  
o   I nfiltr at e i n t h e  ar e a  of  bl a n c hi n g  or is c h e mi a  as  w ell 
o   I nj e ct  a  mi ni m u m  of  5 0  u nits i nt o  e a c h  ar e a; i n v esti g at ors  ar e fr e e t o  us e l ar g er  d os es  as 
t h e y s e e fit. 
o   H y al ur o ni d as e  m a y  b e r e p e at e d  as  n e e d e d.  
•   H ot  P a c ks  –  T o w els  or  g el  p a c ks  w ar m e d i n  a  mi cr o w a v e  c a n  b e  a p pli e d  t o t h e  ar e a  of  d e cr e as e d 
bl o o d fl o w. 
•   M o nit or t h e s u bj e ct  a n d t h e  ar e a  of  bl a n c hi n g is c h e mi a.  If  bl a n c hi n g  p ersists  aft er  2 4  h o urs, – 
c o nsi d er  h y p er b ari c  o x y g e n  tr e at m e nts.  
 
If sig ns/s y m pt o ms  of  vis u al  c h a n g es,  o pt h al m o pl e gi a,  bli n d n ess,  o c ul a r  p ai n ( us u all y i m m e di at el y) 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
4 9  
 
o c c u r : 
•   Dis p e ns e  As piri n  3 2 5  m g -  H a v e  p ati e nt  c h e w  or  pl a c e  t h e t a bl et s u bli n g u all y f or  m a xi m u m r a pi d 
a bs or pti o n 
•   M ass a g e t h e  gl o b e  wit h r e p e at e d i n w ar d  c o m pr essi o n  a n d r el e as e  –  t his  m a y fr e e  a n y  e m b oli c 
m at eri al  
•   I nfiltr ati o n  wit h  h y al ur o ni d as e i nt o  ar e a  b ei n g  c orr e ct e d  or  a u g m e nt e d 
•   H a v e st aff  c all  o p ht h al m ol o g y:   I ns ert  p h ysi ci a n  a n d  c ell  p h o n e  n u m b er or  o n -c all 
o p ht h al m ol o g y  at  n e ar est  c e nt er  wit h  o n - c all  o p ht h al m ol o g y, a n d  arr a n g e tr a ns p ort  
o   Bri n g  h y al ur o ni d as e  wit h t h e s u bj e ct t o t h e  o p ht h al m ol o gist  –  at l e ast  3 0 0  u nits. 
•   If tr a ns p ort ti m e t o  o p ht h al m ol o g y  or  E R is  m or e t h a n  6 0  mi n ut es,  c o nsi d er  p erf or mi n g 
r etr o b ul b ar  h y al ur o ni d as e  a d mi nistr ati o n,  3 0 0- 6 0 0  u nits  at i nf eri or, l at er al  or bit al ri m t hr o u g h 
or bit al s e pt u m  wit h  1 - 1. 5 i n c h  2 7  g a u g e  n e e dl e  a v oi di n g  gl o b e 
Aft er  a b o v e  m e as ur es,  e x p e dit e t o  e m er g e n c y r o o m, t h e r eti n a  c a n t ol er at e  a p pr o xi m at el y  9 0  mi n ut es 
of is c h e mi a  u ntil  d a m a g e  b e c o m es  p er m a n e nt. 
If st r o k e s y mpt o ms  a r e  r e c o g ni z e d:  
•   Dis p e ns e  As piri n  3 2 5  m g -  H a v e  p ati e nt  c h e w t his  or t h e  as piri n  m a y  b e  pl a c e d s u bli n g u all y  f or 
m a xi m u m r a pi d  a bs or pti o n 
•   I nfiltr ati o n  wit h  h y al ur o ni d as e i nt o  ar e a  b ei n g  c orr e ct e d  or  a u g m e nt e d 
•   C all f or tr a ns p ort t o  E R i m m e di at el y  
•   I nf or m l o c al str o k e t e a m  d uri n g tr a ns p ort 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
5 0  
 
P N 4 0 0 8 2  I N S T R U C TI O N S  F O R  U S E  
 
P N 4 0 0 8 2 I nj e ct a bl e  H y al ur o ni c  A ci d  G el  wit h  0. 3 %  Li d o c ai n e 
 
C a uti o n:  F e d er al  L a w r estri cts t his  d e vi c e t o i n v esti g ati o n al  us e.  T his  d e vi c e is li mit e d  b y  F e d er al ( or 
U nit e d  St at es) l a w t o i n v esti g ati o n al  us e 
D E S C RI P TI O N  
P N 4 0 0 8 2 is  a  g el  of  h y al ur o ni c  a ci d  g e n er at e d  b y  Str e pt o c o c c us s p e ci es  of  b a ct eri a,  c h e mi c all y 
cr ossli n k e d  wit h  B D D E, st a bili z e d  a n d s us p e n d e d i n  p h os p h at e  b uff er e d s ali n e  at  p H = 7  wit h  0. 3 % 
li d o c ai n e. 
I N DI C A TI O N 
P N 4 0 0 8 2 is i n di c at e d f or s u b m u c os al i m pl a nt ati o n f or li p  a u g m e nt ati o n  a n d  d er m al i m pl a nt ati o n f or 
c orr e cti o n  of  p eri or al r h yti ds i n  p ati e nts  o v er t h e  a g e  of  2 1. 
C O N T R AI N DI C A TI O N S  
•   P N 4 0 0 8 2  is  c o ntr ai n di c at e d f or  p ati e nts  wit h s e v er e  all er gi es  m a nif est e d  b y  a  hist or y  of 
a n a p h yl a xis  or  hist or y  or  pr es e n c e  of  m ulti pl e s e v er e  all er gi es.  
•   P N 4 0 0 8 2  c o nt ai ns tr a c e  a m o u nts  of  gr a m  p ositi v e  b a ct eri al  pr ot ei ns  a n d is  c o ntr ai n di c at e d f or 
p ati e nts  wit h  a  hist or y  of  all er gi es t o s u c h  m at eri al.  
•   P N 4 0 0 8 2  is  c o ntr ai n di c at e d f or  p ati e nts wit h  bl e e di n g   dis or d ers. 
•   P N 4 0 0 8 2  is  c o ntr ai n di c at e d f or i m pl a nt ati o n i n  a n at o mi c al s p a c es  ot h er t h a n t h e  d er mis  or 
s u b m u c os al i m pl a nt ati o n f or li p  a u g m e nt ati o n.  
•   P N 4 0 0 8 2  s h o ul d  n ot  b e  us e d i n  p ati e nts  wit h  pr e vi o us  h y p ers e nsiti vit y t o l o c al  a n est h eti cs  of t h e 
a mi d e t y p e, s u c h  as  li d o c ai n e. 
W A R NI N G S  
•   D ef er  us e  of  P N 4 0 0 8 2  at s p e cifi c sit es i n  w hi c h  a n  a cti v e i nfl a m m at or y  pr o c ess (s ki n  er u pti o ns 
s u c h  as  c ysts,  pi m pl es, r as h es,  or  hi v es)  or i nf e cti o n is  pr es e nt  u ntil t h e  pr o c ess  h as  b e e n 
c o ntr oll e d. 
•   I nj e cti o n sit e r e a cti o ns ( e. g., li p s w elli n g, li p  p ai n,  a n d  c o nt usi o n) t o P N 4 0 0 8 2,  i n cl u di n g s h ort-
t er m  mi n or  or  m o d er at e i nfl a m m at or y s y m pt o ms st arti n g s h ortl y  aft er tr e at m e nt  of li ps    
•   P N 4 0 0 8 2  m ust  n ot  b e i m pl a nt e d i nt o  bl o o d  v ess els.  L o c ali z e d s u p erfi c i al  n e cr osis  a n d s c arri n g 
m a y  o c c ur  aft er i nj e cti o n i n  or  n e ar  v ess els, s u c h  as i n t h e li ps,  n os e,  or  gl a b ell ar  ar e a. It is 
t h o u g ht t o r es ult fr o m t h e i nj ur y,  o bstr u cti o n,  or  c o m pr o mis e  of  bl o o d v ess els.  
•   D el a y e d  o ns et i nfl a m m at or y  p a p ul es  h a v e  b e e n r e p ort e d f oll o wi n g t h e  us e  of  d er m al fill ers. 
I nfl a m m at or y  p a p ul es t h at  m a y  o c c ur r ar el y s h o ul d  b e  c o nsi d er e d  a n d tr e at e d  as  a s oft tiss u e 
i nf e cti o n. 
•   I nj e cti o ns  of  4. 0  m L  or  gr e at er ( u p p er  a n d l o w er li p  c o m bi n e d)  p er tr e at m e nt s essi o n i n cr e as es 
t h e  o c c urr e n c e  of i nj e cti o n sit e r e a cti o ns. If  a  v ol u m e  of  m or e t h a n  3  m L is  n e e d e d t o  a c hi e v e 
o pti m al  c orr e cti o n,  a f oll o w- u p tr e at m e nt s essi o n is  r e c o m m e n d e d. 
•   As  wit h  all  d er m al fill er  pr o c e d ur es,  P N 4 0 0 8 2  s h o ul d  n ot  b e  us e d i n v as c ul ar ri c h  ar e as.  Us e  of 
si mil ar  pr o d u cts  i n t h es e  ar e as, s u c h  as  gl a b ell a  a n d  n os e,  h as r es ult e d i n  c as es  of  v as c ul ar 
e m b oli z ati o n  a n d s y m pt o ms  c o nsist e nt  wit h  o c ul ar  v ess el  o c cl usi o n, s u c h  as  bli n d n ess.   

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P R E C A U TI O N S  
•   P N 4 0 0 8 2  is  p a c k a g e d f or si n gl e  us e.  D o  n ot r est erili z e.  D o  n ot  us e if  p a c k a g e is  o p e n e d  or 
d a m a g e d.  
•   T h e s af et y  or  eff e cti v e n ess  of  P N 4 0 0 8 2  f or t h e tr e at m e nt  of  a n at o mi c r e gi o ns  ot h er t h a n li ps  or 
p eri or al r h yti ds  h as  n ot  b e e n  est a blis h e d i n  c o ntr oll e d  cli ni c al st u di es. 
•   As  wit h  all tr a ns c ut a n e o us  pr o c e d ur es,  P N 4 0 0 8 2  i m pl a nt ati o n  c arries  a ris k  of i nf e cti o n.  St a n d ar d 
pr e c a uti o ns  ass o ci at e d  wit h i nj e ct a bl e  m at eri als s h o ul d  b e f oll o w e d.  
•   T h e s af et y  of  P N 4 0 0 8 2  f or  us e  d uri n g  pr e g n a n c y, i n  br e astf e e di n g f e m al es  or i n  p ati e nts  u n d er  2 2 
y e ars  h as  n ot  b e e n   est a blis h e d,  a n d t h es e i n di vi d u als  ar e  e x cl u d e d fr o m t his st u d y. 
•   S u bj e cts  wit h  k n o w n s us c e pti bilit y t o  k el oi d f or m ati o n  ar e  e x cl u d e d fr o m t his st u d y.  F or m ati o n 
of  k el oi ds  m a y  o c c ur  aft er  d er m al fill er i nj e cti o ns.  
•   H y p er pi g m e nt ati o n  m a y  o c c ur  aft er  d er m al fill er i nj e cti o ns.  S u bj e cts  wit h  k n o w n 
h y p er pi g m e nt ati o n  ar e  e x cl u d e d fr o m t his st u d y. 
•   P N 4 0 0 8 2  s h o ul d  b e  us e d  wit h  c a uti o n i n  p ati e nts  o n i m m u n os u p pr essi v e t h er a p y. 
•   Br uisi n g  or  bl e e di n g  m a y  o c c ur  at  P N 4 0 0 8 2  i nj e cti o n sit es.  P ati e nts  w h o  h a v e  u n d er g o n e t h er a p y 
wit h t hr o m b ol yti cs,  a nti c o a g ul a nts,  or i n hi bit ors  of  pl at el et  a g gr e g ati o n i n t h e  3  w e e ks  pr e c e di n g 
tr e at m e nt  wit h P N 4 0 0 8 2  h a v e  n ot  b e e n st u di e d.  
•   Aft er  us e, s yri n g es  a n d  n e e dl es s h o ul d  b e  h a n dl e d  as  p ot e nti al  bi o h a z ar ds.  Dis p os al s h o ul d  b e i n 
a c c or d a n c e  wit h  a c c e pt e d  m e di c al  pr a cti c e  a n d  a p pli c a bl e l o c al, st at e  a n d f e d er al  r e q uir e m e nts. 
•   T h e s af et y  of  P N 4 0 0 8 2  wit h  c o n c o mit a nt  d er m al t h er a pi es s u c h  as  e pil ati o n,  U V irr a di ati o n,  or 
l as er,  m e c h a ni c al  or  c h e mi c al  p e eli n g  pr o c e d ur es  h as  n ot  b e e n  e v al u at e d i n  c o ntr oll e d  cli ni c al 
tri als. 
•   P ati e nts s h o ul d  mi ni mi z e  e x p os ur e  of t h e tr e at e d  ar e a t o  e x c essi v e s u n,  U V l a m p  e x p os ur e  a n d 
e xtr e m e  c ol d  w e at h er  at l e ast  u ntil  a n y i niti al s w elli n g  a n d r e d n ess  h as  r es ol v e d. 
•   If l as er tr e at m e nt,  c h e mi c al  p e eli n g  or  a n y  ot h er  pr o c e d ur e  b as e d  o n  a cti v e  d er m al r es p o ns e is 
c o nsi d er e d  aft er tr e at m e nt  wit h  P N 4 0 0 8 2 , t h er e is  a  p ossi bl e ris k  of  eli citi n g  a n i nfl a m m at or y 
r e a cti o n  at t h e i m pl a nt sit e.  T his  als o  a p pli es if P N 4 0 0 8 2  is  a d mi nist er 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  aft er s u c h  a  pr o c e d ur e.  
•   I nj e cti o n  of P N 4 0 0 8 2  i nt o  p ati e nts  wit h  a  hist or y  of  pr e vi o us  h er p eti c  er u pti o n  m a y  b e  ass o ci at e d 
wit h r e a cti v ati o n  of t h e  h er p es.  
H O W  S U P P LI E D  
P N 4 0 0 8 2  is s u p pli e d i n  a  dis p os a bl e  gl ass s yri n g e  wit h  a  L u er-L o k ® fitti n g. P N 4 0 0 8 2  is  p a c k e d  wit h t w o 
1. 0  m L s yri n g es   a n d t w o st erili z e d  n e e dl e(s) 3 0  G  x  ½ ” i n  a  p e el tr a y  c o nt ai n e d i n  a  c art o n.  A  p ati e nt 
r e c or d l a b el is  a  p art  of t h e s yri n g e l a b el.  T his l a b el is t o  b e  att a c h e d t o  p ati e nt r e c or ds t o  e ns ur e 
tr a c e a bilit y  of t h e  pr o d u ct.  T h e  c o nt e nts  of t h e s yri n g e  ar e st eril e. 
S H E L F  LI F E  A N D  S T O R A G E  
P N 4 0 0 8 2  m ust  b e  us e d  pri or t o t h e  e x pir ati o n  d at e  pri nt e d  o n t h e  p a c k a g e.  St or e  at  a t e m p er at ur e  of  5 t o 
2 5°  C ( 7 7°  F).  D o  n ot fr e e z e.  Pr ot e ct fr o m s u nli g ht.  
D o  n ot  us e if t h e  p a c k a g e is  d a m a g e d.   
 
 

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I N J E C TI O N  T E C H NI Q U E S  
1.   St u d y  d e vi c e  c a n  b e  i nj e ct e d  b y  a  n u m b er  of  diff er e nt t e c h ni q u es t h at  d e p e n d  o n t h e tr e ati n g 
i n v esti g at or’s  e x p eri e n c e  a n d  pr ef er e n c e,  a n d  p ati e nt c h ar a ct eristi cs.  
2.   S e ri al  p u n ct u r e  i n v ol v es  m ulti pl e,  cl os el y s p a c e d i nj e cti o ns  al o n g  wri n kl es, f ol ds  or t h e 
v er milli o n  b or d er.  Alt h o u g h s eri al  p u n ct ur e  all o ws  pr e cis e  pl a c e m e nt  of t h e fill er, it  pr o d u c es 
m ulti pl e  p u n ct ur e  w o u n ds t h at  m a y  b e  u n d esir a bl e t o s o m e  p ati e nts.  
3.   Li n e a r t h r e a di n g (i n cl u d es  r et r o g r a d e  a n d  a nt e g r a d e)  is  a c c o m plis h e d  b y f ull y i ns erti n g t h e 
n e e dl e i nt o t h e  c e nt er  of t h e  ar e a t o  b e  c orr e ct e d  or  a u g m e nt e d  a n d i nj e cti n g t h e fill er  al o n g t h e 
tr a c k  as  a  “t hr e a d. ”  Alt h o u g h t hr e a di n g is  m ost  c o m m o nl y  pr a cti c e d  aft er t h e  n e e dl e h as  b e e n 
f ull y i ns ert e d  a n d is  b ei n g  wit h dr a w n, it  c a n  als o  b e  p erf or m e d  w hil e  a d v a n ci n g t h e  n e e dl e - 
a nt e gr a d e t e c h ni q u e).  T o  e n h a n c e t h e li p, t h e r etr o gr a d e li n e ar t hr e a di n g t e c h ni q u e is t h e  m ost 
a d vis a bl e.  
4.   S eri al t hr e a di n g is  a t e c h ni q u e t h at  utili z es  el e m e nts  of  b ot h  a p pr o a c h es.    
  
N ot e!  T h e  c orr e ct i nj e cti o n t e c h ni q u e is  cr u ci al f or t h e fi n al r es ult  of t h e tr e at m e nt.  
5.   T h e f oll o wi n g t e c h ni q u es s h o ul d  b e  a v oi d e d  as t h e y  m a y r es ult i n  a n i n cr e as e i n s h ort- t er m 
e pis o d es  of  br uisi n g, s w elli n g, r e d n ess,  p ai n,  or t e n d er n ess  at t h e i nj e cti o n sit e: 
•   Diss e cti o n  of t h e s u b- e pi d er m al  pl a n e  wit h l at er al  m o v e m e nt  of t h e  n e e dl e  –  “f a n ni n g ”  
•   R a pi d fl o w r at e ( > 0. 3  m L/ mi n)  of i m pl a nt  m at eri al i nj e cti o n  
•   Hi g h i nj e cti o n  v ol u m es  
•   T h e  us e  of  n e e dl es  ot h er t h a n t h os e  pr o vi d e d i n  t h e tr e at m e nt  kit 
6.   T h e  us e  of  c a n n ul as is  pr o hi bit e d 
7.   W h e n t h e i nj e cti o n is  c o m pl et e d, t h e tr e at e d sit e s h o ul d  b e  g e ntl y   m ass a g e d s o t h at it  c o nf or ms 
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.   M ass a gi n g t h at s u bst a nti all y  d ef or ms t h e li ps, or 
c a us es  bl a n c h i n g  of  c o m pr ess e d tiss u es, is  e x c essi v e,  a n d s h o ul d  b e  a v oi d e d  e x c e pt  as  d es cri b e d 
b el o w. 
8.   If  e x c essi v e  m at eri al is i m pl a nt e d  or irr e g ul arl y i m pl a nt e d,  m ass a g e t h e  ar e a s o m e w h at  m or e 
fir ml y t h a n f or t h e  us u al i m pl a nt ati o n  pr o c e d ur e t o  o bt ai n  o pti m al r es ults. 
9.   If  bl a n c hi n g  of t h e tiss u es is  o bs er v e d  d uri n g  or  dir e ctl y  aft er i nj e cti o n,  p a us e t h e  pr o c e d ur e  a n d 
m ass a g e t h e  ar e a  g e ntl y  u ntil t h e  c ol or r et ur ns.  If t h e  c o n diti o n  p ersists,  c o nt a ct t h e  M e di c al 
M o nit or . 
1 0.  T h e li ps s h o ul d  b e  a u g m e nt e d t o  a c hi e v e t h e  m a xi m u m  d esir a bl e  a p p e ar a n c e f or  b ot h t h e tr e ati n g 
i n v esti g at or  a n d t h e s u bj e ct.   S u bj e cts s h o ul d  b e  pr o vi d e d  a s m all  h a n d  mirr or t o  o bs er v e t h e 
r es ults  a n d f urt h er i nj e cti o ns  c o n d u ct e d  u ntil  m a xi m u m  b e n efit  h as  b e e n  o bt ai n e d.   C ar e s h o ul d 
b e t a k e n t o  e ns ur e t h at t h e li ps  ar e s y m m etri c fr o m ri g ht t o l eft  a n d t h at t h e  u p p er  a n d l o w er li ps 
h a v e r el ati v e  pr o p orti o n alit y.  
1 1.  T h e  p eri or al  ar e a s h o ul d  b e  c orr e ct e d  A F T E R t h e  u p p er  a n d l o w er li ps  h a v e  b e e n  c orr e ct e d.  
S o m e  c orr e cti o n  of  p eri or al r h yti ds  m a y  o c c ur  wit h li p  a u g m e nt ati o n, t h us it is  b est t o  a d dr ess 
a n y r e m ai ni n g  p eri or al  c orr e cti o n  n e e ds  aft er t h e li p i nj e cti o ns  h a v e  b e e n  c o m pl et e d.   
1 2.  If t h e tr e at e d  ar e a is s w oll e n  dir e ctl y  aft er t h e i nj e cti o n,  a n i c e  p a c k  c a n  b e  a p pli e d  o n t h e sit e f or 
a s h ort  p eri o d. I c e s h o ul d  b e  us e d  wit h  c a uti o n if t h e  ar e a is still  n u m b fr o m  a n est h eti c t o  a v oi d 
t h er m al i nj ur y. 
1 3.  S u bj e cts  s h o ul d  b e  e n c o ur a g e d t o  a v oi d  a r e c u m b e nt  p ositi o n f or s e v er al  h o urs  aft er i nj e cti o ns t o 
r e d u c e s w elli n g.   T h e  us e  of i c e,  c ol d  p a c ks  or  ot h er t h er a pi es t o r e d u c e s w elli n g s h o ul d  o nl y  b e 

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p erf or m e d  at i nstr u cti o n  of t h e i n v esti g at or.   T h e s u bj e ct s h o ul d  b e  i nstr u ct e d t o  c o nt a ct t h e sit e if 
s u bst a nti al s w elli n g  o c c ur s.  
 
 

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R E S T Y L A N E ®  SI L K I N S T R U C TI O N S  F O R  U S E  
 
 
 

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P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 2  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 3  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 4  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 5  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 6  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 7  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 8  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
7 9  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
8 0  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
8 1  
 
 
 
 

P R O  2 0 1 8 -0 2  
C o nfi d e nti al  
V ersi o n  4. 0  
Pr ot o c ol   
0 2 O C T 2 0 1 8  
8 2