A Photo-irritation and Photo-sensitisation Study in Healthy Subjects for Three Developmental Cosmetic Facial Products
Phase: NA
Conditions: Skin Care
Sponsor: GlaxoSmithKline

Clinical Protocol 
212378 
A Photo-irritation and Photo-sensitisation study in 
Healthy Subjects for Three Developmental Cosmetic 
Facial Products 
NCT04006795 
GlaxoSmithKline Consumer Healthcare 
980 Great West Road, Brentford, 
Middlesex, TW8 9GS, 
United Kingdom (UK) 
1. Protocol approval date: 27-Mar-2019
2. Final Amendment to Protocol approval date: 08-Aug-2019
Copyright: GlaxoSmithKline. This document contains confidentiality statements that are not relevant for 
this publicly available version 
Property of GSK Consumer Healthcare - Confidential 
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH SP1963/
SOP-208661 : Template Version : 14 Mar 2019

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
T his d oc u me nt c o ntai ns c o nfi de ntialit y state me nts t hat are n ot rele va nt f or t his p u blicl y 
a vaila ble versi o n
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
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C LI NI C A L P R O T O C O L
A P h ot o-irrit ati o n a n d P h ot o- s e n siti s ati o n st u d y i n H e alt h y 
S u bj e ct s f or T hr e e D e v el o p m e nt al C o s m eti c F a ci al 
Pr o d u ct s
Pr ot o c ol N u m b er:
2 1 2 3 7 8
C o m p o u n d/ Pr o d u ct N a m e:
D e v el o p m e nt al c o s m eti c f a ci al s er u m, l oti o n a n d 
cr e a m
U nit e d St at e s ( U S) I n v e sti g ati o n al N e w Dr u g 
(I N D) N u m b er:
N ot A p pli c a bl e
E ur o p e a n Cli ni c al Tri al s D at a b a s e ( E u dr a C T) 
N u m b er:
N ot A p pli c a bl e
Ot h er R e g ul at or y A g e n c y I d e ntifi e d N u m b er:
N ot A p pli c a bl e
P h a s e:
N ot A p pli c a bl e
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
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S p o n s or I nf or m ati o n
S p o n s or N a m e & L e g al 
R e gi st er e d A d dr e s s
Gl a x o S mit h Kli n e C o n s u m er H e alt h c ar e 
( U K) Tr a di n g Li mit e d
9 8 0 Gr e at W e st R o a d,
Br e ntf or d,
Mi d dl e s e x,
T W 8 9 G S,
U nit e d Ki n g d o m ( U K)
S p o n s or C o nt a ct D et ail s
Gl a x o S mit h Kli n e C o n s u m er H e alt h c ar e 
( G S K C H)
R u a H u n gri a  1 2 4 0 - 4⁰ a n d ar, J ar di m E ur o p a
S ã o P a ul o/ S P – Br a zil, C E P 0 1 4 5 5- 0 0 0
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
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D o c u m e nt Hi st or y
D o c u m e nt
V er si o n
S u m m ar y of C h a n g e s 
Ori gi n al pr ot o c ol
1. 0
N ot a p pli c a bl e ( N/ A)
A m e n d m e nt 1
2. 0
Mi n or c h a n g e s t o i n cr e a s e t h e pr o d u ct dr yi n g ti m e 
b ef or e irr a di ati o n, cl arif y I T A s e cti o n ( 8. 1. 6) a n d 
a m e n d t h e pr e s e nt ati o n of t a bl e s i n s e cti o n 1 2.
A m e n d m e nt 2
A me n d me nts i nc or p orate all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he re q uest of 
c o u ntr y healt h a ut h orities, i nstit uti o nal re vie w b oar ds/et hics c o m mittees (I R Bs/ E Cs), etc.  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
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Pri n ci p al I n v e sti g at or Pr ot o c ol A gr e e m e nt P a g e

I c o nfir m a gree me nt t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol a n d a n y 
a me n d me nts acc or di n g t o t he c urre nt I nter nati o nal C o nfere nce o n Har m o nisati o n G o o d 
Cli nical Practice (I C H G C P) g ui deli nes.

I ac k n o wle d ge t hat I a m res p o nsi ble f or o verall st u d y c o n d uct. I a gree t o pers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.

I a gree t o e ns ure t hat all ass ociates, c ollea g ues a n d e m pl o yees assisti n g i n t he c o n d uct of 
t he st u d y are i nf or me d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n place t o e ns ure site staff 
recei ves all a p pr o priate i nf or mati o n t hr o u g h o ut t he st u d y.

I a gree t o c o n d uct t his st u d y i n f ull c o nf or ma nce wit h t he la ws a n d re g ulati o ns of t he 
c o u ntr y i n w hic h t he researc h is c o n d ucte d a n d t he Declarati o n of Helsi n ki.
I n vesti gat or Na me:
I n vesti gat or Q ualificati o ns:
I n vesti gat or Si g nat ure:
Date of Si g nat ure/ A gree me nt:
D D- M m m- Y Y Y Y
P P D
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P P D
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
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T a bl e of C o nt e nt s
S p o ns or I nf or mati o n............................................................................................................ 2
D oc u me nt Hist or y................................................................................................................ 3
Pri nci pal I n vesti gat or Pr ot oc ol A gree me nt Pa ge................................................................. 4
Ta ble of C o nte nts................................................................................................................. 5
1 
P R O T O C O L S U M M A R Y................................................................................................. 1 0
1. 1 
Sc he d ule of Acti vities............................................................................................ 1 3
2 
I N T R O D U C TI O N............................................................................................................. 1 7
2. 1 
St u d y Rati o nale...................................................................................................... 1 8
2. 2 
Bac k gr o u n d............................................................................................................ 1 9
2. 3  
Mec ha nis m of Acti o n/I n dicati o n ........................................................................... 1 9
3 
S T U D Y O BJ E C TI V E S A N D E N D P OI N T S..................................................................... 2 0
4 
S T U D Y D E SI G N .............................................................................................................. 2 0
4. 1  
O verall Desi g n....................................................................................................... 2 0
4. 2 
Rati o nale f or St u d y Desi g n.................................................................................... 2 4
4. 3 
J ustificati o n f or D ose............................................................................................. 2 6
4. 4 
E n d of St u d y Defi niti o n......................................................................................... 2 6
5 
S T U D Y P O P U L A TI O N.................................................................................................... 2 6
5. 1 
T y pe a n d Pla n ne d N u m ber of S u bjects.................................................................. 2 6
5. 2 
I ncl usi o n Criteria.................................................................................................... 2 7
5. 3 
E xcl usi o n Criteria .................................................................................................. 2 7
5. 4 
Ra n d o misati o n Criteria.......................................................................................... 2 9
5. 5 
Lifest yle C o nsi derati o ns ........................................................................................ 2 9
5. 5. 1 
Pre g na nc y.............................................................................................. 3 0
5. 6 
Scree n Fail ures....................................................................................................... 3 0
5. 7 
S p o ns or’s Q ualifie d Me dical Pers o n nel................................................................. 3 0
5. 8 
Trai ne d E val uat or a n d Der mat ol o gist Q ualificati o ns ............................................ 3 1
6 
I N V E S TI G A TI O N A L/ S T U D Y P R O D U C T S................................................................... 3 1
6. 1 
I n vesti gati o nal/ St u d y Pr o d uct S u p plies................................................................. 3 1
6. 1. 1  
D osa ge F or m a n d Pac ka gi n g................................................................. 3 2
6. 1. 2 
Pre parati o n a n d Dis pe nsi n g................................................................... 3 3
6. 2  
A d mi nistrati o n ....................................................................................................... 3 3
6. 2. 1  
D osi n g Err ors......................................................................................... 3 4
6. 2. 2  
O ver d ose................................................................................................ 3 5
6. 3 
I n vesti gati o nal/ St u d y Pr o d uct St ora ge................................................................... 3 5
6. 4 
I n vesti gati o nal/ St u d y Pr o d uct Acc o u nta bilit y....................................................... 3 5
6. 4. 1  
Destr ucti o n of I n vesti gati o nal/ St u d y Pr o d uct S u p plies......................... 3 6
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
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Bli n di n g a n d All ocati o n/ Ra n d o misati o n................................................................ 3 6
6. 6 
Brea ki n g t he Bli n d................................................................................................. 3 6
6. 7 
C o m plia nce............................................................................................................ 3 7
6. 8 
C o nc o mita nt Me dicati o n/ Treat me nt(s).................................................................. 3 7
7  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D S U BJ E C T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ......................................................................... 3 7
7. 1 
S u bject Disc o nti n uati o n/ Wit h dra wal..................................................................... 3 7
7. 2 
L ost t o F oll o w u p................................................................................................... 3 8
8 
S T U D Y P R O C E D U R E S................................................................................................... 3 8
8. 1  
Visit 1/ Scree ni n g.................................................................................................... 3 8
8. 1. 1 
I nf or me d C o nse nt.................................................................................. 3 9
8. 1. 2  
De m o gra p hics........................................................................................ 3 9
8. 1. 3  
Me dical Hist or y a n d Pri or Me dicati o n/ Treat me nt ................................ 3 9
8. 1. 4 
I ncl usi o n/ E xcl usi o n Criteria.................................................................. 3 9
8. 1. 5  
Der mat ol o gist Assess me nt .................................................................... 4 0
8. 1. 6 
I n di vi d ual T y p ol o g y A n gle (I T A°) ....................................................... 4 0
8. 1. 7 
S u bject Eli gi bilit y.................................................................................. 4 0
8. 2  
Visit 2..................................................................................................................... 4 0
8. 2. 1  
M E D Irra diati o n .................................................................................... 4 1
8. 3  
Visit 3..................................................................................................................... 4 1
8. 3. 1  
M E D Deter mi nati o n.............................................................................. 4 2
8. 4 
I n d ucti o n P hase - Da y 1 Visit 4 ( M o n da y)............................................................ 4 2
8. 4. 1 
I n d ucti o n P hase Ra n d o misati o n............................................................ 4 2
8. 4. 2 
Baseli ne Gra di n g................................................................................... 4 3
8. 4. 3 
Pr o d uct A p plicati o n a n d Patc h A p plicati o n.......................................... 4 3
8. 5 
I n d ucti o n P hase - Da y 2 Visit 5 ( T ues da y)............................................................ 4 3
8. 5. 1 
Patc h Re m o val....................................................................................... 4 4
8. 5. 2 
C uta ne o us Irritati o n Assess me nts.......................................................... 4 4
8. 5. 3 
Test Site Irra diati o n............................................................................... 4 4
8. 5. 4 
C uta ne o us Irritati o n Assess me nt P ost Irra diati o ns................................ 4 4
8. 6 
I n d ucti o n P hase Da y 3 Visit 6 ( We d nes da y)......................................................... 4 5
8. 7 
I n d ucti o n P hase Da y 4 Visit 7 ( T h urs da y)............................................................. 4 5
8. 8 
I n d ucti o n P hase Da y 5 Visit 8 ( Fri da y) ................................................................. 4 5
8. 9 
Rest P hase.............................................................................................................. 4 6
8. 1 0 
C halle n ge P hase Da y 3 6 Visit 1 9 ( M o n da y).......................................................... 4 6
8. 1 0. 1 
C halle n ge P hase Ra n d o misati o n ........................................................... 4 6
8. 1 1 
C halle n ge P hase Da y 3 7 Visit 2 0 ( T ues da y) ......................................................... 4 7
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
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8. 1 2 
C halle n ge P hase Da y 3 7 t o 4 0 Visit 2 1 t o Visit 2 3 ( We d nes da y t o Fri da y).......... 4 7
8. 1 3 
Fi nal Visit Da y 4 0 Visit 2 3.................................................................................... 4 7
8. 1 4 
St u d y C o ncl usi o n................................................................................................... 4 7
8. 1 5 
F oll o w- u p Visit...................................................................................................... 4 8
9 
S T U D Y A S S E S S M E N T S ................................................................................................. 4 8
9. 1 
Scree ni n g Assess me nts.......................................................................................... 4 8
9. 2 
Safet y a n d Ot her Assess me nts............................................................................... 4 8
9. 2. 1 
Patc h Assess me nts................................................................................. 4 8
1 0
A D V E R S E E V E N T A N D S E RI O U S A D V E R S E E V E N T S............................................ 4 9
1 0. 1  
Defi niti o n of a n A d verse E ve nt ( A E) .................................................................... 4 9
1 0. 2  
Defi niti o n of a Seri o us A d verse E ve nt ( S A E)....................................................... 5 0
1 0. 3 
Re p orti n g of A d verse E ve nts................................................................................. 5 1
1 0. 3. 1 
Re p orti n g Peri o d.................................................................................... 5 1
1 0. 4 
Re p orti n g Pr oce d ures............................................................................................. 5 1
1 0. 4. 1 
Re p orti n g of a n A d verse E ve nt ............................................................. 5 2
1 0. 4. 2 
Re p orti n g of a Seri o us A d verse E ve nt .................................................. 5 2
1 0. 5 
E val uati n g A d verse E ve nts.................................................................................... 5 3
1 0. 5. 1  
Assess me nt of I nte nsit y......................................................................... 5 3
1 0. 5. 2  
Assess me nt of Ca usalit y........................................................................ 5 4
1 0. 6 
F oll o w- u p of A d verse E ve nts ................................................................................ 5 4
1 0. 7  
Wit h dra wal D ue t o a n A d verse E ve nt.................................................................... 5 5
1 0. 7. 1 
S p o ns or’s Re p orti n g Re q uire me nts t o Re g ulat or y A ut h orities a n d 
Et hics C o m mittees................................................................................. 5 5
1 0. 8 
Pre g na nc y............................................................................................................... 5 5
1 0. 8. 1 
Ti me Peri o d f or C ollecti n g Pre g na nc y I nf or mati o n.............................. 5 5
1 0. 8. 2  
Acti o n t o be Ta ke n if Pre g na nc y Occ urs............................................... 5 6
1 1
D A T A M A N A G E M E N T .................................................................................................. 5 6
1 1. 1 
Case Re p ort F or m.................................................................................................. 5 7
1 1. 2  
Data Ha n dli n g........................................................................................................ 5 7
1 1. 2. 1  
Data Q ueries.......................................................................................... 5 7
1 2
S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A A N A L Y S E S................................... 5 8
1 2. 1 
Sa m ple Size Deter mi nati o n.................................................................................... 5 8
1 2. 2 
Statistical Met h o ds a n d A nal ytical Pla n................................................................ 5 8
1 2. 2. 1  
Defi niti o n of A nal ysis P o p ulati o ns ....................................................... 5 8
1 2. 2. 2 
E xcl usi o n of Data fr o m A nal ysis .......................................................... 5 8
1 2. 2. 3  
De m o gra p hic a n d Baseli ne C haracteristics........................................... 5 8
1 2. 2. 4 
St u d y Pr o d uct C o m plia nce.................................................................... 5 8
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
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1 2. 2. 5 
Pri or a n d C o nc o mita nt Me dicati o ns...................................................... 5 8
1 2. 2. 6 
Pri mar y A nal ysis(es)............................................................................. 5 9
1 2. 2. 7 
Sec o n dar y A nal ysis(es)......................................................................... 5 9
1 2. 2. 8 
Safet y A nal ysis(es)................................................................................ 6 0
1 2. 2. 9  
Ha n dli n g of Dr o p o uts a n d Missi n g Data............................................... 6 0
1 2. 2. 1 0
I nteri m A nal ysis .................................................................................... 6 0
1 3
S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S.............................................................. 6 0
1 3. 1  
Q ualit y C o ntr ol ...................................................................................................... 6 0
1 3. 2  
Q ualit y Ass ura nce.................................................................................................. 6 1
1 3. 3 
Re g ulat or y a n d Et hical C o nsi derati o ns.................................................................. 6 1
1 3. 3. 1 
I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee..................................... 6 1
1 3. 3. 2 
Et hical C o n d uct of t he St u d y................................................................. 6 1
1 3. 3. 3 
S u bject I nf or mati o n a n d C o nse nt.......................................................... 6 2
1 3. 3. 4 
S u bject Recr uit me nt .............................................................................. 6 2
1 3. 3. 5 
Re p orti n g of Safet y Iss ues a n d Seri o us Breac hes of t he Pr ot oc ol or 
I C H G C P ............................................................................................... 6 2
1 3. 4 
P osti n g of I nf or mati o n o n P u blicl y A vaila ble Cli nical Trial Re gisters................. 6 3
1 3. 5 
Pr o visi o n of St u d y Res ults t o I n vesti gat ors........................................................... 6 3
1 3. 6 
Rec or ds Rete nti o n.................................................................................................. 6 3
1 3. 7 
C o n diti o ns f or Ter mi nati n g t he St u d y ................................................................... 6 4
1 4
R E F E R E N C E S .................................................................................................................. 6 4
1 5
A P P E N DI C E S................................................................................................................... 6 5
1 5. 1  
A P P E N DI X 1- A B B R E VI A TI O N S...................................................................... 6 5
1 5. 2  
A p pe n di x 2- Sc ori n g of patc h test reacti o ns acc or di n g t o I C D R G........................ 6 6
1 5. 3  
A p pe n di x 3 - Fitz patric k S ki n T y pe Gra di n g......................................................... 6 7
1 5. 4  
A p pe n di x 4 S pecificati o n of t he S olar Si m ulat or O ut p ut...................................... 6 7
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
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Li st of i n t e xt t a bl e s
Ta ble 1- 1 
St u d y Sc he d ule...................................................................................... 1 3
Ta ble 3- 1 
St u d y O bjecti ves a n d E n d p oi nts............................................................ 2 0
Ta ble 6- 1 
I n vesti gati o nal/ St u d y Pr o d uct S u p plies................................................. 3 2
Ta ble 8- 1  
A p plicati o n site se q ue nces- i n d ucti o n p hase......................................... 4 3
Ta ble 8- 2  
A p plicati o n site se q ue nces- c halle n ge p hase......................................... 4 6
Ta ble 1 5- 1                 A b bre viati o ns ......................................................................................... 6 5
Ta ble 1 5- 2 
Sc ori n g of patc h cells acc or di n g t o I C D R G.......................................... 6 6
Ta ble 1 5- 3 
- % R C E E acce pta nce li mits f or t he U V s olar si m ulat or o ut p ut........... 6 8
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 0  of 6 8
1 
P R O T O C O L S U M M A R Y 
B a c k gr o u n d a n d R ati o n al e
A c os metic pr o d uct t hat is freel y a vaila ble t o t he c o ns u mer m ust be safe w he n a p plie d u n der 
n or mal or reas o na bl y f oreseea ble c o n diti o ns of use. As a ge neral re q uire me nt, t he safet y a n d 
c o m pati bilit y of a ne w f or m ulati o n s h o ul d be c o nfir me d bef ore it is c o m mercialise d ( G ui deli ne 
f or t he Safet y E val uati o n of C os metic Pr o d ucts; A gê ncia Naci o nal de Vi gilâ ncia Sa nitária, 
A N VI S A, 2 0 1 2), ( C os metics E ur o pe, 2 0 0 4 ).
C o m pati bilit y st u dies, perf or me d as patc h tests, ai m t o c o nfir m t he l ocal t olera nce of t o pical 
c os metic pr o d ucts d uri n g t he first a p plicati o n t o t he s ki n, t heref ore pr o vi di n g ass ura nce t hat t he 
pr o d uct is safe f or use u n der ma xi mize d c o n diti o ns ( A N VI S A, 2 0 1 2 ).
P h ot o-irritati o n assess me nts ai m t o de m o nstrate t he a bse nce of irritati o n p ote ntial of a pr o d uct 
w he n a p plie d t o t he s ki n a n d e x p ose d t o ultra vi olet ra diati o n ( U V R).  P h ot o-se nsitisati o n 
assess me nts ai m t o de m o nstrate t he a bse nce of aller gic p ote ntial of a pr o d uct a p plie d t o t he s ki n 
w he n e x p ose d t o U V R.
P h ot o-irritati o n p ote ntial will pri maril y be e val uate d t hr o u g h t he re peate d occl u de d a p plicati o n 
a n d U V e x p os ure of t he st u d y pr o d ucts o ver 3 wee ks (i n d ucti o n p hase). P h ot o-se nsitisati o n 
p ote ntial will pri maril y be e val uate d t hr o u g h a s u bse q ue nt se mi- occl u de d a p plicati o n a n d U V 
e x p os ure (c halle n ge p hase) after a 2- wee k rest peri o d.  S u bjects w h o partici pate i n t his st u d y 
s hall be healt h y a d ult males a n d fe males wit h n o pri or h y perse nsiti vit y t o t o pical pr o d ucts wit h 
n o acti ve der mat oses o n t heir u p per bac k.
Pri or t o t he c o n d uct of a n y st u d y pr oce d ures or a p plicati o n of st u d y pr o d ucts, pr os pecti ve test 
areas will be e val uate d b y a trai ne d bli n de d e val uat or t o c o nfir m t he y are free a n y si g ns or 
s y m pt o ms of c uta ne o us irritati o n.
At scree ni n g, t he mi ni mal er yt he ma d ose ( M E D) will be deter mi ne d f or eac h s u bject t o e ns ure 
t he d ose of U V ra diati o n t o be a d mi nistere d i n t he i n d ucti o n a n d c halle n ge p hase is c o ntr olle d 
a p pr o priatel y. O nl y s u bjects w h o prese nt a vali d 
M E D will be c o nsi dere d eli gi ble f or 
ra n d o misati o n. 
O nce ra n d o mise d, c o ntr olle d a m o u nts of eac h of t he t hree test pr o d ucts a n d a refere nce pr o d uct 
( 0. 9 M sali ne) will t he n be a p plie d i n d u plicate t o defi ne d areas of s ki n ( 0. 0 2 m L/c m2  of eac h 
pr o d uct) via cells wit hi n se mi- occl usi ve patc h s yste m t o t he u p per bac k of eac h s u bject. Eac h 
patc h s hall re mai n i n place f or 2 4 h o urs, after w hic h it will be re m o ve d, a n d eac h test site 
e val uate d a n d rec or de d b y a trai ne d e val uat or f or si g ns of c uta ne o us irritati o n.  
St u d y pr o d ucts will t he n be rea p plie d t o t he s ki n test sites, a n d o ne series of test sites will be 
e x p ose d t o a c o ntr olle d d ose of U V ra diati o n a n d t he ot her series will n ot. B ot h t he irra diate d 
a n d n o n-irra diate d sites will be e val uate d i m me diatel y after c o m pleti o n of t he U V e x p os ure 
pr oce d ures a n d a gai n t he f oll o wi n g da y. T his pr oce d ure s hall be re peate d t wice- wee kl y f or 3 
wee ks (a t otal of 6 patc h a p plicati o ns per series). 
S u bjects will t he n e nter a 2- wee k rest p hase d uri n g w here n o i nter ve nti o ns are ma de. T his will 
be f oll o we d b y a 2 4- h o ur c halle n ge e x p os ure of eac h st u d y pr o d uct u n der se mi- occl usi ve 
c o n diti o ns. Test materials will be a p plie d t o naï ve test sites o n t he u p per bac k i n d u plicate. O nce 
t he patc h s yste ms are re m o ve d, o ne series will be e x p ose d t o U V ra diati o n a n d t he ot her s hall 
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 1  of 6 8
n ot.  B ot h sets of test sites will be e val uate d b y a trai ne d e val uat or f or si g ns of c uta ne o us 
irritati o n i m me diatel y, 2 4, 4 8 a n d 7 2- h o urs after U V e x p os ure of t he irra diate d sites.
P h ot o-irrita nt reacti o ns are m ost ofte n c haracterise d b y i nte nse dela ye d er yt he ma (i.e. a n 
e xa g gerate d s u n b ur n reacti o n) a n d are fre q ue ntl y f oll o we d b y h y per pi g me ntati o n a n d peeli n g 
of da ma ge d s ki n. T he ac ute as pects of p h ot o-irrita nt reacti o ns ma y be gi n wit hi n a fe w mi n utes 
t o h o urs after irra diati o n a n d te n d t o res ol ve wit hi n a fe w da ys t o wee ks.  H y per pi g me ntati o n 
ma y ta ke se veral m o nt hs t o years t o clear. W hereas t he ac ute as pects of p h ot o- irrita nt reacti o ns 
t y picall y prese nt s o o n after irra diati o n, p h ot o-se nsitisati o n reacti o ns sel d o m occ ur after t he first 
e x p os ure t o t he p h ot o-aller ge n. Si nce p h ot o-se nsitisati o n is a n i m m u n ol o gical pr ocess i n nat ure, 
m ulti ple e x p os ures t o t he p h ot o-acti vate d aller ge n a n d a late nt peri o d of se veral da ys t o wee ks 
are t y picall y re q uire d bef ore t he i m m u ne s yste m is rea d y t o res p o n d. O nce a s u bject has bee n 
se nsitise d, s u bse q ue nt e x p os ures t o t he p h ot o-aller ge n a n d U V ra diati o n will elicit c uta ne o us 
res p o nses q uite ra pi dl y wit hi n 2 4- 7 2 h o urs ( Bea ni 2 0 1 7).
After t he trai ne d e val uat or has gra de d all t he patc h cells acc or di n g t o t he I C D R G sc ori n g Ta ble 
1 5- 2 ( A p pe n di x 2),  a bli n de d der mat ol o gist will e val uate e ver y p ositi ve reacti o n ( defi ne d as a 
sc ore of ‘ + ’  or greater) i n t he c halle n ge p hase t o f urt her classif y it as p ote ntial se nsitisati o n 
( or n ot) a n d pr o vi de a narrati ve descri pti o n of t he e ve nt. T he l ocati o n of p ositi ve reacti o ns will 
be deter mi ne d after u n bli n di n g t o deter mi ne w het her a reacti o n was p ote ntiall y p h ot o-i nitiate d.
T he o bjecti ve of t his cli nical st u d y is t o assess t he p h ot o-irritati o n a n d p h ot o-se nsitisati o n 
p ote ntial of t hree de vel o p me ntal c os metic f or m ulati o ns c o m pare d t o a refere nce pr o d uct 
( ne gati ve c o ntr ol) after d u plicate, re peate d se mi- occl usi ve patc h a p plicati o ns t o healt h y h u ma n 
s u bjects b y f oll o wi n g a c o n ve nti o nal p h ot o-irritati o n a n d p h ot o-se nsitisati o n met h o d ol o g y 
u n der s u per visi o n of a der mat ol o gist.
O bj e cti v e s a n d E n d p oi nt s
O bj e cti v e s
E n d p oi nt s
Pri m ar y
T o e v al u at e t h e c ut a n e o u s p h ot o-
s e n siti s ati o n p ot e nti al of t hr e e c o s m eti c 
f a ci al s ki n c ar e pr o d u ct s c o m p ar e d t o 
s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a p ot e nti al s e n siti s ati o n 
r e a cti o n w hi c h i s c o n si d er e d p h ot o-i niti at e d.
S e c o n d ar y
T o e v al u at e t h e c ut a n e o u s p h ot o-irrit ati o n 
p ot e nti al of t hr e e c o s m eti c f a ci al s ki n c ar e 
pr o d u ct s c o m p ar e d t o s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a p h ot o-i niti at e d r e a cti o n 
s c or e of ‘ +’ or gr e at er w hi c h n ot c o n si d er e d a p ot e nti al 
s e n siti s ati o n r e a cti o n.
T o e v al u at e t h e c ut a n e o u s s e n siti s ati o n 
p ot e nti al of t hr e e c o s m eti c f a ci al s ki n c ar e 
pr o d u ct s c o m p ar e d t o s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a p ot e nti al s e n siti s ati o n 
r e a cti o n w hi c h i s n ot c o n si d er e d p h ot o-i niti at e d.
T o e v al u at e t h e c ut a n e o u s irrit ati o n 
p ot e nti al of t hr e e c o s m eti c f a ci al s ki n c ar e 
pr o d u ct s c o m p ar e d t o s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a n o n- p h ot oi niti at e d 
r e a cti o n s c or e of ‘ +’ or gr e at er w hi c h i s n ot c o n si d er e d 
a p ot e nti al s e n siti s ati o n r e a cti o n.
S af et y
T o e v al u at e t h e g e n er al s af et y of t hr e e 
c o s m eti c f a ci al s ki n c ar e pr o d u ct s
Fr e q u e n c y a n d s e v erit y of A d v er s e E v e nt s
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2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 2  of 6 8
St u d y Desi g n
T his will be a si n gle-ce nter, ra n d o mise d, e val uat or (si n gle) bli n d st u d y i n healt h y a d ult s u bjects 
wit h n o der mat ol o gical dis or ders a n d wit h a Fitz patric k s ki n p h ot ot y pe II t o I V. S u bjects will 
be e x p ose d t o a d u plicate series of re peate d se mi- occl usi ve patc h a p plicati o ns of 3 t o pical 
c os metic f or m ulati o ns a n d a refere nce pr o d uct (sali ne s ol uti o n) t o e val uate t he p h ot o-
se nsitisati o n a n d p h ot o-irritati o n p ote ntial of t he st u d y pr o d ucts u n der ma xi mize d c o n diti o ns of 
use. O nl y o ne series of patc hes will be e x p ose d t o U V ra diati o n. T he st u d y will be c o n d ucte d 
u n der t he s u per visi o n of a der mat ol o gist. 
St u d y Pr o d ucts
T he t hree st u d y pr o d ucts are de vel o p me ntal c os metic m oist urisers (a ser u m, l oti o n a n d crea m), 
i nte n de d t o be use d t o picall y b y healt h y i n di vi d uals wit h dr y facial s ki n.
I n b ot h t he i n d ucti o n a n d c halle n ge p hases, a c o ntr olle d q ua ntit y ( 0. 0 2 m L/c m2) of eac h of t he 
st u d y pr o d ucts will be a p plie d t o a cell c o ntai ne d wit hi n a n a d hesi ve se mi- occl usi ve patc h 
s yste m. T he n u m ber of cells a vaila ble i n eac h patc h s yste m will be 6, of w hic h 4 will be use d 
f or t he pr o d ucts a n d 2 will be left bla n k. I n t his st u d y, eac h of t he st u d y pr o d ucts will be 
dis pe nse d i nt o 4 a djace nt cells, i n t w o d u plicate series of patc hes, as per t he ra n d o misati o n 
sc he d ule. T hree cells will be use d f or t he test pr o d ucts (ser u m, l oti o n a n d crea m) a n d a f o urt h 
f or t he refere nce pr o d uct (sali ne s ol uti o n).  N o ot her pr o d ucts will be a p plie d t o s u bjects 
e nr olle d i n t his st u d y.
T y pe a n d Pl a n ne d N u m ber of S u bjects
Healt h y male a n d fe male v ol u nteers a ge d 1 8 t o 6 5 wit h Fitz patric k s ki n p h ot ot y pe II t o I V a n d 
n o der mat ol o gical dis or ders will be e nr olle d i nt o t his st u d y. 
A p pr o xi matel y 8 0 healt h y s u bjects will be scree ne d t o ra n d o mise at least 4 0 s u bjects t o e ns ure 
at least 2 5 e val ua ble s u bjects c o m plete t he e ntire st u d y.  N o f or mal p o wer calc ulati o n has bee n 
perf or me d as t he sa m ple size is sta n dar d i n cli nical testi n g practices a n d is c o nsiste nt wit h t he 
A N VI S A g ui deli nes ( A N VI S A, 2 0 1 2 ).
T he f oc us of t he statistical a nal ysis will be t he e val uati o n t he pr o p orti o n of s u bjects p ote ntiall y 
p h ot o-se nsitise d ( p ote ntial se nsitisati o n reacti o n i n t he U V-e x p ose d series of patc hes) a n d t he 
fre q ue nc y of p ositi ve irritati o n reacti o ns (sc ores of ‘ +’ or greater) t o t he i n vesti gati o nal pr o d ucts.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 3  of 6 8
1. 1 
S c h e d ul e of A cti viti e s
T he sc he d ule of acti vities ta ble pr o vi des a n o ver vie w of t he s u bject visits a n d st u d y pr oce d ures.  
T he i n vesti gat or ma y sc he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d o n t he sc he d ule of acti vities, t o c o n d uct e val uati o ns or assess me nts 
re q uire d t o pr otect t he well- bei n g of t he s u bject.
T a bl e 1- 1 
St u d y S c h e d ul e
St u d y P h a s e
S cr e e ni n g
I n d u cti o n
R e st
C h all e n g e
St u d y W e e k
M a xi m u m 2 
W e e k 
D ur ati o n
1
2
3
4/ 5
6
                       St u d y                                    
Pr o c e d ur e/
A s s e s s m e nt
VI SI T 1
VI SI T 2 
VI SI T 3 
VI SI T 4 D A Y 1
VI SI T 5 D A Y 2
VI SI T 6 D A Y 3
VI SI T  7 D A Y 4
VI SI T 8 D A Y 5
VI SI T 9 D A Y 8
VI SI T 1 0 D A Y 9
VI SI T  1 1 D A Y 1 0
VI SI T 1 2 D A Y 1 1
VI SI T 1 3 D A Y 1 2
VI SI T 1 4 D A Y 1 5
VI SI T 1 5 D A Y 1 6
VI SI T 1 6 D A Y 1 7
VI SI T 1 7 D A Y 1 8
VI SI T 1 8 D A Y 1 9
-
VI SI T 1 9 D A Y 3 6
VI SI T 2 0 D A Y 3 7
VI SI T 2 1 D A Y 3 8
VI SI T 2 2 D A Y 3 9
VI SI T 2 3 D A Y 4 0
D a y of W e e k
-
-
-
M o n
T u e
W e d
T h u
Fri
M o n
T u e
W e d
T h u
Fri
M o n
T u e
W e d
T h u
Fri
-
M o n
T u e
W e d
T h u
Fri
I nf or m e d C o n s e nt
X
D e m o gr a p hi c s
X
M e di c al Hi st or y
X
C urr e nt/ C o n c o mit a nt 
m e di c ati o n r e vi e w
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fit z p atri c k S ki n 
T y p e A s s e s s m e nt
X
I n di vi d u al T y p ol o g y 
A n gl e I T A°
X
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 4  of 6 8
St u d y P h a s e
S cr e e ni n g
I n d u cti o n
R e st
C h al l e n g e
St u d y W e e k
M a xi m u m 2 
W e e k 
D ur ati o n
1
2
3
4/ 5
6
                       St u d y                                    
Pr o c e d ur e/
A s s e s s m e nt
VI SI T 1
VI SI T 2 
VI SI T 3 
VI SI T 4 D A Y 1
VI SI T 5 D A Y 2
VI SI T 6 D A Y 3
VI SI T  7 D A Y 4
VI SI T 8 D A Y 5
VI SI T 9 D A Y 8
VI SI T 1 0 D A Y 9
VI SI T  1 1 D A Y 1 0
VI SI T 1 2 D A Y 1 1
VI SI T 1 3 D A Y 1 2
VI SI T 1 4 D A Y 1 5
VI SI T 1 5 D A Y 1 6
VI SI T 1 6 D A Y 1 7
VI SI T 1 7 D A Y 1 8
VI SI T 1 8 D A Y 1 9
-
VI SI T 1 9 D A Y 3 6
VI SI T 2 0 D A Y 3 7
VI SI T 2 1 D A Y 3 8
VI SI T 2 2 D A Y 3 9
VI SI T 2 3 D A Y 4 0
D a y of W e e k
-
-
-
M o n
T u e
W e d
T h u
Fri
M o n
T u e
W e d
T h u
Fri
M o n
T u e
W e d
T h u
Fri
-
M o n
T u e
W e d
T h u
Fri
I n cl u si o n/ E x cl u si o n 
Crit eri a
X
X a
D er m at ol o gi st 
A s s e s s m e nt b
X
X
X
X
X
X
S u bj e ct Eli gi bilit y
X
C o nti n u e d Eli gi bilit y
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pr o vi si o n al M E D u 
irr a di ati o n 
X
M E D u 
D et er mi n ati o n
X  c
R a n d o mi s ati o n
X
X
A c cli m ati z ati o n t o 
St a n d ar d C o n diti o n s 
d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
B a s eli n e Gr a di n g of 
T e st Sit e s e
X
X
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 5  of 6 8
St u d y P h a s e
S cr e e ni n g
I n d u cti o n
R e st
C h al l e n g e
St u d y W e e k
M a xi m u m 2 
W e e k 
D ur ati o n
1
2
3
4/ 5
6
                       St u d y                                    
Pr o c e d ur e/
A s s e s s m e nt
VI SI T 1
VI SI T 2 
VI SI T 3 
VI SI T 4 D A Y 1
VI SI T 5 D A Y 2
VI SI T 6 D A Y 3
VI SI T  7 D A Y 4
VI SI T 8 D A Y 5
VI SI T 9 D A Y 8
VI SI T 1 0 D A Y 9
VI SI T  1 1 D A Y 1 0
VI SI T 1 2 D A Y 1 1
VI SI T 1 3 D A Y 1 2
VI SI T 1 4 D A Y 1 5
VI SI T 1 5 D A Y 1 6
VI SI T 1 6 D A Y 1 7
VI SI T 1 7 D A Y 1 8
VI SI T 1 8 D A Y 1 9
-
VI SI T 1 9 D A Y 3 6
VI SI T 2 0 D A Y 3 7
VI SI T 2 1 D A Y 3 8
VI SI T 2 2 D A Y 3 9
VI SI T 2 3 D A Y 4 0
D a y of W e e k
-
-
-
M o n
T u e
W e d
T h u
Fri
M o n
T u e
W e d
T h u
Fri
M o n
T u e
W e d
T h u
Fri
-
M o n
T u e
W e d
T h u
Fri
P at c h R e m o v al
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X
X
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X
Gr a di n g of T e st 
Sit e s Pri or t o U V 
Irr a di ati o n f,
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X
Pr o d u ct A p pli c ati o n 
a n d U V Irr a di ati o n g
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X
Gr a di n g of T e st 
Sit e s Aft er U V 
Irr a di ati o n h,
X
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X
X
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X
X
X
X
X
X
X
X i
X i
X i
Pr o d u ct a n d P at c h 
A p pli c ati o n
X
X
X
X
X
X
X
A d v er s e E v e nt s j
X
X
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St u d y C o n cl u si o n/
E xit fr o m St u d y/
X
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 6  of 6 8
N ot e s:

Vi sit 1 a n d Vi sit 2 c o ul d o c c ur o n t h e s a m e d a y b ut Vi sit 2 m u st b e wit hi n 7 d a y s of Vi sit 1.

Vi sit 4 will st art o n t h e fir st M o n d a y aft er a v ali d M E D h a s b e e n r e c or d e d.

A ‘ p at c h s y st e m’ c o nt ai n s i n di vi d u al c ell s. E a c h of t h e st u d y pr o d u ct s a n d t h e s ali n e s ol uti o n 
(r ef er e n c e pr o d u ct) will b e a p pli e d i nt o s e p ar at e si n gl e c ell s. T h e or d er of a p pli c ati o n of t h e 
pr o d u ct s i nt o t h e c ell s will b e r a n d o mi s e d f or e a c h s u bj e ct. T h e s a m e s e q u e n c e wit hi n e a c h 
s u bj e ct will b e u s e d t hr o u g h o ut t h e i n d u cti o n p h a s e o n b ot h p at c h e s, b ut t h e s e q u e n c e will c h a n g e 
f or e a c h s u bj e ct f or t h e c h all e n g e p h a s e.

S u bj e ct s s h o ul d a v oi d mi s si n g t h e fir st d a y of a p pli c ati o n d uri n g t h e i n d u cti o n p h a s e, or t h e d a y of 
a p pli c ati o n d uri n g t h e c h all e n g e P h a s e.

S u bj e ct s s h o ul d a v oi d mi s si n g 2 or m or e c o n s e c uti v e vi sit s or m or e t h a n 2 alt er n at e vi sit s
F o ot n ot e s:
a.    A s s e s s m e nt of i n cl u si o n crit eri a 6 ( o nl y) b y a q u alifi e d d er m at ol o gi st.
b.    A bli n d e d d er m at ol o gi st will r e vi e w o v er all s u bj e ct eli gi bilit y at t h e s cr e e ni n g vi sit a n d t h e fi n al vi sit 
a n d will al s o r e vi e w a n y e v al u at or r e a cti o n s c or e t h at i s ‘ +’ or gr e at er i n t h e c h all e n g e P h a s e t o 
pr o vi d e a n arr ati v e a n d i nt er pr et ati o n w h et h er t h e r e a cti o n i s a p ot e nti al s e n siti s ati o n r e a cti o n.
c.    Pr o vi si o n al M E D u gr a di n g m u st o c c ur 1 6- 2 4 h o ur s aft er c o m pl eti o n of t h e M E D u irr a di ati o n. It 
m a y t a k e m ulti pl e att e m pt s t o r e c or d a v ali d M E D f or a s u bj e ct.
d.    A p pr o xi m at el y 1 5- 3 0 mi n ut e s f oll o wi n g p at c h r e m o v al, s u bj e ct s will r e st i n st a n d ar d r o o m 
c o n diti o n s ( 1 8- 2 6 ° C) pri or t o t h e t e st ar e a a s s e s s m e nt. 
e.    B a s eli n e gr a di n g of n aï v e t e st sit e s will b e p erf or m e d pri or t o t h e p at c h a p pli c ati o n at Vi sit 4 
(i n d u cti o n p h a s e) a n d Vi sit 1 9 ( c h all e n g e p h a s e) u si n g t h e s c ori n g s y st e m d et ail e d i n gr a di n g 
s c al e T a bl e 1 5- 2 A p p e n di x 2.
f.    A p pr o xi m at el y 3 0 mi n ut e s u p t o 1 h o ur aft er e a c h p at c h i s r e m o v e d, a tr ai n e d, bli n d e d e v al u at or 
will e v al u at e t h e t e st sit e s f or vi s u al si g n s of r e a cti o n s u si n g t h e s c ori n g s y st e m d et ail e d i n T a bl e 
1 5- 2 A p p e n di x 2 . 
g.     U V irr a di ati o n will o c c ur aft er pr o d u ct a p pli c ati o n. O n e s eri e s of t e st sit e s will b e e x p o s e d t o U V 
r a di ati o n w hil e t h e s e c o n d s eri e s of t e st sit e s will n ot b e e x p o s e d t o U V r a di ati o n.
h.    B ot h s eri e s of t e st sit e s will b e e v al u at e d b y a bli n d e d a n d tr ai n e d e v al u at or, i m m e di at el y aft er U V 
e x p o s ur e of t h e irr a di at e d s eri e s of sit e s u si n g t h e s c ori n g s y st e m d et ail e d i n gr a di n g s c al e T a bl e 
1 5- 2 A p p e n di x 2.
i.    Gr a di n g of c h all e n g e sit e s (irr a di at e d a n d n o n-irr a di at e d) will o c c ur 2 4 ( ± 4), 4 8 ( ± 4) a n d 7 2 ( ± 4) 
h o ur s aft er U V e x p o s ur e of t h e irr a di at e d s eri e s of sit e s.
j.     A d v er s e E v e nt s ( A E s) a n d t h er ef or e all S eri o u s A d v er s e E v e nt s ( S A E s) will b e c oll e ct e d 
i m m e di at el y aft er a s u bj e ct pr o vi d e s writt e n c o n s e nt t o p arti ci p at e i n t h e st u d y b y c o m pl eti n g t h e 
I nf or m e d C o n s e nt F or m (I C F).
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 7  of 6 8
2 
I N T R O D U C TI O N
I n rece nt years t he c os metic i n d ustr y has gr o w n c o nsi dera bl y, al o n g wit h its c o ncer n f or 
de vel o pi n g safe a n d effecti ve pr o d ucts.  T his i n d ustr y a ware ness, a n d c o ns u mer a n d re g ulat or y 
a ge nc y re q uire me nts ha ve le d c os metic ma n ufact urers t o a d o pt pr oce d ures t hat pr o vi de t he m 
wit h a better u n dersta n di n g of t heir pr o d ucts.  T his i ncl u des t he c o n d uct of cli nical tests t o 
assess safet y a n d efficac y, w hic h are ofte n c o or di nate d b y der mat ol o gists or ot her e x perts 
bef ore mar keti n g a pr o d uct.  T hese pr oce d ures pr o vi de greater ass ura nce of safet y f or t he 
c o m pa nies, i ncrease t heir cre di bilit y, a n d i ncrease c o nfi de nce a m o n g c o ns u mers.
A c os metic pr o d uct t hat is freel y a vaila ble t o t he c o ns u mer m ust be safe w he n a p plie d u n der 
n or mal or reas o na bl y f oreseea ble c o n diti o ns of use ( A N VI S A, 2 0 1 2 ). T h us, t he ra w materials 
use d i n t he pr o d uct f or m ulati o n m ust be of pr o ve n safet y a n d wit h esta blis he d use i n t he 
c os metic i n d ustr y.  As a ge neral re q uire me nt, t he safet y of t he fi nal f or m ulati o n m ust als o be 
c o nfir me d bef ore it is mar kete d.
S ki n c o ntact wit h t o pical pr o d ucts s uc h as c os metics ma y tri g ger differe nt t y pes of reacti o ns 
i ncl u di n g ecze mat o us c o ntact der matitis, urticaria, ac ne a n d s p ots.  C o ntact der matitis ca n arise 
fr o m t w o 
mec ha nis ms: pri mar y irritati o n, t hr o u g h t he acti o n of irrita nt s u bsta nces; or 
se nsitisati o n, i n t he prese nce of a n aller ge nic i n gre die nt.
Cli nical st u dies t o e val uate t he irritati o n a n d se nsitisati o n p ote ntial of a pr o d uct m ust ta ke i nt o 
acc o u nt a n u m ber of varia bles: c o m p o ne nts use d i n t he f or m ulati o n, i n gre die nt c o nce ntrati o n, 
a bs or pti o n, a m o u nt a p plie d, s ki n c o n diti o n, a p plicati o n directi o ns a n d fre q ue nc y, as well as t he 
c u m ulati ve effect ( D o o ms- G o osse ns, 1 9 9 3 ).
A c o m m o n met h o d t o assess t he p ote ntial of a t o pical pr o d uct t o ca use irritati o n or se nsitisati o n 
i n v ol ves re peate d a p plicati o ns of a pr o d uct t o t he s ki n u n der se mi- occl usi ve patc hes (Bas ketter, 
2 0 0 8 ).  T he se mi- occl usi o n pr o vi des a hi g her de gree of c o ntact bet wee n t he c o m p o ne nts of t he 
pr o d uct f or m ula a n d t he s ki n (e xa g gerate d use c o n diti o ns). T heref ore, it is c o nsi dere d t o be a 
se nsiti ve met h o d t o assess t he p h ot o-irritati o n a n d p h ot o-se nsitisati o n p ote ntial of t o picall y 
a p plie d pr o d ucts. 
Se veral t y pes of s u bsta nces d o n ot prese nt a n i n here nt irrita nt or aller ge nic p ote ntial; h o we ver, 
t he y ma y pr o v o ke s ki n reacti o ns w he n e x p ose d t o s u nli g ht, eit her beca use ultra vi olet ra diati o n 
c o n verts t he m i nt o ot her s u bsta nces, or beca use t he y are p h ot o-i nitiate d t o e xcite d states ca pa ble 
of i nteracti n g wit h t he s ki n ( Bill hi mer, 1 9 9 0 ). S pecificall y, t o picall y a p plie d a ge nts ca n ca use 
c o ntact der matitis or i nteract wit h s u nli g ht t o ca use p h ot o-irrita nt reacti o ns. T hese reacti o ns 
occ ur o n first e x p os ure t o t he pr o d uct a n d us uall y rese m ble e xa g gerate d s u n b ur n a n d ma y be 
c haracterise d b y a se nsati o n of pric kli n g a n d b ur ni n g. 
S ki n se nsitisati o n is a n i m m u n ol o gical pr ocess i n w hic h t he res p o nsi ve ness t o a s pecific 
c he mical aller ge n is i ncrease d. B y defi niti o n, s ki n se nsitisati o n is i n d uce d w he n a s usce pti ble 
i n di vi d ual is e x p ose d t o a n i n d ucti ve c he mical aller ge n. T his aller ge n ca uses a s ki n i m m u ne 
res p o nse t hat, at a certai n ra n ge, will res ult i n t he de vel o p me nt of c o ntact se nsitisati o n (Ki m ber 
et al.). 
T he p h ot o-irritati o n test meas ures t he p ote ntial of a test pr o d uct t o pr o d uce p h ot o-irrita nt 
reacti o ns i n h u ma n s u bjects u p o n e xa g gerate d a p plicati o n. E val uat or c o m paris o n of c uta ne o us 
res p o nses t o test pr o d uct al o ne, test pr o d uct e x p ose d t o U V ra diati o n a n d a n irra diate d, 
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 8  of 6 8
refere nce pr o d uct site pr o vi des a n assess me nt of t he p h ot o-irrita nt t o xic p ote ntial of t he test 
pr o d uct.  
T o picall y a p plie d pr o d ucts ma y c o ntai n o ne or m ore i n gre die nts t hat ca n be c o n verte d t o a 
p h ot o-a nti ge n b y U V ra diati o n. I n certai n i n di vi d uals, t he p h ot o-a nti ge n ca n t he n tri g ger a n 
i nfla m mat or y res p o nse b y t he i m m u ne s yste m a n d pr o d uce a n aller gic reacti o n u p o n s u bse q ue nt 
e x p os ure t o t he pr o d uct i n s u nli g ht. 
T he p h ot o-se nsitisati o n test meas ures t he p ote ntial of st u d y pr o d ucts t o pr o d uce aller gic 
reacti o ns i n t he prese nce of U V ra diati o n. T his test c o nsists of t hree p hases: a 3- wee k i n d ucti o n 
p hase c o nsisti n g of t w o parallel re peate d 2 4 h o ur patc h a p plicati o ns o n t he bac ks of healt h y 
s u bjects ( o ne of w hic h is s u bse q ue ntl y e x p ose d t o U V ra diati o n u p o n patc h re m o val, a n d 
e val uati o n of c uta ne o us res p o nses of b ot h sites) after eac h patc h re m o val; a 2 wee k Rest p hase; 
a n d a fi nal c halle n ge p hase, c o nsisti n g of t w o parallel 2 4 h o ur se mi- occl usi ve patc h a p plicati o ns 
t o nai ve sites, o ne set of w hic h is s u bse q ue ntl y e x p ose d t o U V ra diati o n u p o n patc h re m o val, 
a n d e val uati o n of c uta ne o us res p o nses of b ot h sites 2 4, 4 8 a n d 7 2 h o urs after patc h re m o val.
T he i ncl usi o n of a n i n d ucti o n a n d c halle n ge p hase f or t w o series of patc hes ( o ne wit h a n d o ne 
wit h o ut e x p os ure t o U V ra diati o n) e na bles si m ulta ne o us e val uati o n of t he p ote ntial f or c o ntact 
irritati o n, p h ot o-irritati o n, c o ntact se nsitisati o n a n d p h ot o-se nsitisati o n.
T he o bjecti ve of t his cli nical st u d y is t o assess t he p h ot o-se nsitisati o n a n d p h ot o-irritati o n 
p ote ntial of t hree c os metic st u d y pr o d ucts u n der e xa g gerate d c o n diti o ns of use wit h c o ntr olle d 
pr o d uct a p plicati o n a n d u n der s u per visi o n of a der mat ol o gist.
2. 1 
St u d y R ati o n al e
G S K C H has de vel o pe d t hree t o pical c os metic f or m ulati o ns (a l oti o n, crea m a n d ser u m) 
i nte n de d t o be use d i n dail y facial s ki n care r o uti nes. T hese pr o d ucts are desi g ne d t o be s uita ble 
f or use b y healt h y a d ult c o ns u mers wit h dr y facial s ki n. T he st u d y pr o d ucts are t o be a p plie d 
directl y t o t he s ki n after clea nsi n g, wit h t he i nte nt of deli veri n g i n gre die nts directl y o nt o t he 
s ki n. 
As t he ne w f or m ulati o ns are i nte n de d f or facial a p plicati o n, c o ns u mers w h o a p pl y t he pr o d ucts 
will be e x p ose d t o ultra vi olet ra diati o n fr o m t he s u n. T heref ore, cli nical data is re q uire d t o 
c o nfir m t hat t he de vel o p me ntal f or m ulati o ns ha ve l o w p h ot o-se nsitisati o n p ote ntial.
A m o n g t he se veral t y pes of safet y assa ys i n h u ma ns, patc h tests are c urre ntl y t he m ost 
wi des prea d pr ot oc ols c o n d ucte d i n or der t o i n vesti gate t he p ote ntial ris k f or p ossi ble irritati o n 
a n d se nsitisati o n a ge nts t hat, w he n i n c o ntact wit h t he h u ma n s ki n a n d e x p os ure t o U V R ma y 
tri g ger a reacti o n.
Vis ual assess me nt will be perf or me d i n a r o o m wit h matte, ne utral wall c ol o urs wit h s ufficie nt 
a n d u nif or m ill u mi nati o n. As o nl y o ne series of u n pr otecte d s ki n sites will be e x p ose d t o U V 
ra diati o n f or t he detecti o n of t he pr o visi o nal M E D u, t he gra der will, necessaril y, n ot be bli n de d 
at t his p oi nt i n t he st u d y.
C o m plete i nf or mati o n f or t he de vel o p me ntal c os metic facial l oti o n, ser u m, crea m a n d t he 
c o m parat or sali ne s ol uti o n ma y be f o u n d i n t he si n gle refere nce safet y d oc u me nt ( S R S D), 
w hic h f or t his st u d y is t he Safet y State me nt.
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2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 1 9  of 6 8
2. 2  
B a c k gr o u n d
Cli nical st u dies t o e val uate t he irritati o n a n d se nsitisati o n p ote ntial of a pr o d uct m ust ta ke i nt o 
acc o u nt a n u m ber of varia bles: c o m p o ne nts use d i n t he f or m ulati o n, i n gre die nt c o nce ntrati o n, 
a bs or pti o n, a m o u nt a p plie d, s ki n c o n diti o n, a p plicati o n directi o ns a n d fre q ue nc y, as well as t he 
c u m ulati ve effect ( D o o ms- G o osse ns, 1 9 9 3 ). C o m pati bilit y st u dies, perf or me d as patc h tests, 
ai m t o c o nfir m t he l ocal t olera nce of t o pical c os metic pr o d ucts d uri n g t he first a p plicati o n t o 
t he s ki n, t heref ore pr o vi di n g ass ura nce t hat t he pr o d uct is safe f or use u n der ma xi mize d 
c o n diti o ns ( A N VI S A, 2 0 1 2 ).
A c o m m o n met h o d t o assess t he p ote ntial of a t o pical pr o d uct t o ca use irritati o n or se nsitisati o n 
i n v ol ves re peate d a p plicati o ns of a pr o d uct t o t he s ki n u n der se mi- occl usi ve patc hes (Bas ketter, 
2 0 0 8 ).  T he test re peate dl y e x p oses s u bjects t o t he pr o d ucts d uri n g a 3- wee k i n d ucti o n peri o d, 
w hic h is f oll o we d b y a 2- wee k rest peri o d a n d a fi nal c halle n ge at a pre vi o usl y u ne x p ose d site. 
T he test sites are gra de d f or vis ual si g ns of reacti o ns t hr o u g h o ut t he i n d ucti o n a n d c halle n ge 
peri o ds. Ge nerall y, t he classificati o n of cli nical o utc o mes f oll o ws t he scale rec o m me n de d b y 
t he I nter nati o nal C o ntact Der matitis Researc h gr o u p (I C D R G) (Fre gert, 1 9 7 4 ).
T he se mi- occl usi o n pr o vi des a hi g her de gree of c o ntact bet wee n t he c o m p o ne nts of t he pr o d uct 
f or m ula a n d t he s ki n. T heref ore, it is c o nsi dere d t o be a se nsiti ve met h o d t o assess t he p h ot o-
irritati o n a n d p h ot o-se nsitisati o n p ote ntial of t o picall y a p plie d pr o d ucts. 
T he o bjecti ve of t his cli nical st u d y is t o assess t he p h ot o-se nsitisati o n a n d p h ot o-irritati o n 
p ote ntial of t hree de vel o p me ntal c os metic f or m ulati o ns a n d a refere nce pr o d uct (sali ne s ol uti o n) 
b y re peate d se mi- occl usi ve patc h a p plicati o ns t o healt h y h u ma n s u bjects, u n der t he s u per visi o n 
of a der mat ol o gist.
2. 3  
M e c h a ni s m of A cti o n/I n di c ati o n
T he E ur o pea n U ni o n C os metics Directi ve defi nes a c os metic as a n y s u bsta nce or pre parati o n 
i nte n de d t o be place d i n c o ntact wit h t he e xter nal parts of t he h u ma n b o d y wit h a vie w 
e xcl usi vel y or mai nl y t o clea ni n g, perf u mi n g, c ha n gi n g a p peara nce a n d/ or c orrecti n g b o d y 
o d o urs a n d/ or pr otecti n g or kee pi n g i n g o o d c o n diti o n ( E ur o pea n C o m missi o n ( E C), 2 0 0 9). 
T his is a c o nsiste nt defi niti o n of c os metic pr o d ucts per A N VI S A ( A N VI S A, 2 0 1 2 ).
T he i n vesti gati o nal pr o d ucts i n t his st u d y are c os metic m oist urisers; a ser u m, l oti o n a n d crea m 
i nte n de d f or t o pical a p plicati o n t o healt h y a d ults wit h dr y s ki n i m me diatel y after clea nsi n g.
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 0  of 6 8
3 
S T U D Y O B J E C TI V E S A N D E N D P OI N T S
T a bl e 3- 1 
St u d y O bj e cti v e s a n d E n d p oi nt s
O bj e cti v e s
E n d p oi nt s
Pri m ar y
T o e v al u at e t h e c ut a n e o u s p h ot o-
s e n siti s ati o n p ot e nti al of t hr e e c o s m eti c 
f a ci al s ki n c ar e pr o d u ct s c o m p ar e d t o 
s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a p ot e nti al s e n siti s ati o n 
r e a cti o n w hi c h i s c o n si d er e d p h ot o-i niti at e d.
S e c o n d ar y
T o e v al u at e t h e c ut a n e o u s p h ot o-irrit ati o n 
p ot e nti al of t hr e e c o s m eti c f a ci al s ki n c ar e 
pr o d u ct s c o m p ar e d t o s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a p h ot o-i niti at e d r e a cti o n 
s c or e of ‘ +’ or gr e at er w hi c h n ot c o n si d er e d a p ot e nti al 
s e n siti s ati o n r e a cti o n.
T o e v al u at e t h e c ut a n e o u s s e n siti s ati o n 
p ot e nti al of t hr e e c o s m eti c f a ci al s ki n c ar e 
pr o d u ct s c o m p ar e d t o s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a p ot e nti al s e n siti s ati o n 
r e a cti o n w hi c h i s n ot c o n si d er e d p h ot o-i niti at e d.
T o e v al u at e t h e c ut a n e o u s irrit ati o n 
p ot e nti al of t hr e e c o s m eti c f a ci al s ki n c ar e 
pr o d u ct s c o m p ar e d t o s ali n e s ol uti o n.
Pr o p orti o n of s u bj e ct s wit h a n o n- p h ot o-i niti at e d 
r e a cti o n s c or e of ‘ +’ or gr e at er w hi c h i s n ot c o n si d er e d 
a p ot e nti al s e n siti s ati o n r e a cti o n.
S af et y
T o e v al u at e t h e g e n er al s af et y of t hr e e 
c o s m eti c f a ci al s ki n c ar e pr o d u ct s
Fr e q u e n c y a n d s e v erit y of A d v er s e E v e nt s
S uccess criteri a: 
A test pr o d uct will be c o nsi dere d t o ha ve l o w p h ot o-se nsitisati o n p ote ntial if t he pr o p orti o n of 
s u bjects wit h a p ote ntial p h ot o-se nsitisati o n reacti o n are c o m para ble f or t he test pr o d uct a n d 
sali ne. 
T he h y p ot hesis is t hat t he st u d y pr o d ucts will ha ve l o w p h ot o-se nsitisati o n p ote ntial. T heref ore, 
it is e x pecte d t hat t he vast maj orit y of res p o nses will be ne gati ve. N o f or mal statistical 
c o m paris o n bet wee n treat me nt gr o u ps s hall be ma de.
4 
S T U D Y D E SI G N 
4. 1  
O v er all D e si g n
T his will be a si n gle-ce nter, ra n d o mise d, e val uat or (si n gle) bli n d st u d y i n healt h y a d ult s u bjects 
a ge d 1 8 t o 6 5 years wit h n o der mat ol o gical dis or ders t o e val uate t he c uta ne o us p h ot o- irritati o n 
a n d p h ot o- se nsitisati o n p ote ntial of t hree c os metic facial s ki ncare pr o d ucts.
A p pr o xi matel y 8 0 healt h y s u bjects will be scree ne d t o ra n d o mise at least 4 0 s u bjects t o e ns ure 
at least 2 5 e val ua ble s u bjects c o m plete t he e ntire st u d y.
T here will be a t otal of 5 differe nt test areas, l ocate d o n t he bac k of eac h s u bject, w hic h will be 
use d i n t his st u d y acr oss t he scree ni n g, i n d ucti o n a n d c halle n ge p hases:

1 test area t o deter mi ne t he pr o visi o nal M E D u i n scree ni n g;
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 1  of 6 8

2 test areas f or test pr o d ucts a n d refere nce pr o d uct (sali ne s ol uti o n) i n t he i n d ucti o n 
p hase ( 1 series will be e x p ose d t o U V ra diati o n, t he ot her series will n ot); 

2 test areas f or test pr o d ucts a n d refere nce pr o d uct (sali ne s ol uti o n) i n t he c halle n ge 
P hase ( 1 series will be e x p ose d t o U V ra diati o n, t he ot her series will n ot).
T he 4 test areas i n t he i n d ucti o n a n d c halle n ge p hases will eac h u n der g o a p plicati o ns of a n 
a d hesi ve patc h s yste m. Wit hi n eac h patc h s yste m, t here will be 6 circ ular cells, of w hic h 4 will 
be use d t o h ost t he st u d y pr o d ucts a n d 2 will be left bla n k. I n t his st u d y, eac h of t he st u d y 
pr o d ucts will be dis pe nse d i nt o 4 a djace nt cells, i n t w o d u plicate series of patc hes, as per t he 
ra n d o misati o n sc he d ule. T hree cells will be use d f or t he test pr o d ucts (ser u m, l oti o n a n d crea m) 
a n d a f o urt h f or t he refere nce pr o d uct (sali ne s ol uti o n).  
S u bjects will be e x p ose d t o d u plicate, re peate d i ns ult se mi- occl usi ve patc h a p plicati o ns of t he 
test pr o d ucts a n d refere nce pr o d uct (sali ne s ol uti o n) o ver a t hree- wee k i n d ucti o n p hase, a n d a 
f urt her si n gle a p plicati o n of t he test pr o d ucts a n d refere nce pr o d uct i n a c halle n ge p hase.
D uri n g scree ni n g, s u bjects will si g n a n i nf or me d c o nse nt f or m a n d u n der g o a der mat ol o gical 
assess me nt t o e ns ure t he y ha ve n o der mat oses o n t heir d ors u m ( bac k) t hat mi g ht i m pact t heir 
safet y or c o nf o u n d st u d y o utc o mes, a n d t o e ns ure a Fitz patric k P h ot ot y pe of II t o I V. 
S u bjects will als o u n der g o a c ol ori metr y a nal ysis of t heir s ki n t y pe usi n g t he I n di vi d ual 
T y p ol o g y A n gle (I T A°) w hic h will be use d t o esti mate M E D.
Eac h s u bject’s me dical hist or y a n d me dicati o n hist or y will be re vie we d, as well as i ncl usi o n 
a n d e xcl usi o n criteria after w hic h, site staff will re vie w lifest yle c o nsi derati o ns a n d st u d y visit 
re q uire me nts wit h eli gi ble s u bjects. 
S u bjects w h o meet all s pecifie d i ncl usi o n a n d e xcl usi o n criteria a n d w h o a gree t o c o m pl y wit h 
all lifest yle g ui deli nes a n d restricti o ns will be c o nsi dere d eli gi ble f or e nr oll me nt i n t his st u d y. 
Visit 1 (scree ni n g) ma y be c o m bi ne d wit h visit 2 ( M E D irra diati o n) if c o n ve nie nt f or t he s u bject 
a n d st u d y site. H o we ver, visit 2 s h o ul d occ ur n o later t ha n 7 da ys after visit 1.  
At visit 2, eli gi ble s u bjects will ret ur n t o t he st u d y site a n d a n ot her der mat ol o gical assess me nt 
will be c o n d ucte d f or i ncl usi o n criteri o n 6 t o e ns ure s u bjects re mai n eli gi ble t o c o nti n ue i n t he 
st u d y (if visits 1 a n d 2 are n ot c o m bi ne d). A n y c ha n ges t o c o nc o mita nt me dicati o ns will als o 
be re vie we d. 
T he M E D of eac h s u bject will t he n be deter mi ne d i n a t w o-ste p pr oce d ure, see secti o n 8. 2. 1 
( M E D Irra diati o n) a n d 8. 3. 1 ( M E D Deter mi nati o n)  f or details. T his ste p is critical t o e ns ure t he 
selecti o n of U V d oses f or t he assess me nt of p h ot o-se nsitisati o n a n d p h ot o-irritati o n are 
a p pr o priate f or eac h s u bject, e na bli n g a r o b ust U V-c halle n ge of t he patc he d sites wit h o ut 
res ulti n g i n U V-i n d uce d er yt he ma (s u n b ur n). 
I n t his st u d y, o ne series of patc he d sites will be re peate dl y e x p ose d t o 0. 3 M E D of U V ra diati o n 
( 2 9 0- 4 0 0 n m) a n d a sec o n d c o ntr olle d d ose of 2. 5 J/c m2 U V A ( 3 4 0- 4 0 0 n m) ra diati o n per t he 
st u d y sc he d ule. 
I n d ucti o n P h ase ( visits 4- 1 8): 
D uri n g t he i n d ucti o n p hase ( visits 4- 1 8) t here will be 6 patc h a p plicati o n visits o ver 3 wee ks. 
Eac h patc h will c o ntai n a se gre gate d sa m ple of eac h of t he test pr o d ucts a n d sali ne s ol uti o n. 
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 2  of 6 8
D u plicate series of eac h patc h will be a p plie d t o t he assi g ne d test areas o n M o n da ys a n d 
We d nes da ys a n d s hall re mai n i n place f or 2 4 ( ± 4) h o urs. 
M o n d a y:  S u bjects will arri ve at site a n d will assi g ne d t o a ra n d o m se q ue nce of st u d y pr o d ucts 
wit hi n t he 4 cells of t he patc h s yste m, per t he ra n d o misati o n sc he d ule. T he l ocati o n of t he test 
areas o n t he bac k of eac h s u bject will be deter mi ne d b y t he i n vesti gat or or desi g nee base d o n 
t he c o n diti o n of t he s ki n (e. g. free of m oles, der mat oses etc.) a n d will n ot be ra n d o mise d.  
S u bjects will be seate d i n sta n dar d r o o m c o n diti o ns ( 1 8- 2 6° C) a n d i nstr ucte d t o a v oi d c o ntact 
bet wee n t he test area o n t heir bac k a n d a n y ot her s urface. T he area f or patc h a p plicati o n will be 
desi g nate d bet wee n t he sca p ula a n d waistli ne a n d a wa y fr o m t he s pi nal mi d-li ne. Baseli ne 
assess me nt of t he test site area will t he n be perf or me d b y a trai ne d, bli n de d e val uat or per t he 
gra di n g scale i n Ta ble 1 5- 2 ( A p pe n di x 2 ). T his will act as t he baseli ne rea di n g f or t he i n d ucti o n 
p hase. 
N ote, t he sec o n d a n d t hir d M o n da y visits (i.e. visits 9 a n d 1 4) will n ot i ncl u de t he 
ra n d o misati o n ste p. H o we ver, t hese visits will i ncl u de a n assess me nt f or si g ns a n d s y m pt o ms 
of irritati o n b y a trai ne d, bli n de d e val uat or f oll o wi n g U V irra diati o n t he prece di n g T h urs da y 
(i.e. visits 7 a n d 1 2).
Fi g ur e 4- 1 
E x a m pl e l a y o ut of t h e p at c h o n t h e d or s u m ( s h o w n a d h e si v e si d e d o w n) 
T w o se mi- occl usi ve patc hes wit h 6 cells la belle d A- F will be use d. F o ur cells ( A- D) will be 
use d i n t his st u d y ( 1 f or eac h test pr o d uct a n d 1 f or t he sali ne s ol uti o n). T w o cells ( E- F) will 
re mai n e m pt y. 
A c o ntr olle d a m o u nt ( 0. 0 2 m L/c m 2) of eac h st u d y pr o d uct will be dis pe nse d i nt o t he a p pr o priate 
se parate cell, 3 cells f or eac h of t he test pr o d ucts a n d 1 cell f or t he sali ne s ol uti o n t o eac h of t he 
patc h s yste ms.  T he assi g n me nt of t he st u d y pr o d ucts t o t he cells wit hi n t he patc h s yste m f or 
eac h s u bject will be ra n d o ml y assi g ne d per t he ra n d o misati o n sc he d ule pr o vi de d. T he se q ue nce 
of t he pr o d ucts t o t he cells f or eac h s u bject will re mai n t he sa me t hr o u g h o ut t he i n d ucti o n p hase. 
A differe nt se q ue nce per t he ra n d o misati o n pr o vi de d will be use d f or eac h s u bject f or t he 
c halle n ge p hase.
A
B
C
D
E
F
A
B
C
D
E
F
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 3  of 6 8
T ues d a y:  S u bjects will arri ve at site after 2 4 ( ± 4) h o urs of patc h a p plicati o n.  T he patc hes will 
be re m o ve d, a n d t he treate d areas ca n be li g htl y wi pe d wit h sali ne s ol uti o n.  S u bjects will be 
i nstr ucte d t o rest f or 1 5- 3 0 mi n utes i n sta n dar d r o o m c o n diti o ns (te m perat ure 1 8- 2 6 ° C), 
a v oi di n g c o ntact of t he bac k area wit h a n y ot her s urface.  After 3 0 mi n utes ( ma xi m u m of 1 
h o ur), t he test sites will be e val uate d b y a trai ne d, bli n de d e val uat or per t he scale i n Ta ble 1 5- 2 
A p pe n di x 2 . 
After assess me nt of t he test sites, st u d y pr o d ucts will be rea p plie d directl y t o t he pre vi o usl y 
treate d s ki n sites i n t he sa me se q ue nce ( per t he ra n d o misati o n sc he d ule).  After a 1 5- 3 0 mi n ute 
dr yi n g peri o d, o ne area of s ki n treate d wit h t he st u d y pr o d ucts will be irra diate d wit h 2. 5 J/c m 2 
U V A ra diati o n wit h a Sc h ott U G 1 1 + W G 3 3 5  filter ( or e q ui vale nt) i n place, a n d t he n wit h 0. 3 
M E Ds of U V A + U V B ra diati o n (filters U G 1 1 + W G 3 2 0). T he d u plicate area treate d wit h t he 
st u d y pr o d ucts will n ot recei ve irra diati o n d uri n g t he irra diati o n pr oce d ure. Assess me nt of t he 
irra diate d a n d n o n-irra diate d sites f or si g ns of irritati o n will occ ur i m me diatel y after t he U V 
e x p os ure pr oce d ures are c o m plete d, a n d a n y reacti o n will be gra de d as per gra di n g scale Ta ble 
1 5- 2 ( A p pe n di x 2) .
F or eac h p ositi ve reacti o n (a sc ore of ‘ +’ or greater) i n t he c halle n ge p hase, a der mat ol o gist 
( bli n de d) will f urt her classif y it as p ote ntial se nsitisati o n ( or n ot) a n d pr o vi de a narrati ve 
descri pti o n of t he e ve nt. T he der mat ol o gist will n ot be sc ori n g t he reacti o ns. 
If a s u bject de vel o ps a sc ore of ‘ Str o n g’ ( + +) or greater at a n y p oi nt d uri n g t he i n d ucti o n p hase, 
t he ne xt patc h will be a p plie d t o a n a djace nt naï ve (i.e. pre vi o usl y u ntreate d) site. If a sc ore of 
‘ Str o n g’ ( + +) or greater occ urs at t he naï ve site, n o f urt her patc h a p plicati o ns will be ma de. 
S uc h reacti ve s u bjects will, h o we ver, pr o gress t o t he rest a n d c halle n ge p hase u nless, i n t he 
o pi ni o n of t he I n vesti gat or, it w o ul d be u n wise t o d o s o.
We d nes d a y:  S u bjects will arri ve at site after 2 4 ( ± 4) h o urs after irra diati o n a n d will be seate d 
f or at least 1 5- 3 0 mi n utes t o t he e n vir o n me nt of sta n dar d r o o m c o n diti o ns ( 1 8- 2 6° C) a n d 
i nstr ucte d t o a v oi d c o ntact of t he bac k area wit h a n y ot her s urface. Test sites will be e val uate d 
f or si g ns of irritati o n b y a trai ne d, bli n de d e val uat or as per gra di n g scale Ta ble 1 5- 2 ( A p pe n di x 
2) . 
D u plicate patc hes will t he n be a p plie d t o t he bac k, please see M o n da y assess me nts f or f urt her 
details o n patc h a p plicati o n.
T h urs d a y:  T ues da y assess me nts t o be re peate d. 
Fri d a y:   S u bjects will arri ve at site after 2 4 ( ± 4) h o urs after irra diati o n a n d will be seate d f or 
at least 1 5- 3 0 mi n utes t o t he e n vir o n me nt of sta n dar d r o o m c o n diti o ns ( 1 8- 2 6° C) a n d i nstr ucte d 
t o a v oi d c o ntact of t he bac k area wit h a n y ot her s urface. Test sites will be e val uate d f or si g ns 
of irritati o n b y a trai ne d, bli n de d e val uat or as per gra di n g scale Ta ble 1 5- 2 ( A p pe n di x 2).  
T he pr ocess of patc h a p plicati o ns, gra di n g a n d U V-e x p os ure s hall be re peate d f or a n a d diti o nal 
t w o wee ks.
Rest P h ase ( 2 wee ks): 
O nce t he i n d ucti o n p hase is c o m plete, s u bjects will e nter a 2- wee k rest p hase, d uri n g w hic h 
t here will be n o pr o d uct or patc h a p plicati o ns.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 4  of 6 8
C h alle n ge P h ase  ( Visits 1 9- 2 3): 
O nce t he rest p hase i n c o m plete, s u bjects will ret ur n f or t he c halle n ge p hase ( visits 1 9- 2 3). 
Ra n d o misati o n f or c halle n ge p hase will occ ur o n visit 1 9 ( da y 3 6). T he or der t o w hic h t he st u d y 
pr o d ucts are assi g ne d t o t he cells wit hi n t he patc h s yste m are ra n d o mise t o re d uce t he 
o p p ort u nit y f or bias t hr o u g h o utc o mes o bser ve d i n t he i n d ucti o n p hase.
T he c halle n ge p hase will c o nsist of a d u plicate parallel series of pr o d uct a p plicati o ns u n der 
se mi- occl usi ve patc hes t o 2 naï ve areas (i.e. pre vi o usl y u ntreate d) of t he bac k, bet wee n t he 
s h o ul der li ne a n d waist, a n d a wa y fr o m t he s pi nal mi d-li ne. 
T hese areas will be e val uate d b y t he trai ne d, bli n de d e val uat or pri or t o a n y patc h a p plicati o n t o 
pr o vi de a baseli ne f or i nter pretati o n. T w o patc hes c o ntai ni n g st u d y pr o d ucts as per t he 
ra n d o misati o n se q ue nce f or t he s u bject’s c halle n ge p hase, will t he n be a p plie d. 
M o n d a y/ T ues d a y: 
After ra n d o misati o n f or t he c halle n ge p hase all  assess me nts as per t he 
I n d ucti o n p hase are t o be re peate d. 
We d nes d a y/ T h urs d a y/ Fri d a y:  F urt her test site assess me nts f or si g ns of c uta ne o us irritati o n 
will be c o n d ucte d 2 4 ( ± 4), 4 8 ( ± 4), a n d 7 2 ( ± 4) h o urs after U V e x p os ure as per gra di n g scale 
Ta ble 1 5- 2 ( A p pe n di x 2 ).
E n d of St u d y ( Visit 2 3): 
At visit 2 3/ Da y 4 0, after t he c halle n ge p hase is c o m plete, a fi nal cli nical assess me nt b y a 
q ualifie d der mat ol o gist will be perf or me d t o e ns ure t hat it is me dicall y a p pr o priate t o e xit eac h 
s u bject fr o m t he st u d y. After all st u d y assess me nts are c o m plete d, s u bjects will be disc har ge d 
fr o m t he st u d y site. 
A d diti o nall y, t he der mat ol o gist will use t he t otal b o d y of data f or a s u bject (a n y p ositi ve 
reacti o ns w hic h occ urre d o ver t he c halle n ge p hase) t o j u d ge w het her a p ositi ve reacti o n is a 
p ote ntial se nsitisati o n reacti o n or n ot. 
A d verse e ve nts a n d c o nc o mita nt me dicati o ns will be assesse d t hr o u g h o ut t he st u d y. 
4. 2  
R ati o n al e f or St u d y D e si g n
C o m pati bilit y st u dies re prese nt t he first c o ntact of t he fi nis he d pr o d uct i n h u ma ns a n d see k t o 
pr o ve t he safet y of pr o d uct u n der 
ma xi mise d c o n diti o ns, wit h c o ntr olle d a m o u nt a n d 
a p plicati o n area. T he a p plicati o n of st u d y pr o d ucts wit hi n a se mi occl usi ve patc h all o ws f or a 
cli nical assess me nt u n der ma xi mize d c o n diti o ns a n d is gl o ball y acce pte d, bei n g wi del y use d i n 
t he literat ure.
T here will be a bli n de d e val uat or (trai ne d o n t he I C D R G sc ori n g s yste m) t o assess all patc h 
sites f or t he d urati o n of t he st u d y. T he i nte nsit y of a n y vis ual si g ns of irritati o n will be rec or de d 
acc or di n g t o t he q ua ntit y a n d gra de of t he reacti o ns, Ta ble 1 5- 2 ( A p pe n di x 2 ). T he trai ne d 
e val uat or is res p o nsi ble f or gra di n g t he reacti o ns, a n d t he trai ne d e val uat or’s sc ore will be 
c o nsi dere d is fi nal.
T his st u d y will be c o n d ucte d u n der t he s u per visi o n of a der mat ol o gist. S u bjects will be assesse d 
b y a der mat ol o gist as a prere q uisite t o e nr ol me nt, a n d a gai n at st u d y e n d.  F or pr o d ucts wit h 
s pecific safet y a p peals, t he st u d y m ust be f oll o we d u p b y a s pecialist ( der mat ol o gist) ( A N VI S A, 
2 0 1 2). 
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 5  of 6 8
F or eac h s u bject w h o prese nts a p ositi ve reacti o n (i.e. a reacti o n sc ore of ‘ +’ or greater) i n t he 
c halle n ge p hase a bli n de d der mat ol o gist will f urt her classif y t he reacti o n as p ote ntial 
se nsitisati o n ( or n ot) at t he fi nal visit a n d pr o vi de a si n gle narrati ve descri pti o n t o s u m marise 
t he e ntiret y of t he s u bject’s e x perie nce of t he e ve nt. As se nsitisati o n a n d irritati o n ca n occ ur i n 
t he c halle n ge p hase, it is p ossi ble t o rec or d a p ositi ve reacti o n i n t he c halle n ge p hase w hic h is 
n ot a se nsitisati o n reacti o n. T he der mat ol o gist m ust c o nsi der h o w t he reacti o n prese nts/e v ol ves 
o ver ti me, t o ascertai n w het her it is c haracteristic of a se nsitisati o n reacti o n. T he der mat ol o gist 
will rec or d t heir o pi ni o n i n t he narrati ve a n d wit h a c hec k- b o x i n t he C R F.
T he narrati ve m ust i ncl u de t he test site, start a n d fi nis h date of t he e ve nt, a descri pti o n of h o w 
t he e ve nt e v ol ves o ver ti me, a n y acti o n ta ke n (e. g. m o ve d patc h) a n d w het her t he der mat ol o gist 
c o nsi ders t he reacti o n t o be a p ote ntial se nsitisati o n reacti o n. If a clear dia g n osis ca n n ot be 
ma de, t he n t he der mat ol o gist s h o ul d i ncl u de t his i n t he narrati ve. 
T he ac ute as pects of p h ot o-irrita nt reacti o ns ma y be gi n wit hi n a fe w mi n utes t o h o urs after 
irra diati o n a n d te n d t o res ol ve wit hi n a fe w da ys t o wee ks.  W hereas t he ac ute as pects of p h ot o-
irrita nt reacti o ns t y picall y prese nt s o o n after irra diati o n, p h ot o- se nsitisati o n reacti o ns sel d o m 
occ ur after t he first e x p os ure t o t he p h ot o-aller ge n. Si nce p h ot o-se nsitisati o n is a n 
i m m u n ol o gical pr ocess i n nat ure, m ulti ple e x p os ures t o t he p h ot o-acti vate d aller ge n a n d a late nt 
peri o d of se veral da ys t o wee ks are t y picall y re q uire d bef ore t he i m m u ne s yste m is rea d y t o 
res p o n d. O nce a s u bject has bee n se nsitise d, s u bse q ue nt e x p os ures t o t he p h ot o-aller ge n a n d 
li g ht will elicit c uta ne o us res p o nses q uite ra pi dl y wit hi n 2 4- 7 2 h o urs ( Bea ni 2 0 1 7).
A s u bject ma y e x perie nce p ositi ve reacti o ns i n a n y of t he f oll o wi n g patter ns:
1.
At O N L Y t he U V-e x p ose d site,
2.
At O N L Y t he N o n- U V-e x p ose d site,
3.
At B O T H t he U V-e x p ose d a n d n o n- U V-e x p ose d sites.
T he l ocati o n of p ositi ve reacti o ns will be deter mi ne d after u n bli n di n g t o deter mi ne w het her a 
reacti o n is p ote ntiall y p h ot o-i nitiate d:

P ositi ve reacti o ns w hic h occ ur at O N L Y t he U V-e x p ose d site will be c o nsi dere d p h ot o-
i nitiate d.

P ositi ve reacti o ns w hic h occ ur at O N L Y t he n o n- U V-e x p ose d site will n ot be 
c o nsi dere d p h ot o-i nitiate d.

P ositi ve reacti o ns w hic h occ ur at B O T H t he U V-e x p ose d a n d n o n- U V-e x p ose d sites 
will be c o nsi dere d p h ot o-i nitiate d if t he ma xi m u m sc ore at t he U V-e x p ose d site is m ore 
se vere t ha n t he ma xi m u m sc ore at t he n o n- U V-e x p ose d site. If t he ma xi m u m sc ore at 
t he U V-e x p ose d site is e q ual t o or l o wer t ha n t he n o n- U V-e x p ose d site, t he n it will n ot 
be c o nsi dere d p h ot o-i nitiate d. 
T he i ncl usi o n of e val uati o ns at 2 4, 4 8 a n d 7 2- h o urs f or d u plicate sites treate d wit h st u d y 
pr o d ucts, wit h or wit h o ut U V R, i n a c u m ulati ve a p plicati o n via a n i n d ucti o n p hase, late nt rest 
p hase, a n d c halle n ge p hase, per mits si m ulta ne o us e val uati o n of t he p ote ntial f or c o ntact 
irritati o n, p h ot o-irritati o n, c o ntact se nsitisati o n a n d p h ot o-se nsitisati o n. 
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 6  of 6 8
4. 3 
J u stifi c ati o n f or D o s e
T he prere q uisite f or a patc h test is t he re q uire me nt t hat t he w h ole test site is c o vere d wit h t he 
test pr o d uct, wit h o ut s prea di n g or o verla p pi n g i nt o ot her test sites. Pre vi o us w or k (Isa kss o n, 
2 0 0 7 ) has s h o w n t hat t he o pti mal d ose t o f ulfil t hese re q uire me nts is 0. 0 2 ml/c m2.
T he test pr o d uct will be distri b ute d o ver t he patc h test filter pa per discs (se mi occl usi ve patc h 
a p plicati o n) i n t he a m o u nt of 0. 0 2 ml a n d a p plie d t o desi g nate d sites o n t he bac k. A s o di u m 
c hl ori de ( Na Cl) sali ne s ol uti o n ( 0. 9 %) will be use d as t he refere nce pr o d uct a n d will als o be 
a p plie d t o t he bac k t hr o u g h se mi- occl usi ve a p plicati o n a n d dis pe nse d at t he sa me d ose.
T he se mi- occl usi ve patc hes will be ma de of a h y p oaller ge nic material a n d c o ntai n r o u n d cells 
of a n a bs or be nt material. O ne of t he cells will c o ntai n t he refere nce pr o d uct a n d t hree ot her 
cells will be fille d wit h eac h of t he test pr o d ucts acc or di n g t o t he s u p plie d ra n d o misati o n 
all ocati o n f or t he i n d ucti o n a n d c halle n ge p hase. O nl y pr o d ucts of t he s p o ns or, G S K C H, will 
be teste d i n t his st u d y.
P h ot oreacti o ns t o e x o ge n o us a ge nts t y picall y occ ur i n res p o nse t o U V A li g ht ( 3 1 5- 4 0 0 
na n o meters ( n m) rat her t ha n at t he s h orter wa vele n gt hs of U V B or U V C. T heref ore, U V A 
irra diati o n is ma n dat or y. H o we ver, s o me m olec ules ha ve t heir acti o n s pectr u m i n U V B.  
C o nse q ue ntl y, t o pre ve nt missi n g detecti o n of a n y p h ot oreacti o ns, b ot h U V A a n d U V B 
irra diati o n i n parallel are n o w c o nsi dere d ma n dat or y (Bea ni 1 9 8 7 ). T he p h ot o- reacti o ns ca n be 
di vi de d i nt o t w o t y pes of res p o nses; p h ot o-irritati o n a n d p h ot o-se nsitisati o n ( N or bert, 2 0 0 5 ). 
A d ose of 0. 3 M E D a n d 2. 5 J/c m 2 has bee n c h ose n t o e ns ure t hat t he t otal d ose a d mi nistere d 
will be s ufficie nt t o pr o vi de e val uati o n of p h ot o-se nsitisi n g a n d p h ot o-irrita nt reacti o n p ote ntial 
wit h c o nsi derati o n of t he e x p os ure of t he s u bjects ( Bea ni 2 0 1 7 ). 
4. 4 
E n d of St u d y D efi 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 he or s he has c o m plete d all p hases of t he 
st u d y i ncl u di n g t he last visit or t he last sc he d ule d pr oce d ure s h o w n i n t he Sc he d ule of Acti vities.
T he e n d of t his st u d y is defi ne d as t he date of t he last s u bject’s last visit.
5 
S T U D Y P O P U L A TI O N
5. 1 
T y p e a n d Pl a n n e d N u m b er of S u bj e ct s
Healt h y male a n d fe male s u bjects a ge d 1 8 t o 6 5 wit h n o der mat ol o gical dis or ders, a n d wit h a 
Fitz patric k s ki n p h ot ot y pe II t o I V will be e nr olle d i nt o t his st u d y. 
A p pr o xi matel y 8 0 healt h y s u bjects will be scree ne d t o ra n d o mise at least 4 0 s u bjects t o e ns ure 
at least 2 5 e val ua ble s u bjects wit h n o der mat ol o gical dis or ders a n d wit h a Fitz patric k s ki n 
pr ot ot y pe II t o I V c o m plete t he e ntire st u d y. T his sa m ple size is sta n dar d i n cli nical testi n g 
practices a n d is c o nsiste nt wit h t he A N VI S A g ui deli nes ( A N VI S A, 2 0 1 2 ).
T his st u d y ca n f ulfill its o bjecti ves o nl y if a p pr o priate s u bjects are e nr olle d.  A n e nr olle d s u bject 
is o ne w h o has a gree d t o partici pate i n t he cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d 
c o nse nt pr ocess directl y or via t heir le gall y a ut h orise d re prese ntati ve a n d s uccessf ull y met 
eli gi bilit y criteria t o pr ocee d be y o n d t he scree ni n g visit as a p plica ble f or t he pr ot oc ol desi g n.  
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 7  of 6 8
T he f oll o wi n g eli gi bilit y criteria are desi g ne d t o select s u bjects f or w h o m partici pati o n i n t he 
st u d y is c o nsi dere d a p pr o priate.  All rele va nt me dical a n d n o n- me dical c o n diti o ns s h o ul d be 
ta ke n i nt o c o nsi derati o n w he n deci di n g w het her a s u bject is s uita ble f or t his pr ot oc ol.  
S u bject eli gi bilit y t o partici pate i n t he cli nical st u d y s h o ul d be re vie we d a n d d oc u me nte d b y a n 
a p pr o priate me m ber of t he i n vesti gat or’s st u d y tea m bef ore s u bjects are i ncl u de d i n t he st u d y.
5. 2 
I n cl u si o n Crit eri a
S u bject eli gi bilit y s h o ul d be re vie we d a n d d oc u me nte d b y t he I n vesti gat or or a me dicall y 
q ualifie d pers o n or desi g nee bef ore s u bjects are i ncl u de d i n t he st u d y.
A n i n di vi d ual m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o 
t he st u d y:
1.
S u bject pr o visi o n of a si g ne d a n d date d i nf or me d c o nse nt d oc u me nt i n dicati n g t hat 
t he s u bject has bee n i nf or me d of all perti ne nt as pects of t he st u d y bef ore a n y 
assess me nt is perf or me d.
2.
S u bject is male or fe male w h o, at t he ti me of scree ni n g, is  bet wee n t he a ges of 1 8 a n d 
6 5 years, i ncl usi ve.
3.
A s u bject w h o is willi n g a n d a ble t o c o m pl y wit h sc he d ule d visits, treat me nt pla n, a n d 
ot her st u d y pr oce d ures.
4.
A s u bject i n g o o d ge neral a n d me ntal healt h wit h, i n t he o pi ni o n of t he i n vesti gat or or 
me dicall y q ualifie d desi g nee, n o cli nicall y si g nifica nt or rele va nt a b n or malities i n 
me dical hist or y or u p o n der mal e xa mi nati o n, or c o n diti o n, t hat w o ul d i m pact t he 
s u bject’s safet y, well bei n g or t he o utc o me of t he st u d y, if t he y were t o partici pate i n 
t he st u d y, or affect t he i n di vi d ual’s a bilit y t o u n dersta n d a n d f oll o w st u d y pr oce d ures 
a n d re q uire me nts.
5.
Fitz patric k p h ot ot y pe II t o I V (see A p pe n di x 3 ).
6.
Healt h y, i ntact s ki n at t he pr o p ose d test area d ors u m ( bel o w t he s h o ul der, a b o ve t he 
waist), as e val uate d b y a der mat ol o gist, t o e ns ure s u bject is free of cli nicall y rele va nt 
der mat ol o gical c o n diti o ns.
5. 3 
E x cl u si o n Crit eri a
A n i n di vi d ual w h o meets a n y of t he f oll o wi n g e xcl usi o n criteria will n ot be eli gi ble f or 
e nr oll me nt i nt o t he st u d y:
1.    A s u bject w h o is a n e m pl o yee of t he i n vesti gati o nal site, eit her directl y i n v ol ve d i n 
t he c o n d uct of t he st u d y or a me m ber of t heir i m me diate fa mil y; or a n e m pl o yee of 
t he i n vesti gati o nal site ot her wise s u per vise d b y t he i n vesti gat or; or, a G S K C H 
e m pl o yee directl y i n v ol ve d i n t he c o n d uct of t he st u d y or a me m ber of t heir 
i m me diate fa mil y.
2.    A s u bject w h o has partici pate d i n ot her st u dies i n v ol vi n g i n vesti gati o nal pr o d uct(s) 
wit hi n 3 0 Da ys pri or t o st u d y e ntr y a n d/ or d uri n g st u d y partici pati o n.
3.    A s u bject w h o has partici pate d i n ot her st u dies i ncl u di n g n o n- me dici nal, c os metic 
st u dies wit hi n 7 Da ys pri or t o st u d y e ntr y a n d/ or d uri n g st u d y partici pati o n.
4.    A s u bject wit h, i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d desi g nee, a n 
ac ute or c hr o nic me dical or ps yc hiatric c o n diti o n or la b orat or y a b n or malit y t hat ma y 
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 8  of 6 8
i ncrease t he ris k ass ociate d wit h st u d y partici pati o n or i n vesti gati o nal pr o d uct 
a d mi nistrati o n or ma y i nterfere wit h t he i nter pretati o n of st u d y res ults a n d, i n t he 
j u d g me nt of t he i n vesti gat or or me dicall y q ualifie d desi g nee, w o ul d ma ke t he s u bject 
i na p pr o priate f or e ntr y i nt o t his st u d y.
5.    A s u bject w h o is pre g na nt (self-re p orte d).
6.    A s u bject w h o is breastfee di n g.
7.    A s u bject wit h k n o w n or s us pecte d i nt olera nce or h y perse nsiti vit y t o t he st u d y 
materials/ pr o d uct ( or cl osel y relate d c o m p o u n ds) or a n y of t heir state d i n gre die nts, t o 
h y p oaller ge nic ta pe, or t o t he c ott o n patc hes.
8.    A s u bject w h o, i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d desi g nee, 
s h o ul d n ot partici pate i n t he st u d y. 
9.    A s u bject u n willi n g or u na ble t o c o m pl y wit h t he Lifest yle C o nsi derati o ns  descri be d 
i n t his pr ot oc ol. 
1 0.    A s u bject wit h c urre nt or rece nt ( wit hi n last 6 m o nt hs bef ore t he start of t he st u d y) 
hist or y of at o pic lesi o ns a n d/ or ecze ma, ps oriasis or s ki n ca ncer 
1 1.   A s u bject wit h a hist or y of aller gic reacti o ns t o t o pical- use pr o d ucts, c os metics or 
me dicati o ns or t heir i n gre die nts.
1 2.  A s u bject wit h a n y hist or y of si g nifica nt diseases or me dical c o n diti o ns k n o w n t o 
alter s ki n a p peara nce or p h ysi ol o gic res p o nse (e. g. dia betes) w hic h c o ul d, i n t he 
o pi ni o n of t he I n vesti gat or, precl u de t o pical a p plicati o n of t he i n vesti gati o nal 
pr o d ucts a n d/ or i nterfere wit h t he e val uati o n of t he test site reacti o n.
1 3.   A s u bject c o nsi dere d i m m u ne-c o m pr o mise d.
1 4.   A s u bject wit h acti ve der mat osis (l ocal or disse mi nate d) t hat mi g ht i nterfere wit h t he 
res ults of t he st u d y.
1 5.   Hist or y of diseases a g gra vate d or tri g gere d b y ultra vi olet ra diati o n.
1 6.   A s u bject c urre ntl y usi n g a n y me dicati o n, w hic h i n t he o pi ni o n of t he i n vesti gat or, 
ma y affect t he e val uati o n of t he i n vesti gati o nal pr o d uct, or place t he s u bject at u n d ue 
ris k (e. g. a n y p h ot ose nsitisi n g me dicati o n s uc h as tetrac ycli ne, t hiazi des, 
fl u or o q ui n ol o nes, etc.) wit hi n o ne m o nt h pri or t o i ncl usi o n.
1 7.  A s u bject w h o has use d a n y of t he f oll o wi n g t o pical or s yste mic me dicati o ns u p t o 
t w o wee ks bef ore t he scree ni n g visit: i m m u n o-s u p pressa nts, a nti hista mi nes, n o n-
ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI D S), a n d partic ular as piri n ( > 2 0 0 m g/ d), 
wit hi n t w o wee ks pri or t o i ncl usi o n a n d/ or c ortic oster oi ds.
1 8.  A s u bject w h o has use d oral or t o pical treat me nt wit h vita mi n A aci d a n d/ or its 
deri vati ves u p t o 1 m o nt h bef ore t he scree ni n g visit.
1 9.  A s u bject w h o has bee n vacci nate d u p t o 1 m o nt h bef ore t he scree ni n g visit or is 
i nte n di n g t o recei ve a vacci nati o n d uri n g t heir partici pati o n i n t he st u d y.
2 0.  C urre ntl y recei vi n g aller g y i njecti o ns or recei ve d a n aller g y i njecti o n wit hi n 7 da ys 
pri or t o Visit 1 or e x pects t o be gi n i njecti o ns d uri n g st u d y partici pati o n.
2 1.  A s u bject wit h a n y s ki n mar ks o n t he bac k t hat mi g ht i nterfere wit h t he e val uati o n of 
p ossi ble s ki n reacti o ns (e. g. pi g me ntati o n dis or ders, vasc ular malf or mati o ns, scars, 
tatt o os, e xcessi ve hair, n u mer o us frec kles, o pe n s ores, pi m ples, or c ysts).
2 2.  A s u bject t hat i nte n ds bat hi n g (i n t he sea or a p o ol), usi n g a sa u na, or parta ki n g i n 
water s p orts, or acti vities t hat lea d t o i nte nse s weati n g f or t he d urati o n of t he st u d y.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 2 9  of 6 8
2 3. A s u bject w h o has use d a tra nsc uta ne o us electrical ner ve sti m ulati o n ( T E N S) mac hi ne 
1 da y bef ore t he scree ni n g visit or i nte n ds t o use a T E N S mac hi ne at a n y p oi nt 
d uri n g t he st u d y.
2 4.  Hist or y of se nsitisati o n i n a pre vi o us patc h st u d y.
2 5.  Hist or y of a b n or mal reacti o n t o s u n e x p os ure.
2 6.  I nte nse s u nli g ht e x p os ure or s u n ta n ni n g sessi o ns u p t o 3 0 da ys bef ore t he Scree ni n g 
e val uati o n.
2 7.  Rece nt hist or y ( wit hi n t he last 5 years) of alc o h ol or ot her s u bsta nce a b use.
2 8.  A s u bject w h o has pre vi o usl y bee n e nr olle d i n t his st u d y. 
5. 4  
R a n d o mi s ati o n Crit eri a
S u bjects will be ra n d o mise d i nt o t he st u d y pr o vi de d t he y ha ve satisfie d all s u bject selecti o n 
criteria.
Please n ote t hat s u bjects will be ra n d o mise d t wice i n t his st u d y.  Ra n d o misati o n f or i n d ucti o n 
p hase will occ ur o n M o n da y Visit 4, da y 1 a n d ra n d o misati o n f or c halle n ge p hase will occ ur 
o n M o n da y Visit 1 9, da y 3 6.) 
T w o se mi- occl usi ve patc hes wit h 6 cells la belle d A- F will be use d. F o ur cells ( A- D) will be 
use d i n t his st u d y ( 1 f or eac h test pr o d uct a n d 1 f or t he sali ne s ol uti o n). T w o cells ( E- F) will 
re mai n e m pt y. 
Fi g ure 5- 1 E x a m ple of t he se mi- occl usi ve a d hesi ve p atc h s yste m (s h o w n a d hesi ve si de 
d o w n)
T he se q ue nce of eac h of t he test pr o d ucts t o t he cells wit hi n t he patc h s yste m f or eac h s u bject 
will be ra n d o ml y assi g ne d per t he ra n d o misati o n se q ue nces pr o vi de d. T he se q ue nce of t he 
pr o d ucts t o t he cells f or eac h s u bject will re mai n t he sa me t hr o u g h o ut t he i n d ucti o n p hase, a n d 
a differe nt se q ue nce per t he ra n d o misati o n pr o vi de d will be pr o vi de d f or eac h s u bject f or t he 
c halle n ge p hase. F or m ore details o n t he ra n d o misati o n, please refer t o secti o ns 8. 4. 1 I n d ucti o n 
P hase Ra n d o misati o n a n d 8. 1 0. 1 C halle n ge P hase Ra n d o misati o n.
5. 5 
Lif e st yl e C o n si d er ati o n s
D uri n g t he e ntire st u d y ( Scree ni n g – Last S u bject Last Visit ( L S L V)) t he f oll o wi n g s h o ul d be 
a v oi de d:

A p pl yi n g a n y ot her pr o d uct t o t he test site ( d ors u m).
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 0  of 6 8

Use of c os metics, m oist urisers, a n d ot her t o pical pr o d ucts o n t he bac k area.

C ha n gi n g a n y c os metic ha bits, i ncl u di n g pers o nal h y gie ne.

C ha n gi n g dietar y ha bits e. g. i ntr o d ucti o n of ne w pr o d ucts d uri n g t he st u d y i ncl u di n g 
b ut n ot li mite d t o s oa p, la u n dr y deter ge nt, or fa bric s ofte ner.

Getti n g t he patc h test site wet: d uri n g s h o wers, bat hi n g, s wi m mi n g, h ot t u bs, sa u nas 
a n d stea m r o o ms. T he st u d y site will pr o vi de i nstr ucti o ns o n h o w t o s h o wer or bat he 
t hr o u g h o ut t he st u d y.

Re m o vi n g t he patc hes.

Weari n g ti g ht or restricti ve cl ot hi n g t hat ca n re m o ve t he patc h t hr o u g h fricti o n or 
ca use re d ness.

I nte nti o nal e x p os ure t o artificial ultra vi olet ( U V) li g ht or c os metic pr oce d ures 
(i ncl u des ta n ni n g be ds, I nte nse P ulse d Li g ht, etc.) are pr o hi bite d o n t he test areas f or 
t he d urati o n of t he st u d y.

Use of a T E N S mac hi ne 

Missi n g t he first da y of a p plicati o n d uri n g t he i n d ucti o n p hase or t he da y of 
a p plicati o n d uri n g t he c halle n ge p hase.

Missi n g t w o or m ore c o nsec uti ve visits or m ore t ha n 2 alter nati ve visits.
5. 5. 1 
Pr e g n a n c y
F or G S K C H st u dies i n w hic h n o dr u g is utilise d a pre g na nc y test will n ot be re q uire d. S u bjects 
will nee d t o pr o vi de ver bal c o nfir mati o n of ne gati ve pre g na nc y stat us.
5. 6 
S cr e e n F ail ur e s
Scree 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 are 
n ot s u bse q ue ntl y ra n d o mise d. T o e ns ure tra ns pare nt re p orti n g of scree n fail ure s u bjects, a 
mi ni mal set of scree n fail ure i nf or mati o n will i ncl u de de m o gra p h y, scree n fail ure details (e. g. 
wit h dra wal of c o nse nt), eli gi bilit y criteria, a n d a n y a d verse e ve nts or i nci de nts as a p plica ble. 
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) ma y n ot 
be re-scree ne d.
5. 7 
S p o n s or’ s Q u alifi e d M e di c al P er s o n n el
C o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y q ualifie d me dical pers o n nel f or t he st u d y is 
d oc u me nte d i n t he  St u d y C o ntact List l ocate d i n t he i n vesti gat or st u d y master file hel d at t he 
st u d y site.
T he c o ntact n u m ber is o nl y t o be use d b y i n vesti gati o nal staff see ki n g a d vice o n me dical 
q uesti o ns or pr o ble ms i n t he e ve nt t hat t he esta blis he d c o m m u nicati o n pat h wa ys bet wee n t he 
i n vesti gati o nal site a n d t he st u d y tea m are n ot a vaila ble.  
T he c o ntact n u m ber is n ot i nte n de d f or direct use b y st u d y s u bjects.  T o facilitate access t o 
a p pr o priatel y q ualifie d me dical pers o n nel o n st u d y-relate d me dical q uesti o ns or pr o ble ms, 
s u bjects will be pr o vi de d wit h a c o ntact car d.  T he c o ntact car d will pr o vi de, as a mi ni m u m, 
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 1  of 6 8
pr ot oc ol i de ntifiers, t he s u bject’s st u d y i de ntificati o n n u m ber, c o ntact i nf or mati o n f or t he 
i n vesti gati o nal site, a n d c o ntact details i n t he e ve nt t hat t he i n vesti gati o nal site ca n n ot be 
reac he d t o pr o vi de a d vice o n a me dical q uesti o n or pr o ble m i de ntifie d b y a healt hcare 
pr ofessi o nal ot her t ha n t he i n vesti gat or.  
5. 8 
Tr ai n e d E v al u at or a n d D er m at ol o gi st Q u alifi c ati o n s 
T he patc h test site assess me nt will be c o n d ucte d i n a 2-ste p pr ocess:
Ste p 1 : A trai ne d, bli n de d e val uat or will sc ore t he test sites f or si g ns of irritati o n  per I C D R G 
scale (A p pe n di x 2 ) at all ti me p oi nts s pecifie d i n t he st u d y sc he d ule. T he trai ne d e val uat or sc ore 
will be c o nsi dere d fi nal. T he trai ne d e val uat or d oes n ot nee d t o be me dicall y q ualifie d. All 
practical eff orts will be ma de t o e ns ure t he sa me trai ne d e val uat or will be use d t o e val uate all 
s u bjects i n t he st u d y.  T he e val uat or(s) will be trai ne d b y a der mat ol o gist i n t he I C D R G scale, 
t his will be d oc u me nte d i n t he site master file.
Ste p 2:  F or eac h s u bject w h o prese nts a p ositi ve reacti o n (i.e. a reacti o n sc ore of ‘ +’ or greater) 
i n t he c halle n ge p hase a bli n de d der mat ol o gist will f urt her classif y t he reacti o n as p ote ntial 
se nsitisati o n ( or n ot) at t he fi nal visit a n d pr o vi de a si n gle narrati ve descri pti o n t o s u m marise 
t he e ntiret y of t he s u bject’s e x perie nce of t he e ve nt. As se nsitisati o n a n d irritati o n ca n occ ur i n 
t he c halle n ge p hase, it is p ossi ble t o rec or d a p ositi ve reacti o n i n t he c halle n ge p hase w hic h is 
n ot a se nsitisati o n reacti o n. T he der mat ol o gist m ust c o nsi der h o w t he reacti o n prese nts/e v ol ves 
o ver ti me, t o ascertai n w het her it is c haracteristic of a se nsitisati o n reacti o n. T he der mat ol o gist 
will rec or d t heir o pi ni o n i n t he narrati ve a n d wit h a c hec k- b o x i n t he C R F.
T he narrati ve m ust i ncl u de t he start a n d fi nis h date of t he e ve nt, a descri pti o n of h o w t he e ve nt 
e v ol ves o ver ti me, a n y acti o n ta ke n (e. g. m o ve d patc h), a n d dia g n osis ( p ote ntial se nsitisati o n 
reacti o n, or ot her as a p pr o priate). If a clear dia g n osis ca n n ot be ma de, t he n t he der mat ol o gist 
s h o ul d i ncl u de t his i n t he narrati ve.  
A der mat ol o gist will assess t he o verall s u bject eli gi bilit y at t he Scree ni n g Visit a n d c o nti n ue d 
eli gi bilit y i n t he st u d y at Visit 2 (if n ot c o m bi ne d) t o e ns ure t he s u bject is free of a n y pre-
e xisti n g der mat ol o gical pat h ol o g y. T his will c o nfir m if s u bjects w o ul d re q uire a n y f oll o w u p 
assess me nts.  A d diti o nall y, a fi nal assess me nt at Visit 2 3 ( Last Visit) b y a q ualifie d 
der mat ol o gist will c o nfir m if it is me dicall y a p pr o priate t o e xit t he s u bject fr o m t he st u d y at t he 
fi nal visit  (E d war d a n d N or ma n, 1 9 8 2 ). 
6 
I N V E S TI G A TI O N A L/ S T U D Y P R O D U C T S
F or t he p ur p oses of t his st u d y, per I nter nati o nal C o nfere nce o n Har m o nizati o n (I C H) g ui deli nes, 
a n d G S K p olic y, i n vesti gati o nal pr o d uct is defi ne d as a p har mace utical f or m of a n acti ve 
i n gre die nt, a n o n- me dici nal pr o d uct ( mar kete d or i n vesti gati o nal), or a place b o, bei n g teste d or 
use d as a refere nce ( p ositi ve or ne gati ve c o ntr ol), i n a cli nical trial. T his i ncl u des a pr o d uct wit h 
a mar keti n g a ut h orisati o n w he n use d or asse m ble d (f or m ulate d or pac ka ge d) i n a wa y differe nt 
fr o m t he a p pr o ve d f or m, or w he n use d f or a n u na p pr o ve d i n dicati o n, or w he n use d t o gai n 
f urt her i nf or mati o n a b o ut a n a p pr o ve d use. 
6. 1 
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s
T he f oll o wi n g st u d y pr o d ucts will be s u p plie d b y t he Cli nical S u p plies De part me nt, G S K C H:
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 2  of 6 8
T a bl e 6- 1 
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s
Ot her ite ms t o be s u p plie d b y t he cli nical i n vesti gati o nal site:

Se mi- occl usi ve patc h s yste m ( D ura p ore ® ta pe 3 MT M  a n d pa per filter)

Sali ne s ol uti o n (f or clea nsi n g t he patc he d sites as nee de d, f oll o wi n g patc h re m o val)

C ott o n pa ds/ w o ol (f or clea nsi n g t he patc he d sites as nee de d, f oll o wi n g patc h re m o val)
S u p plies pr o vi de d b y t he cli nical i n vesti gati o nal site m ust als o be st ore d i n c o m plia nce wit h t he 
la bel re q uire me nts i n a sec ure place wit h li mite d or c o ntr olle d access.
Detaile d i nstr ucti o ns f or t he ret ur n of st u d y pr o d uct/st u d y s u p plies f or t he acc o u nta bilit y c hec ks 
a n d s u bse q ue nt destr ucti o n w hic h will be pr o vi de d b y G S K C H d uri n g t he c o urse of t he st u d y 
i n ti me f or st u d y cl ose o ut visit.
6. 1. 1  
D o s a g e F or m a n d P a c k a gi n g
T he t hree de vel o p me ntal f or m ulati o ns will be s u p plie d t o t he cli nical site as la belle d pac ka ge d 
b ottles or t u bes f or dis pe nsi n g a n d a p plicati o n b y t he site staff. T he sali ne s ol uti o n will be 
s u p plie d i n its c o m mercial pac ka gi n g f or dis pe nsi n g a n d a p plicati o n b y t he site staff. A d diti o nal 
sali ne s ol uti o n f or clea nsi n g of t he test site areas as nee de d will be pr o vi de d b y t he 
i n vesti gati o nal site. 
T he c o nte nt of t he pr o d uct la bels will be i n acc or da nce wit h all a p plica ble re g ulat or y 
re q uire me nts a n d will be t he res p o nsi bilit y of t he G S K C H Gl o bal Cli nical S u p plies gr o u p.
Eac h st u d y la bel will c o ntai n, b ut n ot be li mite d t o, pr ot oc ol n u m ber, directi o ns f or use a n d 
st ora ge re q uire me nts.
T e st Pr o d u ct 1
T e st Pr o d u ct 2
T e st Pr o d u ct 3
R ef er e n c e pr o d u ct 
( N e g ati v e C o ntr ol)
Pr o d uct N a me
D e v el o p m e nt al 
S er u m
D e v el o p m e nt al 
L oti o n
D e v el o p m e nt al 
Cr e a m
S ali n e S ol uti o n: S o di u m 
C hl ori d e ( N a Cl; 0. 9 %)
P ac k Desi g n
4 0 m L P u m p 
P a c k
5 0 m L T u b e
5 0 m L T u b e
5 0 0 m L
Pr o d uct 
M a n uf act uri n g 
C o de ( M F C)
N/ A – C o m m er ci al 
Pr o d u ct
A p pli c ati o n 
q u a ntit y
D o s e: 0. 0 2 m L/ c m 2  
E a c h pr o d u ct will b e di s p e n s e d i nt o a n i n di vi d u al c ell wit hi n t h e p at c h s y st e m 
a c c or di n g t o t h e r a n d o mi s ati o n s e q u e n c e f or t h e i n d u cti o n p h a s e a n d t h e c h all e n g e 
p h a s e a n d r e m o v e d/r e a p pli e d a s p er st u d y s c h e d ul e. 
R o ut e of 
a d mi ni str ati o n
T o pi c al d er m al a p pli c ati o n vi a s e mi- o c cl u si v e p at c h t o t h e d or s u m.
A p pli c ati o n 
I n str u cti o n
A p pli e d o n- sit e b y t e c h ni ci a n
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C CI
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 3  of 6 8
Care s h o ul d be ta ke n wit h t he s u p plie d pr o d ucts a n d t heir la bels s o t hat t he y are mai ntai ne d i n 
g o o d c o n diti o n. It is i m p orta nt t hat all la bels re mai n i ntact a n d le gi ble f or t he d urati o n of t he 
st u d y. S u bjects s h o ul d be i nstr ucte d t o n ot re m o ve or deface a n y part of t he st u d y la bel.
All pr o d ucts s u p plie d are f or use o nl y i n t his cli nical st u d y a n d s h o ul d n ot be use d f or a n y ot her 
p ur p ose.
6. 1. 2 
Pr e p ar ati o n a n d Di s p e n si n g 
T he test pr o d ucts; t hree de vel o p me ntal f or m ulati o ns a n d t he sali ne s ol uti o n will be dis pe nse d 
b y q ualifie d u n bli n de d site pers o n nel acc or di n g t o t he ra n d o misati o n se q ue nce i nt o t he cells of 
t he patc h s yste m f or t he i n d ucti o n p hase a n d t he c halle n ge p hase a n d a p plicati o n sc he d ules.
S u bjects will be assi g ne d t o t he se q ue nce of pr o d ucts wit hi n t he patc h i n acc or da nce wit h t he 
ra n d o misati o n sc he d ule ge nerate d b y a n a p pr o ve d G S K C H ve n d or, pri or t o t he start of t he 
i n d ucti o n p hase a n d a differe nt se q ue nce f or t he c halle n ge p hase, usi n g vali date d s oft ware. See 
secti o n 8. 4. 1 Ra n d o misati o n criteria  a n d 8. 1 0. 1 Ra n d o misati o n .
St u d y pr o d ucts will be a p plie d t o t he cells of t he patc h b y q ualifie d u n bli n de d site pers o n nel. 
T he patc h will t he n be a p plie d t o d ors u m of eac h s u bject as per t he st u d y sc he d ule. T hese staff 
me m bers will n ot be i n v ol ve d i n a n y safet y assess me nts or ot her as pects of t he st u d y t hat c o ul d 
be i nfl ue nce d b y t he k n o wle d ge of pr o d uct/se q ue nce a s u bject has bee n assi g ne d t o. 
A n a d diti o nal bli n de d me m ber of site staff s h o ul d e ns ure t he dis pe nsi n g pr oce d ures are 
c o m plete d acc uratel y per t he ra n d o misati o n se q ue nce f or eac h s u bject f or eac h a p plicati o n da y 
of t he i n d ucti o n p hase a n d t he c halle n ge as per st u d y sc he d ule a n d t he ra n d o misati o n se q ue nces 
pr o vi de d.
I n t his st u d y eac h of t he st u d y pr o d ucts will be dis pe nse d at a d ose of 0. 0 2 m L/c m2 i nt o 
i n di vi d ual cells of a se mi- occl usi ve patc h s yste m a n d a p plie d t o t he desi g nate d area o n t he bac k 
usi n g s uita ble meas uri n g a p parat us (f or e. g. a pi pette).
6. 2  
A d mi ni str ati o n
I n d ucti o n P h ase:
O n Visit 4/ Da y 1 of t he i n d ucti o n p hase, t he test site f or t he a p plicati o n of t he patc h will be 
desi g nate d a b o ve t he waist bet wee n t he sca p ula a n d waistli ne a n d a wa y fr o m t he s pi nal mi d-
li ne. Test sites will n ot o verla p wit h t he site pre vi o usl y use d f or t he pr o visi o nal 
M E D u 
assess me nt.  Baseli ne gra di n g/assess me nt of t he a p plicati o n test site will t he n be perf or me d. 
T he site of eac h of t he pr o d ucts t o t he i n di vi d ual cells of t he patc h will t he n be ra n d o ml y 
assi g ne d, per t he s u p plie d ra n d o misati o n sc he d ule. T his se q ue nce will be differe nt wit hi n t he 
i n d ucti o n a n d c halle n ge p hase. 
T w o se mi- occl usi ve patc hes wit h 6 cells la belle d A- F will be use d. F o ur cells ( A- D) will be 
use d i n t his st u d y ( 1 f or eac h test pr o d uct a n d 1 f or t he sali ne s ol uti o n). T w o cells ( E- F) will 
re mai n e m pt y. 
A c o ntr olle d a m o u nt ( 0. 0 2 m L/c m 2) of eac h st u d y pr o d uct will be dis pe nse d i nt o t he a p pr o priate 
se parate cell, 3 cells f or eac h of t he test pr o d ucts a n d 1 cell f or t he sali ne s ol uti o n.  T he 
assi g n me nt of t he st u d y pr o d ucts t o t he cells wit hi n t he patc h s yste m wit hi n eac h s u bject will 
be ra n d o ml y assi g ne d per t he ra n d o misati o n sc he d ule pr o vi de d. T he se q ue nce of t he pr o d ucts 
t o t he cells f or eac h s u bject will re mai n t he sa me f or t he i n d ucti o n p hase, a n d a differe nt 
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 4  of 6 8
se q ue nce per t he ra n d o misati o n pr o vi de d will be ge nerate d f or eac h s u bject f or t he c halle n ge 
p hase.
T here will be si x patc h a p plicati o ns t o d u plicate sites o n t he d ors u m o ver t hree c o nsec uti ve 
wee ks i n t he i n d ucti o n p hase, wit h patc hes bei n g a p plie d o n M o n da y a n d We d nes da y. D uri n g 
t he c halle n ge p hase, a p plicati o n will be ma de t o d u plicate naï ve sites o nce o n a M o n da y. 
Eac h patc h will re mai n i n place f or 2 4 ( ± 4) h o urs. T he patc h will c o ntai n eac h of t he test 
pr o d ucts a n d t he sali ne s ol uti o n wit hi n i n di vi d ual cells of t he patc h s yste m. T he patc h will t he n 
be re m o ve d, a n d t he area ma y be ge ntl y wi pe d wit h sali ne s ol uti o n. S u bjects will be i nstr ucte d 
t o rest f or 1 5- 3 0 mi n utes i n sta n dar d r o o m c o n diti o ns ( 1 8- 2 6° C) a v oi di n g c o ntact of t he bac k 
area wit h a n y ot her s urface.  After 3 0 mi n utes ( ma xi m u m of 1 h o ur), t he test sites will be 
e val uate d as per t he scale i n A p pe n di x 2 .
Rest P h ase :
After t he fi nal i n d ucti o n patc h re m o val a n d e val uati o n, s u bjects will e nter a mi ni m u m 2- wee k 
rest p hase. D uri n g t his ti me t here will be n o pr o d uct or patc h a p plicati o ns. S u bjects will be 
re mi n de d t o c o nti n ue t o f oll o w t he Lifest yle C o nsi derati o ns  t hr o u g h o ut t he rest p hase. 
C h alle n ge P h ase :
T w o naï ve (i.e. pre vi o usl y u ntreate d/ patc he d) area of s ki n o n t he bac k, bet wee n t he s h o ul der 
li ne a n d waist a n d a wa y fr o m t he s pi nal mi d-li ne, will be selecte d f or t he c halle n ge patc h. T his 
area will be e val uate d b y t he bli n de d e val uat or pri or t o a n y patc h a p plicati o n t o pr o vi de a 
baseli ne f or i nter pretati o n. A ne w patc h, wit h eac h of t he cells fille d wit h a c o ntr olle d a m o u nt 
( 0. 0 2 m L/c m2) of t he all ocate d st u d y pr o d ucts as per t he ra n d o misati o n se q ue nce f or t he 
s u bject’s c halle n ge p hase, will t he n be a p plie d. 
T he a p plicati o n pr ocess will f oll o w t he sa me pr ocess as t he i n d ucti o n p hase.
6. 2. 1  
D o si n g Err or s
D osi n g err ors ma y res ult i n t his st u d y fr o m t he a d mi nistrati o n of: 

t he wr o n g pr o d uct a p plicati o n se q ue nce bef ore a n d after patc h re m o val

at t he wr o n g ti me, 

or at t he wr o n g d osa ge. 

i nc orrect irra diati o n a p plicati o n.
S uc h d osi n g err ors occ urri n g t o a st u d y s u bject are t o be ca pt ure d i n t he C R F.  I n t he e ve nt of 
d osi n g err or, t he s p o ns or s h o ul d be n otifie d i m me di atel y a n d u n der n o circ u mst a nce s h o ul d 
t his e xcee d 2 4 h o urs.
D osi n g err ors are re p orta ble irres pecti ve of t he prese nce of a n ass ociate d A E, i ncl u di n g:

D osi n g err ors i n v ol vi n g s u bject e x p os ure t o a n y of t he st u d y pr o d ucts;

P ote ntial d osi n g err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o or d o 
n ot i n v ol ve t he partici pati n g s u bject.
If a d osi n g err or is acc o m pa nie d b y a n A E, as deter mi ne d b y t he i n vesti gat or, t he d osi n g err or 
a n d, a n y ass ociate d a d verse e ve nt(s) are t o be ca pt ure d i n t he C R F A E f or m. 
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 5  of 6 8
6. 2. 2  
O v er d o s e
A n o ver d ose is a deli berate or i na d verte nt a d mi nistrati o n of a pr o d uct at a n a m o u nt hi g her t ha n 
s pecifie d i n t he pr ot oc ol.
O ver d ose is n ot li kel y t o occ ur i n t his st u d y.  
Li mite d q ua ntities of t he st u d y pr o d ucts will be s u p plie d, dis pe nse d b y site staff a n d cl osel y 
m o nit ore d b y t he site f or eac h s u bject.
O ver d ose per se is n ot a n A E. H o we ver, a n y cli nical se q uelae of a n o ver d ose s h o ul d be re p orte d 
as a n A E (a n d seri o us a d verse e ve nt ( S A E), if a p pr o priate). F or re p orti n g, f oll o w t he A E a n d 
S A E re p orti n g i nstr ucti o ns.
6. 3 
I n v e sti g ati o n al/ St u d y Pr o d u ct St or a g e  
T he i n vesti gat or, or desi g nee, will e ns ure t hat all st u d y pr o d ucts are st ore d i n a sec ure d area 
wit h c o ntr olle d access u n der re q uire d st ora ge c o n diti o ns a n d i n acc or da nce wit h a p plica ble 
re g ulat or y re q uire me nts a n d t he pr o d uct la bel a n d t he Cli nical st u d y s u p plies c hec klist.  
Site s yste ms m ust be ca pa ble of meas uri n g a n d d oc u me nti n g (f or e xa m ple, via a l o g), at a 
mi ni m u m, dail y mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns (as 
a p plica ble, i ncl u di n g fr oze n, refri gerate d, a n d/ or r o o m-te m perat ure pr o d ucts).  T his s h o ul d be 
ca pt ure d fr o m t he ti me of first pr o d uct recei pt t hr o u g h o ut t he st u d y.  E ve n f or c o nti n u o us 
m o nit ori n g s yste ms, a l o g or site pr oce d ure t hat e ns ures acti ve dail y e val uati o n f or e xc ursi o ns 
s h o ul d be a vaila ble.  T he o perati o n of t he te m perat ure- m o nit ori n g de vice a n d st ora ge u nit (f or 
e xa m ple, refri gerat or), as a p plica ble, s h o ul d be re g ularl y i ns pecte d t o e ns ure it is mai ntai ne d i n 
w or ki n g or der. 
A n y e xc ursi o ns fr o m t he pr o d uct-la bel st ora ge c o n diti o ns s h o ul d be re p orte d t o a p pr o priate site 
staff u p o n disc o ver y a n d c o m m u nicate d t o s p o ns or as s o o n as p ossi ble as per t he i nf or mati o n 
pr o vi de d i n t he Cli nical st u d y s u p plies c hec klist.  T he site s h o ul d acti vel y p urs ue o pti o ns f or 
ret ur ni n g t he pr o d uct t o t he st ora ge c o n diti o ns as descri be d i n t he la beli n g, as s o o n as p ossi ble.  
E xc ursi o ns fr o m t he st ora ge re q uire me nts, i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d as 
a pr ot oc ol de viati o n a n d re p orte d t o t he S p o ns or.  
O nce a n e xc ursi o n is i de ntifie d, t he affecte d pr o d uct ( or pr o d ucts) m ust be q uara nti ne d a n d n ot 
use d u ntil t he s p o ns or pr o vi des d oc u me ntati o n of per missi o n t o use. Use of a n y of t he affecte d 
pr o d uct(s) pri or t o s p o ns or a p pr o val will be c o nsi dere d a pr ot oc ol de viati o n.  
6. 4 
I n v e sti g ati o n al/ St u d y Pr o d u ct A c c o u nt a bilit y
All pr o d ucts s u p plie d are f or use o nl y i n t his cli nical st u d y a n d s h o ul d n ot be use d f or a n y ot her 
p ur p ose. 
All st u d y pr o d ucts m ust be recei ve d b y a desi g nate d pers o n at t he st u d y sites, ha n dle d a n d st ore d 
safel y a n d pr o perl y, a n d ke pt i n a sec ure d l ocati o n t o w hic h o nl y t he staff ha ve access. U p o n 
recei pt, all st u d y pr o d ucts s h o ul d be st ore d acc or di n g t o t he i nstr ucti o ns s pecifie d o n t he pr o d uct 
la bels. St u d y pr o d ucts are t o be dis pe nse d o nl y t o s u bjects e nr olle d i n t he st u d y i n acc or da nce 
wit h t he pr ot oc ol, b y a ut h orise d site staff.
T he i n vesti gati ve site m ust mai ntai n a de q uate rec or ds d oc u me nti n g t he recei pt, use, l oss, or 
ot her dis p ositi o n of all t he pr o d uct s u p plies. All st u d y pr o d ucts will be acc o u nte d f or usi n g t he 
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 6  of 6 8
i n vesti gati o nal/st u d y pr o d uct acc o u nta bilit y f or m/rec or d. T he i n vesti gat or is res p o nsi ble f or 
st u d y pr o d uct acc o u nta bilit y, rec o nciliati o n, a n d rec or d mai nte na nce. 
T he acc o u nta bilit y rec or ds m ust be a vaila ble f or i ns pecti o n b y t he st u d y m o nit or d uri n g t he 
st u d y. M o nit ori n g of pr o d uct acc o u nta bilit y will be perf or me d b y t he m o nit or d uri n g site visits 
a n d at t he c o m pleti o n of t he st u d y. 
6. 4. 1  
D e str u cti o n of I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
At t he c o ncl usi o n of t he st u d y, t he Pri nci pal I n vesti gat or or a n a p pr o priate desi g nee, a n d a 
re prese ntati ve of G S K C H (st u d y m o nit or) will i n ve nt or y all use d a n d u n use d st u d y pr o d ucts 
a n d s u n dr y ite ms.  T he i n vesti gati o nal/st u d y pr o d uct acc o u nta bilit y rec or d f or ret ur ne d st u d y 
pr o d ucts will t he n be c o m plete d. All st u d y pr o d uct ( use d a n d u n use d) f or t his cli nical st u d y 
(i ncl u di n g e m pt y c o ntai ners), will be ret ur ne d f or destr ucti o n t o t he G S K C H Cli nical S u p plies 
De part me nt or desi g nate d ve n d or usi n g t he ret ur n i nstr ucti o ns pr o vi de d. 
6. 5  
Bli n di n g a n d All o c ati o n/ R a n d o mi s ati o n
All s u bjects will be ce ntrall y ra n d o mise d usi n g a n I nteracti ve Res p o nse Tec h n ol o g y (I R T). 
Bef ore t he st u d y is i nitiate d, trai ni n g, l o gi n i nf or mati o n a n d directi o ns f or t he I R T will be 
pr o vi de d t o t he site staff. 
St u d y pr o d ucts will be dis pe nse d t o t he cells of t he patc h acc or di n g t o t he i nstr ucti o ns recei ve d 
(se q ue nce) t hr o u g h t he I R T at t he a p pr o priate st u d y visits f or t he i n d ucti o n p hase a n d t he 
c halle n ge p hase.
Please n ote t hat s u bjects will be ra n d o mise d t wice i n t his st u d y.  Ra n d o misati o n f or i n d ucti o n 
p hase will occ ur o n M o n da y Visit 4, da y 1 a n d ra n d o misati o n f or c halle n ge p hase will occ ur 
o n M o n da y Visit 1 9, da y 3 6.) F or m ore details o n t he ra n d o misati o n, please refer t o secti o ns 
8. 4. 1. Ra n d o misati o n criteria  a n d 8. 1 0. 1. Ra n d o misati o n.  
T he i n vesti gat or’s k n o wle d ge of t he pr o d uct all ocati o n s h o ul d n ot i nfl ue nce t he decisi o n t o 
e nr oll a partic ular s u bject or affect t he or der i n w hic h s u bjects are e nr olle d.
T his st u d y is descri be d as e xa mi ner- bli n d (t he cli nical e val uat or a n d der mat ol o gist will be 
bli n de d t o t he pr o d uct a n d irra diati o ns recei ve d). T he st u d y statisticia n, data ma na ge me nt staff, 
ot her e m pl o yees of t he S p o ns or a n d ve n d ors acti n g o n be half of t he s p o ns or, w h o ma y i nfl ue nce 
st u d y o utc o mes will als o be bli n de d t o t he pr o d uct all ocati o n a n d irra diati o ns recei ve d. 
Dis pe nsi n g staff will n ot be i n v ol ve d i n a n y assess me nt pr oce d ures d uri n g t his st u d y
T o e ns ure t he trai ne d e val uat or a n d der mat ol o gists re mai ns bli n de d t hr o u g h o ut t he st u d y, staff 
i n v ol ve d i n t he pre parati o n a n d dis pe nsi n g of st u d y pr o d ucts will w or k i n a se parate area. T he 
trai ne d e val uat or or Der mat ol o gist is n ot per mitte d i n a n y area w here st u d y pr o d uct is st ore d, 
dis pe nse d, or i n use. 
Dis pe nsi n g staff will n ot be i n v ol ve d i n a n y assess me nt pr oce d ures d uri n g t his st u d y.
6. 6  
Br e a ki n g t h e Bli n d
At t he i nitiati o n of t he st u d y, t he st u d y site will be i nstr ucte d o n t he met h o d f or brea ki n g t he 
bli n d.  T he met h o d will be a n electr o nic pr ocess.
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 7  of 6 8
T he electr o nic s yste m will be pr o gra m me d wit h bli n d- brea ki n g i nstr ucti o ns. I n case of a n 
e mer ge nc y, t he i n vesti gat or has t he s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g of a 
s u bject’s pr o d uct assi g n me nt is warra nte d. S u bject safet y m ust al wa ys be t he first c o nsi derati o n 
i n ma ki n g s uc h a deter mi nati o n. If t he i n vesti gat or deci des t hat u n bli n di n g is warra nte d, t he 
i n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact t he s p o ns or pri or t o u n bli n di n g a s u bject’s 
pr o d uct assi g n me nt u nless t his c o ul d dela y e mer ge nc y treat me nt of t he s u bject.
If a s u bject’s pr o d uct assi g n me nt is u n bli n de d, t he s p o ns or m ust be n otifie d wit hi n 2 4 h o urs 
after brea ki n g t he bli n d. T he date a n d reas o n t hat t he bli n d was br o ke n m ust be rec or de d i n t he 
s o urce d oc u me ntati o n a n d case re p ort f or m, as a p plica ble.
A n y A E ass ociate d wit h brea ki n g t he bli n d m ust be rec or de d a n d re p orte d as s pecifie d i n t his 
pr ot oc ol. T he st u d y site ma y als o be re q uire d be re q uire d t o i nf or m t he I R B/ E C if t he bli n d is 
br o ke n.
6. 7  
C o m pli a n c e
St u d y pr o d ucts will be a d mi nistere d u n der t he s u per visi o n of i n vesti gat or site pers o n nel at t he 
cli nical site. 
6. 8  
C o n c o mit a nt M e di c ati o n/ Tr e at m e nt( s)
A n y me dicati o ns, treat me nts or vacci ne (i ncl u di n g o ver-t he-c o u nter or prescri pti o n me dici nes, 
vita mi ns, a n d/ or her bal s u p ple me nts) ta ke n d uri n g t he st u d y, after si g ni n g t he i nf or me d c o nse nt, 
m ust be rec or de d i n t he C R F wit h i n dicati o n, reas o n f or use, u nit d ose, dail y d ose, a n d start a n d 
st o p dates of a d mi nistrati o n.  
All s u bjects 
will be q uesti o ne d a b o ut c o nc o mita nt 
me dicati o n/treat me nts at eac h site visit.
Me dicati o n/treat me nts ta ke n wit hi n 3 0 da ys of first a p plicati o n of pr o d uct will be d oc u me nte d 
as a pri or me dicati o n/treat me nt.  Me dicati o ns/treat me nts ta ke n after first a p plicati o n of pr o d uct 
will be d oc u me nte d as c o nc o mita nt me dicati o n/treat me nts.
S u bjects will a bstai n fr o m all c o nc o mita nt treat me nts, e xce pt f or c o ntrace pti ves a n d t h ose use d 
f or t he treat me nt of a d verse e ve nts.
7  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
S U B J E C T DI S C O N TI N U A TI O N/ WI T H D R A W A L
7. 1 
S u bj e ct Di s c o nti n u ati o n/ Wit h dr a w al 
A s u bject ma y wit h dra w fr o m t he st u d y at a n y ti me at his or her o w n re q uest or ma y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or or s p o ns or f or safet y, be ha vi oral 
reas o ns, or t he i na bilit y of t he s u bject t o c o m pl y wit h t he pr ot oc ol-re q uire d sc he d ule of st u d y 
visits or pr oce d ures.  
T he f oll o wi n g circ u msta nces re q uire disc o nti n uati o n of st u d y pr o d uct a n d/ or pre mat ure s u bject 
wit h dra wal:

Pr ot oc ol vi olati o n t hat ma y i m pact t he s u bject’s safet y

Wit h dra wal of i nf or me d c o nse nt
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 8  of 6 8

S u bject l ost t o f oll o w- u p 

U n bli n di n g of t he s u bject 

Pre g na nc y
If a s u bject is disc o nti n ue d or pre mat urel y wit h dra ws fr o m t he st u d y, t he reas o n(s) f or 
disc o nti n uati o n or wit h dra wal a n d t he ass ociate d date m ust be d oc u me nte d i n t he rele va nt 
secti o n(s) of t he C R F. 
7. 2 
L o st t o F oll o w u p
A s u bject will be c o nsi dere d l ost t o f oll o w u p if he or s he re peate dl y fails t o ret ur n f or sc he d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he st u d y site. 
If a s u bject fails t o ret ur n t o t he site f or a re q uire d st u d y visit t he site m ust atte m pt t o c o ntact 
t he s u bject a n d resc he d ule t he misse d visit as s o o n as p ossi ble a n d c o u nsel t he s u bject o n t he 
i m p orta nce of mai ntai ni n g t he assi g ne d visit sc he d ule a n d ascertai n w het her or n ot 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.
Bef ore a s u bject is dee me d l ost t o f oll o w u p, t he i n vesti gat or or desi g nee m ust 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 ne 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 hese 
c o ntact atte m pts s h o ul d be d oc u me nte d. If c o ntact is ma de wit h t he s u bject, t he i n vesti gat or 
s h o ul d i n q uire a b o ut t he reas o n f or wit h dra wal, re q uest t hat t he s u bject ret ur n all pr o d ucts t hat 
t he y ha d bee n dis pe nse d a n d if a p pr o priate re q uest t hat t he s u bject ret ur n f or a fi nal visit a n d 
f oll o w- u p wit h t he s u bject re gar di n g a n y u nres ol ve d a d verse e ve nts ( A Es).
Fi nal safet y assess me nts ma y be carrie d o ut w he n t he s u bject ret ur ns t o t he st u d y site, at t he 
i n vesti gat or’s discreti o n, w hic h c o ul d i ncl u de t he f oll o wi n g:
S h o ul d t he s u bject c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o ha ve wit h dra w n 
fr o m t he st u d y a n d l ost t o f oll o w u p. 
Lac k of c o m pleti o n of all or a n y of t he earl y ter mi nati o n pr oce d ures will n ot be vie we d as 
pr ot oc ol de viati o ns s o l o n g as t he s u bject’s safet y was preser ve d.
If t he s u bject wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or discl os ure of f ut ure 
i nf or mati o n, n o f urt her e val uati o ns s h o ul d be perf or me d, a n d n o a d diti o nal data s h o ul d be 
c ollecte d.  T he s p o ns or ma y retai n a n d c o nti n ue t o use a n y data c ollecte d bef ore s uc h 
wit h dra wal of c o nse nt.
8 
S T U D Y P R O C E D U R E S
T his secti o n lists t he pr oce d ures t o be c o m plete d at eac h pla n ne d st u d y visit.  T he ti mi n g of 
eac h pr oce d ure is liste d i n t he Sc he d ule of Acti vities secti o n.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g all pr oce d ures are esse ntial a n d re q uire d 
f or st u d y c o n d uct.
8. 1 
Vi sit 1/ S cr e e ni n g
Pri or t o t he scree ni n g visit, tele p h o ne scree ni n g of i ntereste d s u bjects ma y be c o n d ucte d usi n g 
a tele p h o ne scri pt. T his will be c o n d ucte d b y t he site recr uit me nt staff or desi g nee.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 3 9  of 6 8
Scree ni n g pr oce d ures will be c o n d ucte d b y t he I n vesti gat or, or s uita bl y q ualifie d desi g nee.
T he f oll o wi n g pr oce d ures will be c o m plete d:
8. 1. 1 
I nf or m e d C o n s e nt
T he i n vesti gat or, or desi g nee, m ust o btai n i nf or me d c o nse nt fr o m eac h s u bject partici pati n g i n 
t his st u d y after a de q uate e x pla nati o n of t he ai ms, met h o ds, o bjecti ves, a n d p ote ntial hazar ds of 
t he st u d y. T w o c o pies of t he i nf or me d c o nse nt f or m (I C F) will be si g ne d a n d date d b y t he 
s u bject, t he s u bject will retai n o ne c o p y a n d t he ot her will be ke pt at site.
T he i n vesti gat or, or desi g nee, m ust als o e x plai n t o t he 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 it at a n y ti me.  A p pr o priate f or ms f or d oc u me nti n g 
a si g ne d a n d date d c o nse nt will be pr o vi de d b y eit her t he i n vesti gat or or b y G S K C H.
T he i n vesti gat or, or desi g nee, s h o ul d si g n a n d date eac h c o p y of t he I C F t o c o nfir m t hat t he 
c o nse nt pr ocess was c o m plete d c orrectl y after t he s u bject has si g ne d.  
T he ti me t he s u bject si g ne d t he i nf or me d c o nse nt f or m will als o be ca pt ure d o n t he I nf or me d 
C o nse nt F or m as t his is t he p oi nt at w hic h all A d verse E ve nts will be ca pt ure d fr o m. T he date 
a n d ti me of c o nse nt will be tra nscri be d t o t he C R F.
If, d uri n g a s u bject’s partici pati o n i n t he st u d y, a n y ne w i nf or mati o n bec o mes a vaila ble t hat 
ma y affect t he s u bject’s willi n g ness t o partici pate i n t he st u d y, eac h o n g oi n g s u bject s h o ul d 
recei ve a c o p y of t his ne w i nf or mati o n a n d be re-c o nse nte d i nt o t he st u d y. Eac h s u bject s h o ul d 
be pr o vi de d wit h a c o p y of t he si g ne d a n d date d a me n de d c o nse nt f or m. T he date of re-c o nse nt 
will be rec or de d o n t he C R F.
After si g ni n g t he I C F, s u bjects will u n der g o t he scree ni n g assess me nts t o c o nfir m t hat t he y 
meet all t he i ncl usi o n criteria a n d n o ne of t he e xcl usi o n criteria. If t he s u bject is c o nfir me d 
eli gi ble b y t he i n vesti gat or ( or desi g nee) t o partici pate i n t he st u d y t he s u bject is c o nsi dere d 
e nr olle d i n t he st u d y.
8. 1. 2  
D e m o gr a p hi c s
T he f oll o wi n g de m o gra p hic i nf or mati o n will be rec or de d i n t he C R F: year of birt h, ge n der a n d 
race. Fitz patric k s ki n t y pe assess me nt (A p pe n di x 3 - Fitz patric k S ki n T y pe Gra di n g ) will als o 
be c o n d ucte d b y a trai ne d der mat ol o gist a n d rec or de d o n t he C R F.
Race of s u bjects will be rec or de d i n acc or da nce wit h F D A G ui da nce f or I n d ustr y: C ollecti o n 
of Race a n d Et h nicit y Data i n Cli nical Trials, 2 0 0 5.
8. 1. 3  
M e di c al Hi st or y a n d Pri or M e di c ati o n/ Tr e at m e nt
Details of rele va nt me dical a n d s ur gical hist or y (i n t he last 1 year), i ncl u di n g aller gies or dr u g 
se nsiti vit y, will be d oc u me nte d i n t he C R F.
Pri or 
me dicati o ns/treat me nts, i ncl u di n g prescri pti o n a n d n o n- prescri pti o n dr u gs, dietar y 
s u p ple me nts a n d her bal re me dies, ta ke n i n t he last 3 0 da ys a n d pri or t o si g ni n g t he i nf or me d 
c o nse nt f or m, will be d oc u me nte d i n t he C R F.
8. 1. 4 
I n cl u si o n/ E x cl u si o n Crit eri a
I ncl usi o n a n d e xcl usi o n criteria i nf or mati o n will be d oc u me nte d i n t he C R F.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 0  of 6 8
8. 1. 5  
D er m at ol o gi st A s s e s s m e nt
A der mat ol o gist will assess t he s u bject t o c o nfir m t he y are free of a n y pre-e xisti n g 
der mat ol o gical pat h ol o g y at t he Scree ni n g visit. 
T his assess me nt will be re peate d at Visit 2 (if n ot c o m bi ne d wit h visit 1) t o e ns ure t he s u bject 
re mai ns free of a n y pre-e xisti n g der mat ol o gical pat h ol o g y a n d t hat t he y are t heref ore s uita ble 
t o c o nti n ue i n t he st u d y.
C o nfir mati o n of s u bject eli gi bilit y a n d c o nti n ue d eli gi bilit y will be d oc u me nte d i n t he C R F.
8. 1. 6 
I n di vi d u al T y p ol o g y A n gl e (I T A°)
A tri-sti m ul us s pectr o p h ot o meter, m o del K ô nica Mi n olta C M 2 5 0 0 D w hic h utilizes t he L *, a *, 
b * c ol o ur s pace will be use d t o meas ure t he c ol o ur of eac h s u bject’s s ki n ( d ors u m).  
T he s pectr o p h ot o meter will meas ure t hree L * a n d t hree b * c ol o ur c o or di nates of t he s ki n o n 
differe nt l ocati o ns o n t he bac k ( bet wee n t he s h o ul der li ne a n d waist, o n eit her si de of t he 
s pi nal mi d-li ne) f or eac h s u bject. T he a vera ge ( mea n) L * a n d b * val ues are t o be i n p utte d i nt o 
t he e C R F a n d t he I T A mea n will be calc ulate d a ut o maticall y i n t he C R F as per e q uati o n 1.
                
*arc ta n ge nt is e x presse d i n ra dia ns.
T he mea n I T A° a n d hist orical data will be use d t o esti mate t he M E D u f or eac h s u bject. T he 
esti mate d M E D u will be rec or de d o n t he C R F.
8. 1. 7 
S u bj e ct Eli gi bilit y
T he i n vesti gat or a n d/ or me dicall y q ualifie d desi g nee will re vie w i ncl usi o n/e xcl usi o n criteria, 
me dical hist or y, pri or me dicati o ns t o c o nfir m s u bject eli gi bilit y t o partici pate i n t he cli nical trial. 
T his will be d oc u me nte d i n t he C R F.
T o pre pare f or st u d y partici pati o n, s u bjects will be i nstr ucte d i n t he Lifest yle G ui deli nes  a n d 
a n y C o nc o mita nt Me dicati o n/ Treat me nt(s)  re q uire me nts of t he pr ot oc ol.
8. 2 
Vi sit 2
Visit 1 ca n be c o m bi ne d wit h Visit 2.
At Visit 2 a n y c urre nt a n d c o nc o mita nt t hera p y ta ke n will be re vie we d, a n d c o nti n ue d eli gi bilit y 
will be c hec ke d bef ore a n y patc h a p plicati o n. T his will be re vie we d a gai n bef ore eac h 
s u bse q ue nt visit.
A q ualifie d der mat ol o gist will c hec k f or s u bject c o nti n ue d eli gi bilit y i n t he st u d y ( At Visit 2 
o nl y if visits are n ot c o m bi ne d).
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 


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







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


1 4 1 5 9
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1 8 0
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5 0
*
 ta n ge nt
arc
I T A
b
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C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 1  of 6 8
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
8. 2. 1  
M E D Irr a di ati o n
A U V d ose is t he res ult of m ulti pl yi n g t he U V s o urce irra dia nce b y t he e pis o de d urati o n. I n t his 
st u d y, a s olar si m ulat or wit h 6 li g ht g ui des e x p osi n g all s u b-sites will be use d. Bef ore U V R 
e x p os ure of eac h test site, irra dia nce val ues will be meas ure d a n d rec or de d wit h a ra di o meter 
w hic h has bee n cali brate d wit h a s pectr ora di o metric meas ure me nt of t he s olar si m ulat or o ut p ut.
A s uita ble war m- u p ti me of at least 1 0 mi n utes will be all o we d f or t he U V R s olar si m ulat or t o 
sta bilise bef ore starti n g e x p os ures. T his is t o e ns ure a c o nsiste nt irra dia nce o ver t he w h ole 
e x p os ure peri o d. U V e x p os ures a n d M E D assess me nts will be c o n d ucte d i n sta ble c o n diti o ns, 
wit h t he s u bject l yi n g h oriz o ntall y o n t heir fr o nt ( pr o ne) a n d i n a r o o m wit h sta n dar d r o o m 
c o n diti o ns ( 1 8- 2 6° C).  
Test sites i nte n de d f or U V R e x p os ure s hall be free fr o m ble mis hes a n d ha ve a n e ve n c ol o ur 
t o ne.
T he M E D of eac h s u bject will be deter mi ne d i n a t w o-ste p pr oce d ure. Firstl y, t he i n vesti gat or 
or desi g nee will a d mi nister a series of 6 c o ntr olle d d oses of U V ra diati o n ( 2 9 0- 4 0 0 n m) t o t he 
bac k of eac h s u bject (eit her si de of t he s pi ne, bet wee n t he s h o ul der li ne a n d waist) usi n g a 
m ulti p ort s olar si m ulat or li g ht 1 5 0 or 3 0 0 W. U V irra diati o n will be c o n d ucte d b y a trai ne d 
tec h nicia n wit h t he s u bject l yi n g h oriz o ntall y o n t heir fr o nt a n d i n a r o o m wit h c o ntr olle d 
te m perat ure ( 1 8- 2 6° C).
T he t otal d ose of U V ra diati o n a d mi nistere d b y eac h p ort of t he s olar si m ulat or will 
pr o gressi vel y i ncrease b y 1. 2 5 u nits. T he preli mi nar y d ose ( M E D u) will be defi ne d b y t he mea n 
I T A° a n d t he ti me of irra diati o n f or eac h s u bject will var y t o reac h t he d ose.  
I n t his st u d y, t he 1st s u b-site will ha ve t he m ost i nte nse f or m of ra diati o n a n d t he 6t h s u b-site 
will ha ve t he least i nte nse f or m of ra diati o n. T he d ose of U V ra diati o n a d mi nistere d f or t he 
M E D assess me nt will be c h ose n s o t hat t he 3
r d of t he 6 s u b-sites will be irra diate d wit h t he 
esti mate d M E D. 
T he mi ni m u m area of eac h e x p os ure s u b-site will be 0. 5 c m 2. T he mi ni m u m dista nce bet wee n 
b or ders of eac h e x p os ure s u b-site (s p ots) will be at least 0. 8 c m.
A n y e xtra ne o us e x p os ure of t he test sites t o U V R li g ht (artificial or nat ural) will be a v oi de d 
d uri n g t his peri o d a n d f or a peri o d of 2 4 h o urs after e x p os ure. A n y a d diti o nal U V e x p os ure t o 
t he test area will i n vali date t he w h ole test f or t he s u bject c o ncer ne d.
S uccessf ul c o n d uct of t he M E D irra diati o n pr oce d ure will be rec or de d i n t he C R F.
8. 3 
Vi sit 3
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 2  of 6 8
8. 3. 1  
M E D D et er mi n ati o n
At visit 3 ( 1 6- 2 4 h o urs after U V irra diati o n), a trai ne d e val uat or will e val uate t he e x p ose d s ki n 
f or si g ns of visi ble er yt he ma. T he M E D is deter mi ne d as t he l o west d ose of U V ra diati o n 
re q uire d t o i n d uce u nif or m, u na m bi g u o us er yt he ma. T he M E D will be use d t o deter mi ne t he 
s u bse q ue nt d oses of U V ra diati o n t o be a d mi nistere d i n t he i n d ucti o n a n d c halle n ge p hases of 
t he st u d y a n d will var y fr o m s u bject t o s u bject. It ma y n ot be p ossi ble t o rea d a vali d M E D f or 
s o me s u bjects, i n w hic h case t his pr ocess s h o ul d be re peate d b y a dj usti n g t he ra n ge of U V d oses 
a d mi nistere d. 
T he M E D assess me nt will be assesse d vis uall y b y a trai ne d e val uat or wit h t he s u bject l yi n g 
h oriz o ntall y o n t heir fr o nt a n d i n a r o o m-c o ntr olle d te m perat ure ( 1 8- 2 6° C). Vis ual assess me nt 
will be perf or me d i n a r o o m wit h matte, ne utral wall c ol o urs wit h s ufficie nt a n d u nif or m 
ill u mi nati o n.
T he pr o visi o nal M E D of eac h s u bject will be rec or de d o n t he C R F wit h u nits of mJ/c m 2.
If a s u bject fails t o prese nt a vali d M E D, f urt her irra diati o n at a naï ve site ma y be re q uire d wit h 
a n a dj uste d ra n ge of U V d oses. I n or der f or a s u bject t o pr o gress t o ra n d o misati o n, t he y m ust 
prese nt a vali d M E D.
S uccessf ul c o n d uct of t he M E D deter mi nati o n pr oce d ure will be rec or de d i n t he C R F.
8. 4 
I n d u cti o n P h a s e - D a y 1 Vi sit 4 ( M o n d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
8. 4. 1 
I n d u cti o n P h a s e R a n d o mi s ati o n 
Eac h s u bject will be assi g ne d a n d i de ntifie d b y a u ni q ue Scree ni n g S u bject N u m ber se q ue ntiall y 
as t he y si g n t heir i nf or me d c o nse nt. A n y refere nce ma de t o a n i n di vi d ual s u bject wit hi n t he 
st u d y m ust be d o ne usi n g t heir u ni q ue Scree ni n g S u bject N u m ber. T his will re mai n t he sa me 
f or eac h s u bject t hr o u g h o ut t he st u d y d urati o n.
All s u bjects w h o meet t he criteria f or e ntr y i nt o t he st u d y will be ce ntrall y ra n d o mise d usi n g 
I nteracti ve Res p o nse Tec h n ol o g y (I R T). Bef ore t he st u d y is i nitiate d, trai ni n g, l o gi n 
i nf or mati o n a n d directi o ns f or t he I R T will be pr o vi de d t o t he st u d y site. St u d y pr o d ucts will 
be dis pe nse d acc or di n g t o t he i nstr ucti o n recei ve d t hr o u g h t he I R T s yste m at t he a p pr o priate 
st u d y visits.
T w o se mi- occl usi ve patc hes wit h 6 cells a p plie d o n t he s u bject d ors u m. F o ur cells ( A, B, C a n d 
D) of t he patc h will be use d i n t his st u d y ( 3 cells f or eac h of t he test pr o d ucts a n d 1 cell f or t he 
refere nce pr o d uct (sali ne s ol uti o n). T he t w o cells E a n d F will al wa ys re mai n e m pt y. See als o 
5. 4 Ra n d o misati o n Criteria  a n d 6. 1. 2 Pre parati o n a n d Dis pe nsi n g .
At Visit 4, a ra n d o misati o n n u m ber will be assi g ne d electr o nicall y i n asce n di n g n u merical or der 
t o eac h s u bject w h o is deter mi ne d t o be f ull y eli gi ble. T his ra n d o misati o n n u m ber will i ncl u de 
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 3  of 6 8
t he sites of a p plicati o ns o n t he patc h of eac h treat me nt. T he sites of a p plicati o n will be t he sa me 
f or t he t w o patc hes ( U V-irra diate d, n o n- U V-irra diate d).
T he ra n d o misati o n sc he d ule f or t he i n d ucti o n p hase will f oll o w a 4 x 4 Lati n S q uare ( Willia ms) 
desi g n. A n e xa m ple of a ra n d o misati o n sc he d ule f or t he i n d ucti o n p hase is s h o w n bel o w:
T a bl e 8- 1  
A p pli c ati o n sit e s e q u e n c e s- i n d u cti o n p h a s e
I n d ucti o n p h ase
(s a me se q ue nce t o be use d f or t he U V-irr a di ate d, n o n- U V-
irr a di ate d p atc hes)  
R a n d o mis ati o n 
N u m ber
               P atc h cell 
Cell A
Cell B 
Cell C 
Cell D
Test
Pr o d uct 1
Refere nce 
pr o d uct 
Test
Pr o d uct 2
Test
Pr o d uct 3
Test
Pr o d uct 3
Test
Pr o d uct 1
Refere nce 
pr o d uct
Test
Pr o d uct 2
Test
Pr o d uct 2
Test
Pr o d uct 3
Test
Pr o d uct 1
Refere nce 
pr o d uct
Refere nce 
pr o d uct
Test
Pr o d uct 2
Test
Pr o d uct 3
Test
Pr o d uct 1
8. 4. 2  
B a s eli n e Gr a di n g 
S u bjects will be seate d f or at least 1 5- 3 0 mi n utes t o t he e n vir o n me nt wit h sta n dar d r o o m 
c o n diti o ns ( 1 8- 2 6° C)  a v oi di n g c o ntact of t he bac k area wit h a n y ot her s urface. T he test sites f or 
t he a p plicati o n of t he patc h will be desi g nate d a b o ve t he waist bet wee n t he sca p ula a n d waistli ne 
a n d a wa y fr o m t he s pi nal mi d-li ne.  A bli n de d, trai ne d e val uat or will assess t he test sites f or 
si g ns of c uta ne o us irritati o n per gra di n g scale Ta ble 1 5- 2 ( A p pe n di x 2 ). 
8. 4. 3 
Pr o d u ct A p pli c ati o n a n d P at c h A p pli c ati o n 
T he l ocati o n of t he pr o d ucts wit hi n t he i n di vi d ual cells of t he patc h will be ra n d o ml y assi g ne d, 
per t he s u p plie d ra n d o misati o n sc he d ule.
T here will be 6 patc h a p plicati o ns t o t he sa me site o n t he d ors u m o n d u plicate patc hes, o ver 3 
c o nsec uti ve wee ks d uri n g t he i n d ucti o n p hase, wit h a patc h will be a p plie d o n M o n da ys a n d 
We d nes da y. Eac h patc h will re mai n i n place f or 2 4 ( ± 4) h o urs.  
A p pr o xi matel y 0. 0 2 m L/c m 2 of eac h of t he st u d y pr o d ucts will be a p plie d t o se gre gate d cells 
wit hi n d u plicate se mi- occl usi ve patc hes o n desi g nate d l ocati o ns o n t he bac k i n t he i n d ucti o n 
a n d c halle n ge p hase usi n g s uita ble meas uri n g a p parat us (f or e. g. a pi pette).
O nce t he pr o d uct is a p plie d t o t he patc h cells, t he patc h will be a p plie d t o t he desi g nate d naï ve 
area o n t he bac k as per t he e xa m ple s h o w n i n Fi g ure 4- 1  a d hesi ve si de d o w n.
8. 5 
I n d u cti o n P h a s e - D a y 2 Vi sit 5 ( T u e s d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o 
P P D
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0
P P D
P P D
P P D
C CI

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 4  of 6 8
res p o n d t o a n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es 
rec or de d i n t he C R F.
8. 5. 1 
P at c h R e m o v al
S u bjects will arri ve at site after 2 4 ( ± 4) h o urs of patc h a p plicati o n.  T he patc h will be re m o ve d, 
a n d t he area ma y be ge ntl y wi pe d wit h sali ne s ol uti o n.  S u bjects will be i nstr ucte d t o rest f or 
1 5- 3 0 mi n utes i n sta n dar d r o o m c o n diti o ns ( 1 8- 2 6° C) a v oi di n g c o ntact of t he bac k area wit h 
a n y ot her s urface.  
8. 5. 2  
C ut a n e o u s Irrit ati o n A s s e s s m e nt s
A n y s ki n res p o nse at a patc he d site will be cli nicall y assesse d usi n g scale rec o m me n de d b y t he 
I C D R G. 
After 3 0 mi n utes ( ma xi m u m of 1 h o ur) of patc h re m o val, t he test sites will be e val uate d as per 
t he scale i n Ta ble 1 5- 2 A p pe n di x 2 . T he trai ne d e val uat or will be bli n de d t o treat me nt a n d 
w hic h patc h has bee n U V irra diate d.  Patc h sites will be gra de d usi n g a ma g nif yi n g glass wit h 
a fl u oresce nt da yli g ht la m p. W here e ver p ossi ble t he sa me e x perie nce d trai ne d e val uat or will 
perf or m will be use d t o e val uate all s u bjects i n t he st u d y. T he trai ne d e xa mi ner is res p o nsi ble 
f or gra di n g t he reacti o ns, a n d t he trai ne d e xa mi ner’s sc ore is fi nal.
A n y c uta ne o us ( der mal) irritati o n or se nsitisati o n reacti o ns w hic h occ ur wit hi n t he patc h 
a p plicati o n area a n d ca n be c o m pletel y descri be d b y t he scale i n Ta ble 1 5- 2 A p pe n di x 2  will 
n ot be rec or de d as A Es d uri n g t he st u d y. T hese res p o nses are t y pical effects of occl u de d 
a p plicati o n of t o pical pr o d ucts. Reacti o ns t o t he patc h itself or t he a d hesi ve will als o n ot be 
rec or de d as A Es.
U ne x pecte d or u n us ual reacti o ns w hic h occ ur wit hi n t he patc h test area t hat ca n n ot be 
c o m pletel y descri be d b y t he scale i n Ta ble 1 5- 2 A p pe n di x 2  (e. g., ras h, hi ves) will be rec or de d 
as A Es.
Irritati o n assess me nts will be rec or de d i n t he C R F.
8. 5. 3 
T e st Sit e Irr a di ati o n
After assess me nt of t he test sites, a p pr o xi matel y 0. 0 2 m L/c m 2 of eac h of t he st u d y pr o d ucts will 
be rea p plie d directl y t o t he pre vi o usl y treate d d u plicate sites o n t he s ki n.  After a 1 5- 3 0 mi n ute 
dr yi n g peri o d, o ne area of s ki n treate d wit h t he st u d y pr o d ucts will be irra diate d wit h 2. 5 J/c m 2 
U V A ra diati o n wit h a Sc h ott U G 1 1 + W G 3 3 5  filter ( or e q ui vale nt) i n place, a n d t he n wit h 0. 3 
M E Ds of U V A + U V B ra diati o n (filters U G 1 1 + W G 3 2 0). T he d u plicate area treate d wit h t he 
st u d y pr o d ucts will n ot recei ve irra diati o n d uri n g t he irra diati o n pr oce d ure. 
8. 5. 4  
C ut a n e o u s Irrit ati o n A s s e s s m e nt P o st Irr a di ati o n s
Assess me nt of t he irra diate d a n d n o n-irra diate d sites b y t he bli n de d, trai ne d e val uat or will occ ur 
i m me diatel y after t he U V e x p os ure pr oce d ures are c o m plete d, a n d a n y reacti o n will be gra de d 
as per gra di n g scale Ta ble 1 5- 2 ( A p pe n di x 2 ).
A d diti o nall y, t he der mat ol o gist c o n d ucts a n e val uati o n of e ver y p ositi ve reacti o n ( defi ne d as a 
sc ore of ‘ + ’  or greater) i n t he c halle n ge p hase t o f urt her classif y it as a p ote ntial se nsitisati o n 
reacti o n ( or n ot). 
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 5  of 6 8
8. 6 
I n d u cti o n P h a s e D a y 3 Vi sit 6 ( W e d n e s d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
S u bjects will be seate d f or at least 1 5- 3 0 mi n utes t o t he e n vir o n me nt wit h sta n dar d r o o m 
c o n diti o ns ( 1 8- 2 6° C) a v oi di n g c o ntact of t he bac k area wit h a n y ot her s urface. A trai ne d 
e val uat or will assess t he test sites f or si g ns of c uta ne o us irritati o n per gra di n g scale Ta ble 1 5- 2 
( A p pe n di x 2). 
Patc hes will be re-a p plie d t o t he assi g ne d test areas. Please see secti o n 8. 4 (I n d ucti o n P hase 
Da y 1 Visit 4 M o n da y)  f or details o n patc h a p plicati o n ( please n ote ra n d o misati o n o nl y occ urs 
o n M o n da y Visit 4, Da y 1). 
8. 7 
I n d u cti o n P h a s e D a y 4 Vi sit 7 ( T h ur s d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
T he U V-e x p os ure pr oce d ures a n d patc h assess me nts will be re peate d. Please see secti o n 8. 5 
(I n d ucti o n P hase Da y 2 Visit 5 T ues da y) f or details ( please n ote ra n d o misati o n o nl y occ urs o n 
M o n da y Visit 4, Da y 1). 
8. 8 
I n d u cti o n P h a s e D a y 5 Vi sit 8 ( Fri d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
S u bjects will be seate d f or at least 1 5- 3 0 mi n utes t o t he e n vir o n me nt wit h sta n dar d r o o m 
c o n diti o ns ( 1 8- 2 6° C) a v oi di n g c o ntact of t he bac k area wit h a n y ot her s urface. A trai ne d 
e val uat or will assess t he test sites f or si g ns of c uta ne o us irritati o n per gra di n g scale Ta ble 1 5- 2 
( A p pe n di x 2). 
I n d ucti o n wee k 2 a n d wee k 3 ( M o n da y- Fri da y) will f oll o w t he sa me assess me nts as a b o ve, per 
t he visit sc he d ule. Please n ote ra n d o misati o n o nl y occ urs o n M o n da y, visit 4 ( Da y 1). At 
M o n da y visits 9 a n d 1 4, t he patc he d sites will be assesse d b y a trai ne d, bli n de d e val uat or f or 
si g ns a n d s y m pt o ms of irritati o n. Please see secti o n 8. 5 (I n d ucti o n P hase Da y 2 Visit 5 T ues da y) 
f or details.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 6  of 6 8
8. 9  
R e st P h a s e 
O nce t he i n d ucti o n p hase is c o m plete, s u bjects will e nter a 2- wee k rest p hase, d uri n g w hic h 
t here will be n o pr o d uct or patc h a p plicati o ns.
8. 1 0  
C h all e n g e P h a s e D a y 3 6 Vi sit 1 9 ( M o n d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
S u bjects will be seate d f or at least 1 5- 3 0 mi n utes t o t he e n vir o n me nt of sta n dar d r o o m 
c o n diti o ns ( 1 8- 2 6° C)  a v oi di n g c o ntact of t he bac k area wit h a n y ot her s urface. A trai ne d 
e val uat or will assess t he test sites f or si g ns of c uta ne o us irritati o n per gra di n g scale Ta ble 1 5- 2 
( A p pe n di x 2). 
8. 1 0. 1  
C h all e n g e P h a s e R a n d o mi s ati o n 
At visit 1 9, a n ot her ra n d o misati o n n u m ber will be assi g ne d t o eac h s u bject t hat c o m plete d t he 
i n d ucti o n p hase usi n g t he I R T s yste m. T his ra n d o misati o n n u m ber will be differe nt fr o m t he 
o ne pre vi o usl y assi g ne d at Visit 4 a n d will i ncl u de t he sites of a p plicati o ns of eac h treat me nt 
f or t he c halle n ge p hase. T he test sites of st u d y pr o d ucts a p plicati o n will be pre vi o usl y u ntreate d 
( nai ve) s ki n sites i n t he bac k, bet wee n s h o ul der bla de a n d waistli ne f or t he d u plicate U V-
irra diate d a n d n o n- U V-irra diate d patc h s yste ms.
Ra n d o misati o n sc he d ule f or t he c halle n ge p hase will f oll o w a 4 x 4 Lati n S q uare ( Willia ms) 
desi g n. A n e xa m ple of t he ra n d o misati o n sc he d ule is s h o w n bel o w:
T a bl e 8- 2  
A p pli c ati o n sit e s e q u e n c e s- c h all e n g e p h a s e 
C h alle n ge p h ase
(s a me se q ue nce t o be use d f or t he U V-irr a di ate d, n o n- U V-
irr a di ate d p atc hes)  
R a n d o mis ati o n
N u m ber
            P atc h cell
Cell A
Cell B 
Cell C 
Cell D
Test
Pr o d uct 2
Test
Pr o d uct 3
Test
Pr o d uct 1
Refere nce 
pr o d uct
Refere nce 
pr o d uct
Test
Pr o d uct 1
Test
Pr o d uct 3
Test
Pr o d uct 2
Test
Pr o d uct 3
Refere nce 
pr o d uct
Test
Pr o d uct 2
Test
Pr o d uct 1
Test
Pr o d uct 1
Test
Pr o d uct 2
Refere nce 
pr o d uct
Test
Pr o d uct 3
Please refer t o secti o n 8. 4 (I n d ucti o n P hase Da y 1 Visit 4 M o n da y)  f or assess me nts o n t his da y.
P P D
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0
P P D
P P D
P P D
C CI

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 7  of 6 8
8. 1 1  
C h all e n g e P h a s e D a y 3 7 Vi sit 2 0 ( T u e s d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
Please refer t o secti o n 8. 5 (I n d ucti o n P hase Da y 2 Visit 5 T ues da y)  a n d t he visit sc he d ule f or 
pr oce d ures a n d assess me nts t o be c o n d ucte d o n t his da y.
8. 1 2  
C h all e n g e P h a s e D a y 3 7 t o 4 0 Vi sit 2 1 t o Vi sit 2 3 ( W e d n e s d a y t o 
Fri d a y)
C ha n ges i n c o nc o mita nt me dicati o n or n o n- dr u g treat me nts/ pr oce d ures will be d oc u me nte d i n 
t he C R F. 
S p o nta ne o us re p orti n g of a d verse e ve nts a n d t h ose elicite d b y as ki n g s u bjects t o res p o n d t o a 
n o n-lea di n g q uesti o n s uc h as “ H o w d o y o u feel?” will be assesse d a n d a n y A Es rec or de d i n t he 
C R F.
F urt her test site assess me nts f or si g ns of irritati o n will be c o n d ucte d 2 4 ( ± 4), 4 8 ( ± 4), a n d 7 2 
( ± 4) h o urs after U V e x p os ure as per gra di n g scale Ta ble 1 5- 2 ( A p pe n di x 2 ).
8. 1 3 
Fi n al Vi sit D a y 4 0 Vi sit 2 3
After all assess me nts f or t he c halle n ge p hase ha ve bee n c o m plete d, a fi nal cli nical assess me nt 
b y a q ualifie d der mat ol o gist will be perf or me d t o e ns ure t hat it is me dicall y a p pr o priate t o e xit 
eac h s u bject fr o m t he st u d y. After all st u d y assess me nts are c o m plete d, s u bjects will be 
disc har ge d fr o m t he st u d y site. 
I n a d diti o n, f or eac h s u bject w h o prese nts a p ositi ve reacti o n (i.e. a reacti o n sc ore of ‘ +’ or 
greater) i n t he c halle n ge p hase a bli n de d der mat ol o gist will f urt her classif y t he reacti o n as 
p ote ntial se nsitisati o n ( or n ot) at t he fi nal visit a n d pr o vi de a si n gle narrati ve descri pti o n t o 
s u m marise t he e ntiret y of t he s u bject’s e x perie nce of t he e ve nt. As se nsitisati o n a n d irritati o n 
ca n occ ur i n t he c halle n ge p hase, it is p ossi ble t o rec or d a p ositi ve reacti o n i n t he c halle n ge 
p hase w hic h is n ot a se nsitisati o n reacti o n. T he der mat ol o gist m ust c o nsi der h o w t he reacti o n 
prese nts/e v ol ves o ver ti me, t o ascertai n w het her it is c haracteristic of a se nsitisati o n reacti o n. 
T he der mat ol o gist will rec or d t heir o pi ni o n i n t he narrati ve a n d wit h a c hec k- b o x i n t he C R F.
T he narrati ve m ust i ncl u de t he start a n d fi nis h date of t he e ve nt, a descri pti o n of h o w t he e ve nt 
e v ol ves o ver ti me, a n y acti o n ta ke n (e. g. m o ve d patc h), a n d dia g n osis ( p ote ntial se nsitisati o n 
reacti o n, or ot her as a p pr o priate). If a clear dia g n osis ca n n ot be ma de, t he n t he der mat ol o gist 
s h o ul d i ncl u de t his i n t he narrati ve.  
8. 1 4 
St u d y C o n cl u si o n
T he St u d y C o ncl usi o n pa ge of t he C R F will be c o m plete d f or all s u bjects w het her t he y 
c o m plete d all st u d y pr oce d ures or if t he y were disc o nti n ue d fr o m t he st u d y earl y.  If t he s u bject 
disc o nti n ue d earl y, at a n y p oi nt d uri n g t he st u d y, t he pri mar y reas o n f or wit h dra wal s h o ul d be 
rec or de d o n t he St u d y C o ncl usi o n pa ge.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 8  of 6 8
If a s u bject has a n y cli nicall y si g nifica nt, st u d y-relate d a b n or malities or A Es at t he c o ncl usi o n 
of t he st u d y, t he G S K C H me dical m o nit or ( or desi g nate d re prese ntati ve) s h o ul d be n otifie d 
a n d, t he s u bject ma y be as ke d t o re mai n at t he cli nical site or be as ke d t o ret ur n f or a f oll o w- u p 
visit t o e ns ure a n y iss ue is res ol ve d or dee me d n ot cli nicall y si g nifica nt. 
8. 1 5 
F oll o w- u p Vi sit
T he st u d y site ma y c o ntact a s u bject t o f oll o w u p a n A E p ost-st u d y c o m pleti o n/ wit h dra wal a n d, 
i n s o me circ u msta nces, re q uest t he y ret ur n t o t he site f or a d diti o nal f oll o w- u p visits (fi nal safet y 
assess me nts). If nee de d, a d diti o nal e xa mi nati o ns ma y be carrie d o ut at s uc h visits.
9 
S T U D Y A S S E S S M E N T S
E ver y eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol-re q uire d tests a n d pr oce d ures are c o m plete d 
as descri be d.  H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y be circ u msta nces, 
o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma y ma ke it u nfeasi ble t o c o m plete a n assess me nt.  
I n t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y t o e ns ure t he safet y a n d well- bei n g 
of t he s u bject.  W he n a pr ot oc ol-re q uire d assess me nt ca n n ot be perf or me d, t he i n vesti gat or ( or 
desi g nee) will d oc u me nt t he reas o n f or t he misse d assess me nt as a pr ot oc ol de viati o n a n d a n y 
c orrecti ve a n d pre ve ntati ve acti o ns t hat he or s he has ta ke n t o e ns ure t hat re q uire d pr ocesses 
are a d here d t o as s o o n as p ossi ble.  T he S p o ns or m ust be i nf or me d of a n y misse d assess me nts 
i n a ti mel y ma n ner.
9. 1 
S cr e e ni n g A s s e s s m e nt s
Scree ni n g assess me nts will be perf or me d b y a p pr o priatel y trai ne d staff/cli nical e xa mi ners at 
t he ti mes, a n d i n t he or der, defi ne d i n t he St u d y Pr oce d ures  secti o n of t his pr ot oc ol.
9. 2 
S af et y a n d Ot h er A s s e s s m e nt s
T he f oll o wi n g safet y assess me nts will be perf or me d b y a p pr o priatel y trai ne d staff/cli nical 
e xa mi ners, at t he ti mes a n d i n t he or der defi ne d i n t he St u d y Pr oce d ures  secti o n of t his pr ot oc ol.  
9. 2. 1 
P at c h A s s e s s m e nt s
Patc h testi n g tec h ni q ues a n d sc ori n g reacti o ns b y a gra di n g scale were first sta n dar dise d i n t he 
1 9 3 0s. T he I nter nati o nal C o ntact Der matitis Researc h Gr o u p (I C D R G) p u blis he d t he f oll o wi n g 
n o nli near, descri pti ve gra di n g scale i n 1 9 7 0’s ( Fre gert, 1 9 7 4 ) w hic h c o nti n ues t o be wi del y 
use d a n d will be a d o pte d f or t his cli nical st u d y, Ta ble 1 5- 2 ( A p pe n di x 2) . T heref ore, a n y s ki n 
res p o nse at a patc he d site will be cli nicall y assesse d usi n g scale rec o m me n de d b y t he I C D R G, 
Ta ble 1 5- 2 ( A p pe n di x 2 ). 
Patc h test site assess me nt will be c o n d ucte d i n a 2-ste p pr ocess:
Ste p 1: A trai ne d, bli n de d e val uat or will sc ore t he test sites f or si g ns of reacti o n per I C D R G 
scale (A p pe n di x 2 ) at all ti me p oi nts s pecifie d i n t he st u d y sc he d ule. T he trai ne d e val uat or sc ore 
will be c o nsi dere d fi nal. T he trai ne d e val uat or d oes n ot nee d t o be me dicall y q ualifie d.
Ste p 2: F or eac h s u bject w h o prese nts a p ositi ve reacti o n (i.e. a reacti o n sc ore of ‘ +’ or greater) 
i n t he c halle n ge p hase a bli n de d der mat ol o gist will f urt her classif y t he reacti o n as p ote ntial 
se nsitisati o n ( or n ot) at t he fi nal visit a n d pr o vi de a si n gle narrati ve descri pti o n t o s u m marise 
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 4 9  of 6 8
t he e ntiret y of t he s u bject’s e x perie nce of t he e ve nt. As se nsitisati o n a n d irritati o n ca n occ ur i n 
t he c halle n ge p hase, it is p ossi ble t o rec or d a p ositi ve reacti o n i n t he c halle n ge p hase w hic h is 
n ot a se nsitisati o n reacti o n. T he der mat ol o gist m ust c o nsi der h o w t he reacti o n prese nts/e v ol ves 
o ver ti me, t o ascertai n w het her it is c haracteristic of a se nsitisati o n reacti o n. T he der mat ol o gist 
will rec or d t heir o pi ni o n i n t he narrati ve a n d wit h a c hec k- b o x i n t he C R F.
T he narrati ve m ust i ncl u de t he start a n d fi nis h date of t he e ve nt, a descri pti o n of h o w t he e ve nt 
e v ol ves o ver ti me, a n y acti o n ta ke n (e. g. m o ve d patc h), a n d dia g n osis ( p ote ntial se nsitisati o n 
reacti o n, or ot her as a p pr o priate). If a clear dia g n osis ca n n ot be ma de, t he n t he der mat ol o gist 
s h o ul d i ncl u de t his i n t he narrati ve.  
Please see secti o n 4. 2 Rati o nale f or St u d y Desi g n  f or details o n patc h assess me nt.
If a s u bject de vel o ps a sc ore of ‘ Str o n g’ ( + +) or greater at a n y p oi nt d uri n g t he i n d ucti o n p hase, 
t he ne xt patc h will be a p plie d t o a n a djace nt naï ve (i.e. pre vi o usl y u ntreate d) site. If a sc ore of 
‘ Str o n g’ ( + +) or greater occ urs at t he naï ve site, n o f urt her patc h a p plicati o ns will be ma de. 
S uc h reacti ve s u bjects will, h o we ver, pr o gress t o t he c halle n ge p hase u nless, i n t he o pi ni o n of 
t he I n vesti gat or, it w o ul d be u n wise t o d o s o.
A n y c uta ne o us ( der mal) irritati o n or se nsitisati o n reacti o ns w hic h occ ur wit hi n t he patc h 
a p plicati o n area a n d ca n be c o m pletel y descri be d b y t he scale i n A p pe n di x 2  will n ot be 
rec or de d as A Es d uri n g t he st u d y. T hese res p o nses are t y pical effects of occl u de d a p plicati o n 
of t o pical pr o d ucts. Reacti o ns t o t he patc h itself or t he a d hesi ve will als o n ot be rec or de d as 
A Es.
U ne x pecte d or u n us ual reacti o ns w hic h occ ur wit hi n t he patc h test area t hat ca n n ot be 
c o m pletel y descri be d b y t he scale i n A p pe n di x 2  (e. g., ras h, hi ves) will be rec or de d as A Es.
1 0  
A D V E R S E E V E N T A N D S E RI O U S A D V E R S E E V E N T S
1 0. 1  
D efi niti o n of a n A d v er s e E v e nt ( A E)
A n A E is a n y u nt o war d me dical occ urre nce 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 a st u d y pr o d uct i ncl u di n g a n y was h o ut or lea d-i n pr o d uct ( or me dical de vice), 
w het her or n ot c o nsi dere d relate d t o t he st u d y pr o d uct, i ncl u di n g a n y was h o ut or lea d-i n pr o d uct 
( or me dical de vice).
N O T E: A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), 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 a st u d y pr o d uct i ncl u di n g a n y was h o ut or lea d-i n pr o d uct ( or me dical de vice).
E ve nts Meeti n g t he A E Defi niti o n:  

A n y a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or uri nal ysis) or 
ot her safet y assess me nts (e. g. E C G, ra di ol o gical sca ns, vital si g n meas ure me nts), 
i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y si g nifica nt i n t he 
me dical a n d scie ntific j u d g me nt of t he i n vesti gat or (i.e., n ot relate d t o pr o gressi o n of 
u n derl yi n g disease).

E xacer bati o n of a c hr o nic or i nter mitte nt pre-e xisti n g c o n diti o n i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 0  of 6 8

Ne w c o n diti o ns detecte d or dia g n ose d after st u d y pr o d uct a d mi nistrati o n e ve n t h o u g h 
it ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g- dr u g i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y 
pr o d uct or a c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p orte d as a n 
A E/ S A E u nless it is a n i nte nti o nal o ver d ose ta ke n wit h p ossi ble s uici dal/self- har mi n g 
i nte nt. S uc h o ver d oses s h o ul d be re p orte d re gar dless of se q uelae.
E ve nts N O T meeti n g t he A E defi niti o n: 

A n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs (if a p plica ble) or ot her a b n or mal 
safet y assess me nts w hic h are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y 
t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he s u bject’s c o n diti o n. 

T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of t he 
disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he s u bject’s 
c o n diti o n. 

Me dical or s ur gical pr oce d ure (e. g. e n d osc o p y, a p pe n dect o m y) is n ot t he A E. T he 
c o n diti o n t hat lea ds t o t he pr oce d ure is a n A E (e. g. a p pe n dicitis).

Sit uati o ns w here a n u nt o war d 
me dical occ urre nce di d n ot occ ur (s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).

A ntici pate d da y-t o- da y fl uct uati o ns of pre-e xisti n g disease(s) or c o n diti o n(s) prese nt or 
detecte d at t he start of t he st u d y t hat d o n ot w orse n. 

A n y c uta ne o us ( der mal) irritati o n or se nsitisati o n reacti o ns w hic h occ ur wit hi n t he patc h 
a p plicati o n area a n d ca n be c o m pletel y descri be d b y t he scale i n A p pe n di x 2  will n ot be 
rec or de d as A Es. Reacti o ns t o t he patc h or a d hesi ve ta pe will als o n ot be rec or de d as 
A Es. 
1 0. 2  
D efi niti o n of a S eri o u s A d v er s e E v e nt ( S A E)
A Seri o us A d verse E ve nt ( S A E) is a partic ular cate g or y of a n a d verse e ve nt w here t he a d verse 
o utc o me is seri o us. If a n e ve nt is n ot a n A E per defi niti o n a b o ve, t he n it ca n n ot be a n S A E e ve n 
if seri o us c o n diti o ns are met (e. g. h os pitalisati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y, 
deat h d ue t o pr o gressi o n of disease).
A seri o us a d verse e ve nt is a n y u nt o war d me dical occ urre nce at a n y d ose t hat:

Res ults i n de at h

Is life-t hre ate ni n g 

T he ter m 'life-t hreate ni n g' i n t he defi niti o n of 'seri o us' refers t o a n e ve nt i n w hic h 
t he s u bject was at ris k of deat h at t he ti me of t he e ve nt. It d oes n ot refer t o a n 
e ve nt, w hic h h y p ot heticall y mi g ht ha ve ca use d deat h, if it were m ore se vere;

Re q uires i n p atie nt h os pit alis ati o n or pr ol o n g ati o n of e xisti n g h os pit alis ati o n  

I n ge neral, h os pitalisati o n si g nifies t hat t he s u bject has bee n detai ne d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or 
o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he 
p h ysicia n’s office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g 
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Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 1  of 6 8
h os pitalisati o n are A Es. If a c o m plicati o n pr ol o n gs h os pitalisati o n or f ulfills a n y 
ot her seri o us criteria, t he e ve nt is seri o us. W he n i n d o u bt as t o w het her 
“ h os pitalisati o n” occ urre d, or was necessar y, t he A E s h o ul d be c o nsi dere d 
seri o us.

H os pitalisati o n f or electi ve treat me nt of a pre-e xisti n g c o n diti o n t hat di d n ot 
w orse n fr o m baseli ne is n ot c o nsi dere d a n A E.

Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y

T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct 
n or mal life f u ncti o ns.

T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, 
i nfl ue nsa, a n d acci de ntal tra u ma (e. g. s prai ne d a n kle) w hic h ma y i nterfere wit h or 
pre ve nt e ver y da y life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n

Res ults i n c o n ge nit al a n o m al y/ birt h defect

Ot her sit u ati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g w het her S A E 
re p orti n g is a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical e ve nts t hat 
ma y n ot be i m me diatel y life-t hreate ni n g or res ult i n deat h or h os pitalisati o n b ut 
ma y je o par dise t he s u bject or 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 ot her o utc o mes liste d i n t he a b o ve defi niti o n. T hese e ve nts 
s h o ul d us uall y be c o nsi dere d seri o us.

E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d 
d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalisati o n, or de vel o p me nt of 
dr u g de pe n de nc y or dr u g a b use.
N ote:  Classificati o n of a n A E as ‘seri o us’ is base d o n t he o utc o me of t he e ve nt a n d is a fact or 
i n deter mi ni n g re p orti n g re q uire me nts.
1 0. 3  
R e p orti n g of A d v er s e E v e nt s
1 0. 3. 1  
R e p orti n g P eri o d 
All A Es, a n d t heref ore all S A Es will be c ollecte d i m me diatel y after a s u bject pr o vi des c o nse nt 
t o partici pate i n t he st u d y b y t he c o m pleti o n (si g nat ure) of t he I C F a n d u ntil 5 da ys f oll o wi n g 
last a d mi nistrati o n of t he st u d y pr o d uct ( or last pr oce d ure). 
Me dical occ urre nces t hat be ga n bef ore o btai ni n g i nf or me d c o nse nt will be rec or de d i n t he 
Me dical Hist or y/ C urre nt Me dical C o n diti o ns secti o n of t he C R F n ot t he A E secti o n.
Details rec or de d b y t he s u bject o n a diar y or si milar d oc u me nt t hat meet t he defi niti o n of a n A E 
m ust als o be disc usse d wit h t he s u bjects a n d tra nscri be d i n t he A E secti o n of t he C R F. 
1 0. 4  
R e p orti n g Pr o c e d ur e s
T he i n vesti gat or a n d a n y desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g a n d re p orti n g 
e ve nts t hat meet t he defi niti o n of a n A E a n d re mai n res p o nsi ble f or f oll o wi n g u p o n A Es t hat 
are seri o us, c o nsi dere d relate d t o t he st u d y pr o d uct(s), partici pati o n i n t he st u d y, or a st u d y 
pr oce d ure, or t hat ca use d t he s u bject t o disc o nti n ue t he st u d y pr o d uct or st u d y. 
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 2  of 6 8
T he i n vesti gat or ( or me dicall y q ualifie d desi g nee) is t o re p ort all directl y o bser ve d A Es a n d all 
A Es s p o nta ne o usl y re p orte d b y t he st u d y s u bject. I n a d diti o n, eac h st u d y s u bject will be 
q uesti o ne d a b o ut A Es. 
Eac h A E is t o be assesse d t o deter mi ne if it meets t he criteria f or a S A E.  If a n S A E occ urs, 
e x pe dite d re p orti n g will f oll o w l ocal a n d i nter nati o nal re g ulati o ns, as a p pr o priate.
W he n a n A E occ urs, it is t he res p o nsi bilit y of t he i n vesti gat or ( or me dicall y q ualifie d desi g nee) 
t o re vie w all d oc u me ntati o n (e. g. h os pital pr o gress n otes, la b orat or y, a n d dia g n ostics re p orts) 
relate d t o t he e ve nt.
T he i n vesti gat or or site staff will t he n rec or d all rele va nt i nf or mati o n re gar di n g a n A E i n t he 
C R F a n d all details relati n g t o a n S A E i n t he pa per S A E F or m pr o vi de d.
It is n ot  acce pta ble f or t he i n vesti gat or ( or me dicall y q ualifie d desi g nee) t o se n d p h ot oc o pies 
of t he s u bject’s me dical rec or ds t o G S K C H i n lie u of c o m pleti o n of t he A E C R F pa ge/ S A E 
f or m.
T here ma y be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d b y G S K 
C H.  I n t his i nsta nce, all s u bject i de ntifiers, wit h t he e xce pti o n of t he s u bject n u m ber, will be 
re dacte d o n t he c o pies of t he me dical rec or ds pri or t o s u b missi o n t o G S K C H.
T he i n vesti gat or ( or me dicall y q ualifie d desi g nee) will atte m pt t o esta blis h a dia g n osis of t he 
e ve nt base d o n si g ns, s y m pt o ms, a n d/ or ot her cli nical i nf or mati o n.  T he dia g n osis will be t he 
d oc u me nte d as t he A E/ S A E w here k n o w n a n d n ot t he i n di vi d ual si g ns/s y m pt o ms. (e. g. u p per 
res pirat or y tract i nfecti o n, seas o nal aller g y, etc. i nstea d of r u n n y n ose).
A Es elicite d b y t he i n vesti gat or ( or me dicall y q ualifie d desi g nee) i n a sta n dar d ma n ner at t he 
st u d y visits s h o ul d als o be rec or de d i n t he A E secti o n of t he C R F a n d/ or usi n g t he S A E f or m 
(s u bject t o t he classificati o n of t he A E). Care will be ta ke n n ot t o i ntr o d uce bias w he n 
q uesti o ni n g a s u bject a b o ut a n y c ha n ges i n t heir healt h. O pe n-e n de d a n d n o n-lea di n g ver bal 
q uesti o ni n g s h o ul d be use d.
1 0. 4. 1  
R e p orti n g of a n A d v er s e E v e nt
All A Es will be re p orte d o n t he A E pa ge of t he C R F b y t he i n vesti gat or or site staff.  It s h o ul d 
be n ote d t hat t he f or m f or c ollecti o n of S A E i nf or mati o n is n ot t he sa me as t he A E C R F.  W here 
t he sa me data are c ollecte d, t he A E C R F pa ge a n d t he S A E f or m m ust be c o m plete d i n a 
c o nsiste nt ma n ner.  F or e xa m ple, t he sa me A E ter m s h o ul d be use d o n b ot h.  A Es s h o ul d be 
re p orte d usi n g c o ncise me dical ter mi n ol o g y o n t he C R F as well as o n t he f or m f or c ollecti o n of 
S A E i nf or mati o n.
1 0. 4. 2  
R e p orti n g of a S eri o u s A d v er s e E v e nt
I n a d diti o n t o rec or di n g t he details of eac h A E o n t he A E C R F pa ge, a n S A E f or m s h o ul d be 
c o m plete d, as f ull y as p ossi ble. Har d c o pies of t he ‘ pa per’ S A E f or m will be pr o vi de d i n t he 
i n vesti gat or st u d y master file. Ori gi nal S A E f or ms will be retai ne d i n t he i n vesti gat or st u d y 
master file.
It is esse ntial t o e nter t he f oll o wi n g i nf or mati o n: 

Pr ot oc ol a n d s u bject i de ntifiers

S u bject de m o gra p h y
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 3  of 6 8

Descri pti o n of e ve nts, wit h dia g n osis if a vaila ble

I n vesti gat or o pi ni o n of relati o ns hi p t o st u d y pr o d uct ( or st u d y pr oce d ure, if a p pr o priate)

Criteri o n f or seri o us ness.
T he f oll o wi n g are desira ble a n d are of partic ular rele va nce f or i n vesti gat or a n d G S K C H 
assess me nt of t he S A E re p ort:

Date of o nset of A E 

Date A E st o p pe d, if rele va nt

St u d y pr o d uct start date

St u d y pr o d uct e n d date if rele va nt

Acti o n ta ke n i n relati o n t o t he st u d y pr o d uct

O utc o me if k n o w n
T he S A E f or m, c o m plete d as f ull y as p ossi ble, m ust be sca n ne d a n d e- maile d t o t he G S K C H 
Cli nical O perati o ns Safet y Re p orti n g e mail b o x wit h t he st u d y n u m ber a n d s u bject n u m ber i n 
t he s u bject li ne of t he e mail i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 
h o urs  after st u d y site pers o n nel lear n of t he e ve nt. T he i n vesti gat or will s u b mit a n y u p date d 
S A E data t o t he s p o ns or, i m me di atel y a n d u n der n o circ u mst a nce s h o ul d t his e xcee d 2 4 
h o urs of it bei n g a vaila ble. T he G S K C H St u d y Ma na ger s h o ul d als o be n otifie d of t he sit uati o n 
b y tele p h o ne or e mail.
E m ail Seri o us A d verse E ve nts t o:
T he G S K C H St u d y Ma na ger or desi g nee will be res p o nsi ble f or f or war di n g t he S A E f or m t o 
t he Case 
Ma na ge me nt 
Gr o u p, 
Gl o bal Cli nical Safet y a n d P har mac o vi gila nce 
mail b o x 
(
).
T he i nitial re p ort will be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q ueste d b y t he 
G S K C H st u d y ma na ger.
1 0. 5 
E v al u ati n g A d v er s e E v e nt s 
1 0. 5. 1  
A s s e s s m e nt of I nt e n sit y
T he i n vesti gat or or me dicall y q ualifie d desi g nee will ma ke a n assess me nt of i nte nsit y f or eac h 
A E re p orte d d uri n g t he st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories:

Mil d:  A n e ve nt t hat is easil y t olerate d b y t he s u bject, ca usi n g mi ni mal disc o mf ort a n d 
n ot i nterferi n g wit h e ver y da y acti vities.

M o derate:  A n e ve nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or mal e ver y da y 
acti vities

Se vere:  A n e ve nt t hat pre ve nts n or mal e ver y da y acti vities. 
N O T E: A n A E t hat is assesse d as se vere s h o ul d n ot be c o nf use d wit h a n S A E. Se vere is a 
cate g or y utilise d f or rati n g t he i nte nsit y of a n e ve nt; a n d b ot h n o n-seri o us A Es a n d S A Es ca n 
P P D
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0
P P D
C CI

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 4  of 6 8
be assesse d as se vere. F or e xa m ple, a hea dac he ma y be se vere (i nterferes si g nifica ntl y wit h t he 
s u bject's us ual f u ncti o n) b ut w o ul d n ot be classifie d as seri o us u nless it met o ne of t he criteria 
f or S A Es, liste d a b o ve. A n e ve nt is defi ne d as ‘seri o us’ w he n it meets at least 1 of t he pre defi ne d 
o utc o mes as descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.
1 0. 5. 2  
A s s e s s m e nt of C a u s alit y
T he ca usalit y assess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y re p orti n g 
re q uire me nts. F or eac h A E (seri o us a n d n o n-seri o us), t he i n vesti gat or ( or me dicall y q ualifie d 
desi g nee) m ust  pr o vi de a n assess me nt of ca usalit y o n t he A E C R F pa ge a n d t he S A E f or m 
(s u bject t o t he classificati o n of t he A E). T he i n vesti gat or will als o d oc u me nt i n t he me dical 
n otes t hat he/s he has re vie we d t he A E a n d assesse d ca usalit y, w here a p plica ble. 
A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a relati o ns hi p ca n n ot be r ule d o ut. 
Ge nerall y, t he facts (e vi de nce) or ar g u me nts t o s u g gest a ca usal relati o ns hi p s h o ul d be pr o vi de d.
T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p a n d will als o c o ns ult 
t he I n vesti gat or Br oc h ure (I B), Safet y State me nt a n d/ or Pr o d uct I nf or mati o n, f or mar kete d 
pr o d ucts, i n t he deter mi nati o n of his/ her assess me nt.  Alter nati ve ca uses, s uc h as u n derl yi n g 
disease(s), c o nc o mita nt t hera p y, ot her ris k fact ors, a n d t he te m p oral relati o ns hi p of t he e ve nt t o 
t he st u d y pr o d uct will be c o nsi dere d a n d i n vesti gate d.
F or eac h A E/ S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat he/s he has re vie we d 
t he A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y.
T he i n vesti gat or’s assess me nt of ca usalit y m ust be pr o vi de d f or all A Es (seri o us a n d n o n-
seri o us); t he i n vesti gat or m ust rec or d t he ca usal relati o ns hi p i n t he C R F, as a p pr o priate, a n d 
re p ort s uc h a n assess me nt i n acc or da nce wit h t he S A E re p orti n g re q uire me nts if a p plica ble.
T here ma y be sit uati o ns w he n a n S A E has occ urre d, a n d t he i n vesti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o G S K.  H o we ver, it is ver y i m p ort a nt t h at t he 
i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y f or e ver y e ve nt pri or t o t he i niti al 
tr a ns missi o n of t he S A E d at a t o G S K C H. T he i n vesti gat or ma y c ha n ge his/ her o pi ni o n of 
ca usalit y i n li g ht of f oll o w- u p i nf or mati o n a n d se n d a n S A E f oll o w- u p re p ort wit h t he u p date d 
ca usalit y assess me nt. 
1 0. 6 
F oll o w- u p of A d v er s e E v e nt s 
After t he i nitial re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y f oll o w u p wit h eac h s u bject 
a n d pr o vi de f urt her i nf or mati o n o n t he s u bject’s c o n diti o n.
All A Es (seri o us a n d n o n-seri o us) will be f oll o we d u ntil res ol uti o n, u ntil t he c o n diti o n sta bilizes, 
u ntil t he e ve nt is ot her wise e x plai ne d, or u ntil t he s u bject is l ost t o f oll o w- u p.  
T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as ma y be i n dicate d or as re q ueste d b y G S K C H t o el uci date 
as f ull y as p ossi ble t he nat ure a n d/ or ca usalit y of t he A E. T his ma y i ncl u de a d diti o nal la b orat or y 
tests or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her healt h care 
pr ofessi o nals.
Ne w or u p date d i nf or mati o n will be rec or de d o n t he A E C R F pa ge a n d o n t he S A E f or m (s u bject 
t o t he classificati o n of t he A E).
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 5  of 6 8
T he i n vesti gat or will s u b mit a n y u p date d S A E data t o G S K C H wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n.
I n vesti gat ors are n ot o bli ge d t o acti vel y see k A Es i n f or mer s u bjects.  H o we ver, if t he 
i n vesti gat or lear ns of a S A E, i ncl u di n g deat h, at a n y ti me after a s u bject has bee n disc har ge d 
fr o m t he st u d y, a n d c o nsi ders t he e ve nt reas o na bl y relate d t o t he st u d y pr o d uct or st u d y 
partici pati o n, t he i n vesti gat or will pr o m ptl y n otif y G S K C H b y e maili n g t he i nf or mati o n t o t he 
G S K C H Cli nical O perati o ns Safet y Re p orti n g e mail b o x 
. 
T he G S K C H St u d y Ma na ger or desi g nee will be res p o nsi ble f or f or war di n g t he i nf or mati o n t o 
t he Case Ma na ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d P har mac o vi gila nce gr o u p mail b o x at 
G S K (
).
T he i n vesti gat or will s u b mit a n y u p date d S A E data t o G S K C H wit hi n t he desi g nate d re p orti n g 
ti me fra mes.
1 0. 7  
Wit h dr a w al D u e t o a n A d v er s e E v e nt 
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o ot her ca uses, acc or di n g 
t o t he defi niti o n of a n A E n ote d earlier, a n d rec or de d o n t he a p pr o priate A E C R F pa ge. 
W he n a s u bject wit h dra ws beca use of a n S A E, t he S A E m ust be re p orte d i n acc or da nce wit h 
t he re p orti n g re q uire me nts defi ne d.
1 0. 7. 1 
S p o n s or’ s R e p orti n g R e q uir e m e nt s t o R e g ul at or y A ut h oriti e s a n d 
Et hi c s C o m mitt e e s
G S K C H has a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t he l ocal re g ulat or y a ut h orit y a n d 
ot her re g ulat or y a ut h orities a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n.  Pr o m pt 
n otificati o n of S A Es b y t he i n vesti gat or t o G S K C H is esse ntial s o t hat le gal o bli gati o ns a n d 
et hical res p o nsi bilities t o war ds t he safet y of s u bjects are met.
G S K C H will c o m pl y wit h c o u ntr y s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g 
t o t he re g ulat or y a ut h orit y, I R B/ E C a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x pecte d seri o us a d verse reacti o ns 
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o 
i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a S A E or ot her s pecific 
safet y i nf or mati o n e. g. s u m mar y or listi n g of S A E fr o m t he s p o ns or will re vie w a n d t he n file it 
al o n g wit h t he I n vesti gat or’s Br oc h ure i n t he i n vesti gat or st u d y master file, a n d will n otif y t he 
I R B/I E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
1 0. 8 
Pr e g n a n c y
1 0. 8. 1 
Ti m e P eri o d f or C oll e cti n g Pr e g n a n c y I nf or m ati o n
Pre g na nc y i nf or mati o n will be c ollecte d o n all pre g na ncies re p orte d w hile a fe male s u bject is 
partici pati n g i n t he st u d y fr o m t he si g ni n g of i nf or me d c o nse nt u ntil 5 da ys after last 
a d mi nistrati o n of st u d y pr o d uct.
P P D
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0
P P D
C CI

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 6  of 6 8
1 0. 8. 2  
A cti o n t o b e T a k e n if Pr e g n a n c y O c c ur s
T he i n vesti gat or will rec or d pre g na nc y i nf or mati o n o n t he a p pr o priate f or m sca n a n d e- mail it 
t o t he 
G S K 
C H 
Cli nical 
O perati o ns 
Safet y 
Re p orti n g e mail b o x 
 wit hi n 2 4 h o urs of lear ni n g of t he s u bject bec o mi n g pre g na nt. T he G S K C H 
St u d y Ma na ger or desi g nee will be res p o nsi ble f or f or war di n g t he pre g na nc y f or m t o t he Case 
Ma na ge me nt 
Gr o u p, 
Gl o bal 
Cli nical 
Safet y 
a n d 
P har mac o vi gila nce 
mail b o x 
. 
Ori gi nal pre g na nc y i nf or mati o n f or ms 
will be retai ne d i n t he 
i n vesti gat or st u d y master file. 
T he s u bject will be f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y. I nf or mati o n o n t he 
stat us of t he m ot her a n d i nfa nt / ne o nate (i ncl u di n g c o nc o mita nt me dicati o ns ta ke n b y t he 
m ot her d uri n g t he pre g na nc y) will be f or war de d b y t he i n vesti gat or t o t he G S K C H Cli nical 
O perati o ns Safet y Re p orti n g e mail b o x a n d t he G S K C H St u d y Ma na ger or desi g nee will 
f or war d t his i nf or mati o n t o t he Case 
Ma na ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d 
P har mac o vi gila nce gr o u p mail b o x at G S K 
. Ge nerall y, f oll o w- u p will 
be n o l o n ger t ha n 6 t o 8 wee ks f oll o wi n g t he esti mate d deli ver y date. A n y ter mi nati o n of t he 
pre g na nc y will be re p orte d.
W hile pre g na nc y itself is n ot c o nsi dere d t o be a n A E, a b n or mal pre g na nc y o utc o mes (e. g. 
s p o nta ne o us a b orti o n, fetal deat h, still birt h, c o n ge nital a n o malies, ect o pic pre g na nc y) are, a n d 
s h o ul d be rec or de d as a n S A E.
A n y fe male s u bject w h o bec o mes pre g na nt w hile partici pati n g will disc o nti n ue st u d y pr o d uct 
use a n d be wit h dra w n fr o m t he st u d y.
1 1  
D A T A M A N A G E M E N T
As use d i n t his pr ot oc ol, t he ter m C R F is u n derst o o d t o refer t o eit her a pa per f or m or a n 
electr o nic data rec or d or b ot h, de pe n di n g o n t he data c ollecti o n met h o d. 
F or t his st u d y, s u bject data will be e ntere d i nt o a n electr o nic C R F (e C R F), usi n g a vali date d 
s yste m. Data relati n g t o S A Es, pre g na nc y a n d i nci de nts will als o be c ollecte d o n pa per f or ms.
T he i n vesti gat or is res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y 
p h ysicall y or electr o nicall y si g ni n g t he C R F.
T he s o urce d oc u me nts (e. g. h os pital rec or ds, cli nical a n d office c harts, la b orat or y n otes, 
me m ora n da, s u bject diaries, q uesti o n naires, e val uati o n c hec klists, p har mac y dis pe nsi n g rec or ds, 
rec or de d data fr o m a ut o mate d i nstr u me nts, micr ofic hes, p h ot o gra p hic ne gati ves, micr ofil m or 
ma g netic me dia, x-ra ys, s u bject files a n d rec or ds ke pt at t he p har mac y, at t he la b orat or y a n d at 
t he me dic o-tec h nical de part me nts i n v ol ve d i n t he cli nical st u d y) w hic h c o ntai n t he s o urce of 
data rec or de d i n t he C R F s h o ul d be s pecifie d.  T he C R F ca n be use d as a s o urce d oc u me nt at 
t he discreti o n of data ma na ge me nt.
Eac h s u bject will be assi g ne d a n d i de ntifie d b y a u ni q ue Scree ni n g S u bject N u m ber. A n y 
refere nce ma de t o a n i n di vi d ual s u bject wit hi n t he st u d y m ust be d o ne usi n g t heir u ni q ue 
Scree ni n g S u bject N u m ber.
P P D
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0
P P D
P P D
C CI

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 7  of 6 8
1 1. 1  
C a s e R e p ort F or m
A C R F is a pri nte d, o ptical, or electr o nic d oc u me nt desi g ne d t o rec or d t he pr ot oc ol re q uire d 
i nf or mati o n t o be re p orte d t o t he s p o ns or o n eac h trial s u bject.
F or eac h s u bject w h o has gi ve n i nf or me d c o nse nt/asse nt t he C R F m ust be c o m plete d a n d si g ne d 
b y t he Pri nci pal I n vesti gat or ( or a ut h orise d desi g nee) t o certif y t hat t he data are c o m plete a n d 
c orrect.  T he i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce data) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he C R F.
Ma na ge me nt of cli nical data will be perf or me d i n acc or da nce wit h T hir d Part y B D M Ve n d or 
a p plica ble sta n dar ds a n d data clea ni n g pr oce d ures wit h o versi g ht b y G S K C H t o e ns ure 
i nte grit y of t he data, f or e xa m ple, t o re m o ve err ors a n d i nc o nsiste ncies i n t he data. 
T o pr otect t he pri vac y of s u bjects, n o Pers o nall y I de ntifia ble I nf or mati o n ( PII) (i ncl u di n g t he 
s u bject's na me or i nitials or f ull birt h date) is t o be rec or de d i n t he C R F or as part of t he q uer y 
te xt.
All C R F pa ges s h o ul d be c o m plete d d uri n g a s u bject assess me nt w he n t he C R F has bee n 
desi g nate d as t he s o urce.  Data t hat is s o urce d else w here s h o ul d be e ntere d i nt o t he C R F i n a n 
a gree d u p o n ti mefra me bet wee n t he I n vesti gat or a n d S p o ns or.  
G S K C H will o btai n a n d retai n all C R Fs a n d ass ociate d st u d y data as a p plica ble at t he 
c o m pleti o n of t he st u d y. 
1 1. 2  
D at a H a n dli n g
D oc u me ntati o n of all data ma na ge me nt acti vities s h o ul d all o w ste p- b y-ste p retr os pecti ve 
assess me nt of data q ualit y a n d st u d y perf or ma nce. 
A n y c ha n ges or c orrecti o ns t o data will be perf or me d i n t he Electr o nic Data Ca pt ure ( E D C) 
S yste m, a n d it will i ncl u de rati o nale f or c ha n ges. T he E D C s yste m has a n a u dit trail, w hic h will 
pr o vi de a c o m plete rec or d of t he c ha n ges a n d c orrecti o ns e n d orse d b y t he I n vesti gat or.
A d verse e ve nts will be c o de d usi n g Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) 
a n d a n y c o nc o mita nt me dicati o ns ter ms (if a p plica ble) usi n g a n i nter nal vali date d me dicati o n 
dicti o nar y, G S K Dr u g.  
1 1. 2. 1  
D at a Q u eri e s
Pr o gra m me d e dit c hec ks will be ge nerate d a ut o maticall y, as t he data are bei n g e ntere d i nt o t he 
s yste m. Re p orts a n d listi n gs o n t he C R F data will als o be r u n, i n a d diti o n t o t he q ueries alrea d y 
pr o gra m me d a n d ge nerate d b y t he s yste m, t o raise ma n ual q ueries as nee de d f or site 
clarificati o n or c orrecti o n. T he Cli nical Dicti o nar y De vel o p me nt a n d Ma na ge me nt Gr o u p will 
raise q ueries as nee de d o n safet y data t o c o de t he ter ms ( A Es a n d Dr u gs or c o nc o mita nt 
me dicati o n) a p pr o priatel y. 
T he st u d y m o nit or will perf or m o n g oi n g re vie w t he of t he C R Fs i n acc or da nce wit h t he 
m o nit ori n g pla n, t o c o nfir m t hat data e ntere d i nt o t he C R F b y a ut h orise d site pers o n nel are 
acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; t hat t he safet y a n d ri g hts of 
partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is bei n g c o n d ucte d i n acc or da nce wit h t he 
c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y a gree me nts, I C H G C P, a n d all a p plica ble 
re g ulat or y re q uire me nts.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 8  of 6 8
A n y q ueries will be ge nerate d i n t he E D C S yste m t o t he I n vesti gat or or desi g nee, e na bli n g t he 
err ors t o be a d dresse d i n parallel wit h Data Ma na ge me nt re vie w. T he st u d y m o nit or ca n als o 
r u n re p orts a n d listi n gs o n t he C R Fs, t o raise ma n ual q ueries as nee de d f or site clarificati o n or 
c orrecti o n.
1 2 
S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A A N A L Y S E S
1 2. 1 
S a m pl e Si z e D et er mi n ati o n
A p pr o xi matel y 8 0 healt h y s u bjects will be scree ne d t o ra n d o mise at least 4 0 s u bjects t o e ns ure 
at least 2 5 e val ua ble s u bjects c o m plete t he e ntire st u d y. N o f or mal p o wer calc ulati o ns ha ve 
bee n perf or me d o n t his st u d y. T his sa m ple size is sta n dar d i n cli nical testi n g practices a n d is 
c o nsiste nt wit h t he A N VI S A g ui deli nes ( A N VI S A, 2 0 1 2 ).
1 2. 2 
St ati sti c al M et h o d s a n d A n al yti c al Pl a n
A d diti o nal details of t he pr o p ose d statistical a nal ysis will be d oc u me nte d i n t he statistical 
re p orti n g a n d a nal ysis pla n ( R A P), w hic h will be writte n f oll o wi n g fi nalisati o n of t he pr ot oc ol 
a n d pri or t o st u d y u n bli n di n g/a nal ysis (as a p pr o priate).
1 2. 2. 1  
D efi niti o n of A n al y si s P o p ul ati o n s
T he Safet y p o p ulati o n i ncl u des all ra n d o mise d s u bjects w h o recei ve d at least o ne d ose of a n y 
st u d y pr o d uct. T his p o p ulati o n will be base d o n t he treat me nt se q ue nce t he s u bject recei ve d.
1 2. 2. 2 
E x cl u si o n of D at a fr o m A n al y si s 
E xcl usi o n of a n y data fr o m t he a nal yses will be deter mi ne d d uri n g a Bli n d Data Re vie w 
Meeti n g pri or t o data base l oc k. A n y reas o ns f or e xcl usi o n fr o m a n a nal ysis p o p ulati o n will be 
liste d, if a p plica ble. 
1 2. 2. 3  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s
De m o gra p hic a n d baseli ne c haracteristics s u m maries will be pr o d uce d f or t he safet y p o p ulati o n.
A ge will be s u m marise d b y t he mea n, sta n dar d de viati o n, me dia n, mi ni m u m a n d ma xi m u m 
val ues i n eac h treat me nt gr o u p. Ge n der, race, a n d Fitz patric k s ki n t y pe will be s u m marise d 
usi n g fre q ue nc y c o u nts a n d perce nta ges f or all s u bjects ( o verall). 
I n di vi d ual t y p ol o g y a n gle pre dicte d M E D a n d meas ure d M E D will be liste d f or eac h s u bject.
1 2. 2. 4 
St u d y Pr o d u ct C o m pli a n c e
Pr o d uct a p plicati o n will be d o ne at st u d y site. A n y pr ot oc ol de viati o n ass ociate d wit h treat me nt 
a p plicati o ns will be re vie we d d uri n g Bli n d Data Re vie w Meeti n g pri or t o data base l oc k.
1 2. 2. 5 
Pri or a n d C o n c o mit a nt M e di c ati o n s
Pri or me dicati o ns, c o nc o mita nt me dicati o ns a n d si g nifica nt n o n- dr u g t hera pies ta ke n d uri n g 
treat me nt will be liste d f or t he safet y p o p ulati o n.
C CI
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 5 9  of 6 8
1 2. 2. 6 
Pri m ar y A n al y si s( e s) 
T he pri mar y a nal ysis will be base d o n t he n u m ber of s u bjects wit h p ote ntial se nsitisati o n 
reacti o ns c o nsi dere d p h ot o- i nitiate d (i.e. p ote ntial p h ot o-se nsitisati o n reacti o ns) a n d will be 
base d o n t he safet y p o p ulati o n. 
T he assess me nt of p ote ntial se nsitisati o n reacti o ns i n t he c halle n ge p hase will be deter mi ne d b y 
t he bli n de d der mat ol o gist. P ote ntial se nsitisati o n reacti o ns will be f urt her classifie d as p ote ntial 
p h ot o-se nsitisati o n reacti o ns usi n g t he f oll o wi n g r ules: 
1.
P ositi ve reacti o ns w hic h occ ur at O N L Y t he U V-e x p ose d site will be c o nsi dere d p h ot o-
i nitiate d.
2.
P ositi ve reacti o ns w hic h occ ur at O N L Y t he n o n- U V-e x p ose d site will n ot be 
c o nsi dere d p h ot o-i nitiate d.
3.
P ositi ve reacti o ns w hic h occ ur at B O T H t he U V-e x p ose d a n d n o n- U V-e x p ose d sites 
will be c o nsi dere d p h ot o-i nitiate d if t he ma xi m u m sc ore at t he U V-e x p ose d site is m ore 
se vere t ha n t he ma xi m u m sc ore at t he n o n- U V-e x p ose d site. If t he ma xi m u m sc ore at 
t he U V-e x p ose d site is e q ual t o or l o wer t ha n t he n o n- U V-e x p ose d site, t he n it will n ot 
be c o nsi dere d p h ot o-i nitiate d. 
T he n u m ber a n d perce nta ge of s u bjects wit h a n y p ote ntial se nsitisati o n c o nsi dere d p h ot o-
i nitiate d reacti o ns vers us t h ose wit h o ut a n y will be prese nte d b y treat me nt gr o u p. N o f or mal 
statistical i nfere nce will be perf or me d.
All p ote ntial se nsitisati o n reacti o ns c o nsi dere d p h ot o-i nitiate d will be liste d.
1 2. 2. 7 
 S e c o n d ar y A n al y si s( e s) 
T he sec o n dar y a nal yses will be base d o n p ositi ve irritati o n reacti o ns (sc ore of ‘ +’ or greater i n 
t he U V-irra diate d a n d n o n- U V irra diate d series of patc hes) assesse d usi n g t he scale descri be d 
i n A p pe n di x 2 a n d will be c o n d ucte d o n t he Safet y p o p ulati o n.
Ev al u ati o n of t he c ut a ne o us p h ot o-irrit ati o n p ote nti al
T he classificati o n of a p ositi ve reacti o n as a p h ot o-i nitiate d reacti o n will use t he sa me criteria 
descri be d i n t he pri mar y e n d p oi nt. 
T he n u m ber a n d perce nta ge of s u bjects wit h a n y p h ot o-i nitiate d reacti o n t hat is n ot c o nsi dere d 
a p ote ntial se nsitisati o n reacti o n, vers us t h ose wit h o ut a reacti o n will be prese nte d b y treat me nt 
gr o u p. N o f or mal statistical i nfere nce will be perf or me d.
All p h ot o-i nitiate d reacti o ns t hat are n ot c o nsi dere d as p ote ntial se nsitisati o n reacti o ns, will be 
liste d.
Ev al u ati o n of t he c ut a ne o us se nsitis ati o n p ote nti al
T he classificati o n of a p ositi ve reacti o n as a p ote ntial se nsitisati o n reacti o n n ot c o nsi dere d 
p h ot o-i nitiate d will use t he sa me criteria descri be d i n t he pri mar y e n d p oi nt. 
T he n u m ber a n d perce nta ge of s u bjects wit h a n y p ote ntial se nsitisati o n n ot c o nsi dere d p h ot o-
i nitiate d vers us t h ose wit h o ut a n y will be prese nte d b y treat me nt gr o u p usi n g t he ma xi m u m 
sc ore. N o f or mal statistical i nfere nce will be perf or me d.
All p ote ntial se nsitisati o n reacti o ns t hat are n ot c o nsi dere d p h ot o-i nitiate d will be liste d.
Ev al u ati o n of t he c ut a ne o us irrit ati o n p ote nti al
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 0  of 6 8
T he classificati o n of a p ositi ve reacti o n as a n irritati o n reacti o n n ot c o nsi dere d p h ot o-i nitiate d 
will use t he sa me criteria descri be d i n t he pri mar y e n d p oi nt. 
T he n u m ber a n d perce nta ge of s u bjects wit h reacti o ns n ot c o nsi dere d p ote ntial se nsitisati o n a n d 
n ot c o nsi dere d as p h ot o-i nitiate d vers us t h ose wit h o ut a n y will be prese nte d b y treat me nt gr o u p 
usi n g t he ma xi m u m sc ore. N o f or mal statistical i nfere nce will be perf or me d.
All irritati o n reacti o ns t hat are n ot c o nsi dere d as p h ot o-i nitiate d, will be liste d.
Narrati ve descri pti o ns of all p ositi ve res p o nses (sc ores of + or greater), i n c halle n ge p hases, 
will be pr o vi de d.
1 2. 2. 8 
S af et y A n al y si s( e s)
Safet y a nal yses will be perf or me d usi n g t he safet y p o p ulati o n acc or di n g t o t he treat me nt t hat 
t he s u bject recei ve d. A d verse e ve nts ( 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). 
A Es will be re gar de d as treat me nt e mer ge nt if t he y occ ur o n or after t he first treat me nt 
a p plicati o n.
Treat me nt E mer ge nt A d verse E ve nts ( b y S yste m Or ga n Class/ Preferre d Ter m), Treat me nt 
E mer ge nt A d verse E ve nts (s ki n site relate d/ n o n-s ki n site relate d), treat me nt-relate d A Es (s ki n 
site relate d/ n o n-s ki n site relate d) will be s u m marise d o verall a n d b y treat me nt gr o u p.
Deat hs, N o n-fatal Seri o us A d verse E ve nts, Treat me nt E mer ge nt A d verse E ve nts lea di n g t o 
st u d y or dr u g disc o nti n uati o n will be liste d.
1 2. 2. 9  
H a n dli n g of Dr o p o ut s a n d Mi s si n g D at a 
Missi n g data will n ot be re place d or i m p ute d. Dr o p o uts will be i ncl u de d i n a nal yses u p t o t he 
p oi nt of disc o nti n uati o n.
1 2. 2. 1 0
I nt eri m A n al y si s 
N o i nteri m a nal ysis is pla n ne d f or t his st u d y.
1 3 
S T U D Y G O V E R N A N C E C O N SI D E R A TI O N S
1 3. 1  
Q u alit y C o ntr ol 
I n acc or da nce wit h a p plica ble re g ulati o ns i ncl u di n g G C P, a n d G S K C H pr oce d ures, G S K C H 
or desi g nee (i.e. t hir d- part y ve n d or) m o nit ors will c o ntact t he site pri or t o t he start of t he st u d y 
t o re vie w wit h t he site staff t he pr ot oc ol, st u d y re q uire me nts, a n d t heir res p o nsi bilities t o satisf y 
re g ulat or y, et hical, a n d G S K C H re q uire me nts.
W he n re vie wi n g data c ollecti o n pr oce d ures, t he disc ussi o n 
will i ncl u de i de ntificati o n, 
a gree me nt a n d d oc u me ntati o n of data ite ms f or w hic h t he C R F will ser ve as t he s o urce 
d oc u me nt.
G S K C H or desi g nee will m o nit or t he st u d y a n d site acti vit y t o verif y t hat t he:

Data are a ut he ntic, acc urate, a n d c o m plete.

Safet y a n d ri g hts of s u bjects are bei n g pr otecte d.
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 1  of 6 8

St u d y is c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her 
st u d y a gree me nts, G C P, a n d all a p plica ble re g ulat or y re q uire me nts.
T he e xte nt a n d nat ure of m o nit ori n g will be descri be d i n a writte n m o nit ori n g pla n o n file at 
G S K C H. T he i n vesti gat or ( or desi g nee) a grees t o all o w t he m o nit or direct access t o all rele va nt 
d oc u me nts a n d a grees t o c o- o perate wit h t he m o nit or t o e ns ure t hat a n y pr o ble ms detecte d i n 
t he c o urse of t hese m o nit ori n g visits are res ol ve d.
1 3. 2  
Q u alit y A s s ur a n c e
T o e ns ure c o m plia nce wit h G C P a n d all a p plica ble re g ulat or y re q uire me nts, G S K C H ma y 
c o n d uct a q ualit y ass ura nce assess me nt a n d/ or a u dit of t he site rec or ds, a n d t he re g ulat or y 
a ge ncies ma y c o n d uct a re g ulat or y i ns pecti o n at a n y ti me d uri n g or after c o m pleti o n of t he 
st u d y. 
I n t he e ve nt of a n assess me nt, a u dit or i ns pecti o n, t he i n vesti gat or (a n d i nstit uti o n) m ust a gree 
t o gra nt t he a d vis or(s), a u dit or(s) a n d i ns pect or(s) direct access t o all rele va nt d oc u me nts a n d 
t o all ocate t heir ti me a n d t he ti me of t heir staff t o disc uss t he c o n d uct of t he st u d y, a n y 
fi n di n gs/rele va nt iss ues a n d t o i m ple me nt a n y c orrecti ve a n d/ or pre ve ntati ve acti o ns t o a d dress 
a n y fi n di n gs/iss ues i de ntifie d.
T he i n vesti gat or(s) will n otif y G S K C H or its a ge nts i m me diatel y of a n y re g ulat or y i ns pecti o n 
n otificati o n i n relati o n t o t he st u d y. F urt her m ore, t he i n vesti gat or will c o o perate wit h G S K C H 
or its a ge nts t o pre pare t he st u d y site f or t he i ns pecti o n a n d will all o w G S K C H or its a ge nt, 
w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n. T he i n vesti gat or will pr o m ptl y a p pl y 
c o pies of t he i ns pecti o n fi n di n g t o G S K C H or its a ge nt. Bef ore res p o nse s u b missi o n t o t he 
re g ulat or y a ut h orit y, t he i n vesti gat or will pr o vi de G S K C H or its a ge nts wit h a n o p p ort u nit y t o 
re vie w a n d c o m me nt o n res p o nses t o a n y s uc h fi n di n gs. 
T he s p o ns or will be a vaila ble t o hel p i n vesti gat ors pre pare f or a n i ns pecti o n.
1 3. 3  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s
1 3. 3. 1 
I n stit uti o n al R e vi e w B o ar d/ Et hi c s C o m mitt e e 
It is t he res p o nsi bilit y of t he i n vesti gat or t o ha ve pr os pecti ve a p pr o val of t he st u d y pr ot oc ol, 
pr ot oc ol a me n d me nts, i nf or me d c o nse nt d oc u me nts, i n vesti gat or br oc h ure/safet y state me nt 
(i ncl u di n g a n y u p dates) a n d ot her rele va nt d oc u me nts, e. g. recr uit me nt a d vertise me nts, if 
a p plica ble, fr o m t he I R B/ E C.  All c orres p o n de nce wit h t he I R B/ E C s h o ul d be retai ne d i n t he 
i n vesti gat or file.  C o pies of I R B/ E C a p pr o vals s h o ul d be f or war de d t o G S K C H pri or t o t he 
i nitiati o n of t he st u d y, a n d als o w he n s u bse q ue nt a me n d me nts t o t he pr ot oc ol are ma de.
T he o nl y circ u msta nce i n w hic h a n a me n d me nt ma y be i nitiate d pri or t o I R B/ E C a p pr o val is 
w here t he c ha n ge is necessar y t o eli mi nate a p pare nt i m me diate hazar ds t o t he s u bjects.  I n t hat 
e ve nt, t he i n vesti gat or m ust n otif y t he I R B/ E C a n d G S K C H i n writi n g i m me diatel y after t he 
i m ple me ntati o n.
1 3. 3. 2 
Et hi c al C o n d u ct of t h e St u d y
T he st u d y will be c o n d ucte d i n acc or da nce wit h le gal a n d re g ulat or y re q uire me nts, as well as 
t he ge neral pri nci ples set f ort h i n t he I nter nati o nal Et hical G ui deli nes f or Bi o me dical Researc h 
I n v ol vi n g H u ma n S u bjects ( C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces 2 0 0 2), 
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
 | 2. 0

G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 2  of 6 8
I nter nati o nal Et hical G ui deli nes f or Healt h- Relate d Researc h I n v ol vi n g H u ma ns ( C o u ncil f or 
I nter nati o nal Or ga nizati o ns of Me dical Scie nces, 2 0 1 6), g ui deli nes f or G C P (I C H 1 9 9 6 a n d 
re visi o n 2), a n d t he Declarati o n of Helsi n ki ( W orl d Me dical Ass ociati o n 2 0 1 3). 
I n a d diti o n, t he st u d y will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol, t he I C H g ui deli ne o n 
G C P, a n d a p plica ble l ocal re g ulat or y re q uire me nts a n d la ws.
1 3. 3. 3 
S u bj e ct I nf or m ati o n a n d C o n s e nt
All parties will e ns ure pr otecti o n of s u bject pers o nal data a n d will n ot i ncl u de s u bject na mes or 
ot her i de ntifia ble data i n a n y re p orts, p u blicati o ns, or ot her discl os ures, e xce pt w here re q uire d 
b y la ws. 
W he n st u d y data are c o m pile d f or tra nsfer t o G S K C H a n d ot her a ut h orise d parties, s u bject 
na mes, a d dresses, a n d ot her i de ntifia ble data will be re place d b y n u merical c o des base d o n a 
n u m beri n g s yste m pr o vi de d b y G S K C H i n or der t o de-i de ntif y st u d y s u bjects.   
T he st u d y site will mai ntai n a c o nfi de ntial list of s u bjects w h o partici pate d i n t he st u d y, li n ki n g 
eac h s u bject’s n u merical c o de t o his or her act ual i de ntit y.  I n case of data tra nsfer, G S K C H 
will mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr otecti o n of s u bjects’ pers o nal data 
c o nsiste nt wit h a p plica ble pri vac y la ws.
T he i nf or me d c o nse nt d oc u me nts m ust be i n c o m plia nce wit h I C H G C P, l ocal re g ulat or y 
re q uire me nts, a n d le gal re q uire me nts, i ncl u di n g a p plica ble pri vac y la ws.
T he i nf or me d c o nse nt d oc u me nts use d d uri n g t he i nf or me d c o nse nt pr ocess m ust be re vie we d 
a n d a p pr o ve d b y t he s p o ns or, a p pr o ve d b y t he I R B/ E C bef ore use, a n d a vaila ble f or i ns pecti o n.
T he i n vesti gat or m ust e ns ure t hat eac h st u d y s u bject,  is f ull y i nf or me d a b o ut t he nat ure a n d 
o bjecti ves of t he st u d y a n d p ossi ble ris ks ass ociate d wit h partici pati o n. 
1 3. 3. 4 
S u bj e ct R e cr uit m e nt 
A d vertise me nts a p pr o ve d b y I R Bs/ E Cs a n d i n vesti gat or data bases ma y be use d as recr uit me nt 
pr oce d ures.   Use of et hics c o m mittee a p pr o ve d, ge neric, prescree ni n g q uesti o n naire t o assess 
basic s u bject c haracteristics t o deter mi ne ge neral eli gi bilit y f or t his st u d y is all o we d.  T his 
ge neric q uesti o n naire ma y be use d b y sites as a p h o ne scri pt a n d/ or t o re vie w i nter nal data bases 
t o i de ntif y s u bjects.  
G S K C H will ha ve a n o p p ort u nit y t o re vie w a n d a p pr o ve t he c o nte nt of a n y st u d y recr uit me nt 
materials directe d t o p ote ntial st u d y s u bjects bef ore s uc h materials are use d. 
1 3. 3. 5  
R e p orti n g of S af et y I s s u e s a n d S eri o u s Br e a c h e s of t h e Pr ot o c ol or 
I C H G C P 
Wit hi n G S K C H a seri o us breac h is defi ne d as a breac h li kel y t o affect t o a si g nifica nt de gree 
t he safet y a n d ri g hts of a s u bject or t he relia bilit y a n d r o b ust ness of t he data ge nerate d i n G S K 
C H-s p o ns ore d h u ma n s u bject researc h st u dies. 
I n t he e ve nt of a n y pr o hi biti o n or restricti o n i m p ose d (i.e., cli nical h ol d) b y a n a p plica ble 
c o m pete nt a ut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he i n vesti gati o nal 
pr o d uct, G S K C H s h o ul d be i nf or me d i m me diatel y. 
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 3  of 6 8
I n a d diti o n, t he i n vesti gat or will i nf or m G S K C H i m me diatel y of a n y ur ge nt safet y meas ures 
ta ke n b y t he i n vesti gat or t o pr otect t he st u d y s u bjects a gai nst a n y i m me diate hazar d, a n d of a n y 
seri o us breac hes of t his pr ot oc ol or of I C H G C P t hat t he i n vesti gat or bec o mes a ware of.
1 3. 4 
P o sti n g of I nf or m ati o n o n P u bli cl y A v ail a bl e Cli ni c al Tri al 
R e gi st er s
St u d y i nf or mati o n fr o m t his pr ot oc ol will be p oste d o n p u blicl y a vaila ble cli nical trial re gisters 
bef ore e nr oll me nt of s u bjects be gi ns i n acc or da nce wit h a p plica ble G S K C H pr ocesses.
G S K i nte n ds t o ma ke a n o n y mize d s u bject-le vel data fr o m t his trial a vaila ble t o e xter nal 
researc hers f or scie ntific a nal yses or t o c o n d uct f urt her researc h t hat ca n hel p a d va nce me dical 
scie nce or i m pr o ve patie nt care. T his hel ps e ns ure t he data pr o vi de d b y trial partici pa nts are 
use d t o ma xi m u m effect i n t he creati o n of k n o wle d ge a n d u n dersta n di n g
1 3. 5 
Pr o vi si o n of St u d y R e s ult s t o I n v e sti g at or s
W here re q uire d b y a p plica ble re g ulat or y re q uire me nts, a n i n vesti gat or si g nat or y will be 
i de ntifie d f or t he a p pr o val of t he cli nical st u d y re p ort.  T he i n vesti gat or will be pr o vi de d 
reas o na ble access t o statistical ta bles, fi g ures, a n d rele va nt re p orts a n d will ha ve t he o p p ort u nit y 
t o re vie w t he c o m plete st u d y res ults at a G S K C H site or ot her m ut uall y-a greea ble l ocati o n.
G S K C H will als o pr o vi de t he i n vesti gat or wit h t he f ull s u m mar y of t he st u d y res ults.  T he 
i n vesti gat or is e nc o ura ge d t o s hare t he s u m mar y res ults wit h t he st u d y s u bjects, as a p pr o priate.
T he pr oce d ures a n d ti mi n g f or p u blic discl os ure of t he res ults s u m mar y a n d f or de vel o p me nt 
of a ma n uscri pt f or p u blicati o n will be i n acc or da nce wit h G S K C H P olic y.
A ma n uscri pt will be pr o gresse d f or p u blicati o n i n t he scie ntific literat ure if t he res ults pr o vi de 
i m p orta nt scie ntific or me dical k n o wle d ge.
1 3. 6  
R e c or d s R et e nti o n
F oll o wi n g cl os ure of t he st u d y, t he i n vesti gat or m ust mai ntai n all site st u d y rec or ds (e xce pt f or 
t h ose re q uire d b y l ocal re g ulati o ns t o be mai ntai ne d else w here), i n a safe a n d sec ure l ocati o n.  
T he rec or ds (st u d y/ site master file) m ust be mai ntai ne d t o all o w eas y a n d ti mel y retrie val, w he n 
nee de d (e. g. f or a G S K C H a u dit or re g ulat or y i ns pecti o n) a n d m ust be a vaila ble f or re vie w i n 
c o nj u ncti o n wit h assess me nt of t he facilit y, s u p p orti n g s yste ms, a n d rele va nt site staff.
W here per mitte d b y l ocal la ws/re g ulati o ns or i nstit uti o nal p olic y, s o me or all of t hese rec or ds 
ca n be mai ntai ne d i n a f or mat ot her t ha n har d c o p y (e. g. micr ofic he, sca n ne d, electr o nic); 
h o we ver, ca uti o n nee ds t o be e xercise d bef ore s uc h acti o n is ta ke n. 
T he i n vesti gat or m ust e ns ure t hat all re pr o d ucti o ns are le gi ble a n d are a tr ue a n d acc urate c o p y 
of t he ori gi nal a n d meet accessi bilit y a n d retrie val sta n dar ds, i ncl u di n g re- ge nerati n g a har d 
c o p y, if re q uire d.  F urt her m ore, t he i n vesti gat or m ust e ns ure t here is a n acce pta ble bac k- u p of 
t hese re pr o d ucti o ns a n d t hat a n acce pta ble q ualit y c o ntr ol pr ocess e xists f or ma ki n g t hese 
re pr o d ucti o ns.
T he i n vesti gat or m ust ass ure t hat t he s u bject’s a n o n y mit y will be mai ntai ne d.  O n C R Fs or ot her 
d oc u me nts s u b mitte d t o G S K C H, s u bjects s h o ul d n ot be i de ntifie d b y t heir na mes or i nitials, 
b ut b y a n i de ntificati o n c o de. T he i n vesti gat or s h o ul d kee p a se parate l o g of s u bjects’ c o des, 
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 4  of 6 8
na mes a n d a d dresses.  D oc u me nts n ot f or s u b missi o n t o G S K C H, e. g. s u bjects’ writte n c o nse nt 
f or ms, s h o ul d be mai ntai ne d b y t he i n vesti gat or i n strict c o nfi de nce.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C F, pertai ni n g t o t he c o n d uct of t his st u d y m ust be 
retai ne d b y t he i n vesti gat or f or 2 5 years fr o m t he iss ue of t he fi nal Cli nical St u d y Re p ort ( C S R) 
or e q ui vale nt s u m mar y, u nless l ocal re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n ger 
rete nti o n peri o d. T he mi ni m u m rete nti o n ti me will meet t he strictest sta n dar d a p plica ble t o t hat 
site f or t he st u d y, as dictate d b y a n y i nstit uti o nal re q uire me nts or l ocal la ws or re g ulati o ns, G S K 
C H sta n dar ds/ pr oce d ures, a n d/ or i nstit uti o nal re q uire me nts.  
N o st u d y d oc u me nt s h o ul d be destr o ye d wit h o ut a pri or writte n a gree me nt bet wee n G S K C H 
a n d t he i n vesti gat or. T he i n vesti gat or m ust n otif y G S K C H of a n y c ha n ges i n t he arc hi val 
arra n ge me nts, i ncl u di n g, b ut n ot li mite d t o, arc hi val at a n off-site facilit y or tra nsfer of 
o w ners hi p of t he rec or ds i n t he e ve nt t he i n vesti gat or is n o l o n ger ass ociate d wit h t he site.
1 3. 7  
C o n diti o n s f or T er mi n ati n g t h e St u d y 
Pre mat ure ter mi nati o n of t his st u d y ma y occ ur beca use of a re g ulat or y a ut h orit y decisi o n, 
c ha n ge i n o pi ni o n of t he I R B/ E C, or st u d y pr o d uct safet y pr o ble ms, or at t he discreti o n of G S K 
C H.  I n a d diti o n, G S K C H retai ns t he ri g ht t o disc o nti n ue de vel o p me ntal s ki n care pr o d ucts at 
a n y ti me.
If a st u d y is pre mat urel y ter mi nate d, G S K C H will pr o m ptl y n otif y t he i n vesti gat or.  After 
n otificati o n, t he i n vesti gat or m ust pr o m ptl y c o ntact all partici pati n g s u bjects a n d s h o ul d ass ure 
a p pr o priate t hera p y/ f oll o w- u p f or t he s u bjects.  As directe d b y G S K C H, all st u d y materials 
m ust be c ollecte d a n d all C R Fs c o m plete d t o t he greatest e xte nt p ossi ble. W here re q uire d b y 
t he a p plica ble re g ulat or y re q uire me nts, G S K C H s h o ul d i nf or m t he re g ulat or y a ut h orit y(ies) 
a n d t he i n vesti gat or s h o ul d pr o m ptl y i nf or m t he I R B/ E C a n d pr o vi de t he I R B/ E C a detaile d 
writte n e x pla nati o n of t he ter mi nati o n or s us pe nsi o n. 
If t he I R B/ E C ter mi nates or s us pe n ds its a p pr o val/fa v ora ble o pi ni o n of a trial, t he i n vesti gat or 
s h o ul d pr o m ptl y n otif y t he G S K C H a n d pr o vi de G S K C H wit h a detaile d writte n e x pla nati o n 
of t he ter mi nati o n or s us pe nsi o n.
U p o n c o m pleti o n or pre mat ure disc o nti n uati o n of t he st u d y, t he G S K C H m o nit or will c o n d uct 
site cl os ure acti vities wit h t he i n vesti gat or or site staff, as a p pr o priate, i n acc or da nce wit h 
a p plica ble re g ulati o ns i ncl u di n g G C P, a n d G S K C H Sta n dar d O perati n g Pr oce d ures.
1 4  
R E F E R E N C E S
1.
A N VI S A, G ui deli ne f or t he Safet y E val uati o n of C os metics Pr o d ucts, 2 0 1 2
2.
A N VI S A; Res ol uti o n 7 9/ 0 0, A n ne x X XI a n d its u p dates
3.
Bas ketter, D. A., Y or k, M., Mc Fa d de n, J. P et al ( 2 0 0 4), Deter mi nati o n of s ki n irritati o n 
p ote ntial i n t he h u ma n 4- h patc h test. C o ntact Der matitis, 5 1: 1 – 4
4.
Bea ni, Jea n Cla u de P h ot ot o xicit y, ( 2 0 1 7) p h ot o irritati o n, a n d P h ot oaller g y Detecti o n a n d 
Assess me nt D OI 1 0. 1 0 0 7/ 9 7 8- 3- 3 1 9- 3 2 3 8 3- 1 _ 1 3 7,
5.
D o o ms- G o osse ns A. C os metics as ca uses of aller gic c o ntact der matitis. C utis 1 9 9 3 ; 5 2: 
3 1 6- 3 2 0.
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2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 5  of 6 8
6.
E d war d, M. Jac ks o n, a n d F M T R o billar d N or ma n. " T he c o ntr olle d use test i n a c os metic 
pr o d uct safet y s u bsta ntiati o n pr o gra m." J o ur nal of T o xic ol o g y: C uta ne o us a n d Oc ular 
T o xic ol o g y 1. 2 ( 1 9 8 2): 1 1 7- 1 3 2
7.
E ur o pea n C o m missi o n ( E C) Re g ulati o n N o 1 2 2 3/ 2 0 0 9 of t he E ur o pea n Parlia me nt a n d of 
t he C o u ncil of 3 0 N o ve m ber 2 0 0 9 o n c os metic pr o d ucts
8.
Fitz patric k, T. B., T he vali dit y a n d practica bilit y of s u n-reacti ve s ki n t y pes I t hr o u g h 
VI. Arc h. Der m at ol. 1 2 4, p p. 8 6 9- 8 7 1, 1 9 8 8
9.
Fre gert S. Ma n ual of c o ntact der matitis: O n be half of t he i nter nati o nal c o ntact der matitis 
researc h gr o u p: M u n ks gaar d; 1 9 7 4.
1 0. F o o d a n d Dr u g A d mi nistrati o n. I C H T o pic E 6: G ui deli ne f or G o o d Cli nical Practice.  Fe d 
Re g  1 9 9 7; 6 2 ( 9 0): 2 5 6 9 1- 7 0 9.
1 1. G ui da nce f or I n d ustr y; S ki n Irritati o n a n d Se nsitisati o n Testi n g of Ge neric Tra ns der mal 
Dr u g Pr o d ucts, U. S. De part me nt of Healt h a n d H u ma n Ser vices
1 2. F o o d a n d Dr u g A d mi nistrati o n Ce nter f or Dr u g E val uati o n a n d Researc h ( C D E R) Fe deral 
Re gister. 1 9 9 9; 6 4( 3 8): 9 5 1 6.
1 3. I C H T o pic 6 G ui deli ne f or G o o d Cli nical Practice C P M P/I C H/ 1 3 5/ 9 5 1 7t h J ul y 1 9 9 6.
1 4. Isa kss o n, M., Gr U V A ber ger, B., Fric k- E n gfel dt, M. a n d Br uze, M. ( 2 0 0 7), W hic h test 
c ha m bers s h o ul d be use d f or acet o ne, et ha n ol, a n d water s ol uti o ns w he n patc h testi n g? 
C o ntact Der matitis, 5 7: 1 3 4 – 1 3 6. d oi: 1 0. 1 1 1 1/j. 1 6 0 0- 0 5 3 6. 2 0 0 7. 0 1 0 9 4. x
1 5. Ki m ber I, Bas ketter D, Bert h ol d K , et al. S ki n se nsitizati o n testi n g i n p ote nc y a n d ris k 
assess me nt. T o xic ol o gical Scie nces. 2 0 0 1; 5 9( 2): 1 9 8- 2 0 8
1 6.
Mc Na mee P M, A pi A M, Bas ketter D A, et al. A re vie w of critical fact ors i n t he c o n d uct 
a n d i nter pretati o n of t he h u ma n re peat i ns ult patc h test. Re g ul T oxic ol P h ar m ac ol  2 0 0 8; 
5 2 : 2 4- 3 4.
1 7. Nati o nal Healt h S ur veilla nce A ge nc y Brazil ( A N VI S A). G ui deli ne f or t he Safet y 
E val uati o n of C os metic Pr o d ucts.  Brasília; 2 0 1 2.
1 8.
W orl d Me dical Ass ociati o n Declarati o n of Helsi n ki, 6 4t h Ge neral Asse m bl y, F ortaleza 
2 0 1 3.
1 5  
A P P E N DI C E S
1 5. 1  
A P P E N DI X 1- A B B R E VI A TI O N S
T a bl e 1 5- 1                  A b br e vi ati o n s
A b br e vi ati o n
T er m
A E
a d v er s e e v e nt
C R F
c a s e r e p ort f or m
c m 2
C e nti m et er s q u ar e d
E C
et hi c s c o m mitt e e
e C R F
El e ctr o ni c C a s e R e p ort F or m
F S F V
Fir st S u bj e ct Fir st Vi sit
G C P
G o o d Cli ni c al Pr a cti c e
I C H
I nt er n ati o n al C o nf er e n c e o n H ar m o ni s ati o n
C CI
2 1 2 3 7 8 | Pr ot oc ol Cli nical Pr ot oc ol _  |  
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 6  of 6 8
A b br e vi ati o n
T er m
I D
i d e ntifi c ati o n
I E C
I n d e p e n d e nt Et hi c s C o m mitt e e
I R B
i n stit uti o n al r e vi e w b o ar d
I R C
i nt er n al r e vi e w c o m mitt e e
L S L V
l a st s u bj e ct l a st vi sit 
M E D
Mi ni m al Er yt h e m al D o s e
M e d D R A
m e di c al Di cti o n ar y f or R e g ul at or y A cti viti e s
m L
Millilit er
N/ A
n ot a p pli c a bl e
PI
pri n ci p al i n v e sti g at or
P T
Pr ef err e d T er m
S A E
s eri o u s a d v er s e e v e nt
S m P C
s u m m ar y of pr o d u ct c h ar a ct eri sti c s
S O C
S y st e m Or g a n Cl a s s
S O P
st a n d ar d o p er ati n g pr o c e d ur e
S R S D
si n gl e r ef er e n c e st u d y d o c u m e nt
S S
s af et y st at e m e nt
U V R
Ultr a Vi ol et R a di ati o n
1 5. 2  
A p p e n di x 2-  S c ori n g of p at c h t e st r e a cti o n s a c c or di n g t o I C D R G. 
Patc h testi n g tec h ni q ues a n d sc ori n g reacti o ns b y a gra di n g scale were first sta n dar dize d i n t he 
1 9 3 0s. T he I nter nati o nal C o ntact Der matitis Researc h Gr o u p (I C D R G) p u blis he d t he f oll o wi n g 
n o nli near, descri pti ve gra di n g scale i n 1 9 7 0’s ( Fre gert, 1 9 7 4 ) w hic h c o nti n ues t o be wi del y 
use d a n d will be a d o pte d f or t his cli nical st u d y Ta ble 1 5- 2. T heref ore, a n y s ki n res p o nse at a 
patc he d site will be cli nicall y assesse d usi n g scale rec o m me n de d b y t he I C D R G. 
A trai ne d, bli n de d e val uat or will sc ore t he test sites f or si g ns of irritati o n per I C D R G scale at 
all ti me p oi nts s pecifie d i n t he st u d y sc he d ule. T he e val uat or sc ore will be c o nsi dere d fi nal. 
F or eac h s u bject w h o prese nts a p ositi ve reacti o n (i.e. a reacti o n sc ore of ‘ +’ or greater) i n t he 
c halle n ge p hase a bli n de d der mat ol o gist will f urt her classif y t he reacti o n as p ote ntial 
se nsitisati o n ( or n ot) at t he fi nal visit a n d pr o vi de a si n gle narrati ve descri pti o n t o s u m marise 
t he e ntiret y of t he s u bject’s e x perie nce of t he e ve nt. As se nsitisati o n a n d irritati o n ca n occ ur i n 
t he c halle n ge p hase, it is p ossi ble t o rec or d a p ositi ve reacti o n i n t he c halle n ge p hase w hic h is 
n ot a se nsitisati o n reacti o n. T he der mat ol o gist m ust c o nsi der h o w t he reacti o n prese nts/e v ol ves 
o ver ti me, t o ascertai n w het her it is c haracteristic of a se nsitisati o n reacti o n. T he der mat ol o gist 
will rec or d t heir o pi ni o n i n t he narrati ve a n d wit h a c hec k- b o x i n t he C R F.
T he narrati ve m ust i ncl u de t he start a n d fi nis h date of t he e ve nt, a descri pti o n of h o w t he e ve nt 
e v ol ves o ver ti me, a n y acti o n ta ke n (e. g. m o ve d patc h), a n d dia g n osis ( p ote ntial se nsitisati o n 
reacti o n, or ot her as a p pr o priate). If a clear dia g n osis ca n n ot be ma de, t he n t he der mat ol o gist 
s h o ul d i ncl u de t his i n t he narrati ve.  
T a bl e 1 5- 2 
S c ori n g of p at c h c ell s a c c or di n g t o I C D R G
  -
N e g ati v e r e a cti o n
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 7  of 6 8
+ ?
D o u btf ul r e a cti o n; f ai nt er yt h e m a o nl y
 +
W e a k ( n o n- v e si c ul ar) p o siti v e r e a cti o n; er yt h e m a, i nfiltr ati o n a n d p o s si bl y 
p a p ul e s
+ +
Str o n g ( v e si c ul ar) p o siti v e r e a cti o n; er yt h e m a, i nfiltr ati o n, p a p ul e s a n d 
v e si cl e s
+ + +
E xtr e m e p o siti v e r e a cti o n; b ull o u s r e a cti o n, i nt e n s e er yt h e m a a n d i nfiltr ati o n, 
c o al e s ci n g v e si cl e s
(I R)
Irrit a nt r e a cti o n
( N T)
N ot t e st e d
If a s u bject de vel o ps a sc ore of ‘ Str o n g’ ( + +) or greater at a n y p oi nt d uri n g t he i n d ucti o n p hase, 
t he ne xt patc h will be a p plie d t o a n a djace nt naï ve (i.e. pre vi o usl y u ntreate d) site. If a sc ore of 
‘ Str o n g’ ( + +) or greater occ urs at t he naï ve site, n o f urt her patc h a p plicati o ns will be ma de. 
S uc h reacti ve s u bjects will, h o we ver, pr o gress t o t he c halle n ge p hase u nless, i n t he o pi ni o n of 
t he I n vesti gat or, it w o ul d be u n wise t o d o s o.
A n y der mal irritati o n or se nsitisati o n reacti o ns w hic h occ ur wit hi n t he patc h a p plicati o n area 
a n d ca n’t be c o m pletel y descri be d b y t he scale i n Ta ble 1 5- 2 ( A p pe n di x 2), will n ot be rec or de d 
as A Es d uri n g t he st u d y. Reacti o ns t o t he patc h itself will als o n ot be rec or de d as A Es. T hese 
res p o nses are t y pical effects of occl u de d a p plicati o n of t o pical pr o d ucts. 
U ne x pecte d or u n us ual reacti o ns w hic h occ ur wit hi n t he patc h area t hat ca n n ot be c o m pletel y 
descri be d b y t he scale i n Ta ble 1 5- 2 ( A p pe n di x 2), (e. g., ras h, hi ves) will be rec or de d as A Es. 
1 5. 3  
A p p e n di x 3 - Fit z p atri c k S ki n T y p e Gr a di n g
T he Fitz patric k scale is a n u merical classificati o n t hat is wi del y use d b y der mat ol o gists t o 
classif y a pers o n’s s ki n t y pe b y t heir res p o nse t o s u n e x p os ure ( Fitz patric k, 1 9 8 8). 
S ki n T y pe
S u n b ur n a n d T a n ni n g Hist or y
I
Al w a y s b ur n s e a sil y; n e v er t a n s ( p al e w hit e s ki n)
II
Al w a y s b ur n s e a sil y; t a n s mi ni m all y ( w hit e s ki n)
III
B ur n s m o d er at el y; t a n s gr a d u all y (li g ht br o w n s ki n)
I V
B ur n s mi ni m all y, al w a y s t a n s w ell ( m o d er at e br o w n s ki n)
V
R ar el y b ur n s, t a n s pr of u s el y ( d ar k br o w n s ki n)
VI
N e v er b ur n s ( d e e pl y pi g m e nt e d d ar k br o w n t o bl a c k s ki n)
1 5. 4  
A p p e n di x 4 S p e cifi c ati o n of t h e S ol ar Si m ul at or O ut p ut
A m ulti p ort s olar si m ulat or utilizi n g a 3 0 0 W xe n o n arc la m p fitte d wit h 6 li q ui d li g ht g ui des 8 
m m i n dia meter a n d t w o filters ( Sc h ott W G 3 2 0/ 1 m m dic hr oic mirr or a n d U G 1 1/ 1 m m) will 
be use d f or t his st u d y. 
T he acc urac y of t he S P F meas ure d is de pe n de nt o n t he a bs or ba nce c haracteristics of t he 
s u nscree n filteri n g s yste m t o be teste d i n c o nj u ncti o n wit h t he s o urce s pectr u m. T heref ore, it is 
i m p orta nt t o defi ne t he s o urce b y t he s pectral distri b uti o n of its er yt he mal efficac y as well as 
its o verall s pectral irra dia nce c haracteristics. 
T h us, t he s o urce s pectra s pecificati o n is descri be d i n ter ms of c u m ulati ve er yt he mal 
effecti ve ness b y s uccessi ve wa vele n gt h ba n ds fr o m < 2 9 0 n m u p t o 4 0 0 n m. T he er yt he mal 
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G S K C o ns u mer Healt hcare
Cli nical Pr ot oc ol
Pr ot oc ol N u m ber: 2 1 2 3 7 8 
 
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi de ntial 
Ma y n ot be use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H
S P 1 9 6 3/ S O P- 2 0 8 6 6 1 : Te m plate Versi o n : 1 4 Mar 2 0 1 9
Pa ge 6 8  of 6 8
effecti ve ness of eac h wa vele n gt h ba n d is e x presse d as t he perce nta ge relati ve c u m ulati ve 
er yt he mal effecti ve ness ( % R C E E) a n d will fall wit hi n t he li mits defi ne d i n Ta ble 1. 
T he s pectral o ut p ut of t he s olar si m ulat or will ha ve bee n c o nfir me d wit hi n t he past 1 8 m o nt hs 
or after 3 0 0 0 h o urs of la m p r u n ni n g ti me, w hic he ver is s o o ner, or after c ha n gi n g a n y si g nifica nt 
p h ysical c o m p o ne nt of t he s olar si m ulat or, b y cali brate d s pectr ora di o metric meas ure me nt.  T he 
s pectr ora di o meter use d t o meas ure t he s pectral o ut p ut of t he s olar si m ulat or will be fitte d wit h 
a d o u ble m o n oc hr o mat or a n d its res ol uti o n ba n d wi dt h will be < 2 n m wit h meas ure me nts ma de 
i n ste ps n ot e xcee di n g t he ba n d wi dt h.  T he s pectr ora di o meter will ha ve bee n cali brate d wit hi n 
t he past 1 8 m o nt hs a gai nst sta n dar d li g ht s o urces f or its res p o nse t o s pectral irra dia nces, f or its 
wa vele n gt h acc urac y a n d f or li nearit y of si g nal res p o nses at all wa vele n gt hs o ver a n irra dia nce 
ra n ge c o veri n g t he act ual s o urce meas ure me nt ra n ge. 
T he t otal irra dia nce of t he s olar si m ulat or will als o be meas ure d a n d m ust n ot e xcee d 1 6 0 0 
W/ m
2.
T he t otal ra di o metric pr o p orti o n of t he U V A II ( 3 2 0 n m t o 3 4 0 n m) irra dia nce of t he si m ulat or 
will be > 2 0 % of t he t otal U V ( 2 9 0 n m t o 4 0 0 n m) irra dia nce. A d diti o nall y, t he U V A I re gi o n 
( 3 4 0 n m t o 4 0 0 n m) irra dia nce will be > 6 0 % of t he t otal U V irra dia nce.
T a bl e 1 5- 3 
- % R C E E a c c e pt a n c e li mit s f or t h e U V s ol ar si m ul at or o ut p ut
Me as ure d % R C E E
S pectr al R a n ge
n m
L o wer Li mit
U p per Li mit
< 2 9 0
-
< 0. 1
2 9 0 t o 3 0 0
1. 0
8. 0
2 9 0 t o 3 1 0
4 9. 0
6 5. 0
2 9 0 t o 3 2 0
8 5. 0
9 0. 0
2 9 0 t o 3 3 0
9 1. 5
9 5. 5
2 9 0 t o 3 4 0
9 4. 0
9 7. 0
2 9 0 t o 4 0 0
9 9. 9
1 0 0. 0
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