A Multicenter, Open-label Extension Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Orally Administered GLPG1690 in Subjects With Systemic Sclerosis
Phase: PHASE2
Conditions: Systemic Sclerosis
Sponsor: Galapagos NV

-1 - 
 
 
C o nfi de nti alit y St ate me nt  
T he i nf or mati o n c o ntai ne d i n t his d oc u me nt is pri vile ge d a n d c o nfi de ntial. It is t he pr o pert y of Gala pa g os N V a n d 
ma y n ot be use d, discl ose d, re pr o d uce d or ot her wise disse mi nate d wit hi n y o ur or ga nizati o n or c o m m u nicate d t o a n y 
t hir d parties wit h o ut t he e x press writte n a ut h orizati o n of Gal a pa g os N V. 
 
 
C LI NI C A L S T U D Y P R O T O C O L  
Pr oj e ct N u m b er:   
G L P G 1 6 9 0  
St u d y N u m b er :  
G L P G 1 6 9 0 - C L-2 0 6  
Pr ot o c ol v er si o n :  
2. 0 0  
D at e:  
8 -J a n -2 0 2 0  
A m e n d m e nt:   
1  
 
 
St u d y Titl e   
A m ulti c e nt er , o p e n -l a b el e xt e n si o n st u d y t o e v al u at e t h e l o n g-t er m s af et y, 
t ol er a bilit y a n d effi c a c y of or all y a d mi ni st er e d G L P G 1 6 9 0 i n s u bj e ct s wit h 
s y st e mi c s cl er o si s  
St at u s  
Fi n al  
D e v el o p m e nt 
P h a s e:  
2  
 
 
E u dr a C T N o:   
2 0 1 9 -0 0 1 2 7 9 -3 4   
C T. g o v N o:   
N C T 0 3 9 7 6 6 4 8  
I N D N o 
1 4 0 6 9 1  
S p o n s or:  
G al a p a g o s N V, G e n er a al D e Witt el a a n L 1 1 A 3, 2 8 0 0 M e c h el e n, B el gi u m  
M e di c al L e a d er : 
, M D 
G e n er al Pr ot o c ol  
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-2 - 
 
E M E R G E N C Y C O N T A C T I N F O R M A TI O N  
I n case of a seri o us a d verse e ve nt ( S A E), a special sit uati o n (see S ecti o n 8. 1. 6 ) or i n cas e of 
pre g n a nc y  d uri n g t he cli nical st u d y t he i n vesti gat or m ust re p ort t his i m me diatel y, a n d u n der n o 
circ u msta nces later t ha n 2 4 h o urs f oll o wi n g t he k n o wle d ge of t he S A E or pre g na nc y, as f oll o ws:   
  
Fa x 
 
or  
E -mail: 
 
 
I n case of me dical q u esti o ns d uri n g t he c o urse of t he st u d y, t he i n vesti gat or m ust c o ntact t he 
c o ntract r esearc h or ga nizati o n ( C R O)  m e dical m o nit or . F or ur ge nt me dical safet y q uesti o ns, t he 
i n vesti gat or ca n c o nt act t he safet y h otli ne:  
 
C o ntact Safet y H otli ne:  
E M E A: 
 
N ort h A merica: 
 
 
 
S p o ns or co ntact  n u m ber : 
  
 
 
 

 
-3 - 
 
 
T A B L E O F C O N T E N T S  
E M E R G E N C Y C O N T A C T I N F O R M A TI O N  ........................................................................... 2  
T A B L E O F C O N T E N T S  ........................................................................................................ 3  
C LI NI C A L S T U D Y P R O T O C O L HI S T O R Y  ............................................................................ 7  
S U M M A R Y O F C H A N G E S  ................................................................................................... 8  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S ..................................................1 2  
P R O T O C O L S Y N O P SI S  ......................................................................................................1 6  
1.  
I N T R O D U C TI O N ...........................................................................................................1 9  
1. 1.   
B a c k gr o u n d - N o n cli ni c al St u di e s  .......................................................................2 0  
1. 1. 1.   
P h y si c al, C h e mi c al, P h ar m a c e uti c al Pr o p erti e s, a n d F or m ul ati o n  .......2 0  
1. 1. 2.   
P h ar m a c ol o g y  .....................................................................................2 0  
1. 1. 2. 1.   
Pri m ar y a n d S e c o n d ar y P h ar m a c ol o g y  ..............................2 0  
1. 1. 2. 2.   
S af et y P h ar m a c ol o g y  .........................................................2 1  
1. 1. 3.   
N o n cli ni c al P h ar m a c o ki n eti c s a n d Pr o d u ct M et a b oli s m  ......................2 1  
1. 1. 4.   
T o xi c ol o g y  ..........................................................................................2 2  
1. 1. 4. 1.   
G e n er al T o xi c ol o g y  ............................................................2 2  
1. 2.   
B a c k gr o u n d - Cli ni c al St u di e s  ............................................................................2 3  
1. 2. 1.   
Cli ni c al S af et y  .....................................................................................2 3  
1. 2. 2.   
Cli ni c al Effi c a c y  ...................................................................................2 4  
1. 2. 3.   
C li ni c al P h ar m a c o ki n eti c s ...................................................................2 4  
1. 2. 4.   
Cli ni c al P h ar m a c o d y n a mi c s  ................................................................2 5  
2.  
C LI NI C A L S T U D Y O B J E C TI V E S  ..................................................................................2 5  
2. 1.   
Pri m ar y O bj e cti v e ...............................................................................................2 5  
2. 2.   
Ot h er  O bj e cti v e s  ................................................................................................2 5  
3.  
I N V E S TI G A TI O N A L P L A N ............................................................................................2 6  
3. 1.   
Cli ni c al St u d y D e si g n  .........................................................................................2 6  
3. 2.   
E n d of St u d y D efi niti o n  ......................................................................................2 7  
3. 3.   
Cli ni c al St u d y R ati o n al e  .....................................................................................2 7  
3. 3. 1.   
D o s e R ati o n al e  ...................................................................................2 7  
3. 3. 2.   
Cli ni c al St u d y D e si g n R ati o n al e  ..........................................................2 7  
3. 4.   
E n d p oi nt s  ...........................................................................................................2 7  
3. 4. 1.   
Pri m ar y E n d p oi nt  ................................................................................2 8  
3. 4. 2.   
Ot h er E n d p oi nt s  ..................................................................................2 8  
3. 5.   
P ot e nti al Ri s k s a n d B e n efit s  ..............................................................................2 8  
3. 6.   
Cli ni c al St u d y P o p ul ati o n  ...................................................................................2 9  
3. 6. 1.   
I n cl u si o n Crit eri a .................................................................................2 9  
3. 6. 2.   
E x cl u si o n Crit eri a  ................................................................................3 0  
3. 6. 3.   
P r o hi biti o n a n d R e stri cti o n s ................................................................3 0  
3. 6. 3. 1.   
Pr e c a uti o n s f or S e x u al I nt er c o ur s e  ....................................3 0  
3. 6. 3. 1. 1.   
F e m al e s u bj e ct s .............................................3 0  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
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9. 2. 3.   
Ar c hi vi n g  .............................................................................................5 9  
9. 2. 4.   
P arti ci p ati o n C ar d s  ..............................................................................6 0  
9. 3.   
C o nfi d e nti alit y  ....................................................................................................6 0  
9. 4.   
Et hi c al  C o n si d er ati o n s  .......................................................................................6 1  
9. 4. 1.   
I n d e p e n d e nt Et hi c s C o m mitt e e / I n stit uti o n al R e vi e w B o ar d ...............6 1  
9. 4. 2.   
I nf or m e d C o n s e nt ...............................................................................6 1  
9. 5.   
D at a Q u alit y C o ntr ol/ A s s ur a n c e  .........................................................................6 2  
9. 5. 1.   
M o nit ori n g  ...........................................................................................6 2  
9. 5. 2.   
A u dit a n d I n s p e cti o n  ...........................................................................6 2  
1 0.  R E F E R E N C E S  ..............................................................................................................6 3  
1 1.  A P P E N DI C E S  ...............................................................................................................6 4  
SI G N A T U R E P A G E –  S P O N S O R  ........................................................................................6 9  
SI G N A T U R E P A G E –  I N V E S TI G A T OR  ...............................................................................7 0  
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-9 - 
 
 
 
E ve nts meeti n g t he f oll o wi n g defi ne d criteria m ust be re p orte d as a seri o us a d verse e ve nt ( S A E) a n d 
In vesti gati o nal Me dici nal Pr o d uct (I M P)  m ust be disc o nti n ue d:  
  A S T or A L T ≥8 x U L N  
  A S T or A L T ≥3 x U L N wit h si g ns of se vere li ver da ma ge (i.e. wit h t he a p peara nce of fati g ue, na usea, 
v o miti n g, ri g ht u p per q ua dra nt pai n or te n der ness, fe ver, ras h a n d/ or e osi n o p hilia [ > 5 %], a n d/ or t otal 
bilir u bi n ≥1. 5 x U L N or inter nati o nal n or malize d rati o [I N R] > 1. 5)  
T he i n vesti gati o ns a n d ste ps t o be ta ke n b y t he i n vesti gat or ha ve bee n descri be d i n Secti o n 3 .6 . 4. 
A p plic a ble Secti o ns:  
Secti o n 3 .6 . 4 Treat me nt Disc o nti n uati o n ( T e m p oraril y a n d Per ma ne ntl y), S u bj ect Wit h dra wal a n d St u d y 
T er mi nati o n  
Secti o n 8. 1. 5. Cli nical La b orat or y A b n or malities a n d O ther A b n or mal Assess me nts as A d verse E ve nts or 
Seri o us A d verse E ve nts  
H y dr o x yc hl or o q ui ne has bee n a d de d t o t he list of me dicati o n k n o w n t o pr ol o n g Q T i nter val (t o be use d wit h 
ca uti o n)  i n A p pe n di x 5, a n d felo di pi ne was re m o ve d fr o m t he list of pr o hi bite d me dicati o n ( Errat u m 2, 
2 7 -A u g -2 0 1 9 ). 
S u b o x o ne was re m o ve d fr o m t he list of k n o w n str o n g c yt oc hr o me P 4 5 0 ( C Y P) C Y P 3 A 4 i n hi bit ors beca use 
its c o nstit ue nts, nal o x o ne a n d b u pe n o p hi ne are n ot k n o w n t o be str o n g i n hi bit ors. 
T he pr o hi biti o n of B -cell de pleti n g a ge nts has bee n br oa de ne d t o “ ot her m o n ocl o nal a nti b o dies”.  
Restricti o ns o n t he c o ns u m pti o n of d o u ble -stre n gt h gra pefr uit j uice ha ve bee n a d de d i n Se cti o n 3. 6. 3. 3.  
A p plic a ble Secti o ns :  
Secti o n 3. 6 . 3. 2 Pri or a n d C o nc o mita nt Me dicati o ns  
Secti o n 3. 6. 3. 3 F o o d a n d Be vera ge Restricti o ns  
A p pe n di x 2 K n o w n Str o n g C Y P 3 A 4 I n d ucers a n d P ote nt P -g p I n d ucers  
A p pe n di x 3  K n o w n Str o n g C Y P 3 A 4 I n hi bit ors  
A p pe n di x 5 Me dicati o n K n o w n t o Pr ol o n g Q T i nter val  
T he E C G para meter Q T c B  will n ot be deri ve d.  
A p plic a ble Secti o n:   
Secti o n 5 . 6. 5 1 2-lea d Electr ocar di o gra m 
T he pr ot oc ol was u p date d wit h g ui da nce f or male s u bj ects t o wit h dra w if t he y i nte n d t o fat her a c hil d.  
A p plic a ble Secti o ns:  
Secti o n 3. 5  P ote ntial Ris ks a n d Be nefits  
Secti o n  3. 6. 3. 1. 2 Preca uti o ns f or Se x ual I nterc o urse: Male s u bj ects  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-1 0 - 
 
T he pr ot oc ol was u p date d t o c orrect t he Safet y h otli ne n u m b er a n d e -mail  a d dress ( Errat u m 1 , 2 3-J ul-2 0 1 9 ). 
A p plic a ble Secti o ns :  
E mer ge nc y C o ntact I nf or mati o n  
Mi n or e dits a n d a d mi nistrati ve u p dates t hr o u g h o ut t he pr ot oc ol.   
A p plic a ble Secti o ns :  
List of A b bre viati o ns a n d Defi niti o n of T er ms  
Secti o n 3. 3  Cli nical St u d y Rati o nale  
Secti o n 3. 6. 3. 3 F o o d a n d Be vera ge Restricti o ns  
Secti o n 3. 6. 4 Treat me nt Disc o nti n uati o n  ( T e m p oraril y a n d Per ma ne ntl y), S u bj ect Wit h dra wal a n d St u d y 
T er mi nati o n  
Secti o n 4. 4 St ora ge  
Secti o n 5. 6. 2 Cli nical La b orat or y E val uati o ns  
Secti o n 6. 3. 2 I nteri m A nal ysis  
A p pe n di x 2  
A p pe n di x 5  
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-1 1 - 
 
 
U p date t o Versi o n 1. 0 0  (0 9 -A pr -2 0 1 9 ) 
T he o ver all re as o n f or t his u p d ate : 
A d diti o n of E u dra C T n u m ber  a n d pr ot oc ol clarificati o ns. 
T he c h a n ges ma de t o C S P G L P G 1 6 9 0 -C L -2 0 6 Versi o n  1. 0 0 date d 3 0 -Ja n-2 0 1 9, are liste d  bel o w, reflecti n g a 
brief rati o nale of eac h c ha n ge a n d t he a p plica ble secti o ns.  
T he pr ot oc ol  E u dra C T n u m ber  a d de d 
A p plic a ble Se cti o ns: 
Title pa ge  
T he pr ot oc ol was u p date d t o clarif y t hat d osi n g of I n vesti gati o nal Me dici nal Pr o d uct (I M P) i n t his st u d y starts 
o n t he da y after t he R oll o ver visit  
A p plic a ble Secti o ns :  
S y n o psis  
Secti o n 3. 1 Cli nical St u d y desi g n  
Secti o n 5. 8 Sc he d ule of  Acti vities  
T he list of safet y la b orat or y para meters was u p date d t o ali g n wit h t he pri or G L P G 1 6 9 0-C L -2 0 4 st u d y  
A p plic a ble Secti o ns :  
Secti o n 5. 6. 2 Cli nical La b orat or y E val uati o ns  
Clarificati o ns ha ve bee n ma de t hr o u g h o ut t he pr ot oc ol.  
 
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-1 2 - 
 
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S  
A b bre vi ati o ns  
A D L   
acti vities of dail y li vi n g  
A E  
a d verse e ve nt  
A L T   
ala ni ne a mi n otra nsferas e  
A S T   
as partate a mi n otra nsferas e  
 
 
A T X   
a ut ota xi n 
 
  
B C R P   
breast c a ncer resista nce pr otei n  
B W  
b o d y wei g ht  
C R F   
case re p ort f or m  
 
 
C R O   
c o ntract r esearc h or ga nizati o n  
C S P   
cli nical st u d y pr ot o c ol  
C T C A E   
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
C Y P   
c yt o c hr o me P 4 5 0  
E C G   
electr ocar di o gra m  
E D  
earl y disc o nti n uati o n  
E N P P   
ect o n ucle oti de p yr o p h os p hatase/ p h os p h o diesterase  
E o T  
e n d of treat me nt  
E U  
E ur o pea n U ni o n  
F A S   
f ull a nal ysis set 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-1 3 - 
 
 
 
F S H   
f ollicle sti m ulati n g h or m o ne 
 
 
G C P   
G o o d Cli nical Practice(s)  
G G T   
ga m ma gl uta m yl tra nsferase  
GI  
gastr oi ntesti nal  
G L P   
G o o d La b orat or y Practice  
I B 
i n vesti gat or’s br oc h ure 
I C5 0 
5 0 % i n hi bit or y c o n ce ntrati o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts f or 
P har mace uticals f or H u m a n Use  
I E C 
I n d e pe n de nt Et hics C o m mittee 
I L-6   
i nterle u ki n 6  
I M P  
i n vesti gati o nal me dici nal pr o d uct 
I N R 
i nter nati o nal n or malize d rati o 
I P F 
i di o pat hic p ul m o nar y fi br osis 
I R B 
I nstit uti o nal Re vie w B oar d 
L F T   
li ver f u ncti o n test 
L P A   
l ys o p h os p hati dic aci d 
L P C   
lys o p h os p hati d yl c h oli ne  
L P D   
l ys o p h os p h oli pase D  
M A T E   
m ulti dr u g a n d t o xi n e xtr usi o n  tra ns p orter 
M CI D   
Mi ni mal Cli nicall y I m p orta nt Differe nce  
M M F   
m yc o p h e n olate m ofetil  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-1 5 - 
 
Defi niti o n of Ter ms  
Q Tc F   
Q T i nter val c orrecte d f or heart rate  usi n g Fri derici a’s f or m ula:  
Q Tc F = Q T/ R R 1/ 3 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-1 6 - 
 
P R O T O C O L S Y N O P SI S  
T itle of St u d y 
A m ultice nter, o pe n -l a bel e xte nsi o n st u d y t o e val u ate t he l o n g-ter m safet y, t olera bilit y a n d 
efficac y of orall y a d mi nistere d G L P G 1 6 9 0 i n s u bjects wit h s yste mic s cler osis. 
P h ase of De vel o p me nt : 2  
Pl a n ne d N u m ber o f S u bjects  
U p t o 3 0  s u bjects ma y  roll o ver fr o m St u d y G L P G 1 6 9 0-C L -2 0 4 i nt o t his o p e n -la bel 
e xte nsi o n  ( O L E) st u d y. 
St u d y D ur ati o n  
Eac h s u bject will be i n t h e st u d y f or u p t o 1 1 6 wee ks ( 1 0 4 wee ks of treat me nt a n d 1 2 wee ks 
of f oll o w -u p).   
St u d y Desi g n  
A n o pe n -la bel, m ultice nt er, si n gl e-ar m, 1 0 4 -wee k e xte nsi o n st u d y f or s u bjects wit h 
s yste mic scler osis w h o c o m plete d t he 2 4-wee k  d o u ble -bli n d treat me nt peri o d of St u d y 
G L P G 1 6 9 0 -C L -2 0 4.  
O bjecti ves a n d E n d p oi nts  
O bjecti ves  
E n d p oi nts  
Pri m ary  
 
T o e val uate t he l o n g-ter m safet y a n d t olera bilit y of 
G L P G 1 6 9 0 i n s u bj ects wit h s yste mic scler osis . 
I nci de nce of treat me nt-e mer ge nt a d verse e ve nts 
( T E A Es), seri o us a d verse e ve nts ( S A Es), A Es o ver 
ti me. 
Key Sec o n d ary  
 
N ot a p plica ble  
 
 
M ai n Criteri a f or I ncl usi o n a n d E xcl usi o n  
Ke y I ncl usi o n Criteria  
 
Male or fe m ale s u bjects w h o c o m plete d t he 2 4 -wee k treat me nt peri o d of St u d y 
G L P G 1 6 9 0 -C L -2 0 4 a n d w h o acc or di n g t o t he i n vesti gat or’s j u d g m e nt ma y be nefit 
fr o m l o n g-ter m treat me nt wit h G L P G 1 6 9 0. 
Ke y E x cl usi o n Criteria  
 
A n y c o n diti o n or circ u msta nces t hat, i n t he o pi ni o n of t he i n vesti gat or, ma y ma ke a 
s u bject u nli kel y or u na bl e t o c o m plete t he st u d y or c o m pl y wit h st u d y pr oce d ures a n d 
re q uire me nts. 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-1 9 - 
 
1.   
I N T R O D U C TI O N 
S yste mic S cler osis  
S yste mic scler osis (scler o der ma) is a rare a ut oi m m u ne disease of t he c o n n ecti ve tiss ue wit h t he 
hi g hest m ortalit y rate of all r he u matic diseas es. T he disease h as a fe male pre d o mi na nce ( 3: 1) a n d 
a pea k o nset i n t he f o urt h deca d e of life. S yste mic scler osis has 3  maj or pat h o ge ni c c o m p o ne nts: 
(i) fi br osis wit h t hic ke ni n g of t he s ki n a n d i n ner or ga ns, (ii) i nfla m mati o n, a n d (iii) vasc ul o pat h y. 
Maj or or ga ns affecte d are t he s ki n, t he l u n g ( p ul m o nar y fi br osis a n d p ul m o nar y arterial 
h y perte nsi o n), t he ki d ne ys, t he  gastr oi ntesti nal ( GI) tract, t he m usc ul os kel etal s yste m, t he 
retr o perit o neal s pace, a n d t he heart. C urre nt treat me nt o pti o ns f or s yste mi c scler osis are li mite d 
a n d i ncl u de t o pical s ki n treat me nts, n o nster oi dal a nti -i nfla m mat or y dr u gs, ster oi ds, a n d ot her 
i m m u n os u p pressa nts ( met hotre x ate, m yc o p he n ol ate m ofetil  [ M M F], azat hi o pri ne, 
c ycl o p h os p ha mi de).  
At prese nt, t here are n o a p pr o ve d dr u gs f or t he treat me nt of s yste mic s cler osis, i n dicati n g a hi g h 
u n met me dical nee d.  
M o de of Acti o n  
G L P G 1 6 9 0 is a n o v el, p ote nt,  a n d selecti ve s mall -m olec ule i n hi bit or of a ut ota xi n ( A T X ), 
tar geti n g dis ease rele va nt si g nal tra ns d u cti o n pat h wa ys, c urre ntl y i n de vel o p me nt f or t he 
treat me nt of s yste mic scl er osis. 
A T X, als o k n o w n as ect o n ucle oti de p yr o p h os p hat ase/ p h os p h o diesteras e ( E N P P) 2 or 
l ys o p h os p h oli pase D ( L P D), is a ~ 1 2 0 -k Da pr otei n t hat bel o n gs t o t he E N P P e nz y me fa mil y. 
A T X is t he o nl y E N P P e nz y m e wit h L P D acti vit y a n d is res p o nsi ble f or t he h y dr ol ysis of 
l ys o p h os p hati d yl c h oli ne ( L P C) t o pr o d u ce t he bi o acti ve li pi d l ys o ph os p hati dic aci d ( L P A). T he 
ter m L P A c o vers s e veral c he mical s pe cies a ble t o acti vate L P A rece pt ors d e pe n di n g o n t he nat ure 
of t he fatt y aci d si de c hai n o n t he gl ycer ol bac k b o ne. T he m ost a b u n da nt L P A s pecies i n h u ma n 
plas ma is L P A C 1 8: 2 wit h a fatt y aci d si de c hai n of 1 8 car b o n at o ms i ncl u di n g t w o  u nsat urate d 
b o n ds  ( Ba n d o h, et al. 2 0 0 0). Literat ur e data ha ve i de ntifie d t he A T X/ L P C a xis as t he mai n s o urce 
of L P A i n bl o o d ( Ta na ka, et al. 2 0 0 6, Ts u da, et al. 2 0 0 6).  
L P A acts t hr o u g h 6  differe nt G -pr otei n c o u ple d rece pt ors ( L P A 1 -6) w here b y mai nl y L P A 1 -3 
ha ve bee n ass ociat e d wit h t he pat h o ge nic ( pr o -i nfla m mat or y a n d pr o-fi br otic) effects of L P A. 
Tar geti n g t he A T X p at h wa y b y a nta g o nizi n g L P A 1 i n a p re vi o us P hase 2 a st u d y ( S A R 1 0 0 8 4 2) i n 
s yste mic scler osis was w ell t olerate d a n d res ulte d i n cli nical i m pr o ve me nts of s ki n pat h ol o gies 
( m o difie d R o d na n S ki n S c ore [ m R S S]) a n d s ki n bi o mar kers, s u g gesti n g t hat tar geti n g t he A T X 
pat h wa y is pr o misi n g i n m o d ulat i n g s ki n pat h ol o gies i n s yste mic scler osis ( Alla n ore, et al. 2 0 1 8). 
A vaila ble literat ur e a n d n o ncli nical p har mac ol o g y data ge nerate d b y Gala pa g os s u g gest t hat 
i nter ve nti o ns tar geti n g t he A T X/ L P A pat h wa y c o ul d lea d t o a ne w class of t hera p y f or dis ease 
m o dificati o n i n s yste mic scler osis . 
F or m ore d etails, refer t o t he latest versi o n of t he i n vesti gat or’s br oc h ure (I B) a n d rele va nt 
u p dates/a d de n da.  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-2 1 - 
 
T he ef fi cac y of G L P G 1 6 9 0 was assesse d i n a m uri ne m o del of c hr o nic graft-vers us -h ost disease 
rese m bli n g k e y c o m p o ne nts of der mal a n d p ul m o nar y s yste mic scler osis disease ma nifest ati o ns 
b y e v al uati n g cli nical sc ori n g, der mal t hic ke ni n g, h y dr o x y pr oli ne c o nte nt, a n d m y ofi br o blast 
c o u nts. I n t his m o del , G L P G 1 6 9 0 s h o we d effi cac y f or s ki n a n d l u n g rea d-o ut para meters si milar 
t o t hat of ni nte da ni b. 
1. 1. 2. 2.   
S af et y P h ar m a c ol o g y  
T he safet y p h ar mac ol o g y pac ka ge c o n d uct e d t o i n vesti gate t h e p ote ntial effect of G L P G 1 6 9 0 o n 
car di o vas cular, res pirat or y, a n d ce ntr al ner v o us s yste ms di d n ot s h o w a n y bi ol o gicall y rel e va nt 
effects.  
1. 1. 3.   
N o n cli ni c al P h ar m a c o ki n eti c s a n d Pr o d u ct M et a b oli s m  
T he a bs ol ute oral bi oa v aila bilit y was m o derate i n r o de nts ( 2 5 % t o 3 6 %), l o w i n m o n ke ys ( 1 4 %), 
a n d hi g h i n d o gs ( 1 0 2 %).  
G L P G 1 6 9 0 was hi g hl y b o u n d t o plas ma pr otei ns: 9 9. 1 % i n h u ma n a n d 9 7. 9 -9 9. 6 % i n rat, d o g, 
m o use, ra b bit, a n d m o n k e y.  
O verall, G L P G 1 6 9 0 di d n ot e xte nsi vel y distri b ute i nt o tiss ues as s h o w n b y t he l o w v ol u me of 
distri b uti o n at stea d y stat e ra n gi n g  fr o m 0. 3 5 L/ k g i n t he m o use t o 0. 5 5 L/ k g i n t he m o n ke y. I n 
rat, [1 4C] -G L P G 1 6 9 0 was wi del y distri b ute d t hr o u g h o ut t he b o d y. Hi g hest c o nce ntrati o ns of 
ra di oacti vit y were o bser ve d i n c onte nts of t he GI  tract, gla n d ular tiss ues, li ver, a n d u veal tract. 
G L P G 1 6 9 0 a n d/ or meta b olites  s h o we d s o me affi nit y f or mel a ni n-c o ntai ni n g tiss ues, li ke u veal 
tract a n d me ni n ges. 
After oral a d mi nistrati o n, dr u g -relat e d material is e x crete d mai nl y i n feces i n rat (a b o ut 9 0 % or 
greater). I n bile d u ct -ca n n ulate d rats, a b o ut 5 0 % of  orall y a d mi nistere d ra di oacti vit y was 
rec o vere d i n bile. 
U p o n re peate d o nce dail y ( q. d.) oral d osi n g of G L P G 1 6 9 0, n o si g nifica nt acc u m ulati o n was 
o bser ve d i n plas ma, e x ce pt i n male rats ( 2 0  m g/ k g/ da y) a n d d o gs ( 5 0/ 6 5  m g/ k g/ da y at Wee k  3 9). 
Se x  differe nces  i n P K pr ofiles were o bs er ve d i n rats b ut n ot i n d o gs. 
T he t otal plas ma cleara n ce of G L P G 1 6 9 0 was l o w i n mice, rats, m o n ke ys, a n d d o gs, ra n gi n g 
bet wee n 3 % a n d 2 3 % of t he he patic bl o o d fl o w. T heref ore, G L P G 1 6 9 0 is e x pecte d t o u n der g o a 
l o w first pass effect after oral d osi n g.  
T he pri mar y c yt o c hr o me P 4 5 0 ( C Y P) e nz y m e i n v ol ve d i n G L P G 1 6 9 0 met a b olis m was C Y P 3 A 4. 
I n vitr o met a b olis m st u dies i n he pat oc ytes re veale d 2 6 p ote ntial meta b olites. Meta b olites f or me d 
i n h u ma n he pat oc ytes were all pres e nt t o a si milar or hi g her e xte nt i n rat a n d/ or d o g h e pat oc ytes, 
t he a ni mal s pecies sel ect e d f or t o xicit y st u dies.  
A n i n vitr o st u d y wit h G L P G 1 6 9 0 i n h u ma n he p at oc ytes s h o we d n o cli nicall y rele va nt i n d ucti o n 
of h u ma n C Y P 2 B 6 a n d C Y P 2 C e nz y mes. Wea k i n d ucti o n of  C Y P 1 A 2 a n d C Y P 3 A 4 ca n n ot be 
e x cl u de d at a G L P G 1 6 9 0 d ose of 6 0 0 m g i n h u ma n, wit h a ma xi mal decrease of ar o u n d 3 0 % i n 
t he e x p os ure of a se nsiti ve pr o be s u bstrat e f or b ot h C Y P e nz y m es. 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-2 2 - 
 
A n i n vitr o st u d y wit h G L P G 1 6 9 0 i n h u ma n li ver micr os o mes i n dicate d n o cli nicall y rele va nt 
i n hi biti o n of t he maj orit y of C Y P e nz y m es. W ea k c o m petiti ve re versi ble i n hi biti o n  of C Y P 2 C 8 
a n d C Y P 3 A 4/ 5  ca n n ot b e e x cl u de d at a G L P G 1 6 9 0 d ose of 6 0 0 m g i n h u ma n, wit h a ma xi mal 
i ncreas e of a p pr o xi matel y 1. 7 - a n d 1. 5 -f ol d, res pecti vel y, i n t he e x p os ure of a se nsiti ve pr o be 
s u bstrate. 
G L P G 1 6 9 0 de m o nstrate d a str o n g ti me -d e pe n d e nt, irre versi ble i n hi biti o n p ote ntial a gai nst 
C Y P 2 C 8 -me diate d meta b olis m. T his c o ul d li kel y lea d t o a pr o n o u nce d i nteracti o n wit h a 
se nsiti ve C Y P 2 C 8 pr o be s u bstrate (i ncrease d e x pos ure) if c o -a d mi nistere d wit h a G L P G 1 6 9 0 
d ose of 6 0 0 m g i n h u ma n.  
N o i nteracti o n of G L P G 1 6 9 0 is e x pecte d wit h re nal u pta ke tra ns p orters, or ga nic cati o n 
tra ns p orter ( O C T) 2, or ga nic a ni o n tra ns p orter ( O A T) 1 a n d O A T 3 a n d he p atic effl u x tra ns p orters 
P -gl yc o pr ot ei n ( P -g p) a n d breast c a ncer resista nce pr otei n ( B C R P). F or t he he patic u pta ke 
tra ns p orters O A T P 1 B 1, O A T P 1 B 3, a n d O C T 1, a n d t he m ulti dr u g a n d t o xi n e xtr usi o n ( M A T E) 
effl u x tra ns p orters M A T E 1 ( he patic/r e nal) a n d M A T E 2 K (re nal), a cli nical i nteracti o n wit h 
G L P G 1 6 9 0 ca n n ot be r ul e d o ut, h o we ver s u bsta ntial i nteracti o ns are n ot a ntici pate d. F or t he 
i ntesti nal effl u x P-g p a n d B C R P tra ns p orters a n d t he he patic effl u x bile salt e x p ort p u m p 
tra ns p orters a n i nteracti o n ca n n ot be r ule d o ut. 
1. 1. 4.   
T o xi c ol o g y  
1. 1. 4. 1.   
G e n er al T o xi c ol o g y  
A c o m pre he nsi v e t o xic ol o g y pr o gra m has bee n c o n d ucte d wit h G L P G 1 6 9 0. T his pr o gra m 
i ncl u des G o o d La b orat or y Practice ( G L P) oral re p eat d ose t o xicit y st u dies of u p t o 2 6 wee ks i n 
rats a n d 3 9 wee ks i n d o gs, e m br y ofetal de v el o p me nt st u dies i n rats an d ra b bits,  fertilit y st u dies i n 
male a n d fe m ale rats, n o n -T gras H 2 mice preli mi nar y st u dies, preli mi nar y carci n o ge nicit y st u dies,  
a n d i n vi v o a n d i n vitr o ge n ot o xicit y st u dies. A d diti o nal t o xic ol o g y st u dies c o n d ucte d i ncl u de  
p h ot ot o xicit y st u dies a n d d ose -ra n ge fi n di n g st u dies i n rats a n d d o gs. 
I n rats, n o G L P G 1 6 9 0-relate d m ortalit y was o bser ve d. T he d ose-li miti n g a d verse effects 
c o nsiste d of re d u ce d f o o d c o ns u m pti o n a n d mar k e dl y d ecrease d b o d y wei g ht ( B W) gai n at 
1 0 0 0  m g/ k g/ da y i n t he 4 -wee k t o xicit y st u d y , hist o pat h ol o gical c ha n ges i n t he testes wit h 
re d uce d s p er m para meters at ≥1 3 0 m g/ k g/ da y i n t he 1 3- a n d 2 6-wee k G L P st u dies, a n d t he 
prese nce of vac u olate d al ve olar macr o p ha ges, wit h al ve olar a m or p h o us material a n d peri vasc ular 
i nfla m mat or y cell i nfiltrati o n i n t he l u n gs of fe mal es i n t he 2 6-wee k G L P st u d y. T he n o o bser ve d 
a d verse effects le vel ( N O A E L) val ues i n rats were set at 4 0 a n d 1 3 0 m g/ k g/ da y i n mal es a n d 
fe males, res pecti vel y, i n t he 2 6-wee k G L P st u d y.  
I n re peat oral d ose t o xicit y st u dies i n d o gs, t he d ose-li miti n g effects c orres p o n de d t o decrease d 
w hite bl o o d cell c o u nt a n d f o o d c o ns u m pti o n, e mesis a n d B W l oss, ass ociate d wit h p o or cli nical 
c o n diti o ns at d oses ≥1 0 0 m g/ k g/ da y i n t he 1 3 - a n d 3 9-wee k G L P st u dies, res pecti vel y. Q T 
pr ol o n gati o n (i n 4 -, 1 3 -, a n d 3 9-wee k st u dies), w hic h was c o nsi dere d n o n -a d verse, were als o 
o bser ve d i n re peat or al d ose t o xicit y st u dies i n d o gs. A d diti o nal fi n di n gs i n d o gs c o nsiste d of 
a d verse altere d s p er m para meters a n d i nfla m mat or y cell i nfiltrates i n t he li ver a n d mi ni mal bile 
d uct h y p er plasia at 1 5 0/ 1 0 0 m g/ k g/ da y (i n t he 1 3 -wee k G L P t o xicit y st u d y) a n d Q T pr ol o n gati o n 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-2 3 - 
 
(i n 4-, 1 3- a n d 3 9-wee k st u dies). T he N O A E L val ue i n d o gs was set at 5 0/ 6 5  m g/ k g/ da y i n t he 
3 9 -wee k G L P st u d y.  
Male a n d fe male fertilit y st u dies i n rats  s h o we d t hat t here were n o effects of G L P G 1 6 9 0 o n 
mati n g perf or ma nce, fertilit y, or re pr o d ucti o n i n eit her male or fe male rats at t he differe nt d ose 
le vels teste d. As t he effects o n s per m a n d testis pr o ve d re versi ble a n d ha d n o f u ncti o nal i m pact 
o n a ni mal fertilit y para m eters, t he ris k of a n i m pact o n male fertilit y i n a d ult s u bjects is 
c o nsi dere d l o w. I n males, t he n o o bser ve d effect l e vel ( N O E L) f or m ati n g perf or ma n ce a n d 
fertilit y was set at 4 0 0 m g/ k g/ da y a n d t h e N O A E L f or s per m c ha n ges was deter mi ne d at  
4 0  m g/ k g/ da y; t he latter is i n li ne wit h pre vi o us st u dies (i.e.  1 3 -wee k rat st u d y). I n fe mal es, t he 
N O E L f or mati n g perf or ma nce a n d fertilit y was c o nsi dere d t o be 1 2 0  m g/ k g/ da y.   
I n re pr o d ucti ve e m br y ofetal de vel o p me nt st u dies wit h G L P G 1 6 9 0 i n rats a n d rab bits, maj or 
e xter nal, visceral, a n d s k eletal a b n or malities were see n i n fet uses of b ot h s pecies as well as 
i ncreas e d i nci de nces of p osti m pla ntati o n l osses. I n rats, t he mater nal a n d de vel o p me ntal 
N O A E Ls were det er mi ne d at 6 0 m g/ k g/ da y a n d 1 0 m g/ k g/ da y, re s p ecti vel y. I n ra b bits, t he 
mater nal a n d de vel o p me ntal N O A E Ls were det er mi ne d at 1 5 m g/ k g/ da y a n d 5 m g/ k g/ da y, 
res pecti vel y. 
G L P G 1 6 9 0 s h o we d n o ge n ot o xic effects i n vitr o or i n vi v o.  
G L P G 1 6 9 0 s h o we d a p h ot ot o xic p ote ntial i n vitr o. H o we ver, t his p ote ntial has n ot bee n 
c o nfir me d i n a n i n vi v o  st u d y i n fe mal e pi g m e nte d L o n g-E va ns rats, i n vesti gati n g t he p h ot ot o xic 
effects o n t he e yes a n d t h e s ki n. N o e vi de nce of c uta ne o us or oc ular p h ot ot o xicit y was n ote d at 
d oses of 1 0 0 a n d 3 0 0 m g/ k g.  
1. 2.   
B a c k gr o u n d - Cli ni c al S t u di e s 
1. 2. 1.   
Cli ni c al S af et y  
I n cli nical p har mac ol o g y st u dies, G L P G 1 6 9 0 has bee n a d mi nistere d t o 8 5 healt h y s u bjects as 
si n gle d oses ( d os e ra n ge: 2 0 t o 1 5 0 0 m g) a n d t o 9 6 healt h y s u bjects i n re peate d d oses ( d ose 
ra n ge: 1 0 0 t o 1 0 0 0 m g f or eit her 7 or 1 4 d a ys).  
A d mi nistrati o n of G L P G 1 6 9 0  i n t hese P hase 1 st u dies was c o nsi dere d safe a n d well t olerate d. N o 
deat hs, ot her seri o us treat me nt -e mer ge nt a d verse e ve nts ( T E A Es), T E A Es lea di n g t o I M P 
disc o nti n uati o n, or cli nicall y si g nifica nt a b n or malities relate d t o la b orat o r y para meters, 
electr ocar di o gra m ( E C G), vital si g ns, or p h ysical e x a mi nati o ns were re p orte d d uri n g a n y of t hese 
P hase  1 st u dies. A ll T E A Es were at m ost m o derat e i n se verit y.  
A d mi nistrati o n of oral d oses of G L P G 1 6 9 0 6 0 0 m g q. d. as a ca ps ul e f or 1 2 wee ks i n 1 7 s u bjects 
wit h I P F was well t olerate d ( P hase 2a S t u d y G L P G 1 6 9 0-C L -2 0 2). N o deat hs were re p orte d. 
Seri o us T E A Es were e x perie nce d b y o ne s u bject i n t he G L P G 1 6 9 0 6 0 0 m g q. d. g r o u p 
(c h ola n gi ocarci n o ma le d t o per ma ne nt disc o nti n uati o n) a n d b y 2  s u bjects i n t he place b o gr o u p 
(atri o ve ntric ular bl oc k sec o n d de gree i n o ne s u bject, le d t o per ma ne nt disc o nti n uati o n; a n d l o wer 
res pirat or y tr act i nfecti o n, uri nar y tract i nfecti o n, a n d acute ki d ne y i nj ur y i n t he ot her s u bject , 
w h o re mai ne d o n tr eat me nt i n t he st u d y ). 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-2 4 - 
 
N o ne of t hese s eri o us T E A Es were c o nsi dere d rel ate d t o I M P acc or di n g t o t he i n vesti gat or. N o 
n ota ble differe nces were o bser ve d i n t he i nci de n ces of treat me nt -e mer ge nt a b n or mal ities bet wee n 
s u bjects wit h I P F treat e d wit h G L P G 1 6 9 0 6 0 0 m g q. d. or place b o. T he maj orit y of T E A Es were 
mil d t o m o derate i n se verit y. N o cli nicall y si g nifica nt a b n or malities relat e d t o la b orat or y 
para meters, electr ocar di o gra m ( E C G), vital si g ns or p h ysica l e xa mi nati o ns were re p orte d. 
1. 2. 2.   
Cli ni c al Effi c a c y  
D uri n g 1 2 wee ks of treat me nt of  s u bjects wit h I P F i n S t u d y G L P G 1 6 9 0-C L -2 0 2, f orce d vital 
ca pacit y ( F V C) val ues re mai ne d sta ble i n t he maj orit y of s u bjects ta ki n g G L P G 1 6 9 0 6 0 0 m g q. d. , 
a n d decli ne d i n s u bject s t a ki n g place b o. 
1. 2. 3.   
Cli ni c al P h ar m a c o ki n eti c s  
G L P G 1 6 9 0 f or m ulate d as a li q ui d s us pe nsi o n was ra pi dl y a bs or be d wit h a me dia n ti me t o 
ma xi m u m o bser ve d plas ma c o nce ntr ati o n (t
ma x ) of 0. 5 t o 2 h o urs. Stea d y -state e x p os ure of 
G L P G 1 6 9 0 i ncreas e d a p pr o xi matel y (sli g ht o ver pr o p orti o nalit y) i n pr o p orti o n wit h t he d ose 
bet wee n 3 0 0  t o 10 0 0  m g t otal dail y d ose. E xcreti o n of u nc ha n ge d G L P G 1 6 9 0 i n h u ma n uri ne 
was l o w ( < 1. 8 % i n 2 4  h o urs) a n d ra pi d. T here was n o i m pact o n t he uri nar y 6 -β -O H -
c ortis ol/c ortis ol ra ti o after re peate d d osi n g s u g gesti n g a lac k of C Y P 3 A 4 i n d ucti o n b y 
G L P G 1 6 9 0.  
Gi ve n as ta blet, f o o d d ecrease d t h e rate of a bs or pti o n of G L P G 1 6 9 0 b ut t here was n o cli nicall y 
rele va nt differe nce i n t he bi oa vaila bilit y of G L P G 1 6 9 0. A hi g her bet w ee n-s u bject varia bilit y was 
o bser ve d i n fast e d state, wit h f o ur  s u bjects o ut of 1 2 ha vi n g 5- t o 1 0-f ol d l o wer e x p os ure t ha n t he 
ot her s u bjects. T he rate of eli mi nati o n was n ot i m pacte d b y f o o d. T he o verall mea n ter mi nal 
eli mi nati o n half -life (t1/ 2) after a si n gle d ose as tablets was  a p pr o xi matel y 1 1  h . 
G L P G 1 6 9 0 e x p os ure is re d uce d u p t o 9 0 % b y t he str o n g C Y P 3 A 4/ p ote nt P -g p i n d ucer rifa m pi n  
( b y 6. 0- a n d 9. 3-f ol d f or Cma x  a n d area u n d er t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 
2 4 h  [ A U C0 -2 4 h], res pecti vel y). E x p os ure of G L P G 1 6 9 0, as meas ure d b y t he area u n der t he 
plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o e xtra p olate d t o i nfi nit y ( A U C0 -∞), was 3- a n d 
4 -f ol d great er w h e n a d mi nistere d i n c o m bi nati o n wit h itrac o naz ole (a str o n g C Y P 3 A 4 a n d p ote nt 
P -g p i n hi bit or) a n d v ori c o naz ole (a str o n g C Y P 3 A 4 i n hi bit or), res pecti vel y, t ha n w h e n as 
a d mi nistere d al o ne. Ma xi m u m e x p os ure ( C ma x ) of G L P G 1 6 9 0 i ncreas e d sli g htl y f oll o wi n g 
a d mi nistrati o n of G L P G 1 6 9 0 i n c o m bi nati o n wit h itrac o naz ole or v oric o n az ole c o m pare d wit h 
a d mi nistrati o n of  G L P G 1 6 9 0 o nl y ( C ma x  val ues were 1. 4 -f ol d greater f oll o wi n g a d mi nistrati o n i n 
c o m bi nati o n wit h itrac o naz ole or v oric o naz ole). T his i ncrease is u nli kel y t o be cli nicall y 
si g nifica nt. G L P G 1 6 9 0 ca n t heref ore b e classifie d as a m o deratel y se nsiti ve s u bstrate o f C Y P 3 A 4 
as it de m o nstrate d a n i ncrease i n A U C of ≥2 t o < 5 -f ol d wit h str o n g i n de x i n hi bit ors. 
T he P K of G L G 1 6 9 0 was si milar bet wee n Ca ucasia n a n d J a pa nese healt h y male s u bjects. T he 
P K of G L P G 1 6 9 0 i n s u bj ects wit h I P F was n ot mar ke dl y differe nt fr o m t h ose o bser ve d i n h ealt h y 
s u bjects at t he sa me d ose le vel. 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-2 6 - 
 
3.   
I N V E S TI G A TI O N A L P L A N 
3. 1.   
Cli ni c al S t u d y D e si g n 
T his is a n o pe n -la bel, m ultice nter, si n gl e-ar m, 1 0 4 -wee k  e xte nsi o n st u d y f or s u bjects wit h 
s yste mic scler osis w h o c o m plete d t he 2 4-wee k d o u ble -bli n d treat me nt peri o d of 
St u d y  G L P G 1 6 9 0 -C L -2 0 4 . U p t o 3 0 s u bjects ma y r oll o ver fr o m St u d y G L P G 1 6 9 0 -C L -2 0 4 i nt o 
t his O L E  st u d y. 
A sc he matic dia gr a m of t he cli nical st u d y d esi g n is pr o vi de d i nFi g ure  1 Fi g ure  1 : Sc he matic 
St u d y O ver vi e w . 
 
Fi g ure  1 : 
Sc he m atic St u d y O ver vie w  
D = Da y, E o T =e n d of  st u d y, F U = F oll o w -u p, V = Visit, W = W ee k.  
 
F or t he i n - a n d e x cl usi o n criteria please refer t o Secti o n 3. 6. 1 , “I ncl usi o n Criteria” a n d 
Secti o n  3. 6. 2 , “E x cl usi o n Criteria ”.  
S u bjects will e nter t h is O L E  st u d y at t he R oll o ver v isit o n Da y 1, w hic h will occ ur o n t he sa m e 
da y as t he Wee k 2 4 visit (t he last visit of t he treat me nt peri o d) of  t he prece di n g G L P G 1 6 9 0-C L -
2 0 4 st u d y. S u bjects w h o r oll o ver t o t his O L E st u d y will partici pat e i n t he p ost treat me nt foll o w -
u p peri o d of t he O L E st u d y i nstea d of F oll o w -u p i n St u d y G L P G 1 6 9 0 -C L -2 0 4.  
After t he R oll o ver v isit, the s u bse q ue nt visits  d uri n g t he o pe n -la bel treat me nt peri o d will ta ke 
place at Wee ks 2, 4, 8 , 1 6, 2 8, 4 0 , 5 2, 6 4, 7 6, 8 8, a n d at Wee k 1 0 4 ( E n d of Treat me nt [E o T ]). I n 
case of wit h dra wal, a n E arl y Disc o nti n uati o n ( E D) visit will be sc he d ule d. After  t he 1 0 4 -wee k 
o pe n -la bel treat me nt peri o d (or earl y dis c o nti n uati o n of treat me nt) , 2  f oll o w-u p visit s will be 
pla n ne d 4  wee ks a n d 1 2 wee ks after t he last a d mi nistrati o n of I M P . A d diti o nal u nsc he d ule d visits 
are all o we d f or a n y safet y ass ess me nts if cli nicall y i n dicat e d . 
S u bjects will recei ve 6 0 0  m g  G L P G 1 6 9 0,  oral l y q. d. , starti n g t he da y after t he R ollo ver visit.  F or 
detaile d i nf or mati o n re gar di n g d osa ge f or m, p ac ka gi n g a n d la bel i n g of t he I M P please refer t o 
Secti o n 4. 2 , “D osa ge a n d A d mi nistrati o n ” a n d Secti o n  4. 3 , “Pac ka gi n g, La b eli n g a n d 
Distri b uti o n ”. 
Eac h s u bject will  be i n t h e st u d y f or u p t o 1 1 6 wee ks ( 1 0 4 wee ks of treat me nt a n d 1 2 wee ks of 
f oll o w-u p).  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-2 9 - 
 
at t his sta ge of de vel o p m e nt , G L P G 1 6 9 0 s h o ul d n ot be gi ve n t o pre g na nt or lactati n g w o me n. I n 
a d diti o n, hi g hl y effecti ve c o ntrace pti ve meas ures/ pre ve nti ve e x p o s ure meas ures s h o ul d be ta ke n 
b y w o me n of c hil d beari n g p ote ntial ( W O C B P)  a n d b y me n  t o pre ve nt pre g na nc y a n d t o a v oi d t he 
ris k of e x p os ure of t he e m br y o or fet us. Det a ile d i nf or mati o n o n c o ntrace pti ve meas ures is gi ve n 
i n Secti on 3. 6. 3. 1 . 
Q T I nter v al Pr ol o n g ati o n  
T he p ote ntial effect of G L P G 1 6 9 0 o n Q T i nter val pr ol o n gati o n is u n der i n vesti gati o n . 
C o nse q ue ntl y, s u bjects meeti n g t he st o p pi n g r ules f or Q T/ Q Tc -c ha n ges  will be e x cl u de d. T he 
c hr o nic use or i nitiati o n of me dicati o n k n o w n t o pr ol o n g t he Q T i nter val n ee ds t o be e v al uate d o n 
a case -b y -case b asis. Peri o dic E C G rec or di n g a n d m o nit ori n g wit h ce ntral rea di n g will be 
i m ple me nte d f or t he d urati o n of t he st u d y. A list i nte n de d as g ui da nce f or t he i n vesti gat or is 
pr o vi de d i n A p pe n di x  5 . 
Dr u g -dr u g I nter acti o n  
F or p ote ntial c o n c o mita nt me dicati o n i nteracti o ns, s pecific m o nit ori n g a n d g ui da nce will be 
i m ple me nte d d uri n g t he st u d y (refer t o Secti o n 3. 6. 3. 2 ).  
S peci al P o p ul ati o ns  
As t here is li mite d cli nical e x perie nce wit h G L P G 1 6 9 0 s o far, t he I M P s h o ul d n ot be 
a d mi nistere d t o s u bjects wit h m o derate t o se vere re nal i m pair me nt or h e p atic i m pair me nt.  
Refer t o t he latest I B f or G L P G 1 6 9 0 a n d rele va nt u p dates/a d de n da f or a d diti o nal i nf or mati o n o n 
t he safet y of t he I M P. 
3. 6.   
Cli ni c al St u d y P o p ul ati o n  
3. 6. 1.   
I n cl u si o n Crit eri a 
S u bjects 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 p artici pati o n i n t his 
st u d y: 
1.  Male or fe m ale s u bjects w h o c o m plete d t he 2 4 -wee k treat me nt peri o d of St u d y G L P G 1 6 9 0 -
C L -2 0 4 a n d w h o  acc or di n g t o t he i n vesti gat or’s j u d g me nt  ma y b e ne fit fr o m l o n g-ter m 
treat me nt wit h G L P G 1 6 9 0. 
2.  A ble a n d willi n g t o c o m pl y wit h t he pr ot oc ol re q uire me nts a n d t o si g n t h e i nf or me d c o ns e nt 
f or m (I C F) as a p pr o ve d b y t he I n d e pe n d e nt Et hics C o m mittee (I E C) / I nstit uti o nal Re vie w 
B oar d ( I R B), pri or t o t he eli gi bilit y e v al uati o n.  
3.  S u bject m ust be a ble a n d willi n g t o c o m pl y wit h restricti o ns o n c o nc o mita nt me dicati o n as  
descri be d i n Secti o n 3. 6. 3. 2 . 
4.  Fe male s u bjects of c hil d beari n g p ote ntial m ust ha ve a ne gati ve  uri ne pre g n a nc y test . 
5.  Fe male s u bjects of c hil d beari n g p ote ntial or male s u bjects wit h fe male  part ners of 
c hil dbeari n g p ote ntial are willi n g t o c o m pl y wit h t he c o ntrace pti ve met h o ds descri be d i n  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 0 - 
 
Secti o n  3. 6. 3. 1  d uri n g t h e cli nical st u d y  a n d f or at least 9 0 da ys after t he last d ose of t he I M P 
f or male s u bjects a n d at l east 3 0  da ys after t he last d ose of t he I M P f or fe m ale s u bjects. 
 
3. 6. 2.   
E x cl u si o n Crit eri a  
S u bjects meeti n g o ne or m ore of t he f oll o wi n g criteria ca n n ot b e e nr olle d i n t his cli nical st u d y:  
1.  I n v esti gat or or ot her st u d y staff or relati ve t here of w h o is directl y i n v ol ve d i n t he c o n d uct of 
t he st u d y. 
2.  A n y c o n diti o n or circ u msta nces t hat , i n t he o pi ni o n of t he i n vesti gat or, ma y ma ke a s u bject 
u nli kel y or u na bl e t o c o m plete t he st u d y or c o m pl y wit h st u d y pr oce d ures a n d re q uire me nts.  
3.  Persiste nt a b n or mal la b orat or y v al ues (i ncl u di n g a n d n ot li mi te d t o he mat ol o g y, li ver a n d 
re nal f u n cti o n val ues), acc or di n g t o t he i n v esti gat or’s cli nical j u d g me nt (c o nsi deri n g 
s yste mic scler osis diseas e- a n d me dicati o n -rel ate d c ha n ges). 
4.  Fe male s u bject i nte n di n g t o bec o me pre g n a nt or breastfee d.  
5.  A hist or y of bei n g a d mitte d t o a n i nstit uti o n u n der a n a d mi nistrati ve or c o urt or der, if 
a p plica ble b y l ocal le gisl ati o n.  
 
3. 6. 3.   
Pr o hi biti o n a n d R e stri cti o n s  
3. 6. 3. 1.   
Pr e c a uti o n s f or S e x u al Int er c o ur s e  
Hi g hl y effecti ve c o ntrace pti ve meas ures f or b ot h fe males of c hil d beari n g p ote ntial a n d males 
m ust be d oc u me nte d i n t he s o urce d o c u me nts.  
3. 6. 3. 1. 1.  F e m al e S u bj e ct s  
I n li ne wit h the Hea ds of Me dici nes A ge n cies’  Cli nical Trial Facilitati o n Gr o u p rec o m me n d ati o n, 
fe male s u bjects are c o nsi dere d of n o n-c hil d beari n g p ote ntial if t he y meet o ne of t he f oll o wi n g 
criteria:  
 
N o me nses f or 1 2 or m ore m o nt hs wit h o ut a n alter nati ve me dical ca use. A hi g h f ollicle 
sti m ulati n g h or m o ne ( F S H) le vel i n t he p ostme n o pa usal  ra n ge ma y be use d t o c o nfir m a 
p ost me n o pa usal  state i n w o me n n ot usi n g h or m o nal c o ntrace pti o n or h or mo nal re place me nt 
t hera p y. H o we ver, i n t he a bse nce of 1 2 m o nt hs of a me n orr hea, a si n gle F S H meas ure m e nt is 
i ns ufficie nt. 
 
Per ma ne ntl y s ur gicall y st erile ( bilateral o o p h orect o m y, i.e. s ur gical re m o val of o varies, 
bilateral sal pi n gect o m y or h ysterect o m y, i.e. s ur gi cal re m o val of uter us). 
All ot her fe male s u bjects are c o nsi d ere d t o be of c hil d beari n g p ot e ntial ( W O C B P) a n d m ust use 
o ne of t he f oll o wi n g hi g hl y effecti ve met h o ds of birt h c o ntr ol d uri n g t he cli nical st u d y a n d f or at 
least 3 0 da ys  after t he last d os e of I M P:  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 1 - 
 
 
C o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) ( oral, i ntra va gi n al, tra ns d er mal) h or m o nal 
c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n pl us a barrier met h o d 1 
 
Pr o gester o ne -o nl y h or m o nal ( oral, i njecta bl e, i m pla nta ble) c o ntrace pti o n ass oc iate d wit h 
i n hi biti o n of o v ulati o n pl us a barrier met h o d1 
 
I ntr a uteri ne de vice 
 
I ntr a uteri ne h or m o ne-rel easi n g s yst e m 
 
Bilateral t u bal occl usi o n  
 
Se x u al a bsti ne nce defi ne d as refrai ni n g fr o m het er ose x ual i nterc o urse is c o nsi dere d a hi g hl y 
effecti ve c o ntr ace pti ve m eas ure o nl y if it is t he preferre d a n d us ual lifest yle of t he s u bject. T he 
relia bilit y of se x ual a bsti ne nce n ee ds t o be e v al uat e d i n relati o n t o t he d urati o n of t he cli nical 
st u d y.  
Peri o dic a bsti ne nce ( e. g. cale n dar, s y m pt ot her mal, p ost o v ulati o n  met h o ds), declarati o n of 
a bsti ne nce f or t he d urati o n of a cli nical st u d y, wit h dra wal, s per mici des o nl y , a n d lactati o nal 
a me n orr hea met h o d are n ot acce p t a ble as met h o ds of c o ntrace pti o n. 
I n case a W O C B P has a vasect o mize d part ner, pr o vi de d t hat part ner is t he s ole se x ual part ner of 
t he W O C B P cli nical st u d y partici pa nt a n d t hat t he vasect o mize d part ner has recei v e d me dical 
assess me nt of t he s ur gical s ucces s, t he n s he is n ot re q uire d t o use a n a d diti o nal f or m of 
c o ntrace pti o n.  
Wit hi n t hese li mits, t he s pecific f or ms of c o ntrace pti o n e m pl o ye d are left t o t he discreti o n of t he 
s u bject, t he i n vesti gat or, a n d/ or t he s u bject’s p h ysicia n. 
W O C B P will be re q ueste d t o d o a m o nt hl y uri ne pre g na nc y t est d uri n g t h e treat me nt peri o d. I n 
m o nt hs wit h n o st u d y visit, t he m o nt hl y pre g na n c y test  will be perf or me d at h o me b y t h e s u bject 
usi n g h o me testi n g kits. T he site will i nstr uct t he s u bjects o n h o w t o use a n d rea d t he pre g na n c y 
tests. T he o utc o me m ust be d oc u me nte d o n t he s u bject diar y car d a n d t h e site will o btai n t he 
res ults a n d rec or d i n t he case re p ort f or m ( C R F). I n case of a p ositi ve uri ne pre g na nc y t est at 
h o me, t he s u bjec t s h o ul d i m me diatel y c o ntact t he cli nical st u d y ce nter a n d t he i n vesti gat or m ust 
re p ort t his i m me diatel y, a n d u n der n o circ u msta n ces later t ha n 2 4 h o urs after bei n g ma de a ware . 
T he safet y of G L P G 1 6 9 0  d uri n g breastf ee di n g is u n k n o w n. N ursi n g w o me n  are n ot all o we d t o 
ta ke part i n t his cli nical st u d y. 
3. 6. 3. 1. 2.  M al e S u bj e ct s  
Me n s h o ul d be a d vise d n ot t o fat her a c hil d w hile recei vi n g treat me nt a n d m ust use effecti ve 
c o ntrace pti o n d uri n g a n d u p t o 9 0 da ys after treat me nt.  
                                                 
1 As t here is n o c urre nt data a vaila ble re gar di n g p ote ntial i nteracti o ns bet wee n I M P a n d h or m o nal c o ntrace pti ves, 
fe male s u bj ects w h o use h or m o nal c o ntrace pti o n s h o ul d s u p ple me nt t his wit h a barrier met h o d ( prefera bl y male 
c o n d o m).  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 2 - 
 
N o n -vasect o mize d male s u bjects wit h fe male part n ers of c hil d beari n g p ote ntial m ust be willi n g 
t o use a c o n d o m fr o m t he ti me of t he first d ose of I M P, d uri n g t he cli nical st u d y a n d f or at least 
9 0 da ys  after t h e last d ose of I M P, i n a d diti o n t o ha vi n g t heir fe male part ner use o ne  of t he 
f oll o wi n g f or ms of c o ntr ace pti o n: 
 
C o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) ( oral, i ntra va gi n al, tra ns d er mal) h or m o nal 
c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n  
 
Pr o gester o ne -o nl y h or m o nal ( oral, i njecta bl e, i m pla nta ble) c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o n 
 
I ntr a uteri ne de vice 
 
I ntr a uteri ne h or m o ne-rel easi n g s yst e m 
Se x ual a bsti ne nce defi ne d as refrai ni n g fr o m heter ose x ual i nterc o urse is c o nsi dere d a hi g hl y 
effecti ve c o ntrace pti ve meas ure o nl y if it is t he preferre d a n d us ual lifest yl e o f t he s u bject. T he 
relia bilit y of se x ual a bsti ne nce nee ds t o b e e v al uat e d i n relati o n t o t h e d urati o n of t he cli nical st u d y.  
Peri o dic a bsti ne nce ( e. g. cale n dar, s y m pt ot her mal a n d p ost o v ulati o n  met h o ds), declarati o n of 
a bsti ne nce f or t he d urati o n of a cli n ical st u d y, wit h dra wal, s per mici des o nl y a n d lactati o nal 
a me n orr hea met h o d are n ot acce pt a ble met h o ds of c o ntrace pti o n.  
I n a cas e w here t he fe mal e part ner of a mal e s u bject has u n der g o n e d oc u me nte d s ur gi cal 
sterilizati o n t hat was perf or me d m ore t ha n o n e  ye ar bef ore scree ni n g, t he n t he s u bject is n ot 
re q uire d t o use a n a d diti o nal f or m of c o ntrace pti o n. 
Vasect o mize d male s u bjects wit h fe male part ners of c hil d beari n g p ote ntial are n ot re q uire d t o use 
a n a d diti o nal f or m of c o ntrace pti o n pr o vi di n g t hat s ur gical sterilizati o n has bee n s uccessf ul 
( d oc u me nte d az o os per mi a b y s e me n a n al ysis). 
Male s u bjects w h o wis h t o fat her a c hil d s h o ul d st o p treat me nt wit h I M P a n d wait f or at least 
9 0  da ys b ef ore st o p pi n g t he c o ntrace pti ve meas ures detaile d i n t his secti o n.  
N o s per m d o nati o n is all o we d fr o m t he first d ose of I M P d uri n g t he cli nical st u d y u ntil at least 
9 0  da ys  after t h e last d ose  of I M P . 
3. 6. 3. 2.   
Pri or a n d C o n c o mit a nt M e di c ati o n s  
C o nc o mit a nt Me dic ati o n  
S h o ul d a n y treat me nt ot her t ha n t he I M P be us e d d uri n g t he c o urse of t he st u d y, t he na m e of t he 
me dicati o n, t he d osa ge, t he r o ute, t he reas o n f or me dicati o n, a n d t he start a n d st o p dates of 
a d mi nistrati o n m ust be rec or de d i n t he C R F u ntil foll o w -u p v isit 2.  
C o nc o mita nt me dicati o ns ta ke n f or t he l o n g -t er m treat me nt of pre-e xisti n g c o n diti o ns ca n 
c o nti n ue d uri n g t h e S t u d y G L P G 1 6 9 0 -C L -2 0 6 . It is re q uire d t hat t hese m e dicati o ns co nti n ue 
wit h o ut variati o n of d ose or re gi me n d uri n g t he st u d y.  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 3 - 
 
I n case a d diti o nal c o nc o mita nt me dicati o n nee ds t o be a d mi nistere d or d os e a dj ust me nts f or 
pre -e xisti n g c o n diti o ns nee d t o be perf or me d d uri n g t he st u d y, t he be n efit -ris k t o t he s u bject 
s h o ul d be caref ull y assesse d a n d c o nsi derati o n gi v e n t o t he ti mi n g of a n y n ecessar y i ntr o d uc ti o n 
of ne w me dicati o ns.  
T he f oll o wi n g m e dicati o ns are pr o hi bite d d uri n g t he treat me nt peri o d:  
 
warfari n, a ntifi br otic a ge nts (i ncl u di n g c olc hi ci ne, mi n oc ycli ne, t yr osi n e ki nase i n hi bit ors 
[ nil oti ni b, i mati ni b, dasati ni b, ni nte da ni b], pirfe ni d o ne), or T y p e 1 oral c oll a ge n  
 
stea d y d os e of pre d nis o n e or its e q ui vale nt > 1 0 m g/ da y, met h otre x ate > 2 0 m g/ wee k, 
azat hi o pri ne > 1 5 0  m g/ d a y, M M F  > 3 g/ da y, m yc o p he n olic aci d > 2. 1 6 g/ d a y, lefl u n a mi de 
> 2 0  m g/ da y  
 
cycl o p h os p ha mi de  a n d t h e f oll o wi n g bi ol o gics: t o ciliz u ma b or ot her dr u gs tar geti n g I L -6/I L -
6 rece pt or, a bat ac e pt, a nti -t u m or necr osis fact or dr u gs, rit u xi ma b, beli m u ma b, or ot her 
m o n ocl o nal a nti b o dies   
 
b ose nta n  
 
If d uri n g t he st u d y, t he s u bject’s c o n diti o n necessitates t he use of o ne of t he a b o ve-m e nti o ne d 
me dicati o ns (e x cl u di n g pre d nis o ne or its e q ui vale nt > 1 0 m g/ da y), t he use of I M P s h o ul d be 
i nterr u pte d u ntil res ol uti o n or sta bilizati o n of t his c o n diti o n, prefera bl y after c o ns ultati o n wit h t he 
c o ntract r esearc h or ga nizati o n ( C R O ) me dical m o nit or (as per st u d y c o n tact list) or s p o ns or’s 
st u d y p h ysicia n (if t h e f or mer is n ot a vaila ble).  
Prec a uti o ns W it h C o nc o mit a nt M e dic ati o n K n o w n t o P r ol o n g t he Q T Inter v al  
T he use of me dicati o n k n o w n t o pr ol o n g Q T i nter val d uri n g t he st u d y n ee ds t o be base d o n a 
be nefit -ris k e v al uati o n b y t he i n vesti gat or, e. g. i n t he case of atrial fi brillati o n. I n certai n ot her 
sit uati o ns (e. g. t he i nitiati o n of macr oli des or fl u or o q ui n ol o nes i n case of a l o wer res pirat or y tract 
i nfecti o n), w he n t h e be nefit-ris k e val uati o n necessitates t he ad mi nistrati o n of me dicati o n k n o w n 
t o or p ote ntiall y pr ol o n gi n g Q T, I M P ca n be i nterr u pte d as e val uat e d b y t he i n vesti gat or after 
cli nical assess me nt of t he s u bject’s pr ofile, i ncl u di n g t he baseli ne Q Tc F a n d h o w t his has 
c ha n ge d o v er ti me f or t his s pecific s u bject. If t he i n vesti gat or elects t o c o nti n ue I M P, a d diti o nal 
m o nit ori n g will be perf or me d as per i n vesti gat or’s j u d g me nt. A n o n -e x ha usti ve list of me dicati o n 
k n o w n t o pr ol o n g Q T i nt er val is pr o vi de d i n A p pe n di x 5 . N ote: I n case Q T i nter val pr ol o n gati o n 
is re p orte d i n a s u bject w hile recei vi n g o ne of t hes e me dicati o ns, t he i n vesti gat or s h o ul d f oll o w 
t he la bels a n d Ris k E val u ati o n a n d Miti gati o n Strate gies g ui da nce.  
Prec a uti o ns W it h O t her C o nc o mit a nt M e dic ati o ns 
At d ose l e vels of 6 0 0 m g q. d., G L P G 1 6 9 0 has t he p ote ntial t o s u bsta ntiall y i nfl ue nce t he 
meta b olis m of C Y P 2 C 8 s u bstrates a n d t o p ote ntiall y be i nfl ue n ce d b y k n o w n str o n g 
C Y P 3 A 4/ p ote nt P -g p i n d ucers/i n hi bit ors.  
 
G L P G 1 6 9 0 de m o nstrate d a str o n g ti me -d e pe n d e nt i n hi biti o n p ote ntial a gai nst C Y P 2 C 8 
me diate d meta b olis m. C o nse q ue ntl y, G L P G 1 6 9 0 s h o ul d n ot be use d c o nc o mita ntl y wit h 
me dicati o ns pri maril y or s olel y meta b olize d via C Y P 2 C 8 (see A p pe n di x 1 ). F or ot her 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 4 - 
 
me dicati o ns i n v ol vi n g part of t heir meta b olis m pat h wa y via C Y P 2 C 8, ca uti o n s h o ul d be 
a p plie d o n a case -b y -cas e basis ta ki n g i nt o c o nsi d erati o n t he be n efit -ris k rati o. Stati ns s uc h 
as fl u vastati n a n d pita vastati n are meta b olize d t o s o me de gree b y C Y P 2 C 8, a n d nee d t o be 
use d wit h ca uti o n. Ot her st ati ns s uc h as si m vastati n, l o vastati n, a n d at or vastati n are 
t he oreticall y less meta b olize d b y C Y P 2 C 8. M o nit ori n g of li ver f u ncti o n tests (L F Ts ) a n d 
creati ne ki n ase is i m ple me nte d d uri n g t he st u d y, a n d g ui da nce t o t he s u bject ali g ne d wit h 
g ui da nce f or stati ns i n cli nical practice is t heref ore str o n gl y rec o m me n de d. L o pera mi de is 
als o a s u bstrate of C Y P 2 C 8, a n d s pecial ca uti o n s h o ul d be a p plie d i n ali g n me nt wit h cli nical 
practice.  
 
G L P G 1 6 9 0 is a s u bstrate of C Y P 3 A 4 a n d P -g p, a n d c o ul d t heref ore be i nfl ue nce d b y  t heir 
res pecti ve i n hi bit ors a n d i n d ucers. G L P G 1 6 9 0 e x p os ure is re d uce d u p t o 9 0 % b y t he str o n g 
C Y P 3 A 4/ p ote nt P -g p i n d ucer rif a m pi n. As a c o ns e q ue nce, str o n g i n d ucers of C Y P 3 A 4 
a n d/ or P -g p s h o ul d b e a v oi de d d uri n g t he st u d y t o e ns ure pr o per e x p os ure t o G L P G 1 6 9 0 (s ee 
A p pe n di x 2 ). G L P G 1 6 9 0 e x p os ure i ncreas e d b y 3 t o 4 f ol d w he n c oa d mi nistere d  wit h str o n g 
C Y P 3 A 4 i n hi bit ors a n d d ual str o n g 3 A 4 a n d p ote nt P -g p i n hi bit ors c o m pare d t o G L P G 1 6 9 0 
a d mi nistere d al o ne. T h eref ore  us e of k n o w n str o n g C Y P 3 A 4 i n hi bit ors a n d p ote nt P -g p 
i n hi bit ors is pr o hi bite d d uri n g t he st u d y (see A p pe n di x 3  a n d A p pe n di x 4 ). A nti bi otics fr o m 
t he macr oli de t hera pe utic class are e x cl u de d, u nless t he y are use d f or t he s h ort-ter m 
treat me nt of a l o w er res pirat or y tract i nfecti o n wit h i nterr u pti o n of I M P, w hic h is restarte d as 
s o o n as p ossi ble after t he c o m pleti o n of t he treat m e nt wit h macr oli des. 
 
It is hi g hl y rec o m me n d e d t hat t he C R O me dical m o nit or (as per st u d y c o ntact list) or s p o ns or’s 
st u d y p h ysicia n (if t h e f or mer is n ot a vaila ble) are c o ns ulte d bef ore t he i nitiati o n of ne w c o -
me dicati o n, i n partic ular me dicati o n k n o w n t o pr ol o n g Q T i nter val, t o be a C Y P 2 C 8 s u bstrate, or 
t o i n hi bit or i n d uce P-g p/ C Y P 3 A 4.  
I n cert ai n sit uati o ns, w he n t he be nefit-ris k e val uati o n necessitates t he a d mi nistrati o n of 
me dicati o n e x cl u de d fr o m use d uri n g t he st u d y, t he use of I M P s h o ul d be i nterr u pte d u ntil 
res ol uti o n or sta bilizati o n of t his c o n diti o n, prefera bl y after c o ns ultati o n wit h t he C R O me dical 
m o nit or (as per st u d y c o ntact list) or s p o ns or’s st u d y p h ysicia n (if t he f or mer is n ot a vaila ble) a n d 
restarte d as s o o n as p ossi ble.  
As a r ule, i ncl usi o n of s u bjects wit h sta ble c hr o nic ill ness o n sta ble me dicati o ns t hat are 
meta b olize d/tra ns p orte d b y t he a b o ve -me nti o ne d C Y P/tra ns p orter e nz y mes s h o ul d be deci de d o n 
a case -b y -case b asis if n ot e xcl u de d or pr o hi bite d, ta ki n g i nt o acc o u nt t he me dical hist or y, 
c o nc o mita nt me dicati o n of t he s u bject, t he t hera p e utic i n de x of t he me dicati o n, a n d safet y pr ofile.  
As i n dicate d i n t he st u d y c o ntact list, t he C R O me dical m o nit or s h o ul d be c o ntacte d, or t he 
s p o ns or’s st u d y p h ysicia n i n case t he f or mer is n ot a vaila ble ( w he n dee m e d necessar y b y t he 
i n vesti gat or), s p ecificall y f or me dicati o n wit h a narr o w t hera pe utic i n de x a n d/ or a ris k of 
( u n) pre dict a ble A Es.  
Resc ue M e dic ati o n  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 5 - 
 
If t he s u bject s h o ws a w orse ni n g of his/ her s yste mic scler osis disease c o n diti o n (e. g. ac ute 
e x acer bati o n), all treat me nt o pti o ns are all o we d at t he i n vesti gat or’s discreti o n. T he dec isi o n t o 
c o nti n ue t he I M P s h o ul d be ta ke n o n a case -b y -cas e basis.  
3. 6. 3. 3.   
F o o d a n d B e v er a g e R e stri cti o n s  
T he use of St. J o h n’s W ort is pr o hi bite d d uri n g t he st u d y.  
D o u ble -stre n gt h gra pefr uit j uice is p ote ntiall y a p ote nt C Y P 3 A 4 i n hi bit or a n d t heref ore s h o ul d be 
av oi de d d uri n g t he st u d y.  
3. 6. 3. 4.   
Ot h er Pr o hi biti o n s a n d R e stri cti o n s  
N ot a p plica ble.  
3. 6. 4.   
Tr e at m e nt Di s c o nti n u ati o n ( T e m p or aril y a n d P er m a n e ntl y), S u bj e ct 
Wit h dr a w al a n d St u d y T er mi n ati o n  
A s u bject ma y be wit h dr a w n fr o m t he cli nical st u d y at a n y ti me wit h o ut t he s u bject’s c o ns e nt if 
t he i n vesti gat or or s p o ns or deter mi nes t hat it is n ot i n t he best i nterest of t he s u bject t o c o nti n ue 
partici pati o n. I n s uc h cas e, t he reas o n f or wit h dra wal wil l be d oc u me nte d i n t he s o urce 
d oc u me nts, a n d t he s u bject will c o m plete t he E D  v isit a n d, or foll o w -u p v isit(s) f or safet y 
assess me nts.  
Treat me nt wit h I M P s h o ul d be disc o nti n ue d b y t h e i n vesti gat or ( prefera bl y after disc ussi o n wit h 
t he C R O me dical m o nit or, w h o ma y c o ns ult a n d m ust i nf or m t he s p o ns or’s st u d y p h ysicia n) f or 
a n y of t he f oll o wi n g c o n diti o ns:  
 
Lif e -t hreate ni n g A E  or a n  S A E  t hat places t he s u bject at i m me diate ris k. 
 
Seri o us i nfecti o ns dee me d relate d t o st u d y treat me nt b y t he i n vesti gat or, a n d re q ui ri n g 
pare nteral a nti micr o bial t hera p y a n d/ or h os pitalizati o n . 
 
C o nfir me d pre g na n c y . If a s u bject bec o m es pre g n a nt d uri n g t he st u d y (t o be c o nfir me d b y 
l ocal ser u m pre g n a nc y test; ce ntral meas ure me nt will als o be perf or me d), t he I M P has t o be 
st o p pe d i m me diatel y a n d t he s u bject has t o be f oll o we d u p u ntil birt h or ot her wise 
ter mi nati o n of pre g na n c y. T he s u bject ma y  be u n bli n de d t o t he treat me nt recei ve d d uri n g 
G L P G 1 6 9 0 -C L -2 0 4 if a p pr o priate. R e peat c o u nseli n g o n birt h defect ris k m ust be offere d . 
 
Arr h yt h mia or c o n d u cti o n a b n or malit y, i ncl u di n g b ut n ot li mite d t o pr ol o n ge d Q T i nter val 
c orrecte d f or t he heart rat e usi n g Fri dericia’s f or m ula ( Q Tc F), w h ere t h e se verit y is 
cate g orize d as C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E) Gra d e 3 or 
hi g her ( Q Tc > 5 0 0 ms o n at least 2  se parate E C Gs). 
 
A n i ncreas e f or Q Tc F wit h > 6 0 ms c ha n ge  fr o m t he G L P G 1 6 9 0 -C L -2 0 4 b aseli ne or 
Q Tc F  > 5 0 0 ms at a n y E C G rec or di n g  n ee ds t o be c o nfir me d b y a n E C G rec or di n g as s o o n as 
p ossi ble after t he ori gi nal a b n or mal rec or di n g at t h e sa me visit. If t he a b n or mal rec or di n g is 
disc o vere d after t h e visit, t he rec o r di n g s h o ul d be c o nfir me d as s o o n as p ossi ble. I n case of 
a n a b n or mal E C G o n b ot h of t hese 2  rec or di n gs is c o nfir me d, t he i n vesti gat or nee ds t o se n d 
a n i m me diate alert t o t he C R O me dical m o nit or (as per st u d y c o ntact list) or s p o ns or’s st u d y 
p h ysicia n (if t he f or m er is n ot a vaila ble). If t he E C G a b n or malit y is bef ore I M P i nta ke, I M P 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 6 - 
 
a d mi nistrati o n will be wit h hel d u ntil t he ce ntral rea der has re vie we d t he E C G re gistrati o n. I n 
case of c o nfir mati o n of t he E C G a b n or malit y, I M P will be te m p orarily dis c o nti n ue d f or t his 
s u bject.  
 
I n crease i n L F Ts : 
 
As partate a mi n otra nsferase ( A S T) a n d/ or ala ni ne a mi n otra nsferase ( A L T) ele vati o ns 
> 8 x u p per li mit of n or mal ( U L N).  
 
A S T a n d/ or A L T ele vati o ns > 3 x U L N  wit h si g ns of se vere li ver da m a ge (i.e. wit h t he 
a p peara nce of fati g u e , na usea, v o miti n g, ri g ht u p p er q ua dra nt pai n or te n der ness, fe v er, 
ras h a n d/ or e osi n o p hilia [ > 5 %], a n d/ or t otal bilir u bi n ≥1. 5 x U L N or i nter nati o nal 
n or malize d rati o [I N R] > 1. 5).  
 
A S T or A L T ≥3 x U L N f or m ore t ha n 2 wee ks . 
 
Cli nical la b orat or y test s u g gesti ve of c h olestasis wit h t otal ser u m bile aci d le vels 
> 3 x  U L N o n a s a m ple ta ke n i n faste d state (at least 8  h o urs faste d). If t he r o uti ne 
ra n d o m or p ost pra n dial t otal ser u m bile aci d sa m ple is > 3 x U L N, t he n t he s u bject s h o ul d 
ha ve a faste d sa m ple ta k e n wit hi n 1 t o 5 da ys. T he res ults of t his test will deter mi ne 
w het her t he s u bject s h o ul d disc o nti n ue I M P or n ot.  
 
F or a s u bject ha vi n g:  
 
A S T or A L T ≥8 x U L N  
 
A S T or A L T ≥3 x U L N wit h si g ns of se vere li ver da ma ge (i.e. wit h t he a p peara nce of 
fati g u e, na usea, v o miti n g, ri g ht u p per q ua dra nt pai n or te n der ness, fe v er, ras h a n d/ or 
e osi n o p hilia [ > 5 %], a n d/ or t otal bilir u bi n ≥1. 5 x U L N or I N R > 1. 5)  
 
t he f oll o wi n g ste ps will n ee d t o be perf or me d b y t he i n vesti gat or:  
 
T he site s h o ul d i m me diatel y c o ntact t he s u bject a n d re q uire t he s u bject t o disc o nti n ue I M P 
i m me diatel y. T he s u bject s h o ul d be as ke d t o ret ur n t o t he site wit hi n a 4 8-h o ur wi n d o w fr o m 
a ware ness of t he res ult.   
 
A n assess me nt of ot her c o nc o mita nt me dicati o ns s h o ul d be ma de. T he i n vesti gat or s h o ul d 
c o nsi der w het h e r is i n t he best i nterest of t he s u bj ect t o i nterr u pt c o nc o mita nt me dicati o ns.  
 
A detaile d hist or y i ncl u di n g rele va nt i nf or m ati o n o n alc o h ol use, recreati o nal dr u g use, 
s u p ple me nt c o ns u m pti o n, a n y h er bal re me dies, fa mil y hist or y, se x ual hist or y, tra vel his t or y, 
hist or y of c o ntact wit h a ja u n dice d s u bject, s ur ger y, occ u pati o nal hist or y, bl o o d tra nsf usi o n, 
hist or y of li ver or aller gi c disease, a n d a n y ot her p ote ntial ca uses of a li ver i ns ult s h o ul d be 
c ollecte d.  
 
A detaile d assess me nt of t he s u bject’s cli nica l c o n diti o n a n d re peat la b orat or y tests f or L F T, 
i ncl u di n g al b u mi n, creati ne ki nase, t otal bilir u bi n ( direct a n d i n direct), ga m ma gl uta m yl 
tra nsferase, I N R a n d al kali ne p h os p hatase s h o ul d be d o ne.  
 
F urt her t esti n g f or h e patitis A, B, a n d C, a n d f or a ut oi m m u ne he patitis s h o ul d be d o ne. Ot her 
ca uses of viral he patitis ( C yt o m e gal o vir us  or E pst ei n -Barr vir us  etc) s h o ul d be e x cl u de d.  
Li ver i ma gi n g s h o ul d be c o nsi dere d.  
 
Referral t o a he p at ol o gist or gastr oe nter ol o gist s h o ul d be c o nsi dere d.  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 7 - 
 
 
All t hese cases s h o ul d be re p orte d as S A Es.  
 
E ver y eff ort s h o ul d be m a de t o kee p s u bjects i n t he st u d y a n d o n treat me nt. H o we ver, t he 
i n vesti gat or ca n c o nsi der st o p pi n g t he treat me nt wit h I M P, prefera bl y after c o ns ultati o n wit h t he 
s p o ns or’s st u d y p h ysicia n, i n case of c o ncer ns a b o ut t he s u bject’s safet y, maj or pr ot oc ol 
n o nc o m plia nce, seri o us or se vere A Es or w orse ni n g of t he dis ease c o n diti o n, w hic h i n t he 
i n vesti gat or’s o pi ni o n nee ds a n alter nati ve treat me nt a p pr oac h n ot bei n g c o vere d i n t he cli nical 
st u d y (e. g. resc u e me dicati o n) . 
W he n st u d y treat me nt is disc o nti n ue d, t he s u bject will be re q ueste d t o ret ur n f or t he E D v isit a n d 
t he F oll o w -u p visits.  
S u bjects will be i nf or me d pri or t o cli nical st u d y e ntr y t hat t he y are all o we d t o wit h dra w fr o m t he 
cli nical st u d y. At a n y ti m e a n d f or a n y reas o n, a s u bject’s partici pati o n i n t h e cli nical st u d y m a y 
ter mi nate at his/ her re q uest wit h o ut prej u dice t o his/ her f ut ure me di cal care. T he s u bject will be 
e nc o ura ge d t o s hare t he reas o n(s) f or wit h dra wal s o t his ca n be d oc u me nte d i n t he s o urce 
d oc u me nts, a n d t o c o m plete  t he E D v isit an d F oll o w -u p v isits f or safet y assess me nts, b ut will n ot 
be o bli ge d t o d o s o.  
S u bjects w h o wit h dra w fr o m t he cli nical st u d y wit h o ut c o ntact wit h t he site (l ost -t o-f oll o w-u p) 
s h o ul d be c o ntacte d b y t h e site s o t hat t heir healt h stat us ca n be ass esse d a n d d oc u me nte d i n t he 
s o urce d oc u m e nts. T he site s h o ul d ma ke e ver y eff ort t o u n dersta n d w het her t he s u bject is ali ve, 
i ncl u din g c h ec ki n g t he m e dical rec or ds  a n d c o ntacti n g ge neral practiti o ner or relati ves, if 
n ecessar y. All atte m pts m ust be d oc u me nte d i n t he s o urce d o c u me nts. S u bjects w h o disc o nti n ue 
I M P or t he st u d y will n ot be re place d. 
T he s p o ns or has t he ri g ht t o ter mi nate t he cli nical st u d y at a n y ti me i n case of safet y c o n cer ns or 
if s pecial cir c u msta nces c o ncer ni n g t he I M P or t he c o m pa n y itself occ ur, ma ki n g f urt her 
treat me nt of s u bjects i m p ossi ble. I n t his e ve nt, t he i n vesti gat or(s) a n d rele va nt a ut h orities will be 
i nf or me d of t he reas o n f or cli nical st u d y t er mi nati o n. 
3. 7.   
M e a s ur e s t o Mi ni mi z e Bi a s  
3. 7. 1.   
R a n d o mi z at i o n 
T his is a n o pe n -la bel st u d y wit h o ne d ose le vel of I M P; n o ra n d o mizati o n will be perf or me d. 
At  t he R oll o ver v isit (v isit 1), s u bjects c o nfir me d t o be eli gi ble f or t h is O L E st u d y will be 
e nr olle d. S u bjects will retai n t he s u bject i de ntificati o n n u m ber a ssi g ne d i n G L P G 1 6 9 0-C L -2 0 4 . 
3. 7. 2.   
Bli n di n g a n d U n bli n di n g  
T his is a n o pe n -la bel cli nical st u d y a n d treat me nt i n t his e xte nsi o n st u d y will n ot be bli n de d . 
Bef ore t he u n bli n di n g of t he G L P G 1 6 9 0 -C L -2 0 4 st u d y, t he bli n d of treat me nt recei ve d i n St u d y 
G L P G 1 6 9 0 -C L -2 0 4 ca n be br o ke n o nl y if t he i n v esti gat or dee ms it necessar y f or t he safet y of a 
s u bject. T he i n vesti gat or is e nc o ura ge d t o disc uss c o nsi derati o ns t o brea k t he bli n d wit h t he C R O 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 8 - 
 
me dical m o nit or w he ne v er p ossi ble  a n d w here t he sit uati o n all o ws. H o we ver, t he res p o nsi bilit y 
t o brea k t he treat me nt c o de i n e mer ge n c y sit uati o ns resi des s olel y wit h t he i n vesti gat or. T he 
i n vesti gat or is n ot re q uir e d t o disc uss u n bli n di n g bef ore h a n d if he or s he feels ra pi d e m er ge n c y 
u n bl i n di n g is necessar y, b ut is re q uire d t o i nf or m t he s p o ns or i n a ti mel y fas hi o n after u n bli n di n g 
has occ urre d.  
T he bli n d of treat me nt r ecei ve d i n St u d y G L P G 1 6 9 0 -C L -2 0 4 ca n b e br o ke n b y t he i n vesti gat or 
via i nteracti ve we b res p o nse s yste m. 
4.   
I N V E S TI G A TI O N A L M EDI CI N A L P R O D U C T S  
4. 1.   
I d e ntit y of t h e I nv e sti g ati o n al M e di ci n al Pr o d u ct( s ) 
T he I M P ( G L P G 1 6 9 0) will be s u p plie d t o t he cli nical st u d y ce nter, b y a n d u n der t he 
res p o nsi bilit y of t he s p o ns or, w h o will als o pr o vi de t he i n vesti gat or wit h E ur o pea n U ni o n ( E U) 
Q ualifie d Pers o n release d oc u me nts.  
G L P G 1 6 9 0 will be pr o vi de d as fil m -c oat e d ta blets f or oral use, c o ntai ni n g 2 0 0 m g G 4 5 1 9 9 0 eac h 
( G 4 5 1 9 9 0 is t he c o m p o u n d c o de f or G L P G 1 6 9 0).  
A f ull list of e x ci pie nts use d i n t he fil m -c oate d ta blet f or m ulati o n is a vaila ble i n t he  latest versi o n 
of t he  I B f or G L P G 1 6 9 0 a n d rele va nt u p dates/a d de n da. 
4. 2.   
D o s a g e a n d A d mi ni str ati o n  
T he d ose will be 6 0 0 m g G L P G 1 6 9 0 q. d. (as 3  G L P G 1 6 9 0 fil m -c oate d ta bl ets of 2 0 0  m g).  
T he I M P is t o be ta ke n ar o u n d t he sa me ti me e ver y da y wit h f o o d (e. g. brea kfast, s mall meal, or a 
s nac k) or after f o o d i nta k e, wit h a ma xi m u m of 2 h o urs bet wee n t h e f o o d i nta ke a n d I M P i nta ke. 
S u bjects will be i nstr ucte d t o s wall o w t he ta blets as a w h ole wit h a glass of water a n d t o n ot c h e w 
t he I M P pri or t o s w all o wi n g. 
If a s u bject misses a d os e (e. g. beca use h e/s he f or g ot t o ta ke t he me dicati o n), he/s he s h o ul d ta ke 
t he misse d d ose wit hi n 1 2 h o urs after t he pla n ne d i nta ke ti me a n d wit hi n 2 h o urs of f o o d i nta ke. 
If t he I M P is n ot ta ke n wit hi n 1 2 h o urs after t he pl a n ne d ti me, t he misse d d ose s h o ul d be s ki p pe d. 
4. 3.   
P a c k a gi n g, L a b eli n g a n d Di stri b uti o n  
T he fil m -c oate d t a blet f or oral use will be pac ka ge d i n blisters. A m ulti ple of kits will be 
pr o vi de d t o t he s u bject at eac h cli nical st u d y ce nter visit, pr o vi di n g t he s u bject wit h s uf ficie nt 
ta blets t o c o ver t he p eri o d u ntil t he ne xt sc he d ule d cli nical st u d y ce nter visit. I M P pac k a ges will 
be la bele d wit h cli nical st u d y -s p ecific d etails. 
All ma n ufact uri n g, pac ka gi n g  a n d la beli n g o p erati o ns will be perf or me d acc or di n g t o G o o d 
Ma n ufact ur i n g Practice f or Me dici nal Pr o d ucts a n d t he rele va nt re g ulat or y re q uire me nts. 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-3 9 - 
 
T he distri b uti o n will o nl y occ ur after t he re q uire d l ocal d oc u me ntati o n is o btai ne d , i ncl u di n g 
cli nical st u d y a p pr o val b y C o m pete nt A ut h orities a n d t he I E Cs/I R Bs, d oc u me ntati o n o n w hic h 
t he assess me nt of t he i n v esti gat or’s q ualificati o ns was base d (e. g. c urric ul u m vitae), a n d t he 
si g ne d a n d date d st u d y a gree me nt a n d fi na ncial a gree me nt.  
4. 4.   
St or a g e  
Sites are t o st ore I M P s u p plies i n a sec ure area bel o w 3 0° C , pr otecte d fr o m li g ht, u ntil dis pe nse d. 
Sites will be re q uire d t o m o nit or t he st ora ge te m p erat ure b y usi n g at least a mi n -ma x 
te m perat ur e-rec or di n g de vice a n d t o kee p a mi ni m u m t o ma xi m u m te m perat ure l o g, w hic h m ust 
be c o m plete d eac h w or ki n g da y i n or der t o esta blis h a rec or d o f c o m plia nce wit h t hese st ora ge 
c o n diti o ns. T he i n vesti gat or will i nstr uct s u bjects o n h o w t he I M P s h o ul d be st ore d at h o me. 
4. 5.   
Tr e at m e nt C o m pli a n c e  a n d Dr u g A c c o u nt a bilit y  
T he p har macist or desi g n ate d cli nical st u d y pers o n nel will mai ntai n a l o g of t he t otal  a m o u nt of 
I M P recei ve d at site, a m o u nt dis pe nse d t o t he s u bject, a n d t he a m o u nt of I M P ret ur ne d b y t he 
s u bject t o t he site. I M P s u p plies f or eac h s u bject will be i n ve nt orie d a n d acc o u nte d f or 
t hr o u g h o ut t he cli nical st u d y. At t he e n d of t he treat me nt perio d , t hese rec or ds will be c hec k e d 
a gai nst t he i n ve nt or y b y t he st u d y m o nit or. All cli nical s u p plies will be st ore d i n l oc ke d facilities.  
F or eac h d ose t a ke n at h o me, t he date a n d n u m b er of ta blets ta ke n s h o ul d be rec or de d o n t he 
s u bject diar y car d ( Secti o n 5. 4 ). A n y i nterr u pti o n or c ha n ge i n treat me nt (t o get h er wit h t he reas o n 
f or c ha n ge) s h o ul d be d o c u me nte d o n t he s u bject diar y car d. S u bjects will r et ur n a n y u n us e d I M P 
a n d e m pt y I M P pac ka ges at eac h v isit. At eac h cli nical st u d y ce nter visit, cli nical st u d y ce nt er 
staff will re vie w tr eat me nt c o m plia nce b y assessi n g t he n u m ber of ret ur ne d I M P. Misse d d oses 
s h o ul d be disc usse d t o tr y t o ascertai n t he reas o n(s). E ver y eff ort s h o ul d be ma de t o e ns ure t h e 
pr o per s u bject d os e. S u bjects wit h p o or c o m plia nce will be retrai ne d b y t he cli nical st u d y site. 
U p o n s p o ns or a p pr o val , all u n use d I M P a n d e m pt y I M P pac ka ges s h o ul d b e ret ur ne d t o t he dr u g 
s u p plier/ dr u g d e p ot or will be destr o ye d at t he site. I n case of destr ucti o n b y t he site  or t he 
s u p plier/ dr u g d e p ot, a n acce pta bl e destr ucti o n pr o cess s h o ul d be i n place a n d a destr ucti o n 
certificate s h o ul d be pr o vi de d t o t he  s p o ns or. 
5.   
C LI NI C A L 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 m a de t o e ns ure t hat cli nical st u d y p r ot oc ol (C S P )-re q uire d tests a n d 
pr oce d ures are c o m plete d as descri be d i n t he Sc he d ule of Acti vities (see Secti o n  5. 9 ).  
5. 1.   
Ti mi n g of A s s e s s m e nt s  
T he st u d y assess me nts will be u n derta ke n at ti me p oi nts as s pecifie d i n t he Sc he d ule of Acti vities 
i n Secti o n 5. 9 . A wi n d o w of ±2  da ys is all o we d f or Visit s 2  a n d 3, a wi n d o w of ± 4 da ys is 
all o we d f or V isit 4, a n d a wi n d o w of ± 7  da ys is all o we d f or  V isits 5, 6, 7, 8, 9, 1 0, 1 1,  t he E o T  
Wee k 1 0 4  v isit ( or E D visit ), a n d f or t he 2  f oll o w-u p visits.  
T he I C F n ee ds t o be si g n e d bef ore a n y st u d y pr oce d ure f or t his e xte nsi o n st u d y is carrie d o ut. 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-4 3 - 
 
 
He m at ol o g y :  
he mat ocrit, mea n c or p usc ular v ol u me, mea n c or p usc ular  he m o gl o bi n , mea n c or p usc ular 
he m o gl o bi n c o n ce ntrati o n , he m o gl o bi n, re d bl o o d cell c o u nt, w hite bl o o d cell c o u nt, w hite 
bl o o d cell differe ntial c o u nt (a bs ol ute a n d rel ati ve), a n d platelets.  
 
C o a g ul ati o n:  
I N R, acti vate d partial t hr o m b o plasti n ti me , a n d pr ot hr o m bi n ti me.  
 
Ser u m/ Pl as m a  c he mistr y:  
ra n d o m gl u c ose, urea, creati ni ne, uric aci d, s o di u m, p otassi u m, calci u m, c hl ori de, 
p h os p h or us, A S T, A L T, G G T, t otal bilir u bi n, al kali ne p h os p hatase, lact ate de h y dr o ge nas e, 
t otal ser u m bile aci d, al b u mi n, t otal pr o tei ns, tri gl yceri des, c h olester ol, hi g h de nsit y 
li p o pr otei n, l o w de nsit y li p o pr otei n, creati ne ki nase , a n d C-reacti ve pr otei n. 
 
Uri n al ysis:  
 
Di pstic k: p H, gl uc ose, pr otei ns, bl o o d, le uc oc yt es, ket o nes.  
 
Micr osc o pic e x a mi nati o n of t he se di me nt (c yli n ders, er y t hr oc yt es, le uc oc yt es) if 
i n dicate d. 
 
Pre g n a nc y test f or fe m ales:  
u ri ne di pstic k o n a m o nt hl y basis u ntil t he F U 1 foll o w -u p v isit ( o nl y f or W O C B P). 
U nsc he d ule d F S H la b testi n g ma y be p erf or me d if a fe male s u bj ect re p orts a n a me n orr hea 
≥1 2 m o nt hs d uri n g t he  st u d y. 
 
T he cli nical la b orat or y e val uati o ns will be perf or me d at  visits s pecifie d i n t he Sc he d ule of 
A cti vities i n Secti o n  5. 9  (see als o Secti o n 5. 1 , “Ti mi n g of Assess me nts ”). Refere n ce ra n ges will 
be s u p plie d b y t he ce ntr al la b orat or y. Cli nical la b orat or y val ues o utsi de t h e n or mal ra n ge will be 
fla g ge d a n d cli nical rele va nce will be assesse d b y t he i n vesti gat or. O nl y l a b orat or y test 
a b n or malities j u d ge d as cli nicall y si g nifica nt b y t h e pri nci pal i n vesti gat or s h o ul d be rec or de d as 
A Es . 
T he details of bl o o d a n d uri ne sa m ple ha n dli n g a n d s hi p me nt i nstr ucti o ns will be pr o vi de d i n a 
se parat e la b orat or y ma n ual. 
5. 6. 3.   
P h y si c al E x a mi n ati o n  
P h ysical e xa mi nati o ns will be perf or me d as a p pr o priate f or a n y s y m pt o ms re p orte d b y t he 
s u bject. T he y will be c o n d ucte d b y a p h ysicia n, trai ne d p h ysicia n’s assista nt, or n urse practiti o ner 
as acce pta ble acc or di n g t o l ocal re g ulati o n at v isits s pecifie d i n t he Sc he d ul e of Acti vities i n 
Secti o n 5. 9 . T he pers o n c o n d ucti n g t he p h ysical e x a mi nati o n will d oc u me nt t his i n t he s u bject’s 
me dical rec or ds. Cli nicall y si g nifica nt a b n or mal fi n di n gs s h o ul d be rec or de d as A Es.  
5. 6. 4.   
Vit al Si g n s  
Vital si g n s (s yst olic a n d diast olic bl o o d press ure, heart rate, res pir at or y rate, a n d b o d y 
te m perat ur e) will be rec or de d i n a sta n dar dize d ma n ner (i. e. after t he s u bject has reste d i n a 
s u pi ne p ositi o n f or 5 mi n utes) at visits s pecifie d i n t he S c he d ule of A cti vities i n Secti o n 5. 9 . 
Cli nicall y si g nifica nt a b n or mal val ues s h o ul d be rec or de d as A Es.  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-4 5 - 
 
 
5. 9.   
S c h e d ul e of A cti viti e s  
F or detaile d i nstr ucti o ns o n t he cli nical st u d y pr oce d ures, please see referre d secti o ns a n d Secti o n 5. 1 , “Ti mi n g of Ass ess me nts ”. 
E V E N T  
T R E A T M E N T P E RI O D  
F O L L O W -
U P  
St u d y Visit  
R oll -o ver 
Visit  1  
2   
3   
4   
5   
6   
7   
8   
9   
1 0   
1 1  
E o T   
/ E D  
F U 1   
F U 2  
St u d y Wee k ( W) or D a y ( D) ± 
d a ys ( d)  
D 1  
W 2  
± 2 d  
W 4  
± 2 d  
W 8  
± 4 d  
W 1 6  
± 7 d  
W 2 8  
± 7 d  
W 4 0  
± 7 d  
W 5 2  
± 7 d  
W 6 4  
± 7 d  
W 7 6  
± 7 d  
W 8 8  
± 7 d  
W 1 0 4  
± 7 d  
W 1 0 8  
± 7 d  
W 1 1 6  
± 7 d  
I nf or me d c o nse nt 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
I ncl usi o n/e xcl usi o n criteria 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
Pre g na nc y test  
()1  
 
  
  
  
  
  
  
  
  
  
  
 
 
S y m pt o m -directe d p h ysical 
e xa mi nati o n  
()1  
  
  
  
  
  
  
  
  
  
  
  
  
 
Vital si g ns  
()1 
  
  
  
  
  
  
  
  
  
  
  
 
 
1 2 -Lea d E C G  
()1  
  
  
  
  
  
  
  
  
  
  
  
  
 
Cli nical la b orat or y tests  
()1  
  
  
  
  
  
  
  
  
  
  
  
  
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-4 7 - 
 
 
6.   
S T A TI S TI C A L M E T H O D S  
All statistical met h o d s will be detaile d i n a statistical a nal ysis pla n t hat will be pre pare d pri or t o 
data base l oc k . All rele va nt data c ollecte d i n t his cli nical st u d y will be d oc u me nte d usi n g 
s u m mar y ta bl es, fi g ures, a n d s u bject data listi n gs. 
A n y d e viati o ns fr o m t he pr ot oc ol  are t o b e j ustifie d i n t he statistical a nal ysis pla n. 
6. 1.   
D et er mi n ati o n  of S a m pl e Si z e  
T hirt y  s u bjects ( 2 0 o n 6 0 0 m g oral q. d.  G L P G 1 6 9 0 a n d 1 0 o n place b o) are pla n ne d t o be 
ra n d o mize d i n t he p recedi n g G L P G 1 6 9 0 -C L -2 0 4 st u d y. All s u bjects w h o c o m plete d t he 2 4 -wee k 
d o u ble -bli n d treat me nt i n t his prece di n g st u d y, si g ne d t he I C F of t he O L E  st u d y, a n d are eli gi ble 
f or t he O L E  will be i ncl u de d . T h us , u p t o 3 0 s u bjects ma y r oll o ver a n d b e e nr olle d  i n t his O L E 
st u d y. No f or mal sa m ple siz e calc ulati o n was  perf or me d.  
6. 2.   
P o p ul ati o n f or A n al y s e s  
6. 2. 1.   
All E nr oll e d S u bj e ct s  
All s u bjects w h o were f o u n d eli gi ble t o partici p ate i n t he cli nical st u d y.  
6. 2. 2.   
F ull A n al y si s S et  
T he O L E f ull a n al ysis set ( F A S) is defi n e d as all s u bjects w ho ha d  at least o ne i nta ke of I M P  i n 
t he O L E  st u d y. 
6. 3.   
St ati sti c al A n al y s e s  
6. 3. 1.   
G e n er al St ati sti c al C o n si d er ati o n s  
S u m mar y ta b ulati o ns will be prese nte d a n d will dis pla y t he n u m ber of o bser vati o ns, mea n, 
sta n dar d deviati o ns a n d/ or sta n dar d err or ( as a p pr o priate ), me dia n, mi ni m u m a n d ma xi m u m (f or 
c o nti n u o us varia bl es), a n d t he n u m ber a n d perce nta ge per cate g or y (f or cat e g orical data). I n 
a d diti o n t o ta b ulate d descri pti ve statistics, gra p hical data dis pla ys ma y b e use d t o s u m marize t he 
data. Data will be p o ole d acr oss ce nters a n d c o u ntries.  
Ta bles will be pres e nte d b y ra n d o mizati o n gr o u p of t he prece di n g G L P G 1 6 9 0 -C L -2 0 4 st u d y.  
Baseli ne will be defi ne d as t he last meas ure me nt bef ore t h e first d ose of I M P i n t he prece di n g 
G L P G 1 6 9 0 -C L -2 0 4 st u d y ,   
 f or   
 s afet y. 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-4 9 - 
 
6. 3. 5.   
A n al y s e s of S af et y D at a  
All safet y a nal yses will be perf or me d usi n g t he F A S ( Secti o n 6. 2. 2 ). S u bjects will be a nal yze d 
acc or di n g t o t he pri or treat me nt gr o u p i n t he prece di n g G L P G 1 6 9 0 -C L -2 0 4 st u d y . All safet y d ata 
c ollecte d o n or after t h e first d ose of I M P a d mi nistrati o n i n t he pr ece di n g G L P G 1 6 9 0 -C L -2 0 4  
st u d y u p t o t he last c o ntact after t h e last d ose of I M P, u nless s pecifie d ot her wise, will be 
s u m marize d b y treat me nt gr o u p acc or di n g t o t he I M P recei ve d i n St u d y G L P 1 6 9 0-C L -2 0 4, a n d 
o verall . I n a d diti o n, si milar s u m maries of s afet y d ata c ollecte d o nl y after t he first i nta ke of I M P 
d uri n g t his O L E st u d y will be pr o vi de d.   
Cli nical safet y will be a d dresse d b y ass essi n g A E s, la b orat or y ass ess me nts, p h ysical 
e x a mi nati o ns, vital si g ns,  a n d 1 2 -lea d E C Gs. 
6. 3. 5. 1.   
E xt e nt of E x p o s ur e  
A s u bject’s e xte nt of e x p os ure t o t he I M P will be ge n erat e d fr o m t he I M P a d mi nistrati o n pa ge of 
t he C R F. E x p os ure data will be s u m marize d b y treat me nt gr o u p of t he prece di n g G L P G 1 6 9 0 -C L -
2 0 4 st u d y . D urati o n of e x p os ure t o t he I M P will be e x presse d as t he n um b er of  wee ks  bet w ee n 
t he first (i n C L-2 0 4)  a n d last d ose of I M P, i ncl usi ve, re gar dless of te m p orar y i nterr u pti o ns i n 
I M P a d mi nistrati o n a n d s u m marize d b y treat me nt gr o u p, d efi ne d i n C L-2 0 4 . A si milar s u m mar y 
f or t he d urati o n of e x p os ure fr o m t he first d ose of I M P i n t he O L E u p t o t he last d ose will als o be 
pr o vi de d.  
6. 3. 5. 2.   
A d v er s e E v e nt s  
Cli nical a n d la b orat or y A Es will be c o de d usi n g t h e latest versi o n of t he M e dical Dicti o nar y f or 
Re g ulat or y Acti vities. S yste m Or ga n Class ( S O C), Hi g h -Le vel Gr o u p Ter m, Hi g h -Le ve l Ter m, 
Preferre d Ter m, a n d L o wer -Le v el Ter m will be attac he d t o t he cli nical data base.  
T he f oll o wi n g A Es will be c o nsi dere d as T E A Es : 
A n y A E ( or a n y w orse ni n g of a n A E) wit h a n o nset date o n or after t he I M P start date i n t he 
prece di n g G L P G 1 6 9 0 -C L -2 0 4 st u d y a n d n o later t ha n 3 0 da ys after last d ose of I M P  i n 
G L P G 1 6 9 0 -C L -2 0 6  
S u m maries ( n u m ber a n d perce nt a ge of s u bjects) of T E A Es per s u bj ect b y S O C a n d Preferre d 
Ter m will be pr o vi de d b y treat me nt gr o u p. T E A Es will als o be s u m marize d b y ca usal 
relati o ns hi p to t he I M P a n d se verit y. I n a d diti o n, T E A Es lea di n g t o pre mat ure disc o nti n uati o n of 
t he I M P will be s u m mari ze d a n d liste d. Als o, all S A Es, i ncl u di n g t he n o n-treat me nt-e mer ge nt 
S A Es, will be liste d.  
I n a d diti o n, s u m maries a n d/ or listi n gs will be pr o vi de d f or t he s us pecte d s y m pt o ms/ A Es of   
 
wit h a n o nset date o n or after t he I M P start date u ntil t he e n d of foll o w -u p (i ncl u di n g i nf or m ati o n 
fr o m foll o w -u p v isit 2).  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-5 0 - 
 
6. 3. 5. 3.   
Cli ni c al L a b or at or y E v al u ati o n s  
La b orat or y assess me nts will be a nal yze d d escri pti vel y. C ha n ges  fr o m baseli ne ( Da y 1 pred ose ) i n 
t he G L P G 1 6 9 0 -C L -2 0 4 st u d y a n d s hifts acc or di n g t o n or mal ra n ges will be prese nte d as well. 
A nal ys es will be d o ne per pri or treat me nt gr o u p i n G L P G 1 6 9 0 -C L -2 0 4 . Si milar a nal yses of 
safet y data c ollecte d o nl y d uri n g t his O L E st u d y will be pr o vi de d. 
6. 3. 5. 4.   
P h y si c al E x a mi n ati o n s  
O nl y a b n or mal p ost baseli ne  p h ysic al e xa mi nati o n res ults will be liste d.  
6. 3. 5. 5.   
Vit al S i g n s 
Vital si g ns will be a nal yz e d descri pti vel y. C ha n ges fr o m baseli ne ( Da y 1 pre d ose ) i n G L P G 1 6 9 0 -
C L -2 0 4 a n d s hifts acc or di n g t o n or mal ra n ges will be prese nt e d as well. A nal yses will be d o ne 
per pri or tr eat me nt gr o u p as defi ne d i n G L P G 1 6 9 0 -C L -2 0 4 . Si milar a n al ys es of safet y dat a 
c ollecte d o nl y d uri n g t his O L E st u d y will be pr o vi de d.  
6. 3. 5. 6.   
1 2 -L e a d El e ctr o c ar di o gr a m  
A descri pti ve a n al ysis will be d o ne f or t he 1 2-l ea d E C G. C ha n ges fr o m baseli ne ( Da y 1 pred ose ) 
i n G L P G 1 6 9 0 -C L -2 0 4 a n d s hifts acc or di n g t o n or mal ra n ges will be prese nte d as well. A nal yses 
will be d o ne per pri or treat me nt gr o u p i n G L P G 1 6 9 0 -C L -2 0 4 . Si milar a n al ys es of safet y d ata 
collecte d o nl y d uri n g t his O L E st u d y will be pr o vi de d.  
6. 3. 6.   
A n al y si s of Ot h er A s s e s s m e nt s  
E x pl orat or y efficac y  a n d safet y a n al ys es ma y be a d de d w he n dee me d usef ul t o better u n dersta n d 
t he c ollecte d dat a. I n di vi d ual a n d/ or mea n ± sta n d ar d err or efficac y a n d s afety ma y b e pl otte d 
a gai nst o ne a n ot her.   
6. 3. 7.   
A d diti o n al St ati sti c al C o n si d er ati o n s  
N ot a p plica ble.  
7.   
D A T A M O NI T O RI N G  
A n i n de pe n de nt me dical safet y re vi e w will be i m ple me nte d f or G L P G 1 6 9 0 -C L -2 0 4 as well as f or 
t his G L P G 1 6 9 0-C L -2 0 6 cli nical st u d y. T he re vie w will be c o n d ucte d b y a n i n de pe n de nt cli nicia n 
e x perie nce d i n t he fiel d of s yste mic s cler osis. T he i n de pe n de nt e x pert will re vie w safet y data a n d 
assess a n y p ote ntial safet y iss ues arisi n g d uri n g t h e c o n d u ct of t he cli nical st u d y. T his pr ocess 
will be descri be d i n a s e p arate ‘I n de p e n de nt Me di cal Safet y Re vie w C harter’ . 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-5 1 - 
 
8.   
S A F E T Y R E P O R TI N G  
8. 1.   
D efi niti o n s of A d v er s e E v e nt s,  S eri o u s A d v er s e E v e nt s  a n d 
S p e ci al S it u ati o n s 
8. 1. 1.   
A d v er s e E v e nt s  
A n A E is a n y u nt o war d me dical o cc urre n ce, ne w or w orse ni n g of a n y pre -e xisti n g c o n diti o n, i n a 
cli nical st u d y s u bject a d mi nistere d a me dici nal pr o d uct a n d w hic h d oes n ot necessaril y h a ve t o 
ha ve a ca usal r elati o ns hi p wit h t his treat me nt.  
A n A E ca n t h eref ore b e a n y u nfa v ora bl e a n d u ni nt e n de d si g n ( e. 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 dis ease te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her 
or n ot c o nsi dere d relate d. A Es  ma y als o i ncl u de pre - or p ost treat me nt c o m plicati o ns t hat occ ur as 
a res ult of C S P -s pecifie d pr oce d ures, w ors e ni n g of t he tar gete d disease, o ver d ose, dr u g 
a b use/ mis use re p orts, or occ u pati o nal e x p os ure. Pre -e xisti n g c o n diti o ns t hat i ncrease i n se verit y 
or c ha n ge i n n at ure d uri n g or as a c o ns e q ue n ce of partici pati o n i n t he cli nical st u d y will a ls o be 
c o nsi dere d A Es.  
8. 1. 2.   
S eri o u s A d v er s e E v e nt s  
A n S A E is defi ne d as a n A E t hat:  
 
Res ults i n deat h;  
 
Is life-t hreate ni n g ( N ote: T he ter m ‘life-t hreat e ni n g’ i n t he d efi 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 t hat h y p ot heticall y mi g ht ha ve ca use d  d eat h if it were m ore s e vere.);  
 
Re q uires i n -patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n;  
 
Res ults i n persiste nt or si g nifica nt disa bilit y/i n ca p acit y;  
 
Is a c o n ge nital a n o mal y / birt h defect;  
 
Is me di call y si g nifi ca nt ( me dical a n d scie ntific j u d g me nt s h o ul d be e x ercise d i n deci di n g 
w het her ot her sit uati o ns s h o ul d be c o nsi dere d s eri o us s uc h as i m p orta nt me dical e ve nts t hat 
mi g ht n ot be i m me diatel y life -t hreat e ni n g or res ult i n deat h or h os pitalizati o n b ut mi g ht 
je o par dize t he s u bject or mi g ht re q uire i nter ve nti o n t o pre ve nt o ne of t h e ot her o utc o mes 
liste d i n t he defi niti o n a b o ve). 
8. 1. 3.   
U nli st e d ( U n e x p e ct e d) A d v er s e E v e nt s / R ef er e n c e S af et y I nf or m ati o n  
A n A E is c o nsi dere d u nliste d if t he nat ure or i nte nsit y is n ot c o nsiste nt wit h t he a p plica ble 
pr o d uct refere nce s afet y i nf or mati o n. F or a n I M P, t he e x pecte d ness of a n A E will be deter mi ne d 
b y w het her or n ot it is liste d i n t he refere n ce safet y i nf or m ati o n part of t he I B.  
8. 1. 4.   
A d v er s e E v e nt s of S p e ci al Int er e st  
N ot a p plica ble.  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-5 2 - 
 
8. 1. 5.   
Cli ni c al L a b or at or y A b n or m aliti e s a n d Ot h er A b n or m al A s s e s s m e nt s a s 
A d v er s e E v e nt s  or S eri o u s A d v er s e E v e nt s  
La b orat or y a b n or malities wit h o ut cli nical si g nifica nce base d o n t h e i n vesti gat or’s j u d g me nt  are 
n ot c o nsi dere d A Es or S A Es. H o we ver, la b orat or y a b n or malities (e. g. cli nical c he mistr y, 
he mat ol o g y , a n d uri nal ysis) or ot her a b n or mal (cli nical st u d y -s p ecific) assess me nts (e. g. E C G, 
ra di o gra p h y, vital si g ns) t hat re q uire me dical or s ur gical i nter venti o n, are ass ociate d wit h si g ns 
a n d/ or s y m pt o ms, a n d/ or lea d t o I M P i nterr u pti o n, m o dificati o n or disc o nti n uati o n m ust be 
rec or de d as a n A E or S A E if t he y m eet t he defi niti o n as descri be d i n Secti o ns 8. 1. 1  a n d 8. 1. 2 , 
res pecti vel y. If t he la b orat or y a b n or malit y is part of a s y n dr o me, t he s y n dr o me or dia g n osis is t o 
be re p ort e d (e. g. a ne mia i nstea d of decrease d he m o gl o bi n).  
T he f oll o wi n g li ver e nz y me ele vati o ns s h o ul d be re p orte d as S A Es:  
 
A S T or A L T ≥8 x U L N  
 
A S T or A L T ≥3 x U L N wit h si g ns of se vere li ver da ma ge (i.e. wit h t he a p peara nce of fati g u e, 
na usea, v o miti n g, ri g ht u p per q ua dra nt pai n or te n der ness, fe ver, ras h a n d/ or e osi n o p hilia 
[ > 5 %], a n d/ or t otal bilir u bi n ≥1. 5 x U L N or I N R > 1. 5) 
 
8. 1. 6.   
S p e ci al Sit u ati o n s  
S pecial sit uati o ns are sit uati o ns t hat ha ve a p ossi ble i m pact o n t he safe use of t he I M P. T hese 
sit uati o ns mi g ht be or mi g ht n ot be ass o ciate d wit h AEs . 
 
Pre g n a nc y  
 
A b use or mis use of I M P 
 
A b use of I M P is defi ne d as t he persiste nt or s p ora dic, i nte nti o nal e x cessi ve use of t he 
I M P, w hic h is a cc o m pa ni e d b y h ar mf ul p h ysical or ps yc h ol o gi cal effects. 
 
Mis use of I M P is defi n e d as a sit uati o n w here t h e I M P is i nte nti o nall y a n d 
i na p pr o priatel y use d n ot i n acc or da nce wit h t he pr o d uct i nf or mati o n. 
 
Dr u g i nteracti o n or f o o d i nteracti o n wit h I M P 
 
A dr u g i nteracti o n wit h I M P is defi ne d as a sit uati o n i n w hich t here is e vi d e nce or a 
s us pici o n t hat t he I M P i nteracts wit h a n ot her dr u g w he n b ot h are a d mi nistere d t o get her. 
 
A f o o d i nteracti o n wit h I M P is defi ne d as a sit uati o n i n w hic h t here is e vi d e nce or a 
s us pici o n t hat t he I M P i nteracts wit h a f o o d w he n ta ke n to get her.  
 
 Me dicati o n err or wit h I M P 
 
A me dicati o n err or wit h I M P is defi ne d as a n u ni nte n de d fail ure i n t he dr u g treat me nt 
pr ocess t hat lea ds t o, or h as t he p ote ntial t o lea d t o, har m t o t he s u bject. 
 
Occ u pati o nal e x p os ure t o I M P 
 
Occ u pati o nal e x p os ure t o I M P is defi ne d as a n e x p os ure t o t he I M P as a res ult of o ne’s 
pr ofessi o nal or n o n pr ofessi o nal  occ u pati o n.  
 
O ver d ose wit h I M P 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-5 3 - 
 
A n o ver d ose of I M P is defi ne d as t he a d mi nistrati o n of a q ua ntit y of t he I M P gi ve n per 
a d mi nistrati o n or c u m ulati vel y, w hic h is t he i nta ke of m ore t ha n 3  t a blets/ da y. 
 
 Pr o d uct c o m plai nt or q ualit y defect of I M P 
 
Pr o d uct c o m plai nt or q ualit y d efect of I M P is defi ne d as c o m plai nts or defects of t he 
I M P arisi n g fr o m p ote ntial de viati o n s i n t he ma n ufact ure, pac k a gi n g or distri b uti o n of 
t he I M P. 
8. 2.   
A s s e s s m e nt of A d v er s e E v e nt s  a n d S eri o u s A d v er s e E v e nt s  
T he i n vesti gat or is res p o nsi ble f or assessi n g A Es a n d S A Es f or ca usalit y a n d se verit y. T his is t he 
basis f or t he s p o ns or’s fi nal re vie w a n d c o nfir m ati o n of acc urac y a n d c o m plete ness of e v e nt 
i nf or mati o n a n d ca us alit y assess me nts. 
8. 2. 1.   
A s s e s s m e nt of C a u s alit y  
T he i n vesti gat or is res p o nsi ble f or assessi n g t he ca usal relati o ns hi p t o I M P(s) a d mi nistrati o n or 
st u d y pr oce d ures (e. g. i n vasi ve pr oce d ures s u c h as ve ni p u nct ure) base d o n her/ his cli nical 
j u d g me nt. T he f oll o wi n g decisi o n c h oice will be use d b y t h e i n vestigat or t o descri be t he ca usalit y 
assess me nt bet wee n t he re p orte d e v e nt or la b orat or y test a b n or malit y a n d t he I M P . 
 
U nrel ate d:  
Ti me relati o ns hi p t o I M P i nta ke is i m pr o ba ble. Relate d t o ot her eti ol o gi es s uc h as 
c o nc o mita nt me dicati o ns or s u bject's cli nical st ate. 
 
U nli kel y:  
Ti me relati o ns hi p t o I M P i nta ke is i m pr o ba ble ( b ut n ot i m p ossi ble). C o nc o mita nt disease or 
ot her dr u gs pr o vi de pla usi ble e x pla nati o ns.  
 
P ossi ble:  
Ti me relati o ns hi p t o I M P i nta ke is reas o na bl e. E ve nt or la b orat or y test a b n or malit y c o ul d 
als o be e x plai ne d b y dise ase or ot her dr u gs. I nf or mati o n o n I M P wit h dra wal ma y b e lac ki n g 
or u nclear.  
 
Pr o b a ble:  
Ti me relati o ns hi p t o I M P i nta ke is reas o na bl e. U nli kel y t o be attri b ute d t o c o nc urre nt disease 
or ot her dr u gs. Res p o nse t o wit h dra wal is cli nicall y re as o na bl e a n d rec halle n ge n ot re q uire d.  
 
Cert ai n:  
Ti me relati o ns hi p t o I M P i nta ke is pla usi ble. Ca n n ot be e x plai ne d b y c o n c o mita nt disease or 
ot her dr u gs. Res p o nse t o wit h dra wal is pla usi ble ( p har mac ol o gicall y, p at h ol o gicall y). E v e nt 
defi niti ve p har mac ol o gic all y or p he n o me n ol o gicall y ( i.e. a n o bjecti ve a n d s pecific me dical 
dis or der or a rec o g nize d p har mac ol o gical p he n o m e n o n). Rec h alle n ge satisfact or y, if et hical 
a n d necessar y. 
 
It s h o ul d be e m p hasize d t hat i neffecti ve treat me nt ( w orse ni n g of t he dis ease) s h o ul d n ot be 
c o nsi dere d as ca us all y relate d i n t he c o nte xt of A E re p orti n g.  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-5 4 - 
 
8. 2. 2.   
A s s e s s m e nt of S e v erit y  
T he se verit y of A Es s h o ul d be gra de d usi n g t he C T C A E  versi o n 5. 0. If a C T C A E criteri o n d oes 
n ot e xist, t he i n vesti gat or s h o ul d use t he gra de or a djecti ves: Gra d e  1 ( mil d), Gra de 2 ( m o derat e), 
Gra de 3 (se vere), Gra d e 4 (life -t hreate ni n g) or Gra de 5 (fatal) t o des cri be t he ma xi m u m i nte nsit y 
of t he A E. F or p ur p oses of c o nsiste nc y wit h t he C T C A E, t hese i nte nsit y gra des are defi ne d i n t he 
ta ble bel o w. 
T a ble 1   
Gr a di n g of A E  Se verit y  
Gr a de   
A djecti ve   
Descri pti o n  
Gra de 1   
Mil d  
As y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y; 
i nter ve nti o n n ot i n dicate d  
Gra de 2   
M o derate  
L ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g a ge -a p pr o priate 
i nstr u me ntal A D L *  
Gra de 3   
Se vere   
Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life -t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g; 
li miti n g self-care A D L * *  
Gra de 4   
Life -t hreate ni n g  Ur ge nt i nter ve nti o n i n dicate d  
Gra de 5   
Deat h  
Deat h -relate d A E  
*   
I nstr u me ntal A cti vities of Dail y Li vi n g ( A D L) r ef er t o pre pari n g meals, s h o p pi n g f or gr oceries or cl ot hes, usi n g t he 
  
tele p h o ne, ma na gi n g m o ne y, etc. 
* *   
Self -care A D L r ef er t o bat hi n g, dressi n g a n d u n dressi n g, fee di n g self, usi n g t he t oilet, ta ki n g me dicati o ns, a n d n ot 
  
be dri d de n.  
 
F or A Es ass ociate d wit h la b orat or y a b n or malities, t he e ve nt s h o ul d be gra d e d o n t he basis of t he 
cli nical se verit y i n t he c o nte xt of t he u n derl yi n g c o n diti o ns; t his ma y or ma y n ot be i n a gree m e nt 
wit h t he gra di n g of t he la b orat or y a b n or malit y. T his is u p o n t he i n vesti gat or’s assess me nt.  
If t here is a c ha n ge i n i nte nsit y ( w orse ni n g or i m pr o ve me nt) of a n A E, it m ust be rec or de d. 
8. 2. 3.   
O ut c o m e  
Eac h A E m ust be rate d b y c h o osi n g a m o n g:  
 
Rec o vere d/res ol ve d;  
 
Rec o vere d/re s ol ve d wit h se q uelae; 
 
Rec o veri n g/res ol vi n g;  
 
N ot rec o vere d/ n ot res ol v e d;  
 
Fatal;  
 
U n k n o w n.  

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-5 5 - 
 
8. 3.   
I n v e sti g at or R e q uir e m e nt s a n d I n str u cti o n s f or R e p orti n g Ad v er s e 
E v e nt s , S eri o u s A d v er s e E v e nt s , Pr e g n a n ci e s, a n d O t h er S p e ci al 
S it u ati o n s t o t h e S p o n s or 
8. 3. 1.   
A d v er s e E v e nt s  
T he A E re p orti n g p eri o d f or safet y s ur veilla nce be gi ns w he n t h e s u bject si g ns t he I C F a n d e n ds at 
t he s u bject’s last f oll o w-u p visit (t he last f oll o w -u p visit after t he last d ose of I M P). I n t his 
peri o d, all ne w A Es, re gar dless of ca us e or relati o ns hi p, d eri ve d b y s p o nta ne o us, u ns olicite d 
re p orts of s u bjects, b y o bser vati o n a n d b y r o uti ne o pe n q uesti o ni n g (s uc h as “ H o w d o y o u feel? ”) 
nee d t o be rec or de d i n t he s o urce a n d i n t he C R F.  
I n case a n A E is o n g oi n g at t he ti me of t he last f oll o w-u p visit, t he i n ve sti gat or nee ds t o f oll o w-
u p  o n t he s u bject u ntil A E res ol uti o n or reas o n a bl e sta bilizati o n a n d t o d oc u me nt i n t he s u bject’s 
s o urce d oc u m e ntati o n. N o relate d u p dat es or a d diti o nal data o n t he A E s h o ul d be re p orte d i n t he 
C R F.  
If a s u bject is d oc u m e nte d as lost -t o-f oll o w-u p, o n g oi n g/ u n k n o w n o utc o me A Es will n ot be 
f oll o we d u p.  
If t he A E meets t he criteria f or seri o us n ess, t he S A E f or m m ust be c o m plete d a n d se nt t o t he 
s p o ns or wit hi n 2 4 h o urs (see Secti o n 8. 3. 2 ). 
8. 3. 2.   
S eri o u s A d v er s e E v e nt s  
S u bjects e x perie nci n g a n S A E or a n e mer ge nc y sit uati o n will be e x a mi ne d b y a p h ysi cia n as s o o n 
as p ossi ble. T he s u bject will re mai n u n der o bser vati o n as l o n g as m e dicall y i n dicat e d. 
A p pr o priate la b orat or y tests will be perf or me d u ntil all para meters ret ur n t o n or mal or are 
ot her wise e x plai ne d or st a ble.  
All S A Es, w het her or n ot dee me d I M P -relate d, m ust be rec or de d i n t he C R F a n d o n t he S A E 
f or m. T he i n vesti gat or must re p ort eac h S A E i m me diatel y, a n d u n der n o circ u msta nces s h o ul d 
t his e x cee d 2 4 h o urs f oll o wi n g t he k n o wl e d ge of t he S A E, as is i n dicate d o n p a ge 2  u n der 
“ E mer ge n c y C o ntact I nf or mati o n”.  
T he S A E f or m s h o ul d at least c o ntai n i de ntifiers of t he s u bject a n d  t he re p orter, S A E ter m a n d 
state me nt of relat e d ness t o t he I M P, a n d at a later sta ge if n ot yet a vaila ble wit hi n 2 4 h o urs, t he 
f or m nee ds t o be c o m plete d wit h a clearl y writte n narrati ve d escri bi n g si g ns, s y m pt o ms, a n d 
treat me nt of t he e ve nt, dia g n ostic pr oce d ures, as well as a n y rele va nt la b orat or y data a n d a n y 
se q uelae. 
F oll o w -u p a n d o utc o mes s h o ul d be re p orte d a n d d oc u me nte d i n t he s o urce d oc u me nts f or all 
s u bjects t hat e x perie nce a n S A E. It is i m p orta nt t hat t he i nf or mati o n pr o vi de d o n t he S A E f or m 
mat c hes t he i nf or mati o n rec or de d o n t he C R F f or t he sa me e ve nt.  
C o pies of a d diti o nal la b orat or y tests, c o ns ultati o n re p orts, p ost m orte m  re p orts, h os pital case 
re p orts, a ut o ps y re p orts, a n d ot her d oc u me nts s h o ul d be se nt w he n re q uest e d a n d a v aila ble. O nl y 

G al a p a g o s  
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s u bject i de ntifiers (s u bject n u m ber) s h o ul d a p pear o n t he c o pies, a n d all na mes a n d i nitials s h o ul d 
be blac ke n e d a n d re n dere d ille gi ble. F oll o w -u p re p orts relati ve t o t he s u bject’s s u bse q ue nt c o urse 
m ust be s u b mitte d u ntil t he e ve nt has s u bsi de d or, i n case of  p er ma ne nt i m pair me nt, u ntil t he 
c o n diti o n sta bilizes. 
A n y S A Es t hat occ ur after t he p ost treat me nt f oll o w-u p visit b ut wit hi n 3 0 da ys of t he last d ose of 
I M P(s), re gar dless of ca usalit y, s h o ul d als o be re p orte d ( E mer ge nc y C o ntact I nf or mati o n o n 
pa ge  2 ). I nv esti gat ors are n ot o bli gate d t o acti vel y see k S A Es after t he C S P -defi ne d f oll o w -u p 
peri o d. H o we v er, if t he i n vesti gat or is i nf or m e d a b o ut a n S A E t hat occ urs at a n y ti me after t he 
s u bjects’ p osttreat me nt f oll o w-u p visit a n d t he e ve nt is dee me d rele va nt t o t he use of I M P(s), 
he/s he s h o ul d pr o m ptl y d oc u me nt a n d re p ort t he e ve nt t o t he s p o ns or b y usi n g t he S A E f or m.  
8. 3. 3.   
Pr e g n a n c y  
All i nitial re p orts of pre g na nc y i n fe mal e s u bjects a n d pre g na n cies i n part ners of male s u bjects 
i ncl u de d i n t he cli nical st u d y m ust be rec or de d a n d d oc u me nte d i n t he s o urce d oc u me nts a n d o n 
t he pre g na n c y f or m. T h e i n vesti gat or m ust re p ort eac h pre g na n c y i m me diatel y, a n d u n d er n o 
circ u msta nces s h o ul d t his e x cee d 2 4 h o urs f oll o wi n g t he k n o wle d ge of t he pre g na nc y, as is 
i n dicate d o n p a ge 2  u n d er “ E mer ge nc y C o ntact I nf or mati o n”.  
All  pre g n a ncies s h o ul d b e f oll o we d  u p u ntil deli ver y or pre g na nc y i nterr u pti o n. T he i n vesti gat or 
will c o ntact t he s u bject or part ner of t he s u bject after gi vi n g c o ns e nt, at t he e x pecte d ti me of 
deli ver y f or f oll o w -u p a n d f or i nf or mati o n re gar di n g t he o utc o m e of t he ne w b or n. A b n or mal 
pre g na nc y a n d/ or a b n or mal ne w b or n o utc o mes are c o nsi dere d S A Es a n d m ust be re p orte d usi n g 
t he S A E f or m. 
8. 3. 4.   
R e p orti n g of S p e ci al Sit u ati o n s ( O t h er T h a n Pr e g n a n c y) a n d A s s o ci at e d 
A d v er s e E v e nt s  
I n case a s peci al sit uati o n is n ot ass ociate d wit h a n A E, t he s pecial sit uati o n s h o ul d be re p orte d 
wit hi n 2 4 h o urs b y usi n g t he S pecial Sit uati o ns f or m as i s i n dicate d o n pa ge 2  u n der “ E mer ge nc y 
C o ntact I nf or mati o n” . 
I n case a s peci al sit uati o n is ass ociate d wit h a n A E, t he s pecial sit uati o n s h o ul d be re p orte d 
wit hi n 2 4 h o urs b y usi n g t he S pecial Sit uati o ns f or m a n d t he ass ociate d A E s h o ul d be re p orte d as 
s pecifie d i n Secti o n  8. 3. 1 . 
I n case a s peci al sit uati o n is ass ociate d wit h a n S A E, t he s pecial sit uati o n s h o ul d be re p orte d 
wit hi n 2 4 h o urs b y usi n g t he S A E f or m (a n d n ot t h e S pecial Sit uati o ns f or m) a n d t he ass o ciate d 
S A E s h o ul d be re p orte d as s peci fie d i n S ecti o n 8. 3. 2 . 
8. 4.   
S p o n s or R e p orti n g R e q uir e m e nt s  
De pe n di n g o n rele va nt l o cal le gislati o n or re g ulati o ns, i ncl u di n g t he a p plica ble U nite d State s 
Fe deral Dr u g A d mi nistrati o n C o de of Fe deral Re g ulati o ns, t he E U  Cli nical Trials Directi ve 
( 2 0 0 1/ 2 0/ E C) a n d rele va nt u p dates, a n d ot her c o u ntr y-s p ecific l e gislati o n or re g ulati o ns, t he 
s p o ns or ma y b e re q uire d t o e x pe dite t o w orl d wi de re g ulat or y a ge ncies re p orts of S A Es, seri o us 

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a d verse dr u g reacti o ns  or s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs). T he 
s p o ns or or a s pecifie d desi g nee will n otif y w orl d wi de re g ulat or y a ge n cies a n d t he rele va nt 
I E C/I R B i n c o ncer ne d M e m ber States of a p plica bl e S U S A Rs as o utli ne d i n c urre nt re g ulati o ns. 
Assess me nt of e x pecte d ness f or S A Es will be deter mi ne d usi n g t he refere n ce safet y i nf or mati o n 
secti o n i n t he I B or rele va nt l ocal la bel as a p plica ble. 
All c o ncer ne d i n vesti gat ors will recei ve a safet y letter n otif yi n g t h e m of rele va nt S U S A R re p orts 
ass ociate d wit h a n y I M P(s). T he i n vesti gat or s h o ul d n otif y t he I E C/I R B of S U S A R re p orts as 
s o o n as is practical, w h ere t his is re q uire d b y l ocal re g ulat or y a ge ncies, a n d i n acc or da nce wit h 
t he l ocal i nstit uti o nal p olic y. 
9.   
S P O N S O R’ S A N D I N V E S TI G A T O R’ S R E S P O N SI BI LI TI E S  
T his cli nical st u d y is c o n d ucte d i n acc or da n ce wit h t he c urre nt a p plica ble re g ul ati o ns, I C H -G C P 
G ui deli ne E 6 a n d its u p dates, a n d l ocal et hical a n d le gal re q uire me nts.  
G o o d Cli nical Practice is a n i nter nati o nal et h ical a n d scie ntific q ualit y sta n dar d f or desi g ni n g, 
c o n d ucti n g, rec or di n g a n d re p orti n g st u dies t hat i n v ol ve t he partici pati o n of h u ma n s u bjects. 
C o m plia nce wit h t his sta n dar d pr o vi des p u blic ass ura nce t h at t he ri g hts, safet y a n d well -bei n g of 
cli nical st u d y s u bjects are pr otecte d, c o nsiste nt wit h t he pri nci ples t hat ha v e t heir ori gi n i n t he 
Declarati o n of Helsi n ki, a n d t hat t he cli nical st u d y dat a are cre di ble.  
T he na me a n d a d dress of eac h t hir d  part y ve n d or (e. g. C R O) us e d i n t his st u d y a n d t h e s p o ns or’s 
st u d y tea m me m bers will be mai ntai ne d i n t he i n vesti gat or’s a n d s p o ns or’s files as a p pr o priate.  
9. 1.   
S p o n s or’ s R e s p o n si biliti e s  
9. 1. 1.   
R e g ul at or y A p pr o v al / N otifi c ati o n  
Pri or t o cli nical st u d y start, t his C S P t o get her wit h all rele va nt d oc u m e ntati o n will be s u b mitte d 
t o t he l ocal re g ulat or y aut h orities f or re vie w a n d a p pr o val a n d/ or n otificati o n i n c o m plia nce wit h 
l ocal re q uir e me nts. 
9. 1. 2.   
Cli ni c al St u d y Cl o s ur e C o n si d er ati o n s  
T he s p o ns or res er ves t he ri g ht t o cl ose t he i n v esti gati o nal site or e n d t he cli nical st u d y at a n y 
ti me f or a n y reas o n. I n case of a n earl y ter mi nati o n of t he cli nical st u d y or te m p orar y halt b y t he 
s p o ns or, t he I E C/I R B s h o ul d be n otifie d wit hi n 1 5 cale n dar da ys , u nless ot her wise s pecifie d b y 
t he I E C/I R B, i ncl u di n g a detaile d writte n e x pla nati o n of t he reas o ns f or t he ter mi nati o n/ halt. 
T he e n d of cli nical st u d y declarati o n will be s u b mitte d t o t he re g ulat or y a ut h orities a n d I E C/I R B 
after t he c o m plete cli nica l st u d y has e n d e d i n all partici pati n g ce nters, i n all c o u ntries. T his 
n otificati o n will als o be s u b mitte d wit hi n 9 0 da ys of t he e n d of t he cli nical st u d y i n a gi ve n 
c o u ntr y/ me m b er state or wit hi n t he ti meli nes re q uire d b y t h e l ocal re g ulati o ns.  
Reas o ns f o r t he cl os ure of a n i n vesti gati o nal site ma y i ncl u d e, b ut are n ot li mite d t o:  

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 
S uccessf ul c o m pleti o n of t he cli nical st u d y at t he ce nter.  
 
T he o verall re q uire d n u m ber of s u bjects f or t he cli nical st u d y has b ee n recr uite d.  
 
Fail ure of t he i n vesti gat or t o c o m pl y wit h t he C S P, I C H -G C P g ui deli nes or l ocal 
re q uire me nts. 
 
I n a de q uat e recr uit me nt of s u bjects b y t he i n vesti gat or. 
 
Reas o ns f or earl y ter mi n ati o n of a cli nical st u d y b y t he s p o ns or m a y i ncl u de , b ut are n ot li mite d 
t o: 
 
Safet y c o ncer ns.  
 
S ufficie nt data s u g ges ti n g lac k of efficac y. 
9. 1. 3.   
I n d e m nifi c ati o n 
U n der t he c o n diti o ns of a c o ntract c o ncl u de d bet w ee n i n vesti gat or, site a n d s p o ns or or desi g nee, 
w hic h s hall pre vail, t he s p o ns or s hall, e x ce pt i n case of gr oss ne gli ge n ce or willf ul misc o n d uct, 
i n de m nif y a n d h ol d h armless t he i n vesti gat or a n d his/ her me dical staff fr o m a n y clai m arisi n g 
fr o m t he cli nical st u d y acti vities carrie d o ut i n c o m plia nce wit h t he C S P, s p o ns or’s i nstr ucti o ns 
a n d a p plica ble l ocal re g ulati o ns.  
T he i n vesti gat or m ust n otif y t he s p o ns or i m me diatel y  u p o n n otice of a n y cl ai ms or la ws uits.  
9. 1. 4.   
I n s ur a n c e 
T he s p o ns or s hall mai ntai n i ns ura nce c o v era ge t hat is s ufficie nt t o c o ver its o bli gati o ns a n d t hat 
is c o nsiste nt wit h h u ma n cli nical st u d y l ocal re g ul ati o ns. Pr o vi de d t hat t he s u bject has bee n 
treate d acc ordi n g t o t he C S P a n d s p o ns or’s i nstr ucti o ns, a n y i nj ur y ca use d t o a s u bject w hic h is 
t he direct r es ult of his/ her partici pati o n t o t he cli nical st u d y s h all be c o vere d b y t he s p o ns or’s 
i ns ura nce, e x ce pt i n case of gr oss ne gli ge nce or willf ul misc o n d uct b y t he i n vesti gat or . 
9. 1. 5.   
R e p orti n g  
W here re q uire d b y I E C/I R B per l ocal re q uire me nts, at least o nce a year t he i n vesti gat or will 
pr o vi de t he I E C/I R B wit h a pr o gress re p ort t o all o w re vie w of t he cli nical st u d y (see 
Secti o n  9. 4. 1 ). At t he e n d of t he cli nical st u d y, t he res ults of t he cli nical st u d y will be re p orte d i n 
a cli nical st u d y re p ort. A s u m mar y or f ull re p ort, de pe n di n g o n t he re q uire me nts, will be pr o vi de d 
t o t he i n vesti gat ors, t o t h e a p plica ble re g ulat or y a ut h orities, a n d I E Cs/I R Bs  (if re q uire d b y t he 
a p plica ble re g ulat or y re q uire me nts ) wit hi n o ne year, or 6 m o nt hs f or p e diatric st u dies, after t he 
e n d of t he cli nical st u d y.  
9. 1. 6.   
P u bli c ati o n  
It is u n derst o o d b y t he i n vesti gat or t h at t he s p o ns or s hall be free t o use t he c o m p o u n d -relat e d 
i nf or mati o n, w hic h is ge nerate d d uri n g t h e cli nical st u d y a n d ma y discl ose it t o ot her cli nical 
i n vesti gat ors a n d t o re g ul at or y a ge n cies. As a c o ns e q ue nce, t he i n vesti gat or a grees t o pr o vi d e all 
cli nical st u d y res ults a n d data ge nerate d d uri n g t his cli nical st u d y t o t he s p o ns or.  

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T he i n vesti gat or s hall n ot be a ut h orize d t o s u b mit t he res ults of t his cli nical st u d y a n d a n y data 
f or p u blic discl os ure (e. g. p u blicati o n or prese ntati on) wit h o ut t he pri or writte n a p pr o val of t h e 
s p o ns or, w hic h s hall n ot be u nreas o n a bl y wit h hel d.  
H o we ver, it is u n derst o o d a n d a gree d b y t he i n vesti gat ors t hat t heir res ults a n d/ or fi n di n gs s h all 
n ot be a ut h orize d f or p u blicati o n pri or t o s p o ns or’s p u blicat i o n of t he o verall cli nical st u d y 
res ults. T he i n vesti gat or a grees t h at pri or t o t he p u blicati o n of a n y res ults, he/s he s hall pr o vi de 
t he s p o ns or wit h a draft c o py of t h e i nte n de d p u blicati o n. T he s p o ns or s hall ha ve t he ri g ht t o 
re vie w it a n d t o ma ke a n y co m me nts. I n acc or da n ce wit h ge nerall y acce pte d scie ntific 
c olla b orati o n pri nci ples, c o -a ut h ors hi p wit h a n y st aff me m ber s p o ns or i n v ol ve d i n t he cli nical 
st u d y, will be disc usse d a n d m ut uall y a gree d u p o n bef ore s u b missi o n of a n y ma n uscri pt t o a 
p u blis her.  
9. 2.   
In v e sti g at or’ s R e s p o n si biliti e s  
9. 2. 1.   
Fi n a n ci al Di s cl o s ur e  
T he discl ose d fi na ncial i nterest of t he i n vesti gat ors m ust be c ollecte d bef ore scree ni n g of t he first 
s u bject, f oll o wi n g cli nical st u d y c o m pleti o n at t he i n vesti gat or site, a n d 1 year f oll o wi n g o verall 
cli nical st u d y c o m pleti o n. T he i n vesti gat ors s h o ul d pr o m ptl y u p date t his i nf or mati o n if a n y 
rele va nt c ha n ges o cc ur d uri n g t his peri o d. Discl os a ble fi na nci al i nterests will be rec or de d o n t he 
I n v esti gat or Fi na ncial Discl os ure F or m. 
A n y i n vesti gat or(s) a d d e d  as i n vesti gati o nal staff m ust c o m plete t he I n vesti gat or Fi na nci al 
Discl os ure F or m at t he b e gi n ni n g of t heir partici p ati o n i n t he cli nical st u d y. F or a n y 
i n vesti gat or(s) lea vi n g t h e site pri or t o cli nical st u d y c o m pleti o n, a n I n vesti gat or Fi na ncial 
Discl os ure F or m s h o ul d be o btai ne d at t he e n d of t heir c o ntri b uti o n t o t he cli nical st u d y.  
9. 2. 2.   
S o ur c e D at a a n d D at a C a pt ur e  
T he nat ure a n d l ocati o n of all s o urce d o c u me nts nee d t o be i de ntifie d a n d d o c u me nte d t o e ns ure 
t hat all s o urces of ori gi nal data re q uir e d t o c om plete t he C R F are k n o w n a n d are accessi ble f or 
verificati o n b y t he m o nit or.  
S o urce data ma y b e directl y ca pt ur e d fr o m d e vices tra nsferre d fr o m t hir d part ners ( e. g. l a b orat or y 
data) or e ntere d m a n uall y i nt o t he C R F. T he C R F c o m pleti o n g ui deli nes will be pr o vi de d t o eac h 
i n vesti gati o nal site. 
It is rec o m me n de d t hat t h e a ut h or of a n e ntr y i n t h e s o urce d o c u me nts s h o ul d be i de ntifia ble. 
F oll o wi n g I C H -G C P g ui deli nes, dir ect access t o s p o ns or’s re prese ntati ves t o s o urce d oc u m e nts 
m ust be gra nte d f or t h e p ur p ose of verif yi n g t hat t he data rec or de d o n t he C R F are c o nsiste nt 
wit h t he ori gi nal s o urce d ata.  
9. 2. 3.   
Ar c hi vi n g  
T he i n vesti gat or s hall mai ntai n t he cli nical st u d y -s pecific doc u m e nts as s pecifie d i n Secti o n 8  
“ Esse ntial D oc u me nts f or t he C o n d uct of a Cli nical St u d y” of t he I C H -G C P g ui deli nes a n d as 

G al a p a g o s  
C O N FI D E N TI A L  
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-6 0 - 
 
re q uire d b y t he a p plica bl e re g ulat or y re q uire me nt(s). T he i n vesti gat or s h o ul d ta ke meas ures t o 
pre ve nt acci de ntal or pre mat ure des tr ucti o n of t h ese d oc u me nts. 
Esse ntial d oc u me nts s h o ul d be retai ne d u ntil at least 2 years after t he l ast a p pr o val of a mar keti n g 
a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o pe n di n g or c o nte m plate d mar keti n g 
a p plicati o ns i n a n I C H re gi o n or at leas t 2 years ha ve ela pse d si nce t he f or mal disc o nti n uati o n of 
cli nical de vel o p me nt of t he I M P. T hese d oc u m e nts s h o ul d be retai ne d f or a l o n ger peri o d (if 
re q uire d b y t he a p plica bl e re g ulat or y re q uire me nts or b y a n a gree me nt wit h t he s p o ns or). 
U n der n o cir c u ms ta nce s hall t he i n vesti gat or rel ocate or dis p ose a n y cli nical st u d y d oc u me nts 
bef ore h a vi n g o btai ne d a writte n a p pr o val of t h e s p o ns or.  
If it bec o mes necessar y f or t he s p o ns or or t he a p pr o priate re g ulat or y a ut h orit y t o re vi e w a n y 
d oc u me ntati o n relati n g t o t his cli nical st u d y, t he i n vesti gat or m ust per mit access t o s uc h re p orts. 
T he s u bject is gra nti n g access t o his/ her s o urce data b y si g ni n g t he I C F.  
A n y diffic ult y i n st ori n g ori gi nal d oc u m e nts m ust be disc usse d wit h t he m o nit or pri or t o t he 
i nitiati o n of the cli nical st u d y.  
9. 2. 4.   
P arti ci p ati o n C ar d s  
If t he s u bjects are n ot u n der 2 4-h o ur s u p er visi o n of t he i n vesti gat or or site staff, t he y m ust be 
pr o vi de d wit h a s u bject p artici pati o n car d i n dicati n g t he na me of t he I M P, t he cli nical st u d y 
n u m ber, t he i n vesti gat or' s na me, a n d a 2 4 -h o ur e mer ge nc y c o ntact n u m ber. T he s u bject s h o ul d be 
a d vise d t o kee p t he partici pati o n car d i n his/ her wallet at all ti mes.  
9. 3.   
C o nfi d e nti alit y  
T he s u bject will recei ve all i nf or mati o n as re q uire d b y t he E U Ge n eral D ata Pr otecti o n 
Re g ulati o n, na mel y t he i de ntit y a n d c o ntact details of t he c o ntr oller, t he c o ntact details of t he data 
pr otecti o n officer, t he cli nical researc h p ur p oses, t he le gal basis f or t h e pr ocessi n g, t h e reci pie nts 
of t he pers o nal d ata, t he tra nsfer of t he pers o nal data t o t hi r d c o u ntries a n d res pecti ve safe g uar ds, 
t he rete nti o n peri o ds, t he fair pr ocessi n g of his dat a, a n d all his/ her dat a s u bject’s ri g hts. All 
details are liste d i n t he I C F.  
All i nf or mati o n c o ncer ni n g t he pr o d uct a n d t he s p o ns or’s o perati o ns (s uc h as pate nt a p plicati o ns, 
f or m ulas, ma n ufact uri n g pr ocesses, b asic scie ntifi c data, or f or m ulati o n i nf or mati o n s u p plie d t o 
t he i n vesti gat or b y t h e s p o ns or a n d n ot pre vi o usl y p u blis he d) is c o nsi dere d c o nfi de ntial a n d 
s h o ul d n ot be discl ose d b y t he i n vesti gat or t o a n y t hir d part y wit h o ut t he s p o ns or’s pri or writte n 
a p pr o val. T he i n v esti gat or a grees t o use t his i nf or mati o n o nl y i n acc o m plis hi n g t he cli nical st u d y 
a n d will n ot use it f or ot her p ur p oses.  
I n or der t o per mit eas y i d e ntificati o n of t he i n di vi d ual s u bject d uri n g a n d after t he cli nical st u d y, 
t he i n vesti gat or is r es p o nsi ble f or kee pi n g a n u p d ate d S u bject I d e ntificati o n C o de List. T he 
m o nit or will re vie w t his d oc u me nt f or c o m plet e ness. H o we ver, t he i n vesti gat or m ust g uara ntee 
t he s u bject’s a n o n y mit y will be mai ntai ne d. T heref ore, i n or der t o e ns ure s u bject c o nfi de ntialit y, 
t he S u bject I d e ntificati o n C o de List m ust re mai n at t he ce nter a n d n o c o p y will be ma de. 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 1 - 
 
9. 4.   
Et hi c al C o n si d er ati o n s  
9. 4. 1.   
I n d e p e n d e nt Et hi c s C o m mitt e e / I n stit uti o n al R e vi e w B o ar d  
T his cli nical st u d y ca n o n l y be u n d erta ke n after f ull a p pr o val of t he C S P, I C F, a n y ot her writte n 
i nf or mati o n gi ve n t o s u bj ects a n d s u bject recr uit me nt materials has bee n o btai ne d fr o m t he 
I E C/I R B. T his a p pr o val d oc u me nt m ust be date d a n d clearl y i d e ntif y t he cli nical st u d y a n d t he 
relate d cli nical st u d y d oc u me nts bei n g a p pr o ve d, i ncl u di n g t he s u bject c o m pe nsati o n pr o gra ms, if 
a p plica ble.  
D uri n g t h e c o urse of t he cli nical st u d y, at least t he f oll o wi n g d oc u me nts will be s u b mitte d t o t he 
I E C/I R B, per l ocal re q uir e me nts:  
 
C ha n ges t o t he  I B 
 
Re p orts of A Es t hat are s eri o us, u nliste d , a n d ass o ciate d wit h t he I M P (i n c o m plia nce wit h 
I E C/I R B, per l ocal re q uir e me nts) 
 
C S P a me n d me nts  
 
I C F a me n d me nts 
 
C S P a me n d me nts a n d a p plica ble I C F a me n d me nts m ust pr o m ptl y be s u b mitte d t o t he I E C/I R B 
f or re vie w a n d a p pr o val pri or t o i m ple me ntati o n of t he c ha n ge(s), e x ce pt w he n necessar y t o 
eli mi nate a n i m me diate hazar d t o t he cli nical st u d y s u bjects, or acc or di n g t o l ocal re q uire me nts.  
T he I E C/I R B is res p o nsi ble f or c o nti n u o us re vi e w of t he cli nical st u d y. W here  re q uire d b y 
I E C/I R B, per l ocal re q uir e me nts, at least o nce a year t he i n vesti gat or will pr o vi de t he I E C/I R B 
wit h a pr o gress r e p ort t o all o w re vie w of t he cli nical st u d y. A d diti o nal pr o gress re p orts s h o ul d be 
pr o vi de d acc or di n g t o l ocal le gal r e q uire me nts.  T hese re q u ests a n d (re -)a p pr o vals, if a p plica ble, 
s h o ul d be d oc u me nte d i n writi n g. 
9. 4. 2.   
I nf or m e d C o n s e nt 
T he i n vesti gat or or desi g nate d pers o n nel m ust e x plai n t he cli nical st u d y a n d t he i m plicati o ns of 
partici pati o n ( e. g. o bjecti ves, met h o ds, a ntici pate d be nef its, p ossi ble ris ks) t o p ote ntial s u bjects 
acc or di n g t o a p plica ble re g ul ati o ns pri or t o a n y cli nical st u d y -relate d acti vit y. S u bjects will be 
i nf or me d t hat t heir partici pati o n is v ol u ntar y a n d t hat t he y m a y wit h dra w fr o m t he cli nical st u d y 
at a n y ti me. T he y will be i nf or me d t hat c h o osi n g n ot t o partici pate or t o wit h dra w fr o m t he 
cli nical st u d y will n ot ha ve a n i m pact o n t he care t he s u bject will recei ve f or t he treat me nt of 
his/ her disease.  
T he s u bject will be gi ve n s ufficie nt ti me t o rea d t h e I C F a n d t o a s k a d diti o nal q uesti o ns. After 
t his e x pla nati o n a n d bef ore e ntr y i n t he cli nical st u d y, t he s u bject’s c o nse nt s h o ul d be 
a p pr o priatel y rec or de d b y mea ns of t he s u bject's pers o nall y date d si g nat ure a n d b y t he 
i n vesti gat or’s d ate d si g nat ure. I n case t he s u bject is u na ble t o rea d a n d/ or write, oral c o nse nt i n 
t he prese n ce of at least o ne i m partial wit ness, w h o was als o i ncl u de d w h e n t he affecte d pers o n 
was bei n g i nf or me d, ma y be gi v e n. T he wit ness m a y n ot b e a n y o ne w or ki n g at t he st u d y site n or 
a me m ber of t h e i n vesti gati n g tea m. T he orall y gi ve n c o nse nt s hall be d o c u me nte d i n writi n g, 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 2 - 
 
date d a n d si g ne d b y t he wit ness.  After ha vi n g o bt ai ne d t he c o nse nt, a c o p y of t he si g n e d a n d 
date d I C F m ust be gi ve n t o t he s u bject.  
If ne w i nf or mati o n bec o mes a vaila ble rele va nt t o t he s u bject’s willi n g ness t o partici pate i n t he 
cli nical st u d y, t he s u bject will be i nf or me d i n a ti mel y ma n ner b y mea ns of a n a me n de d I C F. T his 
a me n de d I C F will be si g ne d a n d date d b y t h e s u bject ( or, if a p plica ble, b y a n i n de pe n de nt 
wit ness) a n d t he i n vesti gat or t o d oc u me nt t he willi n g ness of t h e s u bject t o c o nti n ue wit h t he 
cli nical st u d y.  
T his si g ne d a n d d ate d a m e n de d versi o n will be file d t o get her wit h t he i nitial si g ne d a n d date d 
I C F. 
A pre g na nt part ner , w h o a grees t h at i nf or mati o n will be gat h ere d  a b o ut her pre g na n c y will si g n a 
s pecific I C F t o partici pat e i n t he data c ollecti o n. Data a b o ut t he h ealt h of t he ba b y will be 
c ollecte d if t he pare nts a gree wit h t he dat a c ollecti o n a n d si g n a s p ecific I C F.  
9. 5.   
D at a Q u alit y C o ntr ol/ A s s ur a n c e  
9. 5. 1.   
M o nit ori n g  
T his c li nical st u d y will be m o nit ore d b y s p o ns or re prese nt ati ves acc or di n g t o t heir c urre nt 
Sta n dar d O perati n g Pr oce d ures f or t he m o nit ori n g of cli nical st u dies as des cri be d i n t he 
m o nit ori n g pla n.  
T o g uara ntee a d e q uate pr otecti o n of t he s u bjects a n d t o g uara nte e t h e q ualit y of t he d ata, t he 
s p o ns or will e ns ure o versi g ht of a n y cli nical st u d y-relate d d uties a n d f u ncti o ns carrie d o ut o n its 
be half, i ncl u di n g cli nical st u d y -relate d d uties a n d f u ncti o ns t hat are s u bc o ntracte d t o a n ot h er 
part y b y t h e s p o ns or’s c o ntra cte d C R O(s).  
9. 5. 2.   
A u dit a n d I n s p e cti o n  
T o e ns ure c o m plia nce wit h rele va nt r e g ulati o ns, a n i n de pe n de nt q ualit y ass ura nce re prese ntati ve, 
re g ulat or y a ut h orities a n d/ or I E Cs/I R Bs ma y re vi e w t his cli nical st u d y. T his i m plies t hat 
a u dit ors/i ns pect ors will ha ve t he r i g ht t o i ns pect t h e cli nical st u d y ce nter(s) at a n y ti me d uri n g 
a n d/ or after c o m pleti o n of t he cli nical st u d y a n d will ha ve access t o t he data ge n erat e d d uri n g t he 
cli nical st u d y, s o urce d oc u me nts, a n d s u bject's files. B y partici pati n g i n t his cli nical st u d y, 
i n vesti gat ors a gree t o t his re q uire me nt. 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 3 - 
 
1 0.   
R E F E R E N C E S  
Alla n ore, Y, O Distler, A J a gersc h mi dt, S Illia n o, L Le dei n, E B oitiere, I A g ue us o p, C P 
De nt o n, a n d D K ha n na. 2 0 1 8. " L ys o p h os p hati dic Aci d Rece pt or 1 A nta g o nist 
S A R 1 0 0 8 4 2 f or Patie nts Wit h Diff use C uta ne o us S yste mic Scler osis: A D o u ble -Bli n d, 
Ra n d o mize d, Ei g ht -Wee k Place b o -C o ntr olle d St u d y F oll o we d b y a Si xtee n -Wee k 
O pe n -La b el E xte nsi o n St u d y." Art hritis R he u m at ol.  7 0( 1 0): 1 6 3 4 -1 6 4 3.  
Ba n d o h, K, J A o ki, M Taira, M Ts uji m ot o, H A rai, a n d K I n o ue. 2 0 0 0. " L ys o p h os p hati dic aci d 
( L P A) rece pt ors of t h e E D G fa mil y are differe ntiall y acti vate d b y L P A s pecies. 
Str uct ure -acti vit y relati o ns hi p of cl o ne d L P A rece pt ors." F E B S Letters  4 7 8: 5 9 -6 5.  
 
 
 
 
 
 
 
 
 
 
 
 
 
Ta na ka, M, S O k u daira, Y Kis hi, R O h ka wa, a n d S Ise ki. 2 0 0 6. " A ut ota xi n sta bilizes bl o o d 
vessels a n d is re q uir e d f or e m br y o nic vas c ulat ure b y pr o d u ci n g l ys o p h os p h ati dic aci d." 
J o ur n al of Bi ol o gic al C he mistry  2 8 1: 2 5 8 2 2 -3 0.  
Ts u da, S, S O k u daira, K M ori ya -It o, M Ta na ka, a n d J A o ki. 2 0 0 6. " C yclic p h os p hati dic aci d is 
pr o d uce d b y a ut ota xi n i n bl o o d." J o ur n al of Bi ol o gic al C he mistry  2 8 1: 2 6 0 8 1 -8.  
W o osle y R L, Heise C W, R o mer o K A. 2 0 1 8. " Q T Dr u gs Lists." Cre di ble Me ds.  J ul y 2 4. 
w w w. Cre di ble Me ds. or g.  
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 4 - 
 
1 1.   
A P P E N DI C E S  
A p pe n di x 1:  K n o w n C Y P 2 C 8 S u bstr ates  
E xcl u de d me dic ati o n:  
A mi o dar o ne  
B u pre n or p hi ne  
A mi o da q ui ne; C hl or o q ui ne  
Re pa gli ni de  
R osi glitaz o ne,  pi o glitaz o ne  
Vera pa mil  
Z o picl o ne  
 
T his n o n -e x ha usti ve  list is i nte n de d as a g ui da nce f or t he i n vesti gat or. 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 5 - 
 
A p pe n di x 2:  K n o w n Str o n g C Y P 3 A 4 I n d ucers a n d P ote nt P -g p I n d ucers  
E xcl u de d me dic ati o n:  
Bar bit urates  
Car ba maze pi ne  
Gl uc oc ortic oi ds , if stea d y d os e of pre d nis o ne or e q ui vale nt > 1 0 m g/ da y  
M o dafi nil  
O xcar baze pi ne  
P he n o bar bital  
P he n yt oi n  
Pi o glitaz o ne  
Rifa b uti n  
Rifa m pi n  
St. J o h n’s w ort  
 
T his n o n -e x ha usti ve  list is i nte n de d as a g ui da nce f or t he i n vesti gat or. 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 6 - 
 
 
A p pe n di x 3:  K n o w n Str o n g C Y P 3 A 4 I n hi bit ors 
E xcl u de d me dic ati o n:  
Clarit hr o m yci n  
Itrac o naz ole 
Ket oc o naz ole  
Nefaz o d o ne  
T elit hr o m yci n  
 
T his n o n -e x ha usti ve  list is i nte n de d as a g ui da nce f or t he i n vesti gat or. 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 7 - 
 
 
A p pe n di x 4:  K n o w n P ote nt P -g p  I n hi bit ors 
E xcl u de d me dic ati o n:  
A mi o dar o ne  
Azelasti ne  
Azit hr o m yci n –  Clarit hr o m yci n –  Er yt hr o m yci n –  R o xit hr o m yci n –  T elit hr o m yci n  
( u nless use d u n der t he c o n diti o n descri be d i n Secti o n 3. 6. 3. 2 ) 
C ycl os p ori ne  
Itrac o naz ole - Ket oc o naz ole  
T a m o xife n  
Vera pa mil  
 
T his n o n -e x ha usti ve list is i nte n de d as a g ui da nce f or t he i n vesti gat or. 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 8 - 
 
 
A p pe n di x 5:  Me dic ati o n K n o w n t o Pr ol o n g Q T I nte r v al 
Me dicati o ns k n o w n t o pr ol o n g Q T i nter val are t o be use d wit h ca uti o n d uri n g t he st u d y. T he 
f oll o wi n g, bas e d o n t he Cre di ble Me ds list of me dicati o n k n o w n t o pr ol o n g Q T i nter val/ca us e 
T orsa de de P oi ntes ( W o osle y R L 2 0 1 8), is a n o n -e x ha usti ve list of t hese me dicati o ns:  
Dis o p yra mi de  
D ofetili de  
Flecai ni de  
H y dr o x yc hl or o q ui ne  
I b utili de 
Q ui ni di ne  
S otal ol  
 
T his list is i nte n de d as a g ui da nce f or t he i n vesti gat or.  
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-6 9 - 
 
SI G N A T U R E P A G E –  S P O N S O R  
St u d y Title:   
A m ulti ce nter, o pe n-l a bel e xte nsi o n st u d y t o e val u ate t he l o n g -ter m safet y, 
t olera bilit y a n d efficac y of orall y a d mi nistere d G L P G 1 6 9 0 i n s u bjects wit h 
s yste mic scler osis. 
C S P Versi o n:  
2 . 0 0 
Date:   
0 8  J a n uar y 2 0 2 0  
 
 
 
 
A n electr o nic si g n at ure f or t he s p o ns or is pr o vide d at t he e n d of t he d oc u me nt.  
 
T his cli nical st u d y pr ot oc ol  has bee n re vie we d a n d a p pr o ve d b y t he s p o ns or t o e ns ure c o m plia nce 
wit h I nter nati o nal C o u ncil f or Har m o ni sati o n of Tec h nical Re q uire me nts f or P har mace uticals f or 
H u ma n Use (I C H) g ui deli nes f or G o o d Cli nical Practices ( G C P) a n d a p plica ble re g ulat or y 
re q uire me nts. 
 
 
, M D  
  
  
Me dical Lea der  
 Si g nat ure  
 Date  
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
D o c i d  4 0 2 9 9 5 
G L P G 1 6 9 0 -C L -2 0 6  
-7 0 - 
 
SI G N A T U R E P A G E –  I N VE S TI G A T O R  
St u d y Title:   
A m ulti ce nter, o pe n-l a bel e xte nsi o n st u d y t o e val u ate t he l o n g-ter m safet y, 
t olera bilit y a n d efficac y of orall y a d mi nistere d G L P G 1 6 9 0 i n s u bjects wit h 
s yste mic scler osis. 
C S P Versi o n:  
2 . 0 0 
Date:   
0 8  J a n uar y 2 0 2 0  
 
 
 
 
 
I, t he u n dersi g ne d, h a ve rea d t his cli nical st u d y pr ot oc ol a n d will c o n d uct t he st u d y as descri be d 
i n c o m plia nce wit h t he cli nical st u d y pr ot oc ol, i n acc or da n ce wit h I nt er nati o nal C o u ncil f or 
Har m o ni sati o n of Tec h nical Re q uire me nts f or P har mace uticals f or H u ma n Use (I C H) g ui d eli nes 
f or G o o d Cli nical Practices ( G C P) a n d a p plica ble re g ulat or y re q uire me nts.  
 
 
  
  
I n v esti gat or Na me 
 Si g nat ure  
 Date  
 

Si g nat ure Pa ge f or gl p g 1 6 9 0-cl- 2 0 6- pr ot oc ol 1 1 1 5 6
Si g nat ure Pa ge f or gl p g 1 6 9 0-cl- 2 0 6- pr ot oc ol 1 1 1 5 6
A p pr o val
al Direct or P hase I
Tra nslati o nal Me dici ne
1 0-Ja n- 2 0 2 0 0 7: 1 4: 1 4 G M T + 0 0 0 0