Clinical trial NCT05715346
Conditions: Acquired Blepharoptosis
Keywords: Blepharoptosis
Sponsor: Levation Pharma, Ltd.
Start date: 2023-02-23; Completion date: 2023-06-24
Enrollment: 33 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Phase 1/2a, multicenter, randomized, vehicle-controlled, double-masked, multiple-dose, parallel-group study conducted in adult subjects with acquired blepharoptosis.

Detailed description:
This is a Phase 1/2a, multicenter, randomized, vehicle-controlled, double-masked, single-dose, parallel-group study conducted in adult subjects with acquired blepharoptosis. Subjects will receive a one-time application of randomized, double-masked IP. Approximately 30 subjects will be enrolled in this study. Eligible subjects will be randomized to 1 of the following 3 treatment groups in a 1:1:1 ratio and will receive a single dose of double-masked IP externally on the upper eyelid of both eyes (OU):

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: LEV102 1.0% intervention 2: LEV102 2.0% intervention 3: Vehicle
Intervention descriptions: intervention 1: Oxymetazoline ophthalmic gel intervention 2: Oxymetazoline ophthalmic gel intervention 3: Vehicle ophthalmic gel

Protocol documents:
Prot_000.pdf: 
Protocol 
 
Study title: A Phase 1/2a Study of LEV102 Topical Gel in Subjects with Acquired Blepharoptosis 
NCT Number:NCT05715346 
Document Date: 25 May 2023 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
T I T L E P A G E 
C li nic al T ri al P r ot oc ol  
L E V 1 0 2 -C S 0 1  
St u d y Title:   
A  P hase 1/ 2 a St u d y of L E V 1 0 2 T o pical Gel i n S u bjects wit h 
Ac q uire d Ble p har o pt osi s 
St u d y  N u m ber:   
L E V 1 0 2 -C S 0 1  
St u d y P h ase:   
1/ 2a  
Pr o d uct N a me:   
L E V 1 0 2  T o pical G el  
I N D N u m ber:   
1 5 6 8 6 6  
I n dic ati o n:  
Ac q uire d Ble p har o pt osis  
I n vesti g at ors  
M ultice nter  
 
 
S p o ns or:  
Le vati o n P har ma Lt d.  
 
 
S p o ns or C o nt act:  
 
 
 
 
 
 
 
Me dic al M o nit or : 
 
  
 
 
 
 
 
Date  
Ori gi n al  Pr ot oc ol , V 1. 0: 
0 9  A u g ust 2 0 2 2  
A me n d me nt 1, V 2. 0   
3 1  Oct o ber 2 0 2 2  
A me n d me nt 2, V 3. 0   
0 6  Dece m b er 2 0 2 2  
A me n d me nt 3, V 4. 0   
1 7 Ja n uar y  2 0 2 3  
A me n d me nt 4, V 5. 0   
0 6  A pril 2 0 2 3  
A me n d me nt 5, V 6. 0   
2 5  Ma y 2 0 2 3  
 
C o nfi de nti alit y St ate m e nt  
T his d oc u me nt c o ntai ns i nf or mati o n fr o m Le vati o n P har ma Lt d . an d is of c o nfi de ntial, tra de secret, a n d/ or 
pr o prietar y nat ure a n d ma y n ot be discl ose d u nless s uc h discl os ure is re q uire d b y fe deral or state la w or re g ulati o n. 
It is l oa ne d t o y o u f or y o ur c o nfi de ntial re vie w o n be half of Le vati o n P har ma Lt d . onl y a n d is n ot t o be 
p h ot oc o pie d, discl ose d, or tra ns mitte d t o a n y ot her pers o n or part y wit h o ut t he a d va nce writte n a p pr o val of 
Le vati o n P har ma Lt d .  






Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
St u d y P o p ul ati o n:  
T his st u d y is e x pecte d t o e nr oll a p pr o xi matel y 3 0 a d ult s u bjects wit h ac q uire d ble p har o pt osi s. 
Di a g n osis a n d M ai n Criteri a f or I ncl usi o n : 
T he st u d y p o p ulati o n will c o nsist of a d ult s u bjects w h o ha ve ac q uire d ble p har o pt osis. If b ot h e yes q ualif y f or 
t he st u d y, t he e ye wit h t he l o wer M R D 1 val ue at Baseli ne will be desi g nate d as t he st u d y e ye. If M R D 1 val ues 
are t he sa me f or b ot h e yes at Baseli n e, t he ri g ht e ye will be desi g nate d as t he st u d y e ye. Re gar dless of st u d y 
e ye or st u d y q ualificati o n, all e yes i n t his st u d y will recei ve st u d y I P a n d u n der g o st u d y assess me nts.  
 
I ncl usi o n Criteri a:  
S u bjects w h o meet all t he f oll o wi n g i ncl usi o n criteria will be eli gi ble t o partici pate i n t he st u d y. S u bjects m ust:  
1.  B e male or fe male s u bjects 2 5 years of a ge or ol der at t he ti me of Scree ni n g ( Visit 1)  
2.  Ha ve c o m plai nts of aest heticall y u nacce pta ble u p per e yeli d p ositi o n f or b ot h e yes ma ki n g t he m 
desir o us f or ele v ati o n, or ha ve c o m plai nts of s u peri or vis ual fiel d defects i n b ot h e yes t hat i m pact 
acti vities of dail y li vi n g  
3.  P rese nt wit h t he f oll o wi n g at Scree ni n g ( Visit 1):  
a. 
At  least o ne e ye t hat meets b ot h of t he f oll o wi n g criteria: 
i. 
M R D 1 ≤2 . 3 m m ( n o visi ble ce ntral p u pillar y li g ht refle x defa ults t o 0)  
ii. C urre nt c orrecte d  V A , u si n g s u bject’s o w n prescri pti o n e ye glasses, if a p plica ble , i n t he 
q ualif yi n g e ye(s) of + 0. 3  L o g M A R ( L o garit h m of t he Mi ni m u m A n gle of Res ol uti o n) 
or better as assesse d b y E T D R S  
b.  D em o nstrate u p per e yeli d ele vati o n ≥0. 5 m m c ha n ge fr o m baseli ne i n M R D 1 i n b ot h e yes i n 
res p o nse t o a si n gle dr o p of U p nee q ® ( o x y metaz oli ne 0. 1 % o p ht hal mic s ol uti o n) t o eac h e ye 
at Scree ni n g  
N ote: U p nee q ® is preferre d b ut p he n yle p hri ne 2. 5 % o p ht hal mic s ol uti o n ma y be use d 
if U p nee q ® is n ot a vaila ble i n a ti mel y ma n ner.  
4.  I n t he j u d g me nt of t he I n vesti gat or, ha ve n or mal le vat or pal pe brae s u peri oris m uscle f u ncti o n of b ot h 
u p per e yeli d s 
5.  W O C B P m ust a gree t o use a n a p pr o ve d met h o d of birt h c o ntr ol fr o m t he date t he y si g n t he i nf or me d 
c o nse nt f or m ( I C F) u ntil after t he last st u d y visit ( F oll o w -U p Visit)  
6.  Be a ble t o gi ve i nf or me d c o nse nt a n d willi n g t o c o m pl y wit h all st u d y visits a n d e xa mi nati o ns  
 
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 e xcl usi o n criteria at Scree ni n g ( Visit 1) or Baseli ne ( Visit 2) will n ot 
be eli gi ble t o partici pate i n t he st u d y. S u bjects m ust n ot:  
Oc ul ar C o n diti o ns:  
1.  Ha v e a n y ot her oc ular pat h ol o g y ot her t ha n pt osis re q uiri n g treat me nt wit h t o pical prescri pti o n 
o p ht hal mic dr o ps i n eit her e ye (e. g., gla uc o ma)  
N ote: S u bjects  w h o use o ver -t he-c o u nter (O T C ) or prescri pti o n  t o pical o p ht hal mic dr o ps  t o treat 
dr y e ye disease ma y be all o we d wit h S p o ns or a p pr o val.  
2.  H ave narr o w a n gles, gla uc o ma, I O P > 2 3 m m H g or dia g n osis of oc ular h y perte nsi o n, c u p -t o-disc rati o 
of > 0. 7 , or hist or y of a n y gla uc o ma e ye s ur ger y i n eit her e ye 
3.  Ha ve a n y acti ve oc ular or peri -oc ular i nfecti o n; a n y hist or y of rec urre nt or c hr o nic i nfecti o n or 
i nfla m mati o n i n eit her e ye 
4.  Ha ve a hist or y of her petic i nfecti o n i n eit her e ye  
5.  Ha ve a hist or y of c or neal disease ot her t ha n mil d t o m o derate dr y e ye or s ur ger y i n eit her e ye  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
N ote: S u bjects wit h oc ular refracti ve s ur ger y ( e. g., laser-assiste d i n sit u kerat o mile usis, 
p h ot orefracti ve keratect o m y, s mall i ncisi o n le ntic ule e xtracti o n) ≥9 0 da ys pri or t o Scree ni n g 
( Visit 1) are all o we d. 
6.  Pr ese nt wit h a n y p u pillar y a b n or malit y i n eit her e ye  
7.  Pr ese nt wit h a n y ma nifest stra bis m us i n eit her e ye  
8.  Pr ese nt, i n t he o pi ni o n of t he I n vesti gat or, wit h cli nicall y si g nifica nt br o w pt osis i n eit her e ye  
9.  Ha ve as y m metr y ≥3 . 0 m m i n M R D 1 bet wee n e yes or i nter pal pe bral dista nce bet wee n b ot h e yes 
1 0.  Ha ve a n y a nat o mic a b n or malit y of eit her u p per or l o wer e yeli ds i n eit her e ye  t hat o bsc ures eit her 
u p per or l o wer e yeli d mar gi n  
1 1.  Ha ve a n y  hist or y of pt osis s ur ger y i n eit her e y e 
1 2.  Ha ve a hist or y of a n y u p per or l o wer e yeli d s ur ger y, i ncl u di n g ble p har o plast y , s ki n lesi o n, or ot her 
iss ue wit hi n 3 m o nt h of Scree ni n g ( Visit 1)  i n eit her e ye 
1 3.  Ha ve a hist or y of c hr o nic pr o gressi ve e xter nal o p ht hal m o ple gia, H or ner’s s y n dr o me, m yast he nia 
gra vis, Marc us G u n n ja w wi n ki n g, c o n ge nital pt osis, Kear ns -Sa yre S y n dr o me, der mat oc halasis , 
u nc o ntr olle d ble p har os pas m, Ra msa y H u nt s y n dr o me, or mec ha nical pt osis i n eit her e ye  
N ote:  Der mat oc halasis  (e xcess e yeli d s ki n) sh o ul d n ot be c o nsi dere d e xcl usi o nar y if , i n t he 
o pi ni o n of t he I n vesti gat or, it d oes n ot o bsc ure e yeli d mar gi ns or i nterfere wit h q ualit y i ma ge 
ca pt ur e. 
1 4.  Ha ve mec ha nical pt osis, i ncl u di n g pt osis d ue t o or bital or e yeli d t u m or, cicatricial pr ocesses affecti n g 
t he m o ve me nts of t he u p per e yeli d, a n d e n o p ht hal m os i n eit her e ye 
1 5.  Ha ve e yeli d p ositi o n affecte d b y e yeli d or c o nj u ncti val scarri n g i n eit her e ye  
1 6.  Ha ve a vis ual fiel d l oss fr o m a n y ca use ot her t ha n pt osis i n eit her e ye  
1 7.  Ha ve a hist or y of o ptic ne ur o pat h y i n eit her e ye  
1 8.  Ha ve use d t o pical a p plicati o n of bi mat o pr ost (i.e., Latisse) t o t he e yelas hes wit hi n 7 da ys pri or t o 
Scree ni n g ( Visit 1) a n d d uri n g t he st u d y i n eit her e ye  
1 9.  Ha ve use d t o pical a p plicati o n of pil ocar pi ne (i.e., V uit y) wit hi n 7 da ys pri or t o Scree ni n g ( Visit 1) 
a n d d uri n g t he st u d y i n eit her e ye  
2 0.  Ha ve c o nc urre nt disease i n eit her e ye or t hat c o ul d re q uire me dical or s ur gical i nter ve nti o n d uri n g t he 
st u d y peri od  
2 1.  Be  u n willi n g t o disc o nti n ue t he use of u p per e yeli d/e yelas h ma ke u p a n d  O T C c os metic pr o d ucts 
d uri n g t he S cree ni n g visit a n d o n t he da y of t he st u d y treat me nt a n d assess me nts ( Da y 1), i ncl u di n g 
b ut n ot li mite d t o:  
a. 
E y es ha d o w pri mer  
b.  E y es ha d o w 
c. 
E y eli d m oist urizer  
d.  E y eli ner 
e. 
Fa ke e yelas hes ( gl ue d or ma g netic)  
f. 
S k i n care pr o d ucts a p plie d t o t he e yeli d 
N ote: E n ha nce me nts t hat ca n n ot easil y be re m o ve d s h o ul d n ot be c o nsi dere d e xcl usi o nar y if , i n 
t he o pi ni o n of t he I n vesti gat or, t he y d o n ot o bsc ure e yeli d mar gi ns or i nterfere wit h q ualit y i ma ge 
ca pt ur e. 
N ote : S u bjects weari n g ma ke u p d uri n g t he S cree ni n g visit s h o ul d re m o ve t he ma ke u p o n -site 
bef ore i ma ge ca pt ure.  
2 2.  H ave use d o x y metaz oli ne t o pical e ye dr o ps ( U p nee q ®) f or treat me nt of ble p har o pt osis or as a n oc ular 
dec o n gesta nt ( Visi ne L R) wit hi n 7  da ys pri or t o Scree ni n g ( Visit 1) or pla n ne d use d uri n g t he st u d y 
peri o d i n eit her e ye  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
N ote: E ye dr o ps a p plie d d uri n g Scree ni n g ( Visit 1) t o deter mi ne st u d y eli gi bilit y are e xe m pt fr o m 
t his e xcl usi o n. 
2 3.  Ha ve ha d i ntra vitreal i njecti o ns (e. g., L uce ntis, E ylea, A vasti n, Triese nce) wit hi n 7 da ys pri or t o 
Scree ni n g ( Visit 1) or ha ve pla ns f or a n i njecti o n d uri n g t he st u d y i n eit her e ye  
2 4.  Ha ve a hist or y of t h yr oi d e ye disease (i.e., e x o p ht hal m os, u p per e yeli d retracti o n, di pl o pia sec o n dar y 
t o e xtra oc ular m uscle i n v ol ve me nt) i n eit her e ye. H y pert h yr oi dis m t hat is c o ntr olle d o n me dicati o n is 
all o we d  
S yste mic C o n diti o ns:  
2 5.  Ha ve a resti n g heart rate o utsi de n or mal ra n ge of 5 0 -1 1 0 beats per mi n ute w hile sitti n g d uri n g t he 
Scree ni n g visit ( Visit 1)  
2 6.  Ha ve, i n t he o pi ni o n of t he I n vesti gat or, u nc o ntr olle d h y perte nsi o n, u nc o ntr olle d atrial fi brillati o n, or 
hist or y of cli nical car di o vasc ular disease i ncl u di n g str o ke, m y ocar dial i nfarcti o n, or heart fail ure  
2 7.  Ha ve pla ns t o use a n o n -o p ht hal mic α -a dre ner gic a g o nist, i ncl u di n g O T C pr o d ucts (e. g., Afri n), at 
a n y ti me d uri n g t he st u d y  
2 8.  Ha ve use d m o n oa mi ne o xi dase i n hi bit ors ( M A OIs; e. g., is ocar b o xazi d, p he nelzi ne, tra n ylc y pr o mi ne) 
wit hi n 1 4 da ys pri or t o Scree ni n g ( Visit 1) or a ntici pate usi n g M A OIs d uri n g t he st u d y  
2 9.  S u bjects wit h dia betic reti n o pat h y ma y n ot be e nr olle d i n t his st u d y. H o we ver, s u bjects wit h i ns uli n -
de pe n de nt dia betes, dia betes re q uiri n g oral h y p o gl yce mic dr u gs, or diet -c o ntr olle d dia betes are 
all o we d  
3 0.  Ha ve bee n dia g n ose d wit h be ni g n pr ostatic h y pertr o p h y re q uiri n g me dici nal t hera p y; pre vi o us 
pr ostatect o m y is all o we d  
Ge ner al:  
3 1.  Ha ve partici pate d i n ot her i n vesti gati o nal dr u g or de vice cli nical trials wit hi n 3 0 da ys pri or t o 
Scree ni n g ( Visit 1), or be pla n ni n g t o partici pate i n a n y ot her i n vesti gati o nal dr u g or de vice cli nical 
trials wit hi n 3 0 da ys of st u d y c o m pleti o n  
3 2.  Ha ve a hist or y of aller gic reacti o n t o t he i n vesti gati o nal dr u g or a n y of its c o m p o ne nts  
3 3.  Wi t hi n 7 da ys of Scree ni n g ( Visit 1), or a ntici pate d use d uri n g t he st u d y, use of a n y s yste mic, 
i ntra nasal, t o pical der mat ol o gic, or o p ht hal mic α-a dre ner gic a g o nist  (i ncl u di n g bri m o ni di ne) or 
a nta g o nist i ncl u di n g nasal or oc ular or oral dec o n gesta nts i ncl u di n g pse u d oe p he dri ne, o x y metaz oli ne 
t o pical o p ht hal mic s ol uti o n, o x y metaz oli ne t o pical der mat ol o gic crea m 
3 4.  S u bjects w h o are pre g na nt or breast -fee di n g 
3 5.  Ha ve use d U p nee q ® wit hi n 7 da ys of eit her Scree ni n g  ( Visit 1) or Baseli ne  ( Visit 2) 
I n vesti g ati o n al Pr o d uct(s); D ose; a n d M o de of A d mi nist r ati o n:  
•   L E V 1 0 2 T o pical Gel, 2. 0 % ( 1 0 0 µ L)  
•   L E V 1 0 2 T o pical Gel, 1. 0 % ( 1 0 0 µ L)  
Refere nce T her a p y; D ose; a n d M o de of A d mi nistr ati o n:  
•   Ve hicle T o pical Gel ( 1 0 0 µ L)  
D ur ati o n of Tre at m e nt:  
T he d urati o n of t he treat me nt peri o d i n t his st u d y is 1 da y wit h assess me nts t o be c o m plete d at Baseli ne ( bef ore 
I P a d mi nistrati o n), H o ur 0 (after I P a d mi nistrati o n), H o ur 0. 5, H o ur 1, H o ur 2, H o ur 4, H o ur 6, a n d H o ur 8.  
D ur ati o n of St u d y  P artici p ati o n:  
T here are 2  cli nic visits a n d 1  tele p h o ne f oll o w-u p o ver u p t o  5 0 da ys, ( u p to 4 5 da ys f or Scree ni n g  a n d 2 -5 
da ys after t he da y of st u d y treat me nt ). 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 7  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
St atistic al Met h o ds:  
In ge neral, a nal yses i n t his st u d y will e xa mi ne t he differe nces bet wee n i n di vi d ual treat me nt ar ms, as well as 
t he differe nces bet wee n c o m bi ne d ar ms of L E V 1 0 2 T o pical Gel c o m pare d t o ve hicle. C o nti n u o us meas ures 
will be s u m marize d descri pti vel y b y t he mea n, sta n dar d de viati o n ( S D), me dia n, mi ni m u m, a n d ma xi m u m 
val ues. Cate g orical meas ures will be s u m marize d b y t he fre q ue nc y a n d perce nta ge of s u bjects.  
 
F or all e x pl orat or y efficac y a nal yses a n d all safet y a nal yses perf or me d, Baseli ne will be defi ne d as t he 
meas ure me nt o n Da y 1 bef ore I P a d mi nistrati o n a n d n ot fr o m a n y pre vi o us visit. If b ot h e yes q ualif y f or t he 
st u d y, t he e ye wit h t he l o wer M R D 1 val ue at Baseli ne will be desi g nate d as t he st u d y e ye. If M R D 1 val ues are 
t he sa me f or O U at Baseli ne, t he ri g ht e ye will be desi g nate d as t he st u d y e ye. Re gar dless of st u d y e ye or st u d y 
q ualificati o n, all e yes i n t his st u d y will recei ve st u d y I P a n d u n der g o st u d y  assess me nts.  
 
T he sa m ple size of 1 0 s u bjects per ar m ( 3 0 s u bjects t otal f or a t otal of 6 0 e yes) is n ot base d o n f or mal p o wer 
or precisi o n c o nsi derati o ns.  S u bjects will be a nal yze d i n t he gr o u p acc or di n g t o t he I P treat me nt recei ve d. All 
e n d p oi nts will be a nal yze d usi n g t he Safet y A nal ysis Set a n d o nl y o bser ve d data will be i ncl u de d.  
 
S afet y a nal yses will be perf or me d o n all s u bjects i n t he Safet y A nal ysis Set. T he assess m e nt of safet y will be 
base d o n t he s u m mar y of oc ular a n d n o n -oc ular A Es, curre nt c orrecte d V A , I O P, slit la m p bi o micr osc o p y, 
oc ular h y pere mia , ma n ual  p u pill o metr y, i n direct dilate d o p ht hal m osc o p y, vital si g ns, a n d uri ne pre g na nc y test . 
S u m maries will be pr o vi de d b y treat me nt gr o u p, a n d f or oc ular assess me nts se paratel y b y e ye.  
 
S u m mar y statistics f or o bser ve d data a n d c ha n ges fr o m baseli ne ( w here a p pr o priate) f or c urre nt c orrecte d  V A , 
I O P, ma n ual  p u pill o metr y, vital si g ns, a n d t he c o mf ort q uesti o n naire will be prese nte d. A b n or malities i n slit 
la m p bi o micr osc o p y will be s u m marize d b y fre q ue nc y a n d perce nta ge. 
 
S u m mar y statistics f or o bser ve d data , a n d c ha n ges fr o m baseli ne ( w here a p pr o priate) f or M R D 1, L P F T, oc ular 
h y pere mia , a n d s u bject- a n d I nvesti gat or -re p orte d o utc o me q uesti o n naires at p ost-d ose Visit 2, as well as 
c ha n ge fr o m H o ur 2 at H o ur 6 f or L P F T will be prese nte d. S u bjects ac hie vi n g a n i m pr o ve me nt i n M R D 1 fr o m 
baseli ne of 1. 0, 1. 5, 2. 0, a n d 2. 5 m m will be s u m marize d b y ti me p oi nt. S u m mar y statistics f or o bser ve d data 
a n d c ha n ges fr o m baseli ne i n F A C E -Q | Aest hetics q uesti o n naires, as well as t he r es p o nse rates t o i n di vi d ual 
q uesti o ns, will be prese nte d.  
 
A Es will be c o de d usi n g t he Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A)  ( m ost c urre nt versi o n) 
a n d cate g orize d b y s yste m or ga n class ( S O C) usi n g preferre d ter ms ( P T). Se parate s u m maries of A Es  relate d 
t o treat me nt a n d b y se verit y will be prese nte d. T he n u m ber of deat hs a n d seri o us a d verse e ve nts (S A E ) will 
als o be prese nte d, a n d e ve nts lea di n g t o disc o nti n uati o n fr o m t he st u d y will be liste d a n d ta b ulate d.  
 
All data c ollecte d i n t his st u d y will be prese nte d i n data listi n gs f or all s u bjects . 
D ate of Ori gi n al Pr ot oc ol:  0 9  A u g ust 2 0 2 2  
D ate of Pre vi o us  Pr ot oc ol A m e n d m e nt: 0 6 A pril 2 0 2 3  
D ate of M ost Rece nt Pr ot oc ol A m e n d me nt: 2 5  Ma y 2 0 2 3  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 8  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
T A B L E O F C O N T E N T S  
TI T L E P A G E  .............................................................................................................................1  
S Y N O P SI S  .................................................................................................................................2  
T A B L E O F C O N T E N T S  ...........................................................................................................8  
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 2  
1  
I N T R O D U C TI O N .................................................................................................1 4  
1. 1  
Bac k gr o u n d  ......................................................................................................1 4  
1. 2  
St u d y Rati o nale  ................................................................................................1 5  
1. 3  
Ris k/ Be nefit Assess me nt  .................................................................................1 5  
1. 3. 1  
K n o w n P ote ntial Ris ks  .........................................................................1 5  
1. 3. 2  
K n o w n P ote ntial Be nefits  ....................................................................1 6  
1. 3. 3  
Assess me nt of Be nefits a n d Ris ks  .......................................................1 6  
2  
S T U D Y O BJ E C TI V E S  ..........................................................................................1 7  
3  
I N V E S TI G A TI O N A L P L A N ................................................................................1 9  
3. 1  
O verall St u d y Desi g n a n d Pla n  ........................................................................1 9  
3. 2  
Rati o nale f or St u d y Desi g n a n d C o ntr ol Gr o u p  ...............................................2 1  
3. 3  
E n d of St u d y Defi niti o n  ...................................................................................2 2  
4  
S T U D Y P O P U L A TI O N S E L E C TI O N  .................................................................2 3  
4. 1  
St u d y P o p ulati o n  ..............................................................................................2 3  
4. 2  
I n cl usi o n Criteria .............................................................................................2 3  
4. 3  
E xcl usi o n Criteria  ............................................................................................2 4  
4. 4  
Scree n/ Baseli ne Fail ures  ..................................................................................2 7  
5  
S T U D Y T R E A T M E N T( S)  ....................................................................................2 8  
5. 1  
Descri pti o n of I n v esti gati o nal Pr o d uct(s)  ........................................................2 8  
5. 1. 1  
D osa ge a n d A d mi nistrati o n ..................................................................2 8  
5. 2  
Pre parati o n/ St ora ge/ H a n dli n g/ Acc o u nta bilit y  .................................................2 8  
5. 2. 1  
Ac q uisiti o n a n d Acc o u nt a bilit y  ...........................................................2 8  
5. 2. 2  
Pr o d uct F or m ulati o n, A p peara n ce, Pac ka gi n g a n d La beli n g  ...............2 9  
5. 2. 3  
Pr o d uct St ora ge a n d Sta bilit y ...............................................................2 9  
5. 3  
Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Mas ki n g  .............................2 9  
5. 4  
C o nc o mita nt T hera p y .......................................................................................3 0  
6  
S T U D Y P R O C E D U R E S  .......................................................................................3 2  
6. 1  
Dis pe nsi n g St u d y Dr u g  ....................................................................................3 2  
6. 2  
A d verse E v e nts Assess me nts  ...........................................................................3 2  
6. 2. 1  
Defi niti o ns ............................................................................................3 2  
6. 2. 2  
Ti mi n g  ..................................................................................................3 3  
6. 2. 3  
Se verit y  ................................................................................................3 3  
6. 2. 4  
Relati o ns hi p  .........................................................................................3 3  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 9  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
6. 2. 5  
E x pecte d ness  ........................................................................................3 4  
6. 2. 6  
A d verse E v e nt Re p orti n g Re q uire me nts  ..............................................3 4  
6. 2. 7  
Cli nical La b orat or y A d v erse E ve nts  ....................................................3 5  
6. 2. 8  
Treat me nt -E mer ge nt A d verse E ve nts  ..................................................3 5  
6. 3  
Re m o val of S u bjects fr o m t he St u d y or St u d y Dr u g  .......................................3 5  
6. 4  
L ost t o F oll o w -U p  ............................................................................................3 5  
6. 5  
A p pr o priate ness of Meas ure me nts  ...................................................................3 6  
6. 5. 1  
Safet y Assess me nts  ..............................................................................3 6  
6. 5. 2  
Efficac y Assess me nts ...........................................................................3 6  
6. 5. 3  
Ot her Assess me nts  ...............................................................................3 7  
7  
S T U D Y A C TI VI TI E S  ...........................................................................................3 8  
7. 1  
Scree ni n g Visit ( Visit 1; Da y -4 5 t o Da y -7)  ...................................................3 8  
7. 2  
Baseli ne/ Ra n d o mizati o n ( Visit 2; Treat me nt Peri o d; Da y 1)  ..........................3 9  
7. 2. 1  
Baseli ne Assess me nts ( B ef ore I P A d mi nistrati o n)  ..............................3 9  
7. 2. 2  
I P A d mi nistrati o n a n d H o ur 0 Pr oce d ures ( After I P 
A d mi nistrati o n)  ....................................................................................4 0  
7. 2. 3  
H o ur 0. 5 Pr oce d ures  ( ± 1 0 mi n utes) .....................................................4 0  
7. 2. 4  
H o ur 1 Pr oce d ures ( ± 1 5 mi n utes)  ........................................................4 0  
7. 2. 5  
H o ur 2 Pr oce d ures ( ± 1 5 mi n utes)  ........................................................4 0  
7. 2. 6  
H o ur 4 Pr oce d ures ( ± 1 5 mi n utes)  ........................................................4 1  
7. 2. 7  
H o ur 6 Pr oce d ures ( ± 1 5 mi n utes)  ........................................................4 1  
7. 2. 8  
H o ur 8 Pr oce d ures ( ± 6 0 mi n utes)  ........................................................4 1  
7. 3  
Treat me nt F oll o w -U p P h o ne Call [ Visit 3; Da y 2 t o Da y 5]  ...........................4 2  
7. 4  
St u d y Wit h dra wal/ Earl y Ter mi nati o n Pr oce d ures  ...........................................4 2  
8  
Q U A LI T Y C O N T R O L A N D A S S U R A N C E  .......................................................4 3  
9  
P L A N N E D S T A TI S TI C A L M E T H O D S  ..............................................................4 4  
9. 1  
Ge neral C o nsi derati o ns  ....................................................................................4 4  
9. 2  
Deter mi nati o n of Sa m ple Size  .........................................................................4 4  
9. 3  
A nal ysis P o p ulati o ns  ........................................................................................4 4  
9. 4  
De m o gra p hics a n d Baseli ne C haract eristics  ....................................................4 4  
9. 5  
Safet y A nal ysis  ................................................................................................4 5  
9. 5. 1  
A d verse E v e nts  ....................................................................................4 5  
9. 5. 2  
Ot her Safet y E n d p oi nts  ........................................................................4 5  
9. 5. 3  
Pre g na nc y  .............................................................................................4 5  
9. 6  
E x pl orat or y Effi cac y Assess me nts  ..................................................................4 6  
9. 7  
Ta b ulati o n of I n di vi d ual S u bject Data  .............................................................4 6  
1 0  
A D MI NI S T R A TI V E C O N SI D E R A TI O N S  ..........................................................4 7  
1 0. 1  
St u d y A d mi nistrati ve Str uct ure ........................................................................4 7  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 0  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 0. 2  
I nstit uti o nal Re vie w B oar d (I R B) A p pr o val ....................................................4 7  
1 0. 3  
Et hical C o n d uct of t he St u d y  ...........................................................................4 8  
1 0. 4  
S u bject I nf or mati o n a n d C o nse nt .....................................................................4 8  
1 0. 5  
S u bject C o nfi de ntialit y  ....................................................................................4 8  
1 0. 6  
St u d y M o nit ori n g  .............................................................................................4 9  
1 0. 7  
Case Re p ort F or ms a n d St u d y Rec or ds  ...........................................................4 9  
1 0. 8  
St u d y Rec or ds Rete nti o n ..................................................................................5 0  
1 0. 9  
Pr ot oc ol De viati o ns  ..........................................................................................5 0  
1 0. 1 0  
Access t o S o urce D oc u m e ntati o n  ....................................................................5 0  
1 0. 1 1  
P u blicati o n P olic y  ............................................................................................5 0  
1 1  
R E F E R E N C E LI S T  ...............................................................................................5 2  
1 2  
A P P E N DI C E S  .......................................................................................................5 3  
1 2. 1  
A p pe n di x 1: Sc he d ule of Visits a n d Pr oce d ures  ..............................................5 3  
1 2. 2  
A p pe n di x 2: C urre nt C orrecte d Vis u al Ac uit y  ................................................5 5  
1 2. 3  
A p pe n di x 3: Pt osis E val uati o n  .........................................................................5 6  
1 2. 4  
A p pe n di x 4: I ntra oc ul ar Press ure (I O P)  ..........................................................5 7  
1 2. 5  
A p pe n di x 5: Leicester Peri p heral Fiel d Test ( L P F T)  ......................................5 8  
1 2. 6  
A p pe n di x 6: F A C E -Q | Aest hetics Q uesti o n naires  ..........................................5 9  
1 2. 7  
A p pe n di x 7:   
 E xter nal P h ot o gra p h y  ...................................................6 0  
1 2. 8  
A p pe n di x 8: I n vesti gat or -Re p orte d O utc o mes  ................................................6 1  
1 2. 9  
A p pe n di x 9: Ma n ual P u pill o metr y ...................................................................6 2  
1 2. 1 0  
A p pe n di x 1 0: Le vat or Pal pe brae S u peri oris F u ncti o n  .....................................6 3  
1 2. 1 1  
A p pe n di x 1 1: Slit La m p Bi o micr osc o p y  .........................................................6 4  
1 2. 1 2  
A p pe n di x 1 2: B ul bar C o nj u ncti val H y pere mia [ Brie n H ol de n Visi o n 
I nstit ute ( B H VI) Gra di n g Scale ( F or merl y K n o w n as t he C C L R U)] ..............6 6  
1 2. 1 3  
A p pe n di x 1 3: I n direct Dilate d O p ht hal m osc o p y  .............................................6 7  
1 2. 1 4  
A p pe n di x 1 4: I n vesti gati o nal Pr o d uct C o mf ort/ T olera bilit y Assess me nt  .......6 9  
1 2. 1 5  
A p pe n di x 1 5: Vital Si g ns  .................................................................................7 0  
1 2. 1 6  
A p pe n di x 1 6: W o me n of C hil d -beari n g P ote ntial ( W O C B P)  .........................7 1  
1 2. 1 7  
A p pe n di x 1 7: C o m plia nce State me nt a n d S p o ns or A p pr o val  .........................7 2  
1 2. 1 8  
A p pe n di x 1 8: I n vesti gat or’s Si g nat ure  ............................................................7 3  
 
 
 
 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 1  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
T a ble of T a bles  
Ta ble 1  
Me dicati o ns a n d Pr oce d ures N ot Per mitte d  ...............................................3 0  
 
 
T a ble of Fi g ures  
Fi g ure 1  
Cli nical St u d y Dia gra m ..............................................................................2 1  
Fi g ure 2  
M R D 1 Pt osis E val uati o n ............................................................................5 6  
 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 2  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
L I S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S 
A E  
A d verse e ve nt  
B H VI   
Brie n H ol de n Visi o n I nstit ute  
C C L R U   
C or nea a n d C o ntact L e ns Researc h U nit  
C F R  
C o de of Fe d eral Re g ulati o ns  
C O N S O R T   
C o ns oli date d Sta n dar ds of Re p orti n g Trials  
C R F  
Case re p ort f or m 
e C R F  
E lectr o nic case re p ort f or m  
E D C  
Electr o nic Data Ca pt ure  
E T D R S   
Earl y Treat me nt Dia betic Reti n o pat h y St u d y  
F D A  
U nite d States 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  
G L P  
G o o d La b orat or y Practice  
G M P  
G o o d Ma n ufact uri n g Practice  
HI P A A   
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y A ct  
I B  
I n v esti gat or’s Br oc h ure 
I C F 
Inf or me d c o ns e nt f or m  
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n 
I O P 
Intr a oc ular press ure  
I P 
In v esti gati o nal pr o d uct  
I R B 
I nstit uti o nal Re vie w B oar d 
L o g M A R   
L o garit h m of t he Mi ni m u m A n gle of Res ol uti o n  
L P F T   
Leicester Peri p heral Fiel d Test  
M A OI   
M o n oa mi ne o xi dase i n hi bit or  
Me d D R A   
Me dical Dicti o nar y f or R e g ulat or y Acti vities  
M R D 1   
M ar gi n refl e x dista nce 1 
O T C  
O ver -t he-c o u nter  
O U  
O c ul us uter q ue ( b ot h e y es) 
P K  
P har mac o ki netics  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 3  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
P T  
P referre d ter m 
Q C  
Q ualit y c o ntr ol 
S A E  
S eri o us a d verse e ve nt  
S A P  
Statistical A nal ysis Pla n  
S D  
S ta n dar d de viati o n  
S O C  
S yste m or ga n class  
U. S. A.   
U nite d States of A merica  
V A  
V is ual ac uit y  
V A S  
Vis ual A nal o g Scale  
W H O   
W orl d Healt h Or ga nizati o n  
W H O Dr u g   
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
W M A   
W orl d Me dical Ass o ciati o n  
W O C B P   
W o m en of c hil d -b eari n g p ote ntial  
 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 4  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1  
I N T R O D U C TI O N 
1. 1   
B ac k gr o u n d  
B le p har o pt osis, or pt osis, is  a relati vel y c o m m o n, a b n or mal dr o o pi n g of t he u p per e y eli d wit h 
t he e ye hel d i n pri mar y gaze. T his dr o o pi n g ca n affect o ne or b ot h e yes. Base d o n ti me of 
a p peara nce, ble p har o pt osis  is t y picall y classifie d as eit her c o n ge nital or ac q uire d . E sti mates of 
pt osis pre vale nce re p ort rates bet wee n 4. 7 %  a n d 1 3. 5 % i n a d ult p o p ulati o ns, a n d t he i nci de nce 
of pt osis i ncreases wit h a ge. D r o o pi n g of t he u p per e y eli d d ue t o pt osis ca n ne gati vel y i m pact 
patie nt well -bei n g, i ncl u di n g re d uce d i n de pe n d e nce res ulti n g fr o m su peri or vis ual fiel d 
o bstr ucti o n a n d i ncreas e d a p peara n ce -relate d a n xiet y a n d d e pressi o n res ulti n g fr o m pt osis’ 
c haracteristic ‘sl ee p y ’ a p peara n ce . F u ncti o nall y, o bstr ucti o n of t he p u pil as a res ult of pt osis 
ca n lea d t o deficits i n t he s u peri or vis ual fiel d, d etecta ble via vis ual fiel d testi n g a n d  prese nt 
e ve n i n mil d cases, wit h a n o vel static peri metr y test [t he Leicester Peri p heral Fi el d Test 
( L P F T)] detecti n g a vis ual fiel d deficit i n nearl y all pt otic e yes  (H o et al., 2 0 1 1 ). I n lar g e-scale 
st u dies of patie nts wit h u nilateral or bilateral pt osis, i m pr o ve me nt i n t h e s u peri or vis ual fiel d 
f oll o wi n g s ur ger y was ass ociate d wit h si g nifica nt i m pr o ve me nt wit h res pect t o acti vities 
i ncl u di n g perf or mi n g t heir occ u p ati o n, pla yi n g s p orts, a n d wal ki n g wit h o ut assista nce 
(Bac harac h et al., 2 0 2 1 ).  
T he acti ve i n gre die nt i n L E V 1 0 2 T o pical Gel  is o x y metaz oli ne. O x y metaz oli ne is a n α 1- a n d 
α 2 -a dre n oce pt or a g o nist . O x y metaz oli ne was first a p pr o ve d i n t he U nite d States of A merica 
( U. S. A.) i n 1 9 6 4 f or t h e treat me nt of n asal dec o n gesti o n ( Afri n ® Nas al S pra y , 1 9 6 4). 
S u bse q ue ntl y, n u mer o us a d diti o nal o x y metaz oli ne -base d dr u gs ha v e bee n a p pr o ve d b y t he 
U nite d States F o o d a n d Dr u g A d mi nistrati o n ( F D A) f or o p ht hal mic a n d nasal use, i ncl u di n g: 
Oc uclear ® O p ht hal mic S ol uti o n ( 1 9 8 6), Visi ne ® O p ht hal mic S ol uti o n ( 1 9 8 9), K o va n aze ® 
Nasal S pra y ( 2 0 1 6), R h ofa de ® T o pical Crea m ( 2 0 1 7), a n d U p nee q ® E ye dr o ps ( 2 0 2 0). 
O x y metaz oli ne  is als o liste d i n t he F D A’s o ver -t he-co u nter ( O T C) m o n o gra p h f or nasal use 
(F D A, 1 9 9 4 ). 
In a d diti o n t o o x y metaz oli ne’s vas oc o nstrict or effects , w hic h are t hera pe uti c f or t he treat me nt 
of nasal dec o n gesti o n a n d c o nj u ncti val h y pere mi a , o x y metaz oli ne has t hera pe utic effects i n 
t he treat me nt of ac q uir e d ble p har o pt osis i n a d ults. Pres u ma bl y, t his is d ue t o t he sti m ulati o n 
of α -a dre n er gic rece pt or s i n t he s u peri or tarsal m us cle (als o k n o w n as M üller’s m uscle)  ca usi n g 
m uscle c o ntracti o ns  t hat lift t he u p per e y eli d w hile retracti n g t he l o wer e yeli d t o a lesser d e gree 
(Sl o ni m et al., 2 0 2 0 ). 
T he efficac y a n d safet y of a n o x y metaz oli ne 0. 1 % o p ht hal mic s ol uti o n a p pr o ve d f or t he 
treat me nt of ac q uire d ble p har o pt osis i n a d ults ( U p nee qT M , R V L P har mace uticals, I n c., 
Bri d ge water, NJ, U. S. A.) h as b ee n re p orte d. E vi de nce fr o m t w o p hase 3 cli nical trials re veale d 
t hat o nce-dail y use of o x y metaz oli ne 0. 1 % f or 4 2 da ys si g nifica ntl y i m pr o ve d t he s u peri or 
vis ual fiel d a n d u p per e yeli d ele vati o n i n patie nts wit h ac q uire d pt osis a n d acc o m pa n yi n g 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 5  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
s u peri or vis ual fiel d deficit. 
Usi n g t he L P F T, t hese st u dies de m o nstrate d si g nifica nt 
i m pr o ve me nts i n t he s u peri or vis ual fiel d wit h ass ociate d i m pr o ve me nts i n mar gi n refle x 
dista nce 1 ( M R D 1 ) meas ure me nts . M R D 1 is a c o m m o nl y use d assess me nt i n patie nts wit h 
pt osis a n d is defi ne d as t he dista nce ( m m) bet w ee n t he u p per e yeli d mar gi n a n d t he c or neal 
refle x w he n t h e e y e is i n t he pri mar y p ositi o n. These st u dies s h o we d t h at o x y metaz oli ne 0. 1 % 
was ass ociat e d wit h relati vel y l o w a d verse e ve nt ( A E) rat es a n d n o tac h y p h yla xis ( Bac harac h 
et al., 2 0 2 1 ). 
1. 2   
St u d y R ati o n ale  
T he p ur p ose of t his st u d y is t o deter mi ne t he oc ular a n d s yste mic safet y a n d t olera bilit y of a 
si n gle a p plicati o n of L E V 1 0 2 T o pical G el o n t he u p per e yeli ds, as well as t o e val uate t he effect 
of a si n gle a p plicati o n of L E V 1 0 2 T o pical G el  o n t he u p per e y eli ds o n s u p eri or vis ual fiel ds 
a n d u p per e y eli d hei g ht as meas ure d b y M R D 1 . 
U p nee q ® is a t o pical o p ht hal mic f or m ulati o n of o x y metaz oli ne  ( o x y metaz oli ne, 0. 1 %) 
a p pr o ve d b y t he F D A f or t he treat me nt of ac q uire d ble p har o pt osis i n a d ults w h o re p ort bl urre d 
visi o n a n d/ or di mi nis he d s u peri or vis ual fiel ds  (U p nee q ® Pac k a ge I ns ert 2 0 2 1 ; Sl o ni m et al., 
2 0 2 0 ). T he mec ha nis m of acti o n of U p nee q ® is pres u ma bl y sti m ulati n g α -a dre ner gic rece pt ors 
i n the s u peri or tarsal m uscle ca usi n g it t o c o ntract a n d t here b y lift t he u p per e yeli d  w hile 
retracti n g t he l o wer e y eli d t o a less er d e gree (Sl o ni m et al., 2 0 2 0 ). As U p nee q ® a n d L E V 1 0 2 
T o pical G el s h are t he sa me acti ve i n gre die nt, U p nee q ® vali dat es t he mec ha nis m of acti o n i n 
L E V 1 0 2 T o pical G el.  
1. 3   
Ris k/ Be nefit Assess me nt  
1. 3. 1   
K n o w n P ote nti al Ris k s 
L E V 1 0 2 T o pical Ge l is a ne w dr u g a n d has n ot bee n a p pr o ve d b y t he F D A f or use i n a n y 
i n dicati o n. T he acti ve i n gre die nt, o x y metaz oli ne, has b ee n us e d f or o p ht hal mic a n d nas al 
i n dicati o ns si nce t he 1 9 6 0s, an d, i n t hat ti me, p har mac ol o g y, p h ar mac o ki netics  ( P K), a n d 
t o xic ol o g y st u dies ha ve bee n c o n d u cte d o n s yste mic, der mal, a n d oc ular o x y metaz oli ne. 
U p nee q ® ( o x y met az oli ne, 0. 1 %) E ye dr o ps utilizes t he sa me acti ve i n gre die nt as L E V 1 0 2 
T o pical Gel  i n a l o wer c o nce ntr ati o n a n d wit h a differe nt met h o d of a d mi nistrati o n.  B ot h 
U p nee q ® a n d L E V 1 0 2 T o pical Gel are i nte n d e d t o treat ac q uire d ble p har o pt osis  i n a d ults. 
U p nee q ® is i nte n de d f or direct  i nstillati o n t o t he e ye, w hereas L E V 1 0 2 T o pical Gel  is i nte n d e d 
f or e xter nal t o pical a p plicati o n t o t he e xter nal u p per e yeli d. T he m ost c o m m o n  A Es  re p orte d 
f or U p nee q ® (i n ci de nce 1-5 %) ar e pu nctate keratitis , co nj u ncti v al h y pere mia , dr y e y e disease, 
bl urr y visi o n , pai n at t he i nstillati o n site, e ye irritati o n, a n d hea dac he.  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 6  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
R h ofa de ® ( o x y metaz oli ne, 1. 0 %) T o pical Crea m a n d L E V 1 0 2 T o pical Gel  b ot h use t he sa me 
acti ve i n gre di e nt a n d are b ot h i nte n de d f or t o pical der mal a p plicati o n  t o t he face. T h e m ost 
c o m m o n A Es  (i nci de nce > 1 %) f or R h ofa de ® are ap plicati o n site der matitis , worse ni n g 
i nfla m mat or y lesi o ns of r osacea, pr uritis  at t he a p plicati o n site, er yt he ma  at t he a p plicati o n 
site, a n d pai n  at t he a p pli cati o n site . 
F or a d diti o nal i nf or mati o n a b o ut t he p ote ntial ris ks ass ociate d wit h L E V 1 0 2 T o pical Gel , 
p lease see t he I n vesti gat or’s Br oc h ure (I B). 
1. 3. 2   
K n o w n P ote nti al Be nefits  
T his is a first-i n-h u ma n cli nical trial of L E V 1 0 2 T o pical Gel  a n d, th eref ore , t here are n o k n o w n 
healt h  be nefits . Base d o n t he k n o w n effects of U p nee q ®, w hic h has t he sa me acti ve i n gre die nt, 
it is h y p ot hesize d t hat su bjects wit h ac q uire d bl e p har o pt osis ma y e x perie nce a n i ncreas e i n 
M R D 1 val ues w hile usi n g L E V 1 0 2 T o pical Gel , wit h res ulti n g im pr o ve me nt i n t he s u peri or 
vis ual fiel d, i ncreas e d i n de pe n de nt f u ncti o ni n g, a n d hi g her q ualit y of life a n d ps yc h os ocial 
f u ncti o ni n g. 
1. 3. 3   
A ssess me nt of Be nefits a n d Ris ks 
It is t he j u d ge me nt of L e vati o n P har ma Lt d. t hat there is a fa v ora bl e be nefit -ris k rati o f or 
s u bjects wit h ac q uir e d bl e p har o pt osis . T he acti ve i n gre die nt i n t he i n vesti gati o nal pr o d uct (I P), 
o x y metaz oli ne, is alrea d y a p pr o ve d b y t he F D A f or use i n h u ma n s u bjects acr oss m ulti ple 
i n dicati o ns. O x y metaz oli ne has b ee n a p pr o ve d a n d i n use si nce t he 1 9 6 0s. T he acti ve 
i n gre die nt is ge nerall y well t olerate d i n h u ma n s u bjects. 
 






Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 1 9  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
3  
I N V E S TI G A TI O N A L P L A N 
3. 1   
O ver all St u d y Desi g n a n d Pl a n  
T his is a P has e 1/ 2a , m ultice nter, ra n d o mize d, ve hi cle -c o ntr olle d, d o u ble -m as ke d, si n gle-d os e, 
parallel -gr o u p st u d y  c o n d ucte d i n a d ult s u bjects wit h ac q uire d bl e p har o pt osis. S u bjects will 
recei v e a o ne-ti me a p plicati o n of ra n d o mize d, d o u ble -mas ke d I P.  A p pr o xi matel y 3 0 s u bjects 
will be e nr olle d i n t his st u d y. E li gi ble su bjects will be r a n d o mize d t o 1 of t he f oll o wi n g 3 
treat me nt gr o u ps  i n a 1: 1: 1 rati o an d will recei v e a si n gle d ose of d o u ble -mas ke d I P e xt er nall y 
o n t he u p per e y eli d of b ot h e yes ( O U):  
•  L E V 1 0 2 T o pical Gel, 2. 0 % ( 1 0 0 µ L)  
•  L E V 1 0 2 T o pical Gel, 1 . 0 % ( 1 0 0 µ L) 
•  Ve hicle T o pical Gel ( 1 0 0 µ L)  
S cree ni n g Visit ( Visit 1 ; D a y -4 5 t o D a y -7 ) 
A t t he Scree ni n g visit ( Visit 1), s u bjects will r e vie w a n d si g n t he i nf or me d c o nse nt f or m (I C F) 
a n d be gi n was h o ut of pr o hi bite d me dicati o n s/ pr oce d ures not p er mitte d d uri n g  the st u d y . 
S u bjects will c o m plete st u d y i nta ke a n d u n der g o scree ni n g assess me nts, w hic h will i ncl u de 
exter nal p h ot o gr a p h y of O U b ot h bef ore a n d after a d mi nistrati o n of 1 dr o p of si n gle -mas ke d 
U p nee q ® ( o x y metaz oli n e 0. 1 % o p ht h al mic s ol uti o n) O U . (N ote: U p nee q ® is preferre d b ut 
p he n yle p hri ne 2. 5 % o p ht hal mic s ol uti o n ma y be use d if U p nee q ® is n ot a v aila ble i n a ti mel y 
ma n ner .) A  ce ntr al rea di n g ce nter  will re vie w t he i ma ges ca pt ure d d uri n g t he S cree ni n g visit 
t o c o nfir m  st u dy eli gi bilit y . S u bjects weari n g ma ke u p d uri n g t he S cree ni n g visit s h o ul d re m o ve 
t he ma ke u p o n-site bef ore i ma ge ca pt ure.  
S u bjects  s h o ul d be c o nt acte d b y tel e p h o ne o n Da y  -1 , t he da y bef ore Visit 2  (Baseli ne; 
Ra n d o mizati o n; Da y 1),  t o c o nfir m st u d y visit details a n d a p p oi nt me nt ti me, or t o i nf or m 
s u bjects of scree n fail ure. S u bjects w h o re m ai n eli gi ble f or st u d y partici pati o n at t his ti me 
s h o ul d be re mi n de d : 
1.  If t he s u bject n or mall y  w ears c o nt act le nses, t he  s u bject sh o ul d n ot wear c o ntact le nses 
o n  st u d y visit da ys [ Visit 1 ( Scree ni n g); Visit 2 (Baseli ne; Ra n d o mizati o n; Da y 1 )] a n d 
s h o ul d i nstea d wear p res cri pti o n e ye glasses . 
2.  N ot t o a p pl y a n y ma ke u p or  O T C c os metic or t o pical s ki n care pr o d ucts, i ncl u di n g 
s u nscree n or m oist urizer, t o t heir eyeli ds or e yelas hes o n t he da y of st u d y treat me nt 
( Visit 2; Baseli ne; Ra n d o mizati o n; Da y 1). 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 0  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
D a y 1/ Tre at me nt Peri o d ( Visit 2)  
Te n  ( 1 0) t o 4 5 cale n dar da ys after t he Scree ni n g visit, eli gi ble su bjects will ret ur n t o t he st u d y 
site f or ra n d o mizati o n t o 1 of 3 treat me nt gr o u ps  i n a 1: 1: 1 rati o. D o u ble -mas ke d I P will be 
dis pe nse d u si n g a p ositi ve-dis place m e nt pi pette a n d will be a p plie d s m o ot hl y wit h a gl o ve d 
fi n ger t o t he e ntire e xter n al s ki n of t he u p per e y eli d of eac h e ye b y trai ne d st u d y staff. 
N ote: T he Da y 1 a p p oi nt me nt arri val ti me m ust be sc he d ule d f or earl y i n t he m or ni n g t o all o w 
s ufficie nt ti me f or t he H o ur 8 st u d y assess me nts. 
S u bjects will u n der g o st u d y assess me nts a n d a ns wer st u d y q uesti o n naires at  Baseli ne , H o ur 1, 
H o ur 4, a n d H o ur 8. E xter nal p h ot o gra p h y of t he e yes will als o be c o n d ucte d at  Baseli ne, H o ur 
0. 5, H o ur 1, H o ur 2, H o ur 4, H o ur 6, a n d H o ur 8. F or t he p ur p oses of d oc u me ntati o n a n d 
a nal ysis, B aseli ne will be defi ne d as t h e  m eas ure me nts c ollecte d at Da y 1 bef ore a d mi nistrati o n 
of d o u ble -mas ke d st u d y I P . 
T ele p h o ne F oll o w -U p ( Visit 3; D a y 2 -5 ) 
S u bjects will be c o ntacte d b y cli nical site staff f or a f oll o w -u p tele p h o ne i nter vie w  2 -5 da ys 
after t he tr eat me nt peri o d t o c ollect data o n A Es e x perie n ce d i n t he da ys f oll o wi n g I P 
a d mi nistrati o n a n d t o c ollect data o n c o n c o mita nt me dicati o ns . 
A  dia gra m of t he st u d y d esi g n is i ncl u de d bel o w at Fi g ure 1 . 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 1  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
Fi g ure 1   
Cli nic al St u d y Di a gr a m  
 
•   S u bjects s h o ul d b e c o ntacte d b y st u d y staff via  tele p h o ne bef ore st u d y visits t o be re mi n de d of t he f oll o wi n g: 
1.) I f t he s u bject n or mall y  wears c o ntact le nses, t he s u bject s h o ul d n ot wear c o ntact le nses  o n st u d y visit da ys  
an d s h o ul d i nstea d wear prescri pti o n e ye glasses  a n d 2.) N ot t o a p pl y a n y ma ke u p or  O T C c os metic or t o pical 
s ki n care pr o d ucts, i ncl u di n g s u nscree n or m oist urizer , to t heir e yeli ds or e yelas h es o n t he da y of t he 
S cree ni n g visit or o n t he da y of st u d y treat me nt. 
•   Vi sit 3 will be a re m ote visit c o n d ucte d b y tele p h o ne. 
3. 2   
R ati o n ale f or St u d y Desi g n a n d C o ntr ol Gr o u p  
T his st u d y will assess t he oc ular a n d s yste mic safet y a n d t olera bilit y of a si n gle a p plicati o n of 
L E V 1 0 2 T o pical Gel, 2 %  (1 0 0  µ L ), L E V 1 0 2 T o pical Gel, 1 %  (1 0 0  µ L ), a n d matc hi n g ve hicle 
gel ( 1 0 0 µ L) o n t he u p p er e y eli ds of s u bjects wit h ac q uire d bl e p har o pt osis . The matc hi n g 
ve hicle gel is i de ntical i n f or m ulati o n t o L E V 1 0 2, wit h t he e xce pti o n t hat t h e ve hicle g el d oes 
n ot c o ntai n  a n y acti ve dr u g . 
S u bjects will recei ve 1 dr o p of si n gle-mas ke d U p nee q ® ( o x y metaz oli ne 0. 1 % o p ht hal mic 
s ol uti o n) O U at t he S cree ni n g visit a n d will ha ve p h ot o gra p h y ta ke n of t h eir e yes b ot h bef ore 
a n d aft er si n gle-mas ke d d osi n g . (N ote : U p nee q ® is preferre d b ut p h e n yle p hri ne 2. 5 % 
o p ht hal mic s ol uti o n ma y be use d if U p nee q ® is n ot a vaila ble i n a ti mel y ma n ner .) A ce ntral 
rea di n g ce nter will re vi e w t hese i ma ges t o e ns ure all s u bjects e nr olle d i n t he st u d y are 
o x y metaz oli n e or phe n yl e p hri n e r es p o n ders. 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 2  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
S u bjects will recei ve a si n gle d ose of d o u ble -mas ke d I P o n t he u p per e yeli d  O U o n Da y 1 a n d 
will u n der g o st u d y assess me nts at m ulti ple ti me p oi nts o n t hat sa me da y . Do u ble -mas ke d I P 
will be dis pe nse d usi n g a p ositi ve -dis place me nt pi pette a n d will be a p plie d s m o ot hl y wit h a 
gl o ve d fi n ger t o t he e ntire e xter n al s ki n of t he u p p er e y eli d of eac h e y e b y trai ne d st u d y staff . 
T he treat me nt peri o d i n t his st u d y will be  o n Da y 1, a n d s u bjects will be c o nt acte d b y tel e p h o ne 
f or a f oll o w-u p call aft er I P a d mi nistrati o n a n d bef ore bei n g release d fr o m t he st u d y.  
 
 
 
 
 
 T he i nte n de d cli nical d ose of L E V 1 0 2 
T o pical Gel i n t his st u d y will be 1 0 0 µ L per u p per e yeli d at a f or m ulati o n stre n gt h of eit her 
2 % or 1 % . Ass u mi n g d ose pr o p orti o nalit y i n t he s yste mic e x p os ure t o o x y metaz oli ne, the 
esti mate d s yste mic e x p os ure i n h u m a n s u bjects s h o ul d be c o m p ara bl e t o t he s yste mic e x p os ure 
o bser ve d w it h t he mar ket e d pr o d uct, R h ofa d e ®. Th e ma xi m u m d ose of L E V 1 0 2 T o pical Gel 
is calc ulate d as 1 0 0 µ L of 2 % L E V 1 0 2 f or eac h e yeli d ( 20 0 µ L  t otal) = 2  m g per e yeli d or 4  
m g per s u bject f or a si n gle d ose a p plie d t o b ot h u p per e yeli ds. 
B ase d o n  i nf or m ati o n o btai ne d fr o m pu blicl y a vaila ble s o urces a n d t he dat a c ollect e d t o dat e 
o n L E V 1 0 2 T o pical Gel , Le vati o n P har ma Lt d. belie ves t hat t he pr o p ose d d osi n g ( 1 0 0 µ L of 
2 % L E V 1 0 2 a d mi nistere d e xter nall y t o eac h u p per e yeli d, o nce dail y) is wit hi n t he safet y 
ra n ge. Pleas e see t h e I B for a d diti o nal details a b o ut t he n o ncli nical p har mac ol o g y,  t he 
precli nical P K, a n d t o xic ol o g y st u dies  t hat i nf or me d t his e val uati o n of o x y metaz oli n e.  
3. 3   
E n d of St u d y Defi niti o n  
A  s u bject is c o nsi dere d t o ha ve c o m plete d t he st u d y if t he y ha ve bee n ra n d o mize d t o I P , 
u n der g o ne st u d y assess m e nts o n Da y 1, a n d bee n c o ntacte d b y tele p h o ne f or t heir f oll o w -u p 
visit . T h e e n d of t he st u d y is defi ne d as c o m pleti o n of t he last visit or pr oce d ure s h o w n i n t h e 
sc he d ule i n t he st u d y gl o ball y. 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 3  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
4  
S T U D Y P O P U L A TI O N S E L E C TI O N  
4. 1   
St u d y P o p ul ati o n  
T he st u d y p o p ulati o n will c o nsist of a d ult s u bjects w h o ha v e ac q uire d ble p har o pt osis . If b ot h 
e yes q ualif y f or t he st u d y, t he e ye wit h t he l o wer M R D 1 val ue at Baseli ne will be desi g nate d 
as t he st u d y e ye . If M R D 1 val ues are t he s a me f or bot h e yes  at Bas eli ne, t h e ri g ht e y e will b e 
desi g nate d as t h e st u d y e ye . Re g ar dless of st u d y e ye or st u d y q ualificati o n, all e yes i n t his 
st u d y will recei ve st u d y I P a n d u n der g o st u d y assess me nts. 
4. 2   
I ncl usi o n Criteria  
S u bjects w h o meet all  t he foll o wi n g i ncl usi o n criteria will be eli gi ble t o partici pate i n t he st u d y. 
S u bjects m ust:  
1.  Be male or fe m ale s u bjects 2 5 years of a g e or ol der at t he ti me of Scree ni n g ( Visit 1)  
2.  Ha ve c o m plai nts of aest heticall y u nacce pta ble u p per e yeli d p ositi o n f or b ot h e yes 
ma ki n g t he m desir o us f or ele vati o n, or h a ve c o m plai nts of s u peri or vis ual fiel d defects 
i n b ot h e yes t hat i m pact acti vities of dail y li vi n g 
3.  Prese nt wit h t he f oll o wi n g at Scree ni n g ( Visit 1):  
a. At least o ne e ye t h at meets b ot h of t he f oll o wi n g criteria:  
i. M R D 1 ≤2 . 3 m m ( n o visi ble ce ntral p u pillar y li g ht refle x d efa ults t o 0)  
ii. C urre nt c orrect e d  V A , usi n g s u bject’s o w n prescri pti o n e ye glasses, if 
a p plica ble, i n t he q u alif yi n g e ye(s) of + 0.3  L o g M A R ( L o garit h m of t he 
Mi ni m u m A n gle of Res ol uti o n) or better as ass esse d b y E T D R S  
b.  De m o nstrate u p p er e yeli d ele vati o n ≥0. 5 m m c h a n ge fr o m baseli ne i n M R D 1 
i n b ot h e yes i n res p o nse t o a si n gle dr o p of U p nee q ® ( o x y metaz oli ne 0. 1 % 
o p ht hal mic s ol uti o n) t o eac h e y e at Scree ni n g  
N ote: U p nee q ® is preferre d b ut p h e n yle p hri ne 2. 5 % o p ht hal mic s ol uti o n 
ma y be use d if U p n ee q ® is n ot a vaila ble i n a ti mel y ma n ner .  
4.  I n t h e j u d g me nt of t he I n vesti gat or, ha ve n or mal le vat or pal p e brae s u peri oris m uscle 
f u ncti o n of b ot h u p per e y eli ds 
5.  W o me n of c hil d -beari n g p ote ntial ( W O C B P) m ust a gree t o use a n a p pr o ve d m et h o d of 
b irt h c o ntr ol as o utli ne d i n A p pe n di x 1 6 : W o men of C hil d -beari n g P ote ntial ( W O C B P)  
fr o m t he date t he y si g n t he I C F u ntil after t he last st u d y visit ( F oll o w -U p Visit ) 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 4  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
6.  B e a ble t o gi ve i nf or me d c o nse nt a n d willi n g t o c o m pl y wit h all st u d y visits a n d 
e xa mi nati o ns  
4. 3   
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 e xcl usi o n criteria at Scree ni n g ( Visit 1) or Baseli ne 
( Visit 2) will n ot be eli gi ble t o partici pate i n t he st u d y. S u bjects m ust n ot: 
O c ul ar C o n diti o ns  
1.  Ha ve a n y ot h er o c ular p at h ol o g y ot her t h a n pt osis re q uiri n g treat me nt wit h t o pical 
prescri pti o n o p ht hal mic dr o ps i n eit her e ye (e. g., gla uc o ma)  
N ote: S u bjects w h o us e O T C or prescri pti o n t o pi cal o p ht hal mic dr o ps t o treat dr y 
e ye diseas e ma y be all o we d wit h S p o ns or a p pr o val.  
2.  Ha ve narr o w a n gles, gla uc o ma, I O P > 2 3 m m H g or dia g n osis of oc ular h y perte nsi o n, 
c u p-t o-disc rati o of > 0. 7, or hist or y of a n y gla uc o ma e ye s ur ger y i n eit her e ye  
3.  Ha ve a n y acti ve oc ul ar or peri -oc ular i nfecti o n; a n y hist or y of rec urre nt or c hr o nic 
i nfecti o n or i nfla m mati o n i n eit her e ye 
 
4.  Ha ve a hist or y of her petic i nfecti o n i n eit her e ye  
5.  Ha ve a hist or y of c or neal disease ot her t ha n mil d t o m o derate dr y e ye or s ur ger y i n 
eit her e ye  
N ote: 
S u bjects 
wit h o c ular refracti ve s ur ger y (e. g., laser -assiste d i n sit u 
kerat o mile usis, p h ot orefracti ve keratect o m y, s mall i ncisi o n le ntic ule e xtracti o n) 
≥9 0 da ys pri or t o Scree ni n g ( Visit 1) are all o we d.  
6.  Prese nt wit h a n y p u pillar y a b n or malit y i n eit her e ye  
7.  Prese nt wit h a n y ma nifest stra bis m us i n eit her e ye  
8.  Prese nt, i n t he o pi ni o n of t he I n v esti gat or, wit h cli nicall y si g nifica nt br o w pt osis i n 
eit her e ye  
9.  Ha ve as y m metr y ≥3. 0 m m i n M R D 1 bet wee n e yes or i nter pal pe bral dista nce bet wee n 
b ot h e yes  
1 0.  Ha ve a n y a n at o mic a b n or malit y of eit her u p per or l o wer e yeli ds i n eit her e ye t hat 
o bsc ures eit her u p per or l o wer e y eli d mar gi n  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 5  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 1.  Ha ve a n y hist or y of pt osis s ur ger y i n eit her e ye  
1 2.  Ha ve a hist or y of a n y u p per or l o wer e yeli d s ur ger y, i ncl u di n g ble p har o plast y, s ki n 
lesi o n, or ot her iss ue wit hi n 3 m o nt h of Scree ni n g ( Visit 1) i n eit her e ye 
1 3.  Ha ve a hist or y of c hr o ni c pr o gressi ve e xter n al o p ht hal m o ple gia, H or ner’s s y n dr o me, 
m yast he nia gra vis, 
Marc us G u n n ja w wi n ki n g, c o n ge nital pt osis, Kear ns -Sa yre 
S y n dr o me, der mat oc halasis, u nc o ntr olle d ble p har os pas m, Ra msa y H u nt s y n dr o me, or 
mec ha nical pt osis  i n eit her e ye 
N ote:  Der mat oc halasis (e xcess e yeli d s ki n) s h o ul d n ot be c o nsi dere d e x cl usi o nar y 
if, i n t he o pi ni o n of t he I n vesti gat or, it d oes n ot o bsc ure e y eli d mar gi ns or i nterfere 
wit h q ualit y i ma ge ca pt ure.  
1 4.  Ha ve m ec ha ni cal pt osis, i ncl u di n g pt osis d ue t o or bital or e y eli d t u m or, cicatricial 
pr ocesses affecti n g t he m o ve me nts of t he u p per e y eli d, a n d e n o p ht hal m os i n eit her e ye  
1 5.  Ha ve e y eli d p ositi o n affecte d b y e yeli d or c o nj u ncti val scarri n g i n eit her e y e  
1 6.  Ha ve a vis ual fiel d l oss fr o m a n y ca us e ot her t ha n pt osis i n eit her e ye  
1 7.  Ha ve a hist or y of o ptic ne ur o pat h y i n eit her e ye  
1 8.  Ha ve use d t o pical a p plicati o n of bi mat o pr ost (i.e., Latisse) t o t he e yelas hes wit hi n 7 
da ys pri or t o Scree ni n g ( Visit 1)  a n d d uri n g t he st u d y i n eit her e ye  
1 9.  Ha ve us e d t o pical a p plicati o n of pil ocar pi ne (i.e., V uit y) wit hi n 7 d a ys pri or t o 
Scree ni n g ( Visit 1) a n d d uri n g t he st u d y i n eit her e ye  
2 0.  Ha ve c o n c urre nt diseas e i n eit her e y e or t hat c o ul d re q uire me di cal or s ur gical 
i nter ve nti o n d uri n g t he st u d y peri o d 
2 1.  Be u n willi n g t o disc o nti n ue t he use of u p per e y eli d/e yelas h ma ke u p a n d O T C c os metic 
pr o d ucts d uri n g t h e S cree ni n g visit a n d o n t he da y of t he st u d y treat me nt a n d 
assess me nts ( Da y 1), i ncl u di n g b ut n ot li mite d t o:  
a. E yes ha d o w pri mer  
b.  E yes ha d o w  
c. E yeli d m oist urizer  
d.  E yeli ner  
e. Fa ke e yelas h es ( gl ue d or ma g netic)  
f. S ki n care pr o d u cts a p plie d t o t he e yeli d  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 6  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
N ote: E n ha n ce me nts t h at ca n n ot easil y be re m o ve d s h o ul d n ot be c o nsi dere d 
e xcl usi o nar y if, i n t he o pi ni o n of t he I n vesti gat or, t he y d o n ot o bsc ure e yeli d 
mar gi ns or i nterfere wit h q ualit y i ma ge ca pt ure.  
N ote : S u bjects weari n g ma ke u p d uri n g t he S cree ni n g visit s h o ul d re m o ve t he 
ma ke u p o n -site bef ore i ma ge ca pt ure. 
2 2.  Ha ve use d o x y met az oli n e t o pical e ye dr o ps ( U p nee q ®) f or treat me nt of ble p har o pt osis 
or as a n o c ular d ec o n gest a nt ( Visi ne L R) wit hi n 7  da ys pri or t o Scree ni n g ( Visit 1) or 
pla n ne d use d uri n g t he st u d y peri o d i n eit her e y e  
N ote: E y e dr o ps a p plie d d uri n g Scree ni n g ( Visit 1) t o deter mi ne st u d y eli gi bilit y 
are e x e m pt fr o m t his e xcl usi o n.  
2 3.  Ha ve ha d i ntra vitreal i njecti o ns (e. g., L uce ntis, E ylea, A vasti n, Triese n ce) wit hi n 7 
da ys pri or t o Scree ni n g ( Visit 1) or ha ve pla ns f or a n i njecti o n d uri n g t he st u d y i n eit her 
e ye  
2 4.  Ha ve a hist or y of t h yr oi d e ye disease (i.e., e x o p ht hal m os, u p per e yeli d retracti o n, 
di pl o pia sec o n dar y t o e xtra oc ular m uscle i n v ol ve me nt) i n eit her e ye. H y pert h yr oi dis m 
t hat is c o ntr olle d o n me dicati o n is all o we d 
S yste mic C o n diti o ns  
2 5.  Ha ve a resti n g heart rate o utsi de n or mal ra n ge of 5 0 -1 1 0 beats per mi n ute w hile sitti n g 
d uri n g t he Scree ni n g visit ( Visit 1)  
2 6.  Ha ve, i n t he o pi ni o n of t he I n vesti gat or, u nc o ntr olle d h y perte nsi o n, u nc o ntr olle d atrial 
fi brillati o n, or hist or y of cli nical car di o vasc ular disease i ncl u di n g str o ke, m y ocar dial 
i nfarcti o n, or heart fail ure 
2 7.  Ha ve pla ns t o use a n o n -o p ht hal mic α -a dre ner gic a g o nist, i ncl u di n g O T C pr o d ucts 
(e. g., Afri n), at a n y ti me d uri n g t he st u d y 
2 8.  Ha ve use d m o n o a mi ne o xi dase i n hi bit ors ( M A OIs; e. g., is ocar b o xazi d, p he nelzi ne, 
tra n ylc y pr o mi ne) wit hi n 1 4 da ys pri or t o Scree ni n g ( Visit 1) or a ntici pate usi n g M A OIs 
d uri n g t he st u d y  
2 9.  S u bjects wit h dia betic reti n o pat h y ma y n ot be e nr olle d i n t his st u d y. H o we ver, s u bjects 
wit h i ns uli n -de pe n de nt dia betes, dia betes re q uiri n g oral h y p o gl yce mic dr u gs, or diet -
c o ntr olle d dia betes are all o we d  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 7  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
3 0.  Ha ve b ee n dia g n ose d wit h be ni g n pr ostatic h y p ertr o p h y re q uiri n g m e dici n al t hera p y; 
pre vi o us pr ostatect o m y is all o we d  
Ge ner al  
3 1.  Ha ve partici pate d i n ot her i n vesti gati o nal dr u g or de vice cli nical trials wit hi n 3 0 da ys 
pri or t o Scree ni n g ( Visit 1), or be pla n ni n g t o partici pate i n a n y ot her i n vesti gati o nal 
dr u g or de vice cli nical tri als wit hi n 3 0 da ys of st u d y c o m pleti o n  
3 2.  Ha ve a hist or y of aller gic reacti o n t o t he i n vesti gati o nal dr u g or a n y of its c o m p o ne nts  
3 3.  Wit hi n 7 da ys of Scree ni n g ( Visit 1), or a ntici pate d use d uri n g t he st u d y, use of a n y 
s yste mic, i ntra nasal, t o pical der mat ol o gic, or o p ht hal mic α-a dre ner gic a g o nist 
(i ncl u di n g bri m o ni di ne) or a nta g o nist i ncl u di n g nasal or oc ular or oral dec o n gesta nts 
i ncl u di n g pse u d oe p he dri ne, o x y metaz oli ne t o pical o p ht hal mic s ol uti o n, o x y metaz oli ne 
t o pical der mat ol o gic crea m 
3 4.  S u bjects w h o are pre g na nt or breast -fee di n g 
3 5.  Ha ve use d U p nee q ® wit hi n 7 da ys of eit her Scree ni n g ( Visit 1) or Baseli ne ( Visit 2)  
4. 4   
S cree n /B aseli ne F ail ures  
S cree n fail ures are defi ne d as s u bjects w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut w h o  
d o n ot meet t he i ncl usi o n criteria at t he Scree ni n g visit  a n d/ or are det er mi ne d u ns uita ble f or 
t he st u d y beca use t he y meet excl usi o n criteria. T his i ncl u des b ut is n ot li mite d t o e val uati o ns 
c o m plete d b y t he ce ntral rea di n g ce nter  of i ma g es ca pt ure d d uri n g t he Scree ni n g visit.  Baseli ne  
fail ures are defi ne d as s u bjects w h o c o nse nt t o partici pate i n t he cli nical st u d y a n d are eli gi ble 
base d o n scree ni n g criteria  b ut are n ot eli gi ble bas e d o n t he Baseli ne criteria  a n d are t heref ore 
n ot r a n d o ml y assi g ne d t o I P. A mi ni mal set of s cree n fail ure i nf or mati o n is re q uire d t o e ns ure 
tra ns pare nt re p orti n g of scree n a n d bas eli ne fail ure s u bjects, t o m eet t he C o ns oli date d 
Sta n dar ds of Re p orti n g Tr ials ( C O N S O R T) p u blis hi n g re q uire me nts, a n d t o res p o n d t o q ueries 
fr o m re g ulat or y a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, scree n fail ure details, 
eli gi bilit y criteria, a n d a n y seri o us a d verse e v e nts ( S A E).  
R escree ni n g m a y be p er mitte d a ma xi m u m of 1 ti me 2  wee ks after scree n fail ure f or s u bjects 
wit h I O P v al ues at Baseli ne ≥2 3 m m H g. Rescree ni n g ma y be per mitte d a m a xi m u m of 1 ti me 
after a p pr o priate was h o ut peri o ds f or s u bjects w h o prese nte d wit h dis q ualif yi n g me dical 
c o n diti o ns at Baseli ne or pre vi o us/c o nc o mita nt me dicati o ns pr o hi bite d i n  Ta ble 1 . Rescree ni n g 
ma y als o occ ur bas e d u p o n pr ot oc ol a me n d me nts wit h pri or a p pr o val fr o m t he Me dical 
M o nit or a n d S p o ns or . R escree n e d s u bjects s h o ul d be assi g ne d a ne w s u bject n u m ber, a n d t he 
ori gi nal s u bject n u m ber s h o ul d be rec or de d as a scree n fail ure . 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 8  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
5  
S T U D Y T R E A T M E N T( S)  
5. 1   
Descri pti o n of I n vesti g ati o n al Pr o d uct(s) 
L E V 1 0 2 T o pical Gel a n d its matc hi n g ve hicle g el ar e 
 ge ls wit h hi g h 
vis ual visc osit y i nte n de d f or e xter n al t o pical a d mi nistrati o n t o t he e xteri or s ki n of s u bjects’ 
u p per e y eli ds. S ta bilit y st u dies of L E V 1 0 2  sh o w n o micr osc o pic c ha n g es of n ote a n d pr o vi de 
n o res ults i n dicati ve of p h ysical i nsta bilit y of t he f or m ulati o n . 
T he I P c o m p o ne nts are ase ptic; h o we ver, it is n ot p ossi ble t o ter mi nall y sterilize  t he I P usi n g 
t he curre nt ma n ufact uri n g met h o d d ue t o l oss of dr u g s u bsta nce a n d/ or c h a n ges i n visc osit y . 
T he matc hi n g ve hicle gel i n t his st u d y is i de ntical i n f or m ulati o n t o L E V 1 0 2 T o pical Gel, wit h 
t he e xce pti o n t hat t he ve hicle gel d oes n ot c o ntai n a n y acti ve dr u g. 
T he acti ve dr u g i n t his st u d y, o x y metaz oli ne, is a c o m merciall y a v aila ble s y m pat h o mi metic. 
 
 
 
5. 1. 1   
D os a ge a n d A d mi nistr ati o n  
E li gi ble s u bjects will be ra n d o mize d t o 1 of 3 p ossi ble treat me nt gr o u ps i n a 1: 1: 1 rati o. Trai ne d 
st u d y staff will dis pe nse d o u ble-mas ke d I P [ L E V 1 0 2 T o pical Gel, 2. 0 % ( 1 0 0 µ L); L E V 1 0 2 
T o pical Gel, 1 . 0 % (1 0 0 µ L); Ve hicle T o pical Gel ( 1 0 0 µ L)] 
 
will a p pl y t he gel s m o ot hl y wit h a gl o ve d fi n ger t o t he e ntire e xter nal s ki n of  eac h 
s u bject’s u p per e yeli ds ( O U). 
T he I P a d mi nistrati o n i n t his st u d y m ust be sc he d ule d f or earl y i n t he m or ni n g i n or der t o 
acc o m m o date t he H o ur 8 st u d y assess me nts. T his is a 1 -da y, s i n gle-d ose st u d y i n w hic h 
s u bjects ra n d o mize d t o I P will recei v e 1 d os e of d o u ble-mas ke d I P gel ( 1 0 0 µ L) per  u p per 
e yeli d f or a t otal of 2 0 0 µ L p er s u bject f or t he d urati o n of t he st u d y . 
5. 2   
Pre p ar ati o n/ St or a ge/ H a n dli n g/ Acc o u nt a bilit y  
5. 2. 1   
Ac q uisiti o n a n d Acc o u nt a bilit y  
D o u ble -mas ke d I P f or t his st u d y will be pr o vi de d t o eac h st u d y site. O nce t he I P has bee n 
deli vere d t o t he site, it will be st ore d i n a li mite d -access area o nl y accessi ble t o trai ne d st u d y 
staff. Use d a n d u n use d I P will be mai ntai ne d at t he site f or acc o u nta bilit y b y t he cli nical st u d y 
m o nit or . 
W he n a ut h orize d b y t he S p o ns or a n d after t he cli nical st u d y m o nit or has verifie d dr u g 
acc o u nta bilit y is c o m plete a n d acc urate, us e d a n d u n use d d o u ble -m as ke d I P will  eit her b e 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 2 9  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
ret ur ne d t o t he S p o ns or or desi g nee,  or will be dis p ose d / destr o ye d b y t he sites i n a cc or da n ce 
wit h t he re q uire me nts of a p plica ble l ocal a ut h orities a n d re g ulat or y b o dies t o e ns ure dis p osal 
of I P d oes n ot e x p ose h u ma n bei n gs t o ris ks fr o m t he dr u g . 
5. 2. 2   
P r o d uct F or m ul ati o n, A p pe ar a nce, P ac k a gi n g a n d L a beli n g  
L E V 1 0 2 T o pical Gel a n d Ve hicle T o pical Gel will be pac ka ge d i n i de ntical 
 
vials a n d la bel e d i n acc or da nce wit h fe d eral re g ulati o ns f or i n vesti gati o nal ne w dr u gs. La bels 
will i ncl u de ver bati m t he f oll o wi n g state me nt: “ C a uti o n: Ne w Dr u g –  Li mite d b y Fe deral la w 
t o i n vesti gati o nal use.” 
A d diti o nal details ma y als o be i ncl u de d o n t he la bel, pr o vi de d t hat t h ese d etails d o n ot p ose a 
ris k t o st u d y mas ki n g. T his ma y i ncl u de b ut is n ot li mite d t o t he pr ot oc ol n u m ber, I P v ol u me 
per c o ntai ner, st ora g e re q uire me nts, ma n ufact urer, a n d l ot n u m ber . 
5. 2. 3   
Pr o d uct St or a ge a n d St a bilit y  
T he d o u ble -mas k e d I P f or t his st u d y will b e st ore d u pri g ht i n a  li mite d-access area accessi ble 
o nl y t o trai ne d st u d y staff a t a c o ntr olle d r o o m t e m perat ure bet w ee n 2 0° C -2 5° C  (6 8° F -7 7° F ) 
a n d pr otecte d fr o m dir ect s u nli g ht. Te m perat ure e xc ursi o ns ex perie n ce d i n ware h o uses a n d 
d uri n g s hi p pi n g [ n ot t o e xcee d 3 0° C (8 6° F )] are p er mitte d . 
O nce a vial of d o u ble -mas ke d I P has bee n o pe ne d,  it m ust o nl y be use d f or d osi n g a si n gle 
s u bject. O pe ne d a n d u n o pe ne d vials will be mai ntai ne d at t he site f or acc o u nta bilit y b y t he 
cli nical st u d y m o nit or.  
5. 3   
Me as ures t o Mi ni mize Bi as: R a n d o miz ati o n a n d M as ki n g  
E li gi ble s u bjects will be ra n d o mize d i n t he el ectr o nic data ca pt ure ( E D C) s yste m i n a 1: 1: 1 
rati o t o d o u ble -mas ke d I P [ L E V 1 0 2 T o pical Gel, 2. 0 % ( 1 0 0 µ L) ; L E V 1 0 2 T o pical Gel, 1 . 0 % 
(1 0 0 µ L) ; V e hicle T o pi cal Gel ( 1 0 0 µ L) ] wit h o ut stratificati o n b y  st u d y site. T he d o u ble -
mas ke d I P will be dis pe nse d a n d a d mi nistere d t o s u bjects b y trai ne d st u d y staff o nl y.  
T he ra n d o mizati o n sc he d ule will be c o m p uter -ge n erate d i n t he E D C, a n d all I P will be mas ke d 
t o t he S p o ns or, st u d y pers o n nel, a n d st u d y s u bjects t hr o u g h o ut t he st u d y u ntil after t he fi nal 
data base has b ee n l oc ke d. A p pr o priate preca uti o ns m ust be ta ke n t o pre ve nt u na ut h orize d 
access t o t he ra n d o mizati o n sc he me. U nless t he s u bject’s safet y re q uires ot her wise a n d if ti me 
per mits, t he d ecisi o n t o u n mas k a treat me nt assi g n me nt is t o be ma de j oi ntl y b y t he I n vesti gat or 
a n d t he st u d y’s me dical m o nit or after c o ns ult ati o n wit h t he S p o ns or . 
If u n mas ki n g is re q uire d d uri n g t he st u d y, t he i nte grit y of t he st u d y assess me nts a n d c ollecte d 
data will be mai ntai ne d b y li miti n g access t o t he u n mas ke d data.  






Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 2  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
6  
S T U D Y P R O C E D U R E S  
6. 1   
Dis pe nsi n g St u d y Dr u g  
T his is a d o u ble -mas ke d, si n gle -d ose st u d y i n s u bjects wit h ac q uire d ble p har o pt osis. S u bjects 
will n ot ha ve a n y I P dis pe nse d t o t he m . D o u ble -mas ke d I P will be dis pe nse d usi n g a p ositi ve -
dis place me nt pi pette a n d will be a p plie d s m o ot hl y wit h a gl o ve d fi n ger t o t he e ntire e xt er nal 
s ki n of t he u p per e yeli d of eac h e y e b y trai ne d st u d y staff. T he gl o ve d st u d y staff will caref ull y 
r u b t he I P i nt o s u bjects’ u p per e yeli d s ki n u ntil t h e I P h as b ee n f ull y a bs or be d i nt o t he e yeli d 
s ki n. Care will be ta ke n t o e ns ure I P is n ot acci de ntall y i nstille d i nt o s u bjects’ e yes. 
6. 2   
A d verse E ve nts Assess me nts  
A Es will be m o nit ore d t hr o u g h o ut t he st u d y. S u bjects will be e n c o ura g e d t o re p ort a n y a d v erse 
fi n di n gs d uri n g t he st u d y w het her or n ot t he y are relate d t o I P. T hese ca n b e c ollecte d eit her i n 
a n u ns olicite d fas hi o n wit h o ut a n y pr o m pti n g or i n res p o nse t o a g e neral q uesti o n s uc h as: 
“ Ha ve y o u n otice d a n yt hi n g differe nt si nce y o u starte d t he st u d y; be ga n t h e I P, etc.?”  
A ll A Es will be ca pt ure d o n t he a p pr o priate case re p ort f or m ( C R F). I nf or m ati o n t o be c ollecte d 
at mi ni m u m i ncl u des e ve nt descri pti o n, o nset, assess me nt of se verit y, relati o ns hi p t o I P, a n d 
o utc o me . 
6. 2. 1   
Defi niti o ns  
A n A E is a n y u nt o war d me dical occ urre n ce i n a cli nical st u d y s u bject te m p orall y ass ociate d 
wit h t he use of st u d y i nter ve nti o n, w het her or n ot c o nsi dere d relate d t o t he st u d y i nter ve nti o n.  
A n A E ca n t h eref ore b e a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he 
use of I P. 
A n A E or s us pecte d a d verse reacti o n is c o nsi dere d “seri o us” if, i n t he vie w of eit her t he 
I n v esti gat or or S p o ns or, it res ults i n a n y of t he f oll o wi n g o utc o mes:  
•  De at h  
•  A l ife-t hreate ni n g A E 
•  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  
•  A 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  
•  A c o n ge nital a n o mal y or birt h defect  
I m p ort a nt 
me dical e ve nts t hat ma y n ot res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n ma y be c o nsi dere d s eri o us w he n, base d u p o n a p pr o priate me dical j u d g me nt, 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 3  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
t he y ma y je o par dize t he s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
o ne of t he o utc o mes liste d i n t his defi niti o n . 
6. 2. 2   
Ti mi n g  
T he I n vesti gat or will rec or d all A Es wit h start dates occ urri n g a n y ti me after i nf or me d c o nse nt 
is o btai ne d u ntil 7 (f or n o nseri o us A Es) or 3 0 da ys (f or S A Es) after t he last da y of st u d y 
partici pati o n.  At eac h st u d y visit, t he I n vesti gat or will i n q uire a b o ut t he occ urre nce of 
A E/ S A Es si nce t he last visit.  E ve nts will be f oll o we d f or o utc o me i nf or mati o n u ntil res ol uti o n 
or sta bilizati o n . 
A n y me dical c o n diti o n t hat is prese nt at t he ti me t hat t he s u bject is scree ne d will be c o nsi dere d 
as baseli ne a n d n ot re p orte d as a n A E  b ut will be rec or de d as Me dical Hist or y . H o we ver, if t he 
st u d y s u bject’s c o n diti o n deteri orat es at a n y ti me d uri n g t he st u d y, it will be rec or de d as a n 
A E . 
6. 2. 3   
Severity  
T he se verit y of all A Es will be assesse d b y t he I n vesti gat or a n d gra d e d as f oll o ws:  
•  Mil d : Re q uires mi ni mal or n o treat me nt a n d d o es n ot i nterfere wit h t he s u bject’s dail y 
acti vities;  
•  M o der ate:  Res ults i n a l o w le vel of i nc o n ve nie nce or c o n cer n a n d ma y ca use s o me 
i nterfere nce wit h f u ncti o ni n g; 
•  Se vere:  I nt err u pts a s u bject’s us ual dail y acti vit y a n d ma y re q uire s yste mic dr u g 
t hera p y or ot her treat m e nt. Se vere A Es are us uall y p ote ntiall y life-t hreate ni n g or 
i nca pacitati n g. T he t er m “se vere” d o es n ot necess aril y e q uate t o “s eri o us.”  
6. 2. 4   
Rel ati o ns hi p  
A ll A Es m ust ha ve t heir relati o ns hi p t o st u d y i nter ve nti o n assesse d b y t he I n v esti gat or w h o 
e xa mi nes a n d e val uates t he s u bject base d o n te m p oral relati o ns hi p a n d t he I n vesti gat or’s 
cli nical j u d g me nt. T he d e gree of certai nt y a b o ut ca usalit y will be gra de d usi n g t he cate g ories 
bel o w. I n a cli nical st u d y, t he I P m ust al wa ys b e s us pect.  
•  U n rel ate d : N o reas o na bl e p ossi bilit y t hat t he a d mi nistrati o n of t he I P ca use d t he e ve nt, 
n o te m p oral relati o ns hi p bet wee n t he I P a n d e ve nt o nset, or a n alter nate eti ol o g y has 
bee n esta blis he d ; 
•  Re l ate d: Is k n o w n t o occ ur wit h t he I P, is a reas o na ble p ossi bilit y t hat t he I P ca use d 
t he A E, or t here is a te m p oral relati o ns hi p bet wee n t he I P a n d e v e nt. Reas o na ble 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 4  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
p ossi bilit y mea ns t hat t here is e vi de nce t o s u g g est a ca usal relati o ns hi p bet wee n t h e I P 
a n d t he A E. 
6. 2. 5   
E x pecte d ness  
A n A E or s us p ecte d a d v erse reacti o n is c o nsi dere d “ u ne x p ecte d” if it is n ot liste d i n t he I B, 
p ac ka g e i nsert, or de vice la beli n g or is n ot liste d at t he s pecificit y or se v erit y t hat has bee n 
o bser ve d; or, if a n  I B is n ot re q uire d or a v aila ble, 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 pr ot oc ol, as a me n de d. “ U ne x p ecte d,” as use d i n t his defi niti o n, als o refers t o 
A Es or s us pecte d a d verse reacti o ns t hat are me nti o ne d i n t he I n vesti gat or’s Br oc h ure, pac k a ge 
i nsert, or de vice la beli n g as occ urri n g wit h a cl ass of dr u gs  ( or ot her me dical pr o d ucts) or as 
a ntici pate d fr o m t he p har mac ol o gical pr o perties or ot her c haracteristics of t he I P b ut are n ot 
s pecificall y me nti o ne d as occ urri n g wit h t he partic ular I P u n der i n vesti gati o n . 
T he I n v esti gat or will b e res p o nsi ble f or det er mi ni n g w het her a n A E is u ne x pecte d, i. e., if t he 
nat ure, se verit y, or fre q ue nc y of t he e ve nt is n ot c o nsiste nt wit h t he ris k i nf or mati o n pre vi o usl y 
descri be d f or t he I P . 
6. 2. 6   
A dverse Eve nt Re p orti n g Re q uire me nts  
A cc or di n g t o fe deral re g ulati o ns, a n I n v esti gat or m ust i m me diatel y re p or t (i.e., wit hi n 2 4 
h o urs) t o t he S p o ns or a n y S A E, w het h er or n ot c o nsi dere d dr u g relate d, i ncl u di n g t h ose liste d 
i n t he pr ot oc ol or I B an d m ust i ncl u de a n assess me nt of w het her t here is a reas o na ble p ossi bilit y 
t hat t he I P ca use d t he e ve nt . St u d y e n d p oi nts t hat are S A Es (e. g., all-ca use m ortalit y) m ust be 
re p orte d i n acc or da n ce wit h t he pr ot oc ol u nl ess t here is e vi de nce s u g gesti n g a ca us al 
relati o ns hi p bet wee n t he I P a n d t he e ve nt (e. g. , deat h fr o m a na p h yla xis). I n t hat case, t he 
I n v esti gat or m ust i m me diatel y re p ort t h e e v e nt t o t he S p o ns or ( See 2 1 C o de of Fe deral 
Re g ulati o ns ( C F R ) 3 1 2. 6 4( b)) . 
A cc or di n g t o fe deral re g ulati o ns, t he S p o ns or m ust n otif y t he F D A a n d all partici pati n g 
I n v esti gat ors as s o o n as p ossi ble, b ut i n n o case later t ha n 1 5 cale n dar da ys after t he S p o ns or 
deter mi nes t hat a p ote ntial seri o us ris k arisi n g fr o m a cli nical st u d y q u alifies f or re p orti n g.  T he 
S p o ns or m ust re p ort a n y s us pecte d a d verse reacti o n t hat is b ot h s eri o us a n d u ne x pecte d. T he 
S p o ns or m ust re p ort a n A E as a s us pecte d a d verse reacti o n o nl y if t here is e vi de nce t o s u g gest 
a ca usal relati o ns hi p bet wee n t he dr u g a n d t he a d verse e v e nt ( See 2 1 C F R 3 1 2. 3 2(c)( 1)) . 
F urt her m ore, t he S p o ns or m ust als o n otif y t he F D A of a n y u ne x p ecte d fatal or life -t hreat e ni n g 
s us pecte d a d v erse reacti o n as s o o n as p ossi ble b ut i n n o case later t ha n 7 cale n dar d a ys after 
t he S p o ns or's i nitial recei pt of t he i nf or mati o n ( See 2 1 C F R 3 1 2. 3 2(c)( 2)). 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 5  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
6. 2. 7   
C li nic al L a b or at ory A dverse Eve nts 
N ot a p plica ble. Cli nical l a b orat or y tests a n d p har mac o ki netics are n ot bei n g c o n d ucte d f or t his 
st u d y. 
6. 2. 8   
Tre at me nt -E mer ge nt A dverse Eve nts  
T reat me nt-e mer ge nt a d v erse e ve nts  w ill be defi ne d as A Es t hat occ ur i n a s u bject after 
i nf or me d c o nse nt has b ee n si g ne d a n d after t he s u bject has recei ve d I P o n Da y 1.  
6. 3   
Re m o v al of S u bjects fr o m t he St u d y  or St u d y Dr u g  
S u bjects are free t o wit h dra w fr o m p artici pati o n i n t he st u d y at a n y ti me u p o n re q uest. A n 
In v esti gat or ma y disc o nti n ue or wit h dra w a s u bject 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: 
•  Pr e g na nc y  
•  Si g nifica nt st u d y treat me nt/i nter ve nti o n n o n -c o m plia nce  
•  If a n y cli nical a d v erse e ve nt, la b orat or y a b n or malit y, or ot her me dical c o n diti o n or 
sit uati o n occ urs s uc h t hat c o nti n ue d partici pati o n i n t he st u d y w o ul d n ot be i n t he best 
i nterest of t he s u bject 
•  T h e S p o ns or or In vesti gat or ter mi nates t he st u d y  
•  T h e s u bject re q u ests t o be disc o nti n ue d fr o m t he st u d y.  
T he reas o n f or s u bject disc o nti n uati o n or wit h dra wal fr o m t he st u d y will be rec or de d o n t he 
C R F . Su bjects w h o si g n t he i nf or me d c o nse nt f or m a n d d o n ot recei ve I P o n Da y 1  ma y be 
re place d. Su bjects w h o si g n t he i nf or me d c o ns e nt f or m , are ra n d o mize d , ha v e bee n  d os e d wit h  
I P o n Da y 1 , a n d s u bse q ue ntl y wit h dra w, or are wit h dra w n or disc o nti n ue d fr o m t he st u d y, 
ma y n ot be re place d.  
6. 4   
L ost t o F oll o w -U p  
A  s u bject will b e c o nsi d ere d l ost t o f oll o w-u p if  t he s u bject fails t o ret ur n t o t he cli nic f or 
sc he d ule d visits  an d i f t he s u bject ca n n ot be co ntacte d b y t he st u d y site staff . S u bjects will 
si milarl y be c o nsi dere d l ost t o f oll o w-u p if t he s u bject d oes n ot  res p o n d t o ph o ne call s f or t he 
Visit 3 tele p h o ne foll o w -u p ( Da y 2 -5) i n a ti mel y ma n ner . 
T he f oll o wi n g acti o ns m ust be ta ke n if a s u bject fails t o ret ur n t o t he cli nic f or a re q uire d st u d y 
visit:  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 6  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
•  T h e site will atte m pt t o c o ntact t he s u bject a n d res c he d ule t he misse d visit  a n d c o u nsel 
t he s u bject o n t he i m p orta nce of m ai ntai ni n g t he assi g ne d visit sc he d ule a n d ascertai n 
if t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he st u d y;  
•  Be f ore a s u bject is dee me d l ost t o f oll o w-u p, t he I n v esti gat or or desi g nee will ma ke 
e ver y eff ort t o re gai n c o ntact wit h t he s u bject ( w here p ossi ble, 3 tele p h o n e calls a n d, if 
necessar y, a certifie d letter t o t he s u bject’s last k n o w n maili n g a d dress or l ocal 
e q ui vale nt met h o ds).  T h ese c o ntact atte m pts s h o ul d be d o c u me nte d i n t he s u bject’s 
me dical rec or d or st u d y file . 
S h o ul d t he s u bject c o nti n ue t o be u nreac h a ble, t he s u bject will be c o nsi dere d t o h a ve 
wit h dra w n fr o m t he st u d y wit h a pri mar y reas o n of L ost t o F oll o w -U p.  
6. 5   
A p pr o pri ate ness of Me as ure me nts  
6. 5. 1   
S afet y Assess me nts  
T he safet y assess me nts selecte d f or t his st u d y  are all c o m m o n t o ols wit hi n t he fiel d o f 
o p ht hal m ol o g y a n d are g e nerall y rec o g nize d as relia ble, acc urate, a n d rele va nt  i n assessi n g t he 
healt h a n d safet y of s u bjects’ e yes. S afet y assess m e nts i n t his st u d y i ncl u d e: 
•  A E m o nit ori n g ( oc ular a n d n o n -oc ular)  
•  C urre nt C orrecte d V A  (A p pe n di x 2: C urre nt C orrecte d Vis u al Ac uit y ) 
•  I O P (A p pe n di x 4 : I ntra o c ular Press ure (I O P)) 
•  Ma n ual  P u pill o metr y ( A p pe n di x 9 : Ma n ual  P u pill o metr y ) 
•  Slit La m p E xa mi nati o n ( A p pe n di x 1 1 : Slit La m p Bi o micr osc o p y) 
•  C o nj u ncti val H y pere mia E val uati o n  (A p pe n di x 1 2 : B ul bar C o nj u ncti val H y pere mia  
[Brie n H ol de n Visi o n I nstit ute ( B H VI) G ra di n g S cale (F or merl y  K n o w n as t he 
C C L R U )]) 
•  I ndir ect Dilate d O p ht hal m osc o p y  (A p pe n di x 1 3 : I n direct Dilate d O p ht hal m osc o p y) 
•  V ital Si g ns (A p pe n di x 1 5: Vital Si g ns ) 
•  Ur i ne Pre g n a nc y Test [ o nl y f or 
W O C B P (A p pe n di x 1 6 : 
W o men of C hil d -beari n g 
P ote ntial ( W O C B P) )] 
6. 5. 2   
Effic ac y Assess m e nt s 
T he efficac y assess me nts selecte d f or t his st u d y are  a mi x of co m m o n t o ols wit hi n t he fiel d of 
o p ht hal m ol o g y  ge nerall y r ec o g nize d as relia ble, acc urat e, a n d rele va nt a n d n o vel a p pr oac hes 
t o assessi n g pt osis. Efficac y assess me nts i n t his st u d y i ncl u d e: 
•  Le icester Peri p heral Fiel d Test (A p pe n di x 5 : Leicester Peri p heral Fi el d Test ( L P F T) ) 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 7  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
T he L P F T is a n o vel, m o difie d vis ual fiel d test de vel o pe d b y H o et al. ( 2 0 1 1)  t o e val uate 
s u peri or vis ual fiel d defects i n a d va nce of pt osis s ur ger y. T he res ulti n g literat ure 
c o nfir ms t hat pt osis ca n be c o nsi dere d b ot h a f u ncti o nal iss ue  a n d a c os metic iss ue.  T he 
L P F T was s elect e d f or t his st u d y beca use of its F D A -a p pr o ve d use i n cli nical trials f or  
U p nee q ® . 
•  F A C E -Q | 
Aest hetics 
Q uesti o n naires  (A p pe n di x 
6 : F A C E -Q | 
Aest hetics 
Q uesti o n naire s) 
F A C E -Q  is a s u bject-re p orte d o utc o me meas ure t hat has bee n use d s u ccessf ull y in 
n u mer o us cli nical trial setti n gs t o e val uate t he safet y a n d effecti ve n ess of facial  
treat me nts a n d t o i n f or m s u bject care i n cli nical practice . F A C E -Q ca n be use d t o 
meas ur e su bject s atisfacti o n wit h aest hetic facial pr oce d ures a n d pr o d ucts fr o m t he 
s u bjects’ pers pecti ve. 
 
•  In v esti gat or -R e p ort e d O utc o me s (A p pe n di x 8 : I n vesti gat or-Re p orte d O ut c o mes ) 
P ri nci pal I n vesti gat ors will be s u bjecti vel y assessi n g t he  
 p h ot o gra p hs i n a 
ra n d o mize d, mas k e d fas hi o n. 
 
•  E x ter nal P h ot o gra p h y of E yes (A p pe n di x 3: Pt osis E val uati o n ; A p pe n di x 7 :  
 
E xter nal P h ot o gra p h y ) 
I ma ges of s u bjects’ e yes will be ca pt ure d o nsite d uri n g t he cli nic visit a n d s u b mitte d t o 
a ce ntral rea di n g ce nter f or e val uati o n. T hese i ma gi n g assess me nts are c o m m o n t o ols 
wit hi n t he fiel d of o p ht h al m ol o g y a n d are ge nerall y rec o g nize d as relia ble, acc urate, 
a n d rele va nt. Please see t he Ma n ual of Pr oce d ures f or a d diti o nal i nf or mati o n a b o ut t he 
ce ntral r ea di n g ce nter ’s r ole, o perati o ns , a n d q u alificati o ns. 
6. 5. 3   
Ot her Assess m e nts  
T his st u d y will als o i ncl u de a n I P C o mf ort Assess me nt  (A p pe n di x 1 4 : I n v esti gati o nal Pr o d uct 
C o mf ort/ T olera bilit y Assess me nt ). 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 8  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
7  
S T U D Y A C TI VI TI E S  
W ritte n i nf or me d c o nse nt a n d Healt h I ns ura n ce P orta bilit y a n d Acc o u nta bilit y Act ( HI P A A) 
a ut h orizati o n will be o btai ne d fr o m all s u bjects bef ore a n y st u d y -relate d pr oce d ures are 
perf or me d. T he pr oce d ures a n d assess m e nts t hat s h o ul d occ ur at eac h st u d y visit  are detaile d 
at A p pe n di x 1 : Sc he d ule of Visits a n d Pr oce d ures.  
U nless ot her wise n ote d, pr oce d ures a n d assess me nts s h o ul d occ ur i n t he or der liste d . T he 
Scree ni n g visit i n v ol ves U p nee q ®  or p he n yl e p hri ne  i nstillati o n a n d use of dilati n g e ye dr o ps. 
S u bjects w h o n or mall y  wear c o ntact le nses s h o ul d i nstea d use prescri pti o n e ye glasses d uri n g 
all st u d y visits. 
7. 1   
S cree ni n g Visit  (Visit 1; D a y  -4 5 t o D a y -7 ) 
•  S u bject pr o vi des i nf or me d c o nse nt a n d HI P A A a ut h orizati o n  
•  C o llect de m o gra p hic i nf or mati o n a n d me dical, oc ular, a n d s ur gical hist ories  
•  Re c or d a n y co nc o mita nt me dicati o ns  
•  Vi tal si g ns 
•  Ur i ne pre g n a nc y test ( W O C B P o nl y) 
•  F A C E -Q | Aest hetics Q uesti o n naires  
•  C urre nt c orrecte d V A  
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
•  L P F T  
•  Sl it la m p e xa mi nati o n a n d e xter nal e ye e x a m  
•  Ma n ual  p u pill o metr y  
•  Le vat or f u n cti o n tes t 
•  1 st  
 e xter nal p h ot o gra p h y of e y es 
•  A d mi nistrati o n of 1 dr o p of U p nee q ® ( o x y metaz oli ne 0. 1 % o p ht hal mic s ol uti o n) O U  
o  N ote : U p nee q ® is preferre d b ut p he n yle p hri ne 2. 5 % o p ht hal mic s ol uti o n ma y 
be use d if U p nee q ® is n ot a vaila ble i n a ti mel y ma n ner . 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 3 9  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
•  W ait 1 2 0 ( ± 3 0)  mi n utes  
•  2 n d  
 e xter nal p h ot o gra p h y of e y es 
•  IO P  
•  A d mi nistrati o n of  d ilatin g e ye dr o ps  
•  Wa it at least 2 0 mi n utes 
•  I ndir ect dilate d o p ht hal m osc o p y  
•  C o nfir m  i nitial st u d y eli gi bilit y base d o n i ncl usi o n a n d e xcl usi o n criteria 
•  Sc he d ule t he Baseli ne visit ( Visit 2) f or at least 5 cale n dar d a ys fr o m t h e Scree ni n g 
v isit t o all o w U p nee q ® or p he n yle p hri n e was h o ut a n d ce ntral rea di n g ce nter pr ocessi n g 
of i ma ges  
7. 2   
B aseli ne / Ra n d o miz ati o n  ( Visit 2; Tre at me nt Peri o d ; D a y 1) 
S u bjects s h o ul d be c o ntacte d b y site st u d y staff via tele p h o ne bef ore t heir Da y 1 visit t o c o nfir m 
st u d y eli gi bilit y as c o nfir me d b y t he ce ntral rea di n g ce nter. S u bjects s h o ul d be re mi n de d d uri n g 
t his call of t he f oll o wi n g: 1.) If t he s u bject n or mall y  wears c o ntact le nses, t he s u bject s h o ul d 
n ot wear c o ntact le ns es o n st u d y visit da ys a n d s h o ul d i nstea d wear pres cri pti o n e ye glasses 
a n d 2.) N ot t o a p pl y a n y ma ke u p or O T C c os metic or t o pical s ki n care pr o d ucts, i ncl u di n g 
s u nscree n or m oist urizer, to t heir e yeli ds or e yel as hes o n t he da y of st u d y treat me nt . 
7. 2. 1   
B aseli ne Assess m e nts ( Bef ore I P A d mi nistr ati o n) 
•  C o llect n e w me dical, oc ular, a n d s ur gical hist ories  
•  Re c or d co n c o mita nt me dicati o ns  
•  Vit al si g ns 
•  Ur i ne pre g n a nc y test ( W O C B P o nl y) 
•  F A C E -Q | Aest hetics Q uesti o n naires  
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
•  C urre nt c orrecte d V A  
•  L P F T  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 0  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
•  Sl it la m p e xa mi nati o n a n d e xter nal e ye e x a m 
•  Ma n ual  p u pill o metr y  
•   
 e xter nal p h ot o gra p h y of e y es (s u b mitte d f or B aseli ne meas ure me nt o nl y, n ot 
f or st u d y eli gi bilit y ) 
•  I OP  
•  C o nfir m c o nti n ue d st u d y eli gi bilit y base d o n i ncl usi o n a n d e xcl usi o n criteria  
7. 2. 2   
I P A d mi nistr ati o n a n d H o ur 0 Pr oce d ures  ( After I P A d mi nistr ati o n)  
•  Ra n d o mizati o n  
•  D o u ble -mas ke d IP a d mi nistrati o n O U  
•  Re c or d A Es (i m me diatel y after I P a d mi nistrati o n)  
7. 2. 3   
H o ur 0. 5 Pr oce d ures  ( ± 1 0 mi n utes) 
•  R ecor d A Es  
•   
 e xter nal p h ot o gra p h y of e y es 
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
7. 2. 4   
H o ur 1 Pr oce d ures  ( ± 1 5 mi n utes) 
•  R ec or d A Es  
•  Vi tal si g ns 
•  Ma n ual  p u pill o metr y  
•   
 e xter nal p h ot o gra p h y of e y es 
•  I OP  
•  I P c o mf ort assess me nt  
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
7. 2. 5   
H o ur 2 Pr oce d ures  ( ± 1 5 mi n utes) 
•  R ec or d A Es  
•  L P F T  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 1  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
•   
 e xter nal p h ot o gra p h y of e y es 
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
7. 2. 6   
H o ur 4 Pr oce d ures  ( ± 1 5 mi n utes) 
•  Re c or d A Es  
•  F A C E -Q | Aest hetics Q uesti o n naires  
•  Ma n ual  p u pill o metr y  
•   
 e xter nal p h ot o gra p h y of e y es 
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
7. 2. 7   
H o ur 6 Pr oce d ures  ( ± 1 5 mi n utes) 
•  Re c or d A Es  
•  L P F T  
•   
 e xter nal p h ot o gra p h y of e y es 
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
7. 2. 8   
H o ur 8 Pr oce d ures  ( ± 6 0 mi n utes) 
•  Re c or d A Es  
•  Re c or d c o n c o mita nt me dicati o ns  
•  Vi tal Si g ns  
•  F A C E -Q | Aest hetics Q uesti o n naires  
•  C urre nt c orrecte d V A  
•  B ul bar C o nj u ncti val H y pere mia - ( B H VI) G ra di n g S cale  
•  Sl it la m p e xa mi nati o n a n d e xter nal e ye e x a m  
•  Ma n ual  p u pill o metr y  
•   
 e xter nal p h ot o gra p h y of e y es 
•  I OP  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 2  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
7. 3   
T re at me nt F oll o w -U p P h o ne C all [ Visit 3; D a y 2 t o D a y 5 ] 
•  Re c or d A Es  
•  Re c or d c o n c o mita nt me dicati o ns  
•  Re lease s u bjects fr o m st u d y 
7. 4   
St u d y Wit h dr a w al/ E arl y Ter mi n ati o n  Pr oce d ures  
T he d urati o n of t he treat me nt peri o d i n t his st u d y is 1 da y  wit h assess me nts t o be c o m plete d at  
Baseli ne, H o ur 0  (after I P a d mi nistrati o n), H o ur 0. 5, H o ur 1, H o ur 2, H o ur 4, H o ur 6, a n d H o ur 
8 . 
Wi n d o ws f or t h ese ti me p oi nts are descri be d in  A p pe n di x 1 : Sc he d ule of Visits a n d 
Pr oce d ure s.  
S u bjects w h o wit h dra w fr o m t he st u d y or w h o are ter mi nate d fr o m t he st u d y bef ore t he 
Tele p h o ne F oll o w -U p ( Visit 3) ma y b e releas e d  after A Es a n d c o nc o mita nt me dicati o ns  ha v e 
bee n assess e d . T he reas o n f or earl y wit h dra wal/ ter mi nati o n will be rec or de d i n t he s u bject’s 
C R F.  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 3  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
8  
Q U A LI T Y C O N T R O L A N D A S S U R A N C E  
E ac h cli nical site will perf or m i nter nal q u alit y ma na ge m e nt of st u d y c o n d uct, dat a a n d 
bi ol o gical s peci me n c ollecti o n, d oc u me ntati o n a n d c o m pleti o n . A n i n di vi d ualize d q ualit y 
ma na ge me nt pla n  ma y b e de vel o pe d t o d escri be a site’s q ualit y ma na ge me nt . 
Q ualit y c o ntr ol  ( Q C) p r oce d ures will c o m me nce wit h t he be gi n ni n g of data e ntr y a n d Q C 
c hec ks o n t he data bas e will be ge nerate d  t hr o u g h o ut t he st u d y. A n y missi n g data or data 
a n o malies will be c o m m u nicate d t o t he site(s) f or clarificati o n/res ol uti o n.   
F oll o wi n g writte n Sta n dar d O perati n g Pr oce d ures , t he st u d y m o nit ors will verif y t hat t he 
cli nical st u d y is c o n d uct e d a n d d ata are g e nerate d a n d bi ol o gical s peci me ns are c ollecte d, 
d oc u me nte d (rec or de d), a n d re p orte d i n c o m plia nce wit h t he pr ot oc ol, I nter nati o nal C o u ncil 
f or 
Har m o nisati o n (I C H) 
G o o d 
Cli nical Practice ( G C P), a n d a p plica ble re g ulat or y 
re q uire me nts [e. g., G o o d La b orat or y Practice (G L P ), G o o d Ma n ufact uri n g Practices ( G M P)]. 
T he i n vesti gati o nal site 
will pr o vi de direct access t o all st u d y-relate d sites, s o urce 
data/ d oc u me nts, a n d re p orts f or t he p ur p ose of m o nit ori n g a n d a u diti n g b y t he S p o ns or  or t heir 
desi g nee , a n d i ns pecti o n b y l ocal a n d re g ul at or y a ut h orities. 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 4  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
9  
P L A N N E D S T A TI S TI C A L M E T H O D S  
9. 1   
Ge ner al C o nsi der ati o n s 
C o nti n u o us meas ures will be s u m marize d des cri pti vel y b y t he mea n, sta n dar d de viati o n  ( S D), 
me dia n, mi ni m u m, a n d ma xi m u m val ues. Cate g orical meas ures will be s u m marize d b y t he 
fre q ue n c y a n d p erce nta ge of s u bjects. 
A  se parate Statistical A nal ysis Pla n ( S A P) will be pre p are d bef ore u n mas ki n g of st u d y data. 
A n y a me n d me nts or c h a n ges t o t he pla n ne d a n al yses will be des cri be d i n t he S A P  a n d t he 
la n g ua ge i n t he fi nal S A P will s u perse de t he l a n g ua ge i n t his pr ot oc ol i n t he e ve nt of a 
discre pa n c y . 
In ge n eral, a nal yses will e xa mi ne t he differe nces bet wee n i n di vi d ual treat me nt ar ms , as well 
as t he differe nce s bet wee n c o m bi ne d ar ms of L E V 1 0 2 T o pical Gel  co m pare d t o v e hicle. 
F or all e x pl orat or y efficac y a n al yses a n d all s afet y a nal yses perf or me d, Baseli ne will be 
defi ne d as t he m eas ure me nt o n Da y 1 b ef ore I P a d mi nistrati o n  a n d n ot fr o m a n y pre vi o us  visit . 
If b ot h e y es q ualif y f or t he st u d y, t he e ye wit h t he l o wer M R D 1 v al ue at Baseli ne will be 
desi g nate d as t he st u d y e ye. If M R D 1 v al ues are t he sa me f or  O U at Bas eli ne, t he ri g ht e ye 
will be desi g nat e d as t he st u d y e ye. Re g ar dless of st u d y e ye or st u d y q u alificati o n, all e yes i n 
t his st u d y will recei ve st u d y I P a n d u n d er g o st u d y assess me nts. 
9. 2   
Deter mi n ati o n of S a m ple  Siz e 
T he  sa m ple size of 1 0 s u bjects per ar m  ( 3 0 s u bjects t otal f or a t otal of 6 0 e yes) is n ot base d o n 
f or mal p o wer or precisi o n c o nsi derati o ns . 
9. 3   
A n al ysis P o p ul ati o ns  
T he Safet y A nal ysis Set will i ncl u de all s u bjects w h o  recei v e d at least 1  d ose of I P as i n dicate d 
o n t he d osi n g rec or d. S u bjects will be a n al yze d i n t he gr o u p acc or di n g t o t he I P treat me nt 
recei v e d. All e n d p oi nts will be a n al yze d usi n g t h e Safet y A nal ysis Set a n d o nl y o bser ve d d ata 
will be i ncl u de d . 
9. 4   
De m o gr a p hics a n d B aseli ne C h ar acteristics  
D e m o gra p hic c haracteristics , i ncl u di n g a ge ( years), s e x, race, a n d et h nicit y, will be 
s u m marize d b y treat me nt gr o u p a n d o verall. Me dical hist or y [c o de d usi n g t he m ost rece nt 
versi o n of t h e 
Me dical Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A)], a n d pri or a n d 
c o nc o mita nt me dicati o ns (c o de d usi n g t he m ost rece nt versi o n of t he 
W H O Dr u g) will be 
s u m marize d b y treat me nt gr o u p a n d o verall.  


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 5  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
T he n u m ber of s u bj ects w h o were e nr olle d a n d c o m plete d eac h visit of t he st u d y will be 
pr o vi de d, as well as t he reas o ns f or all e nr oll me nt disc o nti n uati o ns, gr o u pe d b y maj or reas o n 
(e. g., l ost t o f oll o w-u p, a d verse e v e nt, p o or c o m plia nce, res c ue d ue t o lac k of efficac y). A list 
of disc o nti n ue d s u bjects  a n d pr ot oc ol de viati o ns will be pr o vi de d . 
9. 5   
S afet y A n al ysi s 
S afet y a nal ys es will be p erf or me d o n all s u bjects i n t he Safet y A nal ysis Set. T he assess me nt 
of safet y will be bas e d o n t he s u m mar y of oc ular a n d n o n -oc ul ar A Es, c urre nt c orrecte d V A , 
I O P, slit la m p bi o micr osc o p y, oc ular h y pere mia, ma n ual  p u pill o metr y , i n direct dilate d 
o p ht hal m osc o p y, vital si g ns,  a n d uri ne pre g na n c y test . S u m maries will be pr o vi de d b y 
treat me nt gr o u p, a n d f or oc ular assess m e nts se paratel y b y e ye.  
9. 5. 1   
A d verse E ve nts  
A Es will be c o de d usi n g Me d D R A ( m ost c urre nt versi o n) a n d cate g orize d b y s yste m or ga n 
class ( S O C) usi n g preferre d ter ms  ( P T). Se parate s u m maries of A Es rel ate d t o treat me nt a n d 
b y se verit y will be pres e nte d. T he n u m ber of d eat hs a n d S A Es will als o be prese nt e d, a n d 
e ve nts lea di n g t o disc o nti n uati o n fr o m t he st u d y will be liste d a n d ta b ulate d.  
9. 5. 2   
Ot her S afet y E n d p oi nts  
S u m mar y statistics f or o bser ve d data a n d c ha n ges fr o m baseli ne ( w here a p pr o priat e) f or 
c urre nt c orrecte d V A , I O P, ma n ual  p u pill o metr y, vital si g ns, a n d t he c o mf ort  q uesti o n naire  
will be prese nte d. A b n or malities i n slit  la m p bi o micr osc o p y will be s u m marize d b y fre q ue nc y 
a n d perce nta ge.  
9. 5. 3   
Pre g n a nc y  
I n di vi d uals w h o are pre g na nt are n ot per mitte d t o partici pate i n t h e st u d y. All pre g na n cies are 
t o be re p orte d fr o m t he ti me i nf or me d c o nse nt is si g ne d u ntil t he defi ne d f oll o w-u p peri o d.  
If a s u bject bec o mes pre g na nt d uri n g t he st u d y or u p u ntil 3 0 da ys after st u d y c o m pleti o n, t h e 
I nv esti gat or m ust  n otif y  Le vati o n P har ma, Lt d, or t heir p har mac o vi gila nce desi g nee, wit hi n 2 4 
h o urs of lear ni n g its occ urre nce b y  c o m pleti n g a Pre g na nc y R e p ort F or m.  
T he pre g na n c y s h o ul d be f oll o we d u p t o deter mi ne o utc o me, i ncl u di n g s p o nta ne o us or 
v ol u ntar y ter mi nati o n, details of t he birt h, a n d t he prese n ce or a bs e nce of a n y birt h defects, 
c o n ge nital a b n or malities, or mater nal a n d/ or ne w b or n c o m plicati o ns. E ver y eff ort s h o ul d be 
ma de t o gat her i nf or m ati o n re gar di n g t he pre g na n c y o utc o me a n d c o n diti o n of t he i nfa nt. It is 
t he res p o nsi bilit y of t he I n vesti gat or t o o btai n t his i nf or mati o n wit hi n 3 0 cale n dar da ys after 
t he i nitial n otificati o n a n d a p pr o xi matel y 3 0 cal e n dar da ys after deli ver y.  
A n y c o m plicati o ns d uri n g pre g na nc y s h o ul d be rec or de d as a n A E a n d c o m plicati o ns s uc h as 
s p o nta ne o us a b orti o n/ miscarria ge or c o n ge nital a b n or malit y s h o ul d be c o nsi dere d S A Es . A Es 
a n d S A Es  m ust be re p orte d t o Le vati o n P har ma, Lt d, or t heir p har mac o vi gila nce desi g nee, 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 6  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
usi n g t he Seri o us A d verse E ve nt F or m  wit hi n 2 4 h o urs of k n o wle d g e of t h e e ve nt.  N ot e: A n 
electi ve a b orti o n is n ot c o nsi dere d a n S A E.  
9. 6   
E x pl or at or y Effic ac y Assess me nts  
S u m mar y statistics f or o bser ve d d ata , a n d c h a n ge s fr o m b aseli ne ( w here a p pr o priate) f or 
M R D 1 , L P F T , oc ular 
h y pere mia , a n d s u bj ect- a n d I nv esti gat or -re p orte d 
o utc o me 
q uesti o n naires  at p ost -d ose Visit 2 , as well as c ha n ge fr o m H o ur 2  at H o ur 6 f or L P F T will be 
prese nte d. S u bjects ac hie vi n g a n i m pr o ve me nt i n M R D 1  fr o m baseli ne of 1. 0, 1. 5, 2. 0, a n d 2. 5  
m m  will be s u m marize d b y ti me p oi nt.  S u m mar y statistics f or o bser ve d data a n d c ha n ges fr o m 
baseli ne i n F A C E -Q | Aest hetics q uesti o n naires , as well as t he res p o nse rates t o i n di vi d ual 
q uesti o ns , will be prese nt e d . 
9. 7   
T a b ul ati o n of I n di vi d u al S u bject D at a  
All data c ollecte d i n t his st u d y will be prese nte d i n data listi n gs f or all s u bjects.  




Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 8  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 0. 3   
Et hic al C o n d uct of t he St u d y  
T his st u d y  will be c o n d ucte d i n c o m plia nce wit h t he st u d y pr ot oc ol a n d i n acc or da n ce wit h 
G C P, as descri be d i n t he I C H Har m o nize d Tri partite G ui deli ne: G ui deli ne f or G o o d Cli nical 
Practice; t he et hical pri nci ples esta blis he d i n t he 
W orl d 
Me dical Ass ociati o n’s ( W M A) 
D eclarati o n of Helsi n ki; a n d a p plica ble l ocal re g ulati o ns . 
1 0. 4   
S u bject I nf or m ati o n a n d C o nse nt  
Inf or me d c o nse nt is a pr ocess t hat is i nitiate d bef ore s u bjects a gree t o partici pate i n a st u d y, 
a n d t he i nf or me d c o ns e nt pr ocess c o nti n ues t hr o u g h o ut s u bjects’ st u d y partici pati o n. C o nse nt 
f or ms will be a p pr o ve d b y t he I nstit uti o nal Re vie w B oar d (I R B) a n d s u bjects will be as ke d t o 
rea d a n d re vi e w t he d o c u me nt. B ef ore a n y st u d y-s pecific pr oce d ures are perf or me d, t h e 
I n v esti gat or ( or desi g nee) will pr o vi de s u bjects t he I C F a n d e x plai n t he res earc h st u d y t o t he 
s u bject a n d a ns wer a n y q uesti o ns t hat ma y arise. A ver bal e x pla nati o n will be pr o vi de d i n 
ter ms s uite d t o t he s u bjects’ c o m pre he nsi o n of t he p ur p oses, pr oce d ures, a n d p ote ntial ris ks of 
t he st u d y a n d of t heir ri g hts as res earc h s u bjects. S u bjects will ha ve t h e o p p ort u nit y t o caref ull y 
re vie w t h e writte n c o nse nt f or m a n d as k q uesti o ns bef ore si g ni n g it. T he s u bjects s h o ul d ha ve 
t he o p p ort u nit y t o disc uss t he st u d y wit h t heir fa mil y or s urr o g ates or t hi n k a b o ut it b ef ore 
a greei n g t o partici pate  i n t he st u d y. T he s u bject will si g n a n d d ate the I C F a n d  pr o vi d e HI P A A 
a ut h orizati o n  bef ore a n y st u d y -s pecific pr oce d ures are d o ne.  S u bjects will recei ve a c o p y of 
t he f ull y si g ne d a n d date d I C F. 
T he I n v esti gat or ( or desi g nee) will e x plai n t o s u bjects t hat t he y are c o m pletel y free t o ref use 
t o e nter t he st u d y or t o wit h dra w fr o m t he st u d y at a n y ti me, wit h o ut gi vi n g a reas o n . Si milarl y, 
t he I n vesti gat or a n d S p o ns or will be f ree t o wit h dra w s u bjects at a n y ti me f or safet y or 
a d mi nistrati ve reas o ns. Ot her re q uire me nts necess ar y f or t he pr otecti o n of t he h u ma n ri g hts of 
s u bjects will als o be e x plai ne d acc or di n g t o c urre nt I C H G C P g ui deli n es a n d t he W M A 
D eclarati o n of Helsi n ki i n its re vise d e diti o n. T h e c o nte nt of t h e I C F will a d here t o  U. S. A. 
F D A r e g ulati o ns a n d I C H g ui deli nes . Once t he I n v esti gat or ( or desi g nee)  is ass ure d t hat 
s u bjects u n dersta n d  t he i m plicati o ns of st u d y partici pati o n, s u bjects will pr o vi de writte n 
i nf or me d c o nse nt t o partici pate i n t he st u d y . 
1 0. 5   
S u bject C o nfi de nti alit y  
S u bject c o nfi de ntialit y a n d pri vac y will be strictl y hel d i n tr ust b y t he partici pati n g 
I n v esti gat ors, t heir staff, a n d t he S p o ns or(s) a n d t heir i nter ve nti o ns. T his c o nfi de ntialit y will 
be e xte n de d t o c o ver testi n g of bi ol o gical s a m ples a n d g e netic tests i n a d diti o n t o t he cli nical 
i nf or mati o n relati n g t o s u bjects. T heref ore, t he st u d y pr ot oc ol, d oc u me ntati o n, data, a n d all 
ot her i nf or mati o n ge nerate d will be hel d i n strict c o nfi de nce.  N o i nf or mati o n c o ncer ni n g t he 
st u d y or t he data will be release d t o a n y u na ut h ori ze d t hir d part y wit h o ut pri or writte n a p pr o val 
of t he S p o ns or.   


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 4 9  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
All researc h acti vities will be c o n d ucte d i n as pri v ate a setti n g as p ossi ble.   
T he st u d y s u bjects’ c o nt act i nf or mati o n will be sec urel y st ore d at eac h cli nical site f or i nter nal 
use d uri n g t he st u d y.  At t he e n d of t he st u d y, all rec or ds will c o nti n ue t o be ke pt i n a sec ure 
l ocati o n f or as l o n g a p eri o d as dict ate d b y t he re vi e wi n g I R B, I nstit uti o nal p olicies, or S p o ns or 
re q uire me nts.  
St u d y s u bject researc h data, w hic h is f or p ur p oses of statistical a nal ysis a n d scie ntific 
re p orti n g, will be tra ns mitte d t o a n d st ore d at Le xitas P har ma Ser vices, I nc . This will n ot 
i ncl u de t he s u bjects’ c o ntact i nf or mati o n or i de ntif yi n g i nf or mati o n. Rat her, i n di vi d ual 
s u bjects a n d t heir researc h data will be i de ntifie d b y a u ni q ue st u d y i de ntificati o n n u m ber.  T he 
st u d y data e ntr y a n d st u d y ma na ge me nt s yste ms use d b y cli nical sites a n d b y Le xitas P har ma 
Ser vices, I n c. staff will b e sec ure d a n d pass w or d pr otecte d. At t h e e n d of t he st u d y, all st u d y 
data bases will be d e -i de ntifie d a n d arc hi ve d at Le xitas P har ma Ser vices, I n c.  
1 0. 6   
St u d y M o nit ori n g  
L e xitas P har ma Ser vices, I n c . will c o n d u ct t he cli nical m o nit ori n g f or t his st u d y. A cli nical 
m o nit ori n g p la n will be use d  a n d will descri be i n detail w h o will c o n d uct t he m o nit ori n g, at 
w hat fre q ue nc y m o nit ori n g will be d o ne, at w hat le vel of d etail m o nit ori n g will be perf or me d, 
a n d t he distri b uti o n of m o nit ori n g re p orts . 
1 0. 7   
C ase R e p ort F or ms a n d St u d y Rec or ds  
D ata c ollecti o n is t he res p o nsi bilit y of t he cli nical st u d y staff at t he site u n der t he s u per visi o n 
of t he site’s I n v esti gat or . The I n vesti gat or is res p o nsi ble f or ens uri n g t he acc urac y, 
c o m plete ness, le gi bilit y, a n d ti meli ness of t he data re p orte d.   
A ll s o urce d oc u me nts s h o ul d be c o m plete d i n a neat, le gi ble ma n ner t o ens ure acc urate 
i nter pretati o n of dat a. 
C o pies of t he st u d y visit w or ks heets will be pr o vi de d f or use as s o urce d oc u me nt w or ks heets 
f or rec or di n g data f or eac h s u bject e nr olle d i n t he st u d y. Data rec or de d i n t he  e C R F deri ve d 
fr o m s o urce d o c u me nts s h o ul d be c o nsiste nt wit h t he data rec or de d o n t he s o urce d oc u m e nts.  
C li nical data (i ncl u di n g A Es, c o nc o mita nt me dicati o ns, a n d e x pecte d a d v erse reacti o ns dat a) 
a n d a n y cli nical la b orat or y data will be e nt ere d i nt o  IB M Cli nical, a  2 1 C F R Part 1 1 -c o m plia nt 
data ca pt ure s yste m pr o vi de d b y Le xitas P har ma Ser vices, I nc. T he d ata s yste m i ncl u des 
pass w or d pr otecti o n a n d i nter nal q ualit y c hec ks, s uc h as a ut o matic ra n ge c hec ks, t o i de ntif y 
data t hat a p pear i nc o nsiste nt, i nc o m plete, or i nacc urate. Cli nical data will be e ntere d directl y 
fr o m t he s o urce d oc u me nts. 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 0  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 0. 8   
St u d y Rec or ds Rete nti o n  
St u d y d oc u me nts s h o ul d be retai ne d f or a mi ni m u m of 2 years after t he last a p pr o val of a 
mar keti n g a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o pe n di n g or c o nte m plate d 
mar keti n g a p plicati o ns i n a n I C H re gi o n or u ntil at least 2 years ha ve ela pse d si nce t he f or mal 
disc o nti n uati o n of cli nical de vel o p me nt of t he st u d y i nter ve nti o n. T hese d o c u me nts s h o ul d be 
retai ne d f or a l o n ger peri o d, h o we ver, if re q uire d b y l ocal re g ulati o ns. N o rec or ds will be 
destr o ye d wit h o ut t he writte n c o nse nt of t he S p o ns or, if  a p plica ble. It is t h e res p o nsi bilit y of 
t he S p o ns or t o i nf or m t he I n v esti gat or w he n t hese d oc u me nts n o l o n ger nee d t o be retai ne d. 
1 0. 9   
Pr ot oc ol D e vi ati o ns  
A pr ot oc ol de vi ati o n is a n y n o nc o m plia nce wit h t he cli nical trial pr ot oc ol, I C H G C P, or 
Ma n ual of Pr oce d ures re q uire me nts. T he n o n c o m plia nce ma y be eit her o n t he p art of t he 
s u bject, t he I n v esti gat or, or t he st u d y site staff. As a res ult of pr ot oc ol d e viati o ns, c orrecti ve 
acti o ns are t o b e de vel o p e d b y t he site a n d i m ple me nte d pr o m ptl y.   
T hese practices are c o nsiste nt wit h I C H G C P:  
4. 5 C o m plia nce wit h Pr ot oc ol, secti o ns 4. 5. 1, 4. 5. 2, a n d 4. 5. 3  
5. 1 Q ualit y Ass ura nce a n d Q ualit y C o ntr ol, secti o n 5. 1. 1  
5. 2 0 N o nc o m plia nce, secti o ns 5. 2 0. 1, a n d 5. 2 0. 2.  
It is t he res p o nsi bilit y of t he site’s I n vesti gat or t o use c o nti n u o us vi gila nce t o i de ntif y a n d 
re p ort pr ot o c ol de viati o ns. All pr ot oc ol d e viati o ns m ust be a d dresse d i n st u d y s o urce 
d oc u me nts  a n d re p orte d t o t he S p o ns or a n d r e vie wi n g I R B per t heir p olicies.  T he site 
In v esti gat or is res p o nsi ble f or k n o wi n g a n d a d heri n g t o t he re vie wi n g I R B re q uire me nts . 
1 0. 1 0   
Access t o S o urce D oc u me nt ati o n  
T he St u d y M o nit or, ot her a ut h orize d re pres e ntati ves of t he S p o ns or, re prese ntati ves of t he I R B, 
re g ulat or y a g e ncies or p h ar mace utical c o m pa n y s u p pl yi n g st u d y pr o d uct will be a ble t o i ns pect 
all d oc u me nts a n d rec or ds re q uire d t o b e mai ntai ne d b y t he I n v esti gat or, i ncl u di n g b ut n ot 
li mite d t o, me dical rec or ds (i.e., office, cli nic, or h os pital) a n d p h ar mac y rec or ds f or t he 
s u bjects i n t his st u d y. T he cli nical st u d y site will per mit access t o s uc h rec or ds.  Data a n d st u d y 
i nte grit y will be mai ntai ne d b y li miti ng access t o u n mas ke d data.  
1 0. 1 1   
P u blic ati o n P olic y  
T his st u d y will c o m pl y wit h t he Cli nical Trials Re gistrati o n a n d Res ults I nf or m ati o n 
S u b missi o n r ule. As s uc h, t his trial will be re gistere d at Cli nical Trials. g o v, a n d res ults 
i nf or mati o n fr o m t his trial will be s u b mitte d t o Cli nical Trials. g o v. I n a d diti o n, e ver y atte m pt 
will be ma de t o p u blis h res ults i n peer -re vie we d j o ur nals. T he i nstit uti o n a n d I n vesti gat ors 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 1  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
partici pati n g i n t his trial s hall ha ve n o ri g ht t o p u blis h or prese nt t he res ults of t his st u d y 
wit h o ut t he pri or writte n c o nse nt of t he S p o ns or . 


Le vati o n P har ma Lt d.  
 
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 2  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 1   
R E F E R E N C E LI S T  
B ac harac h J, L ee 
W W, Harris o n A R, Fre d d o T F. A re vie w of ac q uire d ble p har o pt osis: 
pre vale nce, dia g n osis, a n d c urre nt treat me nt o pti o ns. Eye ( L o n d) 2 0 2 1; 3 5  ( 9): 2 4 6 8-2 4 8 1.  
F o o d a n d Dr u g A d mi nistrati o n ( F D A), De part me nt of Healt h a n d H u ma n Ser vices. C ol d, 
C o u g h, Aller g y, Br o nc h o dilat or, a n d A ntiast h matic Dr u g Pr o d ucts f or O ver -t he-C o u nter 
H u ma n Use; Fi nal M o n o gra p h f or O T C Nas al Dec o n gesta nt Dr u g Pr o d ucts. Fe deral Re gister, 
1 9 9 4; 5 9( 1 6 2): 4 3 3 8 6.  
H o S F, 
M ora ws ki A, S a m pat h R, B ur ns J. 
M o difie d vis ual fiel d test f or pt osis s ur ger y 
( Leicester Peri p heral Fi el d Test). Eye ( L o n d)  2 0 1 1; 2 5( 3): 3 6 5 -3 6 9.  
K ua n g A W, D u B ois J, Attar M, A hl u walia G. Cli nical p har mac o ki netics of o x y metaz oli ne 
crea m f oll o wi n g t o pical facial a d mi nistrati o n f or t he treat me nt of er yt he m a ass ociate d wit h 
r osacea. J Dr u gs Der m at ol . 2 0 1 8; 1 7( 2): 2 1 3-2 2 0.  
R h ofa de ® Pac k a ge I ns ert, 2 0 1 7.  
Sl o ni m C B, F oster S, Jar os M, Ka n narr S R, K ore nfel d M S, S m yt h -Me di na R, et al. Ass o ciati o n 
of O x y metaz oli ne H y dr oc hl ori de, 0. 1 %, S ol uti o n A d mi nistrati o n 
Wit h Vis ual Fiel d i n 
Ac q uire d Pt osis: A P o ole d A nal ysis of 2 Ra n d o mize d Cli nical Tri als. J A M A O p ht h al m ol o gy . 
2 0 2 0; 1 3 8( 1 1): 1 1 6 8 -7 5.  
U p nee q ® Pac k a ge I ns ert, 2 0 2 1.  
W oitac h A S. F o o d a n d Dr u g A d mi nistrati o n ( F D A), Ce nter f or Dr u g E val uati o n a n d Researc h . 
C li nical Re vie w: N D A 2 0 8 5 5 2, R h ofa de ( o x y metaz oli ne) Crea m, 1. 0 % . 2 0 1 6. Refere nce I D: 
4 0 3 9 4 7 2 . 
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 3  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2   
A P P E N D I C E S 
1 2. 1   
A p pe n di x 1 : Sc he d ule of Visits a n d Pr oce d ures 
D a ys/ Wee k s 
Scree ni n g  
( D a y -4 5 t o 
D a y -7 )  
B aseli ne/ R a n d o miz ati o n/ D a y 1  
D a y 2 -5 
( Tele p h o ne 
F oll o w -U p)  
Visit  
1  
2  
3  
Ti m e ( H o urs)  
---  
B aseli ne 1 
H o ur 0  
(I P 
D osi n g)  
0. 5 h o ur  
( ± 1 0 
mi n utes)  
1 h o ur  
( ± 1 5 
mi n utes)  
2 h o urs  
( ± 1 5 
mi n utes)  
4 h o urs  
( ± 1 5 
mi n utes)  
6 h o urs  
( ± 1 5 
mi n utes)  
8 h o urs  
( ± 6 0 
mi n utes)  
 
I nf or me d c o nse nt 
X  
  
  
  
  
  
  
  
 
 
I ncl usi o n/ E x cl usi o n 
criteria  
X   
X  
  
  
  
  
  
  
 
 
Ra n d o mizati o n  
 
 
X 2  
  
  
  
  
  
 
 
IP a d mi nistrati o n O U   
 
  
X 2  
  
  
  
  
  
 
 
De m o gra p hics  
X  
  
  
  
  
  
  
  
 
 
Me dical/ Oc ular/ S ur gical 
hist or y  
X   
X   
  
  
  
  
  
  
 
 
Vital si g ns 3 
X   
X   
  
  
X   
  
  
  
X   
 
Uri ne pre g na nc y test 4  
X   
X   
  
  
  
  
  
  
 
 
C urre nt c orrecte d V A   
X   
X   
  
  
  
  
  
  
X   
 
I O P 
X   
X   
  
  
X   
  
  
  
X   
 
Leicester Peri p heral 
Fiel d Test  
X   
X   
  
  
  
X   
  
X   
 
 
Le vat or f u ncti o n  
X  
  
  
  
  
  
  
  
 
 
 
N ote : A ll o p ht hal mic assess me nts m ust be c o n d ucte d o n b ot h e yes at eac h ti me p oi nt. 
1 Baseli ne assess me nts are t o be perf or me d o n Da y 1 bef ore t he a p plicati o n of IP b y t he st u d y staff. 
2 St u d y -eli gi ble s u bjects o nl y . 
3 Vital si g ns will i ncl u de resti n g heart rate a n d sitti n g bl o o d press ure.  
4 W o me n of c hil d -beari n g p ote ntial o nl y; uri ne pre g na nc y test  


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 4  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
D a ys/ Wee k s 
Scree ni n g  
( D a y -4 5 t o 
D a y -7 )  
B aseli ne/ R a n d o miz ati o n/ D a y 1  
D a y 2 -5 
( Tele p h o ne 
F oll o w -U p)  
Visit  
1  
2  
3  
Ti m e ( H o urs)  
---  
B aseli ne 1 
H o ur 0  
(I P 
D osi n g)  
0. 5 h o ur  
( ± 1 0 
mi n utes)  
1 h o ur  
( ± 1 5 
mi n utes)  
2 h o urs  
( ± 1 5 
mi n utes)  
4 h o urs  
( ± 1 5 
mi n utes)  
6 h o urs  
( ± 1 5 
mi n utes)  
8 h o urs  
( ± 6 0 
mi n utes)  
 
F A C E -Q | Aest hetics 
q uesti o n naires  
X   
X   
  
  
  
  
X   
  
X   
 
B H VI  assess me nt  
X   
X   
  
X   
X   
X   
X   
X   
X   
 
 e xter nal 
p h ot o gra p h y of e yes 5 , 6  
X   
X   
  
X   
X   
X   
X   
X   
X   
 
Ma n ual  p u pill o metr y   
X   
X   
  
  
X   
  
X   
  
X   
 
I P c o mf ort assess me nt  
 
  
  
  
X   
  
  
  
 
 
A d mi nistrati o n of 1 dr o p 
of o x y metaz oli ne  O U or 
p he n yle p hri ne  O U  
X  
  
  
  
  
  
  
  
 
 
Slit la m p e xa mi nati o n 
a n d e xter nal e ye e xa m 
X   
X   
  
  
  
  
  
  
X   
 
I n direct dilate d 
o p ht hal m osc o p y  
X  
  
  
  
  
  
  
  
 
 
A E assess me nt  
 
  
X   
X   
X   
X   
X   
X   
X   
X  
Rec or d c o nc o mita nt 
me dicati o ns  
X   
X   
  
  
  
  
  
  
X   
X  
E xit st u d y  
 
  
  
  
  
  
  
  
  
X  
 
5 T o i ncl u de M R D 1 a n d i nter pal pe bral dista nce meas ure me nts b y ce ntral rea di n g ce nter. O nl y M R D 1  val ues at Scree ni n g will be use d f or  deter mi ni n g st u d y 
eli gi bilit y. M R D 1 val ues at Baseli ne will be use d f or assessi n g efficac y . 
6 P h ot o gra p h y will be ta ke n of s u bjects’ e yes d uri n g t he Scree ni n g visit: 1.) Bef ore t he i nstillati o n of o x y metaz oli ne  O U or p he n yle p hri ne  O U a n d 2.) 
A p pr o xi matel y 1 2 0 ( ± 3 0)  mi n utes after t he a d mi nistrati o n of e ye dr o ps. O nl y res p o n ders as defi ne d i n  A p pe n di x 7 :  
E xter nal P h ot o gra p h y  w ill be 
eli gi ble f or c o nti n uati o n i n t he st u d y.  


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 5  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 2   
A p pe n di x 2: C urre nt C orrecte d Vis u al Ac uit y  
N ote: Vis ual ac uit y ( V A) testi n g  m ust p rece de a n y e xa mi nati o n re q uiri n g c o ntact wit h t he e ye or 
e yeli d a n d m ust  prece de p u pil dilati o n, i nstillati o n of st u d y d yes, e xter n al p h ot o gra p h y of t h e e y es, 
or a p plicati o n of t o pical gels as detaile d i n t he or d er of ass ess me nts f or t he pr ot oc ol.  
D ista nce V A will be ass esse d O U w it h an  E T D R S c hart  at a 4-meter dista nce  usi n g a L o g M A R 
scale. Dista n ce V A s h o ul d be assesse d c o nsiste ntl y t hr o u g h o ut t he st u d y usi n g t he sa me met h o d, 
e q ui p me nt, a n d li g hti n g c o n diti o ns at eac h site. C urre nt c orrecte d V A testi n g will be perf or me d 
usi n g s u bjects ’ o w n prescri pti o n e ye glasses, if a p plica ble ; s u bjects w h o d o n ot ac hie ve a +0. 0 
L o g M A R sc ore usi n g t heir prescri pti o n e ye glass es , if a p plica ble, will be as ke d t o ma ke t heir best 
eff ort w hile vie wi n g t he E T D R S c hart t hr o u g h a p i n h ole occl u der. 
S u bjects will be i nstr uct e d t o rea d t he letters o n t he E T D R S c hart f r o m t he t o p left-h a n d c or ner 
al o n g eac h r o w, o n e letter at a ti me t h e n d o w n eac h r o w, o n e at a ti me . T here are no n u m bers o n 
t he c hart, o nl y letters. If a s u bject rea ds a n u m ber, t he e xa mi ner s h o ul d re mi n d t he s u bject t hat the 
c hart c o nt ai ns n o n u m bers, a n d t he e x a mi ner s h o ul d t he n re q u est a letter i nstea d of a n u m ber  fr o m 
t he s u bject. S u bjects s h o ul d be e nc o ura ge d t o g uess if a letter a p pears u n clear. If a s u bject i de ntifies 
a letter as 1 of 2 p ossi ble letters, t he e xa mi ner s h o ul d as k t he s u bject t o pic k 1 letter o nl y.  
S u bjects will be i nstr ucte d t o r ea d sl o wl y at a rate of a b o ut 1 letter/s ec o n d. If at a n y p oi nt t he 
s u bject rea ds t o o q uic kl y,  t he e xa mi ner s h o ul d st o p t he s u bject a n d re mi n d t he s u bject t o rea d 
sl o wl y i n or der t o ac hie ve t he best i de ntificati o n of eac h letter. If a su bject l oses  t heir place me nt 
i n t he c hart, t he e xa mi ner s h o ul d as k t he s u bject t o g o bac k t o t he li ne w here t h e place was l ost.  
T he s u bject s h o ul d n ot p r ocee d t o t he ne xt letter u ntil t he y ha ve gi ve n a defi nite res p o nse. If a 
s u bject c ha n g es a res p o nse bef ore m o vi n g o n t o t he ne xt letter, t he e x a mi ner m ust acce pt t he 
c ha n ge.  
A t t he en d of t h e test, t he e xa mi ner will co u nt t he n u m ber of letters i nc orrectl y i de ntifie d  u p t o a n d 
i ncl u di n g t he last li ne rea d an d will rec or d t he res ults o n t he s o urce d o c u me nt. A V A letter sc ore 
will be calc ulate d a n d rec or de d i n t he S o urce D oc u me nt W or ks heets a n d i n t he e C R F. 
Eac h letter has a sc ore val ue of 0. 0 2 l o g u nits. Si nce t here are 5 letters per li ne, t he t otal sc ore f or 
a li ne o n t he L o g M A R c hart re pres e nts a c ha n ge of 0. 1 l o g u nits. T he f or m ula use d i n calc ulati n g 
t he sc ore is: 
C alc ul ati o ns : L o g M A R V A = Baseli ne val ue + ( n X 0. 0 2)   
w here:   
t he baseli ne val ue is t he L o g M A R n u m ber of t he l ast li ne rea d (at least 1 letter rea d 
c orrectl y i n t his li ne), a n d  
“ n” is t he t otal n u m ber of letters misse d u p t o a n d i ncl u di n g t he last li ne rea d, a n d  
“ 0. 0 2” is t he val ue f or eac h letter  




L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 7  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 4   
A p pe n di x 4 : I ntr a oc ul ar Press ure (I O P) 
IO P will be meas ure d i n m m H g a n d s h o ul d be c o n d ucte d after t h e slit la m p bi o micr osc o p y e x a m 
is c o m plete d a n d bef ore d ilati o n of s u bjects’ e yes.  
IO P meas ure m e nts will be perf or me d utilizi n g i Care or a n ot her t o n o met er t hat d oes n ot re q uire 
t he use of c ol ore d d y es or l ocal a n est hetic, a n d t hat d oes n ot e m pl o y a n air p uff t o meas ure I O P . 
T he sa me met h o d s h o ul d be use d c o nsiste ntl y f or t h e sa m e s u bject f or all visits a n d I O P 
assess me nts. M eas ure me nts will be ta ke n wit h t he s u bject seate d . T w o c o ns ec uti ve meas ure me nts 
will be ta ke n i n eac h e ye  a n d rec or de d i n t he s o urce d oc u me nt. T he mea n of t he t w o meas ure me nts 
will be a ut o maticall y calc ulate d i n E D C. I f t he t w o meas ure me nts differ b y > 1. 0 m m H g, a t hir d 
meas ure me nt will be ta ke n a n d r ec or de d i n t he s o urce d o c u me nt. T he me dia n of t he t hree sc ores 
will t he n be a ut o maticall y calc ulate d i n E D C . 
  
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 8  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 5   
A p pe n di x 5 : Leicester Peri p her al Fiel d Test ( L P F T)  
 
T he L P F T is a c ust o mize d vis ual fiel d test desi g ne d t o assess pt osis ( H o et al., 2 0 1 1 ). 
T he L P F T will be c o n d u cte d usi n g a H u m p hre y Vis ual Fiel d A nal yzer . C li nical st u d y staff will 
i nstr uct s u bjects t o kee p t heir c hi n a n d f ore hea d a g ai nst t he c hi n a n d f ore h ea d rests, a n d t o e ns ure 
t hat t heir facial feat ur es re mai n f ull y rela xe d d uri n g t he assess me nt. S u bjects will be i nstr ucte d t o 
l o o k at t he ce nter of t he fi xati o n tar get t hr o u g h o ut t he test. C orrecti ve le nses are n ot necessar y wit h 
t he LP F T . 
T he L P F T will be sc ore d base d o n a n eli gi bilit y sc ore a n d a t otal s c ore.  
L P F T Eli gi bilit y Sc ore  = T he t otal n u m ber of p oi nts misse d i n t he t o p 2 r o ws o n t he L P F T  
( mi ni m u m 0; ma xi m u m 1 7) 
L P F T T ot al Sc ore  = T he t otal n u m ber of p oi nts see n i n t he t o p 4 r o ws o n t he L P F T  ( mi ni m u m 0; 
ma xi m u m 3 5 ) 
L P F T assess me nts will be perf or m e d i n b ot h e yes se paratel y. Thirt y -fi ve p oi nts are teste d i n t he 
s u peri or fiel d w hile 1 4 p oi nts are i ncl u de d i n t he i nferi or fiel d . T he i nferi or fiel d test ser ves as a 
refere nce b ut s h o ul d n ot be use d f or t h e a nal ysis. 
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 5 9  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 6   
A p pe n di x 6 : F A C E -Q | Aest hetics Q uesti o n n aire s  
T he F A C E -Q © is a s u bj ect -re p orte d o ut c o me meas ure t h at ca n be use d t o meas ure o utc o mes of 
facial pr oce d ures a n d pr o d ucts fr o m t he s u bject’s pers pecti ve. T his i nstr u me nt has bee n use d t o 
e val uate t he s afet y a n d effecti ve ness of faci al aest hetic treat me nts i n  n u mer o us cli nical trial 
setti n gs a n d t o i nf or m patie nt care i n cli nical practice. T he F A C E -Q © is c o m p ose d of a s et of 3 9 
i n de pe n de ntl y f u ncti o ni n g scales/c hec klists t hat 
meas ure 3 o verarc hi n g d o mai ns: Facial 
A p peara nce, Healt h -Relate d Q ualit y of Life, a n d A d verse Effects. F or t he p ur p oses of  t his st u d y a 
m o d ular a p pr oac h will be use d  wit h t he m o d ules liste d bel o w . 
T he differe nt q uesti o n naire  m o d ules will be p rese nte d se paratel y, a n d su bjects will n ot ha ve access 
t o t he q uesti o n naires t he y c o m plete d at pre vi o us cli nic visits or at pre vi o us ti me p oi nts . 
F A C E -Q | Aest hetics © Sc ales  ( M o d ul ar A p pr o ac h) 
1.  Satisfacti o n wit h E yes  ( 7 ite ms) 
2.  A p praisal of U p p er E y eli ds  ( 7 ite ms) 
3.  A p praisal of L o wer E y eli ds  ( 7 ite ms) 
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 0  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 7   
A p pe n di x 7 :  
E xter n al P h ot o gr a p h y  
S u bjects will ha ve e xter nal p h ot o gra p hs ta ke n of b ot h e yes via   
 p h ot o gra p h y f or M R D 1 
meas ure me nts  a n d inter pal pe bral dista nce meas ure me nts  b y a  ce ntral rea di n g ce nter at t he 
Scree ni n g visit b ot h bef ore a n d a p pr o xi mat el y  1 2 0 ( ± 3 0)  m i n utes after i nstillati o n of 1 dr o p of 
si n gle-mas ke d o x y metaz oli ne  i n eac h e ye. (N ote : U p nee q ® is preferre d b ut p he n yle p hri ne 2. 5 % 
o p ht hal mic s ol uti o n ma y be use d if U p nee q ® is n ot a vaila ble i n a ti mel y ma n ner .) S u bjects 
weari n g ma ke u p d uri n g t he Scree ni n g visit s h o ul d re m o ve t he ma ke u p o n -site bef ore i ma ge 
ca pt ure. 
T he s u bjects will be as ke d t o mai ntai n a ne utral e x pressi o n t o e ns ure t h at t heir facial feat ures 
re mai n f ull y rel a xe d f or all i ma ge assess me nts. A ce ntral rea di n g ce nter will re vie w t he i ma ges 
ca pt ure d d uri n g t he Scree ni n g visit t o deter mi ne st u d y eli gi bilit y . O nl y s u bjects w h o de m o nstrate 
a p ositi ve s hift i n u p per e yeli d el e vati o n  ( M R D 1) ≥0. 5 m m  i n res p o ns e t o a si n gle dr o p of 
o x y metaz oli ne  o p ht hal mic s ol uti o n or p he n yle p hri ne  o p ht hal mic s ol uti o n will be eli gi ble f or st u d y 
partici pati o n . 
T hr o u g h o ut t he da y of Visit 2 ( Baseli ne; Ra n d o mizati o n; Da y 1; Treat me nt Peri o d), s u bjects will 
ha ve a d diti o nal e xter nal p h ot o gra p hs ta ke n of t heir e yes at Baseli ne (bef ore IP a d mi nistrati o n), 
H o ur 0. 5, H o ur 1, H o ur 2, H o ur 4, H o ur 6, a n d H o ur 8 . 
 
 
 
 
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 1  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 8   
A p pe n di x 8 : I n vesti g at or-Re p orte d O utc o mes  
A fter t he last s u bject h as c o m plete d t h e st u d y, Pri nci pal In vesti gat or s will re vie w b atc he d 
m as ke d/a n o n y mize d   
p h ot o gra p hs of all s u bjects’ e yes as d oc u me nte d at B aseli ne, H o ur 
4 , a n d H o ur 8. 
 p h ot o gra p hs will be pr o vi de d t o t he Pri nci pal In vesti gat ors i n a ra n d o m ma n ner a n d 
s h o ul d n ot be or ga nize d b y site, s u bject, or ti me p oi nt . Eac h In vesti g at or will assess t he 
p h ot o gra p hs bas e d o n  t h eir s u bjecti ve i m pressi o n of v ari o us para meters of s u bjects’ e yes , u p p er 
e yeli ds, an d l o wer e yeli d s. 
A d diti o nal details  f or t his In vesti gat or -re p orte d assess me nt ma y be f o u n d i n t he 
M a n ual of 
Pr oce d ures . 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 2  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 9   
A p pe n di x 9 : M a n u al  P u pill o metr y  
T he p u pil size will be meas ure d i n a m bie nt r o o m li g ht . The s u bject s h o ul d be as ke d t o f oc us 
strai g ht a hea d o n a tar get at a dista nce t o a v oi d acc o m m o dati o n w hile seate d i n t he e xa m c hair. 
T he s u bject s h o ul d be i nstr ucte d n ot t o bli n k d uri n g t he meas ure me nt. T he I n vesti gat or s h o ul d t he n 
ta ke t he p u pil meas ure m e nt car d a n d place it directl y bel o w t he p u pil w hile a v oi di n g t he li ne of 
si g ht, a gai n t o a v oi d sti m ulati n g acc o m m o dati o n. T he I n vesti gat or s h o ul d t he n matc h t he p u pil 
size t o t he cir cle size o n t he car d t o deter mi ne t he p u pil size. After a brief rest peri o d, t he pr ocess 
s h o ul d be re p eate d t o m eas ure p u pil dia meter i n t he fell o w e ye. Eac h m eas ure m e nt s h o ul d be 
rec or de d i n t he e C R F. 
If s u bjects’ e yes b ec o m e dr y d uri n g t h e assess me nt, artificial tears ma y be a d mi nistere d a n d 
rec or de d as c o n c o mita nt me dicati o n . 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 3  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 0   
A p pe n di x 1 0 : Le v at or P al pe br ae S u peri oris F u ncti o n  
L e vat or p al pe brae s u peri oris  f u ncti o n of eac h s u bject will be assesse d b y I n vesti gat ors at t he 
Scree ni n g visit. I n v esti gat ors will place a si n gle fi n ger fir ml y o n t he s u bject’s br o w t o is olate t he 
le vat or m uscle an d n e gat e t he mec h a nical acti vit y of t he fr o ntalis m uscle . 
T he s u bject will be i nstr ucte d t o g aze d o w n war d . I n vesti gat ors will place a r uler at t h e u p per e yeli d 
mar gi n a n d i nstr uct s u bjects t o s hift t heir g aze fr o m stari n g d o w n war d t o stari n g up war d . T he ne w 
p ositi o n of t he u p per e ye li d will be n ote d a n d t he differe n ce b et wee n t he t w o meas ure me nts will 
be rec or de d as t he le v at or pal pe brae s u peri oris f u ncti o n . N or mal le vat or f u ncti o n is t y picall y 1 3 -
1 7 m m .


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 4  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 1   
A p pe n di x 1 1 : Slit L a m p Bi o micr osc o p y 
T he slit la m p bi o micr osc o p y e xa m s h o ul d be perf or me d wit h t he slit la m p usi n g a bea m wi dt h a n d 
i nte nsit y t hat pr o vi des o pti mal e val uati o n of t he a nteri or s e g me nt. T he slit la m p e xa m s h o ul d be 
perf or me d wit h o ut  fl u orescei n. 
T he slit la m p e xa mi nati o n m ust be perf or me d bef ore a n y pr oce d ures t hat w o ul d re q uire c o ntact 
wit h t he e ye or e yeli ds a n d pri or t o t he i nstillati o n of a n y dilati n g e ye dr o ps or t o pical gels. T he 
I n v esti gat or s h o ul d use t heir sta n dar d e xa mi nati o n tec h ni q ue. This pr oce d ure will be perf or me d i n 
t he sa me ma n ner f or all s u bjects o bser ve d at t he I n vesti gat or’s site. W h e n p ossi ble, t he sa me 
e xa mi ner s h o ul d c o n d uct all slit la m p bi o micr osc o p y e xa mi nati o ns at eac h visit f or a gi ve n s u bject 
t hr o u g h o ut t he st u d y. 
T he  I n vesti gat or must e x a mi ne t he e y eli ds, c o nj u ncti va, c or nea, a nteri or c ha m ber, iris/ p u pil, a n d 
t he le ns of eac h e ye f or e vi de nce of er yt he m a a n d/ or e d e ma, o pacities or ot her si g ns of 
a b n or malities a n d rec or d a gra di n g f or eac h tiss ue/str uct ure as s pecifie d b el o w. O bser va ti o ns will 
be d oc u me nte d o n t he a p pr o priate C R F.  
T he f oll o wi n g as pects of t he e ye will be e v al uate d, a n d c orres p o n di n g data c ollecte d.  
C or ne a:    
I n cl u des all c or neal la y ers 
N or m al:   
A bse nce of acti ve i nfl a m mati o n, i nfecti o n, or str u ct ural c ha n g es/a b n or malities  
A b n or m al:  Prese nce of acti ve i nfla m mati o n, i nfecti o n, or str u ct ural c ha n g es/a b n or malities 
i ncl u di n g f ocal scarri n g a n d fi ne de p ositi o n 
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  
 
A nteri or 
C h a m ber :  I n cl u des A nteri or  C ha m ber  
N or m al:   
A bse nce of acti ve i nfl a m mati o n, i nfecti o n, or str u ct ural c ha n g es/a b n or malities  
A b n or m al:  Prese nce of acti ve i nfla m mati o n, i nfecti o n, or str u ct ural c ha n g es/a b n or malities 
i ncl u di n g f ocal scarri n g a n d fi ne de p ositi o n 
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  
 
Iris/ P u pil:  I n cl u des all Iris a n d P u pil 
N or m al:   
A bse nce of acti ve i nfl a m mati o n, i nfecti o n, or str u ct ural c ha n g es/a b n or malities  
A b n or m al:  Prese nce of acti ve i nfla m mati o n, i nfecti o n, or str u ct ural c ha n g es/a b n or malities 
i ncl u di n g f ocal scarri n g a n d fi ne de p ositi o n 
 
Cli nicall y si g nifica nt  


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 5  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
N ot cli nicall y si g nifica nt  
 
E yeli ds:   
I n cl u des e y eli d e de ma a n d e yeli d er yt he ma 
N or m al:  
A bse nce of acti ve i nfl a m mat or y si g ns or si g nifica nt str uct ural 
c ha n ges/a b n or malities or disc har ge  
A b n or m al:  Prese nce of acti ve i nfla m mat or y si g ns or si g nifica nt str uct ural 
c ha n ges/a b n or malities or disc har ge  
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  
C o nj u ncti v a:  I n cl u des peri o c ular tiss ues, a n d t he b ul bar, pal p e bral a n d li m bal c o nj u ncti va  
N or m al:  
A bse nce of acti ve i nfl a m mat or y si g ns or si g nifica nt str uct ural 
c ha n ges/a b n or malities or disc har ge  
A b n or m al:  
Prese nce of acti ve i nfla m mat or y si g ns or si g nifica nt str uct ural 
c ha n ges/a b n or malities or disc har ge  
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  
Le ns  
P ha kic  
  
Pse u d o p ha kic  
  
A p ha kic  
Le ns O p acit y  ( P h a kic o nly) 
N o ne ( 0)   
N o ne prese nt or less t ha n mil d  
Mil d  ( 1)  
Yell o w le ns disc ol orati o n or s mall le ns o pacit y (a xial or peri p heral)  
M o derate  ( 2)  
A m ber le ns disc ol orati o n or me di u m le ns o pacit y (a xial or peri p heral)  
Se vere  ( 3)  
Br u nesce nt le ns disc ol orati o n or c o m plete le ns o pacificati o n ( n o re d refle x)  


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 6  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
 
1 2. 1 2   
A p pe n di x 1 2 : B ul b ar C o nj u ncti v al H y pere mi a  [Brie n H ol de n Visi o n I nstit ute 
( B H VI) G r a di n g S c ale (F or merl y  K n o w n as t he C C L R U )] 
I n vesti g at or-R ate d Ass ess m e nt of B ul b ar C o nj u ncti v al H y pere mi a  
In v esti gat ors will rate o verall b ul bar c o nj u ncti val h y pere mia  usi n g t he B rie n H ol de n Visi o n 
I nstit ute ( B H VI) gra di n g scale [f or merl y k n o w n as t h e Cor nea a n d C o ntact Le ns Researc h U nit 
( C C L R U) gra di n g scale]. I n v esti gat or B H VI rati n gs will be rec or de d i n t he e C R F. 
 
Sc ore   
Re d ness  
0   
N o ne  
1   
Ver y Sli g ht  
2   
Sli g ht  
3   
M o derate  
4   
Se vere  
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 7  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 3   
A p pe n di x 1 3 : I n direct Dil ate d O p ht h al m osc o p y 
T his pr oce d ure will occ ur after a p plicati o n of dilati n g e yedr o ps a n d u p o n I n v esti gat or c o nfir mati o n 
wit h a pe n li g ht  O U are f ull y dilate d (rec o m me n d e d ti me of at least 2 0 mi n utes ). As dilati n g dr o ps 
will be a p plie d, i n direct dilate d o p ht hal m osc o p y m ust be perf or me d afte r e xter nal e ye a n d e y eli d 
p h ot o gra p h y, t ests of vis ual ac uit y, a n d I O P ass ess me nts. 
In dir ect d ilate d o p ht hal m osc o p y will i ncl u de assess me nt of t he vitre o us, reti na, mac ula, c h or oi d, 
o ptic ner ve, a n d v ertical o ptic ner ve c u p -t o-dis c rati o. After t he o p ht hal m osc o p y pr oce d ure, t he 
I n v esti gat or will deter mi ne if fi n di n gs are wit hi n n or mal li mits or are a b n or mal. F or a b n or mal 
fi n di n gs at Scree ni n g ( Visit 1), t he I n vesti gat or will deter mi ne  w het her t he a b n or malit y w o ul d 
e xcl u de t he s u bject fr o m st u d y partici pati o n. O bser vati o ns will be d oc u me nte d o n t he a p pr o priat e 
C R F . A b n or malities s h o ul d  be m ar ke d as “cli nicall y si g nifica nt ” or “n ot cli nicall y si g nifica nt .”  
Vitre o us:   
 
N or m al:   
A bse nce of a n y o pacit y  
A b n or m al:  Prese nce of o pacit y  
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  
 
Reti n a:   
 
N or m al:   
A bse nce of acti ve i nfl a m mati o n or si g nifica nt str uct ural c ha n g es 
A b n or m al:  Prese nce of acti ve i nfla m mat or y si g ns or si g nifica nt str uct ural c ha n g es  
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  
 
M ac ul a:   
 
N or m al:   
A bse nce of acti ve i nfl a m mati o n or si g nifica nt str uct ural c ha n g es  
A b n or m al:  Prese nce of acti ve i nfla m mat or y si g ns or si g nifica nt str uct ural c ha n g es  
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 8  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
C h or oi d:   
 
N or m al:   
A bse nce of acti ve i nfl a m mati o n or si g nifica nt str uct ural c ha n g es  
A b n or m al:  Prese nce of acti ve i nfla m mat or y si g ns or si g nifica nt str uct ural c ha n g es  
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt  
 
O ptic Ner ve:  
 
N or m al:   
A bse nce of a n y da m a ge  
A b n or m al:   
Prese nce of a n y d a ma ge  
 
Cli nicall y si g nifica nt  
N ot cli nicall y si g nifica nt 
 
Vertic al O ptic Ner v e C u p -t o-Disc R ati o:  
_ _. _ _ _ _  
 
Ot her:   
I n dicate a n y ot h er dilate d f u n d us o p ht hal m osc o p y fi n di n gs 
  
N o  
 
Yes  
If yes, s pecif y fi n di n g a n d cli nical si g nifica nce 
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 6 9  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 4   
A p pe n di x 1 4 : I n vesti g ati o n al Pr o d uct C o mf ort/ T oler a bilit y Assess me nt  
S u bjects will be as ke d o n t he da y of st u d y treat me nt t o rate  t he c o mf ort/t olera bilit y of t he st u d y I P 
usi n g a Vis ual A nal o g Scale ( V A S) a fter t he I P has bee n a p plie d t o t h eir up per e y eli ds . This 
assess me nt will be f oc use d o n t he c o mf ort of t he I P itself , a n d s u bjects s h o ul d be i nstr ucte d t o 
t hi n k a b o ut t he c o mf ort of t he I P aft er d osi n g a p pli cati o n a n d  i n de pe n de ntl y fr o m t heir e x p erie n ce 
ha vi n g t he I P a p plie d b y st u d y staf f. 
S u bjects will be as ke d t o place a si n gle v ertical mar k al o n g a h oriz o nt al li ne t o i n dicate  t he le vel 
of c o mf ort/ disc o mf ort t he y e x perie n ce d after I P a d mi nistrati o n . S u bjects will als o be pr o vi de d 
wit h a n e m pt y te xt b o x t o c ollect a n y a d diti o nal n otes t he y w o ul d li ke t o s hare a b o ut t heir 
e x perie n ce wit h t he I P i n re gar ds t o its c o mf ort a n d t olera bilit y.  
 
 
 
 
 
 
 
 
C o m me nts ( O pti o n al ): 
 
Please pr o vi de a n y 
a d diti o nal c o m me nts 
y o u w o ul d li ke t o s hare 
a b o ut y o ur e x perie nce 
t o da y wit h t he 
i n vesti gati o nal pr o d uct 
relate d t o t he pr o d u ct’s 
c o mf ort/t olera bilit y  
 
C o mf orta ble  
U nc o mf orta ble  


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 7 0  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 5   
A p pe n di x 1 5: Vit al Si g ns  
S u bject vital si g ns will be assesse d at t he Scree ni n g visit ( Visit 1), Baseli ne ( Visit 2 bef ore I P 
a d mi nistrati o n), a n d d uri n g t he st u d y peri o d after I P a d mi nistrati o n at H o ur 1 a n d H o ur 8. Vital 
si g ns will i ncl u de bl o o d press ure w hile i n a seate d p ositi o n a n d resti n g heart rate.  
 
 
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 7 1  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 6   
A p pe n di x 1 6 : W o men of C hil d -be ari n g P ote nti al ( W O C B P)  
F or t he p ur p oses of t his st u d y, a w o ma n of c hil d -beari n g p ote ntial will be defi ne d as a s u bject wit h  
a uter us w h o is ca pa ble of bec o mi n g pre g n a nt. 
W O C B P m ust a gree t o use o ne of t h e f oll o wi n g met h o ds of birt h c o ntr ol fr o m t he date t he y si g n 
t he I C F u ntil after t h e c o m pleti o n of t he last st u d y visit ( F oll o w-U p Visit):  
a. A b sti ne nce, w he n it is i n li ne wit h t he preferre d a n d us ual lifest yle of t h e s u bj ect, w here 
a bsti ne nce ma y be defi ne d as refrai ni n g fr o m se x u al c o ntact or defi ne d as e n ga gi n g i n 
relati o ns hi ps i n w hic h it is i m p ossi ble f or se x ual c o ntact t o res ult i n pre g na ncy;  
b.  Ma i nte na nce of a m o n o ga m o us relati o ns hi p wit h a male part ner w h o has bee n 
s ur gicall y sterilize d b y vasect o m y ( vasect o m y pr oce d ure m ust ha ve bee n c o n d ucte d at 
least 6 0 da ys pri or t o t he Scree ni n g visit or c o nfir me d via s per m a n al ysis); 
c. Ba rrier met h o d (e. g., c o n d o m or occl usi ve ca p) wit h s per mici dal f oa m/ gel/fil m/crea m 
A N D eit her h or m o nal c o ntrace pti o n ( oral, i m pla nte d or i njecta ble) or a n i ntra uteri ne 
de vice or s yste m.  
N o te: N o n -c hil d-b eari n g p ote ntial  f or t he p ur p oses of t his st u d y is defi ne d as s ur gical sterilizati o n 
(i.e., bilateral o o p h orect o m y, h ysterect o m y, or t u bal li gati o n), p ost me n o pa usal ( defi ne d as n ot 
ha vi n g a me nstr ual peri o d f or at least 1 2 c o ns ec uti ve m o nt hs pri or t o Scree ni n g) , or me di cal 
c o nfir mati o n of i nfertilit y.  
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 7 2  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 7   
A p pe n di x 1 7 : C o m pli a nce St ate me nt a n d S p o ns or A p pr o v al  
St u d y  Title:  
A P hase 1/ 2a St u d y of L E V 1 0 2 T o pical Gel i n S u bjects wit h 
Ac q uire d Ble p har o pt osis  
St u d y  N u m ber:   
L E V 1 0 2 -C S 0 1  
Fi n al  D ate:   
2 5  Ma y 2 0 2 3  
 
T h is st u d y will be c o n d ucte d i n acc or da nce wit h I nt er nati o nal C o u ncil f or Har m o nisati o n G o o d 
Cli nical Practice (I C H G C P), wit h t he U nite d Stat es  of A merica C o de of Fe deral Re g ulati o ns 
( C F R) a p plica ble t o cli nical st u dies ( 4 5 C F R Part 4 6, 2 1 C F R Part 5 0, 2 1 C F R Part 5 6, 2 1 C F R 
Part 3 1 2, a n d/ or 2 1 C F R Part 8 1 2), a n d as sti p ulate d i n t he Declarati o n of Helsi n k i wit h res pect 
t o t he use of h u ma n s u bjects i n cli nical st u dies a n d i n vesti gati o ns. 
S p o ns or’s Re prese nt ati ve:  
 
 
 
 
Na me ( pri nte d)  
C hief Me dical Officer  
Si g nat ure  
Date  
 
Me dic al M o nit or:  
 
 
 
Na me ( pri nte d)  
Si g nat ure  
Date  
 
 


L e vati o n P har ma Lt d.  
L E V 1 0 2 T o pical Gel  
Cli nical Trial Pr ot oc ol  
C o nfi de nti al  
 
Pa ge 7 3  of 7 3  
Cli nical Trial Pr ot oc ol, Versi o n 6 . 0, A me n d me nt 5 , 2 5 Ma y 2 0 2 3  
1 2. 1 8   
A p pe n di x 1 8 : I n vesti g at or’s Si g n at ure 
 
A  P h ase 1/ 2 a St u d y of L E V 1 0 2 T o pic al Gel i n  
S u bjects wit h Ac q uire d Ble p h ar o pt osis  
 
L E V 1 0 2 -C S 0 1  
 
Versi o n N o .: 6 . 0 
Iss u e Date: 2 5  Ma y 2 0 2 3  
I ha v e rea d t he cli nical trial pr ot oc ol a n d u n dersta n d it.  I a gree t o c o n d uct t he st u d y as o utli ne d 
i n t his d oc u me nt a n d i n acc or da n ce wit h G o o d Cli nical Practice G ui deli nes, all l ocal a n d 
fe deral re q uir e me nts a n d re g ulati o ns, a n d i n c o m plia nce wit h t h ose prece pts set f ort h i n t he 
Declarati o n of Helsi n ki wit h res pect t o t he use of h u ma n s u bjects i n cli nical st u d ies a n d 
i n vesti gati o ns.  
T he I n v esti gat or will ass ure t hat n o de viati o n fr o m, or c ha n ges t o t he pr ot oc ol will ta ke place 
wit h o ut pri or a gree me nt fr o m t he S p o ns or a n d d oc u me nte d a p pr o val fr o m t he I R B, e x ce pt 
w here necessar y t o eli mi nate a n i m me diate hazar d(s) t o t he st u d y s u bjects. All pers o n nel 
i n v ol ve d i n t he c o n d uct of t his st u d y ha ve c o m plete d H u ma n S u bjects Pr otecti o n a n d I C H G C P 
Trai ni n g.  
T he pr ot oc ol, i nf or me d c o nse nt f or m(s), recr uit me nt materials, a n d all s u bject materials will 
be s u b mitte d t o t he I R B f or re vie w a n d a p pr o val.  A p pr o val of b ot h t he pr ot oc ol a n d t he c o ns e nt 
f or m m ust be o btai ne d b ef ore a n y s u bject is e nr olle d. A n y a me n d me nt t o t he pr ot oc ol will 
re q uire re vi e w a n d a p pr o val b y t he I R B bef ore t he c ha n ges are i m ple me nte d t o t he st u d y. All 
c ha n ges t o t he c o nse nt f or m will be I R B a p pr o ve d; a deter mi nati o n will be ma de re gar di n g 
w het her a n e w c o ns e nt nee ds t o be o btai ne d fr o m s u bje cts w h o pr o vi de d c o nse nt, usi n g a 
pre vi o usl y a p pr o ve d c o nse nt f or m.  
F urt her, I a gree t o mai nt ai n t he c o nfi de ntialit y of all i nf or mati o n recei ve d or de vel o pe d i n 
c o n necti o n wit h t his pr ot oc ol.  
 
Si g n at ure of I n vesti g at or:  
 
 
 
Na me ( pri nte d)  
Si g nat ure  
Date  
 

SAP_001.pdf: 
SAP 
 
Study title: A Phase 1/2a Study of LEV102 Topical Gel in Subjects with Acquired Blepharoptosis 
NCT Number:NCT05715346 
Document Date: 25 May 2023 


Levation Pharma Ltd 
 
  LEV102-CS01  
Statistical Analysis Plan 
Confidential  
Final Version 3.0 2023-06-06  
 
Page 1 of 51 
A Phase 1/2a Study of LEV102 Topical Gel in Subjects with Acquired Blepharoptosis 
 
 
Protocol No: 
LEV102-CS01 
Protocol Date: 
2023-05-25 (6.0) 
Sponsor: 
 
 
 
 
    Levation Pharma Ltd. 
 
    
 
    
 
 
 
SAP Version: 
3.0 
SAP Date: 
2023-06-06 
Prepared by: 
. 
 
 
 
 
 
Confidentiality Statement  
This document contains information from Levation Pharma Ltd. and is of confidential, trade 
secret, and/or proprietary nature and may not be disclosed unless such disclosure is required by 
federal or state law or regulation. It is loaned to you for your confidential review on behalf of the 
sponsor only and is not to be photocopied, disclosed, or transmitted to any other person or party 
without the advance written approval of the sponsor. 
 
 


Levation Pharma Ltd 
 
  LEV102-CS01  
Statistical Analysis Plan 
Confidential  
Final Version 3.0 2023-06-06  
 
Page 2 of 51 
SIGNATURE PAGE 
 
 
 
 
____________________________________    
 
_________________ 
 
 
 
 
 
 
 
  
. 
 
 
 
 
_____________________________________    
 
_________________ 
  
 
 
 
 
 
  
 
. 
 
 
 
 
 
_____________________________________    
 
_________________ 
  
 
 
 
 
 
 
  
. 
 
 
 
 
 
_____________________________________    
 
_________________ 
                                 
 
 
 
 
. 
 
 


Levation Pharma Ltd 
 
  LEV102-CS01  
Statistical Analysis Plan 
Confidential  
Final Version 3.0 2023-06-06  
 
Page 3 of 51 
TABLE OF CONTENTS 
LIST OF TABLES .......................................................................................................................... 5 
LIST OF FIGURES ........................................................................................................................ 5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................. 6 
PROTOCOL SYNOPSIS ............................................................................................................... 8 
9.5. 
Efficacy and Safety Variables ............................................................................................ 14 
9.5.1. 
Efficacy and Safety Measurements Assessed and Flow Chart ................................... 14 
9.5.1.1. 
Visit and Procedure Schedule ............................................................................. 16 
9.5.1.2. 
Demographics and Baseline Characteristics ....................................................... 16 
9.5.1.2.1. Demographics and Disease Characteristics ..................................................... 16 
9.5.1.2.2. Medical History ............................................................................................... 17 
9.5.1.2.3. Prior and Concomitant Medications and Therapies ........................................ 17 
9.5.1.3. 
Efficacy Assessments .......................................................................................... 18 
9.5.1.3.1 Leicester Peripheral Field Test ...................................................................... 19 
9.5.1.3.2 FACE-Q | Aesthetics Questionnaires ............................................................. 19 
9.5.1.3.3 Investigator-Reported Outcomes ................................................................... 20 
9.5.1.3.4 External Photography of Eye ......................................................................... 20 
9.5.1.4. 
Safety Assessments ............................................................................................. 20 
9.5.1.4.1. Adverse Events ................................................................................................ 21 
9.5.1.4.2. Current corrected VA ...................................................................................... 22 
9.5.1.4.3. Intraocular Pressure (IOP) ............................................................................... 23 
9.5.1.4.4. Manual Pupillometry ....................................................................................... 23 
9.5.1.4.5. Slit Lamp Biomicroscopy ................................................................................ 24 
9.5.1.4.6. Indirect Dilated Ophthalmoscopy .................................................................... 25 
9.5.1.4.7. Conjunctival Hyperemia Evaluation ............................................................... 26 
9.5.1.4.8. Vital Signs ....................................................................................................... 27 
9.5.1.4.9. Urine Pregnancy Test (only for women of child-bearing potential (WOCBP))
 
27 
9.5.1.4.10. IP Comfort Assessment ................................................................................... 27 
9.5.2. 
Appropriateness of Measurements ............................................................................. 28 
9.5.3. 
Primary Efficacy Variables ........................................................................................ 28 
9.5.3.1. 
Efficacy Endpoints .............................................................................................. 28 


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Page 4 of 51 
9.5.3.2. 
Safety Endpoints ................................................................................................. 28 
9.5.4. 
Drug Concentration Measurements ............................................................................ 29 
9.6. 
Data Quality Assurance ..................................................................................................... 30 
9.6.1. 
Training and Education of Investigators and Study Site Personnel ........................... 30 
9.6.2. 
Monitoring of Study Sites........................................................................................... 30 
9.6.3. 
Data Entry and Verification of Database Used for Analysis and Reporting .............. 31 
9.6.4. 
Clinical Study Report ................................................................................................. 31 
9.6.5. 
Inter-Laboratory Standardization Methods ................................................................ 31 
9.7. 
Statistical Methods Planned in the Protocol and Determination of Sample Size .............. 32 
9.7.1. 
Statistical and Analytical Plans .................................................................................. 32 
9.7.1.1. 
Analysis Populations ........................................................................................... 37 
9.7.1.2. 
Analysis of Subject Disposition .......................................................................... 37 
9.7.1.3. 
Analysis of Demographic and Baseline Characteristics ..................................... 38 
9.7.1.3.1. Demographics and Disease Characteristics ..................................................... 38 
9.7.1.3.2. Medical History ............................................................................................... 39 
9.7.1.3.3. Prior and Concomitant Medications ................................................................ 39 
9.7.1.4. 
Analysis of Study Medication Compliance and Exposure .................................. 40 
9.7.1.5. 
Analysis of Efficacy and Safety Endpoints ......................................................... 40 
9.7.1.5.1. Efficacy Endpoint Analyses ............................................................................ 40 
9.7.1.5.1.1. Leicester Peripheral Field Test (LPFT) ................................................... 40 
9.7.1.5.1.2. Margin Reflex Distance 1 ....................................................................... 42 
9.7.1.5.1.3. Conjunctival Hyperemia Evaluation ....................................................... 42 
9.7.1.5.1.4. FACE-Q | Aesthetics ............................................................................... 42 
9.7.1.5.1.5. Investigator Report Outcome .................................................................. 43 
9.7.1.5.2. Safety Endpoint Analysis ................................................................................ 44 
9.7.1.5.2.1. Adverse Events ........................................................................................ 44 
9.7.1.5.2.2. Current Corrected Visual Acuity............................................................. 45 
9.7.1.5.2.3. Intraocular Pressure (IOP) ....................................................................... 45 
9.7.1.5.2.4. Manual Pupillometry ............................................................................... 45 
9.7.1.5.2.5. Slit Lamp Biomicroscopy........................................................................ 45 
9.7.1.5.2.6. Indirect Dilated Ophthalmoscopy ........................................................... 45 


Levation Pharma Ltd 
 
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Final Version 3.0 2023-06-06  
 
Page 5 of 51 
9.7.1.5.2.7. Vital Signs ............................................................................................... 46 
9.7.1.5.2.8. Investigational-Product (IP) Comfort Assessment .................................. 46 
9.7.2. 
Determination of Sample Size .................................................................................... 46 
9.8. 
Changes in the Conduct of the Study or Planned Analyses ............................................... 47 
9.8.1. 
Protocol Amendments ................................................................................................ 47 
9.8.2. 
Changes from Protocol-Specified Analyses ............................................................... 49 
9.8.3. 
SAP Amendments....................................................................................................... 49 
REFERENCES ............................................................................................................................. 49 
APPENDIX I: Schedule of Procedures and Assessments ............................................................ 49 
 
LIST OF TABLES 
Table 1. Medications and Procedures NOT Permitted ................................................................. 17 
Table 2. FACE-QTM  –  Satisfaction with Eyes Conversion Table ............................................... 34 
Table 3. FACE-QTM – Appraisal of Lower Eyelids Conversion Table ........................................ 35 
Table 4. FACE-QTM - Appraisal of Upper Eyelids Conversion Table.......................................... 36 
 
LIST OF FIGURES 
Figure 1 
Clinical Study Diagram .............................................................................................. 16 
 


Levation Pharma Ltd 
 
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Statistical Analysis Plan 
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Final Version 3.0 2023-06-06 
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
ATC 
Anatomical Therapeutic Chemical 
BHVI 
Brien Holden Vision Institute 
CCLRU 
Cornea and Contact Lens Research Unit 
CFR 
Code of Federal Regulations 
CFB 
Change from Baseline 
CFH2 
Change from Hour 2 
CI 
Confidence Interval 
CRF 
Case report form 
CS 
Clinically significant 
eCRF 
Electronic case report form 
EDC 
Electronic Data Capture 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice  
GMP 
Good Manufacturing Practice 
IB  
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IOP 
Intraocular pressure 
IRO 
Investigator Report Outcome 
IP 
Investigational product  
IRB 
Institutional Review Board 
LS 
Least Square 
LogMAR 
Logarithm of the Minimum Angle of Resolution 
LPFT 
Leicester Peripheral Field Test 


Levation Pharma Ltd 
 
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Statistical Analysis Plan 
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Page 7 of 51 
Final Version 3.0 2023-06-06 
 
MAOI 
Monoamine oxidase inhibitor 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed-Effect Model Repeated Measure  
MRD1 
Margin reflex distance 1 
NCS 
Not clinically significant 
OD 
Oculus dexter 
OS 
Oculus sinister 
OTC 
Over-the-counter 
OU 
Oculus uterque (both eyes) 
PT 
Preferred term 
QC 
Quality control 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan  
SD 
Standard deviation 
SOC 
System organ class 
TEAE 
Treatment Emergent Adverse Events 
U.S.A. 
United States of America 
VA 
Visual acuity  
VAS 
Visual Analog Scale  
WHO 
World Health Organization 
WHODrug 
World Health Organization Drug Dictionary 
WOCBP 
Women of child-bearing potential  
 
 
 


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Statistical Analysis Plan 
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Page 8 of 51 
Final Version 3.0 2023-06-06 
 
PROTOCOL SYNOPSIS 
Sponsor: 
Levation Pharma Ltd. 
Name of Finished Product: 
TBD 
Name of Active Ingredient: 
Oxymetazoline 
Study Title: 
A Phase 1/2a Study of LEV102 Topical Gel in Subjects with Acquired Blepharoptosis 
Study Number: 
LEV102-CS01 
Study Phase: 1/2a 
Primary Objective and Endpoints: 
Objective(s) 
Endpoint(s) 
Primary: 
1. Assess the ocular and systemic safety and 
tolerability of a single application of 
LEV102 Topical Gel on the upper eyelids 
in subjects with acquired blepharoptosis 
• 
The incidence and severity of systemic and ocular adverse 
events (AE) 
• 
Current corrected visual acuity (VA), using subject’s own 
prescription eyeglasses, if applicable, in both eyes as measured
by Early Treatment Diabetic Retinopathy Study (ETDRS) at 
the Screening visit, Baseline, and Hour 8 
• 
Intraocular pressure (IOP) measured in both eyes at the 
Screening visit, Baseline, Hour 1, and Hour 8 
• 
Slit lamp examination of both eyes at the Screening visit, 
Baseline, and Hour 8 
• 
Manual pupillometry of both eyes as measured at the 
Screening visit, Baseline, Hour 1, Hour 4, and Hour 8 
• 
Heart rate and blood pressure as measured at the Screening 
visit, Baseline, Hour 1, and Hour 8 
• 
Subject-reported investigational product (IP) comfort 
questionnaire [Visual Analog Scale (VAS)] at Hour 1 


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Statistical Analysis Plan 
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Final Version 3.0 2023-06-06 
 
Exploratory Objectives and Endpoints: 
Exploratory: 
Endpoint(s) 
1. Evaluate the effect of a single application 
of LEV102 Topical Gel on the upper 
eyelids on superior visual fields and upper 
eyelid height 
2. Gather additional information to guide the 
development of further clinical studies 
• 
Continuous and categorical analysis in both eyes of change 
from baseline in margin reflex distance 1 (MRD1) of 1.0, 
1.5, 2.0, and 2.5 mm at Hour 0.5, Hour 1, Hour 2, Hour 4, 
Hour 6, and Hour 8 
• 
Change from baseline in the number of points/dots seen in 
superior visual field section (top 4 rows) of Leicester 
Peripheral Field Test (LPFT) at Hour 2 and Hour 6, as well 
as change from Hour 2 at Hour 6 
• 
Change from baseline in both eyes of ocular hyperemia 
grade using Brien Holden Vision Institute (BHVI) grading 
scale [formerly known as the Cornea and Contact Lens 
Research Unit (CCLRU) grading scale] at Hour 0.5, Hour 1, 
Hour 2, Hour 4, Hour 6, and Hour 8 
• 
Change from baseline in FACE-Q | Aesthetics© 
(Satisfaction with Eyes; Appraisal of Upper Eyelids; 
Appraisal of Lower Eyelids) questionnaires at Hour 4 and 
Hour 8 
• 
Change from baseline in Investigator-reported outcome 
questionnaire at Hour 4 and Hour 8  
Study Design/Conduct: 
This is a Phase 1/2a, multicenter, randomized, vehicle-controlled, double-masked, single-dose, parallel-group study 
conducted in adult subjects with acquired blepharoptosis. Subjects will receive a one-time application of randomized, 
double-masked IP. 
STUDY ASSESSMENTS 
Safety Assessments 
• 
AE monitoring (ocular and non-ocular)  
• 
Current corrected VA 
• 
IOP 
• 
Manual Pupillometry 
• 
Slit Lamp Examination 
• 
Indirect Dilated Ophthalmoscopy  
• 
Conjunctival Hyperemia Evaluation  
• 
Vital Signs 
• 
Urine Pregnancy Test [only for women of child-bearing potential (WOCBP)] 
Efficacy Assessments 
• 
Leicester Peripheral Field Test 
• 
FACE-Q | Aesthetics Questionnaires 
• 
Investigator-reported Outcome Questionnaire 
• 
External Photography of Eyes 
Other Assessments 
• 
IP Comfort Assessment 


Levation Pharma Ltd 
 
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Statistical Analysis Plan 
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Page 10 of 51 
Final Version 3.0 2023-06-06 
 
Study Population:  
This study is expected to enroll approximately 30 adult subjects with acquired blepharoptosis. 
Diagnosis and Main Criteria for Inclusion: 
The study population will consist of adult subjects who have acquired blepharoptosis. If both eyes qualify for the 
study, the eye with the lower MRD1 value at Baseline will be designated as the study eye. If MRD1 values are the 
same for both eyes at Baseline, the right eye will be designated as the study eye. Regardless of study eye or study 
qualification, all eyes in this study will receive study IP and undergo study assessments. 
 
Inclusion Criteria:  
Subjects who meet all the following inclusion criteria will be eligible to participate in the study. Subjects must: 
1. Be male or female subjects 25 years of age or older at the time of Screening (Visit 1) 
2. Have complaints of aesthetically unacceptable upper eyelid position for both eyes making them desirous for 
elevation, or have complaints of superior visual field defects in both eyes that impact activities of daily 
living 
3. Present with the following at Screening (Visit 1): 
a. 
At least one eye that meets both of the following criteria: 
i. 
MRD1 ≤2.3 mm (no visible central pupillary light reflex defaults to 0) 
ii. Current corrected VA, using subject’s own prescription eyeglasses, if applicable, in the 
qualifying eye(s) of +0.3 LogMAR (Logarithm of the Minimum Angle of Resolution) or better 
as assessed by ETDRS 
b. Demonstrate upper eyelid elevation ≥0.5 mm change from baseline in MRD1 in both eyes in 
response to a single drop of Upneeq® (oxymetazoline 0.1% ophthalmic solution) to each eye at 
Screening 
Note: Upneeq® is preferred but phenylephrine 2.5% ophthalmic solution may be used if 
Upneeq® is not available in a timely manner.  
4. In the judgment of the Investigator, have normal levator palpebrae superioris muscle function of both upper 
eyelids 
5. WOCBP must agree to use an approved method of birth control from the date they sign the informed 
consent form (ICF) until after the last study visit (Follow-Up Visit) 
6. Be able to give informed consent and willing to comply with all study visits and examinations 
 
Exclusion Criteria: 
Subjects who meet any of the following exclusion criteria at Screening (Visit 1) or Baseline (Visit 2) will not be 
eligible to participate in the study. Subjects must not: 
Ocular Conditions:  
1. Have any other ocular pathology other than ptosis requiring treatment with topical prescription ophthalmic 
drops in either eye (e.g., glaucoma) 
             Note: Subjects who use OTC or prescription topical ophthalmic drops to treat dry eye disease may  
             be allowed with Sponsor approval.  
2. Have narrow angles, glaucoma, IOP >23 mmHg or diagnosis of ocular hypertension, cup-to-disc ratio of 
>0.7, or history of any glaucoma eye surgery in either eye 
3. Have any active ocular or peri-ocular infection; any history of recurrent or chronic infection or 
inflammation in either eye 
4. Have a history of herpetic infection in either eye 
5. Have a history of corneal disease other than mild to moderate dry eye or surgery in either eye 
 


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           Note: Subjects with ocular refractive surgery (e.g., laser-assisted in situ keratomileusis, photorefractive  
           keratectomy, small incision lenticule extraction) ≥90 days prior to Screening (Visit 1) are allowed.  
6. Present with any pupillary abnormality in either eye 
7. Present with any manifest strabismus in either eye 
8. Present, in the opinion of the Investigator, with clinically significant brow ptosis in either eye 
9. Have asymmetry ≥3.0 mm in MRD1 between eyes or interpalpebral distance between both eyes 
10. Have any anatomic abnormality of either upper or lower eyelids in either eye that obscures either upper or 
lower eyelid margin  
11.  Have any history of ptosis surgery in either eye 
12. Have a history of any upper or lower eyelid surgery, including blepharoplasty, skin lesion, or other issue 
within 3 month of Screening (Visit 1) in either eye 
13. Have a history of chronic progressive external ophthalmoplegia, Horner’s syndrome, myasthenia gravis, 
Marcus Gunn jaw winking, congenital ptosis, Kearns-Sayre Syndrome, dermatochalasis, uncontrolled 
blepharospasm, Ramsay Hunt syndrome, or mechanical ptosis in either eye 
              Note: Dermatochalasis (excess eyelid skin) should not be considered exclusionary if, in the opinion of the  
              Investigator, it does not obscure eyelid margins or interfere with quality image capture.  
 
14. Have mechanical ptosis, including ptosis due to orbital or eyelid tumor, cicatricial processes affecting the 
movements of the upper eyelid, and enophthalmos in either eye 
15. Have eyelid position affected by eyelid or conjunctival scarring in either eye 
16. Have a visual field loss from any cause other than ptosis in either eye 
17. Have a history of optic neuropathy in either eye 
18. Have used topical application of bimatoprost (i.e., Latisse) to the eyelashes within 7 days prior to Screening 
(Visit 1) and during the study in either eye 
19. Have used topical application of pilocarpine (i.e., Vuity) within 7 days prior to Screening (Visit 1) and 
during the study in either eye 
20. Have concurrent disease in either eye or that could require medical or surgical intervention during the study 
period 
21. Be unwilling to discontinue the use of upper eyelid/eyelash makeup and OTC cosmetic products during the 
Screening visit and on the day of the study treatment and assessments (Day 1), including but not limited to: 
a. 
Eyeshadow primer 
b. Eyeshadow 
c. 
Eyelid moisturizer 
d. Eyeliner 
e. 
Fake eyelashes (glued or magnetic) 
f. 
Skin care products applied to the eyelid 
 
              Note: Enhancements that cannot easily be removed should not be considered exclusionary if, in the  
              opinion of the Investigator, they do not obscure eyelid margins or interfere with quality image capture.  
              Note: Subjects wearing makeup during the screening visit should remove the makeup on-site                       
              before image capture.  
 
22. Have used oxymetazoline topical eye drops (Upneeq®) for treatment of blepharoptosis or as an ocular 
decongestant (Visine LR) within 7 days prior to Screening (Visit 1) or planned use during the study period 
in either eye 


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Note: Eyedrops applied during Screening (Visit 1) to determine study eligibility are exempt from this 
exclusion. 
23. Have had intravitreal injections (e.g., Lucentis, Eylea, Avastin, Triesence) within 7 days prior to Screening 
(Visit 1) or have plans for an injection during the study in either eye 
24. Have a history of thyroid eye disease (i.e., exophthalmos, upper eyelid retraction, diplopia secondary to 
extraocular muscle involvement) in either eye. Hyperthyroidism that is controlled on medication is allowed 
Systemic Conditions: 
25. Have a resting heart rate outside normal range of 50-110 beats per minute while sitting during the Screening 
visit (Visit 1) 
26. Have, in the opinion of the Investigator, uncontrolled hypertension, uncontrolled atrial fibrillation, or history 
of clinical cardiovascular disease including stroke, myocardial infarction, or heart failure 
27. Have plans to use a non-ophthalmic α-adrenergic agonist, including OTC products (e.g., Afrin), at any time 
during the study 
28. Have used monoamine oxidase inhibitors (MAOIs; e.g., isocarboxazid, phenelzine, tranylcypromine) within 
14 days prior to Screening (Visit 1) or anticipate using MAOIs during the study 
29. Subjects with diabetic retinopathy may not be enrolled in this study. However, subjects with insulin-
dependent diabetes, diabetes requiring oral hypoglycemic drugs, or diet-controlled diabetes are allowed 
30. Have been diagnosed with benign prostatic hypertrophy requiring medicinal therapy; previous 
prostatectomy is allowed 
General: 
31. Have participated in other investigational drug or device clinical trials within 30 days prior to Screening 
(Visit 1), or be planning to participate in any other investigational drug or device clinical trials within 30 
days of study completion  
32. Have a history of allergic reaction to the investigational drug or any of its components 
33. Within 7 days of Screening (Visit 1), or anticipated use during the study, use of any systemic, intranasal, 
topical dermatologic, or ophthalmic α-adrenergic agonist (including brimonidine) or antagonist including 
nasal or ocular or oral decongestants including pseudoephedrine, oxymetazoline topical ophthalmic 
solution, oxymetazoline topical dermatologic cream 
34. Subjects who are pregnant or breast-feeding 
35. Have used Upneeq® within 7 days of either Screening (Visit 1) or Baseline (Visit 2) 
Investigational Product(s); Dose; and Mode of Administration:  
• 
LEV102 Topical Gel, 2.0% (100 µL) 
• 
LEV102 Topical Gel, 1.0% (100 µL) 
Reference Therapy; Dose; and Mode of Administration: 
• 
Vehicle Topical Gel (100 µL) 
Duration of Treatment:  
The duration of the treatment period in this study is 1 day with assessments to be completed at Baseline (before IP 
administration), Hour 0 (after IP administration), Hour 0.5, Hour 1, Hour 2, Hour 4, Hour 6, and Hour 8. 
Duration of Study Participation: 
There are 2 clinic visits and 1 telephone follow-up over up to 50 days, (up to 45 days for Screening and 2-5 days after 
the day of study treatment). 
Statistical Methods: 
In general, analyses in this study will examine the differences between individual treatment arms, as well as the 
differences between combined arms of LEV102 Topical Gel compared to vehicle. Continuous measures will be 


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summarized descriptively by the mean, standard deviation (SD), median, minimum, and maximum values. 
Categorical measures will be summarized by the frequency and percentage of subjects. 
 
For all exploratory efficacy analyses and all safety analyses performed, Baseline will be defined as the measurement 
on Day 1 before IP administration and not from any previous visit. If both eyes qualify for the study, the eye with the 
lower MRD1 value at Baseline will be designated as the study eye. If MRD1 values are the same for OU at Baseline, 
the right eye will be designated as the study eye. Regardless of study eye or study qualification, all eyes in this study 
will receive study IP and undergo study assessments. 
 
The sample size of 10 subjects per arm (30 subjects total for a total of 60 eyes) is not based on formal power or 
precision considerations. Subjects will be analyzed in the group according to the IP treatment received. All endpoints 
will be analyzed using the Safety Analysis Set and only observed data will be included. 
 
Safety analyses will be performed on all subjects in the Safety Analysis Set. The assessment of safety will be based 
on the summary of ocular and non-ocular AEs, current corrected VA, IOP, slit lamp biomicroscopy, ocular 
hyperemia, manual pupillometry, indirect dilated ophthalmoscopy, vital signs, and urine pregnancy test. Summaries 
will be provided by treatment group, and for ocular assessments separately by eye.  
 
Summary statistics for observed data and changes from baseline (where appropriate) for current corrected VA, IOP, 
manual pupillometry, vital signs, and the comfort questionnaire will be presented. Abnormalities in slit lamp 
biomicroscopy will be summarized by frequency and percentage. 
 
Summary statistics for observed data and changes from baseline (where appropriate) for MRD1, LPFT, ocular 
hyperemia, and subject- and investigator-reported outcome questionnaires at post-dose Visit 2, as well as change 
from Hour 2 at Hour 6 for LPFT will be presented. Subjects achieving an improvement in MRD1 from baseline of 
1.0, 1.5, 2.0, and 2.5 mm will be summarized by timepoint. Summary statistics for observed data and changes from 
baseline in FACE-Q | Aesthetics questionnaires, as well as the response rates to individual questions, will be 
presented. 
 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) (most current version) and 
categorized by system organ class (SOC) using preferred terms (PT). Separate summaries of AEs related to treatment 
and by severity will be presented. The number of deaths and serious adverse events (SAE) will also be presented, and 
events leading to discontinuation from the study will be listed and tabulated. 
 
All data collected in this study will be presented in data listings for all subjects. 
Date of Original Protocol: 09 August 2022 
Date of Most Recent Protocol Amendment: 25 May 2023 
 


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9.5. 
EFFICACY AND SAFETY VARIABLES 
9.5.1. 
Efficacy and Safety Measurements Assessed and Flow Chart 
This is a Phase 1/2a, multicenter, randomized, vehicle-controlled, double-masked, single-dose, 
parallel-group study conducted in adult subjects with acquired blepharoptosis. Subjects will receive 
a one-time application of randomized, double-masked IP. Approximately 30 subjects will be 
enrolled in this study. Eligible subjects will be randomized to 1 of the following 3 treatment groups 
in a 1:1:1 ratio and will receive a single dose of double-masked IP externally on the upper eyelid of 
both eyes (OU): 
• LEV102, 2.0% (100 µL) 
• LEV102, 1.0% (100 µL) 
• Vehicle (100 µL) 
Screening Visit (Visit 1; Day -45 to Day -7) 
At the Screening visit (Visit 1), subjects will review and sign the informed consent form (ICF) and 
begin washout of prohibited medications/procedures not permitted during the study. Subjects will 
complete study intake and undergo screening assessments, which will include external photography 
of OU both before and after administration of 1 drop of single-masked Upneeq® (oxymetazoline 
0.1% ophthalmic solution) OU. (Note: Upneeq® is preferred but phenylephrine 2.5% ophthalmic 
solution may be used if Upneeq® is not available in a timely manner.) A central reading center will 
review the images captured during the Screening visit to confirm study eligibility. Subjects wearing 
makeup during the Screening visit should remove the makeup on-site before image capture.  
Subjects should be contacted by telephone on Day -1, the day before Visit 2 (Baseline; 
Randomization; Day 1), to confirm study visit details and appointment time, or to inform subjects of 
screen failure. Subjects who remain eligible for study participation at this time should be reminded: 
1. If the subject normally wears contact lenses, the subject should not wear contact lenses on 
study visit days [Visit 1 (Screening); Visit 2 (Baseline; Randomization; Day 1)] and should 
instead wear prescription eyeglasses. 
2. Not to apply any makeup or OTC cosmetic or topical skin care products, including 
sunscreen or moisturizer, to their eyelids or eyelashes on the day of study treatment (Visit 2; 
Baseline; Randomization; Day 1). 
 
 
 


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Day 1/Treatment Period (Visit 2) 
Seven (7) to 45 calendar days after the Screening visit, eligible subjects will return to the study site 
for randomization to 1 of 3 treatment groups in a 1:1:1 ratio. Double-masked IP will be dispensed 
using a positive-displacement pipette and will be applied smoothly with a gloved finger to the entire 
external skin of the upper eyelid of each eye by trained study staff. 
Note: The Day 1 appointment arrival time must be scheduled for early in the morning to allow 
sufficient time for the Hour 8 study assessments. 
Subjects will undergo study assessments and answer study questionnaires at Baseline, Hour 1, Hour 
4, and Hour 8. External photography of the eyes will also be conducted at Baseline, Hour 0.5, Hour 
1, Hour 2, Hour 4, Hour 6, and Hour 8. For the purposes of documentation and analysis, Baseline 
will be defined as the measurements collected at Day 1 before administration of double-masked 
study IP. 
Telephone Follow-Up (Visit 3; Day 2-5) 
Subjects will be contacted by clinical site staff for a follow-up telephone interview 2-5 days after 
the treatment period to collect data on AEs experienced in the days following IP administration and 
to collect data on concomitant medications. 
A diagram of the study design is included below at Figure 1.  
 
 
 


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Figure 1 
Clinical Study Diagram 
 
• 
Subjects should be contacted by study staff via telephone before study visits to be reminded of the following: 1.) If 
the subject normally wears contact lenses, the subject should not wear contact lenses on study visit days and should 
instead wear prescription eyeglasses and 2.) Not to apply any makeup or OTC cosmetic or topical skin care 
products, including sunscreen or moisturizer, to their eyelids or eyelashes on the day of the screening visit or on the 
day of study treatment. 
• 
Visit 3 will be a remote visit conducted by telephone. 
9.5.1.1. 
Visit and Procedure Schedule 
See Appendix I for a complete visit and procedure schedule. 
9.5.1.2. 
Demographics and Baseline Characteristics 
9.5.1.2.1. Demographics and Disease Characteristics 
Demographic characteristics including age (years), sex, race, ethnicity, eye color, study eye, and 
qualifying eyes will be collected at Visit 1 (Screening) and summarized by treatment group and 
overall. 


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9.5.1.2.2. Medical History 
After providing written informed consent for this study, prospective subjects will be screened to 
obtain medical history, determine whether they meet enrollment criteria, and capture baseline 
measurements. Ocular and non-ocular medical and surgical history will be collected at Screening 
and Baseline and summarized by treatment groups and overall. 
9.5.1.2.3. Prior and Concomitant Medications and Therapies 
For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported in the eCRF are concomitant 
prescription medications, OTC medications, and supplements.  
All medications that a subject has taken within 30 days of Screening (Visit 1) and through to the 
end of Visit 3 (End of Study) or discontinuation from the study will be recorded in the eCRF. The 
generic name of the drug, dose, route of administration, duration of treatment (including start and 
stop dates), frequency, indication, and whether or not the medication was taken due to an adverse 
event will be recorded for each medication. Previous and concomitant medications will be coded 
using the World Health Organization Drug Dictionary (B3 WHO Global, Version September 2022 
or later). 
Medications specifically prohibited by the protocol are listed in Table 1.  
Table 1. Medications and Procedures NOT Permitted 
Medication and Procedures Not Permitted 
Minimum Washout Period(s) 
Glaucoma eye surgery in either eye 
Any history  
Ptosis surgery in either eye 
Any history  
Upper eyelid/eyelash makeup and OTC 
cosmetic products, including but not limited to: 
a. Eyeshadow primer 
b. Eyeshadow 
c. Eyelid moisturizer 
d. Eyeliner 
e. Fake eyelashes (glued or magnetic) 
f. Skin care products applied to the eyelid 
Note: Enhancements that cannot easily be 
removed should not be considered exclusionary 
if, in the opinion of the Investigator, they do not 
obscure eyelid margins or interfere with quality 
image capture.  
Note: Subjects wearing makeup during the 
Screening visit should remove the makeup on-site 
before image capture.  
 
During the Screening visit and for the duration 
of the treatment period of the study (Day 1) 


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Medication and Procedures Not Permitted 
Minimum Washout Period(s) 
Non-ophthalmic α-adrenergic agonist, 
including OTC products (e.g., Afrin) 
Throughout the study 
Any upper or lower eyelid surgery, including 
blepharoplasty, skin lesion, or other issue in 
either eye 
3 months before Screening (Visit 1) and 
throughout the study 
 
 
Participated or plan to participate in any other 
investigational drug or device clinical trials 
30 days before Screening (Visit 1), throughout 
the study, and 30 days after study completion 
Oxymetazoline topical eye drops (Upneeq ®) 
for treatment of blepharoptosis or as an ocular 
decongestant (Visine LR) in either eye 
7 days before Screening (Visit 1) and 
throughout the study, excluding drops used 
during Screening to determine study eligibility 
MAOIs (e.g., isocarboxazid, phenelzine, 
tranylcypromine) 
14 days before Screening (Visit 1) and 
throughout the study 
Topical application of bimatoprost (i.e., 
Latisse) to the eyelashes 
7 days before Screening (Visit 1) and 
throughout the study 
Topical application of pilocarpine (i.e., Vuity) 
in either eye 
7 days before Screening (Visit 1) and 
throughout the study 
Intravitreal injections (e.g., Lucentis, Eylea, 
Avastin, Triesence) in either eye 
7 days before Screening (Visit 1) and 
throughout the study 
Systemic, intranasal, topical dermatologic, or 
ophthalmic α-adrenergic agonist (including 
brimonidine) or antagonist including nasal or 
ocular or oral decongestants including 
pseudoephedrine, oxymetazoline topical 
ophthalmic solution, oxymetazoline topical 
dermatologic cream, Upneeq® 
7 days before Screening (Visit 1) and 
throughout the study 
 
9.5.1.3. 
Efficacy Assessments 
In general, efficacy analyses will be performed for study eye and for qualified eye. In addition, they 
will be stratified by abnormal clinically significant and not clinically significant superior visual 
fields loss. Abnormal clinically significant (CS) superior visual field loss is defined as loss 8 or 
more points in superior visual field section (top 4 rows) of Leicester Peripheral Field Test (LPFT) at 
the baseline. If a subject has lost 7 or fewer points in supervisor visual field, then he/she does not 
have a clinically significant (NCS) superior visual field loss. 
Efficacy assessments will be conducted at the timepoints indicated on the Schedule of Procedures 
and Assessments (Appendix I). They are described below.  


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9.5.1.3.1 Leicester Peripheral Field Test  
The LPFT is a customized visual field test designed to assess ptosis (Ho et al., 2011). 
The LPFT will be conducted using a Humphrey Visual Field Analyzer. Clinical study staff will 
instruct subjects to keep their chin and forehead against the chin and forehead rests, and to ensure 
that their facial features remain fully relaxed during the assessment. Subjects will be instructed to 
look at the center of the fixation target throughout the test. Corrective lenses are not necessary with 
the LPFT. 
The LPFT will be scored based on an eligibility score and a total score. 
LPFT Eligibility Score = The total number of points missed in the top 2 rows on the LPFT 
(minimum 0; maximum 17) 
LPFT Total Score = The total number of points seen in the top 4 rows on the LPFT (minimum 0; 
maximum 35) 
LPFT assessments will be performed in both eyes separately. Thirty-five points are tested in the 
superior field while 14 points are included in the inferior field. The inferior field test serves as a 
reference but should not be used for the analysis.  
9.5.1.3.2 FACE-Q | Aesthetics Questionnaires 
FACE-Q is a subject-reported outcome measure that has been used successfully in numerous 
clinical trial settings to evaluate the safety and effectiveness of facial treatments and to inform 
subject care in clinical practice. FACE-Q can be used to measure subject satisfaction with aesthetic 
facial procedures and products from the subjects’ perspective. 
This instrument has been used to evaluate the safety and effectiveness of facial aesthetic treatments 
in numerous clinical trial settings and to inform patient care in clinical practice. The FACE-Q© is 
composed of a set of 39 independently functioning scales/checklists that measure 3 overarching 
domains: Facial Appearance, Health-Related Quality of Life, and Adverse Effects. For the purposes 
of this study a modular approach will be used with the modules listed below. 
The different questionnaire modules will be presented separately, and subjects will not have access 
to the questionnaires they completed at previous clinic visits or at previous timepoints. 
FACE-Q |Aesthetics© Scales (Modular Approach) 
1. Satisfaction with Eyes (7 items) 
2. Appraisal of Upper Eyelids (7 items) 
3. Appraisal of Lower Eyelids (7 items) 


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9.5.1.3.3 Investigator-Reported Outcomes 
Principal Investigators will be subjectively assessing the 
 photographs in a randomized, 
masked fashion. After the last subject has completed the study, Principal Investigators will review 
batched masked/anonymized 
photographs of all subjects’ eyes as documented at Baseline,  
Hour 4, and Hour 8. 
 photographs will be provided to the Principal Investigators in a random manner and should 
not be organized by site, subject, or timepoint. Each Investigator will assess the photographs based 
on their subjective impression of various parameters of subjects’ eyes, upper eyelids, and lower 
eyelids. 
9.5.1.3.4 External Photography of Eye 
Images of subjects’ eyes will be captured onsite during the clinic visit and submitted to a central 
reading center for evaluation. These imaging assessments are common tools within the field of 
ophthalmology and are generally recognized as reliable, accurate, and relevant.  
One of the photography of eye assessments is ptosis evaluation, which measures margin reflex 
distance 1 (MRD1), defined as the distance from the margin of the upper eyelid to the top of the 
corneal light reflex when the eye is held in primary position. Subjects will have external 
photographs taken of both eyes via 
 photography for MRD1 measurements and 
interpalpebral distance measurements by a central reading center at the Screening visit both before 
and approximately 120 (±30) minutes after instillation of 1 drop of single-masked oxymetazoline in 
each eye. (Note: Upneeq® is preferred but phenylephrine 2.5% ophthalmic solution may be used if 
Upneeq® is not available in a timely manner.)   
Investigators will rate overall bulbar conjunctival hyperemia using the Brien Holden Vision 
Institute (BHVI) grading scale.  
9.5.1.4. 
Safety Assessments 
Safety assessments will be performed at the timepoints indicated in the Schedule of Procedures and 
Assessments (Appendix I) and as shown below:   
• AE monitoring (ocular and non-ocular)  
• Current corrected VA 
• IOP 
• Manual Pupillometry 
• Slit Lamp Examination 
• Indirect Dilated Ophthalmoscopy  
• Conjunctival Hyperemia Evaluation  
• Vital Signs 


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• Urine Pregnancy Test [only for women of child-bearing potential (WOCBP)] 
9.5.1.4.1. Adverse Events 
An adverse event is any untoward medical occurrence in a subject or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered related to the 
study intervention.  An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with 
the use of study intervention. 
An AE or suspected adverse reaction is considered “serious” if, in the view of either the Investigator 
or Sponsor, it results in any of the following outcomes:  
• Death 
• A life-threatening AE 
• Subject hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or  
• A congenital anomaly or birth defect 
The severity of all AEs will be assessed by the Investigator and graded as follows:  
 
Grade Level 
Description 
Mild 
Requires minimal or no treatment and does not interfere with the subject’s daily 
activities 
Moderate 
Results in a low level of inconvenience or concern and may cause some interference 
with functioning 
Severe 
Interrupts a subject’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe AEs are usually potentially life-threatening or incapacitating. 
The term “severe” does not necessarily equate to “serious.” 
 
All AEs must have their relationship to study intervention assessed by the Investigator who 
examines and evaluates the subject based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical 
study, the IP must always be suspect. 
 
Causality 
Definition 


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Unrelated 
no reasonable possibility that the administration of the IP caused the event, no 
temporal relationship between the IP and event onset, or an alternate etiology 
has been established 
Related 
It is known to occur with the IP, there is a reasonable possibility that the IP 
caused the AE, or there is a temporal relationship between the IP and event. 
Reasonable possibility means that there is evidence to suggest a causal 
relationship between the IP and the AE.  
 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the IB, package 
insert, or device labeling or is not listed at the specificity or severity that has been observed; or, if an 
IB is not required or available, is not consistent with the risk information described in the protocol, 
as amended. “Unexpected,” as used in this definition, also refers to AEs or suspected adverse 
reactions that are mentioned in the IB, package insert, or device labeling as occurring with a class of 
drugs (or other medical products) or as anticipated from the pharmacological properties or other 
characteristics of the IP, but are not specifically mentioned as occurring with the particular IP under 
investigation. 
The Investigator will be responsible for initially determining whether an AE is unexpected, i.e., if 
the nature, severity, or frequency of the event is not consistent with the risk information previously 
described for the IP.  
9.5.1.4.2. Current corrected VA 
Note: Visual acuity (VA) testing must precede any examination requiring contact with the eye or 
eyelid and must precede pupil dilation, instillation of study dyes, external photography of the eyes, 
or application of topical gels as detailed in the order of assessments for the protocol. 
Distance VA will be assessed OU with an ETDRS chart at a 4-meter distance using a LogMAR 
scale. Distance VA should be assessed consistently throughout the study using the same method, 
equipment, and lighting conditions at each site. Current corrected VA testing will be performed 
using subjects’ own prescription eyeglasses, if applicable; subjects who do not achieve a +0.0 
LogMAR score using their prescription eyeglasses, if applicable, will be asked to make their best 
effort while viewing the ETDRS chart through a pinhole occluder. 
Subjects will be instructed to read the letters on the ETDRS chart from the top left-hand corner 
along each row, one letter at a time then down each row, one at a time. There are no numbers on the 
chart, only letters.  
Subjects will be instructed to read slowly at a rate of about 1 letter/second. At the end of the test, the 
examiner will count the number of letters incorrectly identified up to and including the last line read 


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and will record the results on the source document. A VA letter score will be calculated and 
recorded in the Source Document Worksheets and in the eCRF. 
Each letter has a score value of 0.02 log units. Since there are 5 letters per line, the total score for a 
line on the LogMAR chart represents a change of 0.1 log units. The formula used in calculating the 
score is: 
Calculations: LogMAR VA = Baseline value + (n X 0.02)  
where: the baseline value is the LogMAR number of the last line read (at least 1 letter read correctly 
in this line), and “n” is the total number of letters missed up to and including the last line read, and 
“0.02” is the value for each letter 
9.5.1.4.3. Intraocular Pressure (IOP) 
IOP will be measured in mmHg and should be conducted after the slit lamp biomicroscopy exam is 
completed and before dilation of subjects’ eyes. 
IOP measurements will be performed utilizing iCare or another tonometer that does not require the 
use of colored dyes or local anesthetic, and that does not employ an air puff to measure IOP. The 
same method should be used consistently for the same subject for all visits and IOP assessments. 
Measurements will be taken with the subject seated. Two consecutive measurements will be taken 
in each eye and recorded in the source document. The mean of the two measurements will be 
automatically calculated in EDC. If the two measurements differ by >1.0 mmHg, a third 
measurement will be taken and recorded in the source document. The median of the three scores 
will then be automatically calculated in EDC. 
9.5.1.4.4. Manual Pupillometry 
The pupil size will be measured in ambient room light. The subject should be asked to focus straight 
ahead on a target at a distance to avoid accommodation while seated in the exam chair. The subject 
should be instructed not to blink during the measurement. The Investigator should then take the 
pupil measurement card and place it directly below the pupil while avoiding the line of sight, again 
to avoid stimulating accommodation. The Investigator should then match the pupil size to the circle 
size on the card to determine the pupil size. After a brief rest period, the process should be repeated 
to measure pupil diameter in the fellow eye. Each measurement should be recorded in the eCRF. 
If subjects’ eyes become dry during the assessment, artificial tears may be administered and 
recorded as concomitant medication. 


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9.5.1.4.5. Slit Lamp Biomicroscopy 
The slit lamp biomicroscopy exam should be performed with the slit lamp using a beam width and 
intensity that provides optimal evaluation of the anterior segment. The slit lamp exam should be 
performed without fluorescein. 
The slit lamp examination must be performed before any procedures that would require contact with 
the eye or eyelids and prior to the instillation of any dilating or anesthetic eye drops or topical gels. 
The Investigator should use their standard examination technique. This procedure will be performed 
in the same manner for all subjects observed at the Investigator’s site. When possible, the same 
examiner should conduct all slit lamp biomicroscopy examinations at each visit for a given subject 
throughout the study. 
The Investigator must examine the eyelids, conjunctiva, cornea, anterior chamber, iris/pupil, and the 
lens of each eye for evidence of erythema and/or edema, opacities or other signs of abnormalities 
and record a grading for each tissue/structure as specified below. Observations will be documented 
on the appropriate CRF. 
The following aspects of the eye will be evaluated, and corresponding data collected.  
Cornea:  
Includes all corneal layers 
Normal:  
Absence of active inflammation, infection, or structural changes/abnormalities 
Abnormal:  Presence of active inflammation, infection, or structural changes/abnormalities 
including focal scarring and fine deposition 
 
Clinically significant 
Not clinically significant 
 
Eyelids:  
Includes eyelid edema and eyelid erythema 
Normal:  
Absence of active inflammatory signs or significant structural 
changes/abnormalities or discharge 
Abnormal:  Presence of active inflammatory signs or significant structural 
changes/abnormalities or discharge 
 
Clinically significant 
Not clinically significant 
 
Conjunctiva:  Includes periocular tissues, and the bulbar, palpebral and limbal conjunctiva 
Normal:  
Absence of active inflammatory signs or significant structural 
changes/abnormalities or discharge 


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Abnormal:  
Presence of active inflammatory signs or significant structural 
changes/abnormalities or discharge 
 
Clinically significant 
Not clinically significant 
Lens 
Phakic 
 
Pseudophakic 
 
Aphakic 
 
Lens Opacity (Phakic only) 
None (0) 
None present or less than mild 
Mild (1) 
Yellow lens discoloration or small lens opacity (axial or peripheral) 
Moderate (2) 
Amber lens discoloration or medium lens opacity (axial or peripheral) 
Severe (3) 
Brunescent lens discoloration or complete lens opacification (no red reflex) 
 
9.5.1.4.6. Indirect Dilated Ophthalmoscopy 
This procedure will occur after application of dilating eyedrops and upon Investigator confirmation 
with a pen light OU are fully dilated (recommended time of at least 20 minutes). As dilating drops 
will be applied, indirect dilated ophthalmoscopy must be performed after external eye and eyelid 
photography, tests of visual acuity, IOP assessments, and assessments of corneal staining and 
healing. 
Indirect dilated ophthalmoscopy will include assessment of the vitreous, retina, macula, choroid, 
optic nerve, and vertical optic nerve cup-to-disc ratio. After the ophthalmoscopy procedure, the 
Investigator will determine if findings are within normal limits or are abnormal. For abnormal 
findings at Screening (Visit 1), the Investigator will determine whether the abnormality would 
exclude the subject from study participation. Observations will be documented on the appropriate 
CRF. Abnormalities should be marked as “clinically significant” or “not clinically significant.”  
Vitreous: 
 
Normal:  
Absence of any opacity 
Abnormal:  Presence of opacity 
 
 
Clinically significant 
 
Not clinically significant 
Retina: 
 
Normal:  
Absence of active inflammation or significant structural changes 
Abnormal:  Presence of active inflammatory signs or significant structural changes 
 
 
Clinically significant 


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Not clinically significant 
Macula: 
 
Normal:  
Absence of active inflammation or significant structural changes 
Abnormal:  
Presence of active inflammatory signs or significant structural changes 
               Clinically significant 
Not clinically significant 
Choroid: 
 
Normal:  
Absence of active inflammation or significant structural changes 
Abnormal:  
Presence of active inflammatory signs or significant structural changes 
 
Clinically significant 
              Not clinically significant 
 
 
Optic Nerve: 
 
Normal:  
Absence of any damage 
Abnormal:  
Presence of any damage 
 
 
Clinically significant 
 
Not clinically significant 
 
Vertical Optic Nerve Cup-to-Disc Ratio: 
__. __ __  
 
Other: 
Indicate any other dilated fundus ophthalmoscopy findings 
 
No 
 
Yes 
If yes, specify finding and clinical significance 
 
9.5.1.4.7. Conjunctival Hyperemia Evaluation 
Investigators will rate overall bulbar conjunctival hyperemia using the Brien Holden Vision 
Institute (BHVI) grading scale [formerly known as the Cornea and Contact Lens Research Unit 
(CCLRU) grading scale]. The following investigator BHVI ratings will be recorded in the eCRF. 
. 
Score 
Redness 
0 
None 
1 
Very Slight  


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2 
Slight 
3 
Moderate 
4 
Severe  
 
9.5.1.4.8. Vital Signs 
Subject vital signs will be assessed at the Screening visit (Visit 1), Baseline (Visit 2 before IP 
administration), and during the study period after IP administration at Hour 1 and Hour 8. Vital 
signs will include blood pressure while in a seated position and resting heart rate. 
9.5.1.4.9. Urine Pregnancy Test (only for women of child-bearing potential (WOCBP)) 
For the purposes of this study, a woman of child-bearing potential will be defined as a subject with 
a uterus who is capable of becoming pregnant. 
WOCBP must agree to use one of the following methods of birth control from the date they sign the 
ICF until after the completion of the last study visit (Follow-Up Visit): 
a. Abstinence, when it is in line with the preferred and usual lifestyle of the subject, where 
abstinence may be defined as refraining from sexual contact or defined as engaging in 
relationships in which it is impossible for sexual contact to result in pregnancy; 
b. Maintenance of a monogamous relationship with a male partner who has been surgically 
sterilized by vasectomy (vasectomy procedure must have been conducted at least 60 
days prior to the Screening visit or confirmed via sperm analysis); 
c. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream 
AND either hormonal contraception (oral, implanted or injectable) or an intrauterine 
device or system. 
Note: Non-child-bearing potential for the purposes of this study is defined as surgical sterilization 
(i.e., bilateral oophorectomy, hysterectomy, or tubal ligation), postmenopausal (defined as not 
having a menstrual period for at least 12 consecutive months prior to Screening), or medical 
confirmation of infertility. 
9.5.1.4.10. IP Comfort Assessment 
Subjects will be asked on the day of study treatment to rate the comfort/tolerability of the study IP using 
a Visual Analog Scale (VAS) after the IP has been applied to their upper eyelids. This assessment will 
be focused on the comfort of the IP itself, and subjects should be instructed to think about the comfort of 


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the IP after dosing application and independently from their experience having the IP applied by study 
staff.  
Subjects will be asked to place a single vertical mark along a horizontal 100-mm line to indicate the 
level of comfort/discomfort they experienced after IP administration. For the VAS, 0 mm represents no 
comfort at all and 100 mm represents the most comfortable. There may be differences in the length 
of the line on each CRF page due to photocopy/printing anomalies. Both the subject response and 
total length of the scale will be measured from the left margin of the scale to the nearest ½ 
millimeter.  The VAS score is the ratio of the patient response to the total length of the scale. 
Subjects will also be provided with an empty text box to collect any additional notes they would like to 
share about their experience with the IP in regards to its comfort and tolerability. 
9.5.2. 
Appropriateness of Measurements 
All assessments used in this study are widely used and generally recognized as reliable, accurate, 
and relevant. 
9.5.3. 
Primary Efficacy Variables 
9.5.3.1. 
Efficacy Endpoints 
 
The efficacy endpoint variables are as follows: 
• Change from baseline in the number of points seen in supervisor visual field section (top 
rows) of Leicester Peripheral Field Test (LPFT) at Hours 2 and 6, and as well as change 
from Hour 2 at Hour 6 
• Continuous and categorical analysis in both eyes of change from baseline in margin reflex 
distance 1 (MRD1) of 1.0, 1.5, 2.0, and 2.5 mm at Hours 0.5, 1, 2, 4, 6, and 8 
• Change from baseline on both eyes of ocular hyperemia grade using Brien Holden vision 
Institute (BHVI) grade scale at Hours 0.5, 1, 2, 4, 6, and 8. 
• Change from baseline in FACE-Q | Aesthetics questionnaires at Hours 4 and 8. 
• Change from baseline in Investigator-reported outcome questionnaires at Hours 4 and 8. 
 
9.5.3.2. 
Safety Endpoints 
This is primarily a safety and tolerability study with the following safety endpoints. 
• The incidence and severity of systemic and ocular adverse events (AE) 
• Current corrected visual acuity (VA), using subject’s own prescription eyeglasses, if 
applicable, in both eyes as measured by Early Treatment Diabetic Retinopathy Study 
(ETDRS) at the Screening visit, Baseline, and Hour 8 
• Intraocular pressure (IOP) measured in both eyes at the Screening visit, Baseline, Hour 1, 
and Hour 8  


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• Slit lamp examination of both eyes at the Screening visit, Baseline, and Hour 8 
• Manual pupillometry of both eyes as measured at the Screening visit, Baseline, Hour 1, 
Hour 4, and Hour 8  
• Heart rate and blood pressure as measured at the Screening visit, Baseline, Hour 1, and Hour 
8  
• Subject-report investigational product (IP) comfort questionnaire [Visual Analog Scale 
(VAS)] at Hour 1 
 
9.5.4. 
Drug Concentration Measurements 
Not Applicable. 


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9.6. 
DATA QUALITY ASSURANCE 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  An individualized quality management plan 
will be developed to describe a site’s quality management.   
Quality control (QC) procedures will be implemented beginning with the data entry system and data 
QC checks that will be run on the database will be generated.  Any missing data or data anomalies 
will be communicated to the site(s) for clarification/resolution.   
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical 
trial is conducted and data are generated and biological specimens are collected, documented 
(recorded), and reported in compliance with the protocol, International Council for Harmonisation 
(ICH) Good Clinical Practice (GCP), and applicable regulatory requirements (e.g., Good Laboratory 
Practice [GLP], Good Manufacturing Practices [GMP]).   
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the Sponsor, and inspection by local and 
regulatory authorities.  
9.6.1. 
Training and Education of Investigators and Study Site Personnel 
 
An Investigator Meeting will be held before study initiation and attended by the Investigators and/or 
Sub-Investigators from each study site, study coordinators from each study site, if possible, and 
personnel from the sponsor and the Contract Research Organization (CRO), Lexitas Pharma 
Services, Inc. (hereafter referred to as Lexitas). The purpose of this meeting is to train and instruct 
the Investigators and the study coordinators on the proper conduct of the clinical trial and ensure 
that all participants are aware of their obligations set out by the protocol, ICH guidelines, GCP 
guidelines, and other applicable regulatory requirements. 
9.6.2. 
Monitoring of Study Sites 
Lexitas will conduct the clinical monitoring for this study.  A Clinical Monitoring Plan (CMP) is to 
be used, which will describe in detail who will conduct the monitoring, at what frequency 
monitoring will be done, at what level of detail monitoring will be performed, and the distribution 
of monitoring reports. 


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9.6.3. 
Data Entry and Verification of Database Used for Analysis and 
Reporting 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site’s Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported.   
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets 
for recording data for each participant enrolled in the study. Data recorded in the electronic case 
report form (eCRF) derived from source documents should be consistent with the data recorded on 
the source documents.   
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into Merative Clinical Development, a 21 CFR Part 11-
compliant data capture system provided by Lexitas Pharma Services, Inc. The data system includes 
password protection and internal quality checks, such as automatic range checks, to identify data 
that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the 
source documents. 
9.6.4. 
Clinical Study Report 
The final clinical study report will be reviewed, audited, and approved by medical, clinical, 
statistical, and regulatory staff from the sponsor, and key study contributors from Lexitas. 
9.6.5. 
Inter-Laboratory Standardization Methods 
Not applicable. There will be no clinical safety laboratory data.  


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9.7. 
STATISTICAL METHODS PLANNED IN THE PROTOCOL AND 
DETERMINATION OF SAMPLE SIZE 
This section of the analysis plan describes the analyses explicitly mentioned in the protocol as well 
as additional analyses not explicitly mentioned in the protocol but planned prior to breaking the 
treatment mask. Section 9.8 describes any changes to analyses that were explicitly mentioned in the 
protocol or statistical analysis plan. 
9.7.1. 
Statistical and Analytical Plans 
General Conventions 
Summary statistics for the data collected during this study will be presented to give a general 
description of the subjects studied. Data from all sites will be combined in the computation of these 
descriptive summaries. Categorical variables will be summarized by the frequency and percentage 
of subjects in each category. Continuous variables will be summarized using N, mean, standard 
deviation (SD), median, minimum, and maximum values. 
Number of subjects, minimums, and maximums will be calculated to the same number of decimal 
places as the source data. Means, medians, other quartiles, and confidence limits will be calculated 
to one more decimal place than the source data; standard deviations and standard errors will be 
calculated to two more decimal places than source data. Percentages will be calculated to the 
nearest one decimal place. Zero count cells will be displayed as “0” with percentage of (0%). 
Summaries will be performed by the treatment group and presented in the order of LEV102, 2.0%, 
LEV102, 1.0%, and Vehicle. 
In general, analyses will examine the differences between individual treatment arms, as well as the 
differences between combined arms of LEV102 Topical Gel compared to vehicle. In addition, 
safety analyses related to ocular endpoints will be performed by study eye and non-study eye. Non-
study eye refers to fellow eye. 
Study eye is defined as follows: 
• If both eyes qualify for the study, the eye with the lower MRD1 value at Baseline will be 
designated as the study eye.  
• If MRD1 values are the same for OU at Baseline, the right eye will be designated as the 
study eye.  
Regardless of study eye or study qualification, all eyes in this study will receive study IP and 
undergo study assessments. 
Summary of safety analysis will be presented by treatment arm: 


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• LEV102, 2.0%  
• LEV102, 1.0% 
• Vehicle 
In addition, summary of efficacy analysis will be presented by combined arm (LEV102, 2.0% or 
LEV102, 1.0%) as well. 
No formal hypotheses for efficacy have been defined. Summary statistical analyses are exploratory 
only without any significance testing. 
For all exploratory efficacy analyses and all safety analyses performed, baseline assessments are to 
be performed on Day 1 before the application of IP. 
All data collected in this study will be presented in individual subject data listings for all subjects. 
Computations for all results will be performed using SAS (Version 9.4, SAS/STAT 15.2 or higher) 
computer software package (SAS Institute, Inc, 2013, 2020), unless otherwise specified. 
Strata and Covariates 
For analysis of continuous efficacy endpoints, mixed-effect model repeated measure (MMRM) 
models will model the change from baseline of each endpoint as the dependent variable with the 
baseline measurement of the corresponding endpoint as a covariate and treatment, time, and 
treatment by time interaction as fixed effects. A random effect for site will be added to account for 
site-to-site variability. 
Subgroups 
All efficacy analysis will be stratified by abnormal clinically significant (CS) superior visual field 
loss and abnormal not clinically significant (NCS) superior visual field loss based on baseline LPFT 
values.  
  
Multiplicity 
Not applicable because the statistical analyses are exploratory.  
Missing Data and Outliers 
Every attempt will be made to capture all study data. No imputations will be performed, only 
observed data will be summarized in general except for imputation of missing responses for items in 
FACE-Q questionnaires per the standard grading rules.  
To score a scale in each of 3 modules i.e. Satisfaction with Eyes, Appraisal of Upper Eyelids, and 
Appraisal of Lower Eyelids in FACE-Q, the raw scores for the set of items or questions in a module 
are added together to produce a total raw score for each module. If missing data is less than 50% of 
the scale’s items, replace missing data with the mean of the completed items. The following 3 


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Conversion Tables below are utilized to convert the raw scale summed score into a score from 0 
(worst) to 100 (best). 
Table 2. FACE-QTM  –  Satisfaction with Eyes Conversion Table  
 
Sum score 
Equivalent Rasch Transformed Score (0-100) 
7 
0 
8 
10 
9 
16 
10 
20 
11 
24 
12 
28 
13 
32 
14 
35 
15 
39 
16 
43 
17 
47 
18 
51 
19 
55 
20 
59 
21 
63 
22 
68 
23 
72 
24 
77 
25 
81 
26 
86 


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27 
92 
28 
100 
 
Table 3. FACE-QTM – Appraisal of Lower Eyelids Conversion Table  
 
Sum Score 
Equivalent Rasch Transformed Score (0-100) 
7 
0 
8 
10 
9 
17 
10 
23 
11 
28 
12 
32 
13 
36 
14 
39 
15 
42 
16 
46 
17 
49 
18 
52 
19 
55 
20 
58 
21 
61 
22 
64 
23 
68 
24 
72 
25 
77 


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26 
82 
27 
90 
28 
100 
 
Table 4. FACE-QTM - Appraisal of Upper Eyelids Conversion Table 
 
Sum  Score 
Equivalent Rasch Transformed Score (0-100) 
7 
0 
8 
8 
9 
15 
10 
21 
11 
26 
12 
30 
13 
34 
14 
38 
15 
42 
16 
46 
17 
49 
18 
53 
19 
56 
20 
59 
21 
63 
22 
66 
23 
70 
24 
74 


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25 
78 
26 
83 
27 
90 
28 
100 
 
Visit Windows 
The nominal visits listed in the eCRF will be used in the summaries. In general, unscheduled visits 
will not be summarized in tables unless otherwise noted. 
Missing Dates 
Missing dates that occur for prior or concomitant medications or adverse events will be queried for 
a date. If no date is obtained, the following imputation rules will apply: 
• For start dates, if the given year (or year-month) is the same as study drug administration, 
the start date will be imputed as study drug administration date; otherwise, missing month-
day (or day) will be imputed as ’01-01’ (or ’01’). 
• For stop dates, missing months will be imputed as ‘12’ and missing days will be imputed as 
the last day of the month. If this creates a date after discontinuation/completion, the date of 
discontinuation/completion will be used. 
Imputed dates will only be used to classify events or medications, such as occurring before or after 
the start of treatment. Imputed dates will only be used in tables. Listings will display the available 
date data. 
Interim Analysis 
There is no planned interim analysis. 
9.7.1.1. 
Analysis Populations 
The Safety Analysis Set will include all randomized subjects who received at least 1 dose of IP as 
indicated on the dosing record. Subjects will be analyzed in the group according to the IP treatment 
received. All endpoints will be analyzed using the Safety Analysis Set and only observed data will 
be included with the exception noted for the FACE-Q questionnaires. 
9.7.1.2. 
Analysis of Subject Disposition 
The number of subjects randomized at each site will be summarized by treatment group and overall. 


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Subjects’ enrollment and disposition during the study will be summarized by treatment groups, and 
overall. The reasons for discontinuation will be displayed in the order as they appear on the eCRF. 
Summary tables will include the following. The percentages will be calculated based on the number 
of subjects randomized who received at least one dose of study therapy.  
• Number of subjects screened;  
• Number and percentage of subjects dosed; 
• Number and percentage of subjects in Safety Analysis Set; 
• Number and percentage of subjects treated who completed the study; 
• Number and percentage of subjects treated who discontinued from the study; 
• The reasons for study discontinuation; 
• Number and percentage of subjects completing each study visit; 
A listing of subjects who do not meet all inclusion criteria or meet exclusion criteria will be 
provided. 
A table of protocol deviations will be presented by its classifications and categories, in overall using the 
Safety Analysis Set. There are three protocol deviation (PD) classifications, i.e. minor, major, and 
critical, and following 8 PD categories: 
• 
Informed consent  
• 
Inclusion and exclusion criteria  
• 
Study visit schedule 
• 
Study assessment 
• 
Missed procedure 
• 
Investigational product  
• 
Concomitant medication 
• 
Other 
9.7.1.3. 
Analysis of Demographic and Baseline Characteristics 
9.7.1.3.1. Demographics and Disease Characteristics 
Demographic characteristics including age (years), age group (<55 year old, ≥ 55 year old), sex, 
race, ethnicity, overall average levator function by study eye and non-study eye will be summarized 
descriptively by treatment groups and overall using the Safety Analysis Set. Similarly, for 
categorical parameters, the percentages will be calculated based on the number of subjects with 
non-missing observations.  


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9.7.1.3.2. Medical History 
Medical history will be coded using MedDRA Version 25.1 or later. The frequency and percentage 
of subjects with any medical history will be summarized by treatment group and overall using the 
Safety Analysis Set. System organ class (SOC) will be sorted alphabetically and preferred term (PT) 
within each SOC will be sorted by overall descending order of frequency according to following 
rules in order: 
• Descending frequency within Treatment 1 (LEV102, 2.0%): n = 10 
• Descending frequency within Treatment 2 (LEV102, 1.0%): n = 10 
• Descending frequency within Control (Topical Gel): n = 10 
• PT in alphabetical order 
The medical history will include both the ocular and the general (non-ocular) history. Ocular 
medical history and general (non-ocular) medical history will be summarized separately. Ocular and 
non-ocular medical histories are identified according to which CRF the event is recorded. Ocular 
medical history will be summarized if a term occurs for either eye (i.e., at the subject-level). 
9.7.1.3.3. Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHODrug) (B3 WHO Drug Global, Version Sep 2022 or later) for anatomical 
therapeutic chemical (ATC) classification and preferred drug name.  
The frequency and percentage of subjects with coded medications will be summarized by treatment 
group and overall using the Full Analysis Set. A subject who used multiple medications will be 
counted only once for each ATC and preferred drug name. Therapeutic Subgroup (ATC level 3) is 
sorted alphabetically, and preferred term is sorted by descending frequency overall within each 
Level 3 term according to following rules in order: 
• Descending frequency within Treatment 1 (LEV102, 2.0%): n = 10 
• Descending frequency within Treatment 2 (LEV102, 1.0%): n = 10 
• Descending frequency within Control (Topical Gel): n = 10 
• PT in alphabetical order 
Prior and concomitant medications will be summarized separately. Ocular medications are defined 
as those medications for which an eye has been specified (OD, OS, or OU). Ocular and non-ocular 
medications will be summarized separately. Ocular medications will be summarized separately for 
OD, OS, and either eye. 


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Prior medications are defined as any medications stopped prior to the date of first dose of study 
medication. Concomitant medications are defined as any medications that (1) start prior to the date 
of first dose of study medication and are ongoing; or (2) start on or after the date of first dose of study 
medication; or (3) stop through the end of study (Visit 3). Medications taken after Day 5 or withdrawal 
from the study are not considered concomitant. 
9.7.1.4. 
Analysis of Study Medication Compliance and Exposure 
Because this is a Phase 1/2a single-dose study, compliance and exposure will not be summarized in 
the table, but they will be presented in a listing. 
9.7.1.5. 
Analysis of Efficacy and Safety Endpoints 
The primary objective of this study is to assess the ocular and systemic safety and tolerability of a 
single application of LEV102 Topical Gel on the upper eyelids in subjects with acquired 
blepharoptosis; therefore, the study is not powered for the primary efficacy endpoint. However, 
several exploratory efficacy endpoints are collected and analyzed. All qualifying eyes will be used 
for analyses of efficacy. For some of those efficacy endpoints, such as LPFT, BHVI, and MRD1, 
they will be analyzed by study eye and qualified eyes. In addition, it will be stratified by abnormal 
clinically significant superior visual field loss and not clinically significant superior visual field 
loss. 
All analyses comparing LEV102 to vehicle will be conducted on pooled LEV102 arms versus the 
vehicle arm. Additional analyses will explore each arm individually against the vehicle arm. 
Further, treatment estimates and 95% CI will be reported for LEV102 pooled and each dose 
separately vs. the vehicle arm.   
9.7.1.5.1. Efficacy Endpoint Analyses 
9.7.1.5.1.1. Leicester Peripheral Field Test (LPFT) 
The observed and change from baseline in the number of points seen in superior visual field section 
(top 4 rows) of LPFT at Hours 2 and 6, as well as change from Hour 2 at Hour 6 will be shown by 
treatment group. In addition, visual field status, i.e. abnormal clinically significant superior visual 
field loss and not clinically significant superior visual field loss, change from baseline to both Hour 
2 and Hour 6 as well as change from Hour 2 to Hour 6 will be shown by treatment groups. 
Moreover, the mean CFB in LPFT score will be analyzed using a MMRM model. The model will 
include treatment, hour, and treatment by hour interaction as fixed effects, with a random effect for 
site. An unstructured covariance among repeated measurements between qualifying eyes is 
assumed. The two primary groups for comparison are all subjects randomized to LEV102 Topical 
Gel (pooling 2.0% and 1.0% doses) vs. subjects randomized to vehicle. In addition, two dosing 


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groups will be compared using CFB in LPFT score to determine if there is a significant difference 
in CFB. 
Sample analysis code: 
proc mixed data = indata; 
class subject center hour treatment; 
 
model change = baseline hour treatment hour*treatment / solution DDFM = KR; 
 
repeated / type = un subject = subject; 
 
random center; 
 
lsmeans hour*treatment / slice = hour diff cl; 
run; 
Should the model not converge, compound symmetry will be assumed. Comparisons among 
individual arms will be obtained from the lsmeans statement. Comparisons between the combined 
active arm and vehicle (least-squares means, treatment differences, 95% confidence intervals) will 
be obtained using estimate statements. Assume treatments are ordered: 
1. LEV102, 2.0%;  
2. LEV102, 1.0% 
3. Vehicle  
 
And baseline, Hour 2, and Hour 6 are ordered numerically. Let 𝑛2% and 𝑛1% be the total number of 
subjects in LEV102, 2.0% and LEV102, 1.0% arms in the safety analysis set. The percent of 
subjects in each arm are define as follows: 
𝑝= 
𝑛1.0% 
𝑛1.0%+𝑛2.0% . 
 
To generate the estimates for the combined LEV102 1.0% and 2.0% for Hour 2 and Hour 6, see the 
below code. 
 
 
 
 
 
 
    
        
      
        
 
 
 
 
 
 
 
 
      
 
       
  
 
    
 
 
 
 
 
 
     
        
      
        
 
 
 
 
 
 
 
 
                
 
       
  
 
   
 
 


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9.7.1.5.1.2. Margin Reflex Distance 1 
First, spaghetti plots of response profiles for margin reflex distance 1 (MRD1) over time will be 
presented by each subject and across three treatment groups. Means and SD for MRD1 over time will 
be shown by treatment group in the same Figure. Summary statistics for observed data and changes 
from baseline for MRD1 of 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm at Hour 0.5, Hour 1, Hour 2, Hour 
4, Hour 6, and Hour 8 will be shown by treatment group. The mean CFB in MRD1 values will be 
analyzed using a MMRM model as well. In addition, a comparison between mean maximum MRD1 
change from baseline at post-dosing (Visit 2), i.e. maximum mean difference between anytime point 
tested and hour 0 at Baseline, and mean Upneeq® response values at Screening (Visit 1) after single 
drop of Upneeq® (oxymetazoline 0.1% ophthalmic solution) to each eye will be performed within 
each treatment group. Bar graphs of maximum change in MRD1 from Baseline and mean Upneeq® 
response at Screening will be shown within a treatment group. Furthermore, MMRM model will be 
utilized to determine if Upneeq® response values at Screening has any impact on MRD1 change from 
Baseline at each post-dosing hours while controlling baseline covariates.  
 
Moreover, a comparison between MRD1 change at Hour 2 from baseline and Upneeq’s response at 
Hour 2 will be conducted within each treatment group. 
9.7.1.5.1.3.Conjunctival Hyperemia Evaluation 
Spaghetti plots of response profiles for Brien Holden Vision Institute (BHVI) grading scale over 
time will be presented by each subject and grouped by Treatment group. The observed and change 
from baseline in ocular hyperemia grade using the BHVI grading scale at Screening and Hour 0 , 
Hour 0.5, Hour 1, Hour 2, Hour 4, Hour 6, and Hour 8 at the Baseline visit will be presented by 
Treatment group. The status of change includes improvement in ≥1 units or worsening ≥1 units in 
terms of the grading scale. 
9.7.1.5.1.4. FACE-Q | Aesthetics 
The FACE-Q© is a subject-reported outcome measure that can be used to measure outcomes of 
facial procedures and products from the subject’s perspective. This instrument has been used to 


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evaluate the safety and effectiveness of facial aesthetic treatments in numerous clinical trial settings 
and to inform patient care in clinical practice. The FACE-Q© is composed of a set of 39 
independently functioning scales/checklists that measure 3 overarching domains: Facial 
Appearance, Health-Related Quality of Life, and Adverse Effects.  
There is no overall or total FACE-Q score. Instead, the FACE-Q in this study is composed of the 
following three independently functioning scales or modules that are each scored separately and 
produces each single item visual analogue scale.  
 
1. Satisfaction with Eyes (7 items) 
2. Appraisal of Upper Eyelids (7 items) 
3. Appraisal of Lower Eyelids (7 items) 
To score a scale, the raw scores for the set of items in a scale or modules are added together to 
produce a total raw score.  
Once a total raw score for the scale or module for a patient is computed, the Conversion Table can 
be used to convert the raw score into a score that ranges from 0 (worst) to 100 (best). If missing data 
is less than 50% of the scale’s items, within person mean for the completed items can be imputed 
for the missing items prior to computing a total raw score. For example, if there is a 7-item scale or 
module in this study, and someone has not responded to all the items, but has responded to ≥4 
items, all other items for that person can be imputed with a within-person mean (rounded to the 
nearest integer), and a summed score can be calculated. 
Summary statistics for observed data and changes from baseline in each module for FACE-Q | 
Aesthetics questionnaires will be presented at Screening, baseline, Hours 4 and 8 by treatment 
group. In addition, MMRM model will be utilized to determine if MRD1 change from Baseline at 
each post-dosing hours has any impact on FACE-Q from Baseline at each post-dosing hours while 
controlling baseline covariates. The response to individual questions will be presented in the listing. 
9.7.1.5.1.5.   Investigator Report Outcome 
Spaghetti plots of response profiles for investigator reported outcome (IRO) by each subject over 
time will be shown across three treatment groups. Frequency and distribution of IRO will be 
presented across Screening, Baseline, and Visit 2 (Hour 4 and 8). In addition, changes from hour 0 
at Baseline in IRO questionnaires will be shown for Hour 4 and Hour 8 by each question and total 
score for treatment groups. Moreover, Impact of change in MRD1 on IRO  will be evaluated by 
Ordinal Model for Multi-nominal Data to determine the probability for IRO improvement based on 
change in MRD1 from Baseline. 


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9.7.1.5.2. Safety Endpoint Analysis 
Safety analyses will be performed on all subjects in the Safety Analysis Set. The assessment of 
safety will be based on the summary of ocular and non-ocular AEs, current corrected VA, IOP, 
manual pupillometry, slit lamp biomicroscopy, indirect dilated ophthalmoscopy, conjunctival 
hyperemia evaluation, vital signs, urine pregnancy tests, and a comfort questionnaire. Summaries 
will be provided by treatment group, and for ocular assessments separately by eye.  
9.7.1.5.2.1. Adverse Events 
AEs are coded using MedDRA Version 25.1 or later. Ocular AEs are defined as those events for 
which an eye has been specified (OD, OS, or OU). Treatment-emergent adverse events (TEAEs) 
will be defined as AEs that start on or after the date of the first dose of double-masked study 
medication through the end of Visit 3 or early withdrawal. Pretreatment adverse events are events that 
begin prior to the date of double-masked study medication. Summaries of AE will focus on those 
events that are treatment-emergent. 
Ocular and non-ocular TEAEs are summarized separately. In all summaries of TEAEs, percentages 
are calculated based on the number of subjects in each treatment group of the Safety Analysis 
Set. Overall summaries of TEAEs by treatment group will include:   
 
• The number of TEAEs and serious TEAEs reported;   
• The number and percentage of subjects who experienced any TEAEs;  
• The number and percentage of subjects who experienced any serious TEAEs and the reason 
for seriousness;   
• The number and percentage of subjects with any TEAEs leading to study termination; 
• The number and percentage of subjects with any TEAE by worst severity and worst 
relationship.  
 
Summaries of the frequency and percentage of subjects with TEAEs by SOC and preferred term by 
treatment group will include:  
 
• All TEAEs by SOC and preferred term;  
• All TEAEs by SOC, preferred term, and maximum severity;  
• All TEAEs by SOC, preferred term, and maximum relationship. 
  
System organ class (SOC) will be sorted alphabetically, and preferred term (PT) within each SOC 
will be sorted by overall descending order of frequency according to the following rules in order: 
• Descending frequency within Treatment 1 (LEV102 , 2.0%): n = 10 
• Descending frequency within Treatment 2 (LEV102, 1.0%): n = 10 


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• Descending frequency within Control (Vehicle), n=10  
• PT in alphabetical order.  
Subjects are counted only once for each SOC and PT. In summaries of maximum severity and 
maximum relationship, subjects with multiple occurrences of events will only be counted once at 
the maximum severity/relationship per SOC and PT.  
 
Any TEAEs that have a missing severity will be presented as severe in the summary table but will 
be presented with a missing severity in the data listing. Any AEs that have a missing study 
relationship will be presented with a relationship of “Related” in the summary table but will be 
presented with a missing relationship in the data listing.  
 
All TEAEs are displayed in listings. In addition, separate listings will be provided for:  
• Subjects with any adverse event leading to study termination;  
• Subjects with any serious adverse event;  
• Subject deaths. 
9.7.1.5.2.2. Current Corrected Visual Acuity 
Summary statistics for observed and change from Baseline for current corrected visual acuity for 
study eye and non-study eye will be presented by treatment groups. 
9.7.1.5.2.3. Intraocular Pressure (IOP) 
Descriptive summaries of the observed values at each scheduled visit as well as the change from 
baseline at each post-baseline visit will be shown by treatment groups.  
9.7.1.5.2.4. Manual Pupillometry 
Descriptive summaries of the observed values in pupil diameter at each scheduled visit as well as 
the change from baseline at each post-baseline visit for study eye and non-study eye will be 
presented by treatment groups.  
9.7.1.5.2.5. Slit Lamp Biomicroscopy  
The frequency and percentage of subjects with observed values of normal and abnormal as well as 
the categorical shift from baseline at each post-baseline visit will be tabulated for each parameter at 
each scheduled visit by eye and treatment group.  
9.7.1.5.2.6. Indirect Dilated Ophthalmoscopy 
Indirect dilated ophthalmoscopy will be presented in a listing.  


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9.7.1.5.2.7. Vital Signs 
Descriptive summaries of the observed values of vital signs at the Screening, Baseline, and at Hours 
1 and 8 will be presented for each parameter by treatment group. Vital signs include heart rate 
(bpm), systolic, and diastolic blood pressure. 
9.7.1.5.2.8. Investigational-Product (IP) Comfort Assessment  
Investigational-Product (IP) comfort assessment will be conducted at 1 hour after dosing. 
Descriptive summaries of the observed scores of Comfort/Tolerability Rating Scale of the IP at 1 
hour after dosing will be presented for each treatment group.  
9.7.2. 
Determination of Sample Size 
The sample size of 10 subjects per arm (30 subjects total for a total of 60 eyes) is not based on  
formal power or precision considerations. 


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9.8. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSES 
9.8.1. 
 Protocol Amendments 
Date 
Description 
Substantive/Non-Substantive 
25 May 2023 
Protocol Amendment 
5 (Version 6.0) 
Revise Investigator-reported exploratory outcome 
endpoint  as described in Protocol Clarification 
Memo_12Apr2023 - signed 
• Revise screening window  
• Add a note to exclusion criterion #1  
• Add a note to exclusion criterion #5  
• Revise exclusion criterion #9  
• Revise exclusion criterion #10  
• Revise exclusion criterion #13  
• Revise exclusion criterion #21  
• Revise exclusion criterion #22  
• Revise exclusion criterion #24  
• Remove exclusion criterion #27  
• Additional updates were made for consistency with the 
changes outlined above or changes administrative in 
nature.  
 
 
12 April 2023 
Protocol Clarification 
Memo_12Apr2023 - 
signed 
 
Investigator Reported Outcome visit changes from 
Baseline, Hour 1, and Hour 8 to Baseline. Hour 4, 
and Hour 8. 
 
06 April 2023 
Protocol Amendment 4 
(Version 5.0) 
• Revise threshold for MRD1 from 2.0 mm to 
2.3 mm 
• 
Rescreening may also occur based upon 
protocol amendments with prior approval from 
the Medical Monitor and Sponsor. 
• 
MRD1 is defined as the distance from the 
margin of the upper eyelid to the top of the 
corneal light reflex when the eye is held in 


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primary position (normal MRD1 is 4.0-4.5 
mm). 
 
17 January 
2023 
Protocol Amendment 3 
(Version 4.0) 
• Revise the timing of the Leicester 
Peripheral Field Test to occur at Screening, 
Baseline, Hour 2, and Hour 6 
• Clarify that exclusionary ophthalmic α-
adrenergic agonist includes brimonidine 
• Additional updates were made for 
consistency with the changes outlined above 
or changes administrative or stylistic in 
nature or as clarifications 
06 December 
2022 
Protocol Amendment 2 
(Version 3.0) 
• Update the Safety Analysis section in the 
protocol to include pregnancy details. This 
section provides details on the data 
collection and follow-up activities that will 
occur if a subject becomes pregnant during 
the study or up until 30 days after study 
completion. Additional details have been 
added to describe follow-up procedures and 
how the data will be utilized. 
 
• Revise and update list of procedures in 
Section 7 (Study Activities) to include 
Bulbar Conjunctival Hyperemia to match 
Appendix 1: Schedule of Visits and 
Procedures 
 
• Revise and update Appendix 11: Slit Lamp 
Biomicroscopy to remove “anesthetic 
drops” as these are not permitted in the 
study. 
 
• Revise and update Appendix 11: Slit Lamp 
Biomicroscopy to add “Anterior Chamber
” and “Iris/Pupil” assessment tables. 
 


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• Revise and update Appendix 13: Indirect 
Dilated Ophthalmoscopy to remove “
assessments of corneal staining and healing
” as this is not applicable. 
• Additional updates were made for 
consistency with the changes outlined above 
or changes administrative or stylistic in 
nature 
30 August 
2022 
Protocol Amendment 1 
(Version 2.0) 
This is a substantiative amendment; changes were 
made based on FDA comments on 26 July, 01 
August, 03 August and 18 August 2022. Details 
can be found in the corresponding Summary of 
Changes document. 
19 May 2022 
Original Protocol 
(Version 1.0) 
N/A 
9.8.2. 
Changes from Protocol-Specified Analyses 
There are no changes from protocol-specific analyses. 
9.8.3. 
SAP Amendments 
There were five (5) amendments made to the SAP since the original protocol was approved.  
REFERENCES 
1. Ho SF, Morawski A, Sampath R, Burns J. Modified visual field test for ptosis surgery 
(Leicester Peripheral Field Test). Eye (Lond) 2011;25(3):365-369. 
2. Levation Pharma Ltd.,  2023. A Phase 1/2a Study of LEV 102 Topical Gel in Subjects with 
Acquired Blepharoptosis. The Study Protocol. Version 6. 
3. SAS Institute Inc. (2020). SAS/STAT User’s Guide. SAS Institute Inc., Cary, NC, USA. 
 
 
 


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APPENDIX I: SCHEDULE OF PROCEDURES AND ASSESSMENTS 
Days/Weeks 
Screening 
(Day -45 to 
Day -10)  
Baseline/Randomization/Day 1 
Day 2-5 
(Telephone 
Follow-Up) 
Visit 
1 
2 
3 
Time (Hours) 
--- 
Baseline1 
Hour 0 
(IP 
Dosing) 
0.5 hour  
(±10 
minutes) 
1 hour  
(±15 
minutes) 
2 hours  
(±15 
minutes) 
4 hours  
(±15 
minutes) 
6 hours  
(±15 
minutes) 
8 hours  
(±60 
minutes) 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
criteria  
X 
X 
 
 
 
 
 
 
 
 
Randomization 
 
 
X2 
 
 
 
 
 
 
 
IP administration OU  
 
 
X2 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical/Ocular/Surgical 
history 
X 
X 
 
 
 
 
 
 
 
 
Vital signs3 
X 
X 
 
 
X 
 
 
 
X 
 
Urine pregnancy test4 
X 
X 
 
 
 
 
 
 
 
 
 
Note: All ophthalmic assessments must be conducted on both eyes at each timepoint. 
1 Baseline assessments are to be performed on Day 1 before the application of IP by the study staff. 
2 Study-eligible subjects only. 
3 Vital signs will include resting heart rate and sitting blood pressure. 
4 Women of child-bearing potential only; urine pregnancy test 


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Days/Weeks 
Screening 
(Day -45 to 
Day -10)  
Baseline/Randomization/Day 1 
Day 2-5 
(Telephone 
Follow-Up) 
Visit 
1 
2 
3 
Time (Hours) 
--- 
Baseline1 
Hour 0 
(IP 
Dosing) 
0.5 hour  
(±10 
minutes) 
1 hour  
(±15 
minutes) 
2 hours  
(±15 
minutes) 
4 hours  
(±15 
minutes) 
6 hours  
(±15 
minutes) 
8 hours  
(±60 
minutes) 
 
Current corrected VA 
X 
X 
 
 
 
 
 
 
X 
 
IOP 
X 
X 
 
 
X 
 
 
 
X 
 
Leicester Peripheral Field 
Test 
X 
X 
 
 
 
X 
 
X 
 
 
Levator function 
X 
 
 
 
 
 
 
 
 
 
FACE-Q | Aesthetics 
questionnaires 
X 
X 
 
 
 
 
X 
 
X 
 
BHVI assessment  
X 
X 
 
X 
X 
X 
X 
X 
X 
 
 external 
photography of eyes5, 6 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Manual pupillometry 
X 
X 
 
 
X 
 
X 
 
X 
 
IP comfort assessment 
 
 
 
 
X 
 
 
 
 
 
 
5 To include MRD1 and interpalpebral distance measurements by central reading center. Only MRD1 values at Screening will be used for determining study 
eligibility. MRD1 values at Baseline will be used for assessing efficacy. 
6 Photography will be taken of subjects’ eyes during the Screening visit: 1.) Before the instillation of oxymetazoline OU or phenylephrine OU and 2.) Approximately 
120 (±30) minutes after the administration of eye drops. Only responders will be eligible for continuation in the study. 


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Days/Weeks 
Screening 
(Day -45 to 
Day -10)  
Baseline/Randomization/Day 1 
Day 2-5 
(Telephone 
Follow-Up) 
Visit 
1 
2 
3 
Time (Hours) 
--- 
Baseline1 
Hour 0 
(IP 
Dosing) 
0.5 hour  
(±10 
minutes) 
1 hour  
(±15 
minutes) 
2 hours  
(±15 
minutes) 
4 hours  
(±15 
minutes) 
6 hours  
(±15 
minutes) 
8 hours  
(±60 
minutes) 
 
Administration of 1 drop 
of oxymetazoline OU or 
phenylephrine OU  
X 
 
 
 
 
 
 
 
 
 
Slit lamp examination 
and external eye exam 
X 
X 
 
 
 
 
 
 
X 
 
Indirect dilated 
ophthalmoscopy 
X 
 
 
 
 
 
 
 
 
 
AE assessment 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Record concomitant 
medications 
X 
X 
 
 
 
 
 
 
X 
X 
Exit study 
 
 
 
 
 
 
 
 
 
X