A Multicenter, Double-blind, Randomized, Controlled, Roll-over Retreatment Study of the Safety and Pain Associated With Injections of PN40082, RV001 With Topical Anesthetic or RV001 for Lip Augmentation
Phase: PHASE3
Conditions: Lip Augmentation
Sponsor: Prollenium Medical Technologies Inc.



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S Y N O P SI S  
Title of St u d y:  A M ultice nter, D o u ble- bli n d, Ra n d o mize d, C o ntr olle d, R oll- o ver St u d y of t he 
Safet y a n d Pai n Ass ociat e d wit h I njecti o ns of P N 4 0 0 8 2, R V 0 0 1 wit h T o pical A nest hetic or 
R V 0 0 1 f or Li p A u g me nt ati o n  
N a m e of S p o ns or: Pr olle ni u m Me dical Tec h n ol o gies I n c. 
N a m e of Fi nis he d Pr o d uct:  P N 4 0 0 8 2 ®   
De vice C o m p ositi o n:  P N 4 0 0 8 2  - H yal ur o nic aci d gel wit h li d ocai ne ( 0. 3 % w/ w)  
 R V 0 0 1 - H yal ur o nic aci d gel wit h o ut li d ocai ne  
O bjecti ves:  T o e val uate t he safet y of re peat i njecti o ns a n d pai n ass ociate d wit h i njecti o n 
of  P N 4 0 0 8 2 a n d c o m par ati ve pai n ass ociat e d wit h R V 0 0 1 wit h a t o pical a nest hetic a n d R V 0 0 1 
f or li p a u g me ntati o n. 
St u d y Desi g n:  T his is a  m ultice nter, d o u ble- bli n d, ra n d o mize d, c o ntr olle d, r oll- o ver cli nical 
st u d y of treat me nt of s u bjects see ki n g li p a u g me nt ati o n w h o recei ve d treat me nt wit h eit her 
P N 4 0 0 8 2 or Rest yla ne Sil k i n pri or Pr ot oc ol P R O 2 0 1 8- 0 2, a n d P N 4 0 0 8 2 i n pri or Pr ot oc ol 
P R O 2 0 1 8- 0 3. S u bjects meeti n g t he i ncl usi o n/e xcl usi o n criteria will recei ve a si n gle a d diti o nal 
treat me nt wit h eit her R V 0 0 1, R V 0 0 1 wit h a t o pical a nest hetic , or P N 4 0 0 8 2.  T he E val uati n g 
I n v esti gat or will be bli n de d t o t he treat me nt. I njecti o ns of t he st u d y de vice will be perf or me d 
b y a n u n bli n de d Treati n g I n v esti gat or.  
  
At eac h visit t he b li n de d E val uati n g I n vesti gat or e val uati o ns a n d s u bject e v al uati o ns of t he 
treate d areas will be perf or me d a n d r ec or d e d.  Visits  a n d tele p h o ne c o ntacts will occ ur at:  
Visit 1 / Da y 1   – baseli ne a n d treat me nt  
 
   - Da y 3  ( ± 2 d a ys) – Saf et y f oll o w- u p tele p h o ne call 
   - Da y 1 4 ( ± 2 d a ys) – Safet y f oll o w- u p tel e p h o n e call  
 
Visit 2 / Da y 2 8 ( ± 2 da ys) / M o nt h 1 – E n d of St u d y Visit  
 
   - Da y 5 6 ( ± 4 d a ys) / M o nt h 2 – Safet y f oll o w- u p tele p h o ne call 
   - Da y 1 6 8 ( ± 7 d a ys) / M o nt h 6 – E n d of St u d y tele p h o ne call 
Efficac y e val u ati o ns are: 
S u bject pai n sc ore ( V A S) at ti me of i njecti o n 
S u bject pai n sc ore ( V A S) at 1 5 mi n utes a fter i njecti o n 
Li p F ull ness Gra di n g S cale ( L FG S)  - o verall li p f ull ness c o nsi deri n g b ot h li ps 
t o get her, f ull ness of t he u p per li p, a n d f ull ness of t he l o wer li p 

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Peri or al li nes at rest se v erit y scale ( P O L) - o verall peri oral li nes at rest se verit y 
c o nsi deri n g b ot h li ps t o get her, peri oral li nes at rest se verit y of t he u p per li p, a n d 
peri oral li nes at r est se verit y of t he l o wer li p  
Patie nt Gl o bal Aest hetic I m pr o v e me nt ( p G AI)  
I n v esti gat or Gl o bal Aest hetic I m pr o ve me nt (i G AI) 
Safet y of re p eat i njecti o ns, c o m pari n g i nci de nce of re p orte d A Es fr o m all t hree st u dies will be 
a nal yze d.  Safet y will be assesse d b y m o nit ori n g a d verse e v e nts ( A Es) at all st u d y visits.  
Ot her saf et y e val ua ti o ns are li p f u ncti o n, li p se nsati o n, li p te xt ure, li p fir m ness, li p s y m metr y, 
a n d li p m o ve me nt/f u ncti o n. 
Ot her e val u ati o ns are I n v esti gat or Ease of Use Ass ess me nt , S welli n g Assess me nt, a n d S u bject 
Satisfacti o n wit h Li ps Assess me nt.  
N u m ber of St u d y Ce nters:  Fi ve ( 5)  sites i n t he U nite d States 
D ur ati o n of P artici p ati o n: S u bjects will partici pate i n t he st u d y f or a p pr o xi matel y si x ( 6) 
m o nt hs fr o m t he ti me t he y si g n t he i nf or me d c o ns e nt f or m (I C F) t hr o u g h t he fi nal c o ntact  
D ur ati o n of St u d y:  T he st u d y will re q uire a p pr o xi matel y 2 0 m o nt hs fr o m t he be gi n ni n g t o t he 
e n d of t he st u d y (first s u bject si g ni n g t he I C F t o last c o ntact wit h last s u bject)  
N u m ber of S u bjects:  Eli gi ble s u bjects fr o m t he P R O 2 0 1 8- 0 3 st u d y will be e nc o ura ge d t o be 
retreate d d uri n g t heir D a y 1 6 8/ M o nt h 6 tele p h o ne call.  It is a ntici pate d t hat t he n u m ber of 
s u bjects will be less t ha n t he 1 5 8 s u bjects e nr olle d i n t he P R O 2 0 1 8- 0 2 st u d y. 
I ncl usi o n Criteri a:  
1.  C o m plete d Pr ot oc ol P R O 2 0 1 8- 0 3 
O R  
Pr ot oc ol P R O 2 0 1 8- 0 2 a n d di d n ot e nr oll i n Pr ot oc ol P R O 2 0 1 8- 0 3. 
2.  Me n or n o n- pr e g na nt or n o n- breastfee di n g w o me n o ver 2 1 years of a g e  
3.  At P R O 2 0 1 8- 0 2 baseli ne visit ha d a n o verall sc ore of ver y t hi n, or t hi n o n t he L FG S , 
as a gree d u p o n b y t he Tr eati n g a n d E val uati n g I n vesti gat ors, a n d desires at least a 1-
p oi nt i m pr o ve me nt i n o verall L F G S sc ore; O R  
Ha d a Fitz patric k s ki n p h ot ot y pe I V, V or VI a n d has a n L F G S  sc ore of t hic k or f ull, as 
a gree d u p o n b y t he Treati n g a n d E val uati n g I n vesti gat ors, a n d desires treat me nt t o t he 
ver mili o n b o d y of 1 or b ot h li ps 
4.  If fe mal e a n d of c hil d beari n g p ote ntial, a ne gati ve uri ne pre g n a nc y test at 
Visit  1/Da y  1 a n d t he s u bject a grees t o use a d e q uat e c o ntrace pti o n d uri n g t h e st u d y 
peri o d.  
5.  Wil li n g t o gi ve writte n i nf or me d c o nse nt a n d rea d a n d si g n t he A d vers e E ve nt of 
S pecial I nter est ( A E SI)  l etter date d 0 4J U N 1 9. 
 
 

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E xcl usi o n Criteri a:  
1.  W o me n w h o are pr e g na nt, lactati n g, or pla n ni n g a pre g na nc y. 
2.  S u bjects wit h a k n o w n hist or y of aller g y, a n a p h yla xis or h y perse nsiti vit y t o i njecta ble 
h yal ur o nic aci d pr o d ucts, l ocal a nest hetics of t h e a mi de t y pe s uc h as li d ocai ne, or t o 
late x. 
3.  S u bjects wit h a si g nifica nt o n g oi n g a d verse e v e nt fr o m P R O 2 0 1 8- 0 2 or P R O 2 0 1 8- 0 3 
t hat i n t he o pi ni o n of t he i n vesti gat or c o ul d be w orse ne d b y partici p ati o n i n t his st u d y. 
4.  S u bjects t hat e x perie n ce d a n S A E, A E SI, vis ual c h a n ges or ot her seri o us me dical 
c o n diti o ns d uri n g P R O 2 0 1 8- 0 2 or P R O 2 0 1 8- 0 3. 
5.  S u bjects wit h a b n or mal visi o n e val uati o ns ( C o nfr o ntati o nal Vis ual Fiel ds, Oc ular 
M otilit y)  or a b n or mal S nelle n Vis ual Ac uit y at Visit 1 pre-treat me nt as defi ne d i n 
secti o n 7. 6. 5 a n d A p pe n di x 5. 
6.  S u bjects w h o are u n a ble t o wit h h ol d  t hr o m b ol ytics, or i n hi bit ors of platelet 
a g gre gati o n or n o nster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds, e. g., as piri n, 
i b u pr ofe n) or ot h er s u bst a nces k n o w n t o i ncreas e c oa g ulati o n ti me (e. g., her bal 
s u p ple me nts wit h garlic or gi n g k o) wit hi n 1 0 da ys bef ore A N D after a n y i njecti o n 
sessi o n. 
7.  S u bjects wit h cli nicall y si g nifica nt or ga nic disease i ncl u di n g cli nicall y si g nifica nt 
car di o vas c ular, he p atic, p ul m o nar y, ne ur ol o gic, or re nal diseas e or ot her m e dical 
c o n diti o n, seri o us i nterc urre nt ill ness, or e xte n u ati n g circ u msta nce t hat, i n t he o pi ni o n 
of t he i n vesti gat or, precl u de partici pati o n i n t he trial. 
8.  S u bjects wit h li p tatt o os, pierci n gs, facial ha ir, or s cars t hat w o ul d i nterfere wit h 
vis ualizati o n of t he li ps a n d peri oral area f or t he effecti ve ness assess me nts.  
9.  S u bjects wit h a b n or mal li p f u ncti o n, wit h i na bilit y t o effecti vel y si p water t hr o u g h a 
stra w. 
1 0.  S u bjects wit h a b n or mal li p se nsati o n wit h i na bilit y t o feel a 0. 4 G m o n ofila me nt or a 
c ott o n wis p at a n y site o n t he li p.  
1 1.  S u bjects wit h m o derate or se vere a b n or m al li p as y m metr y.  
1 2.  S u bjects wit h a n y mass f or mati o n o n t he li p. 
1 3.  S u bjects wit h de nt ures or a n y de vice c o veri n g all or part of t he u p p er pal ate, a n d/ or 
se vere m al occl usi o n or d e nt ofacial or ma xill ofaci al def or mities as j u d ge d b y t he 
Treati n g I n vesti gat or. S u bjects pla n ni n g t o u n der g o e xte nsi ve de nta l pr o ce d ures s uc h 
as de ntal i m pla nts, m ulti ple t o ot h e xtracti o ns, or oral s ur ger y s h o ul d n ot p artici pate. 
Mi n or de ntal pr oce d ures s uc h as teet h cl ea ni n g a n d re pair of caries are n ot  
e xcl usi o nar y. 
1 4.   S u bjects t hat ha ve u n der g o ne faci al plastic s ur ger y or recei ve d per ma ne nt facial 
i m pla nts (e. g., p ol y met h yl met hacr ylate, silic o ne, p ol ytetrafl u or oet h yle n e, 
p ol yacr yla mi de, lifti n g t hrea ds) a n y w here i n t he face or nec k, or are pla n ni n g t o be 
i m pla nte d wit h a n y of t hese pr o d ucts d uri n g t he st u d y. 

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1 5.  S u bjects t hat ha ve u n der g o ne se mi -per ma n e nt der mal filler treat me nt (e. g., calci u m 
h y dr o x yla patite, p ol y- L- l actic aci d) i n t he l o wer face ( bel o w t h e or bital ri m) wit hi n 1 2 
m o nt hs bef ore e nr oll me nt or are pla n ni n g t o u n der g o s uc h treat me nt d uri n g t he st u d y. 
1 6.  S u bjects t hat ha ve u n der g o ne faci al tiss ue a u g me ntati o n wit h fat i njecti o ns, b ot uli n u m 
t o xi n i njecti o ns i n t he l o wer face ( bel o w t he or bital ri m), mes ot hera p y, or c os metic 
pr oce d ur es i n t he face or nec k (e. g., face- lift, laser, p h ot o- m o d ulati o n, i nte nse p ulse d 
li g ht, ra di o fre q ue n c y, der ma brasi o n, m o derate or greater de pt h c h e mical p eel, 
micr o nee dli n g, or ot her a blati ve pr oce d ures) wit hi n 9 m o nt hs bef ore e nr oll me nt or are 
pla n ni n g t o u n der g o a n y of t hese pr oce d ures d uri n g t he st u d y. 
1 7.  t hat ha ve use d A N Y li p filli n g a ge nts wit hi n 1 2 m o nt hs of st u d y e nr oll me nt 
( h yal ur o nic aci d pr o d ucts, c olla ge n- bas e d pr o d ucts, etc.) ot her t h a n I n vesti g ati o nal 
De vice a d mi nistere d i n P R O 2 0 1 8- 0 2 a n d P R O- 2 0 1 8- 0 3. 
1 8.  S u bjects t hat ha ve use d a n y li p pl u m pi n g pr o d ucts or de vices wit hi n 1 0 da ys bef ore 
e nroll me nt or ar e pla n ni n g t o use s uc h pr o d ucts d uri n g t he st u d y. 
1 9.  S u bjects t hat  ha ve be g u n usi n g a n y o ver-t he-c o u nt er ( O T C) or pres cri pti o n oral or 
t o pical a nti- wri n kle pr o d ucts f or t he li ps or ar o u n d t he m o ut h wit hi n 9 0 da ys bef ore 
e nr oll me nt or ar e pla n ni n g t o be gi n usi n g s uc h pr o d ucts d uri n g t he st u d y ( S u bjects 
w h o ha ve bee n o n a sta bl e re gi me n of s u c h pr o d ucts f or at least 9 0 da ys are eli gi ble 
f or t he st u d y a n d m ust c o nti n ue t heir re gi me n t hr o u g h o ut t he st u d y). 
2 0.  S u bjects t hat ha ve a hist or y or pres e nce of b lee di n g dis or ders. 
2 1.  S u bjects t hat ha ve use d s yste mic c ortic oster oi ds or i m m u n os u p pressi ve me dicati o ns 
wit hi n 3 0 da ys pri or t o treat me nt. 
2 2.  S u bjects t hat are o n a c o nc urre nt re gi me n of li d ocai ne or str uct urall y relate d l ocal 
a nest hetics (e. g., b u pi v acai ne) 
2 3.  S u bjects t hat ha ve a n acti ve i nfla m mati o n (s ki n er u pti o ns s uc h as c ysts, pi m ples, 
ras hes, or hi ves), i nfecti o n ca ncer o us or preca ncer o us lesi o n, or u n heale d w o u n d o n 
t he face. 
2 4.  S u bjects t hat ha ve a hist or y of k n o w n s usce pti bilit y t o kel oi d f or mati o n or 
h y pertr o p hic scars. 
2 5.  S u bjects t hat ha ve p or p h yria. 
2 6.  S u bjects t hat ha ve acti ve her pes la bialias lesi o ns at t he ti me of i njecti o ns.  S u bjects 
wit h a hist or y of her pes l a bialis w h o ha ve ha d f o ur ( 4) or m ore o ut brea ks i n t he 1 2 
m o nt hs pri or t o e nr oll me nt are als o e x cl u de d e v e n i n t he a bse nce of lesi o ns at t he 
baseli ne visit.  
2 7.  S u bjects t hat ha ve i m pair e d car di ac c o n d u cti o n,  se verel y i m paire d he patic f u ncti o n, 
or se ver e re n al d ysf u ncti o n t hat, i n t he o pi ni o n of t he i n vesti gat or, w o ul d place t he m 
at ris k of ass ociate d c o m p licati o ns fr o m t hese ill nesses d uri n g t he c o urse of t he st u d y. 
2 8.  S u bjects t hat ha ve a n y u n c o ntr olle d disease, i.e., a c o n diti o n t hat has n ot bee n 
a p pr o priatel y dia g n os e d, e val uate d, a n d recei ve d me dicall y a p pr o pri ate treat me nt or 
care  

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2 9.  S u bjects t hat ha ve se vere car di o vas c ular disease; e xa m ples i ncl u de b ut are n ot li mite d 
t o Ne w Y or k H eart Ass o ciati o n heart fail ure cl assificati o n III or I V, u nsta ble a n gi na, 
a n d i nter nal pace ma k ers. P ote ntial s u bjects wit h ot her si g nifica nt car di o vas c ular 
diseases s h o ul d be disc usse d wit h t he Me dical M o nit or bef ore e nr olli n g. 
 
 
St u d y De vice  
P N 4 0 0 8 2: a clear, c ol orless gel i n 1. 0 m L pre-fille d s yri n ges wit h 2 5 m g/ m L of sta bilize d 
h yal ur o nic aci d a n d li d ocai ne 0. 3 % w/ w 
R V 0 0 1 wit h a t o pical a nest hetic:  a clear, c ol orless gel  i n 1. 0 m L pre -fille d s yri n ges wit h 
2 5 m g/ m L of sta bilize d h yal ur o nic aci d t o be us e d wit h L M X 4 t o pical li d ocai ne 
R V 0 0 1:  a clear, c ol orless gel  i n 1. 0 m L pre -fille d s yri n ges wit h 2 5 m g/ m L of sta bilize d 
h yal ur o nic aci d t o be us e d al o ne 
St atistic al Met h o ds  
Safet y a n d efficac y r es ults will be s u m marize d des cri pti vel y f or all s u bjects w h o recei ve 
treat me nt i n t his st u d y.  Data will be s u m marize d o verall a n d als o br o k e n d o w n b y t he 
treat me nt ar m.  A d etaile d descri pti o n of statistical a nal ysis of t he data fr o m t his st u d y will be 
i ncl u de d i n a se parate Statistical A nal ysis Pla n ( S A P) d oc u me nt. 
Effic ac y A n al ysis: 
C o m pare s u bject pai n sc ores ( V A S) b et wee n P N 4 0 0 8 1, R V 0 0 1 wit h t o pical  a nest hetic, a n d 
R V 0 0 1.  C ha n ge fr o m baseli ne will be s u m marize d f or L F G S a n d P O L. Ot her efficac y 
varia bles i ncl u de p G AI, i G AI, a n d S welli n g Assess me nt at Visit 2/ M o nt h 1. 
S afet y A n al ysis: 
Safet y of t he treat me nt wit h P N 4 0 0 8 2 or R V 0 0 1 wit h t o pical a nest hetic or R V 0 0 1 will be 
e val uat e d b y t he n at ure, s e verit y, a n d fre q ue n c y of treat me nt- e mer ge nt a d v erse e ve nts 
( T E A Es). All A Es t hat o cc ur d uri n g t he st u d y will be rec or de d w h et her or n ot t he y are 
c o nsi dere d t o be relate d t o treat me nt. A des cri pti o n of t he A E will be rec or de d wit h t he date of 
o nset, date of r es ol uti o n, se verit y of t he A E, relati o ns hi p t o t he st u d y de vice, acti o n ta ke n, a n d 
t he o utc o me. T he fre q ue nc y a n d t y pe of A Es will be e val uat e d f or eac h gr o u p base d o n t he 
pre vi o us treat me nts t hat t he y recei ve d i n t he P R O 2 0 1 8- 0 2 a n d P R O 2 0 1 8- 0 3 pr ot oc ols, a n d 
t he differ e nce i n A Es i n t his pr ot oc ol ( P R O 2 0 1 9- 0 2) bet wee n t h e s u bjects w h o recei ve d 
i njecti o ns t hat c o ntai ne d li d ocai ne, a n d t he gr o u p t hat was treate d wit h t o pical li d ocai ne.  
Safet y of re p eat i njecti o ns, c o m pari n g i nci de nce of re p orte d A Es fr o m all t hree st u dies, P R O 
2 0 1 8- 0 2, P R O 2 0 1 8- 0 3, a n d P R O 2 0 1 9- 0 2 will be disc usse d i n t he cli nical st u d y re p ort.  
A d verse e ve nts will be c o de d t o s yste m or ga n class a n d preferre d ter ms usi n g t he Me dical 
Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A, Versi o n 2 0 or hi g her). 
Fre q u e nc y a n d per ce nta g e of s u bjects re p orti n g treat me nt -e mer g e nt a d verse e ve nts ( T E A Es) 
will be ta b ulate d  o ver all a n d f or eac h treat me nt i n P R O 2 0 1 9- 0 2 b y preferre d ter ms a n d f urt her 
b y se verit y a n d r elati o ns hi p t o st u d y de vice. I n s u m maries of se verit y a n d relati o ns hi p, 
s u bjects re p orti n g m ore t ha n o ne e v e nt i n a treat m e nt ar m t hat are ma p pe d t o t he sa me 

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preferre d t er m will be c o u nte d o nl y o nce i n t hat treat me nt ar m  u n der t he str o n gest se verit y  a n d 
relati o ns hi p, res pecti vel y. I n a d diti o n, vis ual-relat e d T E A Es will be s u m marize d s e paratel y b y 
preferre d t er m.  
 
 
 

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2  
S C H E D U L E O F A C TI VI TI E S  
Visit N u m ber ( M o nt h)  
Visit 1 
P h o ne 
C o nt act  
P h o ne 
C o nt act  
Visit 2  
( M o 1) 
P h o ne 
C o nt act  
( M o 2) 
P h o ne 
C o nt act  
( M o 6 ) 
U nsc he d 
Visit  
Sc he d ule 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 5 6  
D a y 1 6 8   
Sc he d uli n g Wi n d o w  
± 1 4 d a ys of D a y 
1 6 8/ M o nt h 6 
tele p h o ne c all f or 
P R O 2 0 1 8 -0 3  
± 2 d a ys  ± 2 d a ys  ± 2 d a ys  ± 4 d a ys  
± 7 d a ys  
 
I nf or me d c o nse nt an d A E SI Letter  
X  
 
 
 
 
 
 
Me dical hist or y/ de m o gra p hics  
X a 
 
 
 
 
 
 
Vital Si g ns  
X  
 
 
 
 
 
 
Visi o n e val uati o ns ( S nelle n vis ual 
ac uit y, c o nfr o ntati o nal vis ual fiel ds, 
oc ular m otilit y )b 
X 
 
 
X 
 
 
X c 
C o nc o mita nt m e dicati o n/ 
Treat me nt  
X 
X 
X 
X 
X 
X 
X 
I ncl usi o n/e xcl usi o n criteria 
re vie w 
X 
 
 
 
 
 
 
Uri ne pre g na nc y test  d 
X  
 
 
 
 
 
 
Reas o n f or st u d y partici pati o n q uesti o n  
X  
 
 
 
 
 
 
Li p F ull ness Gra di n g Scale ( L F G S)  
( o verall, u p per li p, a n d l o wer li p) 
X 
 
 
X 
 
 
X c 
Peri oral  li nes at rest se verit y scale 
( P O L) ( o verall, u p per li p, a n d l o wer 
li p) 
X 
 
 
X 
 
 
X c 
Li p f u ncti o n  
X e 
 
 
X  
 
 
X c 
Li p se nsati o n  
X e 
 
 
X  
 
 
X c 
Li p te xt ure  
X e 
 
 
X  
 
 
X c 
Li p fir m ness  
X e 
 
 
X  
 
 
X c 
Li p s y m metr y  
X e 
 
 
X  
 
 
X c 
Li p m o ve me nt/f u ncti o n  
X e 
 
 
X  
 
 
X c 
Patie nt G AI ( p G AI)  
X e 
 
 
X  
 
 
X c 
S welli n g Assess me nt  
X e 
 
 
X  
 
 
X c 
I n vesti gat or G AI (i G AI) 
X e 
 
 
X  
 
 
X c 
S u bject Satisfacti o n wit h Li ps  
X e 
 
 
X  
 
 
X c 
Ra n d o mizati o n   
X  
 
 
 
 
 
 
A p plicati o n of Li d ocai ne crea m  or 
i nert crea m 1 5 mi n utes pri or t o 
treat me nt 
X 
 
 
 
 
 
 
Treat me nt wit h st u d y de vice  
X  
 
 
 
 
 
 
I n vesti gat or Ease of Use Assess me nt 
X  
 
 
 
 
 
 
S u bject Pai n sc ore V A S ( i m me diatel y 
after treat me nt , 1 5 mi n utes after 
treat me nt) 
X 
 
 
 
 
 
 
S u bject Pai n sc ore  V A S  
 
 
 
X  
 
 
X  
Treat me nt q uesti o n  
 
 
 
X  
 
 
 
A d verse e ve nt assess me nt  
X  
X  
X  
X  
X  
X  
X  
S u bject Diar y  
Dis pe nse  
 
 
C ollect  
 
 
 
N ote: T he ti mi n g of eac h visit is relati ve t o Da y 1, w hic h is defi ne d as t he da y t he s u bject is  treate d. 
a. T o be u p date d if/as nee de d f or c ha n ges si nce Visit 1 of P R O 2 0 1 8 -0 2 . 
b.  T o be perf or me d pri or t o a n y treat me nt a n d re peate d 3 0 mi n utes f oll o wi n g a n y treat me nt a n d all f oll o w -u p visits.  

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c. If/as nee de d 
d.  F or w o me n of c hil d beari n g p ote ntial, t o be c o m plete d  pri or t o e nr oll me nt.  
e. T o be perf or me d pri or t o treat me nt 
 
 

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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 Ta bles  .............................................................................................................................. 1 4 
List of Fi g ures ............................................................................................................................. 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 4 
5  
I N T R O D U C TI O N ................................................................................................................. 1 5 
6  
S T U D Y O B J E C TI V E S  ......................................................................................................... 1 5 
7  
I N V E S TI G A TI O N A L P L A N ............................................................................................... 1 5 
7. 1  
O verall St u d y Desi g n ........................................................................................................ 1 5  
7. 2  
Be gi n ni n g a n d E n d of St u d y ............................................................................................. 1 6  
7. 3  
St u d y P o p ulati o n ............................................................................................................... 1 6  
7. 3. 1  I n cl usi o n Criteria ......................................................................................................... 1 6 
7. 3. 2  E xcl usi o n Criteria  ........................................................................................................ 1 7 
7. 3. 3  S u bject Wit h dra wal Criteria  ........................................................................................ 1 9 
7. 3. 4  Re place me nt of S u bjects  ............................................................................................. 1 9 
7. 4  
Treat me nts  ......................................................................................................................... 2 0 
7. 4. 1  D osa ge a n d F or m ulati o ns  ............................................................................................ 2 0 
7. 4. 2  Ra n d o mizati o n ............................................................................................................ 2 0  
7. 4. 3  St u d y De vice A d mi nistrati o n  ...................................................................................... 2 0 
7. 4. 4  Bli n di n g of St u d y De vice ............................................................................................ 2 3  
7. 4. 5  Met h o d of Pac ka gi n g, La beli n g, St ora ge, a n d Dis p e nsi n g ......................................... 2 3  
7. 4. 6  St u d y De vice Acc o u nta bilit y ...................................................................................... 2 4  
7. 4. 7  C o nc o mita nt Me dicati o ns ........................................................................................... 2 4  
7. 4. 7. 1  
Preca uti o ns  .......................................................................................................... 2 4 
7. 4. 7. 2  
Me dicati o ns a n d Tr eat me nts Pr o hi bite d D uri n g t he St u d y ................................. 2 4  
7. 4. 7. 3  
C o nc o mita nt Me dicati o ns a n d Treat me nts All o w e d D uri n g t he St u d y .............. 2 5  
7. 4. 8  Assess me nt of C o m plia nce ......................................................................................... 2 5  
7. 5  
St u d y Sc he d ule .................................................................................................................. 2 5  
7. 6  
St u d y Pr oce d ures .............................................................................................................. 2 5  
7. 6. 1  St u d y R oles ................................................................................................................. 2 6  
7. 6. 2  Writte n I nf or m e d C o nse nt ........................................................................................... 2 6  
7. 6. 3  Si g nifica nt Me dical Hist or y/ De m o gra p hic I nf or m ati o n ............................................. 2 6  
7. 6. 4  Vital Si g ns  ................................................................................................................... 2 6 
7. 6. 5  Visi o n E val uati o ns ...................................................................................................... 2 7  
7. 6. 5. 1  
S nelle n Vis ual Ac uit y  ......................................................................................... 2 7 

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7. 6. 5. 2  
C o nfr o ntati o nal Vis ual Fiel ds ............................................................................. 2 7  
7. 6. 5. 3  
Oc ular M otilit y  .................................................................................................... 2 7 
7. 6. 6  Pri or a n d C o nc o mita nt Me d icati o n/ Treat me nt R e vie w  .............................................. 2 8 
7. 6. 7  Re vie w I ncl usi o n/ E xcl usi o n Criteria .......................................................................... 2 8  
7. 6. 8  Uri ne Pre g na n c y Test a n d Acce pt a ble C o ntrace pti ve Met h o ds  .................................. 2 8 
7. 6. 9  Reas o n f or St u d y Partici pati o n Q uesti o n .................................................................... 2 8  
7. 6. 1 0  Li p F ull ness Gra di n g Scale ......................................................................................... 2 8  
7. 6. 1 1  Peri oral Li nes at Rest Se verit y Scale  .......................................................................... 2 9 
7. 6. 1 2  Li p F u ncti o n E val uati o n .............................................................................................. 2 9  
7. 6. 1 3  Li p Se nsati o n E val uati o n ............................................................................................ 2 9  
7. 6. 1 4  Li p Te xt ure E val u ati o n ............................................................................................... 2 9  
7. 6. 1 5  Li p Fir m ness E val uati o n  ............................................................................................. 3 0 
7. 6. 1 6  Li p S y m metr y E val uati o n  ........................................................................................... 3 1 
7. 6. 1 7  Li p M o ve me nt/ F u ncti o n E val uati o n ........................................................................... 3 1  
7. 6. 1 8  Patie nt Gl o bal Aest hetic I m pr o v e me nt ( p G AI) Sc ore  ................................................ 3 1 
7. 6. 1 9  I n v esti gat or Gl o bal Aest hetic I m pr o ve me nt (i G AI) Sc ore ......................................... 3 1 
7. 6. 2 0  S welli n g Assess me nt  ................................................................................................... 3 2 
7. 6. 2 1  S u bject Satisfacti o n wit h Li ps ( Vis ual A nal o g Scale [ V A S])  .................................... 3 2 
7. 6. 2 2  I n v esti gat or Ease of Use Assess me nt .......................................................................... 3 2 
7. 6. 2 3  S u bject Pai n Sc ore – Vis ual A nal o g Scale  .................................................................. 3 3 
7. 6. 2 4  Treat me nt Q u esti o n  ..................................................................................................... 3 3 
7. 6. 2 5  S u bject Diar y Car d  ...................................................................................................... 3 3 
7. 6. 2 6  A d verse E v e nts a n d Seri o us A d verse E v e nts Assess me nt .......................................... 3 3  
7. 7  
Visit -S pecific Pr oce d ur es  .................................................................................................. 3 3 
7. 7. 1  Visit 1/ Da y 1: Treat me nt  ............................................................................................. 3 3 
7. 7. 2  Tele p h o ne C o ntacts o n D a y 3 a n d Da y 1 4 ( ± 2 da ys) ................................................. 3 4  
7. 7. 3  Visit 2/ Da y 2 8 ( ± 2 da ys): M o nt h 1 E n d of St u d y Visit ............................................. 3 5  
7. 7. 4  Tele p h o ne C o ntact o n D a y 5 6 ( M o nt h 2) ± 4 da ys ..................................................... 3 5  
7. 7. 5  E n d of St u d y Tele p h o ne C o ntact o n Da y 1 6 8 ( M o nt h 6) ± 7 da ys .............................. 3 5  
7. 7. 6  U nsc he d ule d Visit  ....................................................................................................... 3 6 
7. 8  
Efficac y E n d p oi nts ............................................................................................................ 3 6  
7. 9  
Assess me nt of Safet y  ........................................................................................................ 3 6 
7. 9. 1  Safet y E n d p oi nts ......................................................................................................... 3 6  
7. 9. 2  Ot her Safet y E v al uati o ns  ............................................................................................. 3 7 
7. 9. 3  Defi niti o ns of Ter ms  ................................................................................................... 3 7 
7. 9. 3. 1  
A d verse E v e nt  ..................................................................................................... 3 7 
7. 9. 3. 2  
S us pecte d A d vers e Reacti o n  ............................................................................... 3 7 
7. 9. 3. 3  
U ne x pect e d A d verse E ve nt ................................................................................. 3 7  
7. 9. 3. 4  
A d verse E v e nts of S peci al I nt erest  ..................................................................... 3 7 
7. 9. 3. 5  
Seri o us A d verse E v e nt ........................................................................................ 3 8  
7. 9. 3. 6  
Pla n ne d H os pitalizati o n  ...................................................................................... 3 8 
7. 9. 4  Pre g na nc y  .................................................................................................................... 3 8 
7. 9. 5  M o nit ori n g A d verse E ve nts ........................................................................................ 3 9  
7. 9. 6  Assess me nt of A d vers e E ve nts ................................................................................... 3 9  
7. 9. 6. 1  
Assess me nt of Se verit y  ....................................................................................... 3 9 
7. 9. 6. 2  
Assess me nt of Ca u salit y ..................................................................................... 3 9 

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7. 9. 6. 3  
Refere n ce Safet y I nf or mati o n f or Assessi n g E x pecte d ness of A d v erse 
E ve nts .................................................................................................................. 4 0  
7. 9. 7  Re p orti n g Safet y O bser v ati o ns ................................................................................... 4 0  
7. 9. 8  Diar y Assess me nts  ...................................................................................................... 4 1 
7. 9. 9  Criteria f or E arl y Ter mi n ati o n of t he St u d y ................................................................ 4 1  
7. 9. 1 0  Wit h dra wal a n d U n bli n di n g of Treat me nt D u e t o Safet y O bser vati o ns ..................... 4 2  
7. 9. 1 0. 1  Wit h dra wal  .......................................................................................................... 4 2 
7. 9. 1 0. 2  U n bli n di n g Treat me nt f or a S u bject D uri n g t he St u d y ....................................... 4 2  
8  
S T A TI S TI C A L M E T H O D S  ................................................................................................ 4 2 
8. 1  
A nal ysis P o p ulati o ns ......................................................................................................... 4 2  
8. 2  
Efficac y A nal ysis  .............................................................................................................. 4 2 
8. 3  
Safe t y A nal ysis ................................................................................................................. 4 2 
8. 4  
Sa m ple Size Deter mi nati o n  ............................................................................................... 4 3 
9  
E T HI C S  .................................................................................................................................. 4 3 
9. 1  
I nf or me d C o nse nt .............................................................................................................. 4 3 
9. 2  
I nstit uti o nal Re vie w B oar d (I R B) ..................................................................................... 4 3 
9. 3  
S u bject C o nfi de ntialit y  ..................................................................................................... 4 3 
9. 4  
St u d y Re gistrati o n ............................................................................................................. 4 4  
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 4 
1 0. 1  Site Re g ulat or y D oc u me nts Re q uire d f or I nitiati o n ......................................................... 4 4  
1 0. 2  Mai nte na nce a n d Rete nti o n of Rec or ds ............................................................................ 4 4  
1 0. 2. 1  Case Re p ort F or ms ( C R Fs)  ......................................................................................... 4 5 
1 0. 2. 2  Pri mar y S o urce D o c u me nts ......................................................................................... 4 6  
1 0. 3  St u d y M o nit ori n g .............................................................................................................. 4 6  
1 0. 4  A u dits a n d I ns p ecti o ns ...................................................................................................... 4 6  
1 0. 5  M o dificati o ns t o t he Pr ot oc ol ............................................................................................ 4 7  
1 0. 6  C o m pleti o n of t he St u d y ................................................................................................... 4 7  
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 7 
1 2  LI S T O F R E F E R E N C E S  ..................................................................................................... 4 8 
1 3  I N V E S TI G A T O R A G R E E M E N T ...................................................................................... 4 9 
1 4  A P P E N DI X 1: FI L L E R FI R S T AI D P R O T O C O L ( C H E S T N U T C., 2 0 1 8)  .................. 5 0 
1 5  A P P E N DI X 2: 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 2 
1 6  A P P E N DI X 3:  R V 0 0 1 I N S T R U C TI O N S F O R U S E  ........................................................ 5 6 
1 7  A P P E N DI X 4:  L M X 4 P A C K A G E I N S E R T  ...................................................................... 6 1 
1 8  A P P E N DI X 5:  VI SI O N E V A L U A TI O N R E S U L T S  ........................................................ 6 5 
 

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List of T a bles  
Ta ble  1. 
Li p Te xt ure Sc ori n g Crit eria .................................................................................. 3 0  
Ta ble 2.  
 Li p Fir m ness Sc ori n g Criteria  ............................................................................... 3 0 
Ta ble  3. 
Li p S y m metr y Sc ori n g Criteria  .............................................................................. 3 1 
 
List of Fi g ures  
Fi g ure 1 Vis ual A n al o g Scale f or S u bject Satisfacti o n  .................................................................. 3 2 
Fi g ure 2 I n v esti gat or Eas e of Use .................................................................................................. 3 2  
Fi g ure 3 Vis ual A n al o g Scale f or S u bject Assess m e nt of Pai n  ..................................................... 3 3 
 
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  
Ter m  
Defi niti o n  
A E  
a d verse e ve nt 
A E SI  
A d verse E ve nt of S pecial I nterest  
C F R  
C o de of Fe deral Re g ulati o ns 
C R F  
case re p ort f or m , pa per or electr o nic 
D C F  
data c orrecti 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 nistrati o n 
G C P  
G o o d Cli nical Practice  
I C F 
inf or me d c o nse nt f or m  
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n  
iG AI  
I n vesti gat or Gl o bal Aest hetic I m pr o ve me nt 
I R B 
Instit uti o nal Re vie w B oar d  
I U D 
i ntra uteri ne de vice 
L F G S  
Li p F ull ness Gra di n g Scale 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
O T C  
o ver- t he-c o u nter 
p G AI  
Patie nt Gl o bal Aest hetic I m pr o ve me nt 
PI  
pri nci pal i n vesti gat or  
P O L  
Peri o ral Li nes Se verit y Scale 
S A E  
seri o us a d verse e ve nt 
S A R  
s us pecte d a d verse reacti o n 
S O P  
sta n dar d o perati n g pr oce d ure 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
V A S  
vis ual a nal o g scale 

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5  
IN T R O D U C TI O N  
P N 4 0 0 8 2 is a sta bilize d h yal ur o nic aci d d er mal fill er wit h li d ocai ne.  R V 0 0 1  is a sta bilize d 
h yal ur o nic aci d d er mal filler .  R V 0 0 1 is hi g hl y h y dr o p hilic a n d is os m olalit y bala nce d, res ulti n g 
i n less s welli n g res p o nse t o i njecti o ns a n d less pai n o n i njecti o n.   
T he p ur p ose of t his st u d y is t o e val uate t he safet y of re peat i njecti o ns a n d p ai n ass ociate d wit h 
i njecti o n of  P N 4 0 0 8 2 a n d c o m parati ve p ai n ass ociate d wit h R V 0 0 1 wit h a t o pical a nest hetic a n d 
R V 0 0 1 f or li p a u g me ntati o n i n s u bjects w h o partici pate d i n P R O 2 0 1 8- 0 2 a n d P R O 2 0 1 8- 0 3. 
6  
S T U D Y O B J E C TI V E S  
T o e val uate t he s afet y of re peat li p a u g me nt ati o n treat me nt a n d p ai n ass oci ate d wit h i njecti o n 
a n d safet y of P N 4 0 0 8 2, R V 0 0 1 wit h t o pical a nest hetic , or R V 0 0 1 f or li p a u g me ntati o n. 
7  
IN V E S TI G A TI O N A L P L A N  
7. 1  
O ver all St u d y Desi g n 
T his is a  m ultice nter, d o u ble- bli n d, ra n d o mize d, c o ntr olle d, r oll- o ver st u d y of t he safet y a n d pai n 
ass ociate d wit h i njecti o ns of  P N 4 0 0 8 2, R V 0 0 1 wit h t o pical a nest hetic , or R V 0 0 1 f or li p 
a u g me ntati o n. 
Visits a n d tele p h o ne c o nt acts will occ ur at:  
Visit 1 / Da y 1 – baseli ne a n d treat me nt . 
  
  -  Da y 3 ( ± 2 d a ys) - Saf et y f oll o w- u p tele p h o ne call 
  -  Da y 1 4 ( ± 2 d a ys) – Safet y f oll o w- u p tel e p h o n e call  
 
Visit 2 / Da y 2 8 ( ± 2 da ys) / M o nt h 1 – E n d of St u d y ( E O S) Visit 
 
  -  Da y 5 6 ( ± 4 d a ys) - Safet y f oll o w-u p tele p h o n e call  
  -  Da y 1 6 8 ( ±7 d a ys)  – E n d of St u d y tele p h o ne call 
E fficac y e val u ati o ns are: 
S u bject pai n sc ore ( V A S) at ti me of i njecti o n, 1 5 mi n utes after i njecti o n  a n d at Visit 2 . 
Li p F ull ness Gra di n g S cale ( L FG S)  - o verall li p f ull ness c o nsi deri n g b ot h li ps 
t o get her, f ull ness of t he u p per li p, a n d f ull ness of t he l o wer li p 
Peri o ral li nes at rest se v erit y scale ( P O L) - o verall peri oral li nes at rest se verit y 
c o nsi deri n g b ot h li ps t o get her, peri oral li nes at rest se verit y of t he u p per li p, a n d 
peri oral li nes at r est se verit y of t he l o wer li p  
Patie nt Gl o bal Aest hetic I m pr o v e me nt ( p G AI)  
I n v esti gat or Gl o bal Aest hetic I m pr o ve me nt (i G AI) 

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Safet y will be assesse d b y m o nit ori n g a d verse e v e nts ( A Es) at all st u d y visits. A d verse e v e nts of 
special interest, i ncl u di n g a n y c ha n g es i n visi o n a n d a n y e ve nts attri b uta bl e t o a n e m b olic or 
isc he mic ca us e (e. g., s ki n i nfarcti o n), will be m o nit ore d . Ot her s afet y e v al u ati o ns are li p 
f u ncti o n, li p se nsati o n, li p te xt ure, li p fir m ness, li p s y m metr y, a n d li p m o ve me nt/f u ncti o n. 
 
Ot her e val u ati o ns are  I n v esti gat or Ease of Use Ass ess me nt, S welli n g Assess me nt , a n d S u bject 
Satisfacti o n wit h Li ps Assess me nt . 
7. 2  
Be gi n ni n g a n d E n d of St u d y  
A s u bject is c o nsi dere d t o be e nr olle d i n t he st u d y w he n he/s he h as pr o vi de d writte n i nf or me d 
c o nse nt. 
A s u bject is c o nsi dere d t o ha ve c o m plete d t h e st u d y after h e/s he has c o m pl ete d t he Da y 1 6 8 
M o nt h 6/ E n d of st u d y tele p h o ne call. 
A s u bject is c o nsi dere d t o ha ve wit h dra w n after h e/s he has wit h dra w n c o nse nt or has bee n 
wit h dra w n u n der t h e c o n diti o ns s pecifie d i n Secti o n  7. 3. 3 . 
A s u bject is c o nsi dere d t o ha ve bee n l ost t o f oll o w- u p if he/s he ca n n ot be c o ntacte d b y t he 
i n vesti gat or. T he i n vesti gat or will d oc u me nt eff orts t o atte m pt t o reac h t he s u bject at least t wice 
b y tele p h o ne a n d will se n d a certifi e d letter bef ore c o nsi deri n g t he s u bject l ost t o f oll o w- u p. T he 
e n d of partici p ati o n f or a s u bject l ost t o f oll o w- u p is d oc u me nte d as t he dat e of t he certifie d 
letter. 
Eac h s u bject will be m o nit ore d f or t he occ urre nce of A Es, i ncl u di n g seri o us a d verse e ve nts 
( S A Es), starti n g i m me diatel y after tr eat me nt i nitiati o n. Eac h s u bject will be f oll o we d f or safet y 
m o nit ori n g u ntil he/s he is disc har ge d fr o m t he st u d y. 
F oll o w- u p pr oce d ur es rel ate d t o pre g na n c y, A Es, or S A Es ma y c o nti n ue be y o n d t he e n d of t he 
st u d y. 
Eac h s u bject will partici p ate i n t he st u d y f or a p pr o xi matel y 6 m o nt hs fr o m t he ti me he/s he si g ns 
t he I C F t hr o u g h t he fi n al c o ntact. After deter mi nati o n of eli gi bilit y at Visit 1/ Da y 1, eac h s u bject 
will be treate d wit h st u d y de vice. 
It is a ntici pated t hat t he d urati o n of t his st u d y will be 2 0 m o nt hs fr o m t he be gi n ni n g t o t he e n d of 
t he st u d y (first s u bject si g ni n g t he I C F t o last c o ntact wit h last s u bject). 
7. 3  
St u d y P o p ul ati o n 
7. 3. 1  I ncl usi o n Criteri a 
S u bject s m ust meet all  of t he f oll o wi n g criteria  t o be eligi ble f or t he st u d y: 
1.  C o m plete d Pr ot oc ol P R O 2 0 1 8- 0 3 
O R  
Pr ot oc ol P R O 2 0 1 8- 0 2 a n d di d n ot e nr oll i n Pr ot oc ol P R O 2 0 1 8- 0 3. 
2.  Me n or n o n- pr e g na nt or n o n- breastfee di n g w o me n o ver 2 1 years of a g e  

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3.  At P R O 2 0 1 8- 0 2 baseli ne visit ha d a n o verall sc ore of ver y t hi n, or t hi n o n t he L FG S , as 
a gree d u p o n b y t he Treati n g a n d E val uati n g I n vesti gat ors, a n d desires at least a 1- p oi nt 
i m pr o ve me nt i n o verall L F GS sc ore; O R  
Ha d a Fitz patric k s ki n p h ot ot y pe I V, V or VI a n d has a n L F G S  sc ore of t hic k or f ull, as 
a gree d u p o n b y t he Treati n g a n d E val uati n g I n vesti gat ors, a n d desires treat me nt t o t he 
ver mili o n b o d y of 1 or b ot h li ps 
4.  If fe mal e a n d of c hil d beari n g p ote ntial, a ne gati ve uri ne pre g n a nc y test at Visit  1/Da y  1 
a n d t he s u bject a grees t o use a de q uat e c o ntrace pti o n d uri n g t he st u d y peri o d.  
5.  Willi n g t o gi ve  writte n i nf or me d c o nse nt a n d rea d a n d si g n t he A d vers e E ve nt of S pecial 
I nterest ( AE SI ) letter d ate d 0 4J U N 1 9. 
 
7. 3. 2  E xcl usi o n Criteri a  
S u bjects  w h o meet  a n y of t he f oll o wi n g criteri a will be e xcl u de d fr o m t he st u d y:  
1.  W o me n w h o are pr e g na nt, lactati n g, or pla n ni n g a pre g na nc y. 
2.  S u bjects wit h a k n o w n hist or y of aller g y, a n a p h yla xis or h y perse nsiti vit y t o i njecta ble 
h yal ur o nic aci d pr o d ucts, l ocal a nest hetics of t h e a mi de t y pe s uc h as li d ocai ne, or t o 
late x. 
3.  S u bjects wit h a si g nifica nt o n g oi n g a d verse e v e nt fr o m P R O 2 0 1 8- 0 2 or P R O 2 0 1 8- 0 3 
t hat i n t he o pi ni o n of t he i n vesti gat or c o ul d be w orse ne d b y partici p ati o n i n t his st u d y. 
4.  S u bjects t hat e x perie n ce d a n S A E,  A E SI, vis ual c h a n ges or ot her seri o us me dical 
c o n diti o ns d uri n g P R O 2 0 1 8- 0 2 or P R O 2 0 1 8- 0 3. 
5.  S u bjects wit h a b n or mal visi o n e val uati o ns ( C o nfr o ntati o nal Vis ual Fiel ds, Oc ular 
M otilit y) or a b n or mal S nelle n Vis ual Ac uit y  at Visit 1 pre-treat me nt as defi ne d i n 
secti o n 7. 6. 5 a n d A p pe n di x 5. 
6.  S u bjects w h o are u n a ble t o wit h h ol d  t hr o m b ol ytics, or i n hi bit ors of platelet a g gre g ati o n  
or n o nster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds, e. g., as piri n, i b u pr ofe n) or ot her 
s u bsta nces k n o w n t o i ncr ease c o a g ulati o n ti me (e. g., her bal s u p ple me nts wit h garlic or 
gi n g k o) wit hi n 1 0 da ys bef ore A N D after a n y i njecti o n sessi o n. 
7.  S u bjects wit h cli nicall y si g nifica nt or ga nic disease i ncl u di n g cli nicall y si g nifica nt 
car di o vas c ular, he p atic, p ul m o nar y, ne ur ol o gic, or re nal diseas e or ot her m e dical 
c o n diti o n, seri o us i nterc urre nt ill ness, or e xte n u ati n g circ u msta nce t hat, i n t he o pi ni o n of 
t he i n vesti gat or, precl u d e partici pati o n i n t he trial.  
8.  S u bjects wit h li p tatt o os, pierci n gs, facial ha ir, or s cars t hat w o ul d i nterfere wit h 
vis ualizati o n of t he li ps a n d peri oral area f or t he effecti ve ness assess me nts.  
9.  S u bjects wit h a b n or mal li p f u ncti o n, wit h i na bilit y t o effecti vel y si p water t hr o u g h a 
stra w. 
1 0.  S u bjects wit h a b n or mal li p se nsati o n wit h i na bilit y t o feel a 0. 4 G m o n ofila me nt or a 
c ott o n wis p at a n y site o n t he li p.  
1 1.  S u bjects wit h m o derate or se vere a b n or m al li p as y m metr y.  

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1 2.  S u bjects wit h a n y mass f or mati o n o n t he li p. 
1 3.  S u bjects wit h de nt ures or a n y de vice c o veri n g all or part of t he u p p er pal ate, a n d/ or 
se vere m al occl usi o n or d e nt ofacial or ma xill ofaci al def or mities as j u d ge d b y t he 
Treati n g I n vesti gat or. S u bjects pla n ni n g t o u n der g o e xte nsi ve de ntal pr o ce d ures s uc h as 
de ntal i m pla nts, m ulti ple t o ot h e xtracti o ns, or oral s ur ger y s h o ul d n ot partici pate. Mi n or 
de ntal pr oce d ures s uc h as teet h clea ni n g a n d re p air of caries are n ot  e xcl usi o nar y. 
1 4.   S u bjects t hat ha ve u n der g o ne faci al plastic s ur ger y or recei ve d per ma ne nt facial 
i m pla nts (e. g., p ol y met h yl met hacr ylate, silic o ne, p ol ytetrafl u or oet h yle n e, 
p ol yacr yla mi de, lifti n g t hrea ds) a n y w here i n t he face or nec k, or are pla n ni n g t o be 
i m pla nte d wit h a n y of t hese pr o d ucts d uri n g t he st u d y. 
1 5.  S u bjects t hat h a ve u n der g o ne se mi- per ma n e nt der mal filler treat me nt (e. g., calci u m 
h y dr o x yla patite, p ol y- L- l actic aci d) i n t he l o wer face ( bel o w t h e or bital ri m) wit hi n 1 2 
m o nt hs bef ore e nr oll me nt or are pla n ni n g t o u n der g o s uc h treat me nt d uri n g t he st u d y. 
1 6.  S u bjects t hat ha ve u n der g o ne faci al tiss ue a u g me ntati o n wit h fat i njecti o ns, b ot uli n u m 
t o xi n i njecti o ns i n t he l o wer f ace ( bel o w t he or bital ri m), mes ot hera p y, or c os metic 
pr oce d ur es i n t he face or nec k (e. g., face- lift, laser, p h ot o- m o d ulati o n, i nte nse p ulse d 
li g ht, ra di o fre q ue n c y, der ma brasi o n, m o derate or greater de pt h c h e mical p eel, 
micr o nee dli n g, or ot her a blati ve pr oce d ures) wit hi n 9 m o nt hs bef ore e nr oll me nt or are 
pla n ni n g t o u n der g o a n y of t hese pr oce d ures d uri n g t he st u d y. 
1 7.  t hat ha ve use d A N Y li p filli n g a ge nts wit hi n 1 2 m o nt hs of st u d y e nr oll me nt ( h yal ur o nic 
aci d pr o d ucts, c olla g e n- b ase d pr o d ucts, etc.) ot her t ha n I n v esti gati o nal De vice 
a d mi nistere d i n P R O 2 0 1 8- 0 2 a n d P R O- 2 0 1 8- 0 3. 
1 8.  S u bjects t hat ha ve use d a n y li p pl u m pi n g pr o d ucts or de vices wit hi n 1 0 da ys bef ore 
e nr oll me nt or ar e pla n ni n g t o use s uc h pr o d ucts d uri n g t he st u d y. 
1 9.  S u bjects t hat  ha ve be g u n usi n g a n y o ver-t he-c o u nt er ( O T C) or pres cri pti o n oral or 
t o pical a nti- wri n kle pr o d ucts f or t he li ps or ar o u n d t he m o ut h wit hi n 9 0 da ys bef ore 
e nr oll me nt or ar e pla n ni n g t o be gi n usi n g s uc h pr o d ucts d uri n g t he st u d y ( S u bjects w h o 
ha ve bee n o n a sta ble re gi me n of s uc h pr o d ucts f or at least 9 0 da ys are eli gi ble f or t he 
st u d y a n d m ust c o nti n ue t heir re gi me n t hr o u g h o ut t he st u d y). 
2 0.  S u bjects t hat ha ve a hist or y or pr es e nce of blee di n g dis or ders.  
2 1.  S u bjects t hat ha ve use d s yste mic c ortic oster oi ds or i m m u n os u p pressi ve me dicati o ns 
wit hi n 3 0 da ys pri or t o treat me nt. 
2 2.  S u bjects t hat are o n a c o nc urre nt re gi me n of li d ocai ne or str uct urall y relate d l ocal 
a nest hetics (e. g., b u pi v acai ne)  
2 3.  S u bjects t hat ha ve a n acti ve i nfla m mati o n (s ki n er u pti o ns s uc h as c ysts, pi m ples, ras hes, 
or hi ves), i nfecti o n ca ncer o us or preca ncer o us lesi o n, or u n heale d w o u n d o n t he face. 
2 4.  S u bjects t hat ha ve a hist or y of k n o w n s usce pti bilit y t o kel oi d f or mati o n or h y pertr o p hic 
scars. 
2 5.  S u bjects t hat ha ve p or p h yria. 

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2 6.  S u bjects t hat ha ve acti ve her pes la bialias lesi o ns at t he ti me of i njecti o ns.  S u bjects wit h 
a hist or y of her p es la bialis w h o ha ve ha d f o ur ( 4) or m ore o ut brea ks i n t he 1 2 m o nt hs 
pri or t o e nr oll me nt ar e als o e xcl u de d e v e n i n t he a bse nce of l esi o ns at t he b aseli ne visit.  
2 7.  S u bjects t hat ha ve i m pair e d car di ac c o n d u cti o n,  se verel y i m paire d he patic f u ncti o n, or 
se vere re nal d ysf u ncti o n t hat, i n t he o pi ni o n of t he i n vesti gat or, w o ul d place t he m at ris k 
of ass o ciate d c o m plicati o ns fr o m t hese ill nesses d uri n g t he c o urse of t he st u d y. 
2 8.  S u bjects t hat ha ve a n y u n c o ntr olle d disease, i.e., a c o n diti o n t hat has n ot bee n 
a p pr o priatel y dia g n os e d, e val uate d, a n d recei ve d me dicall y a p pr o pri ate treat me nt or care 
2 9.  S u bjects t ha t ha ve se vere car di o vas c ular disease; e xa m ples i ncl u de b ut are n ot li mite d t o 
Ne w Y or k Heart Ass ociati o n heart fail ure classificati o n III or I V, u nsta ble a n gi na, a n d 
i nter nal pace ma kers. P ot e ntial s u bjects wit h ot her si g nifica nt car di o vas c ular diseases 
s h o ul d be disc usse d wit h t he Me dical M o nit or bef ore e nr olli n g. 
 
7. 3. 3  S u bject Wit h dr a w al Criteri a  
A s u bject ma y wit h dra w fr o m t he st u d y at a n y ti me f or a n y reas o n. 
A s u bject will be wit h dra w n fr o m t he st u d y if his/ her safet y or well- b ei n g is deter mi ne d t o be at 
risk. Wit h dra wal will be ma de at t he discreti o n of t he i n vesti gat or or at t he s u bject’s re q u est.  
A s u bject m ust wit h dra w fr o m t he st u d y f or a n y of t he f oll o wi n g reas o ns: 
•  T he s u bject or le g al re pr ese ntati ve wit h dra ws c o ns e nt  
•  T here is a si g nifica nt pr ot oc ol vi o lati o n as deter mi ne d b y t he S p o ns or or m e dical 
m o nit or. 
A s u bject ma y be wit h dr a w n fr o m t he st u d y f or a n y of t he f oll o wi n g reas o ns: 
•  L ost t o f oll o w- u p 
•  I n v esti gat or discreti o n 
Wit h dra wal is per m a ne nt; after a s u bject has bee n wit h dra w n, he/s he will n ot be all o we d t o 
e nr oll a gai n. 
If a s u bject is wit h dra w n fr o m t he st u d y f or a n y reas o n, t he E O S  or Earl y Ter mi nati o n 
pr oce d ur es ( Visit 2/ M o nt h 1) s h o ul d be c o m plete d a n d a n y o utsta n di n g data a n d st u d y de vice 
s h o ul d be c ollecte d. D ata, i ncl u di n g t he date a n d pri mar y reas o n f or wit h dra wal, m ust be 
d oc u me nte d o n t he E O S  case r e p ort f or m ( C R F) a n d s o urce d oc u m e nt. 
If a s u bject wit h dr a ws fr o m t he st u d y at a n y ti me d ue t o a n A E, t he reas o n f or wit h dra w al, t he 
nat ure of t he A E, a n d its cli nical c o urse m ust be f ull y d oc u me nte d. T he i n vesti gat or m ust stri ve 
t o f oll o w t he s u bject u ntil t he A E has res ol ve d, b ec o me cli nicall y i nsi g nifica nt, is sta bilize d, or 
t he s u bject is l ost t o f oll o w- u p. F or a n y S A E, f oll o w pr oce d ures pr o vi de d i n Secti o n  7. 9. 7 . 
7. 3. 4  Re pl ace m e nt of S u bjects  
A s u bject w h o  wit h dra ws  fr o m t he st u d y will n ot be re place d.  

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7. 4  
Tre at m e nts  
T he i n vesti gat or will ta ke res p o nsi bilit y  f or a n d will  ta ke all ste ps t o mai ntai n a p pr o priat e 
rec or ds a n d e ns ur e a p pr o priate s u p pl y, ha n dli n g, st ora ge, distri b uti o n, a n d use of st u d y materials 
i n acc or d a nce wit h t he pr ot oc ol a n d a n y a p plica ble la ws a n d re g ulati o ns. 
7. 4. 1  D os a ge a n d F or m ul ati o ns 
Test De vice:  P N 4 0 0 8 2 ( ma n ufact ur e d b y Pr olle ni u m Me dical Tec h n ol o gies) is a clear, c ol orless 
gel i n 1. 0 m L pre -fille d s yri n ges wit h 2 5 m g/ m L of sta bilize d h yal ur o nic aci d a n d li d ocai ne 0. 3 % 
w/ w . T h e st u d y de vice will be pr o vi de d b y t he S p o ns or. 
C o m p ar at or de vice: R V 0 0 1 ( ma n ufact ure d b y Pr olle ni u m Me dical Tec h n ol o gies) is a clear, 
c ol orless gel i n 1. 0 m L pre -fille d s yri n ges wit h 2 5 m g/ m L of sta bilize d h yal ur o nic aci d  t o be 
use d wit h L M X 4, a t o pical li d ocai ne.  T he st u d y d e vice will be pr o vi de d b y t he S p o ns or.  L M X 4 
will be pr o vi de d i n c o m mercial st oc k pac ka gi n g b y t he S p o ns or  
C o m p ar at or de vice: R V 0 0 1 ( ma n ufact ure d b y Pr olle ni u m Me dical Tec h n ol o gies) is a clear, 
c ol orless gel i n 1. 0 m L pre -fille d s yri n ges wit h 2 5 m g/ m L of sta bilize d h yal ur o nic aci d  t o be 
use d al o ne.  T he st u d y de vice will be pr o vi de d b y t he S p o ns or.   
7. 4. 2  R a n d o miz ati o n 
S u bjects w h o satisf y all of t he eli gi bilit y criterial will be ra n d o mize d i n a 1: 1: 1 rati o t o treat me nt 
wit h R V 0 0 1, R V 0 0 1 wit h a t o pical a nest hetic or P N 4 0 0 8 2.  Ra n d o mizati o n will be perf or me d 
acc or di n g t o a c o m p uter- ge nerat e d ra n d o mizati o n sc he me t hat will be ge n erate d a n d mai ntai ne d 
b y a n i n de pe n de nt t hir d p art y.  A seal e d c o p y of t h e ra n d o mizati o n sc h e me s h o ul d be retai ne d at 
eac h site a n d s h o ul d b e a vaila ble t o re g ulat or y a ut h orities at t he ti me of site i ns pecti o n t o all o w 
f or verifi cati o n of t he tr eat me nt i de ntit y f or eac h s u bject.  A u ni q ue ra n d o mizati o n s u bject 
n u m ber will be assi g ne d t o eac h s u bject i n as ce n di n g or der.  Eac h site will recei ve t h e 
ra n d o mizati o n sc he m e.  
7. 4. 3  St u d y De vice  A d mi nistr ati o n   
S u bjects are p h ysicall y mas ke d ( bli n df ol de d) j ust pri or t o a n d d uri n g all i njecti o n pr oce d ures 
i ncl u di n g t he a p plicati o n of t he L M X 4 or i nert crea m t o pre ve nt o bser v ati o n of t he s yri n ges 
c o ntai ni n g st u d y de vice a n d t he t o pical pr o d uct.  A n y u n bli n de d i n vesti gat ors a n d staff s h o ul d be 
re mi n de d N O T t o disc uss t he treat me nt i n t he prese nce of t h e s u bject.  S u bjects will mai ntai n t he 
u ni q ue s u bject n u m ber pr e vi o usl y assi g ne d i n Pr ot oc ol P R O 2 0 1 8- 0 2 a n d P R O 2 0 1 8- 0 3. 
T he s u bject  s h o ul d be p ositi o ne d i n a seate d p ositi o n a n d ma y be recli ne d t o as m uc h as 4 5°. 
A n y ma ke u p s h o ul d be r e m o ve d wit h a ge ntle clea nser or a s pecifi c ma ke u p re m o ver pr o d uct 
(s uc h as N e utr o ge na Clea nsi n g Ma ke u p Re m o ver Faci al Wi pes) . 
T he n o n- ver milli o n ar eas of t he u p per a n d l o wer li ps s h o ul d be pre pare d b y ge ntle was hi n g wit h 
a s ur gical scr u b pr o d uct ( C hl or he xi di ne, Tec h nicare, etc.). 
T o mai ntai n t he s u bject bli n di n g, t he u p per a n d l o wer li p, u p per a n d l o wer ver milli o n a n d a n y 
pla n ne d i njecti o n ar eas i n or ar o u n d t he m o ut h c or ners s h o ul d be c o v ere d wit h a li beral 
a p plicati o n of eit her t he S p o ns or pr o vi de d i nert crea m or t he t o pical a nest h etic acc or di n g t o t he 
ra n d o mizati o n c o de.  T he desi g nate d crea m pr o d u ct s h o ul d be a p plie d i n a la yer t hic k e n o u g h 

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t hat n o s ki n or li p c ol or is visi ble t hr o u g h t he pr o d uct.  I n v esti gat ors s h o ul d use as m uc h crea m 
as necess ar y t o ac hie ve t his res ult a n d n o t be li mite d t o t he c o nte nts of o ne t u be of pr o d uct. 
Wait 1 5 mi n utes bef ore treat me nt a d mi nistrati o n.   
T he a nest hetic crea m or i nert cr ea m s h o ul d be re m o ve d b y wi pi n g fir ml y wit h a dr y ga uze bef ore 
i njecti n g.  O nl y t he area t o be i m me diatel y treate d s h o uld be wi pe d clear of crea m .  Areas n ot yet 
treate d s h o ul d re m ai n c o vere d wit h crea m u ntil m o me nts pri or t o u n der g oi n g i njecti o n. 
T o pre par e t he s yri n ges f or use, t he i n vesti gat or s h o ul d attac h o ne of t he n ee dles i ncl u de d i n t he 
s u bject st u d y de vice kit i n a fir m ma n ner. T he pl u n ger s h o ul d be ge ntl y de presse d t o e x press a n y 
u n wa nte d air u ntil a s mall dr o plet of i m pla nt material a p pears at t he ti p of t he nee dle.  
St u d y de vice  is a d mi nistere d usi n g o nl y a nee dle pr o vi de d i n t he s u bject st u d y de vice kit. T he 
nee dle is i nserte d at a n a p pr o xi mate a n gle of 3 0° parallel t o t he s urface of t he s ki n or li p. F or 
r h yti ds, st u d y de vice  s h o ul d be i njecte d i nt o t he mi d-t o- dee p der mis. St u d y de vice  s h o ul d be 
i njecte d i nt o t he s u b m uc osal la yer f or li p a u g me ntati o n; care s h o ul d  be ta k e n t o a v oi d 
i ntra m usc ular i njecti o n. If st u d y de vice  is i njecte d t o o s u perficiall y t his ma y res ult i n visi ble 
l u m ps a n d/ or bl uis h disc ol orati o n. 
I nject st u d y de vice  a p pl yi n g li g ht t o m o derate, e ve n press ure o n t he pl u n ger. A v oi d i njecti n g 
q uic kl y as ra pi d i njecti o n ca n res ult i n i ncrease d p ai n. It is i m p orta nt t hat t h e i njecti o n is st o p pe d 
j ust bef ore t he nee dle is p ulle d o ut of t he s ki n t o pre ve nt material fr o m lea ki n g o ut or bei n g t o o 
s u perficiall y i m pla nte d i nt o t he s ki n. 
O nl y c orrect or a u g me nt t o 1 0 0 % of t he desire d v ol u me effect. D o n ot o verc orrect or o v erfill.  
T he nee dle m a y be r e place d as nee de d t o e ns ure s u bject c o mf ort. O nl y nee dles pr o vi de d i n t he 
s u bject st u d y de vice kit ma y be use d. Bef ore nee dle re place me nt, t he pl u n ger s h o ul d be 
wit h dra w n sli g htl y a n d o nce t he nee dle has b ee n re place d, t h e pl u n ger re-a d va nce d t o e ns ure t hat 
t he ne w nee dle is prefille d wit h i m pla nt material pri or t o restarti n g i njecti o ns. 
T y pical usa ge f or eac h tr eat me nt sessi o n is s pecifi c t o t he site as well as t he a m o u nt of 
a u g me ntati o n or r h yti ds c orrecti o n desire d. Bas e d o n U. S. cli nical st u dies, t he ma xi m u m v ol u me 
all o we d per tr eat me nt is 1. 5 m L per li p ( 1. 5 f or u p per, 1. 5 f or l o w er) a n d 1. 0 m L f or peri oral 
r h yti d c orrecti o n. T h us, t he ma xi m u m a m o u nt t hat ca n be use d at o ne treat me nt sessi o n is 4. 0 ml. 
A m o u nts of material i njecte d s h o ul d be rec or de d s e parat el y f or t he u p p er li p, l o wer li p, a n d 
peri oral areas.  
I N J E C TI O N T E C H NI Q U E S 
1. St u d y de vice  ca n b e i njecte d b y a n u m ber of differe nt tec h ni q ues t hat de p e n d o n t he 
treati n g i n vesti gat or’s e x perie nce a n d prefere n ce a n d s u bject c h aracteristics.  
2. Seri al p u nct ure i n v ol ves m ulti ple, cl osel y s pace d i njecti o ns al o n g wri n kles, f ol ds, or 
t he ver milli o n b or der. Alt h o u g h serial p u nct ure all o ws precise pl ace me nt of t he filler, it 
pr o d uces m ulti ple p u nct ure w o u n ds t hat ma y be u n desira ble t o s o me s u bjects. 
3. Li ne ar t hre a di n g (i ncl u des retr o g r a de a n d a nte gr a de) is acc o m plis he d b y f ull y 
i nserti n g t he nee dle i nt o t he ce nter of t he area t o be c orrecte d or a u g me nte d a n d i njecti n g 
t he filler al o n g t he trac k as a “t hrea d.” Alt h o u g h t hrea di n g is m ost c o m m o nl y practice d 
after t he n ee dle h as bee n f ull y i nserte d a n d is bei n g wit h dra w n, it ca n als o be perf or me d 
w hile a d va nci n g t he n ee dle (a nte gra de tec h ni q ue). T o a u g me nt t he li p, t he retr o gra de 

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li near t hrea di n g tec h ni q u e is t he m ost a d visa ble. 
4. Serial t hrea di n g is a tec h ni q ue t hat utilizes ele me nts of b ot h  a p pr oac hes.    
N ote! T he c orr ect i njecti o n tec h ni q ue is cr u cial f or t he fi nal res ult of t he treat me nt.  
5. T he f oll o wi n g tec h ni q ues s h o ul d be a v oi de d as t he y ma y res ult i n a n i ncrease i n s h ort-
ter m e pis o des of br uisi n g, s welli n g, re d ness, pai n, or te n der n ess at t he i njecti o n site: 
• 
Dissecti o n of t he s u b- e pi der mal pla ne wit h lateral m o ve me nt of t he nee dl e – 
“fa n ni n g” 
• 
Ra pi d fl o w rate ( >  0. 3 m L/ mi n) of i m pla nt material i njecti o n  
• 
Hi g h i njecti o n v ol u mes  
• 
T he use of nee dles ot her t ha n o nes pr o vi de d i n t he s u bject st u d y de vice kit 
6. T he use of ca n n ulas is pr o hi bite d. 
7. Eff orts s h o ul d be ma de t o kee p t he i njecti o n pr o ce d ure si milar bet w ee n s u bjects.  It is 
u n derst o o d t hat eac h s u bject is s o me w hat differe nt b ut eac h i n vesti gat or s h o ul d stri ve t o 
use t he sa me tec h ni q ues f or eac h s u bj ect.  A d diti o nall y, t he n u m ber of nee dle i nserti o ns 
s h o ul d be ke pt t o t he mi ni m u m necessar y f or eac h s u bject. 
8. W he n t he i njecti o n is c o m plete d, t he treate d site s h o ul d be ge ntl y  massa ge d s o t hat it 
c o nf or ms t o t he c o nt o ur of t he s urr o u n di n g tiss ues. Massa gi n g t hat s u bsta ntiall y def or ms 
t he li ps or ca uses bla n c hi n g of c o m presse d tiss ues is e xcessi ve a n d s h o ul d b e a v oi de d 
e xce pt as d escri be d b el o w.  
9.  If e xcessi ve materi al is i m pla nte d or irre g ularl y i m pla nte d, massa ge t he area s o me w hat 
m ore fir ml y t ha n f or t he us ual i m pla ntati o n pr oce d ure t o o btai n o pti mal res ults. 
10. If bla nc hi n g of t he tiss ues is o bser ve d d uri n g or directl y aft er i njecti o n a n d bec o mes a 
c o ncer n, t h e ar ea ma y b e ge ntl y massa ge d. If bl a nc hi n g persists, c o ntact t he Me dical 
M o nit or . 
11. T he li ps s h o ul d be a u g me nte d t o ac hie v e t he ma xi m u m desira ble a p peara n ce f or b ot h t he 
treati n g i n vesti gat or a n d t he s u bject. S u bjects s h o ul d be pr o vi de d a s mall h a n d mirr or t o 
o bser ve t he r es ults a n d f urt her i njecti o ns c o n d uct e d u ntil ma xi m u m be nefit has b ee n 
o btai ne d. Care s h o ul d be ta ke n t o e ns ure t h at t he li ps are s y m metric fr o m ri g ht t o left 
a n d t hat t he u p per a n d l o wer li ps ha ve relati ve pr o p orti o nalit y.  
12. T he peri or al ar ea s h o ul d be c orrecte d A F T E R t he u p per a n d l o w er li ps ha v e bee n 
c orrecte d. S o me c or recti o n of peri oral r h yti ds ma y occ ur wit h li p a u g me nt ati o n, t h us it is 
best t o a d dress a n y re mai ni n g peri oral c orrecti o n nee ds aft er t he li p i njecti o ns ha ve bee n 
c o m plete d.   
13. If t he treate d area is s w olle n directl y after t he i njecti o n, a n ice pac k ca n be a p plie d o n t he 
site f or a s h ort peri o d if t he i n vesti gat or dee ms it a p pr o priate. Ice s h o ul d be use d wit h 
ca uti o n if t he ar ea is still n u m b fr o m a nest hetic t o a v oi d t her mal  i nj ur y. 
14. S u bjects s h o ul d be e nc o ura ge d t o a v oi d a rec u m be nt p ositi o n f or se veral h o urs after 
i njecti o ns t o re d uce s w elli n g. T he use of ice, c ol d pac ks or ot her t hera pi es t o re d uce 
s welli n g s h o ul d o nl y be perf or me d at i nstr ucti o n of t he i n vesti gat or. T he s u bject s h o ul d 
be i nstr ucte d t o c o ntact t he site if s u bsta ntial s welli n g occ ur s. 

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7. 4. 4  Bli n di n g of St u d y De vice 
I njecti o ns of t he st u d y de vice ar e perf or me d b y t h e u n bli n de d Treati n g I n v esti gat or. T he bli n de d 
E val uati n g I n vesti gat or is n ot all o we d t o retrie ve st u d y s u p plies or t o be prese nt d uri n g o pe ni n g 
of t he st u d y s u p plies or d uri n g t he i njecti o ns. T he Treati n g I n vesti gat or is n ot t o ha ve a n y 
disc ussi o n wit h t he E val uati n g I n v esti gat or or s u bjects re gar di n g t he treat me nts. 
S u bjects are bli n de d t o tr eat me nt assi g n me nt. S u bjects are p h ysicall y mas k e d ( bli n df ol de d) j ust 
pri or t o a n d d uri n g all i njecti o n pr oce d ures t o pre v e nt o bser vati o n of t he s yri n ges c o ntai ni n g 
st u d y de vice. 
S u bjects, i n vesti gat ors, t he S p o ns or’s staff c o n d u cti n g t he st u d y, a n d me m bers of t he 
a d mi nistrati ve tea m will n ot ha ve access t o i n di vi d ual s u bjects’ treat me nt assi g n m e nts. I n t he 
e ve nt of a n e mer g e nc y t h at re q uires brea ki n g of t h e st u d y bli n d, t he ra n d o mizati o n c o de will be 
mai ntai ne d b y eac h i n vesti gat or t hat ca n be o p e ne d t o re veal t he st u d y de vi ce. 
See Secti o n  7. 9. 1 0. 2 f or a descri pti o n of t he met h o d of u n bli n di n g a s u bject d uri n g t he st u d y if 
s uc h acti o n is warra nte d. 
7. 4. 5  Met h o d of P ac k a gi n g, L a beli n g, St or a ge, a n d Dis pe nsi n g 
F or P N 4 0 0 8 2, o ne 1. 0 m L s yri n ge is pac ka g e d al o n g wit h t w o fi ne- ga u ge n ee dles ( 3 0 G) i n a n 
eas y- o pe n tr a y. Eac h s yri n ge is e q ui p pe d wit h a L uer-L o k  as well as a c ust o m fi n ger gri p a n d 
pl u n ger r o d. T he s yri n ges c o ntai n a peel a ble la bel t o be place d o n t he s u bject rec or d f or trac ki n g 
p ur p oses. T w o tra ys are pac ka g e d i n a cart o n. A l a bel t hat i ncl u des t he pr ot oc ol n u m ber a n d 
S p o ns or na me will be attac he d t o eac h cart o n.  
F or R V 0 0 1 wit h t o pical a nest hetic, o ne 1. 0 m L s yri n ge is pac ka ge d al o n g wit h t w o fi ne- ga u ge 
nee dles ( 2 7 G) i n a n eas y - o pe n tra y.  3 0 G fi n e- ga u ge nee dles will be pr o vi de d i n b ul k b y t he 
S p o ns or f or use i nstea d of t he 2 7 G nee dles.   Eac h s y ri n ge is e q ui p pe d wit h a L uer-L o k as well 
as a c ust o m fi n ger gri p a n d pl u n ger r o d. T he s yri n ges c o ntai n a peela ble la bel t o be place d o n t h e 
s u bject rec or d f or tr ac ki n g p ur p oses. T w o tra ys are pac k a ge d i n a cart o n. A la bel t hat i ncl u des 
t he pr ot oc ol n u m ber a n d S p o ns or na me will be attac he d t o eac h cart o n.  B ul k c o m mercial 
s u p plies of L M X 4 will be pr o vi de d. 
F or R V 0 0 1, o ne 1. 0 m L s yri n ge is pac ka g e d al o n g wit h t w o fi ne- ga u ge n ee dles ( 2 7 G) i n a n eas y -
o pe n tra y. 3 0 G fi n e- ga u g e nee dles will be pr o vi de d i n b ul k b y t he S p o ns or f or use i nstea d of t he 
2 7 G nee dles.  E ac h s yri n ge is e q ui p pe d wit h a L u er- L o k as well as a c ust o m fi n ger gri p a n d 
pl u n ger r o d. T he s yri n ges c o ntai n a peel a ble la bel t o be place d o n t he s u bject rec or d f or trac ki n g 
p ur p oses. T w o tra ys are pac ka g e d i n a cart o n. A l a bel t hat i ncl u des t he pr ot oc ol n u m ber a n d 
S p o ns or na me will be attac he d t o eac h cart o n.  T o c o nfir m use of t he 3 0 G nee dles, t he 2 7 G 
nee dles s h o ul d re mai n i n t he retai ne d p ac ka gi n g f or rec o n ciliati o n. 
All st u d y de vice will be st ore d i n a cli mate -c o ntr olle d, li mite d access area.  
T he i n vesti gat or a gr ees t o st ore a n d a d mi nister t h e st u d y de vice o nl y at t he site(s) liste d o n 
F or m  F D A 1 5 7 2 ( or i n v esti gat or a gree m e nt/state me nt). T he i n vesti gat or, s u b-i n vesti gat or(s), or 
q ualifie d desi g nees als o a gree t h at t he st u d y de vice will be a d mi nistere d o nl y t o s u bjects w h o 
ha ve pr o vi de d writte n i nf or me d c o nse nt a n d h a ve met all e ntr y criteri a. T he s t u d y de vice ma y 
n ot be use d f or a n y p ur p ose ot her t ha n as stat e d i n t he pr ot oc ol. 

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7. 4. 6  St u d y De vice  Acc o u nt a bilit y  
St u d y de vice will be a vaila ble o n site f or eac h s u bject. Recei pt of st u d y de vice will be 
d oc u me nte d a n d c o nfir m e d via t he I n vesti gati o nal Pr o d uct Recei pt F or m. All st u d y de vice  m ust 
be ke pt i n a l oc ke d area wit h access r estricte d t o desi g nate d st u d y pers o n n el i n a cli mate -
co ntr olle d, li mite d access area. T he a d mi nistrati o n of st u d y de vice will be rec or de d o n t h e St u d y 
D e vice Dis pe nsi n g L o g. T he site m o nit or will peri o dicall y c hec k t he s u p pl y of st u d y de vice hel d 
b y t he i n vesti gat or or p har macist t o e ns ure acc o u nt a bilit y. At st u d y c o ncl usi o n, all u n use d 
i n vesti gati o nal pr o d uct will be ret ur ne d t o t he S p o ns or a n d d oc u me nte d usi n g t he I n vesti gati o nal 
Pr o d uct Ret ur n F or m. 
I n v ent or y rec or ds m ust b e rea dil y a v aila ble f or i ns pecti o n b y t he st u d y m o nit or a n d/ or a u dit or, 
a n d o pe n t o i ns pecti o n b y re g ulat or y a ut h orities at a n y ti me. 
7. 4. 7  C o nc o mit a nt Me dic ati o ns 
All me dicati o ns a n d ot her treat me nts ta ke n b y t h e s u bject d uri n g t he st u d y a n d 6 m o nt hs pri or t o 
Visit 1 f or s u bjects w h o di d n ot partici pate i n P R O 2 0 1 8- 0 3 are t o be rec or de d o n t he C R F usi n g 
t heir ge neri c na me, if k n o w n, wit h t he c orres p o n di n g i n dicati o n. T he me dicati o ns t o be rec or de d 
i ncl u de prescri pti o n a n d o ver-t he-c o u nter (O T C) me dicati o ns a n d dietar y s u p ple me nts. All 
me dicati o ns ta ke n o n a re g ular basis, i ncl u di n g vita mi ns, as piri n, a n d aceta mi n o p he n, s h o ul d be 
rec or d e d pri or t o use of t he st u d y de vice . 
T he use of a n y c o nc o mit a nt me dicati o n m ust relat e t o t he s u bject’s d oc u me nte d me dical hist or y, 
pr o p h yla xis, or a n A E. 
7. 4. 7. 1  Prec a uti o ns  
S u bjects s h o ul d be gi ve n t he f oll o wi n g a d diti o nal i nstr ucti o ns: 
•  S u bject s h o ul d mi ni mize or a v oi d e xcessi ve nat ural or artificial s u nli g ht e x p os ure a n d 
e xtre me c ol d w eat her  
•  S u bjects s h o ul d a v oi d e pilati o n, laser, mec ha nical or c he mical p eeli n g pr oce d ures d uri n g 
t he st u d y 
7. 4. 7. 2  Me dic ati o ns  a n d Tre at m e nts  Pr o hi bite d D uri n g t he St u d y  
S u bjects will be a d vise d t o a v oi d t he f oll o wi n g f or t he d urati o n of t he st u d y: 
•  F aci al plastic s ur ger y or per ma ne nt facial i m pla nts (e. g., p ol y met h yl met hacr ylate, 
silic o ne, p ol ytetrafl u or oet h yle ne, p ol yacr yla mi de, lifti n g t hrea ds) a n y w h ere i n t he face or 
nec k  
•  S e mi- per ma ne nt der mal filler treat me nt (e. g., calci u m h y dr o x yla patite, p ol y- L-lactic 
aci d) i n t he l o wer face ( b el o w t he  or bital ri m)  
•  Ot her h yal ur o nic aci d fill er materi als or c olla ge n -base d filler materials bel o w t he or bital 
ri m 
•  F aci al tiss ue a u g me ntati o n wit h fat i njecti o ns, b ot uli n u m t o xi n i njecti o ns i n t he l o wer 
face ( bel o w t he or bital ri m), mes ot hera p y, or c os metic pr oce d ures i n t he face or n ec k 
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d er ma br asi o n, m o derate or great er de pt h c h e mical peel, micr o nee dli n g, or ot her a blati ve 
pr oce d ur es) 
•  Use of a n y li p pl u m pi n g pr o d ucts or de vices 
•  Use of a n y O T C or pres cri pti o n, oral or t o pical, a nti- wri n kle pr o d ucts f or t h e li ps or 
ar o u n d t he m o ut h ( S u bjects w h o ha ve b ee n o n a re gi me n of s uc h pr o d u cts f or at least 
9 0 da ys m ust c o nti n ue t heir re gi me n t hr o u g h o ut t he st u d y.) 
7. 4. 7. 3  C o nc o mit a nt Me dic ati o ns a n d Tre at me nts  All o we d D uri n g t he St u d y  
Per mitte d me dicati o ns/treat me nts i ncl u de a n y c o n c o mita nt me dicati o n/treat me nt n ot liste d 
bel o w.  
•  Faci al plastic s ur ger y or per ma ne nt facial i m pla nts (e. g., p ol y met h yl met hacr ylate, 
silic o ne, p ol ytetrafl u or oet h yle ne, p ol yacr yla mi de, lifti n g t hrea ds) a n y w h ere i n t he face or 
nec k  
•  S e mi-per ma ne nt der mal filler treat me nt (e. g., calci u m h y dr o x yla patite, p ol y- L- lactic 
aci d) i n t he l o wer face ( b el o w t he or bital ri m)  
•  F aci al tiss ue a u g me ntati o n wit h fat i njecti o ns, b ot uli n u m t o xi n i njecti o ns i n t he l o wer 
face ( bel o w t he or bital ri m), mes ot hera p y, or c os metic pr oce d ures i n t he face or n ec k 
(e. g., face-lift, las er, p h ot o- m o d ulati o n, i nte nse p ulse d li g ht, ra di o fre q ue n c y, 
der ma br asi o n, m o derate or great er de pt h c h e mical peel, micr o nee dli n g, or ot her a blati ve 
pr oce d ur es)  
•  U se of a n y li p pl u m pi n g pr o d ucts or de vices  
•  Use of a n y O T C or pres cri pti o n oral or t o pical a nti- wri n kle pr o d ucts f or t he li ps or 
ar o u n d t he m o ut h (s u bjects w h o ha ve bee n o n a sta ble re gi me n of s uc h pr o d ucts f or at 
least 9 0 da ys m ust c o nti n ue t heir re gi me n t hr o u g h o ut t he st u d y.) 
7. 4. 8  Assess m e nt of C o m pli a nce  
A d mi nistrati o n of t he st u d y de vice b y t he i n vesti g at or is d oc u me nte d o n t h e C R F. 
7. 5  
St u d y Sc he d ule  
T he visit- b y- visit sc he d ule of st u d y acti vities is pr o vi de d i n Secti o n  2. T he ti mi n g of eac h visit is 
relati ve t o Da y 1, w hi c h is defi ne d as t he d a y t he s u bject is treate d i n P R O 2 0 1 9- 0 2. 
All visits s h o ul d be perf or me d wit hi n t he wi n d o ws s pecifie d o n t he sc h e d ul e of st u d y acti vities. 
E ver y atte m pt s h o ul d be ma de t o ha ve eac h s u bject atte n d eac h visit as sc h e d ule d. If a s u bject is 
u na ble t o atte n d a visit wit hi n t he s pecifie d wi n d o w t he visit s h o ul d be sc he d ule d as cl osel y as 
p ossi ble t o t he a p plica ble wi n d o w. 
7. 6  
St u d y Pr oce d ures  
T he sc he d ule of st u d y acti vities s u m marizes t he st u d y pr oce d ures t o be perf or me d at eac h visit. 
I n di vi d ual st u d y pr oce d ures ar e descri be d bel o w. 

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All cli nical assess me nts ( L F G S, P O L , i G AI, li p f u ncti o n, li p se nsati o n, li p te xt ure, li p fir m ness, 
li p s y m metr y, a n d li p m o ve me nt/f u ncti o n e val uati o ns) m ust be c o n d ucte d b y q ualifie d 
i n vesti gat ors liste d o n F or m F D A 1 5 7 2 w h o h a ve bee n dele g ate d t hese t as ks b y t he pri nci pal 
i n vesti gat or ( PI). T he PI ma y dele gate t his tas k o nl y t o p h ysicia ns, p h ysicia n assista nts, or n urse 
practiti o ners w h o ha v e d oc u me nte d trai ni n g f or t his pr ot oc ol a n d past e x perie nce c o n d ucti n g t he 
assess me nt.  
 
T o mi ni mize varia bilit y of e val uati o n s, t he sa me i n vesti gat or/s u b-i n vesti gat or s h o ul d perf or m 
t hese assess me nts f or a n y gi ve n s u bject a n d a ntici pate e val u ati n g t he s u bject at eac h visit, t o t he 
e xte nt p ossi ble. 
7. 6. 1  St u d y R oles  
Eac h site will desi g nate at least o ne Treati n g I n vesti gat or w h o is eit her a b o ar d certifie d 
der mat ol o gist or b oar d certifie d plastic s ur ge o n a n d at least o ne bli n de d E val uati n g I n v esti gat or. 
I n a d diti o n, o ne or m ore me m bers of t he st u d y site staff ma y b e desi g nate d as u n bli n de d f or t he 
p ur p oses of assisti n g i n t he ma na ge m e nt of st u d y de vice use. A n y st u d y staff desi g nate d as 
u n bli n de d s h o ul d ha ve n o direct c o ntact wit h s u bjects a n d ma y n ot perf or m a n y s u bject 
e val uati o ns, assess me nts or meas ure m e nts (i ncl u di n g vital si g ns, q uesti o n naires, etc.). 
Desi g nati o n of u n bli n de d st u d y staff will be rec or de d i n t he Dele g ati o n of A ut h orities L o g f or m. 
T he Treati n g I n vesti gat or will be res p o nsi ble f or c o n d ucti n g t he i njecti o ns, e ns uri n g t hat t he 
c orrect ra n d o mize d st u d y de vice a n d t o pical pr o d u ct is a d mi nistere d i n acc or da nce wit h t he 
pr ot oc ol a n d ot her st u d y i nstr ucti o ns.  A n y A Es br o u g ht t o t he atte nti o n of t he Treati n g 
I n v esti gat or will be f or w ar de d t o t he bli n de d E v al uati n g I n v esti gat or f or fi nal a dj u dicati o n a n d 
d oc u me ntati o n. 
T he bli n de d E val uati n g I n vesti gat or will be res p o nsi ble f or assi g ni n g gra d es f or t he vari o us 
para meters ( L F G S, P O L, i G AI, li p f u ncti o n, li p se nsati o n etc.). T he bli n de d E val uati n g 
I n v esti gat or will be res p o nsi ble f or rec or di n g A Es a n d deter mi ni n g t heir se v erit y a n d rel ati o ns hi p 
t o t he st u d y de vice or t he i njecti o n pr oce d ure. 
7. 6. 2  Writte n I nf or m e d C o nse nt  
T he st u d y pers o n nel will re vie w t he I C F f or t his st u d y wit h eac h s u bject a n d gi ve t he s u bject a n 
o p p ort u nit y t o ha ve all q uesti o ns a ns were d b ef ore pr ocee di n g wit h a n y st u d y pr oce d ures. A c o p y 
of t he si g ne d I C F will be gi ve n t o e ver y s u bject a n d t he ori gi nal will be mai ntai ne d wit h t he 
s u bject’s rec or ds.  T he st u d y pers o n nel will re vie w t he letter re gar di n g AE SI  date d 0 4J U N 1 9,  
ha ve t he s u bject  si g n t he letter.  A c o p y of t h e si g ne d letter will be gi ve n t o e ver y s u bject a n d t he 
ori gi nal will be mai ntai ne d wit h t he s u bject’s rec or ds.  
7. 6. 3  Si g nific a nt Me dic al Hist or y / De m o gr a p hic I nf or m ati o n 
Me dical hist or y a n d de m o gra p hic i nf or mati o n will be u p date d if/as nee de d  at Visit 1/ Da y 1  t o 
rec or d a n y c h a n ges si nce Visit 1 i n Pr ot oc ol P R O 2 0 1 8- 0 2.  
7. 6. 4  Vit al Si g ns  
V ital si g ns will be rec or d e d. Vital si g ns will i ncl u de sitti n g bl o o d press ure, te m perat ure, heart 
rate, a n d res pirat or y rate.  

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7. 6. 5  Visi o n E v al u ati o ns  
S u bjects will be assesse d wit h S nelle n vis ual ac uit y, c o nfr o ntati o nal vis ual fiel ds, a n d oc ular 
m otilit y b y a trai ne d e val uat or. T hese assess me nts will be perf or me d at Visit 1/ Da y 1 pri or t o 
treat me nt a n d r e peat e d 3 0 mi n utes f oll o wi n g treat me nt a n d at Visit 2/ M o nt h 1 .  N or mal a n d 
a b n or mal fi n di n gs ar e s u m marize d i n A p pe n di x 5.  
7. 6. 5. 1  S nelle n Vis u al Ac uit y  
Site staff trai ne d o n c o n d ucti n g vis ual ac uit y will h ol d t he pr o vi de d S nelle n c hart 6 feet fr o m t he 
s u bject.  T he s u bject will be i nstr ucte d t o wear a n y us ual c orrecti ve e y e wear a n d c o v er o n e e ye 
wit h t he pr o vi de d occl u d e.  T he s u bject will rea d eac h li ne u ntil n o l o n ger ca pa ble.  T h e best 
rea da bl e li ne will be rec or de d f or eac h e ye.   
N or mal fi n di n g :  T he sa me S nelle n Vis ual Ac uit y res ults as t he S nelle n Vis ual Ac uit y res ults 
rec or d e d pre-treat me nt at Visit 1/ baseli ne i n P R O 2 0 1 8- 0 2. 
A b n or mal fi n di n g:  A n y c ha n ge fr o m t he S nelle n Vis ual Ac uit y res ults rec or de d pre-treat me nt at 
Visit 1/ Baseli ne  i n P R O 2 0 1 8- 0 2 will be c o nsi dere d a b n or mal. 
7. 6. 5. 2  C o nfr o nt ati o n al Vis u al Fiel ds  
T he Bli n de d E val uati n g I n vesti gat or will: 
•  Sit face t o face wit h t he s u bject  
•  Ha ve t he s u bject c o ver t heir left e y e wit h ha n d or occl u de 
•  T he i n vesti gat or c o vers t heir ri g ht e ye 
•  I nstr u ct t he s u bject t o c o nti n u o usl y stare at t he i n vesti gat or’s n ose 
•  T he i n vesti gat or stares c o nti n u o usl y at t he s u bject’s n ose 
•  T he i n vesti gat or e xte n ds t heir left ar m wit h fi n ger p oi nte d i n war d fr o m far l eft si de a n d 
gra d uall y m o ves t heir fi n ger t o war d t h e mi dli ne  
•  As k t he s u bject t o i n dicat e w he n t he y s ee t he fi n g er 
•  Re peat test f or t o p of vis ual fiel d (ar m a n d fi n ger u p hi g h) 
•  Re peat test f or b ott o m of vis ual fiel d (ar m a n d fi n ger d o w n l o w) 
•  Re peat all t hree t ests f or t he ot her e ye  
N or mal fi n di n g:  S u bject re p orts seei n g t he fi n ger at a b o ut t he sa me ti me or l ocati o n as t he 
i n vesti gat or. 
A b n or mal fi n di n g:  S u bject d oes n ot see t h e fi n ger at a b o ut t he sa me ti me or l ocati o n as t he 
i n vesti gat or. 
7. 6. 5. 3  Oc ul ar M otilit y  
T he Bli n de d E val uati n g I n vesti gat or will: 
•  Ha ve t he s u bject stare at t he i n vesti gat or 

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•  As k t he s u bject t o “f oll o w m y fi n ger” 
•  T he i n vesti gat or will m o ve t heir fi n ger t o e xtre mes of gaze o n l eft, ri g ht, t o p a n d b ott o m 
N or mal fi n di n g:  O bser v e e yes t o e ns ure c o nsiste nt c o nj u gate gaze t hr o u g h o ut t he test 
A b n or mal fi n di n g:  s u bject d oes n ot ha ve c o nsiste nt c o nj u gate gaze t hr o u g h o ut t he test 
 
7. 6. 6  Pri or a n d C o nc o mit a nt Me dic ati o n/ Tre at me nt  Re vie w  
C o nc o mita nt me dicati o ns (i ncl u di n g prescri pti o n, O T C, a n d dietar y s u p ple me nts ta ke n a n d ot her 
treat me nts a n d c os metic pr o d ucts use d b y t he s u bj ect ) will be re vie we d wit h t he s u bject at eac h 
st u d y visit a n d tele p h o ne c o ntact.  F or s u bjects w h o di d n ot partici pate i n P R O 2 0 1 8- 0 3, pri or 
me dicati o ns/treat me nts, i ncl u di n g t he necess ar y w as h o ut ti mes will be re vie we d wit h t he s u bject.  
A rec or d of pri or m e dicati o ns/treat me nts ta ke n or use d b y t he s u bject wit hi n 6 m o nt hs bef ore 
si g ni n g t he I C F will be o btai ne d at Visit 1/ Da y 1. 
7. 6. 7  Re vie w I ncl usi o n/ E xcl usi o n Criteri a  
T he i ncl usi o n a n d e xcl usi o n criteria will be re vie we d b y t he i n vesti gat or or q ualifie d desi g nee t o 
e ns ure t hat t he s u bject q ualifies f or t he st u d y. 
7. 6. 8  Uri ne Pre g n a nc y Test a n d Acce pt a ble C o ntr ace pti ve Met h o ds  
W o me n of c hil d beari n g p ote ntial, i n a d diti o n t o ha vi n g a ne gati ve uri ne pre g n a nc y test at Visit 1/ 
Da y  1, m ust be willi n g t o use a n acce pta bl e f or m of birt h c o ntr ol d uri n g t he st u d y. T he f oll o wi n g 
are c o nsi d ere d acce pta bl e met h o ds of birt h c o ntr ol f or t he p ur p ose of t his st u d y: oral 
c o ntrace pti ves, c o ntrace pti ve patc hes, c o ntrace pt i v e i m pla nt, va gi nal c o ntrace pti ve, d o u ble 
barrier m et h o ds (e. g., c o n d o m a n d s per mici de), c o ntrace pti ve i njecti o n ( D e p o- Pr o vera ® ), I U D, 
h or m o nal I U D ( Mir e na ® ), a n d a bsti ne nce wit h a d oc u me nte d sec o n d acce pt a ble met h o d of birt h 
c o ntr ol if t he s u bject bec o mes se x uall y acti ve. S u bjects e nteri n g t he st u d y w h o are o n h or m o nal 
c o ntrace pti ves m ust ha ve bee n o n t he met h o d f or at least 9 0 da ys pri or t o t he st u d y a n d c o nti n ue 
t he met h o d f or t he d ur ati o n of t he st u d y. S u bjects w h o ha d use d h or m o nal c o ntrace pti o n a n d 
st o p pe d m ust ha ve st o p pe d n o less t ha n 9 0 da ys pri or t o Visit 1/ Da y 1. 
7. 6. 9  Re as o n f or St u d y P arti ci p ati o n Q uesti o n 
S u bjects will be pr o vi de d wit h t he St u d y Partici pati o n Q uesti o n w hic h as ks,  “ W h y di d y o u 
c h o ose t o e nr oll i n t his st u d y?” wit h t he f oll o wi n g c h oic es:  
•  Was ha p p y wit h r es ults a n d wa nte d a little m ore pr o d uct 
•  F ull ness has di mi nis he d a n d li ps are bac k t o ori gi nal c o n diti o n 
•  Ot her  
7. 6. 1 0  Li p F ull ness Gr a di n g Sc ale   
T he L F G S  is a v ali date d 5- p oi nt p h ot o n u meric rati n g scale t hat was d e vel o pe d t o o bjecti vel y 
q ua ntif y t he 3- di me nsi o nal f ull ness of t he li p. T he scale rati n gs are 0 f or ver y t hi n, 1 f or t hi n, 
2 f or m o derat el y t hic k, 3 f or t hic k, a n d 4 f or f ull ( Carr ut hers et al, 2 0 0 8). P h ot o gra p hs ill ustrati n g 
t he rati n gs will be pr o vi de d t o eac h site. T h e assess me nts of o verall li p f ull ness c o nsi deri n g b ot h 

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li ps t o get her, f ull ness of t he u p per li p, a n d f ull ness of t he l o wer li p will be p erf or me d at eac h 
st u d y visit b y t he Bli n de d E val uati n g I n vesti gat or. 
7. 6. 1 1  Peri o r al Li n es at Rest S e verit y Sc ale  
T he P O L is a 4 - p oi nt rati n g scale t hat c orres p o n ds t o t he m ost se vere peri oral li ne attri b ute w he n 
t he s u bject’s m o ut h is at rest wit h t he f oll o wi n g rati n gs ( C o he n et al, 2 0 1 4) :  
0.  N o ne – a m o ut h wit h n o peri oral li nes 
1. Mil d – a m o ut h wit h a fe w s hall o w peri oral li nes  
2. M o derate – a m o ut h wit h s o me m o derate li nes  
3. Se vere – a m o ut h wit h m a n y dee p li nes or cre vi ces 
T he assess me nts of o v erall peri oral li nes at rest se verit y c o nsi deri n g b ot h li ps t o get her, peri oral 
li nes at rest se verit y of t h e u p per li p, a n d peri oral li nes at rest se verit y of t he l o wer li p will be 
perf or me d at eac h st u d y visit b y t he Bli n de d E val uati n g I n v esti gat or. 
7. 6. 1 2  Li p F u ncti o n E v al u ati o n 
Li p f u ncti o n will be assesse d b y t he Bli n de d E val uati n g I n v esti gat or b y t he s u bject’s a bilit y t o 
si p li q ui d t hr o u g h a stra w pri or t o treat me nt at eac h st u d y visit. 
7. 6. 1 3  Li p Se ns ati o n E v al u ati o n 
Li p se nsati o n will be assesse d b y t he Bli n de d E val uati n g I n vesti gat or a n d t este d via: 1) t he 
m o n ofila me nt test (a s u bject’s a bilit y t o feel t he se nsati o n of a 0. 4 G m o n ofila me nt at 3 p oi nts o n 
t he u p per li p a n d 3 p oi nts o n t he l o wer li p), a n d 2) t he c ott o n wis p test (a s u bject’s a bilit y t o feel 
t he se nsati o n of a c ott o n wis p at 3 p oi nts o n t he u p per li p a n d 3 p oi nts o n t he l o wer li p) pri or t o 
treat me nt at eac h st u d y visit. 
7. 6. 1 4  Li p Te xt ure E v al u ati o n 
Li p te xt ure will be assess e d b y t he Bli n de d E val uati n g I n vesti gat or as n or m al or a b n or mal pri or 
t o treat me nt at eac h st u d y visit ( Ta ble 1 Li p Te xt ure Sc ori ng Criteria ). 
 
 

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T a ble 1. 
Li p Te xt ure Sc ori n g Criteri a  
N or m al  
 
A b n or m al  
 
 
Mil d  
M o der ate  
Se vere  
Te xt ure of t he li p 
is e ve n wit h o ut 
visi ble 
u n d ulati o ns or 
e xcessi ve 
c oarse ness be y o n d 
t hat e x pecte d f or 
state d a ge 
T he li p s h o ws a 
si n gle area of 
te xt ural irre g ularit y 
(a s mall pa p ule, 
area of e xcess 
s m o ot h ness, f ocal 
a bse nce of 
per pe n dic ular li nes) 
ca n be vis ualize d 
o nl y wit h cl ose 
i ns pecti o n 
T he li p s h o ws m ore t ha n o ne 
area of te xt ural irre g ularit y 
(a s mall pa p ule, area of 
e xcess s m o ot h ness, f ocal 
a bse nce of per pe n dic ular 
li nes) ca n be vis ualize d o nl y 
wit h cl ose i ns pecti o n. 
Or  
T he li p s h o ws o ne area of 
te xt ural irre g ularit y (less 
t ha n ¼ of t he li p area) at a 
c o n versati o nal dista nce. 
T he li p s h o ws t w o or m ore 
areas of te xt ural 
irre g ularit y (a s mall 
pa p ule, area of e xcess 
s m o ot h ness, f ocal a bse nce 
of per pe n dic ular li nes) ca n 
be vis ualize d at a 
c o n versati o nal dista nce. 
Or  
T he li p s h o ws o ne area of 
te xt ural irre g ularit y ( m ore 
t ha n ¼ of t he li p area) at 
c o n versati o nal dista nce 
7. 6. 1 5  Li p Fir m ness E v al u ati o n 
Li p fir m ness will be assesse d b y t he Bli n de d E val uati n g I n v esti gat or as n or mal or a b n or mal pri or 
t o treat me nt at eac h st u d y visit (Ta ble 2 . Li p Fir m ness Sc ori n g Criteria ). 
T a ble 2.  
 Li p Fir m ness Sc ori n g Criteri a  
N or m al  
 
A b n or m al  
 
 
Mil d  
M o der ate  
Se vere  
Li p is s u p ple w he n 
c o m presse d laterall y 
a n d s urface dist orte d 
rea dil y wit h mi ni mal 
press ure.  Press ure wit h 
a narr o w dia meter 
i nstr u me nt (c ott o n-
ti p pe d a p plicat or, 
t o ot h pic k, etc.) ca uses a 
f ocal de pressi o n i n t he 
s urface of t he li p.  
U p o n pal pati o n, li p is 
a bse nt of a b n or mal 
str uct ures s uc h as scars 
or l u m ps; n or mal 
pr o d uct feel wit h o ut 
bei n g visi ble.  
Li p is sli g htl y fir m wit h 
lateral c o m pressi o n or 
re q uire d sli g htl y greater 
t ha n n or mal press ure t o 
dist ort t he s urface.  
U p o n pal pati o n, a n 
ab n or mal str uct ure s uc h 
as a scar or l u m p is felt, 
b ut is n ot visi ble. 
Li p is fir m wit h lateral 
c o m pressi o n or re q uires 
disti nctl y greater t ha n 
n or mal press ure t o 
dist ort t he s urface or 
press ure wit h a narr o w 
dia meter i nstr u me nt 
(c ott o n-ti p pe d 
a p plicat or or t o ot h pic k) 
ca uses a br oa der 
de pressi o n i n t he 
s urface of t he li p.  
U p o n pal pati o n, a n 
a b n or mal str uct ure s uc h 
as a scar or l u m p is felt 
a n d is visi ble. 
Li p is ver y fir m wit h 
lateral c o m pressi o n or 
re q uires si g nifica ntl y 
greater t ha n n or mal 
press ure t o dis t ort t he 
s urface.  U p o n 
pal pitati o n, a n 
a b n or mal str uct ure s uc h 
as a scar or l u m p is felt 
a n d is vis uall y 
distracti n g. 
 

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7. 6. 1 6  Li p S y m m etr y E v al u ati o n 
Li p s y m metr y  will be assesse d b y t he Bli n de d E val uati n g I n vesti gat or as n or mal or a b n or mal 
pri or t o treat me nt at eac h st u d y visit ( Ta ble 3. Li p S y m metr y Sc ori n g Criteria ). 
T a ble 3. 
Li p S y m m etr y Sc ori n g Criteri a  
N or m al  
 
A b n or m al  
 
 
Mil d  
M o der ate  
Se vere  
O ne si de of t he li p 
bala nce d or mirr ore d 
t he ot her si de 
O ne si de of t he li p 
s h o ws a 1 m m or less 
differe nce i n hei g ht or a 
1 m m or less differe nce 
i n t he le n gt h of t he 
ver mili o n at re p ose. 
O ne si de of t he li p 
s h o ws a 1. 1 m m t o 2 
m m differe nce i n hei g ht 
or a 1. 1 t o 2 m m 
differe nce i n t he le n gt h 
of t he ver mili o n at 
re p ose   
O ne si de of t he li p 
s h o ws a greater t ha n 2 
m m differe nce i n t he 
hei g ht or a greater t ha n 
2 m m differe nce i n t he 
le n gt h of t he ver mili o n 
at re p ose. 
7. 6. 1 7  Li p M o ve m e nt/ F u ncti o n E v al u ati o n  
Li p m o ve me nt/f u ncti o n will be e val uate d b y t he Bli n de d E val uati n g I n v esti gat or as n or mal or 
a b n or mal pri or t o treat me nt at eac h st u d y visit as t he s u bject’s a bilit y t o p uc ker li ps, bl o wi n g a n d 
pr o n u nciati o n of w or ds t hat be gi n wit h t he letter “ W” s uc h as water, w or k, wee k a n d wi n d. 
7. 6. 1 8  P atie nt Gl o b al Aest hetic I m pr o ve me nt ( p G AI) Sc ore  
T he p G AI s c ore will be r ec or de d at eac h st u d y visit. S u bjects will be as ke d t he q uesti o n “ H o w 
w o ul d y o u rate i m pr o ve me nt i n y o ur a p peara nce c o m pare d t o y o ur i nitial c o n diti o n pri or t o 
e nr olli n g i n Pr ot oc ol P R O 2 0 1 8- 0 2 usi n g t he scal e bel o w?” 
T he p G AI s c ore is a 5 -p oi nt scale wit h t he f oll o wi n g cate g ories:  
1. 
W orse – t he a p peara nce is w orse t ha n t he ori gi nal c o n diti o n. 
2.  N o c ha n ge – t h e a p peara nce is t he sa me as t he ori gi nal c o n diti o n. 
3.  I m pr o v e d – o b vi o us i m pr o ve me nt i n a p peara nce fr o m t he i nitial c o n diti o n. A 
t o uc h- u p mi g ht f urt her i m pr o ve t he res ult. 
4.  
M uc h i m pr o ve d – mar ke d i m pr o ve me nt i n a p peara nce fr o m t he i nitial c o n diti o n, b ut 
n ot c o m pletel y o pti mal. A t o uc h- u p mi g ht sli g htl y i m pr o ve t he res ult. 
5.  Ver y m uc h i m pr o ve d – o pti mal c os metic res ult.  
7. 6. 1 9  I n vesti g at or Gl o b al Aest hetic I m pr o ve me nt (i G AI) Sc ore 
T he i G AI sc ore will be assesse d at eac h st u d y visit  b y t he Bli n de d E val uati n g I n v esti gat or. 
T he i G AI sc ore is a 5 - p oi nt scale wit h t he f oll o wi n g cate g ories: 
1. 
W orse – t he a p peara nce is w orse t ha n t he ori gi nal c o n diti o n. 
2.  N o c ha n ge – t h e a p peara nce is t he sa me as t he ori gi nal c o n diti o n. 
3.  I m pr o v e d – o b vi o us i m pr o ve me nt i n a p peara nce fr o m t he i nitial c o n diti o n. A 
t o uc h- u p mi g ht f urt her i m pr o ve t he res ult. 

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4.  
M uc h i m pr o ve d – mar ke d i m pr o ve me nt i n a p peara nce fr o m t he i nitial c o n diti o n, b ut 
n ot c o m pletel y o pti mal. A t o uc h- u p mi g ht sli g htl y i m pr o ve t he res ult. 
5.  Ver y m uc h i m pr o ve d – o pti mal c os metic res ult.  
7. 6. 2 0  S welli n g Assess m e nt  
S welli n g will  be assesse d b y t he Bli n de d E val uati n g I n v esti gat or at eac h st u d y visit usi n g t he 5-
p oi nt scale wit h t he cate g ories t hat f oll o w. T he I n v esti gat or s h o ul d e xa mi ne b ot h u p per a n d 
l o wer li p si m ulta ne o usl y a n d recall t he de gree of a u g me ntati o n ori gi nall y pr o vi de d f or 
c o m paris o n. T he s u bject s h o ul d n ot be s pecificall y q uesti o ne d re gar di n g s welli n g b ut if t he 
s u bject s p o nta ne o usl y re p orts it, s uc h i nf or mati o n ca n be use d t o assist i n selecti o n of a gra de f or 
s welli n g. 
0.  N o ne – N o s welli n g n oticea ble. Li ps a p pear t he s a me as w he n ori gi nall y a u g me nte d. 
A n y li p e nlar ge me nt is d ue t o t he i m pla nte d pr o d uct o nl y. 
1. 
Mi ni mal – Sli g ht e nlar ge me nt of eit her li p be y o n d t he ori gi nall y pr o vi de d 
a u gme ntati o n. Ma y or m a y n ot be n oticea bl e t o t he s u bject b ut is n oticea bl e t o t he 
i n vesti gat or. 
2. 
Mil d – S o me e nlar ge me nt of eit her li p be y o n d t he ori gi nal a u g me ntati o n t hat is 
easil y n oticea ble t o t he s u bject, b ut t he li ps d o n ot a p pear a b n or mall y lar g e. 
3. 
M o derate – Si g nifica nt e nlar ge me nt of eit her li p be y o n d t he ori gi nal a u g me ntati o n. 
Eit her li p a p pears a b n or mall y lar ge. 
4. 
Se vere – A n y d e gree of s welli n g t hat s u bsta ntiall y i nterferes wit h li p f u ncti o n s uc h 
as c ha n ges i n s p eec h or diffic ult y eati n g or d ri n ki n g. 
7. 6. 2 1  S u bject S atisf acti o n wit h Li ps ( Vis u al A n al o g Sc ale [ V A S])  
S u bjects will be as ke d t o assess t heir o verall satisfacti o n wit h t heir li ps b y usi n g a 1 0 0 m m V A S 
scale fr o m 0 = Ver y U ns atisfie d t o 1 0 0 = Ver y Satisfie d at Visit 2/ M o nt h 1 ( Fi g ure 1).   
Fi g ure 1 Vis u al A n al o g Sc ale f or S u bject S atisf acti o n 
 
  
  
  Ver y     
  
  
  
  
  
  
 Ver y  
  
          U nsatisfie d   
  
  
  
  
  
          Satisfie d  
7. 6. 2 2  I n vesti g at or E ase of Us e Assess me nt 
T he Treati n g I n vesti gat or will ass ess o verall eas e of use b y t he de vice b y circli n g t he a p pr o pri ate 
n u m ber o n t he n u merical rati n g scale fr o m 0 bei n g n ot eas y t o 1 0 bei n g m ost eas y at 
Visit  1/ Da y  1. ( Fi g ure 2) 
Fi g ure 2 I n vesti g at or E ase of Use 
 
 
 
 
 
 
 
 
 
 
 
0             1               2              3             4              5               6             7               8               9          1 0  
N ot Eas y   
  
  
  
        
  
                                                         M ost Eas y  

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7. 6. 2 3  S u bject P ai n Sc ore – Vis u al A n al o g Sc ale 
Pai n fr o m t he i njecti o n sessi o n will be assesse d b y t he s u bject usi n g a 1 0 0- m m V A S scale fr o m  0 
= n o pai n t o 1 0 0 = w orst p ossi ble pai n at Visit 1/ Da y 1 i m me diatel y after t h e i njecti o n , 1 5 
mi n utes p ost t he last i njecti o n of t he sessi o n, a n d at Visit 2.  S u bjects will be as ke d t he q u esti o n 
“ H o w w o ul d y o u r ate y o ur pai n fr o m t he i njecti o n of st u d y material?” a n d will res p o n d b y 
placi n g a mar k o n t he V A S. ( Fi g ure 3) 
 
Fi g ure 3 Vis u al A n al o g Sc ale f or S u bject A ss ess me nt of P ai n 
  
 
7. 6. 2 4  Tre at m e nt Q uesti o n  
At Visit 2 or earl y ter mi n ati o n, s u bjects a n d bli n de d e val uati n g i n vesti gat ors will be as ke d t o 
i de ntif y w hic h treat me nt t he y t h o u g ht ha d bee n a d mi nistere d. 
7. 6. 2 5  S u bject Di ar y C ar d  
A diar y car d will be dis pe nse d t o eac h e nr olle d s u bject at Visit 1/ Da y 1. T h e s u bject will be 
i nstr ucte d t o c o m plete t he diar y car d t o rec or d a n y A Es e x perie nce d d uri n g t he 2 wee ks  after 
recei vi n g treat me nt. T he diar y car d will be c ollect e d at Visit  2/ M o nt h 1.    
7. 6. 2 6  A d verse E ve nts  a n d Seri o us A d verse E ve nts  Assess me nt  
See Secti o n  7. 9  f or i nstr u cti o ns o n t he assess me nt a n d re p orti n g of A Es a n d S A Es a n d 
Secti o n  7. 9. 7  f or i nstr ucti o ns o n re p orti n g S A Es t o t he S p o ns or or desi g nee. 
7. 7  
Visit -S pecific Pr oce d ures  
T he f oll o wi n g secti o ns o utli ne t he pr oce d ures re q uire d at eac h visit. 
7. 7. 1  Vi sit 1/ D a y 1: Tre at m e nt 
Visit is ± 1 4 da ys of Da y 1 6 8/ M o nt h 6 tele p h o ne call f or P R O 2 0 1 8- 0 3 or f or s u bjects e nr olle d 
fr o m P R O 2 0 1 8- 0 2, Visit 1 is Da y 1.   
•  O btai n writte n i nf or me d c o nse nt a n d rea d a n d si g n t he A E SI  l etter date d 0 4J U N 19.  
•  U p date t he me dical h ist or y a n d de m o gra p hic i nf or mati o n as nee de d fr o m e ntr y t o 
Pr ot oc ol P R O 2 0 1 8- 0 2 a n d P R O 2 0 1 8- 0 3  
•  Perf or m vital si g ns (te m perat ure, heart rate, bl o o d press ure, a n d res pirat or y rate) 
•  Visi o n e val uati o n ( S nelle n vis ual ac uit y, c o nfr o ntati o nal vis ual fiel ds, oc ular m otilit y) 
•  O btai n/rec or d  c o nc o mita nt me dicati o ns/treat me nts  

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•  E val uate i ncl usi o n/e xcl usi o n criteria  
•  Perf or m uri ne pre g na n c y test f or all w o me n of c hil d beari n g p ote ntial  
•  Reas o n f or st u d y partici p ati o n q uesti o n 
•  L F G S  assess me nt  
•  P O L assess me nt  
•  Li p f u ncti o n e val uati o n pri or t o treat me nt a d mi nistrati o n  
•  Li p se nsati o n e val uati o n pri or t o treat me nt a d mi nistrati o n  
•  Li p te xt ure e val uati o n pri or t o treat me nt a d mi nistrati o n  
•  Li p fir m ness e val uati o n pri or t o treat me nt a d mi nistrati o n  
•  Li p s y m metr y e val uati o n pri or t o treat me nt a d mi nistrati o n  
•  Li p m o ve me nt/f u ncti o n pri or t o treat me nt a d mi nistrati o n  
•  p G AI assess me nt pri or t o treat me nt a d mi nistrati o n  
•  i G AI assess me nt pri or t o treat me nt a d mi nistrati o n 
•  S welli n g assess me nt  pri or t o treat me nt a d mi nistrati o n  
•  S u bject satisfacti o n wit h li ps ( V A S)  pri or t o treat me nt a d mi nistrati o n  
•  Treat me nt a d mi nistrati o n  waiti n g 1 5 mi n utes after li d ocai ne crea m  or i nert crea m  
a p plicati o n  
•  I n v esti gat or Ease of Use assess me nt 
•  S u bject Pai n Sc ore i m me diatel y after treat me nt ( V A S)  
•  S u bj ect Pai n Sc ore 1 5 mi n utes after treat me nt ( V A S)  
•  Visi o n e val uati o n ( S nelle n vis ual ac uit y, c o nfr o ntati o nal vis ual fiel ds, oc ular m otilit y) 
3 0 mi n utes p ost treat me nt.  
•  Assess A Es  
•  Dis pe nse s u bject diar y car d  
•  Sc he d ule ne xt visit 
•  C o m plete C R Fs  
7. 7. 2  Tele p h o ne C o nt ac ts o n D a y 3 a n d D a y 1 4 ( ± 2 d a ys) 
•  Assess A Es  
•  Assess  c o nc o mita nt me di cati o ns/treat me nts  
•  As k w het her t he s u bj ect is e x perie n ci n g or has e x p erie nce d a n y si g ns/s y m pt o ms of 
visi o n c ha n ges or str o ke si nce t he i njecti o n 
•  C o nfir m a d here n ce t o pr o hi bite d treat me nts/ me dicati o ns 

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7. 7. 3  Visit 2/ D a y 2 8 ( ± 2 d a ys): M o nt h 1 E n d of St u d y Visit  
•  Visi o n e val uati o n ( S nelle n vis ual ac uit y, c o nfr o ntati o nal vis ual fiel ds, oc ular m otilit y) 
•  Assess c o nc o mita nt me di cati o ns/treat me nts  
•  L F G S assess me nt  
•  P O L assess me nt  
•  Li p f u ncti o n e val uati o n  
•  Li p se nsati o n e val uati o n  
•  Li p te xt ure e val uati o n  
•  Li p fir m ness e val uati o n  
•  Li p s y m metr y e val uati o n  
•  Li p m o ve me nt/f u ncti o n 
•  p G AI assess me nt  
•  i G AI assess me nt 
•  S welli n g assess me nt  
•  S u bject satisfacti o n wit h li ps ( V A S)  
•  S u bject Pai n Sc ore ( V A S)  
•  Assess A Es  
•  Treat me nt Q u esti o n  
•  C ollect/ Re vie w  s u bject diar y car d  
•  C o m plete C R Fs  
7. 7. 4  Tele p h o ne C o nt act o n D a y 5 6 ( M o nt h 2) ± 4 d a ys 
•  Assess A Es  
•  Assess c o nc o mita nt me di cati o ns/treat me nts  
•  As k w het her t he s u bj ect is e x perie n ci n g or has e x p erie nce d a n y si g ns/s y m pt o ms of 
visi o n c ha n ges or str o ke si nce t he i njecti o n 
•  C o nfir m a d here n ce t o pr o hi bite d treat me nts/ me dicati o ns   
7. 7. 5  E n d of St u d y Tele p h o ne C o nt act o n D a y 1 6 8 ( M o nt h 6) ± 7 d a ys  
•  Assess A Es  
•  Assess c o nc o mita nt me di cati o ns/treat me nts  
•  As k w het her t he s u bj ect is e x perie n ci n g or has e x p erie nce d a n y si g ns/s y m pt o ms of 
visi o n c ha n ges or str o ke si nce t he i njecti o n 

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•  C o nfir m a d here n ce t o pr o hi bite d treat me nts/ me dicati o ns  
7. 7. 6  U nsc he d ule d Visit  
A n u nsc he d ule d visit is all o we d at a n y ti me if i n t he i n vesti gat or’s o pi ni o n it is warra nte d. T h e 
f oll o wi n g pr oce d ur es ma y be perf or me d at t he U nsc he d ule d Visit if re q uire d. 
•  Visi o n e val uati o n ( S nelle n vis ual ac uit y, c o nfr o ntati o nal vis ual fiel ds, oc ular m otilit y) 
•  Assess c o nc o mita nt me di cati o ns/treat me nts  
•  L F G S assess me nt  
•  P O L assess me n t 
•  Li p f u ncti o n e val uati o n 
•  Li p se nsati o n e val uati o n 
•  Li p te xt ure e val uati o n 
•  Li p fir m ness e val uati o n  
•  Li p s y m metr y e val uati o n  
•  Li p m o ve me nt/f u ncti o n 
•  p G AI assess me nt  
•  i G AI assess me nt 
•  S welli n g assess me nt  
•  S u bject satisfacti o n wit h li ps ( V A S)  
•  S u bject Pai n sc ore ( V A S) 
•  Assess A Es  
•  C o m plete C R Fs  
7. 8  
Effic ac y E n d p oi nts  
Efficac y will be e val u ate d b y t he S u bject Pai n Sc ore i m me diatel y after treat me nt , 1 5 mi n utes 
after tr eat me nt , a n d at Visit 2.  Efficac y will als o be e val uat e d b y L F G S, P O L, p G AI, i G AI , a n d 
S welli n g Assess me nt .  
7. 9  
Assess m e nt of S afet y  
7. 9. 1  S afet y E n d p oi nts  
Safet y of t he treat me nt wit h P N 4 0 0 8 2 or R V 0 0 1 wit h t o pical a nest hetic, or R V 0 0 1 will be 
e val uat e d b y t he n at ure, s e verit y, a n d fre q ue n c y of treat me nt- e mer ge nt a d v erse e ve nts ( T E A Es). 
All A Es t hat occ ur d uri n g t he st u d y will be rec or d e d w het her or n ot t he y are c o nsi dere d t o be 
relate d t o treat me nt. A descri pti o n of t he A E will be rec or de d wit h t he d ate of o nset, date of 
res ol uti o n, se verit y of t he A E, relati o ns hi p t o t he st u d y de vice, acti o n ta ke n, a n d t he outc o me.  
T he fre q u e nc y a n d t y pe of A Es will be e val uat e d f or eac h gr o u p bas e d o n t he pre vi o us 

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treat me nts t hat t he y recei ve d i n t he P R O 2 0 1 8- 0 2 a n d P R O 2 0 1 8- 0 3 pr ot oc ols, a n d t he differe nce 
i n A Es i n t his pr ot oc ol ( P R O 2 0 1 9-0 2) bet wee n t h e s u bjects w h o recei ve d i njecti o ns t hat 
c o ntai ne d li d ocai ne, a n d t he gr o u p t hat was treate d wit h t o pical li d ocai ne. 
7. 9. 2  Ot her S afet y E v al u ati o ns 
A d verse e ve nts of s pecial interest, i ncl u di n g a n y c ha n ges i n visi o n a n d a n y e ve nts attri b uta ble t o 
a n e m b olic or isc he mic ca use ( e. g., s ki n i nfarcti o n), will be e val uate d. Ot her safet y e v al uati o ns 
are li p f u ncti o n, li p se nsati o n, li p te xt ure, li p fir m ness, li p s y m metr y , a n d li p m o ve me nt/f u ncti o n. 
7. 9. 3  Defi niti o n s of Ter ms  
7. 9. 3. 1  A d verse E ve nt  
A n A E is defi ne d as a n y u nt o war d me dical o cc urre nce ass ociate d wit h t he use of a dr u g/ d e vice  
i n h u ma ns, w het her or n ot c o nsi dere d dr u g/ de vi ce-relate d ( 2 1 C o de of Fe deral Re g ulati o ns 
[C F R ] 3 1 2. 3 2 (a) a n d 8 0 3). A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n 
(i ncl u di n g a n a b n or mal l a b orat or y fi n di n g, f or e x a m ple), s y m pt o m, or disease te m p orall y 
ass ociate d wit h t he use of a dr u g / de vice, wit h o ut a n y j u d g me nt a b o ut ca us alit y. 
E x pecte d a d v erse e ve nts are defi ne d as t he e ve nts t hat a p peare d at i njecti o n site s u bse q ue nt t o 
t he first i njecti o n. E x pect e d a d vers e e v e nts ma y i ncl u de b ut are n ot li mite d t o br uisi n g, s welli n g, 
er yt he ma, e d e ma, a n d i nfla m mati o n at i njecti o n site. 
7. 9. 3. 2  S us pecte d A d verse Re a cti o n  
A s us pecte d a d v erse reacti o n ( S A R) is defi ne d as a n y A E f or w hic h t here is reas o na ble 
p ossi bilit y  t hat t he dr u g/ de vice ca use d t he A E ( 2 1 C F R 3 1 2. 3 2 (a)). 
7. 9. 3. 3  U ne x pecte d A d verse E v e nt  
A n A E or S A R is c o nsi dere d u ne x p ecte d if it is n ot c o nsiste nt wit h t he ris k i nf or mati o n 
descri be d i n t he la b eli n g f or t he st u d y de vice. 
7. 9. 3. 4  A d vers e E ve nts of S pe ci al I nterest 
Cer tai n e ve nts will re q uir e m ore detaile d a n d ti mel y re p orti n g. T hese i n cl u de: 
- 
a n y si g nifica nt c ha n g es i n visi o n. A o ne- li ne c ha n ge i n t he S nelle n c hart is c o nsi dere d 
si g nifica nt a n d re q uir es r e p orti n g as a n A E SI. 
- 
a n y e ve nts attri b uta ble t o a n e m b olic or isc he mic ca use (e. g., s ki n i nfarcti o n) 
- 
A n y i nci de nce of a n e v e nt d ue t o a n e m b olic or isc he mic ca use or vis ual dist ur ba nces 
(i ncl u di n g, b ut n ot li mite d t o, a n y l oss of visi o n, bl urr y visi o n, d o u ble visi o n, pai n i n or 
ar o u n d e ye, bli n d s p ot or s ha d o w i n t he vis ual fiel d, tr o u ble m o vi n g e yes, etc.) M U S T be 
i m me diatel y re p orte d t o t he Me dical M o nit or b y p h o ne, e mail or fa x. T he 
i n vesti gat or/c o or di nat or m ust c o m plete t he A E s o urce/ C R F pa g e a n d e m ail or fa x it t o 
t he Me dical m o nit or as s o o n as p ossi ble after t he i n vesti gat or or c o or di n at or has bec o m e 
a war e of its occ urre n ce.  T hese re p orts will i ncl u de t he de pt h of i njecti o n, t he i njecti o n 
v ol u me, t he s y m pt o ms t hat were o bs er ve d, t h e ti me t o o nset, ti me t o res ol uti o n, a n d a n y 

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i nter ve nti o ns t hat were i m ple me nte d. T he S p o ns or will n otif y t he F D A wit hi n 
1 0 w or ki n g da ys re g ar dless of relati o n t o i n vesti gati o nal de vice. 
I n t he e ve nt of bli n d ness or a n y o p ht hal mic si g ns or s y m pt o ms, s u bjects will u n der g o i m me diate 
e val uati o n b y a r eti na s pecialist.  
Refer t o A p pe n di x 1: Filler First Ai d Pr ot oc ol .  
7. 9. 3. 5  Seri o us A d verse E ve nt  
A n S A E is defi ne d as a n y A E or S A R t hat, i n t he vie w of t he i n vesti gat or or S p o ns or, res ults i n 
a n y of t he f oll o wi n g o utc o mes ( 2 1 C F R 3 1 2. 3 2 (a)): 
•  Deat h  
•  Life -t hreate ni n g A E ( N ote: t he ter m “life-t hreat e ni n g” as use d here refers t o a n e ve nt t hat 
i n t he vie w of t he i n vesti gat or or S p o ns or places t he s u bject at i m me diate ris k of deat h at 
t he ti me of t he e ve nt; it d oes n ot i ncl u de a n A E or S A E t hat, ha d it occ urre d i n a m ore 
se vere f or m, mi g ht ha ve ca use d deat h [ 2 1 C F R 3 1 2. 3 2(a)]) 
•  I n p atie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n. See e xcl usi o n t o S A E 
re p orti n g bel o w u n der Pla n ne d H os pitalizati o n. 
•  Persiste nt or si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct 
n or mal life f u ncti o ns 
•  C o n ge nital a n o mal y/ birt h defect 
•  Re q uire d i nter ve nti o n t o pre ve nt per ma ne nt i m pair me nt/ da ma ge 
•  A n y “ ot her” i m p ort a nt me dical e v e nt.  I mp orta nt me dical e ve nts t hat ma y n ot res ult i n 
deat h, be life-t hreat e ni n g, or re q uire h os pitalizati o n ma y be c o nsi dere d seri o us w he n, 
base d u p o n a p pr o priate me dical j u d g me nt, t he y ma y je o par dize t he s u bject a n d ma y 
re q uire me di cal or s ur gical i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d i n t his 
defi niti o n. E xa m ples of s uc h me dical e v e nts i ncl u de aller gic br o nc h os pas m re q uiri n g 
i nte nsi ve treat me nt i n a n e mer ge n c y r o o m or at h o me, bl o o d d yscrasias or c o n v ulsi o ns 
t hat d o n ot res ult i n i n patie nt h os pitalizati o n, or t he de vel o p me nt of dr u g de pe n de nc y or 
dr u g a b use. 
T he F D A c o nsi ders e ve nts s uc h as detac h e d reti na a n d Bell’s Pals y  seri o us a d verse e ve nts.  
7. 9. 3. 6  Pl a n ne d H os pit aliz ati o n  
A h os pitalizati o n pla n ne d b y t he s u bject pri or t o si g ni n g t he I C F is c o nsi d ere d a t hera pe utic 
i nter ve nti o n a n d n ot t he r es ult of a ne w S A E a n d s h o ul d be rec or de d as me dical hist or y. If t he 
pla n ne d h os pitalizati o n or pr oce d ure occ urs as pl a n ne d, t he rec or d i n t he s u bject’s me dical 
hist or y is c o nsi dere d c o m plete. H o we ver, if t he e ve nt/c o n diti o n w orse ns d uri n g t he st u d y, it m ust 
be re p ort e d as a n A E.  
7. 9. 4  Pre g n a nc y  
Pre g na ncies o cc urri n g aft er a d mi nistrati o n of st u d y de vice re q uire i m me diate re p orti n g. T he y 
m ust be re p orte d wit hi n 2 4 h o urs after t h e i n vesti gat or has bec o me a w are of t he pre g n a nc y. A 
pre g na nc y re p ort will be c o m plete d a n d se nt b y fa x t o t he S p o ns or or desi g nee wit hi n 2 4 h o urs 

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of bec o mi n g a w are of t he pre g na nc y. T he i n vesti g at or will c ollect f oll o w - u p i nf or mati o n 
re gar di n g t he o ut c o me of t he pre g na n c y a n d a n y p ost natal se q uelae i n t he i nfa nt t hat m ust als o be 
re p orte d t o t he S p o ns or or desi g nee.  U p o n a ware n ess of t he o utc o me of t h e pre g na nc y, t h e 
Pri nci pal I n v esti gat or  or desi g nee m ust f or w ar d a f oll o w- u p Pre g na n c y Re p ort wit h a n y rele v a nt 
i nf or mati o n t o t he S p o ns or or desi g nee.  
If t he o utc o me of t h e pre g na nc y meets t he criteria f or i m me diate classificati o n of a n S A E (e. g., 
s p o nta ne o us a b orti o n, still birt h, ne o natal deat h, or c o n ge nital a n o mal y), t he i n vestigat or will 
re p ort t he e v e nt b y fa xi n g a c o m plete d S A E re p ort f or m t o t he S p o ns or or desi g nee wit hi n 
2 4 h o urs of bei n g n otifie d of t he pre g n a nc y re p ort. 
T he s u bject s h o ul d i m me diatel y be wit h dra w n fr o m t he st u d y. 
7. 9. 5  M o nit ori n g A d verse E v e nts   
Eac h s u bject will be m o nit ore d f or t he occ urre nce of A Es, i ncl u di n g S A Es, i m me diatel y after 
treat me nt i nitiati o n. Eac h s u bject will be f oll o we d f or safet y m o nit ori n g u ntil disc har ge d fr o m 
t he st u d y. F oll o w- u p pr o ce d ures relate d t o pre g na nc y or A Es or S A Es ma y c o nti n ue be y o n d t he 
e n d of t he st u d y. 
S u bjects will be q uesti o ne d a n d/ or e x a mi ne d b y t he i n vesti gat or or a q u alifie d desi g nee f or 
occ urr e nce of A Es t hr o u g h o ut t he st u d y. T he pres e nce or a bse n ce of s p ecific A Es s h o ul d n ot be 
elicite d fr o m s u bjects. I n a d diti o n, s u bjects will be i nstr ucte d t o rec or d A Es o n t he s u bject di ar y 
car d d uri n g t he 2 wee ks after tr eat me nt , a n d o n t h e s u bject diar y car d dis pe nse d at Visit 2 f or t he 
re mai n der of t he st u d y. S u bjects ha vi n g A Es will be m o nit ore d wit h rele v a nt cli nical assess me nts 
a n d la b orat or y t ests, as deter mi ne d b y t he i n vesti g at or. 
A Es, acti o ns ta ke n as a r es ult of A Es, a n d f oll o w- u p res ults m ust be rec or d e d o n t he C R F, as 
well as i n t he s u bject’s s o urce d oc u m e ntati o n. 
F or all A Es t hat r e q uire t he s u bject t o be wit h dra w n fr o m t he st u d y a n d S A Es, rele va nt cli nical 
assess me nts will b e re peate d as cli nicall y a p pr o priate u ntil fi nal res ol uti o n or sta bilizati o n of t he 
e ve nt(s).  
7. 9. 6  Assess m e nt of A d verse E ve nts  
7. 9. 6. 1  Assess m e nt of Se verit y  
Se verit y of A Es will be gra de d acc or di n g t o t he f oll o wi n g defi niti o ns: 
Mil d : A E t hat was easil y t ole rate d 
M o de rate: A E s ufficie ntl y disc o mf orti n g to i nterfere wit h dail y acti vit y  
Se vere : A E t hat pr e ve nte d n or mal dail y acti vities  
7. 9. 6. 2  Assess m e nt of C a us alit y  
A me dicall y  q ualifie d i n vesti gat or m ust assess t he relati o ns hi p of a n y A E (i ncl u di n g S A Es) t o 
t he use of t he st u d y de vice as u nli kel y relat e d, p ossi bl y relate d, or pr o b a bl y relate d bas e d o n 
a vaila ble i nf or mati o n, usi n g t he f oll o wi n g g ui deli nes:  
U nli kel y relate d : n o te m p oral ass ociati o n, or t he ca use of t h e e ve nt h as bee n i de ntifie d, or 
t he st u d y de vice ca n n ot be i m plicate d  base d o n a v aila ble i nf or mati o n 

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5.  S u bject de m o gra p hics 
6.  Cli nical e ve nt  
a. descri pti o n 
b.  date of o nset 
c. se verit y 
d.  treat me nt (i ncl u di n g h os pitalizati o n) 
e. relati o ns hi p t o st u d y de vice 
f. acti o n ta ke n r e gar di n g st u d y de vice 
g.  if t he A E was f atal or life-t hreate ni n g: 
i. ca use of d eat h ( w het her or n ot t he deat h was relat e d t o st u d y de vice) 
ii. a ut o ps y fi n di n gs (if a vail a ble) 
T he S p o ns or m ust s u b mit a writte n s u m mar y of t h e cli nical c o urs e of a n y life -t hreate ni n g S A E 
a n d relate d s u bj ect i nf or mati o n t o t he F D A wit hi n 7 da ys. Seri o us a n d u ne x pecte d A Es t hat are  
n ot life-t hreate ni n g m ust be re p ort e d t o t he F D A wit hi n 1 5 cale n dar d a ys. A n y seri o us a n d 
u ne x pecte d A E (i ncl u di n g all deat hs) m ust als o be re p orte d t o t he I nstit uti o nal Re vie w B oar d 
(I R B) b y t he i n vesti gat or acc or di n g t o I R B re p orti n g re q uire me nts a n d d o c u me ntati o n of t his 
re p ort se nt t o t he S p o ns or or desi g nee. 
T he i n vesti gat or m ust pr o vi de a f oll o w- u p writte n re p ort w it hi n 5 cale n d ar da ys of re p orti n g t he 
e ve nt t o t he me dical m o nit or.  T he writte n re p ort m ust c o ntai n a f ull descri pti o n of t he e ve nt a n d 
a n y se q uelae.  S u bjects w h o ha ve ha d a n S A E m ust be f oll o we d cli nicall y u ntil all para meters 
(i ncl u di n g la b orat or y) h a ve eit her r et ur ne d t o n or mal or are sta bilize d. 
7. 9. 8  Di ar y Assess m e nts  
Diaries will be re vi e we d b y t he st u d y staff eac h ti me t he y are ret ur n e d b y a s u bject. E ntries will 
be re vie w e d f or c o m plete ness a n d me dical acc urac y. A n y diar y e v e nts liste d b y t he s u bject as 
persisti n g be y o n d t he fi n al rec or di n g da y of t he di ar y will be e val u ate d b y t he I n vesti gat or a n d 
ma y be rec or de d as a n A E  at t he discreti o n of t he I n v esti gat or. 
7. 9. 9  Criteri a f or E arl y Ter mi n ati o n of t he St u d y  
T he trial ma y be ter mi nate d beca use of safet y c o n ce r ns. If ter mi nati o n is dee me d a p pr o priate, 
t here will be ti mel y c o m m u nicati o n wit h t he F D A i n acc or d a nce wit h t he re g ulati o ns ( 2 1 C F R 
8 1 2. 1 5 0 ( de vices)). T he s p o ns or, Pr olle ni u m Me dical Tec h n ol o gies, will i nitiate disc ussi o n as 
s o o n as p ossi ble a b o ut t he a p pr o pri ate c o urs e of acti o n f or t he trial i n q uesti o n a n d f or t he 
i n vesti gati o nal pr o d uct. T here will be i m me diate f oll o w- u p b y t he c o m pa n y t o i n vesti gate a n y 
p ote ntial safet y c o n cer n.  
I n t he e ve nt of a vasc ul ar e m b olic e ve nt lea di n g t o s ki n necr osis, visi o n l oss, or str o ke, 
e nr oll me nt a n d treat me nt at t he i n vesti gati o nal site will be s us pe n de d a n d a r o ot ca use 
i n vesti gati o n will be c o n d ucte d t o deter mi ne t he ca use of t he e m b olic e ve nt a n d w het her t h e 
o utc o me was a ntici pat e d (t he i n vesti gat or di d n ot pr o per l y f oll o w t he treat me nt S O P) or 
u na ntici pate d (t he i n vesti gat or di d pr o perl y f oll o w t he treat me nt S O P). If t h e latter sit uati o n is 

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o bser ve d, t he e ntire st u d y will be i m me diatel y s us pe n de d a n d n o s u bjects will be e nr olle d u ntil 
t he e ve nt ca n be pr o p erl y c haracteri ze d a n d a n a p pr o priate treat me nt strate g y t o a v oi d t his 
u na ntici pate d e ve nt ca n b e de vise d.  
7. 9. 1 0  Wit h dr a w al a n d U n bli n di n g of Tre at me nt  D ue t o S afet y O bser v ati o ns 
7. 9. 1 0. 1  Wit h dr a w al 
See secti o n 7. 3. 3 f or t he criteria f or wit h dra wi n g a s u bject.  If a s u bject is wit h dra w n fr o m t he 
st u d y, t he acti vities s pecifie d f or Visit 2/ M o nt h 1 o n t he sc he d ule of st u d y acti vities ( Secti o n 2) 
s h o ul d be c o m plete d if p ossi ble. 
7. 9. 1 0. 2  U n bli n di n g Tre at m e nt f or a S u bject D uri n g t he St u d y  
U n bli n di n g b y t he i n vesti gat or s h o ul d occ ur o nl y i n t he e ve nt of a n A E or S A E f or w hic h it is 
necessar y t o k n o w t he st u d y treat me nt t o deter mi ne a n a p pr o priate c o urse of t hera p y f or t he 
s u bject. I n t he e v e nt of a n e mer ge n c y t hat re q uires brea ki n g of t he st u d y bli n d, t he I n v esti gat or 
ca n u n bli n d t he s u bject wit h o ut pri or c o ntact wit h t he Me dical M o nit or alt h o u g h t he I n vesti gat or 
will i m me diatel y n otif y t he Me dical M o nit or acc o m pa nie d b y a writte n e x pla nati o n of t he reas o n 
w h y t he bli n d was br o ke n.  I n t he e ve nt of a n e mer ge nc y t hat re q uires brea ki n g of t he st u d y 
bli n d, t he ra n d o mizati o n c o de will be mai ntai ne d b y eac h u n bli n de d Treati n g I n v esti gat or t hat 
ca n be o p e ne d t o re v eal t he st u d y de vice t o t he a p plica ble staff.  I n t he e v e nt t he u n bli n de d 
Treati n g I n vesti gat or is n ot a vaila ble, t he site s h o ul d desi g nate a n ot her u n bli n de d staff me m ber 
n ot i n v ol ve d i n t he st u d y c o n d uct t o access t he ra n d o mizati o n c o de f or t h at s u bject.  N ote t his 
ca n be d o n e WI T H O U T i nf or mi n g t he bli n de d E val uati n g I n v esti gat or a n d t h us mai ntai ni n g t he 
st u d y bli n d.  If u n bli n di n g occ urs, t he s u bject m ust be wit h dra w n fr o m t he 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 he data base l oc k, a detaile d, fi nalize d Statistical A nal ysis Pla n will be c o m plete d a n d 
place d o n file.  T h e Statistical A nal ysis Pla n will c o ntai n a m ore c o m pre he nsi ve e x pla nati o n t ha n 
t hat pr o vi de d her e of t he met h o d ol o g y use d i n t he statistical a nal yses, as well as t he r ules a n d 
data ha n dli n g c o n ve nti o ns use d t o perf or m t he a nal yses a n d t he pr oce d ure use d t o acc o u nt f or 
missi n g data.  Data will be s u m mariz e d o v erall a n d als o br o ke n d o w n b y t h e treat me nt ar m.  
8. 1  
A n al ysis P o p ul ati o ns 
Safet y a n d efficac y r es ults will be s u m marize d des cri pti vel y f or all s u bjects w h o recei ve 
treat me nt i n t his st u d y.   
8. 2  
Effic ac y A n al ysis 
C o m pare s u bject pai n sc ores ( V A S) b et wee n P N 4 0 0 8 2 a n d R V 0 0 1 wit h t o pical a nest hetic  a n d 
R V 0 0 1.  C ha n ge fr o m baseli ne will be s u m marize d f or L F G S a n d P O L. Ot her efficac y vari a bles 
i ncl u de p G AI, i G AI, a n d S welli n g Assess me nt at Visit 2/ M o nt h 1. 
8. 3  
S afet y A n al ysis 
A d verse e ve nts will be c o de d t o s yste m or g a n class a n d preferre d ter ms usi n g t he Me dical 
Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A, Versi o n 2 0 or hi g her). 

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Fre q u e nc y a n d per ce nta g e of s u bjects re p orti n g T E A Es will be ta b ulate d o verall a n d f or eac h 
treat me nt i n P R O 2 0 19- 0 2 b y preferre d t er ms a n d f urt her b y se v erit y a n d relati o ns hi p t o st u d y 
de vice . I n s u m mari es of se verit y a n d relati o ns hi p, s u bjects re p orti n g m ore t ha n o ne e v e nt i n a 
treat me nt ar m t hat are m a p pe d t o t he sa me preferre d ter m will be c o u nte d o nl y o nce i n t hat 
treat me nt ar m u n d er t he str o n gest se verit y a n d relati o ns hi p, res pecti vel y. I n a d diti o n, vis ual 
relate d T E A Es will be s u m marize d se p aratel y b y preferre d t er m. 
8. 4  
S a m ple Size Deter mi n ati o n  
T he ma xi m u m sa m ple size was d eter mi ne d b y t he n u m ber of s u bjects w h o c o m pete d Pr ot oc ol 
P R O  2 0 1 8- 0 2 a n d t he n u m ber of s u bjects w h o r olle d o ver i nt o P R O 2 0 1 8- 0 3. 
9  
E T HI C S  
9. 1  
I nf or m e d C o nse nt 
T he pri nci ples of i nf or me d c o nse nt, acc or di n g t o F o o d a n d Dr u g A d mi nistrati o n ( F D A) 
re g ulati o ns a n d I nter nati o nal C o u ncil f or Har m o nizati o n (I C H) g ui deli nes o n G o o d Cli nical 
Practice ( G C P ), will be f oll o we d. A c o p y of t he pr o p ose d I C F m ust be s u b mitte d wit h t he 
pr ot oc ol t o t he I R B f or a p pr o val. 
T he i nf or me d c o ns e nt pr ocess m ust be c o n d ucte d a n d t he I C F m ust be si g n e d bef ore eac h s u bject 
u n der g oes a n y Visit 1 pr oce d ures t h at are p erf or me d s olel y f or t he p ur p os e of deter mi ni n g 
eli gi bilit y f or t he st u d y, i n c o m plia nce wit h 2 1 C F R Part 5 0. Eac h s u bject’s si g ne d I C F m ust be 
ke pt o n file b y t he i n vesti gat or f or i ns pecti o n b y re g ulat or y a ut h orities at a n y ti me. A c o p y of t he 
si g ne d I C F will be gi ve n t o t he s u bject. A n otati o n will be ma de i n t he s u bject’s me dical rec or d 
i n dicati n g t he date a n d ti me i nf or me d c o nse nt w as o btai ne d. 
9. 2  
I nstit uti o n al Re vie w B o ar d (I R B) 
T he st u d y pr ot oc ol a n d I C F m ust be a p pr o ve d i n writi n g b y a n a p pr o priat e I R B as defi ne d b y 
F D A r e g ulati o ns a n d ot h er a p plica bl e re q uire me nts pri or t o e nr oll me nt of a n y st u d y s u bjects. 
A n y c ha n ges t o t he pr ot oc ol or a c h a n ge of i n v esti gat or a p pr o v e d b y t he S p o ns or m ust als o be 
a p pr o ve d b y t he site’s I R B a n d d oc u me ntati o n of t hat a p pr o val pr o vi d e d t o t he S p o ns or or 
desi g nee. Rec or ds of t he I R B re vi e w a n d a p pr o val of all d oc u me nts pertai ni n g t o t his st u d y m ust 
be ke pt o n file b y t he i n v esti gat or a n d are s u bject t o i ns pecti o n b y re g ulat or y a ut h orities d uri n g 
or after c o m plet i o n of t he st u d y. S A Es m ust als o be re p ort e d t o t he I R B. 
Peri o dic stat us re p orts m ust be s u b mitte d t o t he I R B at least a n n uall y, as well as n otificati o n of 
c o m pleti o n of t he st u d y a n d a fi nal re p ort wit hi n 1 m o nt h of st u d y c o m pleti o n or ter mi nati o n. A 
c o p y of all re p orts s u b mitte d t o t he I R B m ust be se nt t o t he  S p o ns or or desi g nee. 
T he i n vesti gat or will e ns ure t hat a n I R B t hat c o m plies wit h t he re q uire me nts set f ort h i n 2 1 C F R 
Part 5 6 will be res p o nsi ble f or t he i nitial a n d c o nti n ui n g re vie w a n d a p pr o v al of t he st u d y. 
9. 3  
S u bject C o nfi de nti alit y  
All s u bject data will be i de ntifie d o nl y b y a s u bject i de ntificati o n n u m ber a n d s u bject i nitials. 
H o we ver, i n c o m plia nce wit h fe der al g ui deli nes re gar di n g t he m o nit ori n g of cli nical st u dies a n d 
i n f ulfill me nt of his/ her o bli gati o ns t o t he S p o ns or , t he i n vesti gat or m ust per mit t he st u d y 
m o nit or, S p o ns or re prese ntati ve or a u dit or, a n d/ or F D A re pres e ntati ve or ot her re g ul at or y 

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a ut h orit y t o re vie w t he p orti o n of t he s u bject’s me dical rec or d t hat is directl y relate d t o t he st u d y. 
T his s hall i ncl u de all st u d y -rele v a nt d oc u me ntati o n i ncl u di n g me dical hist or y t o verif y 
eli gi bilit y, a d missi o n/ disc har ge s u m maries f or h os pital sta ys occ urri n g w hile t he s u bject is 
e nr olle d i n t he st u d y, a n d a ut o ps y re p orts if a d eat h occ urs d uri n g t he st u d y. 
As part of t he r e q uire d c o nte nt of i nf or me d c o ns e nt, eac h s u bject m ust be i nf or me d t hat his or 
her me dical c hart ma y b e re vie we d b y t h e  S p o ns or, t he S p o ns or’s a ut h orize d re pres e ntati ves, 
F D A or ot h er r e g ulat or y a ut h orit y. If access t o t he me dical r ec or d re q uires a se parate w ai ver or 
a ut h orizati o n, it is t he i n vesti gat or’s res p o nsi bilit y t o o btai n s uc h per missi o n fr o m t he s u bject i n 
writi n g bef ore t he s u bj ect is e ntere d i nt o t he st u d y. 
9. 4  
St u d y Re gistr ati o n 
T he st u d y will be re gister e d b y t he S p o ns or o n a n a p pr o priate free p u blic w e bsite s uc h as 
cli nicaltrials. g o v, w hic h is a ser vice of t he U nite d States Nati o nal I nstit utes of Healt h.  
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  
1 0. 1  Site Re g ul at or y D oc u m e nts Re q uire d f or I niti ati o n  
T h e S p o ns or or desi g nee will recei ve t he f oll o wi n g d oc u me nts pri or t o t he i nitiati o n of t he st u d y: 
•  C o m plete d, si g ne d F or m F D A 1 5 7 2 
•  C urre nt c urri c ula vitae, si g ne d a n d date d, f or t h e PI  a n d c o-i n v esti gat ors na me d o n F or m 
F D A 1 5 7 2 
•  C urre nt lice nse(s) of t he PI a n d c o-i n vesti gat ors n a me d o n F or m F D A  1 5 7 2 
•  D oc u me ntati o n of I R B a p pr o val of t he st u d y pr ot oc ol, i n vesti gat or, a n d I C F 
•  C urre nt I R B me m bers hi p list  
•  A c o p y of t he pr ot o c ol si g nat ure pa g e si g ne d b y t he PI  
•  Ori gi nal N o n- discl os ure A gree me nts f or t he PI  a n d c o-i n vesti gat ors na me d o n F or m 
F D A  1 5 7 2 
•  De bar me nt Certificati o n f or t he  PI  a n d c o-i n vesti gat ors na me d o n F or m F D A 1 5 7 2 
•  Fi na ncial Discl os ur e State me nt f or all i n di vi d uals na me d  o n F or m F D A 1 5 7 2 
1 0. 2  M ai nte n a nce a n d Rete nti o n of Rec or ds  
T he st u d y will be c o n d ucte d acc or di n g t o G C P  as o utli ne d i n I C H g ui deli n es b y t he F D A . It is 
t he res p o nsi bilit y of t he i n vesti gat or t o mai ntai n a c o m pre he nsi ve a n d ce ntralize d fili n g s yste m 
of all rele v a nt d oc u me ntati o n. I n vesti gat ors will be i nstr ucte d t o retai n all st u d y rec or ds re q uire d 
b y t he S p o ns or a n d t he re g ulati o ns i n a sec ure a n d safe facilit y wit h li mite d access. Re g ulati o ns 
re q uire r ete nti o n f or a peri o d of at least 2 years after mar k eti n g a p pr o val a n d n otificati o n fr o m 
t he S p o ns or. T hese r e g ulat or y d oc u me nts s h o ul d be retai ne d f or a l o n g er p eri o d if re q uire d b y 
l ocal re g ulat or y a ut h orities.  

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T hese rec or ds i ncl u de d o c u me nts pertai ni n g t o t he recei pt a n d ret ur n of st u d y de vice , I R B, 
i nf or me d c o nse nt, s o ur ce d oc u me nts, a n d fi nal si g ne d C R Fs . N o d oc ume nts s hall be tra nsferre d 
fr o m t he site or destr o y e d wit h o ut first n otif yi n g t he S p o ns or. 
1 0. 2. 1  C ase Re p ort F or ms ( C R F s)  
C R Fs f or i n di vi d ual s u bjects will be pr o vi de d b y t he S p o ns or or desi g nee. C R Fs m ust be le gi ble 
a n d c o m plete.  C R Fs f or t his st u d y will be mai ntai ne d i n a st u d y bi n der a n d data rec or de d o n 
2- part N C R pa per. O ne c o p y will be ke pt b y t he i n vesti gat or a n d t he ot her c o p y will be c ollecte d 
b y t he st u d y m o nit or. All f or ms s h o ul d be c o m plet e d usi n g a blac k ball p oi nt pe n. Err ors s h o ul d 
be li ne d o ut, b ut n ot o bliter ate d,  a n d t he c orrecti o n i nserte d, i nitiale d, a n d date d b y desi g nate d 
st u d y pers o n nel. F urt h er data c orrecti o ns will be p erf or me d o n s p ecial “ d at a c orrecti o n for ms” 
( D C Fs) t hat will be pr o vi de d t o t he i n vesti gat or i n case of err o n e o us or u ncl ear dat a. The 
i n vesti gat or will ma ke t he c orr ecti o n o n t he D C F a n d si g n t he D C F. T he ori gi nal will be se nt t o 
t he st u d y m o nit or a n d a c o p y retai ne d wit h t he C R Fs. 
A C R F m ust be c o m plete d a n d si g ne d b y t he i n vesti gat or f or eac h s u bject e nr olle d, i ncl u di n g 
t h ose wit h dra w n  fr o m t h e st u d y f or a n y reas o n. T he reas o n f or wit h dra wal  m ust be n ote d o n a 
s u bject’s st u d y ter mi nati o n f or m. 
C R Fs m ust be ke pt c urre nt t o reflect t he s u bject’s stat us at eac h p h ase d uri n g t he c o urse of t he 
st u d y. S u bjects are n ot t o be i de ntifie d o n C R Fs b y na me; a p pr o pri atel y c o de d i de ntificati o n a n d 
t he s u bject’s i nitials m ust be use d. T he i n vesti gat or m ust kee p a se p arat e l o g of t he s u bjects ’ 
na mes a n d a d dresses.  
S o urce d oc u me nts s uc h as t he cli nic c hart are t o b e mai ntai ne d se paratel y fr o m t he C R F  t o all o w 
data verifi cati o n.  Beca us e of t he p ote ntial f or err ors, i nacc uracies, a n d ill e gi bilit y i n tra nscri bi n g 
data o nt o C R Fs , ori gi nals of la b orat or y a n d ot her t est res ults m ust be ke pt o n file wit h t he 
s u bject’s C R F . C R Fs , s o urce d oc u m e nts, a n d c o pi es of test res ults m ust be a vaila ble at all ti mes 
f or i ns pecti o n b y t he st u d y m o nit or. T he f oll o wi n g s h o ul d als o be a vaila ble f or re vie w: 
•  S u bject Scree ni n g L o g, w hic h s h o ul d reflect t he reas o n a n y s u bject scre e n e d f or t he s t u d y 
was f o u n d t o be i neli gi ble 
•  Dele gati o n of A ut h orit y L o g , w hic h will list all site pers o n nel wit h t heir res p o nsi bilities 
as dele gate d b y t h e PI a n d t heir si g nat ures. T his l o g will be mai ntai ne d at t he site 
t hr o u g h o ut t he st u d y 
•  M o nit ori n g L o g , w hic h will list t he date a n d p ur p ose of all m o nit ori n g visits b y t he 
S p o ns or or desi g nee 
•  E nr oll me nt L o g, w hic h will list  s u bject i nitials a n d start a n d e n d dat es f or all e nr olle d 
s u bjects 
•  Pr o d uct I n v e nt or y/ Pac ki n g Sli p, w hic h will list  t he t otal a m o u nt of st u d y de vice s hi p pe d 
t o t he site a n d recei ve d a n d si g ne d f or b y t he i n vesti gat or 
•  St u d y D e vice Dis pe nsi n g L o g, w hic h will list  t he l ot n u m ber a n d t otal a m o u nt of st u d y 
de vice  use d f or eac h  s u bj ect 
•  I C F, w hic h m ust be a v aila ble f or eac h s u bjec t a n d be verifie d f or pr o p er d o c u me ntati o n 
•  All c orres p o n d e nce 

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1 0. 2. 2  Pri m ar y S o urce D oc u m e nts  
T he i n vesti gat or m ust mai ntai n pri mar y s o urce d o c u me nts s u p p orti n g si g nifica nt data f or eac h 
s u bject’s me dical n otes. T hese d oc u me nts, w hic h are c o nsi d ere d “s o urce d ata ,” s h o ul d i ncl u de 
d oc u me ntati o n of: 
•  De m o gra p hic i nf or mati o n 
•  E vi de nce s u p p orti n g t he i n dicati o n f or w hic h t he s u bject is bei n g st u die d 
•  Ge ner al i nf or mati o n s u p p orti n g t he s u bject’s partici pati o n i n t he st u d y 
•  Ge ner al hist or y a n d p h ysical fi n di n gs 
•  H os pitalizati o n or E mer g e nc y R o o m rec or ds (if a p plica ble)  
•  Eac h st u d y visit b y date, i ncl u di n g a n y rele va nt fi n di n gs/ n otes b y t he i n vesti gat or(s), 
occ urr e nce ( or lac k) of A Es , a n d c ha n g es i n me dicati o n usa ge 
•  A n y a d diti o nal visits d uri n g t he st u d y 
•  A n y rele va nt tel e p h o ne c o n versati o ns wit h t he s u bject re gar di n g t he st u d y or p ossi ble 
A Es  
•  A n ori gi nal, si g ne d I C F f or st u d y partici pati o n 
T he i n vesti gat or m ust als o retai n all s u bject -s p ecific pri nt o uts/re p orts of tests a n d pr oce d ures 
perf or me d as a r e q uire m e nt of t he st u d y. D uri n g m o nit ori n g visits t he m o nit or will vali date C R F 
e ntries a gai nst t hese d ata s o urces.  
1 0. 3  St u d y M o nit ori n g  
T he  S p o ns or or desi g nee will be res p o nsi ble f or m o nit ori n g t he st u d y acc or di n g t o G C P a n d 
a p plica ble r e g ulati o ns. T he st u d y will be m o nit o re d b y a Cli nical Researc h Ass ociate ( C R A) i n 
c o m plia nce wit h G C P, I C H g ui deli nes, a n d a p plica ble re g ulati o ns. T he i n vesti gat or will be 
visite d b y a C R A pri or t o t he st u d y a n d at re g ular i nter vals d uri n g t he c o urse of t he st u d y. T hese 
visits are t o verif y a d h ere nce t o t he pr ot oc ol. T h e C R A will re vie w t he I C Fs a n d verif y C R F 
e ntries b y c o m pari n g t he m wit h t he s o urce d oc u m e nts ( h os pital/cli nic/ office rec or ds) t hat will be 
ma de a vaila ble f or t his p ur p ose. T he C R A will re vie w t he mai nte na n ce of re g ulat or y 
d oc u me ntati o n a n d pr o d u ct acc o u nt a bilit y. T he m o nit or will re vie w t he pr o gress of t he st u d y 
wit h t he i n vesti gat or a n d ot her site pers o n nel o n a re g ular b asis. C R Fs ma y be c ollecte d d uri n g 
t hese visits. At t he e n d of t he st u d y, a cl ose o ut m o nit ori n g visit will be perf or me d. M o nit ori n g 
visits will be arra n ge d wit h site pers o n nel i n a d va n ce at a m ut uall y acce pt a ble ti me. S ufficie nt 
ti me m ust be all o we d b y t he site pers o n nel f or t h e m o nit ori n g of C R Fs a n d rele va nt s o urce 
d oc u me nts. T he c o or di n at or a n d/ or i n vesti gat or s h o ul d be a vaila ble t o a ns w er q uesti o ns or 
res ol ve data clarificati o ns. A de q uate ti me a n d s p ace f or t h ese visits s h o ul d be ma de a v aila ble b y 
t he i n vesti gat or a n d st u d y staff. 
1 0. 4  A u dits a n d I ns pecti o ns  
D uri n g t he c o urs e of t he st u d y a n d/ or after it has b ee n c o m plete d, 1 or m ore site s ma y be a u dite d 
b y a ut h orize d r e pres e ntati ves of t he S p o ns or. T he p ur p ose of t he a u dit is t o deter mi ne w het h er or 
n ot t he st u d y is bei n g c o n d ucte d a n d m o nit ore d i n c o m plia nce wit h rec o g nize d G C P/I C H 
g ui deli nes a n d re g ulati o ns. 

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A d diti o nall y, t he st u d y ma y be i ns pecte d b y re g ulat or y a ut h orities . T hese i ns pecti o ns ma y ta ke 
place at a n y ti me d uri n g  or after c o m pleti o n of t he st u d y a n d are b ase d o n l ocal re g ulati o ns. 
1 0. 5  M o dific ati o ns t o t he Pr ot oc ol 
T he pr oce d ures d efi ne d i n t he pr ot oc ol a n d C R Fs will be caref ull y re vie w e d t o e ns ure t hat all 
parties i n v ol ve d wit h t he st u d y f ull y u n dersta n d t he pr ot oc ol. T o e ns ure t he vali dit y of t he data, 
n o de viati o ns fr o m t he pr ot oc ol ( wit h mi ni mal e xce pti o ns ) ma y be ma de u nless t he iss ue is br oa d 
e n o u g h t o warr a nt re visi o n of t he pr ot oc ol. S uc h re visi o ns m ust be s u b mitte d t o a n d ha ve 
d oc u me nte d a p pr o v al fr o m t he S p o ns or a n d I R B pri or t o i m ple me ntati o n. T he o nl y circ u msta nce 
i n w hic h a n a me n d me nt ma y be i nitiate d wit h o ut pri or I R B a p pr o val is t o eli mi nate a n a p pare nt 
i m me diate hazar d t o a s u bject or s u bjects. I n s uc h a case, ho we ver, t he i n vesti gat or m ust n otif y 
t he S p o ns or i m me diatel y a n d t he I R B wit hi n 5 w or ki n g da ys after i m ple me ntati o n. 
1 0. 6  C o m pleti o n of t he St u d y  
T he i n vesti gat or is re q uir e d t o f or war d C R Fs a n d all ot her rele v a nt data a n d rec or ds t o  t he 
S p o ns or or desi g nee. T h e i n vesti gat or will c o m plete a n d re p ort (s u b missi o n of C R Fs) h is/ her 
st u d y i n satisfact or y c o m plia nce wit h t he pr ot oc ol as s o o n as p ossi ble after t he c o m pleti o n of t he 
st u d y. 
T he i n vesti gat or m ust s u b mit a fi nal re p ort t o t he I R B a n d t he S p o ns or wit hi n 1 m o nt h of st u d y 
c o m pleti o n or earl y ter mi nati 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 mati o n relate d t o t his st u d y t hat is s u p plie d b y t he S p o ns or a n d n ot pre vi o usl y p u blis he d 
is c o nsi dere d c o nfi de ntial i nf or mati o n. T his i nf or mati o n i ncl u des b ut is n ot li mite d t o data, 
materials ( pr ot oc ol, C R Fs ), e q ui p me nt, e x peri e nce ( w het her of a s cie ntific, tec h nical, 
e n gi neeri n g, o perati o nal, or c o m merci al nat ure), d esi g ns, s pecificati o ns, k n o w- h o w, pr o d uct 
uses, pr ocess es, f or m ulae, c osts, fi na ncial data, m ar keti n g pla ns a n d direct selli n g s yste ms, 
c ust o mer lists , a n d tec h ni cal a n d c o m mercial i nf or mati o n relati n g t o c ust o mers or b usi ness 
pr ojecti o ns use d b y t he S p o ns or i n its b usi ness. A n y data, i n ve nti o ns, or disc o veries c ollecte d or 
de vel o pe d as a res ult of t his st u d y are c o nsi dere d c o nfi de ntial.  T his c o nfi d e ntial i nf or mati o n 
s hall re mai n t he s ole pr o pert y of t he S p o ns or, s hall n ot be discl ose d t o a n y u na ut h orize d pers o n 
or use d i n a n y u na ut h orize d ma n ner wit h o ut writte n c o nse nt of t he S p o ns or, a n d s hall n ot be 
use d e xce pt i n t he p erf or ma nce of t he st u d y. 
T he i nf or mati o n de vel o p e d d uri n g t he c o urs e of t his st u d y is als o c o nsi dere d c o nfi de ntial a n d 
will b e use d b y t he S p o ns or i n t he de vel o p me nt of t he st u d y me dicati o n. T he i nf or mati o n ma y be 
discl ose d as dee me d n ecessar y b y t he  S p o ns or. T o all o w t he use of t he i nf or mati o n deri ve d fr o m 
t his st u d y, t he i n vesti gat or is o bli ge d t o pr o vi de t he S p o ns or wit h c o m plete test res ults a n d all 
data de vel o p e d i n t he st u d y. T he i nf or mati o n o btai ne d d uri n g t his st u d y ma y be ma de a v aila ble 
t o ot her i n vesti gat ors w h o are c o n d u cti n g si milar st u dies. 
T he i n vesti gat or s hall n ot ma ke a n y p u blicati o n relate d t o t his st u d y wit h o ut t he e x press writte n 
per missi o n of t he S p o ns or. If t he i n vesti gat or w a nts  t o p u blis h or prese nt t he res ults of t his st u d y, 
he or s he a grees t o pr o vi de t he S p o ns or wit h a n a bstract, ma n uscri pt, a n d/ or prese ntati o n f or 
re vie w 6 0 da ys pri or t o s u b missi o n f or p u blicati o n or prese ntati o n. T h e  S p o ns or retai ns t he ri g ht 

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t o delete c o nfi de ntial i nf or mati o n  a n d t o o bject t o s u g geste d p u blicati o n/ prese ntati o n a n d/ or its 
ti mi n g (at t he S p o ns or’s s ole discreti o n). 
1 2  LI S T O F R E F E R E N C E S  
Carr ut hers A, Carr ut hers J, Har das B,  et al. A v ali date d li p f ull ness gra di n g scale. Der mat ol 
S ur g. 2 0 0 8; 3 4 S u p pl 2: S 1 6 1- S 1 6 6. 
C hest n ut C. Rest orati o n of vis ual l oss wit h retr o b ul bar h yal ur o ni dase i njecti o n after h yal ur o nic 
aci d filler. D er mat ol S ur g. 2 0 1 8; 4 4: 4 3 5- 4 4 6. 
C o he n J L, T h o mas J, Par a d kar D, et al. A n i nterrater a n d i ntrarater relia bilit y st u d y of 
3 p h ot o gra p hic scal es f or t he classificati o n of p eri oral aest hetic fi g ures. D er mat ol S ur g. 
2 0 1 4; 4 0: 6 6 3- 6 7 0. 
 
 

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1 3  I N V E S TI G A T O R A G R E E M E N T 
 
Pr ot oc ol N u m ber:  
P R O 2 0 1 9- 0 2 
Pr ot oc ol Title:  
A M ultice nter, D o u ble- bli n d, Ra n d o mize d, C o ntr olle d, R oll- o ver 
St u d y of t he Safet y a n d Pai n Ass ociate d wit h I njecti o ns of  
P N 4 0 0 8 2 or R V 0 0 1 wit h T o pical A nest hetic or R V 0 0 1 f or Li p 
A u g me ntati o n 
 
I h a ve car ef ull y rea d a n d u n dersta n d t he f ore g oi n g pr ot oc ol an d a gree t hat it c o ntai ns all t he 
necessar y i nf or mati o n f or c o n d ucti n g t his st u d y safel y. I will c o n d uct t his st u d y i n strict 
acc or d a nce wit h t his pr ot oc ol, I C H g ui d eli nes f or G o o d Cli nical Practice, t he C o de of Fe deral 
Re g ulati o ns, t he Healt h I ns ura nce P ort a bilit y a n d Acc o u nta bilit y Act ( HI P A A), a n d l ocal 
re g ulat or y g ui deli nes. I will e ns ure t hat t he re q uire me nts f or o btai ni n g i nf or me d c o nse nt are met. 
I will atte m pt t o c o m plete t he st u d y wit hi n t he ti me desi g nate d. I will e ns ure t hat t he ri g hts, 
safet y, an d w elfare of s u bjects u n der m y care are pr otecte d. I will e ns ure c o ntr ol of t he de vices 
u n der i n vesti gati o n i n t his st u d y. I will s u per vise all testi n g of t he de vices i n v ol vi n g h u ma n 
s u bjects. I will pr o vi de c o pies of t he pr ot oc ol a n d all ot her st u d y-relat e d i nf or mati o n s u p plie d b y 
t he s p o ns or t o all pers o n nel res p o nsi ble t o me w h o partici pate i n t he st u d y. I will disc uss t his 
i nf or mati o n wit h t he m t o ass ure t hat t he y are a de q uatel y i nf or me d re gar di n g t he de vice a n d 
c o n d uct of t he st u d y. I a gree t o kee p rec or ds o n all s u bject i nf or mati o n (case re p ort f or ms, 
s hi p me nt a n d de vice r et ur n f or ms, a n d all ot her i nf or mati o n c ollecte d d uri n g t he st u d y) a n d 
de vice dis p ositi o n i n acc or da nce wit h F D A re g ulati o ns. I will n ot e nr oll a n y s u bjects i nt o t his 
pr ot oc ol u ntil I R B a p pr o val a n d s p o ns or a p pr o v al are o btai ne d. 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
I n v esti gat or Na me ( Pri nt) 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _             _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
I n v esti gat or Si g nat ure                                                          Date  
 

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1 4  A P P E N DI X 1: FI L L E R FI R S T AI D P R O T O C O L  ( C H E S T N U T C., 2 0 1 8) 
M ateri als t h at a re nee d e d o n -site: 
•  H yal ur o ni dase ( H yle ne x ) 
•  As piri n 3 2 5 m g 
•  Nitr o gl yceri n paste 
Pr o vi de t he f oll o wi n g c o nt acts t o s u bjects a n d t hese c o nt acts s h o ul d als o  be  p oste d o n-
site f or e as y ref ere nce: 
•  O p ht hal m ol o gist “ o n call”  
•  Cl osest E R wit h str o ke ma na ge me nt ca pa bilit y wit h directi o ns t o E R  
Pre p ar ati o n:  
- T he a b o ve mat erial s s h o ul d be gat here d a n d la bel e d f or e m er ge n c y use o nl y (t o e ns ure 
t he y are a vaila ble s h o ul d a n ur ge nt sit uati o n arise). 
- Staff s h o ul d be e d ucate d re gar di n g t he ur ge nt nat ure of s uc h a n e ve nt a n d t he l ocati o n of 
all materials a n d c o ntact i nf or mati o n.  
- I n v esti gat ors ma y wis h t o fa miliarize t he msel v es wit h t he retr o b ul bar i njecti o n tec h ni q ue 
via literat ure or o n li ne tr ai ni n g.   
It is critical t o rec o g nize a n y i ntra vasc ul ar e v e nts d uri n g i njecti o ns a n d act q uic kl y t o 
ma xi mize li keli h o o d of re versal. As s o o n as a n i ntra vasc ul ar is rec o g nize d, st o p a n y 
f urt her i njecti o ns. 
If a s ki n i nf arcti o n is i de ntifie d: 
•  A p pl y nitr o gl yceri n paste – a p pl y li berall y t o t he affect e d area a n d m assa ge i n ge ntl y, 
e x pect hea dac he c o m plai nt fr o m s u bject b ut d o n ot wit h h ol d t he treat me nt. 
•  Massa ge area  t o h el p pr o m ote d bl o o d fl o w 
•  Dis pe nse As piri n 3 2 5 m g - Ha ve p atie nt c he w t his or t he as piri n ma y be place d 
s u bli n g uall y f or ma xi m u m ra pi d a bs or pti o n 
•  If bla nc hi n g persists, c o nsi der i nfiltrati o n wit h h yal ur o ni dase 
o  I nfiltrate i n t he ar ea w here material w as bei n g i njecte d – t his ma y all o w 
h yal ur o ni dase t o e nter t he sa me vessel t hat w as i n a d verte ntl y ca n n ulate d. 
o  I nfiltrate i n t he ar ea of bla nc hi n g or isc he mia as w ell 
o  I nject a mi ni m u m of 5 0 u nits i nt o eac h area; i n vesti gat ors are free t o use lar ger 
d oses as t he y see fit.  
o  H yal ur o ni dase ma y b e re peate d as n ee de d.  
•  H ot Pac ks – T o wels or g el pac ks war me d i n a micr o wa ve ca n be a p plie d  t o t he area of 
decrease d bl o o d fl o w. 

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•  M o nit or t he s u bject a n d t he area of bla n c hi n g isc h e mia.  If bla n c hi n g persists after 2 4 
h o urs, – c o nsi der h y per baric o x y ge n treat me nts.  
 
If si g ns/s y m pt o ms of vis u al c h a n ges, o pt h al m o ple gi a, bli n d ness, oc ul ar p ai n ( us u all y 
i m m e di atel y) occ ur : 
•  Dis pe nse As piri n 3 2 5 m g - Ha ve p atie nt c he w or  place  t he ta blet s u bli n g uall y f or 
ma xi m u m ra pi d a bs or pti o n 
•  Massa ge t he gl o be wit h re peate d i n w ar d c o m pressi o n a n d releas e – t his ma y free a n y 
e m b olic material  
•  I nfiltrati o n wit h h yal ur o ni dase i nt o area bei n g c orrecte d or a u g me nte d 
•  Ha ve staff call o p ht hal m ol o g y:  I nsert p hysici a n a n d cell p h o ne n u m ber or o n -call 
o p ht hal m ol o g y at ne arest ce nter wit h o n -c all o p ht h al m ol o gy, a n d arra n ge tra ns p ort 
o  Bri n g h yal ur o ni dase w it h t he s u bject t o t he o p ht hal m ol o gist – at least 3 0 0 u nits. 
•  If tra ns p ort ti me t o o p ht hal m ol o g y or E R is m ore t ha n 6 0 mi n utes, c o nsi der perf or mi n g 
retr o b ul bar h y al ur o ni das e a d mi nistrati o n, 3 0 0-6 0 0 u nits at i nferi or, lateral or bital ri m 
t hr o u g h or bital se pt u m wit h 1- 1. 5 i nc h 2 7 ga u ge n ee dle a v oi di n g gl o be 
After a b o v e  meas ures, e x pe dite t o e mer ge n c y r o o m, t he reti na ca n t olerate a p pr o xi matel y 
9 0 mi n utes of isc he mia u ntil da ma ge bec o mes p er ma ne nt. 
If str o ke s y m pt o ms are rec o g nize d: 
•  Dis pe nse As piri n 3 2 5 m g - Ha ve p atie nt c he w t his or t he as piri n ma y be place d 
s u bli n g uall y f or ma xi m u m ra pi d a bs or pti o n 
•  I nfiltrati o n wit h h yal ur o ni dase i nt o area bei n g c orrecte d or a u g me nte d 
•  Call f or tra ns p ort t o E R i m me diatel y  
•  I nf or m l ocal str o ke t ea m d uri n g tra ns p ort 
 
 

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1 5  A P P E N DI X 2: 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 njecta ble H y al ur o nic Aci d G el wit h 0. 3 % Li d ocai ne 
 
Ca uti o n: Fe der al La w r estricts t his de vice t o i n vesti gati o nal use. T his de vice is li mite d b y 
Fe deral ( or U nite d States) la w t o i n vesti gati o nal use  
D E S C RI P TI O N  
P N 4 0 0 8 2 is a gel of h yal ur o nic aci d ge n erate d b y Stre pt oc occ us s pecies of bacteria, c he micall y 
cr ossli n ke d wit h B D D E, sta bilize d a n d s us pe n de d i n p h os p hate b uffere d sali ne at p H = 7 wit h 
0. 3 % li d ocai ne. 
I N DI C A TI O N 
P N 4 0 0 8 2 is i n dicate d f or s u b m uc osal i m pla ntati o n f or li p a u g me ntati o n a n d der mal i m pla ntati o n 
f or c orrecti o n of p eri oral r h yti ds i n patie nts o ver t he a ge 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 ntrai n dicat e d f or patie nts wit h se v ere aller gies ma nifeste d b y a hist or y of 
a na p h yla xis or hist or y or prese nce of m ulti ple se vere aller gi es. 
•  P N 4 0 0 8 2 c o ntai ns trace a m o u nts of gra m p ositi ve bacterial pr otei ns a n d is 
c o ntrai n dicate d f or patie nts wit h a hist or y of aller gies t o s uc h material.  
•  P N 4 0 0 8 2 is c o ntrai n dicat e d f or patie nts wit h blee di n g dis or ders. 
•  P N 4 0 0 8 2 is c o ntrai n dicat e d f or i m pla ntati o n i n a n at o mical s paces ot h er t ha n t he der mis 
or s u b m uc osal i m pla ntati o n f or li p a u g me ntati o n. 
•  P N 4 0 0 8 2 s h o ul d n ot be use d i n patie nts wit h pre vi o us h y perse nsiti vit y t o l ocal 
a nest hetics of t he a mi de t y pe, s uc h as  li d ocai ne. 
W A R NI N G S  
•  Defer use of P N 4 0 0 8 2 at s pecific sites i n w hic h a n acti ve i nfla m mat or y pr o cess (s ki n 
er u pti o ns s uc h as c ysts, pi m ples, ras hes, or hi ves) or i nfecti o n is prese nt u ntil t he pr ocess 
has bee n  c o ntr olle d. 
•  I njecti o n site reacti o ns (e. g., li p s welli n g, li p pai n, a n d c o nt usi o n) t o P N 4 0 0 8 2, i ncl u di n g 
s h ort-ter m mi n or or m o d erate i nfl a m mat or y s y m pt o ms starti n g s h ortl y after treat me nt of 
li ps    
•  P N 4 0 0 8 2 m ust n ot be i m pla nte d i nt o bl o o d vessels. L ocalize d s u perficial n ecr osis a n d 
scarri n g ma y o cc ur after i njecti o n i n or near v essels, s uc h as i n t he li ps, n ose, or gla bellar 
area. It is t h o u g ht t o res ult fr o m t he i nj ur y, o bstr ucti o n, or c o m pr o mise of bl o o d vessels.  
•  Dela ye d o nset i nfl a m mat or y pa p ules ha v e bee n re p orte d f oll o wi n g t he use of der mal 
fillers. I nfla m mat or y p a p ules t hat ma y occ ur rarel y sh o ul d be c o nsi dere d a n d treate d as a 
s oft tiss ue i nfecti o n. 

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•  I njecti o ns of 4. 0 m L or greater ( u p per a n d l o wer li p c o m bi ne d) per treat me nt sessi o n 
i ncreas es t he occ urre n ce of i njecti o n site reacti o ns. If a v ol u me of m ore t ha n 3 m L is 
nee de d t o ac hie ve o pti mal c orrecti o n, a f oll o w- u p treat me nt sessi o n is  rec o m me n de d. 
•  As wit h all der mal filler pr oce d ures, P N 4 0 0 8 2 s h o ul d n ot be use d i n vasc ular ric h areas. 
Use of si milar pr o d ucts i n t hese areas, s uc h as gla bella a n d n ose, has res ult e d i n cases of 
vasc ular e m b oli zati o n a n d s y m pt o ms c o nsiste nt wit h oc ular vessel occl usi o n, s uc h as 
bli n d ness.   
P R E C A U TI O N S  
•  P N 4 0 0 8 2 is pac ka ge d f or si n gle use. D o n ot resterilize. D o n ot use if pac ka g e is o pe ne d 
or da ma g e d.  
•  T he safet y or effecti ve n ess of P N 4 0 0 8 2 f or t he treat me nt of a nat o mic re gi o ns ot her t ha n 
li ps or peri oral r h yti ds has n ot bee n esta blis he d i n c o ntr olle d cli nical st u dies. 
•  As wit h all tra nsc uta ne o us pr oce d ures, P N 4 0 0 8 2 i m pla ntati o n carries a ris k of i nfecti o n. 
Sta n dar d preca uti o ns ass ociate d wit h i njecta ble m aterials s h o ul d be f oll o w e d. 
•  T he safet y of P N 4 0 0 8 2 f or use d uri n g pre g n a nc y, i n breastfee di n g fe mal es or i n patie nts 
u n der 2 2 years has n ot bee n esta blis he d, a n d t hese i n di vi d uals are e xcl u d e d fr o m t his 
st u d y. 
•  S u bjects wit h k n o w n s usce pti bilit y t o kel oi d f or mati o n are e x cl u de d fr o m t his st u d y. 
F or mati o n of kel oi ds ma y occ ur after d er mal filler i njecti o ns.  
•  H y per pi g me ntati o n ma y occ ur after d er mal filler i njecti o ns. S u bjects wit h k n o w n 
h y per pi g me ntati o n ar e e x cl u de d fr o m t his st u d y. 
•  P N 4 0 0 8 2 s h o ul d be use d wit h ca uti o n i n patie nts o n i m m u n os u p pressi ve t hera p y. 
•  Br uisi n g or blee di n g ma y occ ur at P N 4 0 0 8 2 i njecti o n sites. Patie nts w h o ha ve u n der g o ne 
t hera p y wit h t hr o m b ol ytics, a ntic oa g ula nts, or i n hi bit ors of platelet a g gre g ati o n i n t he 3 
wee ks pr ece di n g tr eat me nt wit h P N 4 0 0 8 2 ha ve n ot bee n st u die d.  
•  After use, s yri n ges a n d n ee dles s h o ul d be ha n dl e d as p ote ntial bi o hazar ds. Dis p osal 
s h o ul d be i n acc or d a nce wit h acce pt e d me dical practice a n d a p plica ble l o cal, state a n d 
fe der al re q uir e me nts. 
•  T he safet y of P N 4 0 0 8 2 wit h c o nc o mita nt der mal t hera pies s uc h as e pilati o n, U V 
irra diati o n, or laser, mec ha nical or c h e mical peeli n g pr oce d ures has n ot bee n e val uat e d i n 
c o ntr olle d cli nical  trials. 
•  Patie nts s h o ul d mi ni mize e x p os ure of t h e treat e d area t o e x cessi ve s u n, U V la m p 
e x p os ure a n d e xtre me c ol d weat her at least u ntil a n y i nitial s welli n g a n d re d ness has 
res ol ve d. 
•  If laser tr eat me nt, c h e mical peeli n g or a n y ot her pr oce d ure b ase d o n acti ve der mal 
res p o nse is c o nsi der e d after treat me nt wit h P N 4 0 0 8 2 , t here is a p ossi ble ris k of eliciti n g 
a n i nfla m mat or y reacti o n at t he i m pla nt site. T his als o a p plies if P N 4 0 0 8 2 is a d mi nistere d 
bef ore t h e s ki n has heal e d c o m pletel y after s uc h a pr oce d ure. 

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•  I njecti o n of P N 4 0 0 8 2 i nt o patie nts wit h a hist or y of pre vi o us her p etic er u pti o n ma y be 
ass ociate d wit h reacti vati o n of t he her p es.  
H O W S U P P LI E D  
P N 4 0 0 8 2 is s u p plie d i n a dis p osa ble glass s yri n ge wit h a L uer-L o k ® fitti n g. P N 4 0 0 8 2 is pac ke d 
wit h t w o 1. 0 m L s yri n ges a n d t w o sterilize d nee dle(s) 3 0 G x ½ ” i n a peel tra y c o ntai ne d i n a 
cart o n. A p atie nt rec or d la bel is a part of t h e s yri n ge la bel. T his la bel is t o be attac h e d t o patie nt 
rec or ds t o e ns ure tr acea bilit y of t he pr o d uct. T he c o nte nts of t he s yri n ge are sterile. 
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 be use d pri or t o t he e x pirati o n date pri nte d o n t he pac k a ge. St ore at a te m per at ure 
of 5 t o 2 5° C ( 7 7° F). D o n ot freeze. Pr otect fr o m s u nli g ht.  
D o n ot use if t he pac k a ge is da ma ge d.   
 
I N J E C TI O N T E C H NI Q U E S 
1.  St u d y de vice  ca n b e i njecte d b y a n u m ber of differe nt tec h ni q ues t hat de p e n d o n t he 
treati n g i n vesti gat or’s e x perie nce a n d prefere n ce, a n d patie nt c haracteristics.  
2.  Seri al p u nct ure  i n v ol ves m ulti ple, cl osel y s pace d i njecti o ns al o n g wri n kles, f ol ds or t he 
ver milli o n b or der. Alt h o u g h serial p u nct ure all o ws precise place me nt of t h e filler, it 
pr o d uces m ulti ple p u nct ure w o u n ds t hat ma y be u n desira ble t o s o me patie nts.  
3.  Li ne ar t hre a di n g (i ncl u des retr o g r a de a n d a nte gr a de)  is acc o m plis he d b y f ull y 
i nserti n g t he nee dle i nt o t he ce nter of t he area t o be c orrecte d or a u g me nte d a n d i njecti n g 
t he filler alo n g t he trac k as a “t hrea d.” Alt h o u g h t hrea di n g is m ost c o m m o nl y practice d 
after t he n ee dle h as bee n f ull y i nserte d a n d is bei n g wit h dra w n, it ca n als o be perf or me d 
w hile a d va nci n g t he n ee dle - a nte gra de tec h ni q ue). T o e n h a nce t h e li p, t he retr o gra d e 
li near t hrea di n g tec h ni q u e is t he m ost a d visa ble. 
4.  Serial t hrea di n g is a tec h ni q ue t hat utilizes ele me nts of b ot h  a p pr oac hes.    
 
N ote! T he c orr ect i njecti o n tec h ni q ue is cr u cial f or t he fi nal res ult of t he treat me nt.  
5.  T he f oll o wi n g tec h ni q ues s h o ul d be a v oi de d as t he y ma y res ult i n a n i ncrease i n s h ort-
ter m e pis o des of br uisi n g, s welli n g, re d ness, pai n, or te n der n ess at t he i njecti o n site: 
•  Dissecti o n of t he s u b- e pi der mal pla ne wit h lateral m o ve me nt of t he nee dl e – 
“fa n ni n g” 
•  Ra pi d fl o w rate ( > 0. 3 m L/ mi n) of i m pla nt material i njecti o n  
•  Hi g h i njecti o n v ol u mes  
•  T he use of nee dles ot her t ha n t h ose pr o vi de d i n t he treat me nt kit 
6.  T he use of ca n n ulas is pr o hi bite d 
7.  W he n t he i njecti o n is c o m plete d, t he treate d site s h o ul d be ge ntl y  massa ge d s o t hat it 
c o nf or ms t o t he c o nt o ur of t he s urr o u n di n g tiss ues.  Massa gi n g t hat s u bsta ntiall y def or ms 
t he li ps, or ca uses bla n c hi n g of c o m presse d tiss ues, is e xcessi ve, a n d s h o ul d be a v oi de d 
e xce pt as d escri be d b el o w.  
8.  If e xcessi ve materi al is i m pla nte d or irre g ularl y i m pla nte d, massa ge t he area s o me w hat 
m ore fir ml y t ha n f or t he us ual i m pla ntati o n pr oce d ure t o o btai n o pti mal res ults. 

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9.  If bla nc hi n g of t he tiss ues is o bser ve d d uri n g or directl y aft er i njecti o n, pa use t he 
pr oce d ur e a n d mass a ge t he area ge ntl y u ntil t he c ol or ret ur ns.  If t h e c o n diti o n persists, 
c o ntact t he Me dical M o nit or. 
1 0.  T he li ps s h o ul d be a u g me nte d t o ac hie v e t he ma xi m u m desira ble a p peara n ce f or b ot h t he 
treati n g i n vesti gat or a n d t he s u bject.  S u bjects s h o ul d be pr o vi de d a s mall h a n d mirr or t o 
o bser ve t he r es ults a n d f urt her i njecti o ns c o n d uct e d u ntil ma xi m u m be nefit has bee n 
o btai ne d.  Care s h o ul d be ta ke n t o e ns ure t h at t he li ps are s y m metric fr o m ri g ht t o left a n d 
t hat t he u p per a n d l o w er li ps ha ve relati ve pr o p orti o nalit y.  
1 1.  T he peri or al ar ea s h o ul d be c orrecte d A F T E R t he u p per a n d l o w er li ps ha v e bee n 
c orrecte d.  S o me c orrecti o n of peri oral r h yti ds ma y occ ur wit h li p a u g me nt ati o n, t h us it is 
best t o a d dress a n y re mai ni n g peri oral c orrecti o n nee ds aft er t he li p i njecti o ns ha ve bee n 
c o m plete d.   
1 2.  If t he treate d area is s w olle n directl y after t he i njecti o n, a n ice pac k ca n be a p plie d o n t he 
site f or a s h ort peri o d. Ice s h o ul d be use d wit h ca uti o n if t he area is still n u m b fr o m 
a nest hetic t o a v oi d t her m al  i nj ur y. 
1 3.  S u bjects s h o ul d be e nc o ura ge d t o a v oi d a rec u m be nt p ositi o n f or se veral h o urs after 
i njecti o ns t o re d uce s w elli n g.  T he use of ice, c ol d pac ks or ot her t hera pi es t o re d uce 
s welli n g s h o ul d o nl y be perf or me d at i nstr ucti o n of t he i n vesti gat or.  T he s u bject s h o ul d 
be i nstr ucte d t o c o ntact t he site if s u bsta ntial s welli n g occ ur s.  
 
 

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1 6  A P P E N DI X 3:  R V 0 0 1  I N S T R U C TI O N S F O R U S E 
R V 0 0 1 I nject a ble H y al ur o nic Aci d Gel  
 
C a uti o n: Fe deral La w restricts t his de vice t o i n vesti gati o nal use. T his de vice is li mite d b y 
Fe deral ( or U nite d States) la w t o i n vesti gati o nal use  
 
D E S C RI P TI O N  
 
R V 0 0 1 ( Re va nesse V ers a wit h o ut  li d ocai ne)  is a gel  of h yal ur o nic aci d ge nerat e d b y 
Stre pt oc occ us s pecies  of  bacteria,  c he micall y  cr ossli n ke d  wit h  B D D E,  sta bilize d  a n d  
s us pe n de d i n p h os p hate b uffer e d sali ne at p H = 7. T he pr o d uct w as pre vi o usl y a p pr o ve d o n 
A u g ust  4, 2 0 1 7 f or mi d -t o-dee p d er mal i m pla ntati o n f or t he c orrecti o n of m o derate t o 
se vere  facial  wri n kles  a n d f ol ds, s uc h as nas ol a bial  f ol ds. T he  pr o d uct  is i njecte d b y  
q ualifie d, trai ne d p h ysici a ns i nt o t he der mis of patie nts, usi n g a vari et y of t ec h ni q ues. T h e 
i njecti o ns place a s mall p orti o n of t he gel be n eat h a crease or wri n kle i n t he s ki n a n d t he 
a u g me ntati o n of t he tiss ue pr o d uces a s m o ot hi n g effect o n t he s urface.   
 
I N DI C A TI O N 
R V 0 0 1  is i n dicate d f or s u b m uc osal i m pla ntati o n f or li p a u g me ntati o n a n d der mal 
i m pla ntati o n f or c orr ecti o n of peri oral r h yti ds i n patie nts o ver t he a g e of 2 1. 
 
C O N T R AI N DI C A TI O N S  
 
•  R V 0 0 1 is c o ntrai n dicate d f or patie nts wit h se vere aller gies ma nifest e d b y a hist or y 
of a na p h yla xis or hist or y or prese n ce of m ulti ple s e vere aller gies.  
 
•  R V 0 0 1 c o ntai ns trace a m o u nts of gra m p ositi ve bacterial pr otei ns, a n d is 
c o ntrai n dicate d f or patie nts wit h a hist or y of aller gies t o s uc h material.  
 
•  R V 0 0 1 is c o ntrai n dicate d f or patie nts wit h blee di n g dis or ders. 
 
•  R V 0 0 1 is c o ntrai n dicate d f or i m pla ntati o n i n a nat o mical s paces ot her t ha n t he 
der mis or s u b m uc osal i m pla ntati o n f or li p  a u g me ntati o n. 
 
•  R V 0 0 1 s h o ul d n ot be use d wit h a t o pical a nest heti c i n patie nts wit h pre vi o us 
h y perse nsiti vit y t o l ocal a nest hetics of t he a mi de t y pe, s uc h as li d ocai ne. 
 
W A R NI N G S  
 
•  Defer use of R V 0 0 1 at s p ecific sites i n w hic h a n acti ve i nfla m mat or y pr ocess 
(s ki n er u pti o ns s uc h as c ysts, pi m ples, ras hes, or hi ves) or i nfecti o n is prese nt 
u ntil t he pr ocess has bee n c o ntr olle d. 
 
•  I njecti o n site reacti o ns (e. g., li p s welli n g, li p pai n, a n d c o nt usi o n) t o R V 0 0 1, 
i ncl u di n g s h ort-ter m mi n or or m o derat e i nfla m mat or y s y m pt o ms starti n g 
s h ortl y after treat me nt of li ps    

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•  R V 0 0 1 m ust n ot be i m pla nte d i nt o bl o o d vessels. L ocalize d s u p erficial n ecr osis 
a n d scarri n g ma y occ ur after i njecti o n i n or near v essels, s uc h as i n t he li ps, n ose, 
or gla bellar area. It is t h o u g ht t o res ult fr o m t he i nj ur y, o bstr ucti o n, or 
c o m pr o mise of bl o o d vessels.  
 
•  Dela ye d o nset i nfl a m mat or y pa p ules ha v e bee n re p orte d f oll o wi n g t he use of 
der mal fillers. I nfla m mat or y pa p ules t hat ma y occ ur rarel y s h o ul d be c o nsi dere d 
a n d treate d as a s oft tiss u e  i nfecti o n. 
 
•  I njecti o ns of 4. 0 m L or greater ( u p per a n d l o wer li p c o m bi ne d) per treat me nt 
sessi o n i ncreas es t he occ urre nce of i njecti o n site reacti o ns. If a v ol u me of m ore 
t ha n 3 m L is nee de d t o ac hie ve o pti mal c orrecti o n, a f oll o w- u p treat me nt sessi o n 
is rec o m me n de d. 
 
•  As wit h all der mal filler pr oce d ures, R V 0 0 1 s h o ul d n ot be use d i n vasc ul ar ric h 
areas. Use of si milar pr o d ucts i n t hese areas, s uc h as gla bella a n d n os e, has res ulte d 
i n cases of vas c ular e m b olizati o n a n d s y m pt o ms c o nsiste nt wit h oc ular vessel 
occl usi o n, s uc h as bli n d ness.   
 
P R E C A U TI O N S  
 
•  R V 0 0 1 is pac ka ge d f or si n gle use. D o n ot resterilize. D o n ot use if p ac ka g e is 
o pe ne d or d a ma ge d.  
•  T he safet y or effecti ve n ess of R V 0 0 1 f or t he treat me nt of a nat o mic re gi o ns ot her 
t ha n li ps or peri oral r h yti ds has n ot bee n esta blis h e d i n c o ntr olle d cli nical st u dies.  
•  As  wit h  all  tra nsc uta ne o us  pr oce d ures,  R V 0 0 1 i m pla ntati o n  carries  a  ris k  of  
i nfecti o n.  Sta n dar d  preca uti o ns  ass ociate d  wit h  i njecta ble  materials  s h o ul d  be  
f oll o we d. 
•  T he safet y of R V 0 0 1 f or use d uri n g pre g n a nc y, i n breastfee di n g fe m ales or i n 
patie nts u n der 2 2 years h as n ot bee n  esta blis he d, a n d t hese i n di vi d uals are e xcl u de d 
fr o m t his st u d y. 
•  S u bjects wit h k n o w n s usce pti bilit y t o kel oi d f or mati o n are e x cl u de d fr o m t his 
st u d y. F or mati o n of kel oi ds ma y occ ur after d er mal filler i njecti o ns. 
•  H y per pi g me ntati o n ma y occ ur aft er d er mal filler i njecti o ns. S u bjects wit h k n o w n 
h y per pi g me ntati o n ar e e x cl u de d fr o m t his st u d y. 
•  R V 0 0 1 s h o ul d be use d wit h ca uti o n i n patie nts o n i m m u n os u p pressi ve t hera p y. 
•  Br uisi n g or blee di n g ma y occ ur at R V 0 0 1 i njecti o n sites. Patie nts w h o ha ve 
u n der g o ne t hera p y wit h t hr o m b ol ytics, a ntic oa g ula nts, or i n hi bit ors of platelet 
a g gre gati o n i n t he 3 w ee ks prece di n g treat me nt wit h R V 0 0 1 ha ve n ot bee n 
st u die d.  
•  After use, s yri n ges a n d n ee dles s h o ul d be ha n dl e d as p ote ntial bi o hazar ds. 
Dis p osal s h o ul d be i n acc or da nce wit h acce pte d m e dical practice a n d a p plica ble 
l ocal, state a n d f e der al re q uire me nts. 
•  T he safet y of R V 0 0 1 wit h c o nc o mita nt der mal t hera pies s uc h as e pilati o n, U V 

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irra diati o n,  or  laser,  mec ha nical  or  c h e mical  p eeli n g  pr oce d ures  has  n ot  bee n  
e val uate d i n c o ntr olle d cli nical  trials. 
•  Patie nts s h o ul d mi ni mize e x p os ure of t he treat e d area t o e x cessi ve s u n, U V  la m p 
e x p os ure a n d e xtr e me c ol d weat her at least u ntil a n y i nitial s welli n g a n d re d ness has  
res ol ve d. 
•  If laser tr eat me nt, c h e mical peeli n g or a n y ot her pr oce d ure b ase d o n acti ve der mal 
res p o nse is c o nsi der e d after treat me nt wit h R V 0 0 1 , t here is a p ossi ble ris k of 
eliciti n g a n i nfla m mat or y reacti o n at t he i m pla nt site. T his als o a p plies if R V 0 0 1 is 
a d mi nistere d be f ore t he s ki n has heale d c o m plet el y after s uc h a pr o ce d ure. 
•  I njecti o n of R V 0 0 1 i nt o p atie nts wit h a hist or y of pre vi o us her petic er u pti o n 
ma y be ass ociat e d wit h r eacti vati o n of t he  h er pes.  
 
 

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H O W S U P P LI E D  
R V 0 0 1 is s u p plie d i n a dis p osa ble glass s yri n ge wit h a L uer-L o k ® fitti n g. R V 0 0 1 is pac ke d 
wit h t w o 1. 0 m L s yri n ges a n d t w o sterilize d nee dle(s) 2 7 G x ½” i n a peel tra y c o ntai ne d i n a cart o n. 
A patie nt rec or d la bel is a part of t he s yri n ge la bel. T his la bel is t o be attac he d t o patie nt rec or ds t o 
e ns ure tracea bilit y of t he pr o d uct. T he c o nte nts of t he s yri n ge are sterile.  Sterilize d nee dles, 3 0 G x 
½”, will be s u p plie d a n d use d f or t he st u d y. 
 
S H E L F LI F E A N D S T O R A G E  
 
R V 0 0 1 m ust be us e d pri or t o t he e x pirati o n d ate pri nte d o n t he p ac k a ge. St ore a t a te m perat ure 
of 5 t o 2 5° C ( 7 7° F). D o n ot freeze. Pr otect fr o m s u nli g ht.  
D o n ot use if t he pac k a ge is da ma ge d.   
  
 
Pr olle ni u m Me dical Tec h n ol o gies I nc.  
1 3 8 I n d ustrial Par k wa y N., A ur ora, L 4 G 4 C 3 O ntari o Ca na da 
P h:   
  
9 0 5- 5 0 8- 1 4 6 9 
T oll free:   
8 6 6- 3 5 3- 3 0 1 5 
Fa x:   
  
9 0 5- 5 0 8- 6 7 1 6 
 
I N J E C TI O N T E C H NI Q U E S 
 
15. St u d y de vice  ca n b e i njecte d b y a n u m ber of differe nt tec h ni q ues t hat de p e n d o n t he 
treati n g i n vesti gat or’s e x perie nce a n d prefere n ce, a n d patie nt c haracteristics. T he t o pical 
a nest hetic s u p plie d i n b ul k s h o ul d be a p plie d 1 5 mi n utes pri or t o i njecti o n f or s u bjects 
ra n d o mize d t o r ecei ve t h e t o pical a nest hetic. 
16. Seri al p u nct ure i n v ol ves m ulti ple, cl osel y s pace d i njecti o ns al o n g wri n kles, f ol ds or t he 
ve r milli o n b or der. Alt h o u g h serial p u nct ure all o ws precise place me nt of t h e filler, it 
pr o d uces m ulti ple p u nct ure w o u n ds t hat ma y be u n desira ble t o s o me patie nts.  
17. Li ne ar t hre a di n g (i ncl u des retr o g r a de a n d a nte gr a de) is acc o m plis he d b y f ull y 
i nserti n g t he nee dle i nt o t he ce nter of t he area t o be c orrecte d or a u g me nte d a n d i njecti n g 
t he filler al o n g t he trac k as a “t hrea d.” Alt h o u g h t hrea di n g is m ost c o m m o nl y practice d 
after t he n ee dle h as bee n f ull y i nserte d a n d is bei n g wit h dra w n, it ca n als o be perf or me d 
w hi le a d va nci n g t he n ee dle - a nte gra de tec h ni q ue). T o e n h a nce t h e li p, t he retr o gra d e 
li near t hrea di n g tec h ni q u e is t he m ost a d visa ble. 
18. Serial t hrea di n g is a tec h ni q ue t hat utilizes ele me nts of b ot h  a p pr oac hes.   
N ote! T he c orr ect i njecti o n tec h ni q ue is cr u ci al f or t he fi nal res ult of t he treat me nt.  
 
19. T he f oll o wi n g tec h ni q ues s h o ul d be a v oi de d: 
• 
Dissecti o n of t he s u b- e pi der mal pla ne wit h lateral m o ve me nt of t he nee dl e – 
“fa n ni n g” 
• 
Ra pi d fl o w rate ( > 0. 3 m L/ mi n) of i m pla nt material i njecti o n  

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• 
Hi g h i njecti o n v ol u mes  
• 
T he use of nee dles ot her t ha n t h ose pr o vi de d i n t he treat me nt kit 
• 
T he use of a t o pical a nest hetic ot her t ha n t hat pr o vi de d i n t he kit 
As t he y ma y res ult i n a n i ncrease i n s h ort -ter m e pis o des of br uisi n g, s welli n g, re d ness, 
pai n, or te n der ness at t he i njecti o n site. 
20. T he use of ca n n ulas is pr o hi bite d 
21. W he n t he i njecti o n is c o m plete d, t he treate d site s h o ul d be ge ntl y  massa ge d s o t hat it 
c o nf or ms t o t he c o nt o ur of t he s urr o u n di n g tiss ues.  Massa gi n g t hat s u bsta ntiall y 
def or ms t he li ps, or ca us es bla nc hi n g of c o m press e d tiss ues, is e xcessi ve, a n d s h o ul d be 
a v oi de d e xce pt as des cri be d bel o w. 
22.  If e xcessi ve materi al is i m pla nte d or irre g ularl y i m pla nte d, massa ge t he area s o me w hat 
m ore fir ml y t ha n f or t he us ual i m pla ntati o n pr oce d ure t o o btai n o pti mal  res ults. 
23. If bla nc hi n g of t he tiss ues is o bser ve d d uri n g or directl y aft er i njecti o n, pa use t he 
pr oce d ur e a n d mass a ge t he area ge ntl y u ntil t he c ol or ret ur ns.  If t h e c o n diti o n persists, 
c o ntact t he Me dical M o nit or. 
24. T he li ps s h o ul d be a u g me nte d t o ac hie v e t he ma xi m u m desira ble a p peara n ce f or b ot h t he 
treati n g i n vesti gat or a n d t he s u bject.  S u bjects s h o ul d be pr o vi de d a s mall h a n d mirr or t o 
o bser ve t he r es ults a n d f urt her i njecti o ns c o n d uct e d u ntil ma xi m u m be nefit has bee n 
o btai ne d.  Care s h o ul d be t a ke n t o e ns ure t h at t he li ps are s y m metric fr o m ri g ht t o left 
a n d t hat t he u p per a n d l o wer li ps ha ve relati ve pr o p orti o nalit y.  
25. T he peri or al ar ea s h o ul d be c orrecte d A F T E R t he u p per a n d l o w er li ps ha v e bee n 
c orrecte d.  S o me c orrecti o n of peri oral r h yti ds ma y occ ur wit h li p a u g me nt ati o n, t h us it 
is best t o a d dress a n y r e mai ni n g peri oral c orrecti o n nee ds aft er t he li p i njecti o ns ha ve 
bee n c o m plete d.   
26. If t he treate d area is s w olle n directl y after t he i njecti o n, a n ice pac k ca n be a p plie d o n t he 
site f or a s h ort peri o d. Ice s h o ul d be use d wit h ca uti o n if t he area is still n u m b fr o m 
a nest hetic t o a v oi d t her m al  i nj ur y. 
27. S u bjects s h o ul d be e nc o ura ge d t o a v oi d a rec u m be nt p ositi o n f or se veral h o urs after 
i njecti o ns t o re d uce s w elli n g.  T he use of ice, c ol d pac ks or ot her t hera pi es t o re d uce 
s welli n g s h o ul d o nl y be perf or me d at i nstr ucti o n of t he i n vesti gat or.  T he s u bject s h o ul d 
be i nstr ucte d t o c o ntact t he site if s u bsta ntial s welli n g occ urs.  
 
 
 
 
 

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1 7  A P P E N DI X 4:  L M X 4 P A C K A G E I N S E R T  
 
1.  L M X 4 – LI D O C AI N E C R E A M F E R N D A L E L A B O R A T O RI E S, I N C.  
Discl ai mer: M ost O T C dr u gs are n ot revie we d a n d a p pr ove d by F D A;  h o w ever t hey m ay b e 
m arkete d if t hey c o m ply wit h a p plic a ble re g ul ati o ns a n d p olicies. F D A h as n ot ev al u ate d 
w het her t his pr o d uct c o m plies. 
 
2.  Dr u g F acts 
Acti ve   in g re di e nt  
Li d o cai n e 4 %  w/ w  
 
  3.  P ur p ose 
T o pi c al a nest hetic  
 
  4.  Uses 
te m p oraril y relie v es pai n a n d itc hi n g d ue t o 
mi n or c uts 
mi n or scra pes  
mi n or b ur ns  
s u n b ur n 
mi n or s ki n irritati o ns  
i nsect bites 
  5.  W ar ni n gs 
F or e xt er n al use o nl y.  
D o n ot use  
i n or near t he e yes 
i n lar ge q ua ntities, partic ularl y o ver ra w s urfaces or blistere d   areas 
 
  6.  St o p use a n d as k a d oct or if: 
aller gic r eacti o n occ urs  
c o n diti o n w orse ns or d oes n ot i m pr o ve wit hi n 7 da ys s y m pt o ms clear u p a n d ret ur n wit hi n a 
fe w da ys 
r e d n ess, irrit ati o n, s w elli n g, pai n or ot h er s y m pt o ms be gi n or  i n cr e as e 
 
  7.  Kee p o ut of re a c h of c hil dre n.  
If s w all o w e d, g et m e di cal h el p or c o nt a ct a P ois o n C o ntr ol Ce nter ri g ht a w a y. 
 
  8.  Directi o ns  
 
A d ults a n d c hil dre n 2 years a n d ol der: A p pl y e xter nall y t o t he affecte d area u p t o 3 t o 4 

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ti mes a da y C hil dre n u n der 2 years: C o ns ult a d oct or 
9.  Ot her I nf or m ati o n 
Ma y be a p plie d u n der occl usi ve dressi n g. 
St ore at 2 5° C ( 7 7° F); e x c ursi o ns per mitte d t o 1 5 - 3 0° C ( 5 9-8 6° F) [see U S P C o ntr olle d 
R o o m Te m perat ure]. 
 
  1 0.  I n acti ve i n gre die nts 
be nz yl alc o h ol, car b o mer 9 4 0, c h olester ol, h y dr o g e nate d lecit hi n, p ol ys or bate 8 0, pr o p yle ne 
gl yc ol, tr ola mi ne, vita mi n E acetat e, water  
 
  1 1. P ac k a ge L a bels- Pri nci p al Dis pl a y P a nels  
M a n uf act ure d b y Fer n d al e 
L a b or at ori es, I nc. F er n d al e, MI 
4 8 2 2 0  U. S. A.  
T oll free ( 8 8 8) 5 4 8- 0 9 0 0 
w w w.fer n dalela bs. c o m  
L. M. X. 4 ® is a re gister e d tra de mar k of Fer n dal e I P, I nc. T e ga d er m ™ is a tra de mar k of 3 M 
C or p orati o n. 
 
 
 

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1 8  A P P E N DI X 5:  VI SI O N E V A L U A TI O N R E S U L T S  
S nell e n Vis u al Ac uit y  
N or mal fi n di n gs:  T he sa me S nelle n Vis ual Ac uit y res ults as t he S nelle n Vis ual Ac uit y res ults 
rec or d e d pre-treat me nt at Visit 1/ baseli ne i n P R O 2 0 1 8- 0 2. 
A b n or mal fi n di n gs:  A n y c ha n ge fr o m t he S nelle n Vis ual Ac uit y res ults rec or de d pre- treat me nt 
at Visit 1/ baseli ne i n P R O 2 0 1 8 - 0 2 will be c o nsi d ere d a b n or mal. 
 C o nfr o nt ati o n al Vis u al Fiel ds  
N or mal fi n di n g:  S u bject re p orts seei n g t he fi n ger at a b o ut t he sa me ti me or l ocati o n as t he 
i n vesti gat or. 
A b n or mal fi n di n g:  S u bject d oes n ot see t h e fi n ger at a b o ut t he sa me ti me or l ocati o n as t he 
i n vesti gat or. 
Oc ul ar M otilit y  
N or mal fi n di n g:  O bser v e e yes t o e ns ure c o nsiste nt c o nj u gate gaze t hr o u g h o ut t he test 
A b n or mal fi n di n g:  S u bject d oes n ot ha ve c o nsiste nt c o nj u gate gaze t hr o u g h o ut t he test